Novel Multiscale Modeling Tool Applied to Pseudomonas aeruginosa Biofilm Formation

PubMed Central

Biggs, Matthew B.; Papin, Jason A.

2013-01-01

Multiscale modeling is used to represent biological systems with increasing frequency and success. Multiscale models are often hybrids of different modeling frameworks and programming languages. We present the MATLAB-NetLogo extension (MatNet) as a novel tool for multiscale modeling. We demonstrate the utility of the tool with a multiscale model of Pseudomonas aeruginosa biofilm formation that incorporates both an agent-based model (ABM) and constraint-based metabolic modeling. The hybrid model correctly recapitulates oxygen-limited biofilm metabolic activity and predicts increased growth rate via anaerobic respiration with the addition of nitrate to the growth media. In addition, a genome-wide survey of metabolic mutants and biofilm formation exemplifies the powerful analyses that are enabled by this computational modeling tool. PMID:24147108

Novel multiscale modeling tool applied to Pseudomonas aeruginosa biofilm formation.

PubMed

Biggs, Matthew B; Papin, Jason A

2013-01-01

Multiscale modeling is used to represent biological systems with increasing frequency and success. Multiscale models are often hybrids of different modeling frameworks and programming languages. We present the MATLAB-NetLogo extension (MatNet) as a novel tool for multiscale modeling. We demonstrate the utility of the tool with a multiscale model of Pseudomonas aeruginosa biofilm formation that incorporates both an agent-based model (ABM) and constraint-based metabolic modeling. The hybrid model correctly recapitulates oxygen-limited biofilm metabolic activity and predicts increased growth rate via anaerobic respiration with the addition of nitrate to the growth media. In addition, a genome-wide survey of metabolic mutants and biofilm formation exemplifies the powerful analyses that are enabled by this computational modeling tool.

Bayesian models trained with HTS data for predicting β-haematin inhibition and in vitro antimalarial activity.

PubMed

Wicht, Kathryn J; Combrinck, Jill M; Smith, Peter J; Egan, Timothy J

2015-08-15

A large quantity of high throughput screening (HTS) data for antimalarial activity has become available in recent years. This includes both phenotypic and target-based activity. Realising the maximum value of these data remains a challenge. In this respect, methods that allow such data to be used for virtual screening maximise efficiency and reduce costs. In this study both in vitro antimalarial activity and inhibitory data for β-haematin formation, largely obtained from publically available sources, has been used to develop Bayesian models for inhibitors of β-haematin formation and in vitro antimalarial activity. These models were used to screen two in silico compound libraries. In the first, the 1510 U.S. Food and Drug Administration approved drugs available on PubChem were ranked from highest to lowest Bayesian score based on a training set of β-haematin inhibiting compounds active against Plasmodium falciparum that did not include any of the clinical antimalarials or close analogues. The six known clinical antimalarials that inhibit β-haematin formation were ranked in the top 2.1% of compounds. Furthermore, the in vitro antimalarial hit-rate for this prioritised set of compounds was found to be 81% in the case of the subset where activity data are available in PubChem. In the second, a library of about 5000 commercially available compounds (Aldrich(CPR)) was virtually screened for ability to inhibit β-haematin formation and then for in vitro antimalarial activity. A selection of 34 compounds was purchased and tested, of which 24 were predicted to be β-haematin inhibitors. The hit rate for inhibition of β-haematin formation was found to be 25% and a third of these were active against P. falciparum, corresponding to enrichments estimated at about 25- and 140-fold relative to random screening, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Modeling Cytoskeletal Active Matter Systems

NASA Astrophysics Data System (ADS)

Blackwell, Robert

Active networks of filamentous proteins and crosslinking motor proteins play a critical role in many important cellular processes. One of the most important microtubule-motor protein assemblies is the mitotic spindle, a self-organized active liquid-crystalline structure that forms during cell division and that ultimately separates chromosomes into two daughter cells. Although the spindle has been intensively studied for decades, the physical principles that govern its self-organization and function remain mysterious. To evolve a better understanding of spindle formation, structure, and dynamics, I investigate course-grained models of active liquid-crystalline networks composed of microtubules, modeled as hard spherocylinders, in diffusive equilibrium with a reservoir of active crosslinks, modeled as hookean springs that can adsorb to microtubules and and translocate at finite velocity along the microtubule axis. This model is investigated using a combination of brownian dynamics and kinetic monte carlo simulation. I have further refined this model to simulate spindle formation and kinetochore capture in the fission yeast S. pombe. I then make predictions for experimentally realizable perturbations in motor protein presence and function in S. pombe.

Formative Assessment Probes: Is It a Rock? Continuous Formative Assessment

ERIC Educational Resources Information Center

Keeley, Page

2013-01-01

A lesson plan is provided for a formative assessment probe entitled "Is It a Rock?" This probe is designed for teaching elementary school students about rocks through the use of a formative assessment classroom technique (FACT) known as the group Frayer Model. FACT activates students' thinking about a concept and can be used to…

A recurrent connectionist model of person impression formation.

PubMed

Van Overwalle, Frank; Labiouse, Christophe

2004-01-01

Major findings in impression formation are reviewed and modeled from a connectionist perspective. The findings are in the areas of primacy and recency in impression formation, asymmetric diagnosticity of ability- and morality-related traits, increased recall for trait-inconsistent information, assimilation and contrast in priming, and discounting of trait inferences by situational information. The majority of these phenomena are illustrated with well-known experiments and simulated with an autoassociative network architecture with linear activation update and using the delta learning algorithm for adjusting the connection weights. All of the simulations successfully reproduced the empirical findings. Moreover, the proposed model is shown to be consistent with earlier algebraic models of impression formation (Anderson, 1981; Busemeyer, 1991; Hogarth and Einhorn, 1992). The discussion centers on how our model compares to other connectionist approaches to impression formation and how it may contribute to a more parsimonious and unified theory of person perception.

Active walker model for the formation of human and animal trail systems

NASA Astrophysics Data System (ADS)

Helbing, Dirk; Schweitzer, Frank; Keltsch, Joachim; Molnár, Péter

1997-09-01

Active walker models have recently proved their great value for describing the formation of clusters, periodic patterns, and spiral waves as well as the development of rivers, dielectric breakdown patterns, and many other structures. It is shown that they also allow one to simulate the formation of trail systems by pedestrians and ants, yielding a better understanding of human and animal behavior. A comparison with empirical material shows a good agreement between model and reality. Our trail formation model includes an equation of motion, an equation for environmental changes, and an orientation relation. It contains some model functions, which are specified according to the characteristics of the considered animals or pedestrians. Not only the kind of environmental changes differs: Whereas pedestrians leave footprints on the ground, ants produce chemical markings for their orientation. Nevertheless, it is more important that pedestrians steer towards a certain destination, while ants usually find their food sources by chance, i.e., they reach their destination in a stochastic way. As a consequence, the typical structure of the evolving trail systems depends on the respective species. Some ant species produce a dendritic trail system, whereas pedestrians generate a minimal detour system. The trail formation model can be used as a tool for the optimization of pedestrian facilities: It allows urban planners to design convenient way systems which actually meet the route choice habits of pedestrians.

Co-ordinated spatial propagation of blood plasma clotting and fibrinolytic fronts

PubMed Central

Zhalyalov, Ansar S.; Panteleev, Mikhail A.; Gracheva, Marina A.; Ataullakhanov, Fazoil I.

2017-01-01

Fibrinolysis is a cascade of proteolytic reactions occurring in blood and soft tissues, which functions to disintegrate fibrin clots when they are no more needed. In order to elucidate its regulation in space and time, fibrinolysis was investigated using an in vitro reaction-diffusion experimental model of blood clot formation and dissolution. Clotting was activated by a surface with immobilized tissue factor in a thin layer of recalcified blood plasma supplemented with tissue plasminogen activator (TPA), urokinase plasminogen activator or streptokinase. Formation and dissolution of fibrin clot was monitored by videomicroscopy. Computer systems biology model of clot formation and lysis was developed for data analysis and experimental planning. Fibrin clot front propagated in space from tissue factor, followed by a front of clot dissolution propagating from the same source. Velocity of lysis front propagation linearly depended on the velocity clotting front propagation (correlation r2 = 0.91). Computer model revealed that fibrin formation was indeed the rate-limiting step in the fibrinolysis front propagation. The phenomenon of two fronts which switched the state of blood plasma from liquid to solid and then back to liquid did not depend on the fibrinolysis activator. Interestingly, TPA at high concentrations began to increase lysis onset time and to decrease lysis propagation velocity, presumably due to plasminogen depletion. Spatially non-uniform lysis occurred simultaneously with clot formation and detached the clot from the procoagulant surface. These patterns of spatial fibrinolysis provide insights into its regulation and might explain clinical phenomena associated with thrombolytic therapy. PMID:28686711

The antimicrobial action of resveratrol against Listeria monocytogenes in food-based models and its antibiofilm properties.

PubMed

Ferreira, Susana; Domingues, Fernanda

2016-10-01

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phytoalexin synthesized by plants in response to stress. This compound has several beneficial documented properties, namely anti-inflammatory, antioxidant, neuroprotective and antimicrobial activities. In this study the antimicrobial activity of resveratrol against Listeria monocytogenes and Listeria innocua was investigated. Resveratrol had a minimum inhibitory concentration of 200 µg mL(-1) for the tested strains, with time-kill curves demonstrating bacteriostatic activity. Inhibition of biofilm formation was also assessed, with resveratrol strongly inhibiting biofilm formation by both species even at subinhibitory concentrations. Overall, resveratrol showed antimicrobial properties on planktonic cells and on biofilm formation ability. Considering the potential use of resveratrol as a food preservative, the antimicrobial efficacy of resveratrol in food was studied in milk, lettuce leaf model and chicken juice. Resveratrol retained greater efficacy in both lettuce leaf model and chicken juice, but milk had a negative impact on its antilisterial activity, indicating a possible reduction of resveratrol availability in milk. This study reinforces resveratrol as an antimicrobial agent, pointing out its antibiofilm activity and its potential use as preservative in some food matrices. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

A Hypermedia Model for Teaching Technology.

ERIC Educational Resources Information Center

Savage, Ernest N.

Ohio's Model Industrial Technology Systems (MITS) project was initiated in 1987 to achieve the following: identify good activities in the areas of physical, communication, and bio-related technology; standardize the activities' format; and provide a coding system for their eventual use in a hypermedia system. To date, 220 activities have been…

Multi-physics 3D computational study of leaflet thrombus formation following surgical and transcatheter aortic valve replacement

NASA Astrophysics Data System (ADS)

Vahidkhah, Koohyar; Abbasi, Mostafa; Barakat, Mohammed; Dvir, Danny; Azadani, Ali

2017-11-01

An increasingly recognized complication following surgical/transcatheter aortic valve replacement is thrombosis or blood clot formation on replacement valve leaflets. A predisposing factor in thrombus formation on biomaterial surfaces of a bioprosthetic heart valve is blood stasis. Longer residence time of blood provides an opportunity for platelets and agonists to accumulate to critical concentrations that leads to platelet activation and then thrombosis. In this study, we have developed a fluid-solid interaction (FSI) modeling approach, to quantify blood stasis on the leaflets of bioprosthetic aortic valves with different design operating in a patient-specific geometry. We have validated our FSI model against experimental measurements of valve opening/closing as well as in-vitro particle image velocimetry. We have also embedded in our method a model for transport of platelets and agonists (ADP, TxA2, and thrombin) and their interactions that result in platelets activation and adhesion to biomaterial bioprosthetic surfaces. We have provided quantitative evidence for the correlation between long residence of blood on bioprosthetic aortic valve leaflets and formation of high thrombogenicity risk regions on the leaflets that are characterized by accumulation of activated platelet.

Disulfide Bond Formation and Activation of Escherichia coli β-Galactosidase under Oxidizing Conditions

PubMed Central

Seras-Franzoso, Joaquin; Affentranger, Roman; Ferrer-Navarro, Mario; Daura, Xavier; Villaverde, Antonio

2012-01-01

Escherichia coli β-galactosidase is probably the most widely used reporter enzyme in molecular biology, cell biology, and biotechnology because of the easy detection of its activity. Its large size and tetrameric structure make this bacterial protein an interesting model for crystallographic studies and atomic mapping. In the present study, we investigate a version of Escherichia coli β-galactosidase produced under oxidizing conditions, in the cytoplasm of an Origami strain. Our data prove the activation of this microbial enzyme under oxidizing conditions and clearly show the occurrence of a disulfide bond in the β-galactosidase structure. Additionally, the formation of this disulfide bond is supported by the analysis of a homology model of the protein that indicates that two cysteines located in the vicinity of the catalytic center are sufficiently close for disulfide bond formation. PMID:22286993

Dynamics and Function of Nuclear Bodies during Embryogenesis.

PubMed

Arias Escayola, Dahyana; Neugebauer, Karla M

2018-05-01

Nuclear bodies are RNA-rich membraneless organelles in the cell nucleus that concentrate specific sets of nuclear proteins and RNA-protein complexes. Nuclear bodies such as the nucleolus, Cajal body (CB), and the histone locus body (HLB) concentrate factors required for nuclear steps of RNA processing. Formation of these nuclear bodies occurs on genomic loci and is frequently associated with active sites of transcription. Whether nuclear body formation is dependent on a particular gene element, an active process such as transcription, or the nascent RNA present at gene loci is a topic of debate. Recently, this question has been addressed through studies in model organisms and their embryos. The switch from maternally provided RNA and protein to zygotic gene products in early embryos has been well characterized in a variety of organisms. This process, termed maternal-to-zygotic transition, provides an excellent model for studying formation of nuclear bodies before, during, and after the transcriptional activation of the zygotic genome. Here, we review findings in embryos that reveal key principles in the study of the formation and function of nucleoli, CBs, and HLBs. We propose that while particular gene elements may contribute to formation of these nuclear bodies, active transcription promotes maturation of nuclear bodies and efficient RNA processing within them.

Correlation between Gas Bubble Formation and Hydrogen Evolution Reaction Kinetics at Nanoelectrodes.

PubMed

Chen, Qianjin; Luo, Long

2018-04-17

We report the correlation between H 2 gas bubble formation potential and hydrogen evolution reaction (HER) activity for Au and Pt nanodisk electrodes (NEs). Microkinetic models were formulated to obtain the HER kinetic information for individual Au and Pt NEs. We found that the rate-determining steps for the HER at Au and Pt NEs were the Volmer step and the Heyrovsky step, respectively. More interestingly, the standard rate constant ( k 0 ) of the rate-determining step was found to vary over 2 orders of magnitude for the same type of NEs. The observed variations indicate the HER activity heterogeneity at the nanoscale. Furthermore, we discovered a linear relationship between bubble formation potential ( E bubble ) and log( k 0 ) with a slope of 125 mV/decade for both Au and Pt NEs. As log ( k 0 ) increases, E bubble shifts linearly to more positive potentials, meaning NEs with higher HER activities form H 2 bubbles at less negative potentials. Our theoretical model suggests that such linear relationship is caused by the similar critical bubble formation condition for Au and Pt NEs with varied sizes. Our results have potential implications for using gas bubble formation to evaluate the HER activity distribution of nanoparticles in an ensemble.

The conceptualization and measurement of cognitive reserve using common proxy indicators: Testing some tenable reflective and formative models.

PubMed

Ikanga, Jean; Hill, Elizabeth M; MacDonald, Douglas A

2017-02-01

The examination of cognitive reserve (CR) literature reveals a lack of consensus regarding conceptualization and pervasive problems with its measurement. This study aimed at examining the conceptual nature of CR through the analysis of reflective and formative models using eight proxies commonly employed in the CR literature. We hypothesized that all CR proxies would significantly contribute to a one-factor reflective model and that educational and occupational attainment would produce the strongest loadings on a single CR factor. The sample consisted of 149 participants (82 male/67 female), with 18.1 average years of education and ages of 45-99 years. Participants were assessed for eight proxies of CR (parent socioeconomic status, intellectual functioning, level of education, health literacy, occupational prestige, life leisure activities, physical activities, and spiritual and religious activities). Primary statistical analyses consisted of confirmatory factor analysis (CFA) to test reflective models and structural equation modeling (SEM) to evaluate multiple indicators multiple causes (MIMIC) models. CFA did not produce compelling support for a unitary CR construct when using all eight of our CR proxy variables in a reflective model but fairly cogent evidence for a one-factor model with four variable proxies. A second three-factor reflective model based upon an exploratory principal components analysis of the eight proxies was tested using CFA. Though all eight indicators significantly loaded on their assigned factors, evidence in support of overall model fit was mixed. Based upon the results involving the three-factor reflective model, two alternative formative models were developed and evaluated. While some support was obtained for both, the model in which the formative influences were specified as latent variables appeared to best account for the contributions of all eight proxies to the CR construct. While the findings provide partial support for our hypothesis regarding CR as a one-dimensional reflective construct, the results strongly suggest that the construct is more complex than what can be captured in a reflective model alone. There is a need for theory to better identify and differentiate formative from reflective indicators and to articulate the mechanisms by which CR develops and operates.

Antiplatelet Activity of Morus alba Leaves Extract, Mediated via Inhibiting Granule Secretion and Blocking the Phosphorylation of Extracellular-Signal-Regulated Kinase and Akt

PubMed Central

Rhee, Man Hee; Sung, Yoon-Young; Yang, Won-Kyung; Kim, Seung Hyung; Kim, Ho-Kyoung

2014-01-01

Ethnopharmacological Relevance. Morus alba L. leaves (MAE) have been used in fork medicine for the treatment of beriberi, edema, diabetes, hypertension, and atherosclerosis. However, underlying mechanism of MAE on cardiovascular protection remains to be elucidated. Therefore, we investigated whether MAE affect platelet aggregation and thrombosis. Materials and Methods. The anti-platelet activity of MAE was studied using rat platelets. The extent of anti-platelet activity of MAE was assayed in collagen-induced platelet aggregation. ATP and serotonin release was carried out. The activation of integrin α IIb β 3 and phosphorylation of signaling molecules, including MAPK and Akt, were investigated with cytofluorometer and immunoblotting, respectively. The thrombus formation in vivo was also evaluated in arteriovenous shunt model of rats. Results. HPLC chromatographic analysis revealed that MAE contained rutin and isoquercetin. MAE dose-dependently inhibited collagen-induced platelet aggregation. MAE also attenuated serotonin secretion and thromboxane A2 formation. In addition, the extract in vivo activity showed that MAE at 100, 200, and 400 mg/kg significantly and dose-dependently attenuated thrombus formation in rat arterio-venous shunt model by 52.3% (P < 0.001), 28.3% (P < 0.01), and 19.1% (P < 0.05), respectively. Conclusions. MAE inhibit platelet activation, TXB2 formation, serotonin secretion, aggregation, and thrombus formation. The plant extract could be considered as a candidate to anti-platelet and antithrombotic agent. PMID:24701244

A density functional theory study on the carbon chain growth of ethanol formation on Cu-Co (111) and (211) surfaces

NASA Astrophysics Data System (ADS)

Ren, Bohua; Dong, Xiuqin; Yu, Yingzhe; Wen, Guobin; Zhang, Minhua

2017-08-01

Calculations based on the first-principle density functional theory were carried out to study the most controversial reactions in ethanol formation from syngas on Cu-Co surfaces: CO dissociation mechanism and the key reactions of carbon chain growth of ethanol formation (HCO insertion reactions) on four model surfaces (Cu-Co (111) and (211) with Cu-rich or Co-rich surfaces) to investigate the synergy of the Cu and Co components since the complete reaction network of ethanol formation from syngas is a huge computational burden to calculate on four Cu-Co surface models. We investigated adsorption of important species involved in these reactions, activation barrier and reaction energy of H-assisted dissociation mechanism, directly dissociation of CO, and HCO insertion reactions (CHx + HCO → CHxCHO (x = 1-3)) on four Cu-Co surface models. It was found that reactions on Cu-rich (111) and (211) surfaces all have lower activation barrier in H-assisted dissociation and HCO insertion reactions, especially CH + HCO → CHCHO reaction. The PDOS of 4d orbitals of surface Cu and Co atoms of all surfaces were studied. Analysis of d-band center of Cu and Co atoms and the activation barrier data suggested the correlation between electronic property and catalytic performance. Cu-Co bimetallic with Cu-rich surface allows Co to have higher catalytic activity through the interaction of Cu and Co atom. Then it will improve the adsorption of CO and catalytic activity of Co. Thus it is more favorable to the carbon chain growth in ethanol formation. Our study revealed the factors influencing the carbon chain growth in ethanol production and explained the internal mechanism from electronic property aspect.

Plasma membrane H⁺ -ATPase regulation is required for auxin gradient formation preceding phototropic growth.

PubMed

Hohm, Tim; Demarsy, Emilie; Quan, Clément; Allenbach Petrolati, Laure; Preuten, Tobias; Vernoux, Teva; Bergmann, Sven; Fankhauser, Christian

2014-09-26

Phototropism is a growth response allowing plants to align their photosynthetic organs toward incoming light and thereby to optimize photosynthetic activity. Formation of a lateral gradient of the phytohormone auxin is a key step to trigger asymmetric growth of the shoot leading to phototropic reorientation. To identify important regulators of auxin gradient formation, we developed an auxin flux model that enabled us to test in silico the impact of different morphological and biophysical parameters on gradient formation, including the contribution of the extracellular space (cell wall) or apoplast. Our model indicates that cell size, cell distributions, and apoplast thickness are all important factors affecting gradient formation. Among all tested variables, regulation of apoplastic pH was the most important to enable the formation of a lateral auxin gradient. To test this prediction, we interfered with the activity of plasma membrane H⁺ -ATPases that are required to control apoplastic pH. Our results show that H⁺ -ATPases are indeed important for the establishment of a lateral auxin gradient and phototropism. Moreover, we show that during phototropism, H⁺ -ATPase activity is regulated by the phototropin photoreceptors, providing a mechanism by which light influences apoplastic pH. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Coordinate Stimulation of Macrophages by Microparticles and TLR Ligands Induces Foam Cell Formation1

PubMed Central

Keyel, Peter A; Tkacheva, Olga A.; Larregina, Adriana T.; Salter, Russell D

2012-01-01

Aberrant activation of macrophages in arterial walls by oxidized lipoproteins can lead to atherosclerosis. Oxidized lipoproteins convert macrophages to foam cells through lipid uptake and TLR signaling. To investigate the relative contributions of lipid uptake and TLR signaling in foam cell formation, we established an in vitro assay utilizing liposomes of defined lipid compositions. We found that TLRs signaling through Trif promoted foam cell formation by inducing both NF-KB signaling and Type I IFN production, whereas TLRs that do not induce IFN, like TLR2, did not enhance foam cell formation. Addition of IFNα to TLR2 activator promoted robust foam cell formation. TLR signaling further required PPARα, as inhibition of PPARα blocked foam cell formation. We then investigated the ability of endogenous microparticles (MP) to contribute to foam cell formation. We found that lipid containing MP promoted foam cell formation, which was enhanced by TLR stimulation or IFNα. These MP also stimulated foam cell formation in a human skin model. However, these MP suppressed TNFα production and T cell activation, showing that foam cell formation can occur by immunosuppressive microparticles. Taken together, the data reveal novel signaling requirements for foam cell formation and suggest that uptake of distinct types of MP in the context of activation of multiple distinct TLR can induce foam cell formation. PMID:23018455

A Theoretical Model of Jigsaw-Puzzle Pattern Formation by Plant Leaf Epidermal Cells.

PubMed

Higaki, Takumi; Kutsuna, Natsumaro; Akita, Kae; Takigawa-Imamura, Hisako; Yoshimura, Kenji; Miura, Takashi

2016-04-01

Plant leaf epidermal cells exhibit a jigsaw puzzle-like pattern that is generated by interdigitation of the cell wall during leaf development. The contribution of two ROP GTPases, ROP2 and ROP6, to the cytoskeletal dynamics that regulate epidermal cell wall interdigitation has already been examined; however, how interactions between these molecules result in pattern formation remains to be elucidated. Here, we propose a simple interface equation model that incorporates both the cell wall remodeling activity of ROP GTPases and the diffusible signaling molecules by which they are regulated. This model successfully reproduces pattern formation observed in vivo, and explains the counterintuitive experimental results of decreased cellulose production and increased thickness. Our model also reproduces the dynamics of three-way cell wall junctions. Therefore, this model provides a possible mechanism for cell wall interdigitation formation in vivo.

Bursts of star formation in computer simulations of dwarf galaxies

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

Comins, N.F.

1984-09-01

A three-dimensional Stochastic Self-Propagating Star Formation (SSPSF) model of compact galacies is presented. Two phases of gas, active and inactive, are present, and permanent depletion of gas in the form of long lived, low mass stars and remnants occurs. Similarly, global infall of gas from a galactic halo or through galactic cannibalism is permitted. We base our parameters on the observed properties of the compact blue galaxy I Zw 36. Our results are that bursts of star formation occur much more frequently in these runs than continuous nonbursting star formation, suggesting that the blue compact galaxies are probably undergoing burstsmore » rather than continuous, nonbursting low-level star formation activity.« less

Chaetomium thermophilum formate dehydrogenase has high activity in the reduction of hydrogen carbonate (HCO3 -) to formate.

PubMed

Aslan, Aşkın Sevinç; Valjakka, Jarkko; Ruupunen, Jouni; Yildirim, Deniz; Turner, Nicholas J; Turunen, Ossi; Binay, Barış

2017-01-01

While formate dehydrogenases (FDHs) have been used for cofactor recycling in chemoenzymatic synthesis, the ability of FDH to reduce CO 2 could also be utilized in the conversion of CO 2 to useful products via formate (HCOO - ). In this study, we investigated the reduction of CO 2 in the form of hydrogen carbonate (HCO 3 - ) to formate by FDHs from Candida methylica (CmFDH) and Chaetomium thermophilum (CtFDH) in a NADH-dependent reaction. The catalytic performance with HCO 3 - as a substrate was evaluated by measuring the kinetic rates and conducting productivity assays. CtFDH showed a higher efficiency in converting HCO 3 - to formate than CmFDH, whereas CmFDH was better in the oxidation of formate. The pH optimum of the reduction was at pH 7-8. However, the high concentrations of HCO 3 - reduced the reaction rate. CtFDH was modeled in the presence of HCO 3 - showing that it fits to the active site. The active site setting for hydride transfer in CO 2 reduction was modeled. The hydride donated by NADH would form a favorable contact to the carbon atom of HCO 3 - , resulting in a surplus of electrons within the molecule. This would cause the complex formed by hydrogen carbonate and the hydride to break into formate and hydroxide ions. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Star formation in evolving molecular clouds

NASA Astrophysics Data System (ADS)

Völschow, M.; Banerjee, R.; Körtgen, B.

2017-09-01

Molecular clouds are the principle stellar nurseries of our universe; they thus remain a focus of both observational and theoretical studies. From observations, some of the key properties of molecular clouds are well known but many questions regarding their evolution and star formation activity remain open. While numerical simulations feature a large number and complexity of involved physical processes, this plethora of effects may hide the fundamentals that determine the evolution of molecular clouds and enable the formation of stars. Purely analytical models, on the other hand, tend to suffer from rough approximations or a lack of completeness, limiting their predictive power. In this paper, we present a model that incorporates central concepts of astrophysics as well as reliable results from recent simulations of molecular clouds and their evolutionary paths. Based on that, we construct a self-consistent semi-analytical framework that describes the formation, evolution, and star formation activity of molecular clouds, including a number of feedback effects to account for the complex processes inside those objects. The final equation system is solved numerically but at much lower computational expense than, for example, hydrodynamical descriptions of comparable systems. The model presented in this paper agrees well with a broad range of observational results, showing that molecular cloud evolution can be understood as an interplay between accretion, global collapse, star formation, and stellar feedback.

Chlorination of humic materials: Byproduct formation and chemical interpretations

USGS Publications Warehouse

Reckhow, D.A.; Singer, P.C.; Malcolm, R.L.

1990-01-01

Ten aquatic humic and fulvic acids were isolated and studied with respect to their reaction with chlorine. Yields of TOX, chloroform, trichloroacetic acid, dichloroacetic acid, dichloroacetonitrile, and 1,1,1-trichloropropanone were measured at pH 7 and 12. Humic acids produced higher concentrations than their corresponding fulvic acids of all byproducts except 1,1,1-trichloropropanone. Chlorine consumption and byproduct formation were related to fundamental chemical characteristics of the humic materials. A statistical model was proposed for activated aromatic content based on 13C NMR and base titration data. The values estimated from this model were found to be well correlated with chlorine consumption. Specific byproduct formation was related to UV absorbance, nitrogen content, or the activated aromatic content. ?? 1990 American Chemical Society.

An interfacial mechanism for cloud droplet formation on organic aerosols

DOE PAGES

Ruehl, C. R.; Davies, J. F.; Wilson, K. R.

2016-03-25

Accurate predictions of aerosol/cloud interactions require simple, physically accurate parameterizations of the cloud condensation nuclei (CCN) activity of aerosols. Current models assume that organic aerosol species contribute to CCN activity by lowering water activity. We measured droplet diameters at the point of CCN activation for particles composed of dicarboxylic acids or secondary organic aerosol and ammonium sulfate. Droplet activation diameters were 40 to 60% larger than predicted if the organic was assumed to be dissolved within the bulk droplet, suggesting that a new mechanism is needed to explain cloud droplet formation. A compressed film model explains how surface tension depressionmore » by interfacial organic molecules can alter the relationship between water vapor supersaturation and droplet size (i.e., the Köhler curve), leading to the larger diameters observed at activation.« less

An interfacial mechanism for cloud droplet formation on organic aerosols

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

Ruehl, C. R.; Davies, J. F.; Wilson, K. R.

Accurate predictions of aerosol/cloud interactions require simple, physically accurate parameterizations of the cloud condensation nuclei (CCN) activity of aerosols. Current models assume that organic aerosol species contribute to CCN activity by lowering water activity. We measured droplet diameters at the point of CCN activation for particles composed of dicarboxylic acids or secondary organic aerosol and ammonium sulfate. Droplet activation diameters were 40 to 60% larger than predicted if the organic was assumed to be dissolved within the bulk droplet, suggesting that a new mechanism is needed to explain cloud droplet formation. A compressed film model explains how surface tension depressionmore » by interfacial organic molecules can alter the relationship between water vapor supersaturation and droplet size (i.e., the Köhler curve), leading to the larger diameters observed at activation.« less

An interfacial mechanism for cloud droplet formation on organic aerosols.

PubMed

Ruehl, Christopher R; Davies, James F; Wilson, Kevin R

2016-03-25

Accurate predictions of aerosol/cloud interactions require simple, physically accurate parameterizations of the cloud condensation nuclei (CCN) activity of aerosols. Current models assume that organic aerosol species contribute to CCN activity by lowering water activity. We measured droplet diameters at the point of CCN activation for particles composed of dicarboxylic acids or secondary organic aerosol and ammonium sulfate. Droplet activation diameters were 40 to 60% larger than predicted if the organic was assumed to be dissolved within the bulk droplet, suggesting that a new mechanism is needed to explain cloud droplet formation. A compressed film model explains how surface tension depression by interfacial organic molecules can alter the relationship between water vapor supersaturation and droplet size (i.e., the Köhler curve), leading to the larger diameters observed at activation. Copyright © 2016, American Association for the Advancement of Science.

78 FR 29338 - Applications for New Award; Technical Assistance To Improve State Data Capacity-National...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-20

... formative and summative evaluations of the project; Note: The following Web site provides more information... plan, linked to the project's logic model, for a formative evaluation of the project's activities. The plan must describe how the formative evaluation will use clear performance objectives to ensure...

Ancient oceans and Martian paleohydrology

NASA Technical Reports Server (NTRS)

Baker, Victor R.; Strom, Robert G.; Gulick, Virginia C.; Kargel, Jeffrey S.; Komatsu, Goro; Kale, Vishwas S.

1991-01-01

The global model of ocean formation on Mars is discussed. The studies of impact crater densities on certain Martian landforms show that late in Martian history there could have been coincident formation of: (1) glacial features in the Southern Hemisphere; (2) ponded water and related ice features in the northern plains; (3) fluvial runoff on Martian uplands; and (4) active ice-related mass-movement. This model of transient ocean formation ties these diverse observations together in a long-term cyclic scheme of global planetary operation.

Dune-slope activity due to frost and wind throughout the north polar erg, Mars

PubMed Central

DINIEGA, SERINA; HANSEN, CANDICE J.; ALLEN, AMANDA; GRIGSBY, NATHAN; LI, ZHEYU; PEREZ, TYLER; CHOJNACKI, MATTHEW

2018-01-01

Repeat, high-resolution imaging of dunes within the Martian north polar erg have shown that these dune slopes are very active, with alcoves forming along the dune brink each Mars year. In some areas, a few hundred cubic metres of downslope sand movement have been observed, sometimes moving the dune brink ‘backwards’. Based on morphological and activity-timing similarities of these north polar features to southern dune gullies, identifying the processes forming these features is likely to have relevance for understanding the general evolution/modification of dune gullies. To determine alcove-formation model constraints, we have surveyed seven dune fields, each over 1–4 Mars winters. Consistent with earlier reports, we found that alcove-formation activity occurs during the autumn–winter seasons, before or while the stable seasonal frost layer is deposited. We propose a new model in which alcove formation occurs during the autumn, and springtime sublimation activity then enhances the feature. Summertime winds blow sand into the new alcoves, erasing small alcoves over a few Mars years. Based on the observed rate of alcove erasure, we estimated the effective aeolian sand transport flux. From this, we proposed that alcove formation may account for 2–20% of the total sand movement within these dune fields. PMID:29731538

Dune-slope activity due to frost and wind throughout the north polar erg, Mars.

PubMed

Diniega, Serina; Hansen, Candice J; Allen, Amanda; Grigsby, Nathan; Li, Zheyu; Perez, Tyler; Chojnacki, Matthew

2017-01-01

Repeat, high-resolution imaging of dunes within the Martian north polar erg have shown that these dune slopes are very active, with alcoves forming along the dune brink each Mars year. In some areas, a few hundred cubic metres of downslope sand movement have been observed, sometimes moving the dune brink 'backwards'. Based on morphological and activity-timing similarities of these north polar features to southern dune gullies, identifying the processes forming these features is likely to have relevance for understanding the general evolution/modification of dune gullies. To determine alcove-formation model constraints, we have surveyed seven dune fields, each over 1-4 Mars winters. Consistent with earlier reports, we found that alcove-formation activity occurs during the autumn-winter seasons, before or while the stable seasonal frost layer is deposited. We propose a new model in which alcove formation occurs during the autumn, and springtime sublimation activity then enhances the feature. Summertime winds blow sand into the new alcoves, erasing small alcoves over a few Mars years. Based on the observed rate of alcove erasure, we estimated the effective aeolian sand transport flux. From this, we proposed that alcove formation may account for 2-20% of the total sand movement within these dune fields.

New Particle Formation in the Mid-Latitude Upper Troposphere

NASA Astrophysics Data System (ADS)

Axisa, Duncan

Primary aerosol production due to new particle formation (NPF) in the upper troposphere and the impact that this might have on cloud condensation nuclei (CCN) concentration can be of sufficient magnitude to contribute to the uncertainty in radiative forcing. This uncertainty affects our ability to estimate how sensitive the climate is to greenhouse gas emissions. Therefore, new particle formation must be accurately defined, parametrized and accounted for in models. This research involved the deployment of instruments, data analysis and interpretation of particle formation events during the Mid-latitude Airborne Cirrus Properties Experiment (MACPEX) campaign. The approach combined field measurements and observations with extensive data analysis and modeling to study the process of new particle formation and growth to CCN active sizes. Simultaneous measurements of O3, CO, ultrafine aerosol particles and surface area from a high-altitude research aircraft were used to study tropospheric-stratospheric mixing as well as the frequency and location of NPF. It was found that the upper troposphere was an active region in the production of new particles by gas-to-particle conversion, that nucleation was triggered by convective clouds and mixing processes, and that NPF occurred in regions with high relative humidity and low surface area. In certain cases, mesoscale and synoptic features enhanced mixing and facilitated the formation of new particles in the northern mid-latitudes. A modeling study of particle growth and CCN formation was done based on measured aerosol size distributions and modeled growth. The results indicate that when SO2 is of sufficient concentration NPF is a significant source of potential CCN in the upper troposphere. In conditions where convective cloud outflow eject high concentrations of SO2, a large number of new particles can form especially in the instance when the preexisting surface area is low. The fast growth of nucleated clusters produces a particle mode that becomes CCN active within 24-hours.

Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development

PubMed Central

Jäckel, Sven; Saffarzadeh, Mona; Langer, Florian

2017-01-01

Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity, and the coagulation and complement cascades. Here we show in a tissue factor (TF)–dependent model of flow restriction-induced venous thrombosis that complement factors make distinct contributions to platelet activation and fibrin deposition. Complement factor 3 (C3) deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro. Initial fibrin deposition at the vessel wall over 6 hours in this model was dependent on protein disulfide isomerase (PDI) and TF expression by myeloid cells, but did not require neutrophil extracellular trap formation involving peptidyl arginine deiminase 4. In contrast to C3−/− mice, C5-deficient mice had no apparent defect in platelet activation in vitro, and vessel wall platelet deposition and initial hemostasis in vivo. However, fibrin formation, the exposure of negatively charged phosphatidylserine (PS) on adherent leukocytes, and clot burden after 48 hours were significantly reduced in C5−/− mice compared with wild-type controls. These results delineate that C3 plays specific roles in platelet activation independent of formation of the terminal complement complex and provide in vivo evidence for contributions of complement-dependent membrane perturbations to prothrombotic TF activation on myeloid cells. PMID:28223279

New Natural Pigment Fraction Isolated from Saw Palmetto: Potential for Adjuvant Therapy of Hepatocellular Carcinoma.

PubMed

Tan, Hor-Yue; Wang, Ning; Takahashi, Masao; Feng, Yigang; Li, Hongyun; Feng, Yibin

2016-08-05

For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC) cell lines and human umbilical vein endothelial cells (HUVEC) were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK) activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC.

Skyscrapers in the Desert: Observing Ongoing, Active Star Formation in the Low-Density Wing of the Small Magellanic Cloud

NASA Astrophysics Data System (ADS)

Fulmer, Leah M.; Gallagher, John S.; Hamann, Wolf-Rainer; Oskinova, Lida; Ramachandran, Varsha

2018-01-01

The low-density Wing of the Small Magellanic Cloud exhibits ongoing, active star formation despite a distinctive lack of dense ambient gas and dust, or resources from which to form stars. Our continued work in studying this region reveals that these paradoxical observations may be explained by a process of sequential star formation. We present photometric, clustering, and spatial analyses in support of this scenario, along with a proposed star formation history based on the following evidence: matches to isochrone models, stellar and ionized gas kinematics (VLT, SALT), and regional HI gas kinematics (ATCA, PKS).

A Theoretical Model of Jigsaw-Puzzle Pattern Formation by Plant Leaf Epidermal Cells

PubMed Central

Higaki, Takumi; Kutsuna, Natsumaro; Akita, Kae; Takigawa-Imamura, Hisako; Yoshimura, Kenji; Miura, Takashi

2016-01-01

Plant leaf epidermal cells exhibit a jigsaw puzzle–like pattern that is generated by interdigitation of the cell wall during leaf development. The contribution of two ROP GTPases, ROP2 and ROP6, to the cytoskeletal dynamics that regulate epidermal cell wall interdigitation has already been examined; however, how interactions between these molecules result in pattern formation remains to be elucidated. Here, we propose a simple interface equation model that incorporates both the cell wall remodeling activity of ROP GTPases and the diffusible signaling molecules by which they are regulated. This model successfully reproduces pattern formation observed in vivo, and explains the counterintuitive experimental results of decreased cellulose production and increased thickness. Our model also reproduces the dynamics of three-way cell wall junctions. Therefore, this model provides a possible mechanism for cell wall interdigitation formation in vivo. PMID:27054467

Ability of resveratrol to inhibit advanced glycation end product formation and carbohydrate-hydrolyzing enzyme activity, and to conjugate methylglyoxal.

PubMed

Shen, Yixiao; Xu, Zhimin; Sheng, Zhanwu

2017-02-01

Glycation can generate advanced glycation end products (AGE) and its intermediates methylglyoxal (MGO) and glyoxal in foods, which increase the risk of developing diabetes diseases. In this study, the effect of resveratrol against AGE formation, carbohydrate-hydrolyzing enzyme activity and trapping MGO capability were evaluated. Resveratrol showed a significant inhibition capability against AGE formation in bovine serum albumin (BSA)-fructose, BSA-MGO and arginine-MGO models with inhibition percentages of 57.94, 85.95 and 99.35%, respectively. Furthermore, resveratrol acted as a competitive inhibitor for α-amylase with IC50 3.62μg/ml, while it behaved in an uncompetitive manner for α-glucosidase with an IC50 of 17.54μg/l. A prevention of BSA protein glycation was observed in the BSA-fructose model with addition of resveratrol. Three types of resveratrol-MGO adducts were identified in the model consisting of MGO and resveratrol. The results demonstrated that resveratrol has potential in reducing glycation in foods and retarding carbohydrate-hydrolyzing enzyme activities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modelling in Action. Examining How Students Approach Modelling Real Life Situations. Three Case Studies. Model of the Movement of an Elevator

ERIC Educational Resources Information Center

Rivas, Eugenia Marmolejo

2015-01-01

By means of three case studies, we will present two mathematical modelling activities that are suitable for students enrolled in senior high school and the first year of mathematics at university level. The activities have been designed to enrich the learning process and promote the formation of vital modelling skills. In case studies one and two,…

Intermittent behavior of galactic dynamo activities

NASA Technical Reports Server (NTRS)

Ko, C. M.; Parker, E. N.

1989-01-01

Recent observations by Beck and Golla of far-infrared and radio continuum emission from nearby spiral galaxies suggest that the galactic magnetic field strength is connected to the current star formation rate. The role of star formation on the generation of large-scale galactic magnetic field is studied in this paper. Using a simple galactic model, it is shown how the galactic dynamo depends strongly on the turbulent velocity of the interstellar medium. When the star formation efficiency is high, the ISM is churned which in turn amplifies the galactic magnetic field. Between active star formation epochs, the magnetic field is in dormant state and decays at a negligible rate. If density waves trigger star formation, then they also turn on the otherwise dormant dynamo.

Fgf signaling controls pharyngeal taste bud formation through miR-200 and Delta-Notch activity.

PubMed

Kapsimali, Marika; Kaushik, Anna-Lila; Gibon, Guillaume; Dirian, Lara; Ernest, Sylvain; Rosa, Frederic M

2011-08-01

Taste buds, the taste sensory organs, are conserved in vertebrates and composed of distinct cell types, including taste receptor, basal/presynaptic and support cells. Here, we characterize zebrafish taste bud development and show that compromised Fgf signaling in the larva results in taste bud reduction and disorganization. We determine that Fgf activity is required within pharyngeal endoderm for formation of Calb2b(+) cells and reveal miR-200 and Delta-Notch signaling as key factors in this process. miR-200 knock down shows that miR-200 activity is required for taste bud formation and in particular for Calb2b(+) cell formation. Compromised delta activity in mib(-/-) dramatically reduces the number of Calb2b(+) cells and increases the number of 5HT(+) cells. Conversely, larvae with increased Notch activity and ascl1a(-/-) mutants are devoid of 5HT(+) cells, but have maintained and increased Calb2b(+) cells, respectively. These results show that Delta-Notch signaling is required for intact taste bud organ formation. Consistent with this, Notch activity restores Calb2b(+) cell formation in pharyngeal endoderm with compromised Fgf signaling, but fails to restore the formation of these cells after miR-200 knock down. Altogether, this study provides genetic evidence that supports a novel model where Fgf regulates Delta-Notch signaling, and subsequently miR-200 activity, in order to promote taste bud cell type differentiation.

Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

NASA Astrophysics Data System (ADS)

Chesnutt, Jennifer K. W.; Han, Hai-Chao

2013-10-01

Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD) and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD and arteriole tortuosity play important roles in platelet activation and thrombus formation.

Language competition in a population of migrating agents.

PubMed

Lipowska, Dorota; Lipowski, Adam

2017-05-01

Influencing various aspects of human activity, migration is associated also with language formation. To examine the mutual interaction of these processes, we study a Naming Game with migrating agents. The dynamics of the model leads to formation of low-mobility clusters, which turns out to break the symmetry of the model: although the Naming Game remains symmetric, low-mobility languages are favored. High-mobility languages are gradually eliminated from the system, and the dynamics of language formation considerably slows down. Our model is too simple to explain in detail language competition of migrating human communities, but it certainly shows that languages of settlers are favored over nomadic ones.

Language competition in a population of migrating agents

NASA Astrophysics Data System (ADS)

Lipowska, Dorota; Lipowski, Adam

2017-05-01

Influencing various aspects of human activity, migration is associated also with language formation. To examine the mutual interaction of these processes, we study a Naming Game with migrating agents. The dynamics of the model leads to formation of low-mobility clusters, which turns out to break the symmetry of the model: although the Naming Game remains symmetric, low-mobility languages are favored. High-mobility languages are gradually eliminated from the system, and the dynamics of language formation considerably slows down. Our model is too simple to explain in detail language competition of migrating human communities, but it certainly shows that languages of settlers are favored over nomadic ones.

Measuring star formation rates in blue galaxies

NASA Technical Reports Server (NTRS)

Gallagher, John S., III; Hunter, Deidre A.

1987-01-01

The problems associated with measurements of star formation rates in galaxies are briefly reviewed, and specific models are presented for determinations of current star formation rates from H alpha and Far Infrared (FIR) luminosities. The models are applied to a sample of optically blue irregular galaxies, and the results are discussed in terms of star forming histories. It appears likely that typical irregular galaxies are forming stars at nearly constant rates, although a few examples of systems with enhanced star forming activity are found among HII regions and luminous irregular galaxies.

Modeling Initial Stage of Ablation Material Pyrolysis: Graphitic Precursor Formation and Interfacial Effects

NASA Technical Reports Server (NTRS)

Desai, Tapan G.; Lawson, John W.; Keblinski, Pawel

2010-01-01

Reactive molecular dynamics simulations are used to study initial stage of pyrolysis of ablation materials and their composites with carbon nanotubes and carbon fibers. The products formed during pyrolysis are characterized and water is found as the primary product in all cases. The water formation mechanisms are analyzed and the value of the activation energy for water formation is estimated. A detailed study on graphitic precursor formation reveals the presence of two temperature zones. In the lower temperature zone (less than 2000 K) polymerization occurs resulting in formation of large, stable graphitic precursors, and in the high temperature zone (greater than 2000 K) polymer scission results in formation of short polymer chains/molecules. Simulations performed in the high temperature zone on the phenolic resin composites (with carbon nanotubes and carbon fibers) shows that the presence of interfaces had no substantial effect on the chain scission rate or the activation energy value for water formation.

Star formation suppression and bar ages in nearby barred galaxies

NASA Astrophysics Data System (ADS)

James, P. A.; Percival, S. M.

2018-03-01

We present new spectroscopic data for 21 barred spiral galaxies, which we use to explore the effect of bars on disc star formation, and to place constraints on the characteristic lifetimes of bar episodes. The analysis centres on regions of heavily suppressed star formation activity, which we term `star formation deserts'. Long-slit optical spectroscopy is used to determine H β absorption strengths in these desert regions, and comparisons with theoretical stellar population models are used to determine the time since the last significant star formation activity, and hence the ages of the bars. We find typical ages of ˜1 Gyr, but with a broad range, much larger than would be expected from measurement errors alone, extending from ˜0.25 to >4 Gyr. Low-level residual star formation, or mixing of stars from outside the `desert' regions, could result in a doubling of these age estimates. The relatively young ages of the underlying populations coupled with the strong limits on the current star formation rule out a gradual exponential decline in activity, and hence support our assumption of an abrupt truncation event.

Predictive model for ice formation on superhydrophobic surfaces.

PubMed

Bahadur, Vaibhav; Mishchenko, Lidiya; Hatton, Benjamin; Taylor, J Ashley; Aizenberg, Joanna; Krupenkin, Tom

2011-12-06

The prevention and control of ice accumulation has important applications in aviation, building construction, and energy conversion devices. One area of active research concerns the use of superhydrophobic surfaces for preventing ice formation. The present work develops a physics-based modeling framework to predict ice formation on cooled superhydrophobic surfaces resulting from the impact of supercooled water droplets. This modeling approach analyzes the multiple phenomena influencing ice formation on superhydrophobic surfaces through the development of submodels describing droplet impact dynamics, heat transfer, and heterogeneous ice nucleation. These models are then integrated together to achieve a comprehensive understanding of ice formation upon impact of liquid droplets at freezing conditions. The accuracy of this model is validated by its successful prediction of the experimental findings that demonstrate that superhydrophobic surfaces can fully prevent the freezing of impacting water droplets down to surface temperatures of as low as -20 to -25 °C. The model can be used to study the influence of surface morphology, surface chemistry, and fluid and thermal properties on dynamic ice formation and identify parameters critical to achieving icephobic surfaces. The framework of the present work is the first detailed modeling tool developed for the design and analysis of surfaces for various ice prevention/reduction strategies. © 2011 American Chemical Society

QUIESCENCE CORRELATES STRONGLY WITH DIRECTLY MEASURED BLACK HOLE MASS IN CENTRAL GALAXIES

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

Terrazas, Bryan A.; Bell, Eric F.; Henriques, Bruno M. B.

Roughly half of all stars reside in galaxies without significant ongoing star formation. However, galaxy formation models indicate that it is energetically challenging to suppress the cooling of gas and the formation of stars in galaxies that lie at the centers of their dark matter halos. In this Letter, we show that the dependence of quiescence on black hole and stellar mass is a powerful discriminant between differing models for the mechanisms that suppress star formation. Using observations of 91 star-forming and quiescent central galaxies with directly measured black hole masses, we find that quiescent galaxies host more massive blackmore » holes than star-forming galaxies with similar stellar masses. This observational result is in qualitative agreement with models that assume that effective, more-or-less continuous active galactic nucleus feedback suppresses star formation, strongly suggesting the importance of the black hole in producing quiescence in central galaxies.« less

Enzyme activity and AGE formation in a model of AST glycoxidation by D-fructose in vitro.

PubMed

Bousova, Iva; Vukasović, Danka; Juretić, Dubravka; Palicka, Vladimir; Drsata, Jaroslav

2005-03-01

Non-enzymatic glycation as the chain reaction between reducing sugars and free amino groups of proteins has been shown to correlate with physiological ageing and severity of diabetes. The process involves oxidative steps (glycoxidation). In this paper, the effect of D-fructose as a reactive sugar on aspartate aminotransferase (AST) as a model protein was monitored by measurements of the enzyme activity and formation of fluorescent advanced glycation end products (AGEs). Change in the AST activity was considered as a measure of the overall protein damage caused by glycation, and total AGEs and pentosidine represent, at least partly, the formation of glycoxidation products. Catalytic activity of AST in an incubation mixture containing D-fructose (50 mmol L(-1)), decreased compared to control values to 42% (p < 0.05) and to 11% (p < 0.05) on the 5th and on 21st day of incubation, respectively. In the presence of fructose, total fluorescent AGEs concentration was significantly higher since 5th day of incubation (110%, p < 0.05) and the fluorescent pentosidine concentration from 15th day of incubation (117%, p < 0.05) compared to control values, respectively. Catalytic activity of AST clearly and quantitatively demonstrated functional changes in the enzyme molecule caused by structural modifications initiated by fructose, while the evaluation of AGE formation and especially that of pentosidine by fluorescence measurement was less reliable.

A Simple Explanation of Complexation

ERIC Educational Resources Information Center

Elliott, J. Richard

2010-01-01

The topics of solution thermodynamics, activity coefficients, and complex formation are introduced through computational exercises and sample applications. The presentation is designed to be accessible to freshmen in a chemical engineering computations course. The MOSCED model is simplified to explain complex formation in terms of hydrogen…

A format for the interchange of scheduling models

NASA Technical Reports Server (NTRS)

Jaap, John P.; Davis, Elizabeth K.

1994-01-01

In recent years a variety of space-activity schedulers have been developed within the aerospace community. Space-activity schedulers are characterized by their need to handle large numbers of activities which are time-window constrained and make high demands on many scarce resources, but are minimally constrained by predecessor/successor requirements or critical paths. Two needs to exchange data between these schedulers have materialized. First, there is significant interest in comparing and evaluating the different scheduling engines to ensure that the best technology is applied to each scheduling endeavor. Second, there is a developing requirement to divide a single scheduling task among different sites, each using a different scheduler. In fact, the scheduling task for International Space Station Alpha (ISSA) will be distributed among NASA centers and among the international partners. The format used to interchange scheduling data for ISSA will likely use a growth version of the format discussed in this paper. The model interchange format (or MIF, pronounced as one syllable) discussed in this paper is a robust solution to the need to interchange scheduling requirements for space activities. It is highly extensible, human-readable, and can be generated or edited with common text editors. It also serves well the need to support a 'benchmark' data case which can be delivered on any computer platform.

Active Brownian Particles. From Individual to Collective Stochastic Dynamics

NASA Astrophysics Data System (ADS)

Romanczuk, P.; Bär, M.; Ebeling, W.; Lindner, B.; Schimansky-Geier, L.

2012-03-01

We review theoretical models of individual motility as well as collective dynamics and pattern formation of active particles. We focus on simple models of active dynamics with a particular emphasis on nonlinear and stochastic dynamics of such self-propelled entities in the framework of statistical mechanics. Examples of such active units in complex physico-chemical and biological systems are chemically powered nano-rods, localized patterns in reaction-diffusion system, motile cells or macroscopic animals. Based on the description of individual motion of point-like active particles by stochastic differential equations, we discuss different velocity-dependent friction functions, the impact of various types of fluctuations and calculate characteristic observables such as stationary velocity distributions or diffusion coefficients. Finally, we consider not only the free and confined individual active dynamics but also different types of interaction between active particles. The resulting collective dynamical behavior of large assemblies and aggregates of active units is discussed and an overview over some recent results on spatiotemporal pattern formation in such systems is given.

From sensorimotor learning to memory cells in prefrontal and temporal association cortex: a neurocomputational study of disembodiment.

PubMed

Pulvermüller, Friedemann; Garagnani, Max

2014-08-01

Memory cells, the ultimate neurobiological substrates of working memory, remain active for several seconds and are most commonly found in prefrontal cortex and higher multisensory areas. However, if correlated activity in "embodied" sensorimotor systems underlies the formation of memory traces, why should memory cells emerge in areas distant from their antecedent activations in sensorimotor areas, thus leading to "disembodiment" (movement away from sensorimotor systems) of memory mechanisms? We modelled the formation of memory circuits in six-area neurocomputational architectures, implementing motor and sensory primary, secondary and higher association areas in frontotemporal cortices along with known between-area neuroanatomical connections. Sensorimotor learning driven by Hebbian neuroplasticity led to formation of cell assemblies distributed across the different areas of the network. These action-perception circuits (APCs) ignited fully when stimulated, thus providing a neural basis for long-term memory (LTM) of sensorimotor information linked by learning. Subsequent to ignition, activity vanished rapidly from APC neurons in sensorimotor areas but persisted in those in multimodal prefrontal and temporal areas. Such persistent activity provides a mechanism for working memory for actions, perceptions and symbols, including short-term phonological and semantic storage. Cell assembly ignition and "disembodied" working memory retreat of activity to multimodal areas are documented in the neurocomputational models' activity dynamics, at the level of single cells, circuits, and cortical areas. Memory disembodiment is explained neuromechanistically by APC formation and structural neuroanatomical features of the model networks, especially the central role of multimodal prefrontal and temporal cortices in bridging between sensory and motor areas. These simulations answer the "where" question of cortical working memory in terms of distributed APCs and their inner structure, which is, in part, determined by neuroanatomical structure. As the neurocomputational model provides a mechanistic explanation of how memory-related "disembodied" neuronal activity emerges in "embodied" APCs, it may be key to solving aspects of the embodiment debate and eventually to a better understanding of cognitive brain functions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chandra and ALMA observations of the nuclear activity in two strongly lensed star-forming galaxies

NASA Astrophysics Data System (ADS)

Massardi, M.; Enia, A. F. M.; Negrello, M.; Mancuso, C.; Lapi, A.; Vignali, C.; Gilli, R.; Burkutean, S.; Danese, L.; Zotti, G. De

2018-02-01

Aim. According to coevolutionary scenarios, nuclear activity and star formation play relevant roles in the early stages of galaxy formation. We aim at identifying them in high-redshift galaxies by exploiting high-resolution and high-sensitivity X-ray and millimeter-wavelength data to confirm the presence or absence of star formation and nuclear activity and describe their relative roles in shaping the spectral energy distributions and in contributing to the energy budgets of the galaxies. Methods: We present the data, model, and analysis in the X-ray and millimeter (mm) bands for two strongly lensed galaxies, SDP.9 (HATLAS J090740.0-004200) and SDP.11 (HATLAS J091043.1-000322), which we selected in the Herschel-ATLAS catalogs for their excess emission in the mid-IR regime at redshift ≳1.5. This emission suggests nuclear activity in the early stages of galaxy formation. We observed both of them with Chandra ACIS-S in the X-ray regime and analyzed the high-resolution mm data that are available in the ALMA Science Archive for SDP.9. By combining the information available in mm, optical, and X-ray bands, we reconstructed the source morphology. Results: Both targets were detected in the X-ray, which strongly indicates highly obscured nuclear activity. ALMA observations for SDP.9 for the continuum and CO(6-5) spectral line with high resolution (0.02 arcsec corresponding to 65 pc at the distance of the galaxy) allowed us to estimate the lensed galaxy redshift to a better accuracy than pre-ALMA estimates (1.5753 ± 0.0003) and to model the emission of the optical, millimetric, and X-ray band for this galaxy. We demonstrate that the X-ray emission is generated in the nuclear environment, which strongly supports that this object has nuclear activity. On the basis of the X-ray data, we attempt an estimate of the black hole properties in these galaxies. Conclusions: By taking advantage of the lensing magnification, we identify weak nuclear activity associated with high-z galaxies with high star formation rates. This is useful to extend the investigation of the relationship between star formation and nuclear activity to two intrinsically less luminous high-z star-forming galaxies than was possible so far. Given our results for only two objects, they alone cannot constrain the evolutionary models, but provide us with interesting hints and set an observational path toward addressing the role of star formation and nuclear activity in forming galaxies. The reduced images and data cubes as FITS files are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/610/A53

New Natural Pigment Fraction Isolated from Saw Palmetto: Potential for Adjuvant Therapy of Hepatocellular Carcinoma

PubMed Central

Tan, Hor-Yue; Wang, Ning; Takahashi, Masao; Feng, Yigang; Li, Hongyun; Feng, Yibin

2016-01-01

For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC) cell lines and human umbilical vein endothelial cells (HUVEC) were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK) activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC. PMID:27527161

VizieR Online Data Catalog: Type 2 AGN host galaxies in Chandra-COSMOS (Suh+, 2017)

NASA Astrophysics Data System (ADS)

Suh, H.; Civano, F.; Hasinger, G.; Lusso, E.; Lanzuisi, G.; Marchesi, S.; Trakhtenbrot, B.; Allevato, V.; Cappelluti, N.; Capak, P. L.; Elvis, M.; Griffiths, R. E.; Laigle, C.; Lira, P.; Riguccini, L.; Rosario, D. J.; Salvato, M.; Schawinski, K.; Vignali, C.

2018-01-01

We investigate the star formation properties of a large sample of ~2300 X-ray-selected Type 2 Active Galactic Nuclei (AGNs) host galaxies out to z~3 in the Chandra COSMOS Legacy Survey in order to understand the connection between the star formation and nuclear activity. Making use of the existing multi-wavelength photometric data available in the COSMOS field, we perform a multi-component modeling from far-infrared to near-ultraviolet using a nuclear dust torus model, a stellar population model and a starburst model of the spectral energy distributions (SEDs). Through detailed analyses of SEDs, we derive the stellar masses and the star formation rates (SFRs) of Type 2 AGN host galaxies. The stellar mass of our sample is in the range of 93), and grow slowly through secular fueling processes hosting moderate-luminosity AGNs. (1 data file).

Unbiased Proteomics of Early Lewy Body Formation Model Implicates Active Microtubule Affinity-Regulating Kinases (MARKs) in Synucleinopathies

PubMed Central

Riddle, Dawn M.; Zhang, Bin

2017-01-01

Parkinson's disease (PD) patients progressively accumulate intracytoplasmic inclusions formed by misfolded α-synuclein known as Lewy bodies (LBs). LBs also contain other proteins that may or may not be relevant in the disease process. To identify proteins involved early in LB formation, we performed proteomic analysis of insoluble proteins in a primary neuron culture model of α-synuclein pathology. We identified proteins previously found in authentic LBs in PD as well as several novel proteins, including the microtubule affinity-regulating kinase 1 (MARK1), one of the most enriched proteins in this model of LB formation. Activated MARK proteins (MARKs) accumulated in LB-like inclusions in this cell-based model as well as in a mouse model of LB disease and in LBs of postmortem synucleinopathy brains. Inhibition of MARKs dramatically exacerbated α-synuclein pathology. These findings implicate MARKs early in synucleinopathy pathogenesis and as potential therapeutic drug targets. SIGNIFICANCE STATEMENT Neurodegenerative diseases are diagnosed definitively only in postmortem brains by the presence of key misfolded and aggregated disease proteins, but cellular processes leading to accumulation of these proteins have not been well elucidated. Parkinson's disease (PD) patients accumulate misfolded α-synuclein in LBs, the diagnostic signatures of PD. Here, unbiased mass spectrometry was used to identify the microtubule affinity-regulating kinase family (MARKs) as activated and insoluble in a neuronal culture PD model. Aberrant activation of MARKs was also found in a PD mouse model and in postmortem PD brains. Further, inhibition of MARKs led to increased pathological α-synuclein burden. We conclude that MARKs play a role in PD pathogenesis. PMID:28522732

Evaluation of an Interdisciplinary, Physically Active Lifestyle Course Model

ERIC Educational Resources Information Center

Fede, Marybeth H.

2009-01-01

The purpose of this study was to evaluate a fit for life program at a university and to use the findings from an extensive literature review, consultations with formative and summative committees, and data collection to develop an interdisciplinary, physically active lifestyle (IPAL) course model. To address the 5 research questions examined in…

Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation

PubMed Central

Reinhardt, Christoph; von Brühl, Marie-Luise; Manukyan, Davit; Grahl, Lenka; Lorenz, Michael; Altmann, Berid; Dlugai, Silke; Hess, Sonja; Konrad, Ildiko; Orschiedt, Lena; Mackman, Nigel; Ruddock, Lloyd; Massberg, Steffen; Engelmann, Bernd

2008-01-01

The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased — and, under conditions of decreased platelet adhesion, PDI inhibition reduced — fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet–secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury. PMID:18274674

Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation.

PubMed

Reinhardt, Christoph; von Brühl, Marie-Luise; Manukyan, Davit; Grahl, Lenka; Lorenz, Michael; Altmann, Berid; Dlugai, Silke; Hess, Sonja; Konrad, Ildiko; Orschiedt, Lena; Mackman, Nigel; Ruddock, Lloyd; Massberg, Steffen; Engelmann, Bernd

2008-03-01

The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased - and, under conditions of decreased platelet adhesion, PDI inhibition reduced - fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet-secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury.

D-Galacturonic acid as a highly reactive compound in nonenzymatic browning. 1. Formation of browning active degradation products.

PubMed

Bornik, Maria-Anna; Kroh, Lothar W

2013-04-10

Thermal treatment of an aqueous solution of D-galacturonic acid at pH 3, 5, and 8 led to rapid browning of the solution and to the formation of carbocyclic compounds such as reductic acid (2,3-dihydroxy-2-cyclopenten-1-one), DHCP (4,5-dihydroxy-2-cyclopenten-1-one), and furan-2-carbaldehyde, as degradation products in weak acidic solution. Studies on their formation revealed 2-ketoglutaraldehyde as their common key intermediate. Norfuraneol (4-hydroxy-5-methyl-3-(2H)-furanone) is a typical alkaline degradation product and formed after isomerization. Further model studies revealed reductic acid as an important and more browning active compound than furan-2-carbaldehyde, which led to a red color of the model solution. This red-brown color is also characteristic of thermally treated uronic acid solutions.

Cluster Quantum Chemical Study of the Grignard Reagent Formation

NASA Astrophysics Data System (ADS)

Tulub, A. V.; Porsev, V. V.

The main stages of the Grignard reagent formation are described in a framework of quantum chemical cluster model. We have established two kinds of the adsorption of CH3Hal on Mgn clusters, one of which leads to radical formation and the second is responsible for radical free dissociate adsorption. The charge redistribution in cluster CH3MgnHal result to the strong electrostatic interaction with ether and Grignard reagent formation without any activation barrier.

Ligand-Mediated Activation of an Engineered Gs G Protein-Coupled Receptor in Osteoblasts Increases Trabecular Bone Formation

PubMed Central

Hsiao, Edward C.; Millard, Susan M.; Louie, Alyssa; Huang, Yong; Conklin, Bruce R.; Nissenson, Robert A.

2010-01-01

Age-dependent changes in skeletal growth play important roles in regulating skeletal expansion and in the course of many diseases affecting bone. How G protein-coupled receptor (GPCR) signaling affects these changes is poorly understood. Previously, we described a mouse model expressing Rs1, an engineered receptor with constitutive Gs activity. Rs1 expression in osteoblasts from gestation induced a dramatic age-dependent increase in trabecular bone with features resembling fibrous dysplasia; however, these changes were greatly minimized if Rs1 expression was delayed until after puberty. To further investigate whether ligand-induced activation of the Gs-GPCR pathway affects bone formation in adult mice, we activated Rs1 in adult mice with the synthetic ligand RS67333 delivered continuously via an osmotic pump or intermittently by daily injections. We found that osteoblasts from adult animals can be stimulated to form large amounts of bone, indicating that adult mice are sensitive to the dramatic bone- forming actions of Gs signaling in osteoblasts. In addition, our results show that intermittent and continuous activation of Rs1 led to structurally similar but quantitatively different degrees of trabecular bone formation. These results indicate that activation of a Gs-coupled receptor in osteoblasts of adult animals by either intermittent or continuous ligand administration can increase trabecular bone formation. In addition, osteoblasts located at the bone epiphyses may be more responsive to Gs signaling than osteoblasts at the bone diaphysis. This model provides a powerful tool for investigating the effects of ligand-activated Gs-GPCR signaling on dynamic bone growth and remodeling. PMID:20150184

Integument pattern formation involves genetic and epigenetic controls: feather arrays simulated by digital hormone models

PubMed Central

Jiang, Ting-Xin; Widelitz, Randall B.; Shen, Wei-Min; Will, Peter; Wu, Da-Yu; Lin, Chih-Min; Jung, Han-Sung; Chuong, Cheng-Ming

2015-01-01

Pattern formation is a fundamental morphogenetic process. Models based on genetic and epigenetic control have been proposed but remain controversial. Here we use feather morphogenesis for further evaluation. Adhesion molecules and/or signaling molecules were first expressed homogenously in feather tracts (restrictive mode, appear earlier) or directly in bud or inter-bud regions (de novo mode, appear later). They either activate or inhibit bud formation, but paradoxically co-localize in the bud. Using feather bud reconstitution, we showed that completely dissociated cells can reform periodic patterns without reference to previous positional codes. The patterning process has the characteristics of being self-organizing, dynamic and plastic. The final pattern is an equilibrium state reached by competition, and the number and size of buds can be altered based on cell number and activator/inhibitor ratio, respectively. We developed a Digital Hormone Model which consists of (1) competent cells without identity that move randomly in a space, (2) extracellular signaling hormones which diffuse by a reaction-diffusion mechanism and activate or inhibit cell adhesion, and (3) cells which respond with topological stochastic actions manifested as changes in cell adhesion. Based on probability, the results are cell clusters arranged in dots or stripes. Thus genetic control provides combinational molecular information which defines the properties of the cells but not the final pattern. Epigenetic control governs interactions among cells and their environment based on physical-chemical rules (such as those described in the Digital Hormone Model). Complex integument patterning is the sum of these two components of control and that is why integument patterns are usually similar but non-identical. These principles may be shared by other pattern formation processes such as barb ridge formation, fingerprints, pigmentation patterning, etc. The Digital Hormone Model can also be applied to swarming robot navigation, reaching intelligent automata and representing a self-re-configurable type of control rather than a follow-the-instruction type of control. PMID:15272377

Arctic Stratospheric Temperature In The Winters 1999/2000 and 2000/2001: A Quantitative Assessment and Microphysical Implications

NASA Astrophysics Data System (ADS)

Buss, S.; Wernli, H.; Peter, T.; Kivi, R.; Bui, T. P.; Kleinböhl, A.; Schiller, C.

Stratospheric winter temperatures play a key role in the chain of microphysical and chemical processes that lead to the formation of polar stratospheric clouds (PSCs), chlorine activation and eventually to stratospheric ozone depletion. Here the tempera- ture conditions during the Arctic winters 1999/2000 and 2000/2001 are quantitatively investigated using observed profiles of water vapour and nitric acid, and tempera- tures from high-resolution radiosondes and aircraft observations, global ECMWF and UKMO analyses and mesoscale model simulations over Scandinavia and Greenland. The ECMWF model resolves parts of the gravity wave activity and generally agrees well with the observations. However, for the very cold temperatures near the ice frost point the ECMWF analyses have a warm bias of 1-6 K compared to radiosondes. For the mesoscale model HRM, this bias is generally reduced due to a more accurate rep- resentation of gravity waves. Quantitative estimates of the impact of the mesoscale temperature perturbations indicates that over Scandinavia and Greenland the wave- induced stratospheric cooling (as simulated by the HRM) affects only moderately the estimated chlorine activation and homogeneous NAT particle formation, but strongly enhances the potential for ice formation.

Theoretical Astrophysics - Volume 3, Galaxies and Cosmology

NASA Astrophysics Data System (ADS)

Padmanabhan, T.

2002-12-01

1. Overview: galaxies and cosmology; 2. Galactic structure and dynamics; 3. Friedmann model of the universe; 4. Thermal history of the universe; 5. Structure formation; 6. Cosmic microwave background radiation; 7. Formation of baryonic structures; 8. Active galactic nuclei; 9. Intergalactic medium and absorption systems; 10. Cosmological observations.

Models for predicting disinfection byproduct (DBP) formation in drinking waters: a chronological review.

PubMed

Chowdhury, Shakhawat; Champagne, Pascale; McLellan, P James

2009-07-01

Disinfection for the supply of safe drinking water forms a variety of known and unknown byproducts through reactions between the disinfectants and natural organic matter. Chronic exposure to disinfection byproducts through the ingestion of drinking water, inhalation and dermal contact during regular indoor activities (e.g., showering, bathing, cooking) may pose cancer and non-cancer risks to human health. Since their discovery in drinking water in 1974, numerous studies have presented models to predict DBP formation in drinking water. To date, more than 48 scientific publications have reported 118 models to predict DBP formation in drinking waters. These models were developed through laboratory and field-scale experiments using raw, pretreated and synthetic waters. This paper aims to review DBP predictive models, analyze the model variables, assess the model advantages and limitations, and to determine their applicability to different water supply systems. The paper identifies the current challenges and future research needs to better control DBP formation. Finally, important directions for future research are recommended to protect human health and to follow the best management practices.

Quantitative structure activity relationship (QSAR) of piperine analogs for bacterial NorA efflux pump inhibitors.

PubMed

Nargotra, Amit; Sharma, Sujata; Koul, Jawahir Lal; Sangwan, Pyare Lal; Khan, Inshad Ali; Kumar, Ashwani; Taneja, Subhash Chander; Koul, Surrinder

2009-10-01

Quantitative structure activity relationship (QSAR) analysis of piperine analogs as inhibitors of efflux pump NorA from Staphylococcus aureus has been performed in order to obtain a highly accurate model enabling prediction of inhibition of S. aureus NorA of new chemical entities from natural sources as well as synthetic ones. Algorithm based on genetic function approximation method of variable selection in Cerius2 was used to generate the model. Among several types of descriptors viz., topological, spatial, thermodynamic, information content and E-state indices that were considered in generating the QSAR model, three descriptors such as partial negative surface area of the compounds, area of the molecular shadow in the XZ plane and heat of formation of the molecules resulted in a statistically significant model with r(2)=0.962 and cross-validation parameter q(2)=0.917. The validation of the QSAR models was done by cross-validation, leave-25%-out and external test set prediction. The theoretical approach indicates that the increase in the exposed partial negative surface area increases the inhibitory activity of the compound against NorA whereas the area of the molecular shadow in the XZ plane is inversely proportional to the inhibitory activity. This model also explains the relationship of the heat of formation of the compound with the inhibitory activity. The model is not only able to predict the activity of new compounds but also explains the important regions in the molecules in quantitative manner.

Multiscale computational modeling reveals a critical role for TNF-α receptor 1 dynamics in tuberculosis granuloma formation.

PubMed

Fallahi-Sichani, Mohammad; El-Kebir, Mohammed; Marino, Simeone; Kirschner, Denise E; Linderman, Jennifer J

2011-03-15

Multiple immune factors control host responses to Mycobacterium tuberculosis infection, including the formation of granulomas, which are aggregates of immune cells whose function may reflect success or failure of the host to contain infection. One such factor is TNF-α. TNF-α has been experimentally characterized to have the following activities in M. tuberculosis infection: macrophage activation, apoptosis, and chemokine and cytokine production. Availability of TNF-α within a granuloma has been proposed to play a critical role in immunity to M. tuberculosis. However, in vivo measurement of a TNF-α concentration gradient and activities within a granuloma are not experimentally feasible. Further, processes that control TNF-α concentration and activities in a granuloma remain unknown. We developed a multiscale computational model that includes molecular, cellular, and tissue scale events that occur during granuloma formation and maintenance in lung. We use our model to identify processes that regulate TNF-α concentration and cellular behaviors and thus influence the outcome of infection within a granuloma. Our model predicts that TNF-αR1 internalization kinetics play a critical role in infection control within a granuloma, controlling whether there is clearance of bacteria, excessive inflammation, containment of bacteria within a stable granuloma, or uncontrolled growth of bacteria. Our results suggest that there is an interplay between TNF-α and bacterial levels in a granuloma that is controlled by the combined effects of both molecular and cellular scale processes. Finally, our model elucidates processes involved in immunity to M. tuberculosis that may be new targets for therapy.

Rediscovering the wound haematoma as a site of haemostasis during major arterial haemorrhage

PubMed Central

White, N.J.; Mehic, E.; Wang, X.; Chien, D.; Lim, E.; St. John, A.E.; Stern, S.A.; Mourad, P.D.; Rieger, M.; Fries, D.; Martinowitz, U.

2015-01-01

Background Treatments for major internal bleeding after injury include permissive hypotension to decrease the rate of blood loss, intravenous infusion of plasma or clotting factors to improve clot formation, and rapid surgical haemostasis or arterial embolization to control bleeding vessels. Yet, little is known regarding major internal arterial haemostasis, or how these commonly-used treatments might influence haemostasis. Objectives (1) Use a swine model of femoral artery bleeding to understand the perivascular haemostatic response to contained arterial haemorrhage. (2) Directly confirm the association between hemodynamics and bleeding velocity. (3) Observe the feasibility of delivering an activated clotting factor directly to internal sites of bleeding using a simplified angiographic approach. Methods Ultrasound was used to measure bleeding velocity and in vivo clot formation by elastography in a swine model of contained femoral artery bleeding with fluid resuscitation. A swine model of internal pelvic and axillary artery haemorrhage was also used to demonstrate feasibility of local delivery of an activated clotting factor. Results In this model, clots formed slowly within the peri-wound hematoma , but eventually containing the bleeding. Central hemodynamics correlated positively with bleeding velocity. Infusion of recombinant human activated Factor VII into the injured artery nearby the site of major internal haemorrhage in the pelvis and axillae was feasible. Conclusions We rediscover that clot formation within the peri-wound haematoma is an integral component of haemostasis and a feasible target for treatment of major internal bleeding using activated clotting factors delivered using a simplified angiographic approach. PMID:26414624

Acute tissue injury activates satellite cells and promotes sarcoma formation via the HGF/c-MET signaling pathway.

PubMed

Van Mater, David; Añó, Leonor; Blum, Jordan M; Webster, Micah T; Huang, WeiQiao; Williams, Nerissa; Ma, Yan; Cardona, Diana M; Fan, Chen-Ming; Kirsch, David G

2015-02-01

Some patients with soft-tissue sarcoma (STS) report a history of injury at the site of their tumor. Although this phenomenon is widely reported, there are relatively few experimental systems that have directly assessed the role of injury in sarcoma formation. We recently described a mouse model of STS whereby p53 is deleted and oncogenic Kras is activated in muscle satellite cells via a Pax7(CreER) driver following intraperitoneal injection with tamoxifen. Here, we report that after systemic injection of tamoxifen, the vast majority of Pax7-expressing cells remain quiescent despite mutation of p53 and Kras. The fate of these muscle progenitors is dramatically altered by tissue injury, which leads to faster kinetics of sarcoma formation. In adult muscle, quiescent satellite cells will transition into an active state in response to hepatocyte growth factor (HGF). We show that modulating satellite cell quiescence via intramuscular injection of HGF increases the penetrance of sarcoma formation at the site of injection, which is dependent on its cognate receptor c-MET. Unexpectedly, the tumor-promoting effect of tissue injury also requires c-Met. These results reveal a mechanism by which HGF/c-MET signaling promotes tumor formation after tissue injury in a mouse model of primary STS, and they may explain why some patients develop a STS at the site of injury. ©2014 American Association for Cancer Research.

Propagating Cell-Membrane Waves Driven by Curved Activators of Actin Polymerization

PubMed Central

Peleg, Barak; Disanza, Andrea; Scita, Giorgio; Gov, Nir

2011-01-01

Cells exhibit propagating membrane waves which involve the actin cytoskeleton. One type of such membranal waves are Circular Dorsal Ruffles (CDR) which are related to endocytosis and receptor internalization. Experimentally, CDRs have been associated with membrane bound activators of actin polymerization of concave shape. We present experimental evidence for the localization of convex membrane proteins in these structures, and their insensitivity to inhibition of myosin II contractility in immortalized mouse embryo fibroblasts cell cultures. These observations lead us to propose a theoretical model which explains the formation of these waves due to the interplay between complexes that contain activators of actin polymerization and membrane-bound curved proteins of both types of curvature (concave and convex). Our model predicts that the activity of both types of curved proteins is essential for sustaining propagating waves, which are abolished when one type of curved activator is removed. Within this model waves are initiated when the level of actin polymerization induced by the curved activators is higher than some threshold value, which allows the cell to control CDR formation. We demonstrate that the model can explain many features of CDRs, and give several testable predictions. This work demonstrates the importance of curved membrane proteins in organizing the actin cytoskeleton and cell shape. PMID:21533032

Pattern formation in three-dimensional reaction-diffusion systems

NASA Astrophysics Data System (ADS)

Callahan, T. K.; Knobloch, E.

1999-08-01

Existing group theoretic analysis of pattern formation in three dimensions [T.K. Callahan, E. Knobloch, Symmetry-breaking bifurcations on cubic lattices, Nonlinearity 10 (1997) 1179-1216] is used to make specific predictions about the formation of three-dimensional patterns in two models of the Turing instability, the Brusselator model and the Lengyel-Epstein model. Spatially periodic patterns having the periodicity of the simple cubic (SC), face-centered cubic (FCC) or body-centered cubic (BCC) lattices are considered. An efficient center manifold reduction is described and used to identify parameter regimes permitting stable lamellæ, SC, FCC, double-diamond, hexagonal prism, BCC and BCCI states. Both models possess a special wavenumber k* at which the normal form coefficients take on fixed model-independent ratios and both are described by identical bifurcation diagrams. This property is generic for two-species chemical reaction-diffusion models with a single activator and inhibitor.

Unraveling the Nature of Active Sites in Ethanol Electro-oxidation by Site-Specific Marking of a Pt Catalyst with Isotope-Labeled 13CO.

PubMed

Farias, Manuel J S; Cheuquepán, William; Tanaka, Auro A; Feliu, Juan M

2018-03-15

This works deals with the identification of preferential site-specific activation at a model Pt surface during a multiproduct reaction. The (110)-type steps of a Pt(332) surface were selectively marked by attaching isotope-labeled 13 CO molecules to them, and ethanol oxidation was probed by in situ Foureir transfrom infrared spectroscopy in order to precisely determine the specific sites at which CO 2 , acetic acid, and acetaldehyde were preferentially formed. The (110) steps were active for splitting the C-C bond, but unexpectedly, we provide evidence that the pathway of CO 2 formation was preferentially activated at (111) terraces, rather than at (110) steps. Acetaldehyde was formed at (111) terraces at potentials comparable to those for CO 2 formation also at (111) terraces, while the acetic acid formation pathway became active only when the (110) steps were released by the oxidation of adsorbed 13 CO, at potentials higher than for the formation of CO 2 at (111) terraces of the stepped surface.

What Qualifications and Skills Are Important for Digital Librarian Positions in Academic Libraries? A Job Advertisement Analysis

ERIC Educational Resources Information Center

Choi, Youngok; Rasmussen, Edie

2009-01-01

As academic library functions and activities continue to evolve, libraries have broadened the traditional library model, which focuses on management of physical resources and activities, to include a digital library model, transforming resources and services into digital formats to support teaching, learning, and research. This transition has…

A COMPUTATIONAL ANALYSIS OF BONE FORMATION IN THE CRANIAL VAULT USING A COUPLED REACTION-DIFFUSION-STRAIN MODEL

PubMed Central

LEE, CHANYOUNG; RICHTSMEIER, JOAN T.; KRAFT, REUBEN H.

2017-01-01

Bones of the murine cranial vault are formed by differentiation of mesenchymal cells into osteoblasts, a process that is primarily understood to be controlled by a cascade of reactions between extracellular molecules and cells. We assume that the process can be modeled using Turing’s reaction-diffusion equations, a mathematical model describing the pattern formation controlled by two interacting molecules (activator and inhibitor). In addition to the processes modeled by reaction-diffusion equations, we hypothesize that mechanical stimuli of the cells due to growth of the underlying brain contribute significantly to the process of cell differentiation in cranial vault development. Structural analysis of the surface of the brain was conducted to explore the effects of the mechanical strain on bone formation. We propose a mechanobiological model for the formation of cranial vault bones by coupling the reaction-diffusion model with structural mechanics. The mathematical formulation was solved using the finite volume method. The computational domain and model parameters are determined using a large collection of experimental data that provide precise three dimensional (3D) measures of murine cranial geometry and cranial vault bone formation for specific embryonic time points. The results of this study suggest that mechanical strain contributes information to specific aspects of bone formation. Our mechanobiological model predicts some key features of cranial vault bone formation that were verified by experimental observations including the relative location of ossification centers of individual vault bones, the pattern of cranial vault bone growth over time, and the position of cranial vault sutures. PMID:29225392

Phototropic bending of non-elongating and radially growing woody stems results from asymmetrical xylem formation.

PubMed

Matsuzaki, Jun; Masumori, Masaya; Tange, Takeshi

2007-05-01

Active phototropic bending of non-elongating and radially growing portion of stems (woody stems) has not been previously documented, whereas negative gravitropic bending is well known. We found phototropic bending in woody stems and searched for the underlying mechanism. We inclined 1-year-old Quercus crispula Blume seedlings and unilaterally illuminated them from a horizontal direction perpendicular to ('normal' illumination) or parallel to ('parallel' illumination) the inclination azimuth. With normal illumination, active phototropic bending and xylem formation could be evaluated separately from the negative gravitropic response and vertical deflection resulting from the weight of the seedlings. One-year-old stems with normal illumination bent significantly, with asymmetrical xylem formation towards the illuminated upper surface and side of the stem, whereas those with parallel illumination showed non-significant lateral bending, with asymmetrical xylem formation only on the upper side. A mechanical model was built on the assumption that a bending moment resulted from the asymmetrical xylem formation during phototropic bending of the woody stems. The model fitted the relationship between the observed spatial distributions of the xylem and the observed lateral bending, and thus supported the hypothesis that phototropic bending of woody stems results from asymmetrical xylem formation, as such occurs during gravitropism.

Star formation in Herschel's Monsters versus semi-analytic models

NASA Astrophysics Data System (ADS)

Gruppioni, C.; Calura, F.; Pozzi, F.; Delvecchio, I.; Berta, S.; De Lucia, G.; Fontanot, F.; Franceschini, A.; Marchetti, L.; Menci, N.; Monaco, P.; Vaccari, M.

2015-08-01

We present a direct comparison between the observed star formation rate functions (SFRFs) and the state-of-the-art predictions of semi-analytic models (SAMs) of galaxy formation and evolution. We use the PACS Evolutionary Probe Survey and Herschel Multi-tiered Extragalactic Survey data sets in the COSMOS and GOODS-South fields, combined with broad-band photometry from UV to sub-mm, to obtain total (IR+UV) instantaneous star formation rates (SFRs) for individual Herschel galaxies up to z ˜ 4, subtracted of possible active galactic nucleus (AGN) contamination. The comparison with model predictions shows that SAMs broadly reproduce the observed SFRFs up to z ˜ 2, when the observational errors on the SFR are taken into account. However, all the models seem to underpredict the bright end of the SFRF at z ≳ 2. The cause of this underprediction could lie in an improper modelling of several model ingredients, like too strong (AGN or stellar) feedback in the brighter objects or too low fallback of gas, caused by weak feedback and outflows at earlier epochs.

Shallow Depth Study Using Gravity & Magnetics Data in Central Java - Yogyakarta

NASA Astrophysics Data System (ADS)

Fawzy Ismullah M, Muhammad; Altin Massinai, Muhammad; Maria

2018-03-01

Gravity and magnetics measurements carried out in Karangsambung - Bayat - Wonosari track, Central Java - Yogyakarta region as much as 34 points for subsurface identification. Modeling and interpretation using both data at 3 sections. Section A lies on Karangsambung area and reach to 1900 m. Section A showed formation of 0.000001 - 0.0014 nT and 2.00 - 2.80 g/cm3 like alluvium, basalt and tuff. Section B lies on Wates - Yogyakarta area and reach to 1700 m. Section B showed formation of (-0.01) - 0.02 nT and 2.40 - 3.00 g/cm3 like andesite intrusive and Merapi volcano sediments. Section C lies on Bayat - Wonosari area and reach to 2000 m. Section C showed formation of 0.00016 - 0.0005 nT and 2.30 - 3.14 g/cm3 like limestone, tuff and diorite intrusive. Based on modeling results from 2D structure inversion method can identify the formation of sediments from volcano activity on Karangsambung - Bayat - Wonosari track, Central Java - Yogyakarta region. The method of this study shows potential application for identify the formation of volcano activity from 2D structure.

A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion

PubMed Central

Hetmanski, Joseph H. R.; Zindy, Egor; Schwartz, Jean-Marc; Caswell, Patrick T.

2016-01-01

Cell migration in 3D microenvironments is fundamental to development, homeostasis and the pathobiology of diseases such as cancer. Rab-coupling protein (RCP) dependent co-trafficking of α5β1 and EGFR1 promotes cancer cell invasion into fibronectin (FN) containing extracellular matrix (ECM), by potentiating EGFR1 signalling at the front of invasive cells. This promotes a switch in RhoGTPase signalling to inhibit Rac1 and activate a RhoA-ROCK-Formin homology domain-containing 3 (FHOD3) pathway and generate filopodial actin-spike protrusions which drive invasion. To further understand the signalling network that drives RCP-driven invasive migration, we generated a Boolean logical model based on existing network pathways/models, where each node can be interrogated by computational simulation. The model predicted an unanticipated feedback loop, whereby Raf/MEK/ERK signalling maintains suppression of Rac1 by inhibiting the Rac-activating Sos1-Eps8-Abi1 complex, allowing RhoA activity to predominate in invasive protrusions. MEK inhibition was sufficient to promote lamellipodia formation and oppose filopodial actin-spike formation, and led to activation of Rac and inactivation of RhoA at the leading edge of cells moving in 3D matrix. Furthermore, MEK inhibition abrogated RCP/α5β1/EGFR1-driven invasive migration. However, upon knockdown of Eps8 (to suppress the Sos1-Abi1-Eps8 complex), MEK inhibition had no effect on RhoGTPase activity and did not oppose invasive migration, suggesting that MEK-ERK signalling suppresses the Rac-activating Sos1-Abi1-Eps8 complex to maintain RhoA activity and promote filopodial actin-spike formation and invasive migration. Our study highlights the predictive potential of mathematical modelling approaches, and demonstrates that a simple intervention (MEK-inhibition) could be of therapeutic benefit in preventing invasive migration and metastasis. PMID:27138333

Effects of spiral arms on star formation in nuclear rings of barred-spiral galaxies

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

Seo, Woo-Young; Kim, Woong-Tae, E-mail: seowy@astro.snu.ac.kr, E-mail: wkim@astro.snu.ac.kr

2014-09-01

We use hydrodynamic simulations to study the effect of spiral arms on the star formation rate (SFR) in nuclear rings of barred-spiral galaxies. We find that spiral arms can be an efficient means of gas transport from the outskirts to the central parts, provided that the arms are rotating slower than the bar. While the ring star formation in models with no arms or corotating arms is active only during around the bar growth phase, arm-driven gas accretion both significantly enhances and prolongs the ring star formation in models with slow-rotating arms. The arm-enhanced SFR is larger by a factormore » of ∼3-20 than in the no-arm model, with larger values corresponding to stronger and slower arms. Arm-induced mass inflows also make dust lanes stronger. Nuclear rings in slow-arm models are ∼45% larger than in the no-arm counterparts. Star clusters that form in a nuclear ring exhibit an age gradient in the azimuthal direction only when the SFR is small, whereas no notable age gradient is found in the radial direction for models with arm-induced star formation.« less

Neural dynamics of social tie formation in economic decision-making.

PubMed

Bault, Nadège; Pelloux, Benjamin; Fahrenfort, Johannes J; Ridderinkhof, K Richard; van Winden, Frans

2015-06-01

The disposition for prosocial conduct, which contributes to cooperation as arising during social interaction, requires cortical network dynamics responsive to the development of social ties, or care about the interests of specific interaction partners. Here, we formulate a dynamic computational model that accurately predicted how tie formation, driven by the interaction history, influences decisions to contribute in a public good game. We used model-driven functional MRI to test the hypothesis that brain regions key to social interactions keep track of dynamics in tie strength. Activation in the medial prefrontal cortex (mPFC) and posterior cingulate cortex tracked the individual's public good contributions. Activation in the bilateral posterior superior temporal sulcus (pSTS), and temporo-parietal junction was modulated parametrically by the dynamically developing social tie-as estimated by our model-supporting a role of these regions in social tie formation. Activity in these two regions further reflected inter-individual differences in tie persistence and sensitivity to behavior of the interaction partner. Functional connectivity between pSTS and mPFC activations indicated that the representation of social ties is integrated in the decision process. These data reveal the brain mechanisms underlying the integration of interaction dynamics into a social tie representation which in turn influenced the individual's prosocial decisions. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis.

PubMed

Knight, Jason S; Luo, Wei; O'Dell, Alexander A; Yalavarthi, Srilakshmi; Zhao, Wenpu; Subramanian, Venkataraman; Guo, Chiao; Grenn, Robert C; Thompson, Paul R; Eitzman, Daniel T; Kaplan, Mariana J

2014-03-14

Neutrophil extracellular trap (NET) formation promotes vascular damage, thrombosis, and activation of interferon-α-producing plasmacytoid dendritic cells in diseased arteries. Peptidylarginine deiminase inhibition is a strategy that can decrease in vivo NET formation. To test whether peptidylarginine deiminase inhibition, a novel approach to targeting arterial disease, can reduce vascular damage and inhibit innate immune responses in murine models of atherosclerosis. Apolipoprotein-E (Apoe)(-/-) mice demonstrated enhanced NET formation, developed autoantibodies to NETs, and expressed high levels of interferon-α in diseased arteries. Apoe(-/-) mice were treated for 11 weeks with daily injections of Cl-amidine, a peptidylarginine deiminase inhibitor. Peptidylarginine deiminase inhibition blocked NET formation, reduced atherosclerotic lesion area, and delayed time to carotid artery thrombosis in a photochemical injury model. Decreases in atherosclerosis burden were accompanied by reduced recruitment of netting neutrophils and macrophages to arteries, as well as by reduced arterial interferon-α expression. Pharmacological interventions that block NET formation can reduce atherosclerosis burden and arterial thrombosis in murine systems. These results support a role for aberrant NET formation in the pathogenesis of atherosclerosis through modulation of innate immune responses.

Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation

PubMed Central

Huang, Mengmeng; Wei, Yan; Wang, Jun; Zhang, Yu

2016-01-01

We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1–10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633–0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926–0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation. PMID:27586851

Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation

NASA Astrophysics Data System (ADS)

Huang, Mengmeng; Wei, Yan; Wang, Jun; Zhang, Yu

2016-09-01

We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1-10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633-0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926-0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation.

Opinion formation on social media: An empirical approach

NASA Astrophysics Data System (ADS)

Xiong, Fei; Liu, Yun

2014-03-01

Opinion exchange models aim to describe the process of public opinion formation, seeking to uncover the intrinsic mechanism in social systems; however, the model results are seldom empirically justified using large-scale actual data. Online social media provide an abundance of data on opinion interaction, but the question of whether opinion models are suitable for characterizing opinion formation on social media still requires exploration. We collect a large amount of user interaction information from an actual social network, i.e., Twitter, and analyze the dynamic sentiments of users about different topics to investigate realistic opinion evolution. We find two nontrivial results from these data. First, public opinion often evolves to an ordered state in which one opinion predominates, but not to complete consensus. Second, agents are reluctant to change their opinions, and the distribution of the number of individual opinion changes follows a power law. Then, we suggest a model in which agents take external actions to express their internal opinions according to their activity. Conversely, individual actions can influence the activity and opinions of neighbors. The probability that an agent changes its opinion depends nonlinearly on the fraction of opponents who have taken an action. Simulation results show user action patterns and the evolution of public opinion in the model coincide with the empirical data. For different nonlinear parameters, the system may approach different regimes. A large decay in individual activity slows down the dynamics, but causes more ordering in the system.

Verbalization and imagery in the process of formation of operator labor skills

NASA Technical Reports Server (NTRS)

Mistyuk, V. V.

1975-01-01

Sensorimotor control tests show that mastering operational skills occurs under conditions that stimulate the operator to independent active analysis and summarization of current information with the goal of clarifying the signs and the integral images that are a model of the situation. Goal directed determination of such an image requires inner and external speech, activates and improves the thinking of the operator, accelerates the training process, increases its effectiveness, and enables the formation of strategies in anticipating the course of events.

Transcending Tradition: Situated Activity, Discourse, and Identity in Language Teacher Education

ERIC Educational Resources Information Center

Mantero, Miguel

2004-01-01

This article explores the concept of tradition within language teacher education (LTE) and extends our understanding of the elements involved in the formation of identity in preservice, second language teachers. After reviewing various perspectives of identity formation, a discursive model is offered as an approach to individual development within…

On the Star Formation-AGN Connection at zeta (is) approximately greater than 0.3

NASA Technical Reports Server (NTRS)

LaMassa, Stephanie M.; Heckman, T. M.; Ptak, Andrew; Urry, C. Megan

2013-01-01

Using the spectra of a sample of approximately 28,000 nearby obscured active galaxies from Data Release 7 of the Sloan Digital Sky Survey (SDSS), we probe the connection between active galactic nucleus (AGN) activity and star formation over a range of radial scales in the host galaxy. We use the extinction-corrected luminosity of the [O iii] 5007A line as a proxy of intrinsic AGN power and supermassive black hole (SMBH) accretion rate. The star formation rates (SFRs) are taken from the MPA-JHU value-added catalog and are measured through the 3 inch SDSS aperture. We construct matched samples of galaxies covering a range in redshifts. With increasing redshift, the projected aperture size encompasses increasing amounts of the host galaxy. This allows us to trace the radial distribution of star formation as a function of AGN luminosity. We find that the star formation becomes more centrally concentrated with increasing AGN luminosity and Eddington ratio. This implies that such circumnuclear star formation is associated with AGN activity, and that it increasingly dominates over omnipresent disk star formation at higher AGN luminosities, placing critical constraints on theoretical models that link host galaxy star formation and SMBH fueling. We parameterize this relationship and find that the star formation on radial scales (is) less than 1.7 kpc, when including a constant disk component, has a sub-linear dependence on SMBH accretion rate: SFR in proportion to solar mass(sup 0.36), suggesting that angular momentum transfer through the disk limits accretion efficiency rather than the supply from stellar mass loss.

Formation of magmatic brine lenses via focussed fluid-flow beneath volcanoes

NASA Astrophysics Data System (ADS)

Afanasyev, Andrey; Blundy, Jon; Melnik, Oleg; Sparks, Steve

2018-03-01

Many active or dormant volcanoes show regions of high electrical conductivity at depths of a few kilometres beneath the edifice. We explore the possibility that these regions represent lenses of high-salinity brine separated from a single-phase magmatic fluid containing H2O and NaCl. Since chloride-bearing fluids are highly conductive and have an exceptional capacity to transport metals, these regions can be an indication of an active hydrothermal ore-formation beneath volcanoes. To investigate this possibility we have performed hydrodynamic simulations of magma degassing into permeable rock. In our models the magma source is located at 7 km depth and the fluid salinity approximates that expected for fluids released from typical arc magmas. Our model differs from previous models of a similar process because it is (a) axisymmetric and (b) includes a static high-permeability pathway that links the magma source to the surface. This pathway simulates the presence of a volcanic conduit and/or plexus of feeder dykes that are typical of most volcanic systems. The presence of the conduit leads to a number of important hydrodynamic consequences, not observed in previous models. Importantly, we show that an annular brine lens capped by crystallised halite is likely to form above an actively degassing sub-volcanic magma body and can persist for more than 250 kyr after degassing ceases. Parametric analysis shows that brine lenses are more prevalent when the fluid is released at temperatures above the wet granite solidus, when magmatic fluid salinity is high, and when the high-permeability pathway is narrow. The calculated depth, form and electrical conductivity of our modelled system shares many features with published magnetotelluric images of volcano subsurfaces. The formation and persistence of sub-volcanic brine lenses has implications for geothermal systems and hydrothermal ore formation, although these features are not explored in the presented model.

Silanol-assisted carbinolamine formation in an amine-functionalized mesoporous silica surface: Theoretical investigation by fragmentation methods

DOE PAGES

de Lima Batista, Ana P.; Zahariev, Federico; Slowing, Igor I.; ...

2015-12-15

The aldol reaction catalyzed by an amine-substituted mesoporous silica nanoparticle (amine-MSN) surface was investigated using a large molecular cluster model (Si 392O 958C 6NH 361) combined with the surface integrated molecular orbital/molecular mechanics (SIMOMM) and fragment molecular orbital (FMO) methods. Three distinct pathways for the carbinolamine formation, the first step of the amine-catalyzed aldol reaction, are proposed and investigated in order to elucidate the role of the silanol environment on the catalytic capability of the amine-MSN material. Here the computational study reveals that the most likely mechanism involves the silanol groups actively participating in the reaction, forming and breaking covalentmore » bonds in the carbinolamine step. Furthermore, the active participation of MSN silanol groups in the reaction mechanism leads to a significant reduction in the overall energy barrier for the carbinolamine formation. In addition, a comparison between the findings using a minimal cluster model and the Si 392O 958C 6NH 361 cluster suggests that the use of larger models is important when heterogeneous catalysis problems are the target.« less

Osteoprotective effects of osthole in a mouse model of 5/6 nephrectomy through inhibiting osteoclast formation.

PubMed

Li, Xiaofeng; Xue, Chunchun; Wang, Libo; Tang, Dezhi; Huang, Jian; Zhao, Yongjian; Chen, Yan; Zhao, Dongfeng; Shi, Qi; Wang, Yongjun; Shu, Bing

2016-10-01

The present study aimed to investigate the effects of osthole on osteoclast formation and bone loss in a mouse model of 5/6 nephrectomy. The mice in control and osthole groups were treated 1 month following 5/6 nephrectomy with either a placebo or osthole, respectively. At 2 months post‑nephrectomy, the L4 vertebrae were harvested. The bone mineral density (BMD) of cancellous bone was measured using micro‑CT and tartrate‑resistant acid phosphatase (TRAP) staining was performed to evaluate osteoclast formation. Immunohistochemistry staining and reverse transcription‑quantitative polymerase chain reaction were performed to detect the expression of nuclear factor of activated T‑cells, cytoplasmic‑1 (NFATc‑1), c‑Fos, cathepsin K, Trap, matrix metalloproteinase 9 (Mmp9), osteoprotegerin (Opg) and receptor activator for nuclear factor‑κB ligand (Rankl). Bone marrow cells were cultured with osthole, and osteoclast formation was shown by TRAP staining. Primary calvaria osteoblasts were cultured with osthole, and expression levels of Opg and Rankl were detected. Compared with the sham group, the BMD of mice in model group was significantly reduced. The numbers of osteoclasts and the expression levels of NFATc‑1, c‑Fos, cathepsin K and Mmp9 were significantly increased. Compared with the control group, the mice in the osthole group exhibited increased BMD of the L4 vertebrae, a reduction in osteoclast numbers and decreased expression levels of NFATc‑1, c‑Fos, cathepsin K and Mmp9. In vitro experiments also showed that osteoclast formation was decreased following treatment with osthole. Osteoprotegerin (Opg)/receptor activator for nuclear factor‑κB ligand (Rankl) was upregulated by osthole treatment in the L4 vertebrae and in primary cultures of calvarial osteoblasts. Osthole inhibited osteoclast formation and partially reversed the bone loss induced by 5/6 nephrectomy in mice through the upregulation of OPG/RANKL.

Rediscovering the wound hematoma as a site of hemostasis during major arterial hemorrhage.

PubMed

White, N J; Mehic, E; Wang, X; Chien, D; Lim, E; St John, A E; Stern, S A; Mourad, P D; Rieger, M; Fries, D; Martinowitz, U

2015-12-01

Treatments for major internal bleeding after injury include permissive hypotension to decrease the rate of blood loss, intravenous infusion of plasma or clotting factors to improve clot formation, and rapid surgical hemostasis or arterial embolization to control bleeding vessels. Yet, little is known regarding major internal arterial hemostasis, or how these commonly used treatments might influence hemostasis. (i) To use a swine model of femoral artery bleeding to understand the perivascular hemostatic response to contained arterial hemorrhage. (ii) To directly confirm the association between hemodynamics and bleeding velocity. (iii) To observe the feasibility of delivering an activated clotting factor directly to internal sites of bleeding using a simplified angiographic approach. Ultrasound was used to measure bleeding velocity and in vivo clot formation by elastography in a swine model of contained femoral artery bleeding with fluid resuscitation. A swine model of internal pelvic and axillary artery hemorrhage was also used to demonstrate the feasibility of local delivery of an activated clotting factor. In this model, clots formed slowly within the peri-wound hematoma, but eventually contained the bleeding. Central hemodynamics correlated positively with bleeding velocity. Infusion of recombinant human activated factor VII into the injured artery near the site of major internal hemorrhage in the pelvis and axillae was feasible. We rediscovered that clot formation within the peri-wound hematoma is an integral component of hemostasis and a feasible target for the treatment of major internal bleeding using activated clotting factors delivered using a simplified angiographic approach. © 2015 International Society on Thrombosis and Haemostasis.

Plate motion changes drive Eastern Indian Ocean microcontinent formation

NASA Astrophysics Data System (ADS)

Whittaker, J. M.; Williams, S.; Halpin, J.; Wild, T.; Stilwell, J.; Jourdan, F.; Daczko, N. R.

2016-12-01

The roles of plate tectonic or mantle dynamic forces in rupturing continental lithosphere remain controversial. Particularly enigmatic is the rifting of microcontinents from mature continental rifted margin - several well-studied microcontinent calving events coincide in space and time with mantle plume activity, but the significance of plumes in driving microcontinent formation remains controversial, and a role for plate-driven processes has also been suggested. In 2011, our team discovered two new microcontinents in the eastern Indian Ocean, the Batavia and Gulden Draak microcontinents. These microcontinents are unique as they are the only surviving remnants of the now-destroyed or highly deformed Greater Indian margin and provide us with an opportunity to test existing models of microcontinent formation against new observations. Here, we explore models for microcontinent formation using our new data from the Eastern Indian Ocean in a plate tectonic reconstruction framework. We use Argon dating and paleontology results to constrain calving from greater India at 101-104 Ma. This region had been proximal to the active Kerguelen plume for 30 Myrs but we demonstrate that calving did not correspond with a burst of volcanic activity. Rather, it is likely that plume-related thermal weakening of the Indian passive margin preconditioned it for microcontinent formation but calving was triggered by changes in plate tectonic boundary forces. Changes in the relative motions between Indian and Australia led to increasing compressive forces along the long-offset Wallaby-Zenith Fracture Zone, which was eventually abandoned during the jump of the spreading ridge into the Indian continental margin.

Properties and Expected Number Counts of Active Galactic Nuclei and Their Hosts in the Far-infrared

NASA Astrophysics Data System (ADS)

Draper, A. R.; Ballantyne, D. R.

2011-03-01

Telescopes like Herschel and the Atacama Large Millimeter/submillimeter Array (ALMA) are creating new opportunities to study sources in the far-infrared (FIR), a wavelength region dominated by cold dust emission. Probing cold dust in active galaxies allows for study of the star formation history of active galactic nucleus (AGN) hosts. The FIR is also an important spectral region for observing AGNs which are heavily enshrouded by dust, such as Compton thick (CT) AGNs. By using information from deep X-ray surveys and cosmic X-ray background synthesis models, we compute Cloudy photoionization simulations which are used to predict the spectral energy distribution (SED) of AGNs in the FIR. Expected differential number counts of AGNs and their host galaxies are calculated in the Herschel bands. The expected contribution of AGNs and their hosts to the cosmic infrared background (CIRB) and the infrared luminosity density are also computed. Multiple star formation scenarios are investigated using a modified blackbody star formation SED. It is found that FIR observations at ~500 μm are an excellent tool in determining the star formation history of AGN hosts. Additionally, the AGN contribution to the CIRB can be used to determine whether star formation in AGN hosts evolves differently than in normal galaxies. The contribution of CT AGNs to the bright end differential number counts and to the bright source infrared luminosity density is a good test of AGN evolution models where quasars are triggered by major mergers.

Nitration of benzo[a]pyrene adsorbed on coal fly ash particles by nitrogen dioxide: role of thermal activation.

PubMed

Kristovich, Robert L; Dutta, Prabir K

2005-09-15

Nitration of benzo[a]pyrene (BaP) by nitrogen dioxide (NO2) adsorbed on the surface of thermally activated coal fly ash and model aluminosilicate particles led to the formation of nitrobenzo[a]pyrenes as verified by extraction and gas chromatography/mass spectrometry (GC/MS). In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was utilized to follow the nitration reaction on the surface of zeolite Y. Nitrobenzo[a]pyrene formation was observed along with the formation of nitrous acid and nitrate species. The formation of the BaP radical cation was also observed on thermally activated aluminosilicate particles by electron spin resonance (ESR) spectroscopy. On the basis of GC/MS, DRIFTS, and ESR spectroscopy results, a mechanism of nitration involving intermediate BaP radical cations generated on thermally activated aluminosilicate particles is proposed. These observations have led to the hypothesis that nitration of adsorbed polyaromatic hydrocarbons on coal fly ash by reaction with nitrogen oxides can occur in the smokestack, but with the aging of the fly ash particles, the extent of the nitration reaction will be diminished.

SRC activates TAZ for intestinal tumorigenesis and regeneration.

PubMed

Byun, Mi Ran; Hwang, Jun-Ha; Kim, A Rum; Kim, Kyung Min; Park, Jung Il; Oh, Ho Taek; Hwang, Eun Sook; Hong, Jeong-Ho

2017-12-01

Proto-oncogene tyrosine-protein kinase Src (cSRC) is involved in colorectal cancer (CRC) development and damage-induced intestinal regeneration, although the cellular mechanisms involved are poorly understood. Here, we report that transcriptional coactivator with PDZ binding domain (TAZ) is activated by cSRC, regulating CRC cell proliferation and tumor formation, where cSRC overexpression increases TAZ expression in CRC cells. In contrast, knockdown of cSRC decreases TAZ expression. Additionally, direct phosphorylation of TAZ at Tyr316 by cSRC stimulates nuclear localization and facilitates transcriptional enhancer factor TEF-3 (TEAD4)-mediated transcription. However, a TAZ phosphorylation mutant significantly decreased cell proliferation, wound healing, colony forming, and tumor formation. In a CRC mouse model, Apc Min/+ , activated SRC expression was associated with increased TAZ expression in polyps and TAZ depletion decreased polyp formation. Moreover, intestinal TAZ knockout mice had intestinal regeneration defects following γ-irradiation. Finally, significant correspondence between SRC activation and TAZ overexpression was observed in CRC patients. These results suggest that TAZ is a critical factor for SRC-mediated intestinal tumor formation and regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

PLANETESIMAL FORMATION IN MAGNETOROTATIONALLY DEAD ZONES: CRITICAL DEPENDENCE ON THE NET VERTICAL MAGNETIC FLUX

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

Okuzumi, Satoshi; Hirose, Shigenobu, E-mail: okuzumi@nagoya-u.jp

Turbulence driven by magnetorotational instability (MRI) affects planetesimal formation by inducing diffusion and collisional fragmentation of dust particles. We examine conditions preferred for planetesimal formation in MRI-inactive 'dead zones' using an analytic dead-zone model based on our recent resistive MHD simulations. We argue that successful planetesimal formation requires not only a sufficiently large dead zone (which can be produced by tiny dust grains) but also a sufficiently small net vertical magnetic flux (NVF). Although often ignored, the latter condition is indeed important since the NVF strength determines the saturation level of turbulence in MRI-active layers. We show that direct collisionalmore » formation of icy planetesimal across the fragmentation barrier is possible when the NVF strength is lower than 10 mG (for the minimum-mass solar nebula model). Formation of rocky planetesimals via the secular gravitational instability is also possible within a similar range of the NVF strength. Our results indicate that the fate of planet formation largely depends on how the NVF is radially transported in the initial disk formation and subsequent disk accretion processes.« less

Cyperus rotundus suppresses AGE formation and protein oxidation in a model of fructose-mediated protein glycoxidation.

PubMed

Ardestani, Amin; Yazdanparast, Razieh

2007-12-01

Non-enzymatic glycation, as the chain reaction between reducing sugars and the free amino groups of proteins, has been shown to correlate with severity of diabetes and its complications. Cyperus rotundus (Cyperaceae) is used both as a food to promote health and as a drug to treat certain diseases. In this study, considering the antioxidative effects of C. rotundus, we examined whether C. rotundus also protects against protein oxidation and glycoxidation. The protein glycation inhibitory activity of hydroalcoholic extract of C. rotundus was evaluated in vitro using a model of fructose-mediated protein glycoxidation. The C. rotundus extract with glycation inhibitory activity also demonstrated antioxidant activity when a ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) assays as well as metal chelating activity were applied. Fructose (100mM) increased fluorescence intensity of glycated bovine serum albumin (BSA) in terms of total AGEs during 14 days of exposure. Moreover, fructose caused more protein carbonyl (PCO) formation and also oxidized thiol groups more in glycated than in native BSA. The extract of C. rotundus at different concentrations (25-250microg/ml) has significantly decreased the formation of AGEs in term of the fluorescence intensity of glycated BSA. Furthermore, we demonstrated the significant effect of C. rotundus extract on preventing oxidative protein damages including effect on PCO formation and thiol oxidation which are believed to form under the glycoxidation process. Our results highlight the protein glycation inhibitory and antioxidant activity of C. rotundus. These results might lead to the possibility of using the plant extract or its purified active components for targeting diabetic complications.

The Learners' Mental Models of Television in Mathematics.

ERIC Educational Resources Information Center

Sumalee, Chaijaroen

1999-01-01

Examines the learners' mental models of television in actual media classroom activity by which knowledge was constructed. Findings revealed how media capabilities and the instructional designs that employ them interact with the learners and the task characteristics to influence the formation of the learners' mental models and their learning…

Analysis of the Effect of Water Activity on Ice Formation Using a New Theory of Nucleation

NASA Technical Reports Server (NTRS)

Barahona, Donifan

2013-01-01

In this work a new theory of nucleation is developed and used to investigate the effect of water activity on the formation of ice within super-cooled droplets. The new theory is based on a novel concept where the interface is assumed to be made of liquid molecules trapped by the solid matrix. Using this concept new expressions are developed for the critical ice germ size and the nucleation work, with explicit dependencies on temperature and water activity. However unlike previous approaches, the new theory does not depend on the interfacial tension between liquid and ice. Comparison against experimental results shows that the new theory is able to reproduce the observed effect of water activity on nucleation rate and freezing temperature. It allows for the first time a theoretical derivation of the constant shift in water activity between melting and nucleation. The new theory offers a consistent thermodynamic view of ice nucleation, simple enough to be applied in atmospheric models of cloud formation.

mTORC1 activation blocks BrafV600E-induced growth-arrest, but is insufficient for melanoma formation

PubMed Central

Damsky, William; Micevic, Goran; Meeth, Katrina; Muthusamy, Viswanathan; Curley, David P.; Santhankrishnan, Manjula; Erdelyi, Ildiko; Platt, James T.; Huang, Laura; Theodosakis, Nicholas; Zaidi, M. Raza; Tighe, Scott; Davies, Michael A.; Dankort, David; McMahon, Martin; Merlino, Glenn; Bardeesy, Nabeel; Bosenberg, Marcus

2014-01-01

SUMMARY BrafV600E induces benign, growth-arrested melanocytic nevus development, but also drives melanoma formation. Cdkn2a loss in BrafV600E melanocytes in mice results in rare progression to melanoma, but only after stable growth arrest as nevi. Immediate progression to melanoma is prevented by upregulation of miR-99/100 which downregulates mTOR and IGF1R signaling. mTORC1 activation through Stk11 (Lkb1) loss abrogates growth-arrest of BrafV600E melanocytic nevi, but is insufficient for complete progression to melanoma. Cdkn2a loss is associated with mTORC2 and Akt activation in human and murine melanocytic neoplasms. Simultaneous Cdkn2a and Lkb1 inactivation in BrafV600E melanocytes results in activation of both mTORC1 and mTORC2/Akt, inducing rapid melanoma formation in mice. In this model, activation of both mTORC1/2 is required for Braf-induced melanomagenesis. PMID:25584893

A study of the kinematic dynamo equation with time-dependent coefficients

NASA Technical Reports Server (NTRS)

Ko, Chung-Ming

1990-01-01

During an active star formation epoch the interstellar medium of a galaxy is in a hyperactive state, and the average turbulent velocity is higher than in the long periods between star formation epochs. The galactic magnetic field generated by dynamo action depends strongly on the turbulent velocity, so that generation of magnetic field should vary with star formation activity. This paper is a preliminary study of the kinematic dynamo equation with time-dependent coefficients simulating the time dependence of the star formation activities. Ko and Parker argued in a simple model that the thickness of the dynamo region is the most sensitive dynamo parameter. The present work shows that the effect of inflating the galactic disk suddenly is to transform a stationary magnetic field into a growing field while keeping the profile more or less intact. Plane wave solutions for a dynamo with power-law time-dependent parameters show that the field may decay first and then grow, and vice versa, which is quite different from a constant parameter dynamo.

Novel bioactivity of phosvitin in connective tissue and bone organogenesis revealed by live calvarial bone organ culture models.

PubMed

Liu, Jess; Czernick, Drew; Lin, Shih-Chun; Alasmari, Abeer; Serge, Dibart; Salih, Erdjan

2013-09-01

Egg yolk phosvitin is one of the most highly phosphorylated extracellular matrix proteins known in nature with unique physico-chemical properties deemed to be critical during ex-vivo egg embryo development. We have utilized our unique live mouse calvarial bone organ culture models under conditions which dissociates the two bone remodeling stages, viz., resorption by osteoclasts and formation by osteoblasts, to highlight important and to date unknown critical biological functions of egg phosvitin. In our resorption model live bone cultures were grown in the absence of ascorbate and were stimulated by parathyroid hormone (PTH) to undergo rapid osteoclast formation/differentiation with bone resorption. In this resorption model native phosvitin potently inhibited PTH-induced osteoclastic bone resorption with simultaneous new osteoid/bone formation in the absence of ascorbate (vitamin C). These surprising and critical observations were extended using the bone formation model in the absence of ascorbate and in the presence of phosvitin which supported the above results. The results were corroborated by analyses for calcium release or uptake, tartrate-resistant acid phosphatase activity (marker for osteoclasts), alkaline phosphatase activity (marker for osteoblasts), collagen and hydroxyproline composition, and histological and quantitative histomorphometric evaluations. The data revealed that the discovered bioactivity of phosvitin mirrors that of ascorbate during collagen synthesis and the formation of new osteoid/bone. Complementing those studies use of the synthetic collagen peptide analog and cultured calvarial osteoblasts in conjunction with mass spectrometric analysis provided results that augmented the bone organ culture work and confirmed the capacity of phosvitin to stimulate differentiation of osteoblasts, collagen synthesis, hydroxyproline formation, and biomineralization. There are striking implications and interrelationships of this affect that relates to the evolutionary inactivation of the gene of an enzyme L-gulono-γ-lactone oxidase, which is involved in the final step of ascorbate biosynthesis, in many vertebrate species including passeriform birds, reptiles and teleost fish whose egg yolk contain phosvitin. These represent examples of how developing ex-vivo embryos of such species can achieve connective tissue and skeletal system formation in the absence of ascorbate. Copyright © 2013 Elsevier Inc. All rights reserved.

Nonrandom γ-TuNA-dependent spatial pattern of microtubule nucleation at the Golgi

PubMed Central

Sanders, Anna A. W. M.; Chang, Kevin; Zhu, Xiaodong; Thoppil, Roslin J.; Holmes, William R.; Kaverina, Irina

2017-01-01

Noncentrosomal microtubule (MT) nucleation at the Golgi generates MT network asymmetry in motile vertebrate cells. Investigating the Golgi-derived MT (GDMT) distribution, we find that MT asymmetry arises from nonrandom nucleation sites at the Golgi (hotspots). Using computational simulations, we propose two plausible mechanistic models of GDMT nucleation leading to this phenotype. In the “cooperativity” model, formation of a single GDMT promotes further nucleation at the same site. In the “heterogeneous Golgi” model, MT nucleation is dramatically up-regulated at discrete and sparse locations within the Golgi. While MT clustering in hotspots is equally well described by both models, simulating MT length distributions within the cooperativity model fits the data better. Investigating the molecular mechanism underlying hotspot formation, we have found that hotspots are significantly smaller than a Golgi subdomain positive for scaffolding protein AKAP450, which is thought to recruit GDMT nucleation factors. We have further probed potential roles of known GDMT-promoting molecules, including γ-TuRC-mediated nucleation activator (γ-TuNA) domain-containing proteins and MT stabilizer CLASPs. While both γ-TuNA inhibition and lack of CLASPs resulted in drastically decreased GDMT nucleation, computational modeling revealed that only γ-TuNA inhibition suppressed hotspot formation. We conclude that hotspots require γ-TuNA activity, which facilitates clustered GDMT nucleation at distinct Golgi sites. PMID:28931596

Efficient production of L-asparaginase from Bacillus licheniformis with low-glutaminase activity: optimization, scale up and acrylamide degradation studies.

PubMed

Mahajan, Richi V; Saran, Saurabh; Kameswaran, Karthikeya; Kumar, Vinod; Saxena, R K

2012-12-01

L-Asparaginase has potential as an anti-cancer drug and for prevention of acrylamide formation in fried and baked foods. Production of the enzyme by Bacillus licheniformis (RAM-8) was optimized by process engineering using a statistical modeling approach and a maximum yield of 32.26 IU/ml was achieved. The L-asparaginase exhibited glutaminase activity of only 0.8 IU/ml and would therefore be less prone to cause the side effects associated with asparaginase therapy compared to enzyme preparations with higher glutaminase activities. When production was carried out in a 30-L bioreactor, enzyme production reached 29.94 IU/ml in 15 h. The enzyme inhibited poly-acrylamide formation in 10% acrylamide solution and reduced acrylamide formation in fried potatoes by 80%. Copyright © 2012 Elsevier Ltd. All rights reserved.

Numerical Simulation of the Global Star Formation Pattern in the LMC

NASA Astrophysics Data System (ADS)

Gardiner, L. T.; Turfus, C.

Dottori et al. (1996, ApJ 461, 742) have recently presented evidence for the idea that the observed distribution of young star clusters in the Large Magellanic Cloud (LMC) has resulted from the gravitational perturbation induced by a bar potential offset from the LMC disk center. We have constructed a dynamical model of the LMC to examine the effects of such an off-center perturbation on the global distribution of the gas and star formation activity. We have used a newly developed hybrid N-body/cellular automaton scheme for modeling star formation in galaxies which incorporates the dual mechanisms of gravitational instability and self-propagating star formation, combined with feedback of kinetic energy from star-forming regions into the interstellar medium. We find that a weak rotating bar perturbation, whose center is displaced by 0.6 kpc from the disk center, gives rise to an asymmetric spiral structure which mimics the chains of recent star formation observed in the LMC as well as delineating activity in the bar region. Large gas concentrations are produced where the spiral arms merge in the northern part of the galaxy, and such structures may have observed counterparts in giant star-forming complexes such as Constellation III in the NE part of the LMC.

Understanding the Effect of Aerosol Properties on Cloud Droplet Formation during TCAP Field Campaign Report

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

Cziczo, Daniel

2016-05-01

The formation of clouds is an essential element in understanding the Earth’s radiative budget. Liquid water clouds form when the relative humidity exceeds saturation and condensedphase water nucleates on atmospheric particulate matter. The effect of aerosol properties such as size, morphology, and composition on cloud droplet formation has been studied theoretically as well as in the laboratory and field. Almost without exception these studies have been limited to parallel measurements of aerosol properties and cloud formation or collection of material after the cloud has formed, at which point nucleation information has been lost. Studies of this sort are adequate whenmore » a large fraction of the aerosol activates, but correlations and resulting model parameterizations are much more uncertain at lower supersaturations and activated fractions.« less

Orally Active Multi-Functional Antioxidants Delay Cataract Formation in Streptozotocin (Type 1) Diabetic and Gamma-Irradiated Rats

PubMed Central

Randazzo, James; Zhang, Peng; Makita, Jun; Blessing, Karen; Kador, Peter F.

2011-01-01

Background Age-related cataract is a worldwide health care problem whose progression has been linked to oxidative stress and the accumulation of redox-active metals. Since there is no specific animal model for human age-related cataract, multiple animal models must be used to evaluate potential therapies that may delay and/or prevent cataract formation. Methods/Principal Findings Proof of concept studies were conducted to evaluate 4-(5-hydroxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8), multi-functional antioxidants that can independently chelate redox metals and quench free radicals, on their ability to delay the progression of diabetic “sugar” cataracts and gamma radiation-induced cataracts. Prior to 15 Gy of whole head irradiation, select groups of Long Evans rats received either diet containing compound 4 or 8, or a single i.p. injection of panthethine, a radioprotective agent. Compared to untreated, irradiated rats, treatment with pantethine, 4 and 8 delayed initial lens changes by 4, 47, and 38 days, respectively, and the average formation of posterior subcapsular opacities by 23, 53 and 58 days, respectively. In the second study, select groups of diabetic Sprague Dawley rats were administered chow containing compounds 4, 8 or the aldose reductase inhibitor AL1576. As anticipated, treatment with AL1576 prevented cataract by inhibiting sorbitol formation in the lens. However, compared to untreated rats, compounds 4 and 8 delayed vacuole formation by 20 days and 12 days, respectively, and cortical cataract formation by 8 and 3 days, respectively, without reducing lenticular sorbitol. Using in vitro lens culture in 30 mM xylose to model diabetic “sugar” cataract formation, western blots confirmed that multi-functional antioxidants reduced endoplasmic reticulum stress. Conclusions/Significance Multi-functional antioxidants delayed cataract formation in two diverse rat models. These studies provide a proof of concept that a general cataract treatment focused on reducing oxidative stress instead of a specific mechanism of cataractogenesis can be developed. PMID:21541328

Peptidylarginine Deiminase Inhibition Reduces Vascular Damage and Modulates Innate Immune Responses in Murine Models of Atherosclerosis

PubMed Central

Knight, Jason S.; Luo, Wei; O’Dell, Alexander A.; Yalavarthi, Srilakshmi; Zhao, Wenpu; Subramanian, Venkataraman; Guo, Chiao; Grenn, Robert C.; Thompson, Paul R.; Eitzman, Daniel T.; Kaplan, Mariana J.

2014-01-01

Rationale Neutrophil extracellular trap (NET) formation promotes vascular damage, thrombosis, and activation of interferon-α-producing plasmacytoid dendritic cells in diseased arteries. Peptidylarginine deiminase inhibition is a strategy that can decrease in vivo NET formation. Objective To test whether peptidylarginine deiminase inhibition, a novel approach to targeting arterial disease, can reduce vascular damage and inhibit innate immune responses in murine models of atherosclerosis. Methods and Results Apolipoprotein-E (Apoe)−/− mice demonstrated enhanced NET formation, developed autoantibodies to NETs, and expressed high levels of interferon-α in diseased arteries. Apoe−/− mice were treated for 11 weeks with daily injections of Cl-amidine, a peptidylarginine deiminase inhibitor. Peptidylarginine deiminase inhibition blocked NET formation, reduced atherosclerotic lesion area, and delayed time to carotid artery thrombosis in a photochemical injury model. Decreases in atherosclerosis burden were accompanied by reduced recruitment of netting neutrophils and macrophages to arteries, as well as by reduced arterial interferon-α expression. Conclusions Pharmacological interventions that block NET formation can reduce atherosclerosis burden and arterial thrombosis in murine systems. These results support a role for aberrant NET formation in the pathogenesis of atherosclerosis through modulation of innate immune responses. PMID:24425713

Think Pair Share with Formative Assessment for Junior High School Student

NASA Astrophysics Data System (ADS)

Pradana, O. R. Y.; Sujadi, I.; Pramudya, I.

2017-09-01

Geometry is a science related to abstract thinking ability so that not many students are able to understand this material well. In this case, the learning model plays a crucial role in improving student achievement. This means that a less precise learning model will cause difficulties for students. Therefore, this study provides a quantitative explanation of the Think Pair Share learning model combined with the formative assessment. This study aims to test the Think Pair Share with the formative assessment on junior high school students. This research uses a quantitative approach of Pretest-Posttest in control group and experiment group. ANOVA test and Scheffe test used to analyse the effectiveness this learning. Findings in this study are student achievement on the material geometry with Think Pair Share using formative assessment has increased significantly. This happens probably because this learning makes students become more active during learning. Hope in the future, Think Pair Share with formative assessment be a useful learning for teachers and this learning applied by the teacher around the world especially on the material geometry.

Thermal modeling using enthalpy methods to aid in the study of microstructural changes of multilayered phase change optical memories

NASA Astrophysics Data System (ADS)

Nagpal, Swati; Aurora, Aradhna

1999-11-01

In DOW type of phase change optical memories the focus has been mainly on gestate based systems due to their good overwriting capability and very high order cyclability. To avoid the material deterioration problems such as material flow, high melting point, high viscosity or high-density components such as CrTe, (which have the same refractive index) can be added to the active layer. This has led to an improved performance of overwrite cycles from 105 to 106. Material flow occurs due to void formation. Voids and sinks are formed due to porosity of the active layer because the active layer has a density lower than that of the bulk material. One of the reasons for the formation and coalescence of voids is the way in which the film is deposited viz. Sputtering which makes Ar atoms accumulate in the films during deposition. Also the mechanical strength of the protective layer effects the repeatability of the active layer. All the above mentioned processes occur during melting and re- solidification of the nano-sized spots which are laser irradiated. Since the structure of the protective layers is very important in controlling the void formation, it is very important to study the thermal modeling of the full layer structure.

Glucosamine prevents in vitro collagen degradation in chondrocytes by inhibiting advanced lipoxidation reactions and protein oxidation

PubMed Central

Tiku, Moti L; Narla, Haritha; Jain, Mohit; Yalamanchili, Praveen

2007-01-01

Osteoarthritis (OA) affects a large segment of the aging population and is a major cause of pain and disability. At present, there is no specific treatment available to prevent or retard the cartilage destruction that occurs in OA. Recently, glucosamine sulfate has received attention as a putative agent that may retard cartilage degradation in OA. The precise mechanism of action of glucosamine is not known. We investigated the effect of glucosamine in an in vitro model of cartilage collagen degradation in which collagen degradation induced by activated chondrocytes is mediated by lipid peroxidation reaction. Lipid peroxidation in chondrocytes was measured by conjugated diene formation. Protein oxidation and aldehydic adduct formation were studied by immunoblot assays. Antioxidant effect of glucosamine was also tested on malondialdehyde (thiobarbituric acid-reactive substances [TBARS]) formation on purified lipoprotein oxidation for comparison. Glucosamine sulfate and glucosamine hydrochloride in millimolar (0.1 to 50) concentrations specifically and significantly inhibited collagen degradation induced by calcium ionophore-activated chondrocytes. Glucosamine hydrochloride did not inhibit lipid peroxidation reaction in either activated chondrocytes or in copper-induced oxidation of purified lipoproteins as measured by conjugated diene formation. Glucosamine hydrochloride, in a dose-dependent manner, inhibited malondialdehyde (TBARS) formation by oxidized lipoproteins. Moreover, we show that glucosamine hydrochloride prevents lipoprotein protein oxidation and inhibits malondialdehyde adduct formation in chondrocyte cell matrix, suggesting that it inhibits advanced lipoxidation reactions. Together, the data suggest that the mechanism of decreasing collagen degradation in this in vitro model system by glucosamine may be mediated by the inhibition of advanced lipoxidation reaction, preventing the oxidation and loss of collagen matrix from labeled chondrocyte matrix. Further studies are needed to relate these in vitro findings to the retardation of cartilage degradation reported in OA trials investigating glucosamine. PMID:17686167

Disentangling AGN and Star Formation in Soft X-Rays

NASA Technical Reports Server (NTRS)

LaMassa, Stephanie M.; Heckman, T. M.; Ptak, A.

2012-01-01

We have explored the interplay of star formation and active galactic nucleus (AGN) activity in soft X-rays (0.5-2 keV) in two samples of Seyfert 2 galaxies (Sy2s). Using a combination of low-resolution CCD spectra from Chandra and XMM-Newton, we modeled the soft emission of 34 Sy2s using power-law and thermal models. For the 11 sources with high signal-to-noise Chandra imaging of the diffuse host galaxy emission, we estimate the luminosity due to star formation by removing the AGN, fitting the residual emission. The AGN and star formation contributions to the soft X-ray luminosity (i.e., L(sub x,AGN) and L(sub x,SF)) for the remaining 24 Sy2s were estimated from the power-law and thermal luminosities derived from spectral fitting. These luminosities were scaled based on a template derived from XSINGS analysis of normal star-forming galaxies. To account for errors in the luminosities derived from spectral fitting and the spread in the scaling factor, we estimated L(sub x,AGN) and L(sub x,SF))from Monte Carlo simulations. These simulated luminosities agree with L(sub x,AGN) and L(sub x,SF) derived from Chandra imaging analysis within a 3sigma confidence level. Using the infrared [Ne ii]12.8 micron and [O iv]26 micron lines as a proxy of star formation and AGN activity, respectively, we independently disentangle the contributions of these two processes to the total soft X-ray emission. This decomposition generally agrees with L(sub x,SF) and L(sub x,AGN) at the 3 sigma level. In the absence of resolvable nuclear emission, our decomposition method provides a reasonable estimate of emission due to star formation in galaxies hosting type 2 AGNs.

Alzheimer's disease pathological lesions activate the spleen tyrosine kinase.

PubMed

Schweig, Jonas Elias; Yao, Hailan; Beaulieu-Abdelahad, David; Ait-Ghezala, Ghania; Mouzon, Benoit; Crawford, Fiona; Mullan, Michael; Paris, Daniel

2017-09-06

The pathology of Alzheimer's disease (AD) is characterized by dystrophic neurites (DNs) surrounding extracellular Aβ-plaques, microgliosis, astrogliosis, intraneuronal tau hyperphosphorylation and aggregation. We have previously shown that inhibition of the spleen tyrosine kinase (Syk) lowers Aβ production and tau hyperphosphorylation in vitro and in vivo. Here, we demonstrate that Aβ-overexpressing Tg PS1/APPsw, Tg APPsw mice, and tau overexpressing Tg Tau P301S mice exhibit a pathological activation of Syk compared to wild-type littermates. Syk activation is occurring in a subset of microglia and is age-dependently increased in Aβ-plaque-associated dystrophic neurites of Tg PS1/APPsw and Tg APPsw mice. In Tg Tau P301S mice, a pure model of tauopathy, activated Syk occurs in neurons that show an accumulation of misfolded and hyperphosphorylated tau in the cortex and hippocampus. Interestingly, the tau pathology is exacerbated in neurons that display high levels of Syk activation supporting a role of Syk in the formation of tau pathological species in vivo. Importantly, human AD brain sections show both pathological Syk activation in DNs around Aβ deposits and in neurons immunopositive for pathological tau species recapitulating the data obtained in transgenic mouse models of AD. Additionally, we show that Syk overexpression leads to increased tau accumulation and promotes tau hyperphosphorylation at multiple epitopes in human neuron-like SH-SY5Y cells, further supporting a role of Syk in the formation of tau pathogenic species. Collectively, our data show that Syk activation occurs following Aβ deposition and the formation of tau pathological species. Given that we have previously shown that Syk activation also promotes Aβ formation and tau hyperphosphorylation, our data suggest that AD pathological lesions may be self-propagating via a Syk dependent mechanism highlighting Syk as an attractive therapeutic target for the treatment of AD.

Thermodynamic Derivation of the Activation Energy for Ice Nucleation

NASA Technical Reports Server (NTRS)

Barahona, D.

2015-01-01

Cirrus clouds play a key role in the radiative and hydrological balance of the upper troposphere. Their correct representation in atmospheric models requires an understanding of the microscopic processes leading to ice nucleation. A key parameter in the theoretical description of ice nucleation is the activation energy, which controls the flux of water molecules from the bulk of the liquid to the solid during the early stages of ice formation. In most studies it is estimated by direct association with the bulk properties of water, typically viscosity and self-diffusivity. As the environment in the ice-liquid interface may differ from that of the bulk, this approach may introduce bias in calculated nucleation rates. In this work a theoretical model is proposed to describe the transfer of water molecules across the ice-liquid interface. Within this framework the activation energy naturally emerges from the combination of the energy required to break hydrogen bonds in the liquid, i.e., the bulk diffusion process, and the work dissipated from the molecular rearrangement of water molecules within the ice-liquid interface. The new expression is introduced into a generalized form of classical nucleation theory. Even though no nucleation rate measurements are used to fit any of the parameters of the theory the predicted nucleation rate is in good agreement with experimental results, even at temperature as low as 190 K, where it tends to be underestimated by most models. It is shown that the activation energy has a strong dependency on temperature and a weak dependency on water activity. Such dependencies are masked by thermodynamic effects at temperatures typical of homogeneous freezing of cloud droplets; however, they may affect the formation of ice in haze aerosol particles. The new model provides an independent estimation of the activation energy and the homogeneous ice nucleation rate, and it may help to improve the interpretation of experimental results and the development of parameterizations for cloud formation.

Molecular dynamics exploration of poration and leaking caused by Kalata B1 in HIV-infected cell membrane compared to host and HIV membranes.

PubMed

Nawae, Wanapinun; Hannongbua, Supa; Ruengjitchatchawalya, Marasri

2017-06-15

The membrane disruption activities of kalata B1 (kB1) were investigated using molecular dynamics simulations with membrane models. The models were constructed to mimic the lipid microdomain formation in membranes of HIV particle, HIV-infected cell, and host cell. The differences in the lipid ratios of these membranes caused the formation of liquid ordered (lo) domains of different sizes, which affected the binding and activity of kB1. Stronger kB1 disruptive activity was observed for the membrane with small sized lo domain. Our results show that kB1 causes membrane leaking without bilayer penetration. The membrane poration mechanism involved in the disorganization of the lo domain and in cholesterol inter-leaflet translocation is described. This study enhances our understanding of the membrane activity of kB1, which may be useful for designing novel and potentially therapeutic peptides based on the kB1 framework.

Asymmetric transfer hydrogenation by synthetic catalysts in cancer cells

NASA Astrophysics Data System (ADS)

Coverdale, James P. C.; Romero-Canelón, Isolda; Sanchez-Cano, Carlos; Clarkson, Guy J.; Habtemariam, Abraha; Wills, Martin; Sadler, Peter J.

2018-03-01

Catalytic anticancer metallodrugs active at low doses could minimize side-effects, introduce novel mechanisms of action that combat resistance and widen the spectrum of anticancer-drug activity. Here we use highly stable chiral half-sandwich organometallic Os(II) arene sulfonyl diamine complexes, [Os(arene)(TsDPEN)] (TsDPEN, N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine), to achieve a highly enantioselective reduction of pyruvate, a key intermediate in metabolic pathways. Reduction is shown both in aqueous model systems and in human cancer cells, with non-toxic concentrations of sodium formate used as a hydride source. The catalytic mechanism generates selectivity towards ovarian cancer cells versus non-cancerous fibroblasts (both ovarian and lung), which are commonly used as models of healthy proliferating cells. The formate precursor N-formylmethionine was explored as an alternative to formate in PC3 prostate cancer cells, which are known to overexpress a deformylase enzyme. Transfer-hydrogenation catalysts that generate reductive stress in cancer cells offer a new approach to cancer therapy.

Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo.

PubMed

Lee, Su-Ui; Park, Sang-Joon; Kwak, Han Bok; Oh, Jaemin; Min, Yong Ki; Kim, Seong Hwan

2008-01-01

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone mass and improve bone architecture. In this study, we demonstrated that the ubiquitous plant triterpenoid, ursolic acid, enhances differentiation and mineralization of osteoblasts in vitro. We found that ursolic acid induced the expression of osteoblast-specific genes with the activation of mitogen-activated protein kinases, nuclear factor-kappaB, and activator protein-1. Additionally, noggin, an antagonist of bone morphogenetic proteins (BMPs), inhibited ursolic acid-induced osteoblast differentiation. Noggin also inhibited the activation of Smad and the induction of BMP-2 mRNA expression by ursolic acid in the late stage of osteoblast differentiation. Importantly, ursolic acid was shown to have bone-forming activity in vivo in a mouse calvarial bone formation model. A high proportion of positive immunostaining of BMP-2 was found in the nuclear region of woven bone formed by ursolic acid. These results suggested that ursolic acid has the anabolic potential to stimulate osteoblast differentiation and enhance new bone formation.

Role of cytoskeleton in regulating fusion of nucleoli: a study using the activated mouse oocyte model.

PubMed

Lian, Hua-Yu; Jiao, Guang-Zhong; Wang, Hui-Li; Tan, Xiu-Wen; Wang, Tian-Yang; Zheng, Liang-Liang; Kong, Qiao-Qiao; Tan, Jing-He

2014-09-01

Although fusion of nucleoli was observed during pronuclear development of zygotes and the behavior of nucleoli in pronuclei has been suggested as an indicator of embryonic developmental potential, the mechanism for nucleolar fusion is unclear. Although both cytoskeleton and the nucleolus are important cellular entities, there are no special reports on the relationship between the two. Role of cytoskeleton in regulating fusion of nucleoli was studied using the activated mouse oocyte model. Mouse oocytes were cultured for 6 h in activating medium (Ca²⁺-free CZB medium containing 10 mM SrCl₂) supplemented with or without inhibitors for cytoskeleton or protein synthesis before pronuclear formation, nucleolar fusion, and the activity of maturation-promoting factor (MPF) were examined. Whereas treatment with microfilament inhibitor cytochalasin D or B or intermediate filament inhibitor acrylamide suppressed nucleolar fusion efficiently, treatment with microtubule inhibitor demecolcine or nocodazole or protein synthesis inhibitor cycloheximide had no effect. The cytochalasin D- or acrylamide-sensitive temporal window coincided well with the reported temporal window for nucleolar fusion in activated oocytes. Whereas a continuous incubation with demecolcine prevented pronuclear formation, pronuclei formed normally when demecolcine was excluded during the first hour of activation treatment when the MPF activity dropped dramatically. The results suggest that 1) microfilaments and intermediate filaments but not microtubules support nucleolar fusion, 2) proteins required for nucleolar fusion including microfilaments and intermediate filaments are not de novo synthesized, and 3) microtubule disruption prevents pronuclear formation by activating MPF. © 2014 by the Society for the Study of Reproduction, Inc.

Pattern formation and collective effects in populations of magnetic microswimmers

NASA Astrophysics Data System (ADS)

Vach, Peter J.; Walker, Debora; Fischer, Peer; Fratzl, Peter; Faivre, Damien

2017-03-01

Self-propelled particles are one prototype of synthetic active matter used to understand complex biological processes, such as the coordination of movement in bacterial colonies or schools of fishes. Collective patterns such as clusters were observed for such systems, reproducing features of biological organization. However, one limitation of this model is that the synthetic assemblies are made of identical individuals. Here we introduce an active system based on magnetic particles at colloidal scales. We use identical but also randomly-shaped magnetic micropropellers and show that they exhibit dynamic and reversible pattern formation.

Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

PubMed Central

Radulescu, S; Ridgway, R A; Cordero, J; Athineos, D; Salgueiro, P; Poulsom, R; Neumann, J; Jung, A; Patel, S; Woodgett, J; Barker, N; Pritchard, D M; Oien, K; Sansom, O J

2013-01-01

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach. PMID:22665058

Nucleation in mesoscopic systems under transient conditions: Peptide-induced pore formation in vesicles

NASA Astrophysics Data System (ADS)

Zhdanov, Vladimir P.; Höök, Fredrik

2013-04-01

Attachment of lytic peptides to the lipid membrane of virions or bacteria is often accompanied by their aggregation and pore formation, resulting eventually in membrane rupture and pathogen neutralization. The membrane rupture may occur gradually via formation of many pores or abruptly after the formation of the first pore. In academic studies, this process is observed during interaction of peptides with lipid vesicles. We present an analytical model and the corresponding Monte Carlo simulations focused on the pore formation in such situations. Specifically, we calculate the time of the first nucleation-limited pore-formation event and show the distribution of this time in the regime when the fluctuations of the number of peptides attached to a vesicle are appreciable. The results obtained are used to clarify the mechanism of the pore formation and membrane destabilization observed recently during interaction of highly active α-helical peptide with sub-100-nm lipid vesicles that mimic enveloped viruses with nanoscale membrane curvature. The model proposed and the analysis presented are generic and may be applicable to other meso- and nanosystems.

Three-dimensional representations of salt-dome margins at four active strategic petroleum reserve sites.

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

Rautman, Christopher Arthur; Stein, Joshua S.

2003-01-01

Existing paper-based site characterization models of salt domes at the four active U.S. Strategic Petroleum Reserve sites have been converted to digital format and visualized using modern computer software. The four sites are the Bayou Choctaw dome in Iberville Parish, Louisiana; the Big Hill dome in Jefferson County, Texas; the Bryan Mound dome in Brazoria County, Texas; and the West Hackberry dome in Cameron Parish, Louisiana. A new modeling algorithm has been developed to overcome limitations of many standard geological modeling software packages in order to deal with structurally overhanging salt margins that are typical of many salt domes. Thismore » algorithm, and the implementing computer program, make use of the existing interpretive modeling conducted manually using professional geological judgement and presented in two dimensions in the original site characterization reports as structure contour maps on the top of salt. The algorithm makes use of concepts of finite-element meshes of general engineering usage. Although the specific implementation of the algorithm described in this report and the resulting output files are tailored to the modeling and visualization software used to construct the figures contained herein, the algorithm itself is generic and other implementations and output formats are possible. The graphical visualizations of the salt domes at the four Strategic Petroleum Reserve sites are believed to be major improvements over the previously available two-dimensional representations of the domes via conventional geologic drawings (cross sections and contour maps). Additionally, the numerical mesh files produced by this modeling activity are available for import into and display by other software routines. The mesh data are not explicitly tabulated in this report; however an electronic version in simple ASCII format is included on a PC-based compact disk.« less

A Simple Rule for Dendritic Spine and Axonal Bouton Formation Can Account for Cortical Reorganization after Focal Retinal Lesions

PubMed Central

Butz, Markus; van Ooyen, Arjen

2013-01-01

Lasting alterations in sensory input trigger massive structural and functional adaptations in cortical networks. The principles governing these experience-dependent changes are, however, poorly understood. Here, we examine whether a simple rule based on the neurons' need for homeostasis in electrical activity may serve as driving force for cortical reorganization. According to this rule, a neuron creates new spines and boutons when its level of electrical activity is below a homeostatic set-point and decreases the number of spines and boutons when its activity exceeds this set-point. In addition, neurons need a minimum level of activity to form spines and boutons. Spine and bouton formation depends solely on the neuron's own activity level, and synapses are formed by merging spines and boutons independently of activity. Using a novel computational model, we show that this simple growth rule produces neuron and network changes as observed in the visual cortex after focal retinal lesions. In the model, as in the cortex, the turnover of dendritic spines was increased strongest in the center of the lesion projection zone, while axonal boutons displayed a marked overshoot followed by pruning. Moreover, the decrease in external input was compensated for by the formation of new horizontal connections, which caused a retinotopic remapping. Homeostatic regulation may provide a unifying framework for understanding cortical reorganization, including network repair in degenerative diseases or following focal stroke. PMID:24130472

Experimental and Computational Analysis of Polyglutamine-Mediated Cytotoxicity

PubMed Central

Tang, Matthew Y.; Proctor, Carole J.; Woulfe, John; Gray, Douglas A.

2010-01-01

Expanded polyglutamine (polyQ) proteins are known to be the causative agents of a number of human neurodegenerative diseases but the molecular basis of their cytoxicity is still poorly understood. PolyQ tracts may impede the activity of the proteasome, and evidence from single cell imaging suggests that the sequestration of polyQ into inclusion bodies can reduce the proteasomal burden and promote cell survival, at least in the short term. The presence of misfolded protein also leads to activation of stress kinases such as p38MAPK, which can be cytotoxic. The relationships of these systems are not well understood. We have used fluorescent reporter systems imaged in living cells, and stochastic computer modeling to explore the relationships of polyQ, p38MAPK activation, generation of reactive oxygen species (ROS), proteasome inhibition, and inclusion body formation. In cells expressing a polyQ protein inclusion, body formation was preceded by proteasome inhibition but cytotoxicity was greatly reduced by administration of a p38MAPK inhibitor. Computer simulations suggested that without the generation of ROS, the proteasome inhibition and activation of p38MAPK would have significantly reduced toxicity. Our data suggest a vicious cycle of stress kinase activation and proteasome inhibition that is ultimately lethal to cells. There was close agreement between experimental data and the predictions of a stochastic computer model, supporting a central role for proteasome inhibition and p38MAPK activation in inclusion body formation and ROS-mediated cell death. PMID:20885783

Systems biology derived source-sink mechanism of BMP gradient formation

PubMed Central

Zinski, Joseph; Bu, Ye; Wang, Xu; Dou, Wei

2017-01-01

A morphogen gradient of Bone Morphogenetic Protein (BMP) signaling patterns the dorsoventral embryonic axis of vertebrates and invertebrates. The prevailing view in vertebrates for BMP gradient formation is through a counter-gradient of BMP antagonists, often along with ligand shuttling to generate peak signaling levels. To delineate the mechanism in zebrafish, we precisely quantified the BMP activity gradient in wild-type and mutant embryos and combined these data with a mathematical model-based computational screen to test hypotheses for gradient formation. Our analysis ruled out a BMP shuttling mechanism and a bmp transcriptionally-informed gradient mechanism. Surprisingly, rather than supporting a counter-gradient mechanism, our analyses support a fourth model, a source-sink mechanism, which relies on a restricted BMP antagonist distribution acting as a sink that drives BMP flux dorsally and gradient formation. We measured Bmp2 diffusion and found that it supports the source-sink model, suggesting a new mechanism to shape BMP gradients during development. PMID:28826472

Systems biology derived source-sink mechanism of BMP gradient formation.

PubMed

Zinski, Joseph; Bu, Ye; Wang, Xu; Dou, Wei; Umulis, David; Mullins, Mary C

2017-08-09

A morphogen gradient of Bone Morphogenetic Protein (BMP) signaling patterns the dorsoventral embryonic axis of vertebrates and invertebrates. The prevailing view in vertebrates for BMP gradient formation is through a counter-gradient of BMP antagonists, often along with ligand shuttling to generate peak signaling levels. To delineate the mechanism in zebrafish, we precisely quantified the BMP activity gradient in wild-type and mutant embryos and combined these data with a mathematical model-based computational screen to test hypotheses for gradient formation. Our analysis ruled out a BMP shuttling mechanism and a bmp transcriptionally-informed gradient mechanism. Surprisingly, rather than supporting a counter-gradient mechanism, our analyses support a fourth model, a source-sink mechanism, which relies on a restricted BMP antagonist distribution acting as a sink that drives BMP flux dorsally and gradient formation. We measured Bmp2 diffusion and found that it supports the source-sink model, suggesting a new mechanism to shape BMP gradients during development.

Kinetics and mechanism of nickel ferrite formation under high temperature ultrasonic treatment.

PubMed

Baranchikov, Alexander Ye; Ivanov, Vladimir K; Tretyakov, Yuri D

2007-02-01

The effect of simultaneous ultrasonic and thermal treatment on kinetics and mechanism of nickel ferrite formation was studied. It was established that sonication leads to notable increase of the mean rate of this reaction and decrease of effective activation energy from 190+/-5 to 125+/-7 kJ/mol. XRD data show that ultrasonic treatment significantly affects the microstructure of both initial reagent (Fe(2)O(3)) and reaction product (NiFe(2)O(4)) thus promoting formation of well developed reaction zone. A general model of ferrite formation mechanism under high temperature ultrasonic treatment was proposed.

Evidence for a role of eosinophils in blister formation in bullous pemphigoid.

PubMed

de Graauw, E; Sitaru, C; Horn, M; Borradori, L; Yousefi, S; Simon, H-U; Simon, D

2017-07-01

Bullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear. To investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal-epidermal separation (DES). In an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium, DNase or blocking F(ab') 2 fragments to CD16, CD18, CD32 and CD64. Dermal-epidermal separation was assessed by light microscopy studies and quantified using Fiji software. Following activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal-epidermal junction of ex vivo skin. Dermal-epidermal separation was significantly reduced by blocking any of the following: Fcγ receptor binding (P = 0.048), eosinophil adhesion (P = 0.046), reactive oxygen species (ROS) production (P = 0.002), degranulation (P < 0.0001) or eosinophil extracellular trap (EET) formation (P = 0.048). Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. Dermal-epidermal separation by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An extended model of heartwood secondary metabolism informed by functional genomics.

PubMed

Celedon, Jose M; Bohlmann, Jörg

2018-03-01

The development of heartwood (HW) and the associated accumulation of secondary metabolites, which are also known as 'specialized metabolites' or 'extractives', is an important feature of tree biology. Heartwood development can affect tree health with broader implications for forest health. Heartwood development also defines a variety of wood quality traits that are important in the forest industry such as durability and colour of wood products. In the bioproducts industry, HW provides a source of high-value small molecules such as fragrances and antimicrobials. The HW properties of decay resistance in living trees, durability and colour of wood products, and small molecule bioproducts are largely defined by secondary metabolites, the biosynthesis of which appears to be activated during the onset of HW formation. Traditionally, it is thought that HW formation involves a spike in the activity of secondary metabolism in parenchyma cells in a transition zone between sapwood and HW, followed by programmed cell-death. The resulting HW tissue is thought to consist entirely of dead cells. Here, we discuss a variation of existing models of HW formation, based on the recent discovery of HW-specific transcriptome signatures of terpenoid biosynthesis in sandalwood (Santalum album L.) that invokes the activity of living cells in HW.

An Exploration of the Phases and Structure Formation in Active Nematic Materials Using an Overdamped Continuum Theory

NASA Astrophysics Data System (ADS)

Putzig, Elias

Active nematics are a class of nonequilibrium systems which have received much attention in the form of continuum models in recent years. For the dense, highly ordered case which is of particular interest, these models focus almost exclusively on suspensions of active particles in which the flow of the medium plays a key role in the dynamical equations. Many active nematics, however, reside at an interface or on a surface where friction excludes the effects of long-range flow. In the following pages we shall construct a general model which describes these systems with overdamped dynamical equations. Through numerical and analytical investigation we detail how many of the striking nonequilibrium behaviors of active nematics arise in such systems. We shall first discuss how the activity in these systems gives rise to an instability in the nematic ordered state. This instability leads to phase-separation in which bands of ordered active nematic are interspersed with bands of the disordered phase. We expose the factors which control the density contrast and the stability of these bands through numerical investigation. We then turn to the highly ordered phase of active nematic materials, in which striking nonequilibrium behaviors such as the spontaneous formation, self-propulsion, and ordering of charge-half defects occurs. We extend the overdamped model of an active nematic to describe these behaviors by including the advection of the director by the active forces in the dynamical equations. We find a new instability in the ordered state which gives rise to defect formation, as well as an analog of the instability which is seen in models of active nematic suspensions. Through numerical investigations we expose a rich phenomenology in the neighborhood of this new instability. The phenomenology includes a state in which the orientations of motile, transient defects form long-range order. This is the first continuum model to contain such a state, and we compare the behavior seen here with similar states seen in the experiments and simulations of Stephen DeCamp and Gabriel Redner et. al. [1]. Finally, we propose the measurement of defect shape as a mechanism for the comparison between continuum theories of active nematics and the experimental and simulated realiza- tions of these systems. We present a method for making these measurements which allows for averaging and statistical analysis, and use this method to determine how the shapes of defects depend on the parameters of our continuum theory. We then compare these with the shapes of defects which we measure in the experiments and simulations mentioned above in order to place these systems in the parameter space of our model. It is our hope that this mechanism for comparison between models and realizations of active nematics will provide a key to pairing the two more closely.

Formation, structure, and evolution of boiling nucleus and interfacial tension between bulk liquid phase and nucleus

NASA Astrophysics Data System (ADS)

Wang, Xiao-Dong; Peng, Xiao-Feng; Tian, Yong; Wang, Bu-Xuan

2005-05-01

In this paper, the concept of the molecular free path is introduced to derive a criterion distinguishing active molecules from inactive molecules in liquid phase. A concept of the critical aggregation concentration (CAC) of active molecules is proposed to describe the physical configuration before the formation of a nucleus during vapor-liquid phase transition. All active molecules exist as monomers when the concentration of active molecules is lower than CAC, while the active molecules will generate aggregation once the concentration of the active molecules reaches CAC. However, these aggregates with aggregation number, N, smaller than five can steadily exist in bulk phase. The other excess active molecules can only produce infinite aggregation and form a critical nucleus of vapor-liquid phase transition. Without any outer perturbation the state point of CAC corresponds to the critical superheated or supercooled state. Meanwhile, a model of two-region structure of a nucleus is proposed to describe nucleus evolution. The interfacial tension between bulk liquid phase and nucleus is dependent of the density gradient in the transition region and varies with the structure change of the transition region. With the interfacial tension calculated using this model, the predicted nucleation rate is very close to the experimental measurement. Furthermore, this model and associated analysis provides solid theoretical evidences to clarify the definition of nucleation rate and understand nucleation phenomenon with the insight into the physical nature.

Iron catalyst chemistry in modeling a high-pressure carbon monoxide nanotube reactor

NASA Technical Reports Server (NTRS)

Scott, Carl D.; Povitsky, Alexander; Dateo, Christopher; Gokcen, Tahir; Willis, Peter A.; Smalley, Richard E.

2003-01-01

The high-pressure carbon monoxide (HiPco) technique for producing single-wall carbon nanotubes (SWNTs) is analyzed with the use of a chemical reaction model coupled with flow properties calculated along streamlines, calculated by the FLUENT code for pure carbon monoxide. Cold iron pentacarbonyl, diluted in CO at about 30 atmospheres, is injected into a conical mixing zone, where hot CO is also introduced via three jets at 30 degrees with respect to the axis. Hot CO decomposes the Fe(CO)5 to release atomic Fe. Then iron nucleates and forms clusters that catalyze the formation of SWNTs by a disproportionation reaction (Boudouard) of CO on Fe-containing clusters. Alternative nucleation rates are estimated from the theory of hard sphere collision dynamics with an activation energy barrier. The rate coefficient for carbon nanotube growth is estimated from activation energies in the literature. The calculated growth was found be about an order of magnitude greater than measured, regardless of the nucleation rate. A study of cluster formation in an incubation zone prior to injection into the reactor shows that direct dimer formation from Fe atoms is not as important as formation via an exchange reaction of Fe with CO in FeCO.

Iron catalyst chemistry in modeling a high-pressure carbon monoxide nanotube reactor.

PubMed

Scott, Carl D; Povitsky, Alexander; Dateo, Christopher; Gökçen, Tahir; Willis, Peter A; Smalley, Richard E

2003-01-01

The high-pressure carbon monoxide (HiPco) technique for producing single-wall carbon nanotubes (SWNTs) is analyzed with the use of a chemical reaction model coupled with flow properties calculated along streamlines, calculated by the FLUENT code for pure carbon monoxide. Cold iron pentacarbonyl, diluted in CO at about 30 atmospheres, is injected into a conical mixing zone, where hot CO is also introduced via three jets at 30 degrees with respect to the axis. Hot CO decomposes the Fe(CO)5 to release atomic Fe. Then iron nucleates and forms clusters that catalyze the formation of SWNTs by a disproportionation reaction (Boudouard) of CO on Fe-containing clusters. Alternative nucleation rates are estimated from the theory of hard sphere collision dynamics with an activation energy barrier. The rate coefficient for carbon nanotube growth is estimated from activation energies in the literature. The calculated growth was found be about an order of magnitude greater than measured, regardless of the nucleation rate. A study of cluster formation in an incubation zone prior to injection into the reactor shows that direct dimer formation from Fe atoms is not as important as formation via an exchange reaction of Fe with CO in FeCO.

Active Management of Integrated Geothermal-CO2 Storage Reservoirs in Sedimentary Formations

DOE Data Explorer

Buscheck, Thomas A.

2012-01-01

Active Management of Integrated Geothermal–CO2 Storage Reservoirs in Sedimentary Formations: An Approach to Improve Energy Recovery and Mitigate Risk : FY1 Final Report The purpose of phase 1 is to determine the feasibility of integrating geologic CO2 storage (GCS) with geothermal energy production. Phase 1 includes reservoir analyses to determine injector/producer well schemes that balance the generation of economically useful flow rates at the producers with the need to manage reservoir overpressure to reduce the risks associated with overpressure, such as induced seismicity and CO2 leakage to overlying aquifers. This submittal contains input and output files of the reservoir model analyses. A reservoir-model "index-html" file was sent in a previous submittal to organize the reservoir-model input and output files according to sections of the FY1 Final Report to which they pertain. The recipient should save the file: Reservoir-models-inputs-outputs-index.html in the same directory that the files: Section2.1.*.tar.gz files are saved in.

Active Management of Integrated Geothermal-CO2 Storage Reservoirs in Sedimentary Formations

DOE Data Explorer

Buscheck, Thomas A.

2000-01-01

Active Management of Integrated Geothermal–CO2 Storage Reservoirs in Sedimentary Formations: An Approach to Improve Energy Recovery and Mitigate Risk: FY1 Final Report The purpose of phase 1 is to determine the feasibility of integrating geologic CO2 storage (GCS) with geothermal energy production. Phase 1 includes reservoir analyses to determine injector/producer well schemes that balance the generation of economically useful flow rates at the producers with the need to manage reservoir overpressure to reduce the risks associated with overpressure, such as induced seismicity and CO2 leakage to overlying aquifers. This submittal contains input and output files of the reservoir model analyses. A reservoir-model "index-html" file was sent in a previous submittal to organize the reservoir-model input and output files according to sections of the FY1 Final Report to which they pertain. The recipient should save the file: Reservoir-models-inputs-outputs-index.html in the same directory that the files: Section2.1.*.tar.gz files are saved in.

A mouse model of mitochondrial complex III dysfunction induced by myxothiazol

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

Davoudi, Mina; Kallijärvi, Jukka; Marjavaara, Sanna

2014-04-18

Highlights: • Reversible chemical inhibition of complex III in wild type mouse. • Myxothiazol causes decreased complex III activity in mouse liver. • The model is useful for therapeutic trials to improve mitochondrial function. - Abstract: Myxothiazol is a respiratory chain complex III (CIII) inhibitor that binds to the ubiquinol oxidation site Qo of CIII. It blocks electron transfer from ubiquinol to cytochrome b and thus inhibits CIII activity. It has been utilized as a tool in studies of respiratory chain function in in vitro and cell culture models. We developed a mouse model of biochemically induced and reversible CIIImore » inhibition using myxothiazol. We administered myxothiazol intraperitoneally at a dose of 0.56 mg/kg to C57Bl/J6 mice every 24 h and assessed CIII activity, histology, lipid content, supercomplex formation, and gene expression in the livers of the mice. A reversible CIII activity decrease to 50% of control value occurred at 2 h post-injection. At 74 h only minor histological changes in the liver were found, supercomplex formation was preserved and no significant changes in the expression of genes indicating hepatotoxicity or inflammation were found. Thus, myxothiazol-induced CIII inhibition can be induced in mice for four days in a row without overt hepatotoxicity or lethality. This model could be utilized in further studies of respiratory chain function and pharmacological approaches to mitochondrial hepatopathies.« less

Abietic acid isolated from pine resin (Resina Pini) enhances angiogenesis in HUVECs and accelerates cutaneous wound healing in mice.

PubMed

Park, Jun Yeon; Lee, Yun Kyung; Lee, Dong-Soo; Yoo, Jeong-Eun; Shin, Myoung-Sook; Yamabe, Noriko; Kim, Su-Nam; Lee, Seulah; Kim, Ki Hyun; Lee, Hae-Jeung; Roh, Seok Sun; Kang, Ki Sung

2017-05-05

Resin known as Resina Pini is listed in the Korean and Japanese pharmacopoeias and has been used for treating skin wounds and inflammation. Resin is composed of more than 50% abietic acid and 10% neutral substances. In the present study, the wound-healing effects of abietic acid and the possible underlying mechanism of action were investigated in various in vitro and in vivo models. The effects of abietic acid on tube formation and migration were measured in human umbilical vein vascular endothelial cells (HUVECs). Protein expression of mitogen-activated protein kinase (MAPK) activation was evaluated via Western blotting analysis. The wound-healing effects of abietic acid were assessed using a mouse model of cutaneous wounds. The results showed that abietic acid enhanced cell migration and tube formation in HUVECs. Abietic acid induced significant angiogenic potential, which is associated with upregulation of extracellular signal-regulated kinase (ERK) and p38 expression. Additionally, 0.8μM abietic acid-treated groups showed accelerated wound closure compared to the controls in a mouse model of cutaneous wounds. The current data indicate that abietic acid treatment elevated cell migration and tube formation in HUVECs by the activation of ERK and p38 MAPKs. We suggest that abietic acid can be developed as a wound-healing agent. Copyright © 2017 Elsevier Ltd. All rights reserved.

Patient-derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis.

PubMed

Eyre, Rachel; Alférez, Denis G; Spence, Kath; Kamal, Mohamed; Shaw, Frances L; Simões, Bruno M; Santiago-Gómez, Angélica; Sarmiento-Castro, Aida; Bramley, Maria; Absar, Mohammed; Saad, Zahida; Chatterjee, Sumohan; Kirwan, Cliona; Gandhi, Ashu; Armstrong, Anne C; Wardley, Andrew M; O'Brien, Ciara S; Farnie, Gillian; Howell, Sacha J; Clarke, Robert B

2016-12-01

Breast cancer specific mortality results from tumour cell dissemination and metastatic colonisation. Identification of the cells and processes responsible for metastasis will enable better prevention and control of metastatic disease, thus reducing relapse and mortality. To better understand these processes, we prospectively collected 307 patient-derived breast cancer samples (n = 195 early breast cancers (EBC) and n = 112 metastatic samples (MBC)). We assessed colony-forming activity in vitro by growing isolated cells in both primary (formation) and secondary (self-renewal) mammosphere culture, and tumour initiating activity in vivo through subcutaneous transplantation of fragments or cells into mice. Metastatic samples formed primary mammosphere colonies significantly more frequently than early breast cancers and had significantly higher primary mammosphere colony formation efficiency (0.9 % vs. 0.6 %; p < 0.0001). Tumour initiation in vivo was significantly higher in metastatic than early breast cancer samples (63 % vs. 38 %, p = 0.04). Of 144 breast cancer samples implanted in vivo, we established 20 stable patient-derived xenograft (PDX) models at passage 2 or greater. Lung metastases were detected in mice from 14 PDX models. Mammosphere colony formation in vitro significantly correlated with the ability of a tumour to metastasise to the lungs in vivo (p = 0.05), but not with subcutaneous tumour initiation. In summary, the breast cancer stem cell activities of colony formation and tumour initiation are increased in metastatic compared to early samples, and predict metastasis in vivo. These results suggest that breast stem cell activity will predict for poor outcome tumours, and therapy targeting this activity will improve outcomes for patients with metastatic disease.

Slow Starter Enzymes: Role of Active Site Architecture in the Catalytic Control in the Biosynthesis of Taxadiene by Taxadiene Synthase.

PubMed

Ansbacher, Tamar; Freud, Yehoshua; Major, Dan Thomas

2018-05-23

Taxadiene synthase (TXS) catalyzes the formation of the natural product Taxa-4(5),11(12)-diene (henceforth Taxadiene). Taxadiene is the precursor in the formation of Taxol, which is an important natural anti-cancer agent. In the current study, we present a detailed mechanistic view of the biosynthesis of Taxadiene by TXS, using a hybrid quantum mechanics-molecular mechanics potential in conjunction with free energy simulation methods. The obtained free energy landscape displays initial endergonic steps followed by a step-wise downhill profile, which is an emerging free energy fingerprint for type I terpene synthases. We identify an active site Trp residue (W753) as a key feature of the TXS active site architecture and propose that this residue stabilized intermediate cations via -cation interactions. To validate our proposed active TXS model, we examine a previously reported W753H mutation, which leads to exclusive formation of the side product, cembrene A. The simulations of the W753H mutant show that in the mutant structure, the His side-chain is in perfect position to deprotonate the cembrenyl cation en route to cembrene formation, and that this abortive deprotonation is an energetically facile process. Based on the current model, we propose that an analogous mutation of Y841 to His could possibly lead to verticillane. The current simulations stress the importance of precise positioning of key active site residues in stabilizing intermediate carbocations. In view of the great pharmaceutical importance of taxadiene, a detailed understanding of the TXS mechanism can provide important clues towards a synthetic strategy for taxol manufacturing.

Fracture formation post impact on Enceladus?

NASA Astrophysics Data System (ADS)

Craft, Kathleen; Roberts, James

2017-10-01

Saturn’s small icy moon Enceladus was observed by the Cassini mission to have jets of ice and vapor emanating from its southern polar terrain (SPT), creating a plume. The fact that the activity is only observed in one region has not been well explained. Hypotheses include a regional sea beneath the SPT or a global ocean that is thicker beneath the SPT, which feeds a group of fractures observed there called the tiger stripes. As Enceladus orbits Saturn, stresses acting on the moon may open and close the fractures enabling interior volatiles to escape and form the plume. Here we investigate how these fractures could have formed and the activity begun. We propose that an impact could have either punctured through or caused substantial melt and fracturing in an ice shell connecting to a liquid layer below. Our goal is to determine whether a formation of fractures resembling the tiger stripes could emerge post-impact.Previous work by Roberts and Stickle (LPSC 2017, #1955) modeled an impact into an ice shell over an ocean and calculated penetration depth and melt temperatures and volumes through the shell thickness. Fracturing would occur during and after the impact, the crater would collapse, water would begin to refreeze and subsequent fluid exchange would occur. Working forward from a point after impact and as the ice shell begins refreezing, we performed finite element modeling to simulate the probable formation of fractures based on the resulting stress regime. Here we explore fracture formation for shells ranging from 1 km to 5 km thick (consistent with gravity and libration studies), to explore formation as the shell cools and thickens through time. We emplaced several fractures, penetrating either entirely or partially across the base to surface. Fracture interactions, tidal stress forcing with orbital true anomalies and ocean water pressurization are considered free parameters in the model. We present results for a number of parameter value combinations and quantify fracture formation sensitivities to model parameters.

The engram formation and the global oscillations of CA3.

PubMed

Ventriglia, Francesco

2008-12-01

The investigation on the conditions which cause global population oscillatory activities in neural fields, originated some years ago with reference to a kinetic theory of neural systems, as been further deepened in this paper. In particular, the genesis of sharp waves and of some rhythmic activities, such as theta and gamma rhythms, of the hippocampal CA3 field, behaviorally important for their links to learning and memory, has been analyzed with more details. To this aim, the modeling-computational framework previously devised for the study of activities in large neural fields, has been enhanced in such a way that a greater number of biological features, extended dendritic trees-in particular, could be taken into account. By using that methodology, a two-dimensional model of the entire CA3 field has been described and its activity, as it results from the several external inputs impinging on it, has been simulated. As a consequence of these investigations, some hypotheses have been elaborated about the possible function of global oscillatory activities of neural populations of Hippocampus in the engram formation.

Iceland as a Model for Chemical Alteration on Mars

NASA Technical Reports Server (NTRS)

Bishop, Janice L.; Schiffman, P.; Murad, E.; Southard, R.; DeVincenzi, Donald L. (Technical Monitor)

2001-01-01

Subglacial volcanic activity on Iceland has led to the formation of a variety of silicate and iron oxide-rich alteration products that may serve as a model for chemical alteration on Mars. Multiple palagonitic tuffs, altered pillow lavas, hydrothermal springs and alteration at glacial run-off streams were observed during a recent field trip in Iceland. Formation of alteration products and ferrihydrite in similar environments on Mars may have contributed to the ferric oxide-rich surface material there. The spectral and chemical properties of Icelandic alteration products and ferrihydrites are presented here.

Snakes on a plane: modeling flexible active nematics

NASA Astrophysics Data System (ADS)

Selinger, Robin

Active soft matter systems of self-propelled rod-shaped particles exhibit ordered phases and collective behavior that are remarkably different from their passive analogs. In nature, many self-propelled rod-shaped particles, such as gliding bacteria and kinesin-driven microtubules, are flexible and can bend. We model these ``living liquid crystals'' to explore their phase behavior, dynamics, and pattern formation. We model particles as short polymers via molecular dynamics with a Langevin thermostat and various types of activity, substrate, and environments. For self-propelled polar particles gliding on a solid substrate, we map out the phase diagram as a function of particle density and flexibility. We compare simulated defect structures to those observed in colonies of gliding myxobacteria; compare spooling behavior to that observed in microtubule gliding assays; and analyze emergence of nematic and polar order. Next we explore pattern formation of self-propelled polar particles under flexible encapsulation, and on substrates with non-uniform Gaussian curvature. Lastly, we impose an activity mechanism that mimics extensile shear, study flexible particles both on solid substrates and coupled to a lipid membrane, and discuss comparisons to relevant experiments. Work performed in collaboration with Michael Varga (Kent State) and Luca Giomi (Universiteit Leiden.) Work supported by NSF DMR-1409658.

Specialization in the Human Brain: The Case of Numbers

PubMed Central

Kadosh, Roi Cohen; Bahrami, Bahador; Walsh, Vincent; Butterworth, Brian; Popescu, Tudor; Price, Cathy J.

2011-01-01

How numerical representation is encoded in the adult human brain is important for a basic understanding of human brain organization, its typical and atypical development, its evolutionary precursors, cognitive architectures, education, and rehabilitation. Previous studies have shown that numerical processing activates the same intraparietal regions irrespective of the presentation format (e.g., symbolic digits or non-symbolic dot arrays). This has led to claims that there is a single format-independent, numerical representation. In the current study we used a functional magnetic resonance adaptation paradigm, and effective connectivity analysis to re-examine whether numerical processing in the intraparietal sulci is dependent or independent on the format of the stimuli. We obtained two novel results. First, the whole brain analysis revealed that format change (e.g., from dots to digits), in the absence of a change in magnitude, activated the same intraparietal regions as magnitude change, but to a greater degree. Second, using dynamic causal modeling as a tool to disentangle neuronal specialization across regions that are commonly activated, we found that the connectivity between the left and right intraparietal sulci is format-dependent. Together, this line of results supports the idea that numerical representation is subserved by multiple mechanisms within the same parietal regions. PMID:21808615

Cinnamon bark proanthocyanidins as reactive carbonyl scavengers to prevent the formation of advanced glycation endproducts.

PubMed

Peng, Xiaofang; Cheng, Ka-Wing; Ma, Jinyu; Chen, Bo; Ho, Chi-Tang; Lo, Clive; Chen, Feng; Wang, Mingfu

2008-03-26

Cinnamon bark has been reported to be effective in the alleviation of diabetes through its antioxidant and insulin-potentiating activities. In this study, the inhibitory effect of cinnamon bark on the formation of advanced glycation endproducts (AGEs) was investigated in a bovine serum albumin (BSA)-glucose model. Several phenolic compounds, such as catechin, epicatechin, and procyanidin B2, and phenol polymers were identified from the subfractions of aqueous cinnamon extract. These compounds showed significant inhibitory effects on the formation of AGEs. Their antiglycation activities were not only brought about by their antioxidant activities but also related to their trapping abilities of reactive carbonyl species such as methylglyoxal (MGO), an intermediate reactive carbonyl of AGE formation. Preliminary study on the reaction between MGO and procyanidin B2 revealed that MGO-procyanidin B2 adducts are primary products which are supposed to be stereoisomers. This is the first report that proanthocyanidins can effectively scavenge reactive carbonyl species and thus inhibit the formation of AGEs. As proanthocyanidins behave in a similar fashion as aminoguanidine (AG), the first AGE inhibitor explored in clinical trials, they show great potential to be developed as agents to alleviate diabetic complications.

Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus

PubMed Central

Knight, Jason S.; Zhao, Wenpu; Luo, Wei; Subramanian, Venkataraman; O’Dell, Alexander A.; Yalavarthi, Srilakshmi; Hodgin, Jeffrey B.; Eitzman, Daniel T.; Thompson, Paul R.; Kaplan, Mariana J.

2013-01-01

Recent evidence suggests that enhanced neutrophil extracellular trap (NET) formation activates plasmacytoid dendritic cells and serves as a source of autoantigens in SLE. We propose that aberrant NET formation is also linked to organ damage and to the premature vascular disease characteristic of human SLE. Here, we demonstrate enhanced NET formation in the New Zealand mixed 2328 (NZM) model of murine lupus. NZM mice also developed autoantibodies to NETs as well as the ortholog of human cathelicidin/LL37 (CRAMP), a molecule externalized in the NETs. NZM mice were treated with Cl-amidine, an inhibitor of peptidylarginine deiminases (PAD), to block NET formation and were evaluated for lupus-like disease activity, endothelial function, and prothrombotic phenotype. Cl-amidine treatment inhibited NZM NET formation in vivo and significantly altered circulating autoantibody profiles and complement levels while reducing glomerular IgG deposition. Further, Cl-amidine increased the differentiation capacity of bone marrow endothelial progenitor cells, improved endothelium-dependent vasorelaxation, and markedly delayed time to arterial thrombosis induced by photochemical injury. Overall, these findings suggest that PAD inhibition can modulate phenotypes crucial for lupus pathogenesis and disease activity and may represent an important strategy for mitigating cardiovascular risk in lupus patients. PMID:23722903

Designing and Evaluating Tutoring Feedback Strategies for Digital Learning Environments on the Basis of the Interactive Tutoring Feedback Model

ERIC Educational Resources Information Center

Narciss, Susanne

2013-01-01

This paper describes the interactive tutoring feedback model (ITF-model; Narciss, 2006; 2008), and how it can be applied to the design and evaluation of feedback strategies for digital learning environments. The ITF-model conceptualizes formative tutoring feedback as a multidimensional instructional activity that aims at contributing to the…

Synthesis, X-ray crystallography, spectroscopic characterization and spectroscopic/electrochemical evidence of formation of phenoxy free radical in active center analogs of galactose oxidase - [Cu(Salgly)H₂O] and [Cu(Salphenylalanine)H₂O].

PubMed

Das, Biva; Medhi, Okhil K

2013-03-01

The formation of phenolate free radical is the factor of high turnover for catalytic activity of galactose oxidase (GO) compared to that by inorganic complexes. A new active center analog of GO, [Cu(II)(Salphenylalanine)H(2)O] have been synthesized and its single crystal X-ray analysis was done. In aqueous surfactant micellar solution chemical oxidation as well as electrochemical oxidation of structural models of galactose oxidase - [Cu(II)Salgly·H(2)O] and [Cu(II)(Salphenylalanine)·H(2)O], have been found to generate free radical originating at the phenolate group. Formation of the free radical have been proved by electron paramagnetic resonance spectroscopy, electronic spectroscopy and electrochemistry. Copyright © 2012 Elsevier B.V. All rights reserved.

A framework for evaluating the formation, implementation, and performance of accountable care organizations.

PubMed

Fisher, Elliott S; Shortell, Stephen M; Kreindler, Sara A; Van Citters, Aricca D; Larson, Bridget K

2012-11-01

The implementation of accountable care organizations (ACOs), a new health care payment and delivery model designed to improve care and lower costs, is proceeding rapidly. We build on our experience tracking early ACOs to identify the major factors-such as contract characteristics; structure, capabilities, and activities; and local context-that would be likely to influence ACO formation, implementation, and performance. We then propose how an ACO evaluation program could be structured to guide policy makers and payers in improving the design of ACO contracts, while providing insights for providers on approaches to care transformation that are most likely to be successful in different contexts. We also propose key activities to support evaluation of ACOs in the near term, including tracking their formation, developing a set of performance measures across all ACOs and payers, aggregating those performance data, conducting qualitative and quantitative research, and coordinating different evaluation activities.

A simplified model for glass formation

NASA Technical Reports Server (NTRS)

Uhlmann, D. R.; Onorato, P. I. K.; Scherer, G. W.

1979-01-01

A simplified model of glass formation based on the formal theory of transformation kinetics is presented, which describes the critical cooling rates implied by the occurrence of glassy or partly crystalline bodies. In addition, an approach based on the nose of the time-temperature-transformation (TTT) curve as an extremum in temperature and time has provided a relatively simple relation between the activation energy for viscous flow in the undercooled region and the temperature of the nose of the TTT curve. Using this relation together with the simplified model, it now seems possible to predict cooling rates using only the liquidus temperature, glass transition temperature, and heat of fusion.

Investigating the Relative Contributions of Secondary Ice Formation Processes to Ice Crystal Number Concentrations Within Mixed-Phase Clouds

NASA Astrophysics Data System (ADS)

Sullivan, S.; Nenes, A.

2015-12-01

Measurements of the in-cloud ice nuclei concentration can be three or four orders of magnitude less than those of the in-cloud ice crystal number concentration. Different secondary formation processes, active after initial ice nucleation, have been proposed to explain this discrepancy, but their relative importance, and even the exact physics of each mechanism, are still unclear. We construct a simple bin microphysics model (2IM) including depositional growth, the Hallett-Mossop process, ice-ice collisions, and ice-ice aggregation, with temperature- and supersaturation-dependent efficiencies for each process. 2IM extends the time-lag collision model of Yano and Phillips to additional bins and incorporates the aspect ratio evolution of Jensen and Harrington. Model output and measured ice crystal size distributions are compared to answer three questions: (1) how important is ice-ice aggregation relative to ice-ice collision around -15°C, where the Hallett-Mossop process is no longer active; (2) what process efficiencies lead to the best reproduction of observed ice crystal size distributions; and (3) does ice crystal aspect ratio affect the dominant secondary formation process. The resulting parameterization is intended for eventual use in larger-scale mixed-phase cloud schemes.

Correlating The Star Formation Histories Of MaNGA Galaxies With Their Past AGN Activity

NASA Astrophysics Data System (ADS)

Gonzalez Ortiz, Andrea

2017-01-01

We investigate active galactic nuclei (AGN) as a primary mechanism affecting star formation in MaNGA galaxies. Using the Pipe3D code, we modeled the stellar population from MaNGA spectra and derived the star formation histories of 53 AGN host galaxies. We seek to compare the star formation histories of the host galaxies of AGN with the ages of their radio lobes to better understand the role of AGN feedback in the star formation histories of MaNGA galaxies. MaNGA (Mapping Nearby Galaxies at APO) is one of the three core programs in the fourth generation Sloan Digital Sky Survey(SDSS). MaNGA will investigate the internal kinematics of nearly 10,000 local galaxies through dithered observations using fiber integral field units (IFUs) that vary in diameter from 12" (19 fibers) to 32" (127 fibers). In this poster, we present initial results on the star formation histories of MaNGA AGN host galaxies. This work was supported by the SDSS Research Experience for Undergraduates program, which is funded by a grant from Sloan Foundation to the Astrophysical Research Consortium.

Introducing the pro-coagulant contact system in the numerical assessment of device-related thrombosis.

PubMed

Méndez Rojano, Rodrigo; Mendez, Simon; Nicoud, Franck

2018-06-01

Thrombosis is a major concern in blood-coated medical devices. Contact activation, which is the initial part of the coagulation cascade in device-related thrombosis, is not considered in current thrombus formation models. In the present study, pro-coagulant reactions including the contact activation system are coupled with a fluid solver in order to evaluate the potential of the contact system to initiate thrombin production. The biochemical/fluid model is applied to a backward-facing step configuration, a flow configuration that frequently appears in medical devices. In contrast to the in vivo thrombosis models in which a specific thrombotic zone (injury region) is set a priori by the user to initiate the coagulation reaction, a reactive surface boundary condition is applied to the whole device wall. Simulation results show large thrombin concentration in regions related to recirculation zones without the need of an a priori knowledge of the thrombus location. The numerical results align well with the regions prone to thrombosis observed in experimental results reported in the literature. This approach could complement thrombus formation models that take into account platelet activity and thrombus growth to optimize a wide range of medical devices.

Magnetic suppression of turbulence and the star formation activity of molecular clouds

NASA Astrophysics Data System (ADS)

Zamora-Avilés, Manuel; Vázquez-Semadeni, Enrique; Körtgen, Bastian; Banerjee, Robi; Hartmann, Lee

2018-03-01

We present magnetohydrodynamic simulations aimed at studying the effect of the magnetic suppression of turbulence (generated through various instabilities during the formation of molecular clouds by converging) on the subsequent star formation (SF) activity. We study four magnetically supercritical models with magnetic field strengths B = 0, 1, 2, and 3 μG (corresponding to mass-to-flux ratios of ∞, 4.76, 2.38, and 1.59 times the critical value), with the magnetic field, initially being aligned with the flows. We find that, for increasing magnetic field strength, the clouds formed tend to be more massive, denser, less turbulent, and with higher SF activity. This causes the onset of SF activity in the non-magnetic or more weakly magnetized cases to be delayed by a few Myr in comparison to the more strongly magnetized cases. We attribute this behaviour to the suppression of the non-linear thin shell instability (NTSI) by the magnetic field, previously found by Heitsch and coworkers. This result is contrary to the standard notion that the magnetic field provides support to the clouds, thus reducing their star formation rate. However, our result is a completely non-linear one, and could not be foreseen from simple linear considerations.

Construction and analysis of a modular model of caspase activation in apoptosis

PubMed Central

Harrington, Heather A; Ho, Kenneth L; Ghosh, Samik; Tung, KC

2008-01-01

Background A key physiological mechanism employed by multicellular organisms is apoptosis, or programmed cell death. Apoptosis is triggered by the activation of caspases in response to both extracellular (extrinsic) and intracellular (intrinsic) signals. The extrinsic and intrinsic pathways are characterized by the formation of the death-inducing signaling complex (DISC) and the apoptosome, respectively; both the DISC and the apoptosome are oligomers with complex formation dynamics. Additionally, the extrinsic and intrinsic pathways are coupled through the mitochondrial apoptosis-induced channel via the Bcl-2 family of proteins. Results A model of caspase activation is constructed and analyzed. The apoptosis signaling network is simplified through modularization methodologies and equilibrium abstractions for three functional modules. The mathematical model is composed of a system of ordinary differential equations which is numerically solved. Multiple linear regression analysis investigates the role of each module and reduced models are constructed to identify key contributions of the extrinsic and intrinsic pathways in triggering apoptosis for different cell lines. Conclusion Through linear regression techniques, we identified the feedbacks, dissociation of complexes, and negative regulators as the key components in apoptosis. The analysis and reduced models for our model formulation reveal that the chosen cell lines predominately exhibit strong extrinsic caspase, typical of type I cell, behavior. Furthermore, under the simplified model framework, the selected cells lines exhibit different modes by which caspase activation may occur. Finally the proposed modularized model of apoptosis may generalize behavior for additional cells and tissues, specifically identifying and predicting components responsible for the transition from type I to type II cell behavior. PMID:19077196

Morusinol extracted from Morus alba inhibits arterial thrombosis and modulates platelet activation for the treatment of cardiovascular disease.

PubMed

Lee, Jung-Jin; Yang, Hyun; Yoo, Yeong-Min; Hong, Seong Su; Lee, Dongho; Lee, Hyun-Jung; Lee, Hak-Ju; Myung, Chang-Seon; Choi, Kyung-Chul; Jeung, Eui-Bae

2012-01-01

Morus alba (white mulberry) has been used in traditional Chinese medicine as an anti-headache, diuretic, expectorant, and anti-diabetic agent. In previous studies, extracts of Morus alba demonstrated favorable biological properties, such as antioxidant activity, suppression of lipoxygenase (LOX)-1, cytotoxicity against cancer cells, and inhibition of the invasion and migration of cancer cells. This study further evaluated the effects of morusinol, a flavonoid derived from Morus alba root bark, on platelet aggregation and thromboxane B(2) (TXB(2) formation in vitro and thrombus formation in vivo. The antiplatelet potential of morusinol was measured using in vitro rabbit platelet aggregation and TXB(2) formation assays. Arterial thrombus formation was investigated using an in vivo ferric chloride (FeCl(3)-induced thrombosis model. Morusinol significantly inhibited collagen- and arachidonic acid-induced platelet aggregation and TXB(2) formation in cultured platelets in a concentration-dependent manner. Thrombus formation was reduced by 32.1, 42.0, and 99.0% for collagen-induced TXB(2) formation, and 8.0, 24.1, and 29.2% for arachadonic acid-induced TXB(2) formation, with 5, 10, and 30 µg/mL morusinol, respectively. Moreover, oral morusinol (20 mg/kg) or aspirin (20 mg/kg) for three days significantly increased the time to occlusion in vivo by 20.3±5.0 or 6.8±2.9 min, respectively, compared with the control (1% CMC, carboxymethyl cellulose). Taken together, these results indicate that morusinol may significantly inhibit arterial thrombosis in vivo due to antiplatelet activity. Thus, morusinol may exert beneficial effects on transient ischemic attacks or stroke via the modulation of platelet activation.

Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis

PubMed Central

Wilson, Katina M.; Leo, Lorie; Raimondi, Alejandro; Molkentin, Jeffery D.; Lentz, Steven R.; Di Paola, Jorge

2008-01-01

Many of the cellular responses that occur in activated platelets resemble events that take place following activation of cell-death pathways in nucleated cells. We tested the hypothesis that formation of the mitochondrial permeability transition pore (MPTP), a key signaling event during cell death, also plays a critical role in platelet activation. Stimulation of murine platelets with thrombin plus the glycoprotein VI agonist convulxin resulted in a rapid loss of mitochondrial transmembrane potential (Δψm) in a subpopulation of activated platelets. In the absence of cyclophilin D (CypD), an essential regulator of MPTP formation, murine platelet activation responses were altered. CypD-deficient platelets exhibited defects in phosphatidylserine externalization, high-level surface fibrinogen retention, membrane vesiculation, and procoagulant activity. Also, in CypD-deficient platelet-rich plasma, clot retraction was altered. Stimulation with thrombin plus H2O2, a known activator of MPTP formation, also increased high-level surface fibrinogen retention, phosphatidylserine externalization, and platelet procoagulant activity in a CypD-dependent manner. In a model of carotid artery photochemical injury, thrombosis was markedly accelerated in CypD-deficient mice. These results implicate CypD and the MPTP as critical regulators of platelet activation and suggest a novel CypD-dependent negative-feedback mechanism regulating arterial thrombosis. PMID:17989312

Antischistosomal Activity of Pyrido[1,2-a]benzimidazole Derivatives and Correlation with Inhibition of β-Hematin Formation.

PubMed

Okombo, John; Singh, Kawaljit; Mayoka, Godfrey; Ndubi, Ferdinand; Barnard, Linley; Njogu, Peter M; Njoroge, Mathew; Gibhard, Liezl; Brunschwig, Christel; Vargas, Mireille; Keiser, Jennifer; Egan, Timothy J; Chibale, Kelly

2017-06-09

The extensive use of praziquantel against schistosomiasis raises concerns about drug resistance. New therapeutic alternatives targeting critical pathways within the parasite are therefore urgently needed. Hemozoin formation in Schistosoma presents one such target. We assessed the in vitro antischistosomal activity of pyrido[1,2-a]benzimidazoles (PBIs) and investigated correlations with their ability to inhibit β-hematin formation. We further evaluated the in vivo efficacy of representative compounds in experimental mice and conducted pharmacokinetic analysis on the most potent. At 10 μM, 48/57 compounds resulted in >70% mortality of newly transformed schistosomula, whereas 37 of these maintained >60% mortality of adult S. mansoni. No correlations were observed between β-hematin inhibitory and antischistosomal activities against both larval and adult parasites, suggesting possible presence of other target(s) or a mode of inhibition of crystal formation that is not adequately modeled by the assay. The most active compound in vivo showed 58.7 and 61.3% total and female worm burden reduction, respectively. Pharmacokinetic analysis suggested solubility-limited absorption and high hepatic clearance as possible contributors to the modest efficacy despite good in vitro activity. The PBIs evaluated in this report thus merit further optimization to improve their efficacy and to elucidate their possible mode of action.

Characterizing the Protostars in the Herschel Survey of Cygnus-X

NASA Astrophysics Data System (ADS)

Kirk, James; Hora, J. L.; Smith, H. A.; Herschel Cygnus-X Group

2014-01-01

The Cygnus-X complex is an extremely active region of massive star formation at a distance of ~1.4 kpc which can be studied with higher sensitivity and less confusion than more distant regions. The study of this region is important in improving our understanding of the formation processes and protostellar phases of massive stars. A previous Spitzer Legacy survey of Cygnus-X mapped the distributions of Class I and Class II YSOs within the region and studied the interaction between massive young stars and clusters of YSOs. Using data from the recent Herschel survey of the region, taken with the PACS and SPIRE instrument (70-500 microns), we are expanding this study of star formation to the youngest and most deeply embedded objects. Using these data we will expand the sample of massive protostars and YSOs in Cygnus-X, analyze the population of infrared dark clouds and their embedded objects, construct Spectral Energy Distributions (SEDs) using pre-existing Spitzer and near-IR data sets (1-500 microns), and fit these sources with models of protostars to derive luminosities and envelope masses. The derived luminosities and masses will enable us to create evolutionary diagrams and test models of high-mass star formation. We will also investigate what role OB associations, such as Cyg OB2, play in causing subsequent star formation in neighboring clouds, providing us with a comprehensive picture of star formation within this extremely active complex.

Membrane filtration device for studying compression of fouling layers in membrane bioreactors

PubMed Central

Bugge, Thomas Vistisen; Larsen, Poul; Nielsen, Per Halkjær; Christensen, Morten Lykkegaard

2017-01-01

A filtration devise was developed to assess compressibility of fouling layers in membrane bioreactors. The system consists of a flat sheet membrane with air scouring operated at constant transmembrane pressure to assess the influence of pressure on resistance of fouling layers. By fitting a mathematical model, three model parameters were obtained; a back transport parameter describing the kinetics of fouling layer formation, a specific fouling layer resistance, and a compressibility parameter. This stands out from other on-site filterability tests as model parameters to simulate filtration performance are obtained together with a characterization of compressibility. Tests on membrane bioreactor sludge showed high reproducibility. The methodology’s ability to assess compressibility was tested by filtrations of sludges from membrane bioreactors and conventional activated sludge wastewater treatment plants from three different sites. These proved that membrane bioreactor sludge showed higher compressibility than conventional activated sludge. In addition, detailed information on the underlying mechanisms of the difference in fouling propensity were obtained, as conventional activated sludge showed slower fouling formation, lower specific resistance and lower compressibility of fouling layers, which is explained by a higher degree of flocculation. PMID:28749990

Modeling and Simulation with INS.

ERIC Educational Resources Information Center

Roberts, Stephen D.; And Others

INS, the Integrated Network Simulation language, puts simulation modeling into a network framework and automatically performs such programming activities as placing the problem into a next event structure, coding events, collecting statistics, monitoring status, and formatting reports. To do this, INS provides a set of symbols (nodes and branches)…

Music and the Expressive Arts with Children Experiencing Trauma

ERIC Educational Resources Information Center

Davis, Keith M.

2010-01-01

The creative and expressive use of music can be a powerful therapeutic intervention with children and adolescents who have experienced trauma. In this article, a model for increasing self-awareness and self-understanding including materials, facilitation, and processing of musical activities in group format is presented. Creative activities such…

Women in Technical Education. Annual Report 1990-91.

ERIC Educational Resources Information Center

Texas State Technical Coll., Waco.

First-year activities of Women in Technical Education, a project to develop a model for women in that field, were evaluated. A formative evaluation showed that intense development and implementation activity enabled achievement of first-year goals and objectives during the 1990-91 year. Procedures to accomplish objectives were effective.…

Controlled Volcanism in the Classroom: A Simulation

ERIC Educational Resources Information Center

Erdogan, Ibrahim

2005-01-01

In this extended earth science activity, students create a hands-on model of a volcano to achieve an understanding of volcanic structure, lava flows, formation of lava layers, and the scientific work of archaeologists and geoscientists. During this simulation activity, students have opportunities to learn science as inquiry and the nature of…

In vivo gastroprotective effect of xyloccensin-E and xyloccensin-I from Xylocarpus molluccensis in rats.

PubMed

Lakshmi, Vijai; Mishra, Vaibhav; Palit, Gautam

2015-01-01

Anti-ulcer activities of xyloccensin-E and xyloccensin-I were investigated in various ulcer models in Sprague-Dawley rats. The effects and the mechanism of action of both compounds for anti-secretory and cytoprotective activities were also studied. Both these active molecules improved the depleted levels of mucin and consequently inhibited the formation of erosions in a pyloric ligated ulcer model. Furthermore, xyloccensin-E and xyloccensin-I inhibited H(+)K(+)-ATPase activity in vitro confirming their anti-secretory activity. In conclusion, xyloccensin-E and xyloccensin-I were found to possess anti-ulcerogenic activity which might be due to their anti-secretory activity and subsequent strengthening of the defensive mechanism.

A Myrtus communis extract enriched in myrtucummulones and ursolic acid reduces resistance of Propionibacterium acnes biofilms to antibiotics used in acne vulgaris.

PubMed

Feuillolay, Catherine; Pecastaings, Sophie; Le Gac, Céline; Fiorini-Puybaret, Christel; Luc, Joëlle; Joulia, Philippe; Roques, Christine

2016-03-15

Recent works present evidence of Propionibacterium acnes growing as a biofilm in cutaneous follicles. This formation of clusters is now considered as an explanation for the in vivo resistance of P. acnes to the main antimicrobials prescribed in acne vulgaris. Our objective was to explore this hypothesis and propose a new therapeutic approach focusing on anti-biofilm activity of Myrtacine(®) New Generation (Mediterranean Myrtle extract-Botanical Expertise P. Fabre) alone or combined with antibiotics. Using in vitro models able to promote the growth of adhered bacteria, the loss of sensitivity of P. acnes biofilms (48 h) towards erythromycin and clindamycin was checked considering either sensitive or resistant strains. In the same time, the activity of Myrtacine(®) New Generation against biofilm formation and mature biofilm (48 h) was evaluated. Using a dynamic model of biofilm formation, we noted an inhibition of biofilm formation (addition of Myrtacine(®) New Generation at T 0) and a significant effect on mature biofilm (48 h) for 5 min of contact. This effect was also checked using the static model of biofilm formation for Myrtacine(®) New Generation concentrations ranging from 0.03% to 0.0001%. A significant, dose-dependent anti-biofilm effect was observed and notable even at a concentration lower than the active concentration on planktonic cells, i.e. 0.001%. Finally, the interest of the combination of Myrtacine(®) New Generation with antibiotics was explored. An enhanced efficacy was noted when erythromycin (1000 mg/l) or clindamycin (500 mg/l) was added to 0.001% Myrtacine(®), leading to significant differences in comparison to each compound used alone. The efficiency of Myrtacine(®) New Generation on P. acnes biofilm alone or combined with antibiotics was demonstrated and can lead to consider it as a potent adjunctive product efficient during the antibiotic course for acne vulgaris treatment. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

The Effect of Cryopreserved Human Placental Tissues on Biofilm Formation of Wound-Associated Pathogens.

PubMed

Mao, Yong; Singh-Varma, Anya; Hoffman, Tyler; Dhall, Sandeep; Danilkovitch, Alla; Kohn, Joachim

2018-01-08

Biofilm, a community of bacteria, is tolerant to antimicrobial agents and ubiquitous in chronic wounds. In a chronic DFU (Diabetic Foot Ulcers) clinical trial, the use of a human cryopreserved viable amniotic membrane (CVAM) resulted in a high rate of wound closure and reduction of wound-related infections. Our previous study demonstrated that CVAM possesses intrinsic antimicrobial activity against a spectrum of wound-associated bacteria under planktonic culture conditions. In this study, we evaluated the effect of CVAM and cryopreserved viable umbilical tissue (CVUT) on biofilm formation of S. aureus and P. aeruginosa , the two most prominent pathogens associated with chronic wounds. Firstly, we showed that, like CVAM, CVUT released antibacterial activity against multiple bacterial pathogens and the devitalization of CVUT reduced its antibacterial activity. The biofilm formation was then measured using a high throughput method and an ex vivo porcine dermal tissue model. We demonstrate that the formation of biofilm was significantly reduced in the presence of CVAM- or CVUT-derived conditioned media compared to control assay medium. The formation of P. aeruginosa biofilm on CVAM-conditioned medium saturated porcine dermal tissues was reduced 97% compared with the biofilm formation on the control medium saturated dermal tissues. The formation of S. auerus biofilm on CVUT-conditioned medium saturated dermal tissues was reduced 72% compared with the biofilm formation on the control tissues. This study is the first to show that human cryopreserved viable placental tissues release factors that inhibit biofilm formation. Our results provide an explanation for the in vivo observation of their ability to support wound healing.

Achieving Equity in Education Programs for Disabled Women and Girls. A Model Workshop Manual.

ERIC Educational Resources Information Center

Kratovil, Jane; And Others

The model workshop manual is intended for use with state and local special education and sex equity staff. The manual contains a model workshop format, information on problems faced by disabled students, and suggested workshop activities. A sample workshop agenda, accompanying materials and resources developed, compiled, and field-tested at two…

Effect of modeling factors on the dissolution-diffusion-convection process during CO2 geological storage in deep saline formations

NASA Astrophysics Data System (ADS)

Zhang, Wei

2013-06-01

It is well known that during CO2 geological storage, density-driven convective activity can significantly accelerate the dissolution of injected CO2 into water. This action could limit the escape of supercritical CO2 from the storage formation through vertical pathways such as fractures, faults and abandoned wells, consequently increasing permanence and security of storage. First, we investigated the effect of numerical perturbation caused by time and grid resolution and the convergence criteria on the dissolution-diffusion-convection (DDC) process. Then, using the model with appropriate spatial and temporal resolution, some uncertainty parameters investigated in our previous paper such as initial gas saturation and model boundaries, and other factors such as relative liquid permeability and porosity modification were used to examine their effects on the DDC process. Finally, we compared the effect of 2D and 3D models on the simulation of the DDC process. The above modeling results should contribute to clear understanding and accurate simulation of the DDC process, especially the onset of convective activity, and the CO2 dissolution rate during the convection-dominated stage.

Hydrogeochemical Investigation of Recharge Pathways to Intermediate and Regional Groundwater in Canon de Valle and Technical Area 16, Los Alamos National Laboratory

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

Brady, Brendan W.

In aquifers consisting of fractured or porous igneous rocks, as well as conglomerate and sandstone products of volcanic formations, silicate minerals actively dissolve and precipitate (Eby, 2004; Eriksson, 1985; Drever, 1982). Dissolution of hydrated volcanic glass is also known to influence the character of groundwater to which it is exposed (White et al., 1980). Hydrochemical evolution, within saturated zones of volcanic formations, is modeled here as a means to resolve the sources feeding a perched groundwater zone. By observation of solute mass balances in groundwater, together with rock chemistry, this study characterizes the chemical weathering processes active along recharge pathwaysmore » in a mountain front system. Inverse mass balance modeling, which accounts for mass fluxes between solid phases and solution, is used to contrive sets of quantitative reactions that explain chemical variability of water between sampling points. Model results are used, together with chloride mass balance estimation, to evaluate subsurface mixing scenarios generated by further modeling. Final model simulations estimate contributions of mountain block and local recharge to various contaminated zones.« less

Targeting chronic inflammation in cerebral aneurysms: focusing on NF-kappaB as a putative target of medical therapy.

PubMed

Aoki, Tomohiro; Nishimura, M

2010-03-01

Cerebral aneurysms (CAs) are the main cause of life-threatening subarachnoid hemorrhage. Given its prevalence and endpoint, CA treatment is a public health issue. Effective medical treatment of CAs is lacking because the detailed mechanisms of CA formation are incompletely understood. The aim of this contribution is to review recent articles about CA formation, to suggest the underlying mechanisms of CA formation, and to discuss potential therapeutic targets for treatment. Articles were collected by an internet search of PubMed using the keywords 'intracranial' or 'cerebral aneurysm'. A review of articles about the pathogenesis of CA formation focusing on inflammation. Recent articles demonstrate that inflammation-related-molecule induction and inflammatory cell infiltration in CA walls and the close relationship between inflammatory responses and CA formation. From studies in experimental models, chronic inflammation triggered primarily by NF-kappaB activation in endothelial cells and subsequent macrophage infiltration have critical roles in CA formation. Inhibition of inflammation-related molecules in CA walls results in the decreased incidence of CA formation. Agents with anti-inflammatory activity (particularly anti- NF-kappaB effects) have potential as therapeutic drugs for CAs.

Kinetics of calcium sulfoaluminate formation from tricalcium aluminate, calcium sulfate and calcium oxide

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

Li, Xuerun, E-mail: xuerunli@163.com; Zhang, Yu; Shen, Xiaodong, E-mail: xdshen@njut.edu.cn

The formation kinetics of tricalcium aluminate (C{sub 3}A) and calcium sulfate yielding calcium sulfoaluminate (C{sub 4}A{sub 3}more » $$) and the decomposition kinetics of calcium sulfoaluminate were investigated by sintering a mixture of synthetic C{sub 3}A and gypsum. The quantitative analysis of the phase composition was performed by X-ray powder diffraction analysis using the Rietveld method. The results showed that the formation reaction 3Ca{sub 3}Al{sub 2}O{sub 6} + CaSO{sub 4} → Ca{sub 4}Al{sub 6}O{sub 12}(SO{sub 4}) + 6CaO was the primary reaction < 1350 °C with and activation energy of 231 ± 42 kJ/mol; while the decomposition reaction 2Ca{sub 4}Al{sub 6}O{sub 12}(SO{sub 4}) + 10CaO → 6Ca{sub 3}Al{sub 2}O{sub 6} + 2SO{sub 2} ↑ + O{sub 2} ↑ primarily occurred beyond 1350 °C with an activation energy of 792 ± 64 kJ/mol. The optimal formation region for C{sub 4}A{sub 3}$$ was from 1150 °C to 1350 °C and from 6 h to 1 h, which could provide useful information on the formation of C{sub 4}A{sub 3}$ containing clinkers. The Jander diffusion model was feasible for the formation and decomposition of calcium sulfoaluminate. Ca{sup 2+} and SO{sub 4}{sup 2−} were the diffusive species in both the formation and decomposition reactions. -- Highlights: •Formation and decomposition of calcium sulphoaluminate were studied. •Decomposition of calcium sulphoaluminate combined CaO and yielded C{sub 3}A. •Activation energy for formation was 231 ± 42 kJ/mol. •Activation energy for decomposition was 792 ± 64 kJ/mol. •Both the formation and decomposition were controlled by diffusion.« less

Inhibitory effect of Piper betle Linn. leaf extract on protein glycation--quantification and characterization of the antiglycation components.

PubMed

Bhattacherjee, Abhishek; Chakraborti, Abhay Sankar

2013-12-01

Piper betle Linn. is a Pan-Asiatic plant having several beneficial properties. Protein glycation and advanced glycation end products (AGEs) formation are associated with different pathophysiological conditions, including diabetes mellitus. Our study aims to find the effect of methanolic extract of P. betle leaves on in vitro protein glycation in bovine serum albumin (BSA)-glucose model. The extract inhibits glucose-induced glycation, thiol group modification and carbonyl formation in BSA in dose-dependent manner. It inhibits different stages of protein glycation, as demonstrated by using glycation models: hemoglobin-delta-gluconolactone (for early stage, Amadori product formation), BSA-methylglyoxal (for middle stage, formation of oxidative cleavage products) and BSA-glucose (for last stage, formation of AGEs) systems. Several phenolic compounds are isolated from the extract. Considering their relative amounts present in the extract, rutin appears to be the most active antiglycating agent. The extract of P. betle leaf may thus have beneficial effect in preventing protein glycation and associated complications in pathological conditions.

Modeling biogenic gas bubbles formation and migration in coarse sand

NASA Astrophysics Data System (ADS)

Ye, S.

2011-12-01

Shujun Ye Department of Hydrosciences, School of Earth Sciences and Engineering, Nanjing University, Nanjing 210093, China; sjye@nju.edu.cn Brent E. Sleep Department of Civil Engineering, University of Toronto, Toronto, ON, M5S 1A4 CANADA; sleep@ecf.utoronto.ca Methane gas generation in porous media was investigated in an anaerobic two-dimensional sand-filled cell. Inoculation of the lower portion of the cell with a methanogenic culture and addition of methanol to the bottom of the cell led to biomass growth and formation of a gas phase. The formation, migration, distribution and saturation of gases in the cell were visualized by the charge-coupled device (CCD) camera. Gas generated at the bottom of the cell in the biologically active zone moved upwards in discrete fingers, so that gas phase saturations (gas-filled fraction of void space) in the biologically active zone at the bottom of the cell did not exceed 40-50%, while gas accumulation at the top of the cell produced gas phase saturations as high as 80%. Macroscopic invasion percolation (MIP) at near pore scale[Glass, et al., 2001; Kueper and McWhorter, 1992]was used to model gas bubbles growth in porous media. The nonwetting phase migration pathway can be yielded directly by MIP. MIP was adopted to simulate the expansion, fragmentation, and mobilization of gas clusters in the cell. The production of gas, and gas phash saturations were simulated by a continuum model - compositional simulator (COMPSIM) [Sleep and Sykes, 1993]. So a combination of a continuum model and a MIP model was used to simulate the formation, fragmentation and migration of biogenic gas bubbles. Key words: biogenic gas; two dimensional; porous media; MIP; COMPSIM

Nephrin Regulates Lamellipodia Formation by Assembling a Protein Complex That Includes Ship2, Filamin and Lamellipodin

PubMed Central

Venkatareddy, Madhusudan; Cook, Leslie; Abuarquob, Kamal; Verma, Rakesh; Garg, Puneet

2011-01-01

Actin dynamics has emerged at the forefront of podocyte biology. Slit diaphragm junctional adhesion protein Nephrin is necessary for development of the podocyte morphology and transduces phosphorylation-dependent signals that regulate cytoskeletal dynamics. The present study extends our understanding of Nephrin function by showing in cultured podocytes that Nephrin activation induced actin dynamics is necessary for lamellipodia formation. Upon activation Nephrin recruits and regulates a protein complex that includes Ship2 (SH2 domain containing 5′ inositol phosphatase), Filamin and Lamellipodin, proteins important in regulation of actin and focal adhesion dynamics, as well as lamellipodia formation. Using the previously described CD16-Nephrin clustering system, Nephrin ligation or activation resulted in phosphorylation of the actin crosslinking protein Filamin in a p21 activated kinase dependent manner. Nephrin activation in cell culture results in formation of lamellipodia, a process that requires specialized actin dynamics at the leading edge of the cell along with focal adhesion turnover. In the CD16-Nephrin clustering model, Nephrin ligation resulted in abnormal morphology of actin tails in human podocytes when Ship2, Filamin or Lamellipodin were individually knocked down. We also observed decreased lamellipodia formation and cell migration in these knock down cells. These data provide evidence that Nephrin not only initiates actin polymerization but also assembles a protein complex that is necessary to regulate the architecture of the generated actin filament network and focal adhesion dynamics. PMID:22194892

Effect of Lavender (Lavandula angustifolia) Essential Oil on Acute Inflammatory Response

PubMed Central

Cardia, Gabriel Fernando Esteves; Cavalcante, Heitor Augusto Otaviano; Cassarotti, Larissa Laila; Salvadego, Valter Eduardo Cocco; Spironello, Ricardo Alexandre; Bersani-Amado, Ciomar Aparecida

2018-01-01

Lavandula angustifolia is a plant of Lamiaceae family, with many therapeutic properties and biological activities, such as anticonvulsant, anxiolytic, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of this study was to evaluate the effect of Lavandula angustifolia Mill. essential oil (LEO) on acute inflammatory response. LEO was analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods and showed predominance of 1,8-cineole (39.83%), borneol (22.63%), and camphor (22.12%). LEO at concentrations of 0.5, 1, 3, and 10 μg/ml did not present in vitro cytotoxicity. Additionally, LEO did not stimulate the leukocyte chemotaxis in vitro. The LEO topical application at concentrations of 0.25, 0.5, and 1 mg/ear reduced edema formation, myeloperoxidase (MPO) activity, and nitric oxide (NO) production in croton oil-induced ear edema model. In carrageenan-induced paw edema model, LEO treatment at doses of 75, 100, and 250 mg/kg reduced edema formation, MPO activity, and NO production. In dextran-induced paw edema model, LEO at doses of 75 and 100 mg/kg reduced paw edema and MPO activity. In conclusion, LEO presented anti-inflammatory activity, and the mechanism proposed of LEO seems to be, at least in part, involving the participation of prostanoids, NO, proinflammatory cytokines, and histamine. PMID:29743918

Mathematical study on robust tissue pattern formation in growing epididymal tubule.

PubMed

Hirashima, Tsuyoshi

2016-10-21

Tissue pattern formation during development is a reproducible morphogenetic process organized by a series of kinetic cellular activities, leading to the building of functional and stable organs. Recent studies focusing on mechanical aspects have revealed physical mechanisms on how the cellular activities contribute to the formation of reproducible tissue patterns; however, the understanding for what factors achieve the reproducibility of such patterning and how it occurs is far from complete. Here, I focus on a tube pattern formation during murine epididymal development, and show that two factors influencing physical design for the patterning, the proliferative zone within the tubule and the viscosity of tissues surrounding to the tubule, control the reproducibility of epididymal tubule pattern, using a mathematical model based on experimental data. Extensive numerical simulation of the simple mathematical model revealed that a spatially localized proliferative zone within the tubule, observed in experiments, results in more reproducible tubule pattern. Moreover, I found that the viscosity of tissues surrounding to the tubule imposes a trade-off regarding pattern reproducibility and spatial accuracy relating to the region where the tubule pattern is formed. This indicates an existence of optimality in material properties of tissues for the robust patterning of epididymal tubule. The results obtained by numerical analysis based on experimental observations provide a general insight on how physical design realizes robust tissue pattern formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

SigB is a dominant regulator of virulence in Staphylococcus aureus small-colony variants.

PubMed

Mitchell, Gabriel; Fugère, Alexandre; Pépin Gaudreau, Karine; Brouillette, Eric; Frost, Eric H; Cantin, André M; Malouin, François

2013-01-01

Staphylococcus aureus small-colony variants (SCVs) are persistent pathogenic bacteria characterized by slow growth and, for many of these strains, an increased ability to form biofilms and to persist within host cells. The virulence-associated gene expression profile of SCVs clearly differs from that of prototypical strains and is often influenced by SigB rather than by the agr system. One objective of this work was to confirm the role of SigB in the control of the expression of virulence factors involved in biofilm formation and intracellular persistence of SCVs. This study shows that extracellular proteins are involved in the formation of biofilm by three SCV strains, which, additionally, have a low biofilm-dispersing activity. It was determined that SigB activity modulates biofilm formation by strain SCV CF07-S and is dominant over that of the agr system without being solely responsible for the repression of proteolytic activity. On the other hand, the expression of fnbA and the control of nuclease activity contributed to the SigB-dependent formation of biofilm of this SCV strain. SigB was also required for the replication of CF07-S within epithelial cells and may be involved in the colonization of lungs by SCVs in a mouse infection model. This study methodically investigated SigB activity and associated mechanisms in the various aspects of SCV pathogenesis. Results confirm that SigB activity importantly influences the production of virulence factors, biofilm formation and intracellular persistence for some clinical SCV strains.

P-selectin ligation induces platelet activation and enhances microaggregate and thrombus formation.

PubMed

Théorêt, Jean-François; Yacoub, Daniel; Hachem, Ahmed; Gillis, Marc-Antoine; Merhi, Yahye

2011-09-01

Platelet P-selectin is a thrombo-inflammatory molecule involved in platelet activation and aggregation. This may occur via the adhesive function of P-selectin and its potential capacity to trigger intracellular signaling. However, its impact on platelet function remains elusive. This study was therefore designed to investigate the relationship between the signaling potential of platelet P-selectin and its function in platelet physiology. Human and mouse platelets were freshly isolated from whole blood. Platelet activation was assessed using flow cytometry and western blot analysis, while platelet physiological responses were evaluated through aggregation, microaggregate formation and in a thrombosis model in wild-type and P-selectin-deficient (CD62P(-/-)) mice. Interaction of P-selectin with its high-affinity ligand, a recombinant soluble form of P-Selectin Glycoprotein Ligand-1 (rPSGL-1), enhances platelet activation, adhesion and microaggregate formation. This augmented platelet microaggregates requires an intact cytoskeleton, but occurs independently of platelet α(IIb)β(3). Thrombus formation and microaggregate were both enhanced by rPSGL-1 in wild-type, but not in CD62P(-/-) mice. In addition, CD62P(-/-) mice exhibited thrombosis abnormalities without an α(IIb)β(3) activation defect. This study demonstrates that the role of platelet P-selectin is not solely adhesive; its binding to PSGL-1 induces platelet activation that enhances platelet aggregation and thrombus formation. Therefore, targeting platelet P-selectin or its ligand PSGL-1 could provide a potential therapeutic approach in the management of thrombotic disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

PubMed Central

Parastatidis, Ioannis; Weiss, Daiana; Joseph, Giji; Taylor, W Robert

2013-01-01

Objective Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species (ROS) promotes the development of AAA remains unclear. Here we investigate the effect of the hydrogen peroxide (H2O2) degrading enzyme catalase on the formation of AAA. Approach and Results AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91±0.1 mm vs. 0.76±0.09 mm). Similarly, in a transgenic mouse model, catalase over-expression in the vascular smooth muscle cells (VSMC) preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85±0.14 mm vs. 0.57±0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacologic administration or genetic over-expression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and VSMC apoptosis was evident in aortas of catalase over-expressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic over-expression of catalase in VSMC did not alter the total aortic H2O2 levels. Conclusions The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic VSMC survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity. PMID:23950141

Chondrules: The canonical and noncanonical views

NASA Astrophysics Data System (ADS)

Connolly, Harold C.; Jones, Rhian H.

2016-10-01

Millimeter-scale rock particles called chondrules are the principal components of the most common meteorites, chondrites. Hence, chondrules were arguably the most abundant components of the early solar system at the time of planetesimal accretion. Despite their fundamental importance, the existence of chondrules would not be predicted from current observations and models of young planetary systems. There are many different models for chondrule formation, but no single model satisfies the many constraints determined from their mineralogical and chemical properties and from chondrule analog experiments. Significant recent progress has shown that several models can satisfy first-order constraints and successfully reproduce chondrule thermal histories. However, second- and third-order constraints such as chondrule size ranges, open system behavior, oxidation states, reheating, and chemical diversity have not generally been addressed. Chondrule formation models include those based on processes that are known to occur in protoplanetary disk environments, including interactions with the early active Sun, impacts and collisions between planetary bodies, and radiative heating. Other models for chondrule heating mechanisms are based on hypothetical processes that are possible but have not been observed, like shock waves, planetesimal bow shocks, and lightning. We examine the evidence for the canonical view of chondrule formation, in which chondrules were free-floating particles in the protoplanetary disk, and the noncanonical view, in which chondrules were the by-products of planetesimal formation. The fundamental difference between these approaches has a bearing on the importance of chondrules during planet formation and the relevance of chondrules to interpreting the evolution of protoplanetary disks and planetary systems.

Impact of phloretin and phloridzin on the formation of Maillard reaction products in aqueous models composed of glucose and L-lysine or its derivatives.

PubMed

Ma, Jinyu; Peng, Xiaofang; Ng, Kwan-Ming; Che, Chi-Ming; Wang, Mingfu

2012-02-01

In the present study, the effects of phloretin and phloridzin on the formation of Maillard reaction products in a lysine-glucose model with different reactant ratios were systematically investigated. In terms of the formation of Maillard-type volatiles, phloretin and phloridzin treatmen could significantly reduce their generation, where the effects depend on the ratio of lysine to glucose used in the model systems. Phloretin and phloridzin could also affect the colour development of Maillard reactions; especially phloretin, which could significantly promote the formation of brown products in the system with the lowest ratio of lysine to glucose. Based on the carbon module labelling (CAMOLA) technique and HPLC-DAD-ESI/MS analysis, it was found that phloretin and phloridzin could actively participate in the Maillard reaction and directly react with different reactive carbonyl species. The effect of phloretin and phloridzin treatment in both N(α)-acetyllysine-glucose (AC-glu), and N-acetyl-gly-lys methyl ester acetate salt-glucose (AG-glu) model systems, which are close to the Maillard reactions occurring in real food, where the free amino groups of lysine residues were considered as the reactive site, were further investigated. Similar impacts on the formation of Maillard-type volatiles and brown products as in the lysine-glucose models were observed which can also be explained by the capability of phloretin and phloridzin to quench sugar fragments formed in these model reactions.

The Academic Knowledge Management Model of Small Schools in Thailand

ERIC Educational Resources Information Center

Tumtuma, Chamnan; Chantarasombat, Chalard; Yeamsang, Theerawat

2015-01-01

The Academic Knowledge Management Model of Small Schools in Thailand was created by research and development. The quantitative and qualitative data were collected via the following steps: a participatory workshop meeting, the formation of a team according to knowledge base, field study, brainstorming, group discussion, activities carried out…

Is pigment patterning in fish skin determined by the Turing mechanism?

PubMed

Watanabe, Masakatsu; Kondo, Shigeru

2015-02-01

More than half a century ago, Alan Turing postulated that pigment patterns may arise from a mechanism that could be mathematically modeled based on the diffusion of two substances that interact with each other. Over the past 15 years, the molecular and genetic tools to verify this prediction have become available. Here, we review experimental studies aimed at identifying the mechanism underlying pigment pattern formation in zebrafish. Extensive molecular genetic studies in this model organism have revealed the interactions between the pigment cells that are responsible for the patterns. The mechanism discovered is substantially different from that predicted by the mathematical model, but it retains the property of 'local activation and long-range inhibition', a necessary condition for Turing pattern formation. Although some of the molecular details of pattern formation remain to be elucidated, current evidence confirms that the underlying mechanism is mathematically equivalent to the Turing mechanism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Constraining Feedback in Galaxy Formation: Using Galaxy and AGN Surveys to Shed Light on ``Gastrophysics"

NASA Astrophysics Data System (ADS)

Monaco, P.

2007-12-01

We present some results of the new MORGANA model for the rise of galaxies and active nuclei, and show that the improved physical motivation of the description of star formation and feedback allows to get hints on the physical processes at play. We propose that the high level of turbulence in star-forming bulges is at the base of the observed downsizing of AGNs. In this framework it is also possible to reproduce the recently obtained evidence that most low-redshift accretion is powered by relatively massive, slowly accreting black holes. Besides, we notice that many galaxy formation models (including MORGANA) fail to reproduce a basic observable, namely the number density of 10^{11} M_⊙ galaxies at z˜1, as traced by the GOODS-MUSIC sample. This points to a possibly missing ingredient in the modeling of stellar feedback.

Suppression of aberrant choroidal neovascularization through activation of the aryl hydrocarbon receptor.

PubMed

Choudhary, Mayur; Safe, Stephen; Malek, Goldis

2018-05-01

The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor, initially discovered for its role in regulating xenobiotic metabolism. There is extensive evidence supporting a multi-faceted role for AhR, modulating physiological pathways important in cell health and disease. Recently we demonstrated that the AhR plays a role in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that loss of AhR exacerbates choroidal neovascular (CNV) lesion formation in a murine model. Herein we tested the therapeutic impact of AhR activation on CNV lesion formation and factors associated with aberrant neovascularization. We screened a panel of synthetic drugs and endogenous AhR ligands, assessed their ability to activate AhR in choroidal endothelial cells, and inhibit angiogenesis in vitro. Drugs with an anti-angiogenic profile were then administered to a murine model of CNV. Two compounds, leflunomide and flutamide, significantly inhibited CNV formation concurrent with positive modifying effects on angiogenesis, inflammation, extracellular matrix remodeling, and fibrosis. These results validate the role of the AhR pathway in regulating CNV pathogenesis, identify mechanisms of AhR-based therapies in the eye, and argue in favor of developing AhR as a drug target for the treatment of neovascular AMD. Copyright © 2018 Elsevier B.V. All rights reserved.

Dynamical Properties of a Living Nematic

NASA Astrophysics Data System (ADS)

Genkin, Mikhail

The systems, which are made of a large number or interacting particles, or agents that convert the energy stored in the environment into mechanical motion, are called active systems, or active matter. The examples of active matter include both living and synthetic systems. The size of agents varies significantly: bird flocks and fish schools represent macroscopic active systems, while suspensions of living organisms or artificial colloidal particles are examples of microscopic ones. In this work, I studied one of the simplest realization of active matter termed living (or active) nematics, that can be conceived by mixing swimming bacteria and nematic liquid crystal. Using modeling, numerical simulations and experiments I studied various dynamical properties of active nematics. This work hints into new methods of control and manipulation of active matter. Active nematic exhibits complex spatiotemporal behavior manifested by formation, proliferation, and annihilation of topological defects. A new computational 2D model coupling nematic liquid crystal and swimming bacteria dynamics have been proposed. We investigated the developed system of partial differential equations analytically and integrated it numerically using the highly efficient parallel GPU code. The integration results are in a very good agreement with other theoretical and experimental studies. In addition, our model revealed a number of testable phenomena. The major model prediction (bacteria accumulation in positive and depletion in negative topological defects) was tested by a dedicated experiment. We extended our model to study active nematics in a biphasic state, where nematic and isotropic phases coexist. Typically this coexistence is manifested by formation of tactoids - isotropic elongated regions surrounded by nematic phase, or nematic regions surrounded by isotropic phase. Using numerical integration, we revealed fundamental properties of such systems. Our main model outcome - spontaneous negative charging of isotropic-nematic interfaces - was confirmed by the experiment. The provided modeling and experimental results are in a very good qualitative and quantitative agreement. At last, we studied living nematics experimentally. We worked with swimming bacteria Bacillus subtilis suspended in disodium cromoglycate (DSCG) liquid crystal. Using cylindrical confinement, we were able to observe quantization of nematics' bending instability. Our experimental results revealed a complex interplay between bacteria self-propulsion and nematics' elasticity in the presence of cylindrical confinements of different sizes.

Does intrinsic motivation strengthen physical activity habit? Modeling relationships between self-determination, past behaviour, and habit strength.

PubMed

Gardner, Benjamin; Lally, Phillippa

2013-10-01

Habit formation is thought to aid maintenance of physical activity, but little research is available into determinants of habit strength aside from repeated performance. Previous work has shown that intrinsically motivated physical activity, underpinned by inherent satisfaction derived from activity, is more likely to be sustained. We explored whether this might reflect a tendency for self-determined activity to become more strongly habitual. A sample of 192 adults aged 18-30 completed measures of motivational regulation, intention, behaviour, and habit strength. Results showed that self-determined regulation interacted with past behaviour in predicting habit strength: prior action was more predictive of habit strength among more autonomously motivated participants. There was an unexpected direct effect of self-determined regulation on habit strength, independently of past behaviour. Findings offer possible directions for future habit formation work.

Oral Administration of the Broad-Spectrum Antibiofilm Compound Toremifene Inhibits Candida albicans and Staphylococcus aureus Biofilm Formation In Vivo

PubMed Central

De Cremer, Kaat; Delattin, Nicolas; De Brucker, Katrijn; Peeters, Annelies; Kucharíková, Soña; Gerits, Evelien; Verstraeten, Natalie; Michiels, Jan; Van Dijck, Patrick; Thevissen, Karin

2014-01-01

We here report on the in vitro activity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, including Candida albicans, Candida glabrata, Candida dubliniensis, Candida krusei, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. We validated the in vivo efficacy of orally administered toremifene against C. albicans and S. aureus biofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound. PMID:25288093

The Atomic Dating Game.

ERIC Educational Resources Information Center

Cummo, Evelyn; Matthews, Catherine E.

2002-01-01

Presents an activity designed to provide students with opportunities to practice drawing atomic models and discover the logical pairings of whole families on the periodic table. Follows the format of a television game show. (DDR)

STAT3 activation in pressure-overloaded feline myocardium: role for integrins and the tyrosine kinase BMX.

PubMed

Willey, Christopher D; Palanisamy, Arun P; Johnston, Rebecca K; Mani, Santhosh K; Shiraishi, Hirokazu; Tuxworth, William J; Zile, Michael R; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani

2008-06-27

Growth, survival and cytoskeletal rearrangement of cardiomyocytes are critical for cardiac hypertrophy. Signal transducer and activator of transcription-3 (STAT3) activation is an important cardioprotective factor associated with cardiac hypertrophy. Although STAT3 activation has been reported via signaling through Janus Kinase 2 (JAK2) in several cardiac models of hypertrophy, the importance of other nonreceptor tyrosine kinases (NTKs) has not been explored. Utilizing an in vivo feline right ventricular pressure-overload (RVPO) model of hypertrophy, we demonstrate that in 48 h pressure-overload (PO) myocardium, STAT3 becomes phosphorylated and redistributed to detergent-insoluble fractions with no accompanying JAK2 activation. PO also caused increased levels of phosphorylated STAT3 in both cytoplasmic and nuclear fractions. To investigate the role of other NTKs, we used our established in vitro cell culture model of hypertrophy where adult feline cardiomyocytes are embedded three-dimensionally (3D) in type-I collagen and stimulated with an integrin binding peptide containing an Arg-Gly-Asp (RGD) motif that we have previously shown to recapitulate the focal adhesion complex (FAC) formation of 48 h RVPO. RGD stimulation of adult cardiomyocytes in vitro caused both STAT3 redistribution and activation that were accompanied by the activation and redistribution of c-Src and the TEC family kinase, BMX, but not JAK2. However, infection with dominant negative c-Src adenovirus was unable to block RGD-stimulated changes on either STAT3 or BMX. Further analysis in vivo in 48 h PO myocardium showed the presence of both STAT3 and BMX in the detergent-insoluble fraction with their complex formation and phosphorylation. Therefore, these studies indicate a novel mechanism of BMX-mediated STAT3 activation within a PO model of cardiac hypertrophy that might contribute to cardiomyocyte growth and survival.

Stratigraphic Signatures of Forearc Basin Formation Mechanisms

NASA Astrophysics Data System (ADS)

Mannu, U.; Ueda, K.; Gerya, T.; Willett, S.; Strasser, M.

2014-12-01

Forearc basins are loci of active sedimentation above the landward portion of accretionary prisms. Although these basins typically remain separated from the frontal prism by a forearc high, their evolution has a significant impact on the structure and deformation of the entire wedge. Formation of forearc basins has been proposed as a consequence of changes in wedge stability due to an increase of slab dip in subduction zones. Another hypothesis attributes this to higher hinterland sedimentation, which causes the rear of the wedge to stabilize and eventually develop a forearc basin. Basin stratigraphic architecture, revealed by high-resolution reflection seismic data and borehole data allows interpretation of structural development of the accretionary prism and associated basins with the goal of determining the underlying driving mechanism(s) of basin formation. In this study we supplement data interpretation with thermo-mechanical numerical models including high-resolution isochronal surface tracking to visualize the developing stratigraphy of basins that develop in subduction zone and wedge dynamic models. We use a dynamic 2D thermo mechanical model incorporating surface processes, strain weakening and sediment subduction. The model is a modification of I2VIS model, which is based on conservative, fully staggered finite differences and a non-diffusive marker- in-cell technique capable of modelling mantle convection. In the model different driving mechanisms for basin formation can be explored. Stratigraphic simulations obtained by isochronal surface tracking are compared to reflection pattern and stratigraphy of seismic and borehole data, respectively. Initial results from a model roughly representing the Nankai Trough Subduction Zone offshore Japan are compared to available seismic and Integrated Ocean Drilling (IODP) data. A calibrated model predicting forearc basin stratigraphy will be used to discern the underlying process of basins formation and wedge dynamics.

Comparing models of star formation simulating observed interacting galaxies

NASA Astrophysics Data System (ADS)

Quiroga, L. F.; Muñoz-Cuartas, J. C.; Rodrigues, I.

2017-07-01

In this work, we make a comparison between different models of star formation to reproduce observed interacting galaxies. We use observational data to model the evolution of a pair of galaxies undergoing a minor merger. Minor mergers represent situations weakly deviated from the equilibrium configuration but significant changes in star fomation (SF) efficiency can take place, then, minor mergers provide an unique scene to study SF in galaxies in a realistic but yet simple way. Reproducing observed systems also give us the opportunity to compare the results of the simulations with observations, which at the end can be used as probes to characterize the models of SF implemented in the comparison. In this work we compare two different star formation recipes implemented in Gadget3 and GIZMO codes. Both codes share the same numerical background, and differences arise mainly in the star formation recipe they use. We use observations from Pico dos Días and GEMINI telescopes and show how we use observational data of the interacting pair in AM2229-735 to characterize the interacting pair. Later we use this information to simulate the evolution of the system to finally reproduce the observations: Mass distribution, morphology and main features of the merger-induced star formation burst. We show that both methods manage to reproduce roughly the star formation activity. We show, through a careful study, that resolution plays a major role in the reproducibility of the system. In that sense, star formation recipe implemented in GIZMO code has shown a more robust performance. Acknowledgements: This work is supported by Colciencias, Doctorado Nacional - 617 program.

Activity of a social dynamics model

NASA Astrophysics Data System (ADS)

Reia, Sandro M.; Neves, Ubiraci P. C.

2015-10-01

Axelrod's model was proposed to study interactions between agents and the formation of cultural domains. It presents a transition from a monocultural to a multicultural steady state which has been studied in the literature by evaluation of the relative size of the largest cluster. In this article, we propose new measurements based on the concept of activity per agent to study the Axelrod's model on the square lattice. We show that the variance of system activity can be used to indicate the critical points of the transition. Furthermore the frequency distribution of the system activity is able to show a coexistence of phases typical of a first order phase transition. Finally, we verify a power law dependence between cluster activity and cluster size for multicultural steady state configurations at the critical point.

A Biophysical Model of CRISPR/Cas9 Activity for Rational Design of Genome Editing and Gene Regulation

PubMed Central

Farasat, Iman; Salis, Howard M.

2016-01-01

The ability to precisely modify genomes and regulate specific genes will greatly accelerate several medical and engineering applications. The CRISPR/Cas9 (Type II) system binds and cuts DNA using guide RNAs, though the variables that control its on-target and off-target activity remain poorly characterized. Here, we develop and parameterize a system-wide biophysical model of Cas9-based genome editing and gene regulation to predict how changing guide RNA sequences, DNA superhelical densities, Cas9 and crRNA expression levels, organisms and growth conditions, and experimental conditions collectively control the dynamics of dCas9-based binding and Cas9-based cleavage at all DNA sites with both canonical and non-canonical PAMs. We combine statistical thermodynamics and kinetics to model Cas9:crRNA complex formation, diffusion, site selection, reversible R-loop formation, and cleavage, using large amounts of structural, biochemical, expression, and next-generation sequencing data to determine kinetic parameters and develop free energy models. Our results identify DNA supercoiling as a novel mechanism controlling Cas9 binding. Using the model, we predict Cas9 off-target binding frequencies across the lambdaphage and human genomes, and explain why Cas9’s off-target activity can be so high. With this improved understanding, we propose several rules for designing experiments for minimizing off-target activity. We also discuss the implications for engineering dCas9-based genetic circuits. PMID:26824432

A spatially resolved network spike in model neuronal cultures reveals nucleation centers, circular traveling waves and drifting spiral waves.

PubMed

Paraskevov, A V; Zendrikov, D K

2017-03-23

We show that in model neuronal cultures, where the probability of interneuronal connection formation decreases exponentially with increasing distance between the neurons, there exists a small number of spatial nucleation centers of a network spike, from where the synchronous spiking activity starts propagating in the network typically in the form of circular traveling waves. The number of nucleation centers and their spatial locations are unique and unchanged for a given realization of neuronal network but are different for different networks. In contrast, if the probability of interneuronal connection formation is independent of the distance between neurons, then the nucleation centers do not arise and the synchronization of spiking activity during a network spike occurs spatially uniform throughout the network. Therefore one can conclude that spatial proximity of connections between neurons is important for the formation of nucleation centers. It is also shown that fluctuations of the spatial density of neurons at their random homogeneous distribution typical for the experiments in vitro do not determine the locations of the nucleation centers. The simulation results are qualitatively consistent with the experimental observations.

Time-Resolved Chemical Mapping in Light-Emitting Electrochemical Cells.

PubMed

Jafari, Mohammad Javad; Liu, Jiang; Engquist, Isak; Ederth, Thomas

2017-01-25

An understanding of the doping and ion distributions in light-emitting electrochemical cells (LECs) is required to approach a realistic conduction model which can precisely explain the electrochemical reactions, p-n junction formation, and ion dynamics in the active layer and to provide relevant information about LECs for systematic improvement of function and manufacture. Here, Fourier-transform infrared (FTIR) microscopy is used to monitor anion density profile and polymer structure in situ and for time-resolved mapping of electrochemical doping in an LEC under bias. The results are in very good agreement with the electrochemical doping model with respect to ion redistribution and formation of a dynamic p-n junction in the active layer. We also physically slow ions by decreasing the working temperature and study frozen-junction formation and immobilization of ions in a fixed-junction LEC device by FTIR imaging. The obtained results show irreversibility of the ion redistribution and polymer doping in a fixed-junction device. In addition, we demonstrate that infrared microscopy is a useful tool for in situ characterization of electroactive organic materials.

A spatially resolved network spike in model neuronal cultures reveals nucleation centers, circular traveling waves and drifting spiral waves

NASA Astrophysics Data System (ADS)

Paraskevov, A. V.; Zendrikov, D. K.

2017-04-01

We show that in model neuronal cultures, where the probability of interneuronal connection formation decreases exponentially with increasing distance between the neurons, there exists a small number of spatial nucleation centers of a network spike, from where the synchronous spiking activity starts propagating in the network typically in the form of circular traveling waves. The number of nucleation centers and their spatial locations are unique and unchanged for a given realization of neuronal network but are different for different networks. In contrast, if the probability of interneuronal connection formation is independent of the distance between neurons, then the nucleation centers do not arise and the synchronization of spiking activity during a network spike occurs spatially uniform throughout the network. Therefore one can conclude that spatial proximity of connections between neurons is important for the formation of nucleation centers. It is also shown that fluctuations of the spatial density of neurons at their random homogeneous distribution typical for the experiments in vitro do not determine the locations of the nucleation centers. The simulation results are qualitatively consistent with the experimental observations.

An in vitro model of Mycobacterium leprae induced granuloma formation

PubMed Central

2013-01-01

Background Leprosy is a contagious and chronic systemic granulomatous disease caused by Mycobacterium leprae. In the pathogenesis of leprosy, granulomas play a key role, however, the mechanisms of the formation and maintenance of M. leprae granulomas are still not clearly understood. Methods To better understand the molecular physiology of M. leprae granulomas and the interaction between the bacilli and human host cells, we developed an in vitro model of human granulomas, which mimicked the in vivo granulomas of leprosy. Macrophages were differentiated from human monocytes, and infected with M. leprae, and then cultured with autologous human peripheral blood mononuclear cells (PBMCs). Results Robust granuloma-like aggregates were obtained only when the M. leprae infected macrophages were co-cultured with PBMCs. Histological examination showed M. leprae within the cytoplasmic center of the multinucleated giant cells, and these bacilli were metabolically active. Macrophages of both M1 and M2 types co-existed in the granuloma like aggregates. There was a strong relationship between the formation of granulomas and changes in the expression levels of cell surface antigens on macrophages, cytokine production and the macrophage polarization. The viability of M. leprae isolated from granulomas indicated that the formation of host cell aggregates benefited the host, but the bacilli also remained metabolically active. Conclusions A simple in vitro model of human M. leprae granulomas was established using human monocyte-derived macrophages and PBMCs. This system may be useful to unravel the mechanisms of disease progression, and subsequently develop methods to control leprosy. PMID:23782413

An in vitro model of Mycobacterium leprae induced granuloma formation.

PubMed

Wang, Hongsheng; Maeda, Yumi; Fukutomi, Yasuo; Makino, Masahiko

2013-06-20

Leprosy is a contagious and chronic systemic granulomatous disease caused by Mycobacterium leprae. In the pathogenesis of leprosy, granulomas play a key role, however, the mechanisms of the formation and maintenance of M. leprae granulomas are still not clearly understood. To better understand the molecular physiology of M. leprae granulomas and the interaction between the bacilli and human host cells, we developed an in vitro model of human granulomas, which mimicked the in vivo granulomas of leprosy. Macrophages were differentiated from human monocytes, and infected with M. leprae, and then cultured with autologous human peripheral blood mononuclear cells (PBMCs). Robust granuloma-like aggregates were obtained only when the M. leprae infected macrophages were co-cultured with PBMCs. Histological examination showed M. leprae within the cytoplasmic center of the multinucleated giant cells, and these bacilli were metabolically active. Macrophages of both M1 and M2 types co-existed in the granuloma like aggregates. There was a strong relationship between the formation of granulomas and changes in the expression levels of cell surface antigens on macrophages, cytokine production and the macrophage polarization. The viability of M. leprae isolated from granulomas indicated that the formation of host cell aggregates benefited the host, but the bacilli also remained metabolically active. A simple in vitro model of human M. leprae granulomas was established using human monocyte-derived macrophages and PBMCs. This system may be useful to unravel the mechanisms of disease progression, and subsequently develop methods to control leprosy.

Prevention of artificial dental plaque formation in vitro by plant extracts.

PubMed

Smullen, J; Finney, M; Storey, D M; Foster, H A

2012-10-01

A number of previous studies have shown that plant extracts can inhibit formation of dental plaque. The ability of extracts of Rosmarinus officianalis L., Salvia officianalis L., unfermented cocoa, red grape seed and green tea to inhibit plaque bacteria, glucosyltransferase activity, glucan and plaque formation in an in vitro model using bovine teeth was examined. The antimicrobial activity of the plant extracts against oral bacteria was determined using a standard susceptibility agar dilution technique. Inhibition of growth and acid production from glucose and sucrose by Streptococcus mutans in liquid culture was investigated. Prevention of plaque formation on bovine teeth initiated by Strep. mutans was studied using an artificial mouth. The plant extracts inhibited the growth of oral bacteria and prevented acid production by Strep. mutans. Extracts inhibited glucosyltransferase activity and glucan production and inhibited adhesion to glass. Extracts of R. officianalis L. and S. officianalis L. at 0·25 mg ml(-1) reduced plaque growth by >80%. Green tea extract completely inhibited plaque formation but resulted in a greenish discolouration of the teeth which could not be removed by scrubbing. The plant extracts, particularly those from R. officianalis L. and S. officianalis L., inhibited glucosyltranferase activity, glucan production and plaque formation in vitro. The results suggest that the extracts of R. officianalis L. and S. officianalis L. may be useful as antiplaque agents in foods and dental preparations. Bovine teeth can be used as an alternative to hydroxyapatite for studies of plaque formation, but they need to be carefully sterilized before use. © 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

Self-organization of network dynamics into local quantized states.

PubMed

Nicolaides, Christos; Juanes, Ruben; Cueto-Felgueroso, Luis

2016-02-17

Self-organization and pattern formation in network-organized systems emerges from the collective activation and interaction of many interconnected units. A striking feature of these non-equilibrium structures is that they are often localized and robust: only a small subset of the nodes, or cell assembly, is activated. Understanding the role of cell assemblies as basic functional units in neural networks and socio-technical systems emerges as a fundamental challenge in network theory. A key open question is how these elementary building blocks emerge, and how they operate, linking structure and function in complex networks. Here we show that a network analogue of the Swift-Hohenberg continuum model-a minimal-ingredients model of nodal activation and interaction within a complex network-is able to produce a complex suite of localized patterns. Hence, the spontaneous formation of robust operational cell assemblies in complex networks can be explained as the result of self-organization, even in the absence of synaptic reinforcements.

From first galaxies to QSOs - feeding the baby monsters

NASA Astrophysics Data System (ADS)

Danese, L.; Shankar, F.; Granato, G. L.; Silva, L.; Bressan, A.; de Zotti, G.; Salucci, P.; Cirasuolo, M.

We present a physical model for the coevolution of massive spheroidal galaxies and active nuclei at their centers. Supernova heating is increasingly effective in slowing down the star formation and in driving gas outflows in smaller and smaller dark matter halos. Thus the more massive protogalaxies virializing at early times are the sites of faster star formation. The correspondingly higher radiation drag causes a faster angular momentum loss by the gas and induces a larger accretion rate onto the central black hole. In turn, the kinetic energy of the outflows powered by the active nuclei can unbind the residual gas in a time shorter for larger halos. The model accounts for a broad variety of dynamical, photometric and metallicity properties of early-type galaxies, for the MBH-σ relation and for the local supermassive black-hole mass function.

Applying Rasch analysis to evaluate measurement equivalence of different administration formats of the Activity Limitation scale of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).

PubMed

Twiss, J; McKenna, S P; Graham, J; Swetz, K; Sloan, J; Gomberg-Maitland, M

2016-04-09

Electronic formats of patient-reported outcome (PRO) measures are now routinely used in clinical research studies. When changing from a validated paper and pen to electronic administration it is necessary to establish their equivalence. This study reports on the value of Rasch analysis in this process. Three groups of US pulmonary hypertension (PH) patients participated. The first completed an electronic version of the CAMPHOR Activity Limitation scale (e-sample) and this was compared with two pen and paper administrated samples (pp1 and pp2). The three databases were combined and analysed for fit to the Rasch model. Equivalence was evaluated by differential item functioning (DIF) analyses. The three datasets were matched randomly in terms of sample size (n = 147). Mean age (years) and percentage of male respondents were as follows: e-sample (51.7, 16.0 %); pp1 (50.0, 14.0 %); pp2 (55.5, 40.4 %). The combined dataset achieved fit to the Rasch model. Two items showed evidence of borderline DIF. Further analyses showed the inclusion of these items had little impact on Rasch estimates indicating the DIF identified was unimportant. Differences between the performance of the electronic and pen and paper administrations of the CAMPHOR Activity Limitation scale were minor. The results were successful in showing how the Rasch model can be used to determine the equivalence of alternative formats of PRO measures.

Complementary roles of platelets and coagulation in thrombus formation on plaques acutely ruptured by targeted ultrasound treatment: a novel intravital model.

PubMed

Kuijpers, M J E; Gilio, K; Reitsma, S; Nergiz-Unal, R; Prinzen, L; Heeneman, S; Lutgens, E; van Zandvoort, M A M J; Nieswandt, B; Egbrink, M G A Oude; Heemskerk, J W M

2009-01-01

Atherothrombosis is a major cause of cardiovascular events. However, animal models to study this process are scarce. We describe the first murine model of acute thrombus formation upon plaque rupture to study atherothrombosis by intravital fluorescence microscopy. Localized rupture of an atherosclerotic plaque in a carotid artery from Apoe(-/-) mice was induced in vivo using ultrasound. Rupture of the plaque and formation of localized thrombi were verified by two-photon laser scanning microscopy (TPLSM) in isolated arteries, and by immunohistochemistry. The thrombotic reaction was quantified by intravital fluorescence microscopy. Inspection of the ultrasound-treated plaques by histochemistry and TPLSM demonstrated local damage, collagen exposure, luminal thrombus formation as well as intra-plaque intrusion of erythrocytes and fibrin. Ultrasound treatment of healthy carotid arteries resulted in endothelial damage and limited platelet adhesion. Real-time intravital fluorescence microscopy demonstrated rapid platelet deposition on plaques and formation of a single thrombus that remained subocclusive. The thrombotic process was antagonized by thrombin inhibition, or by blocking of collagen or adenosine diphosphate receptor pathways. Multiple thrombi were formed in 70% of mice lacking CD40L. Targeted rupture of murine plaques results in collagen exposure and non-occlusive thrombus formation. The thrombotic process relies on platelet activation as well as on thrombin generation and coagulation, and is sensitive to established and novel antithrombotic medication. This model provides new possibilities to study atherothrombosis in vivo.

Characterization of a genetically engineered mouse model of hemophilia A with complete deletion of the F8 gene.

PubMed

Chao, B N; Baldwin, W H; Healey, J F; Parker, E T; Shafer-Weaver, K; Cox, C; Jiang, P; Kanellopoulou, C; Lollar, P; Meeks, S L; Lenardo, M J

2016-02-01

ESSENTIALS: Anti-factor VIII (FVIII) inhibitory antibody formation is a severe complication in hemophilia A therapy. We genetically engineered and characterized a mouse model with complete deletion of the F8 coding region. F8(TKO) mice exhibit severe hemophilia, express no detectable F8 mRNA, and produce FVIII inhibitors. The defined background and lack of FVIII in F8(TKO) mice will aid in studying FVIII inhibitor formation. The most important complication in hemophilia A treatment is the development of inhibitory anti-Factor VIII (FVIII) antibodies in patients after FVIII therapy. Patients with severe hemophilia who express no endogenous FVIII (i.e. cross-reacting material, CRM) have the greatest incidence of inhibitor formation. However, current mouse models of severe hemophilia A produce low levels of truncated FVIII. The lack of a corresponding mouse model hampers the study of inhibitor formation in the complete absence of FVIII protein. We aimed to generate and characterize a novel mouse model of severe hemophilia A (designated the F8(TKO) strain) lacking the complete coding sequence of F8 and any FVIII CRM. Mice were created on a C57BL/6 background using Cre-Lox recombination and characterized using in vivo bleeding assays, measurement of FVIII activity by coagulation and chromogenic assays, and anti-FVIII antibody production using ELISA. All F8 exonic coding regions were deleted from the genome and no F8 mRNA was detected in F8(TKO) mice. The bleeding phenotype of F8(TKO) mice was comparable to E16 mice by measurements of factor activity and tail snip assay. Similar levels of anti-FVIII antibody titers after recombinant FVIII injections were observed between F8(TKO) and E16 mice. We describe a new C57BL/6 mouse model for severe hemophilia A patients lacking CRM. These mice can be directly bred to the many C57BL/6 strains of genetically engineered mice, which is valuable for studying the impact of a wide variety of genes on FVIII inhibitor formation on a defined genetic background. © 2015 International Society on Thrombosis and Haemostasis.

Paired and interacting galaxies: Conference summary

NASA Technical Reports Server (NTRS)

Norman, Colin A.

1990-01-01

The author gives a summary of the conference proceedings. The conference began with the presentation of the basic data sets on pairs, groups, and interacting galaxies with the latter being further discussed with respect to both global properties and properties of the galactic nuclei. Then followed the theory, modelling and interpretation using analytic techniques, simulations and general modelling for spirals and ellipticals, starbursts and active galactic nuclei. Before the conference the author wrote down the three questions concerning pairs, groups and interacting galaxies that he hoped would be answered at the meeting: (1) How do they form, including the role of initial conditions, the importance of subclustering, the evolution of groups to compact groups, and the fate of compact groups; (2) How do they evolve, including issues such as relevant timescales, the role of halos and the problem of overmerging, the triggering and enhancement of star formation and activity in the galactic nuclei, and the relative importance of dwarf versus giant encounters; and (3) Are they important, including the frequency of pairs and interactions, whether merging and interactions are very important aspects of the life of a normal galaxy at formation, during its evolution, in forming bars, shells, rings, bulges, etc., and in the formation and evolution of active galaxies? Where possible he focuses on these three central issues in the summary.

An in-depth investigation of the life cycle of sulfate from the Kilauea volcano using satellite observations and EMAC model calculations

NASA Astrophysics Data System (ADS)

Penning de Vries, Marloes; Beirle, Steffen; Brühl, Christoph; Hörmann, Christoph; Wagner, Thomas

2015-04-01

The Kilauea volcano (Hawaii), currently perhaps the most active volcano on Earth, has been continuously erupting since the beginning of 1983. A pronounced degassing phase in March-November 2008 caused the formation of an extensive SO2 plume, which in turn led to the formation of sulfate aerosols. The steady trade winds and lack of interfering sources previously allowed us to determine the life time of SO2 using only satellite-based measurements (no a priori or model information). The current investigation is focused on improving our understanding of the processes contributing to sulfate aerosol formation, processing, and loss. We use space-based aerosol measurements by MODIS, MISR, and CALIOP to characterize the aerosols (amount, size, altitude) and study the evolution of aerosol optical depth as a function of distance from the volcano to determine formation and loss rates. The outcome is compared to results from calculations using the EMAC (ECHAM/MESSy Atmospheric Chemistry) model to test the state of understanding of the sulfate aerosol life cycle.

3-D Hybrid Kinetic Modeling of the Interaction Between the Solar Wind and Lunar-like Exospheric Pickup Ions in Case of Oblique/ Quasi-Parallel/Parallel Upstream Magnetic Field

NASA Technical Reports Server (NTRS)

Lipatov, A. S.; Farrell, W. M.; Cooper, J. F.; Sittler, E. C., Jr.; Hartle, R. E.

2015-01-01

The interactions between the solar wind and Moon-sized objects are determined by a set of the solar wind parameters and plasma environment of the space objects. The orientation of upstream magnetic field is one of the key factors which determines the formation and structure of bow shock wave/Mach cone or Alfven wing near the obstacle. The study of effects of the direction of the upstream magnetic field on lunar-like plasma environment is the main subject of our investigation in this paper. Photoionization, electron-impact ionization and charge exchange are included in our hybrid model. The computational model includes the self-consistent dynamics of the light (hydrogen (+), helium (+)) and heavy (sodium (+)) pickup ions. The lunar interior is considered as a weakly conducting body. Our previous 2013 lunar work, as reported in this journal, found formation of a triple structure of the Mach cone near the Moon in the case of perpendicular upstream magnetic field. Further advances in modeling now reveal the presence of strong wave activity in the upstream solar wind and plasma wake in the cases of quasiparallel and parallel upstream magnetic fields. However, little wave activity is found for the opposite case with a perpendicular upstream magnetic field. The modeling does not show a formation of the Mach cone in the case of theta(Sub B,U) approximately equal to 0 degrees.

Protective mechanisms of adenosine 5'-monophosphate in platelet activation and thrombus formation.

PubMed

Fuentes, E; Badimon, L; Caballero, J; Padró, T; Vilahur, G; Alarcón, M; Pérez, P; Palomo, I

2014-03-03

Platelet activation is relevant to a variety of acute thrombotic events. We sought to examine adenosine 5'-monophosphate (AMP) mechanisms of action in preventing platelet activation, thrombus formation and platelet-related inflammatory response. We assessed the effect of AMP on 1) P-selectin expression and GPIIb/IIIa activation by flow cytometry; 2) Platelet aggregation and ATP secretion induced by ADP, collagen, TRAP-6, convulxin and thrombin; 3) Platelet rolling and firm adhesion, and platelet-leukocyte interactions under flow-controlled conditions; and, 4) Platelet cAMP levels, sP-selectin, sCD40L, IL-1β, TGF-β1 and CCL5 release, PDE3A activity and PKA phosphorylation. The effect of AMP on in vivo thrombus formation was also evaluated in a murine model. The AMP docking with respect to A2 adenosine receptor was determined by homology. AMP concentration-dependently (0.1 to 3 mmol/l) inhibited P-selectin expression and GPIIb/IIIa activation, platelet secretion and aggregation induced by ADP, collagen, TRAP-6 and convulxin, and diminished platelet rolling and firm adhesion. Furthermore, AMP induced a marked increase in the rolling speed of leukocytes retained on the platelet surface. At these concentrations AMP significantly decreased inflammatory mediator from platelet, increased intraplatelet cAMP levels and inhibited PDE3A activity. Interestingly, SQ22536, ZM241385 and SCH58261 attenuated the antiplatelet effect of AMP. Docking experiments revealed that AMP had the same orientation that adenosine inside the A2 adenosine receptor binding pocket. These in vitro antithrombotic properties were further supported in an in vivo model of thrombosis. Considering the successful use of combined antiplatelet therapy, AMP may be further developed as a novel antiplatelet agent.

Volatilization of low vapor pressure--volatile organic compounds (LVP-VOCs) during three cleaning products-associated activities: Potential contributions to ozone formation.

PubMed

Shin, Hyeong-Moo; McKone, Thomas E; Bennett, Deborah H

2016-06-01

There have been many studies to reduce ozone formation mostly from volatile organic compound (VOC) sources. However, the role of low vapor pressure (LVP)-VOCs from consumer products remains mostly unexplored and unaddressed. This study explores the impact of high production volume LVP-VOCs on ozone formation from three cleaning products-associated activities (dishwashing, clothes washing, and surface cleaning). We develop a model framework to account for the portion available for ozone formation during the use phase and from the down-the-drain disposal. We apply experimental studies that measured emission rates or models that were developed for estimating emission rates of organic compounds during the use phase. Then, the fraction volatilized (fvolatilized) and the fraction disposed down the drain (fdown-the-drain) are multiplied by the portion available for ozone formation for releases to the outdoor air (fO3|volatilized) and down-the-drain (fO3|down-the-drain), respectively. Overall, for chemicals used in three specific cleaning-product uses, fvolatilized is less than 0.6% for all studied LVP-VOCs. Because greater than 99.4% of compounds are disposed of down the drain during the use phase, when combined with fO3|volatilized and fO3|down-the-drain, the portion available for ozone formation from the direct releases to outdoor air and the down-the-drain disposal is less than 0.4% and 0.2%, respectively. The results from this study indicate that the impact of the studied LVP-VOCs on ozone formation is very sensitive to what occurs during the use phase and suggest the need for future research on experimental work at the point of use. Copyright © 2016 Elsevier Ltd. All rights reserved.

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

PubMed Central

Dumas, Jerald E.; Prieto, Edna M.; Zienkiewicz, Katarzyna J.; Guda, Teja; Wenke, Joseph C.; Bible, Jesse; Holt, Ginger E.

2014-01-01

There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling. PMID:23941405

FORMATION AND ERUPTION OF A FLUX ROPE FROM THE SIGMOID ACTIVE REGION NOAA 11719 AND ASSOCIATED M6.5 FLARE: A MULTI-WAVELENGTH STUDY

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

Joshi, Bhuwan; Kushwaha, Upendra; Dhara, Sajal Kumar

We investigate the formation, activation, and eruption of a flux rope (FR) from the sigmoid active region NOAA 11719 by analyzing E(UV), X-ray, and radio measurements. During the pre-eruption period of ∼7 hr, the AIA 94 Å images reveal the emergence of a coronal sigmoid through the interaction between two J-shaped bundles of loops, which proceeds with multiple episodes of coronal loop brightenings and significant variations in the magnetic flux through the photosphere. These observations imply that repetitive magnetic reconnections likely play a key role in the formation of the sigmoidal FR in the corona and also contribute toward sustaining themore » temperature of the FR higher than that of the ambient coronal structures. Notably, the formation of the sigmoid is associated with the fast morphological evolution of an S-shaped filament channel in the chromosphere. The sigmoid activates toward eruption with the ascent of a large FR in the corona, which is preceded by the decrease in photospheric magnetic flux through the core flaring region, suggesting tether-cutting reconnection as a possible triggering mechanism. The FR eruption results in a two-ribbon M6.5 flare with a prolonged rise phase of ∼21 minutes. The flare exhibits significant deviation from the standard flare model in the early rise phase, during which a pair of J-shaped flare ribbons form and apparently exhibit converging motions parallel to the polarity inversion line, which is further confirmed by the motions of hard X-ray footpoint sources. In the later stages, the flare follows the standard flare model and the source region undergoes a complete sigmoid-to-arcade transformation.« less

3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep.

PubMed

Ding, Ming; Henriksen, Susan S; Martinetti, Roberta; Overgaard, Søren

2017-11-01

Early fixation of total joint arthroplasties is crucial for ensuring implant survival. An alternative bone graft material in revision surgery is needed to replace the current gold standard, allograft, seeing that the latter is associated with several disadvantages. The incubation of such a construct in a perfusion bioreactor has been shown to produce viable bone graft materials. This study aimed at producing larger amounts of viable bone graft material (hydroxyapatite 70% and β-tricalcium-phosphate 30%) in a novel perfusion bioreactor. The abilities of the bioreactor-activated graft material to induce early implant fixation were tested in a bilateral implant defect model in sheep, with allograft as the control group. Defects were bilaterally created in the distal femurs of the animals, and titanium implants were inserted. The concentric gaps around the implants were randomly filled with either allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while no significant differences between groups were found regarding early implant fixation. The microarchitecture of the bone formed by the synthetic graft materials resembled that of allograft. Histomorphometry revealed that allograft induced significantly more bone and less fibrous tissue (p < 0.05). In conclusion, bone formation was observed in all groups, while the bioreactor-activated graft material did not reveal additional effects on early implant fixation comparable to allograft in this model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2465-2476, 2017. © 2016 Wiley Periodicals, Inc.

Testing the Accuracy of Data-driven MHD Simulations of Active Region Evolution and Eruption

NASA Astrophysics Data System (ADS)

Leake, J. E.; Linton, M.; Schuck, P. W.

2017-12-01

Models for the evolution of the solar coronal magnetic field are vital for understanding solar activity, yet the best measurements of the magnetic field lie at the photosphere, necessitating the recent development of coronal models which are "data-driven" at the photosphere. Using magnetohydrodynamic simulations of active region formation and our recently created validation framework we investigate the source of errors in data-driven models that use surface measurements of the magnetic field, and derived MHD quantities, to model the coronal magnetic field. The primary sources of errors in these studies are the temporal and spatial resolution of the surface measurements. We will discuss the implications of theses studies for accurately modeling the build up and release of coronal magnetic energy based on photospheric magnetic field observations.

Models of Formation and Activity of Spring Mounds in the Mechertate-Chrita-Sidi El Hani System, Eastern Tunisia: Implications for the Habitability of Mars

PubMed Central

Essefi, Elhoucine; Komatsu, Goro; Fairén, Alberto G.; Chan, Marjorie A.; Yaich, Chokri

2014-01-01

Spring mounds on Earth and on Mars could represent optimal niches of life development. If life ever occurred on Mars, ancient spring deposits would be excellent localities to search for morphological or chemical remnants of an ancient biosphere. In this work, we investigate models of formation and activity of well-exposed spring mounds in the Mechertate-Chrita-Sidi El Hani (MCSH) system, eastern Tunisia. We then use these models to explore possible spring mound formation on Mars. In the MCSH system, the genesis of the spring mounds is a direct consequence of groundwater upwelling, triggered by tectonics and/or hydraulics. As they are oriented preferentially along faults, they can be considered as fault spring mounds, implying a tectonic influence in their formation process. However, the hydraulic pressure generated by the convergence of aquifers towards the surface of the system also allows consideration of an origin as artesian spring mounds. In the case of the MCSH system, our geologic data presented here show that both models are valid, and we propose a combined hydro-tectonic model as the likely formation mechanism of artesian-fault spring mounds. During their evolution from the embryonic (early) to the islet (“island”) stages, spring mounds are also shaped by eolian accumulations and induration processes. Similarly, spring mounds have been suggested to be relatively common in certain provinces on the Martian surface, but their mode of formation is still a matter of debate. We propose that the tectonic, hydraulic, and combined hydro-tectonic models describing the spring mounds at MCSH could be relevant as Martian analogs because: (i) the Martian subsurface may be over pressured, potentially expelling mineral-enriched waters as spring mounds on the surface; (ii) the Martian subsurface may be fractured, causing alignment of the spring mounds in preferential orientations; and (iii) indurated eolian sedimentation and erosional remnants are common features on Mars. The spring mounds further bear diagnostic mineralogic and magnetic properties, in comparison with their immediate surroundings. Consequently, remote sensing techniques can be very useful to identify similar spring mounds on Mars. The mechanisms (tectonic and/or hydraulic) of formation and evolution of spring mounds at the MCSH system are suitable for the proliferation and protection of life respectively. Similarly, life or its resulting biomarkers on Mars may have been protected or preserved under the spring mounds. PMID:25370379

Models of formation and activity of spring mounds in the mechertate-chrita-sidi el hani system, eastern Tunisia: implications for the habitability of Mars.

PubMed

Essefi, Elhoucine; Komatsu, Goro; Fairén, Alberto G; Chan, Marjorie A; Yaich, Chokri

2014-08-28

Spring mounds on Earth and on Mars could represent optimal niches of life development. If life ever occurred on Mars, ancient spring deposits would be excellent localities to search for morphological or chemical remnants of an ancient biosphere. In this work, we investigate models of formation and activity of well-exposed spring mounds in the Mechertate-Chrita-Sidi El Hani (MCSH) system, eastern Tunisia. We then use these models to explore possible spring mound formation on Mars. In the MCSH system, the genesis of the spring mounds is a direct consequence of groundwater upwelling, triggered by tectonics and/or hydraulics. As they are oriented preferentially along faults, they can be considered as fault spring mounds, implying a tectonic influence in their formation process. However, the hydraulic pressure generated by the convergence of aquifers towards the surface of the system also allows consideration of an origin as artesian spring mounds. In the case of the MCSH system, our geologic data presented here show that both models are valid, and we propose a combined hydro-tectonic model as the likely formation mechanism of artesian-fault spring mounds. During their evolution from the embryonic (early) to the islet ("island") stages, spring mounds are also shaped by eolian accumulations and induration processes. Similarly, spring mounds have been suggested to be relatively common in certain provinces on the Martian surface, but their mode of formation is still a matter of debate. We propose that the tectonic, hydraulic, and combined hydro-tectonic models describing the spring mounds at MCSH could be relevant as Martian analogs because: (i) the Martian subsurface may be over pressured, potentially expelling mineral-enriched waters as spring mounds on the surface; (ii) the Martian subsurface may be fractured, causing alignment of the spring mounds in preferential orientations; and (iii) indurated eolian sedimentation and erosional remnants are common features on Mars. The spring mounds further bear diagnostic mineralogic and magnetic properties, in comparison with their immediate surroundings. Consequently, remote sensing techniques can be very useful to identify similar spring mounds on Mars. The mechanisms (tectonic and/or hydraulic) of formation and evolution of spring mounds at the MCSH system are suitable for the proliferation and protection of life respectively. Similarly, life or its resulting biomarkers on Mars may have been protected or preserved under the spring mounds.

Hormone-Mediated Pattern Formation in Seedling of Plants: a Competitive Growth Dynamics Model

NASA Astrophysics Data System (ADS)

Kawaguchi, Satoshi; Mimura, Masayasu; Ohya, Tomoyuki; Oikawa, Noriko; Okabe, Hirotaka; Kai, Shoichi

2001-10-01

An ecologically relevant pattern formation process mediated by hormonal interactions among growing seedlings is modeled based on the experimental observations on the effects of indole acetic acid, which can act as an inhibitor and activator of root growth depending on its concentration. In the absence of any lateral root with constant hormone-sensitivity, the edge effect phenomenon is obtained depending on the secretion rate of hormone from the main root. Introduction of growth-stage-dependent hormone-sensitivity drastically amplifies the initial randomness, resulting in spatially irregular macroscopic patterns. When the lateral root growth is introduced, periodic patterns are obtained whose periodicity depends on the length of lateral roots. The growth-stage-dependent hormone-sensitivity and the lateral root growth are crucial for macroscopic periodic-pattern formation.

A kinetic model to explain the maximum in alpha-amylase activity measurements in the presence of small carbohydrates.

PubMed

Baks, Tim; Janssen, Anja E M; Boom, Remko M

2006-06-20

The effect of the presence of several small carbohydrates on the measurement of the alpha-amylase activity was determined over a broad concentration range. At low carbohydrate concentrations, a distinct maximum in the alpha-amylase activity versus concentration curves was observed in several cases. At higher concentrations, all carbohydrates show a decreasing alpha-amylase activity at increasing carbohydrate concentrations. A general kinetic model has been developed that can be used to describe and explain these phenomena. This model is based on the formation of a carbohydrate-enzyme complex that remains active. It is assumed that this complex is formed when a carbohydrate binds to alpha-amylase without blocking the catalytic site and its surrounding subsites. Furthermore, the kinetic model incorporates substrate inhibition and substrate competition. Depending on the carbohydrate type and concentration, the measured alpha-amylase activity can be 75% lower than the actual alpha-amylase activity. The model that has been developed can be used to correct for these effects in order to obtain the actual amount of active enzyme. 2006 Wiley Periodicals, Inc.

Direct Push supported geotechnical and hydrogeological characterisation of an active sinkhole area

NASA Astrophysics Data System (ADS)

Tippelt, Thomas; Vienken, Thomas; Kirsch, Reinhard; Dietrich, Peter; Werban, Ulrike

2017-04-01

Sinkholes represent a natural geologic hazard in areas where soluble layers are present in the subsurface. A detailed knowledge of the composition of the subsurface and its hydrogeological and geotechnical properties is essential for the understanding of sinkhole formation and propagation. This serves as base for risk evaluation and the development of an early warning system. However, site models often depend on data from drillings and surface geophysical surveys that in many cases cannot resolve the spatial distribution of relevant hydrogeological and geotechnical parameters sufficiently. Therefore, an active sinkhole area in Münsterdorf, Northern Germany, was investigated in detail using Direct Push technology, a minimally invasive sounding method. The obtained vertical high-resolution profiles of geotechnical and hydrogeological characteristics, in combination with Direct Push based sampling and surface geophysical measurements lead to a strong improvement of the geologic site model. The conceptual site model regarding sinkhole formation and propagation will then be tested based on the gathered data and, if necessary, adapted accordingly.

Meeting report from the fourth meeting of the Computational Modeling in Biology Network (COMBINE)

PubMed Central

Waltemath, Dagmar; Bergmann, Frank T.; Chaouiya, Claudine; Czauderna, Tobias; Gleeson, Padraig; Goble, Carole; Golebiewski, Martin; Hucka, Michael; Juty, Nick; Krebs, Olga; Le Novère, Nicolas; Mi, Huaiyu; Moraru, Ion I.; Myers, Chris J.; Nickerson, David; Olivier, Brett G.; Rodriguez, Nicolas; Schreiber, Falk; Smith, Lucian; Zhang, Fengkai; Bonnet, Eric

2014-01-01

The Computational Modeling in Biology Network (COMBINE) is an initiative to coordinate the development of community standards and formats in computational systems biology and related fields. This report summarizes the topics and activities of the fourth edition of the annual COMBINE meeting, held in Paris during September 16-20 2013, and attended by a total of 96 people. This edition pioneered a first day devoted to modeling approaches in biology, which attracted a broad audience of scientists thanks to a panel of renowned speakers. During subsequent days, discussions were held on many subjects including the introduction of new features in the various COMBINE standards, new software tools that use the standards, and outreach efforts. Significant emphasis went into work on extensions of the SBML format, and also into community-building. This year’s edition once again demonstrated that the COMBINE community is thriving, and still manages to help coordinate activities between different standards in computational systems biology.

Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation.

PubMed

Scheidegger, F; Ellner, Y; Guye, P; Rhomberg, T A; Weber, H; Augustin, H G; Dehio, C

2009-07-01

The zoonotic pathogen Bartonella henselae (Bh) can lead to vasoproliferative tumour lesions in the skin and inner organs known as bacillary angiomatosis and bacillary peliosis. The knowledge on the molecular and cellular mechanisms involved in this pathogen-triggered angiogenic process is confined by the lack of a suitable animal model and a physiologically relevant cell culture model of angiogenesis. Here we employed a three-dimensional in vitro angiogenesis assay of collagen gel-embedded endothelial cell (EC) spheroids to study the angiogenic properties of Bh. Spheroids generated from Bh-infected ECs displayed a high capacity to form sprouts, which represent capillary-like projections into the collagen gel. The VirB/VirD4 type IV secretion system and a subset of its translocated Bartonella effector proteins (Beps) were found to profoundly modulate this Bh-induced sprouting activity. BepA, known to protect ECs from apoptosis, strongly promoted sprout formation. In contrast, BepG, triggering cytoskeletal rearrangements, potently inhibited sprouting. Hence, the here established in vitro model of Bartonella- induced angiogenesis revealed distinct and opposing activities of type IV secretion system effector proteins, which together with a VirB/VirD4-independent effect may control the angiogenic activity of Bh during chronic infection of the vasculature.

In Vitro Activity of Miltefosine against Candida albicans under Planktonic and Biofilm Growth Conditions and In Vivo Efficacy in a Murine Model of Oral Candidiasis

PubMed Central

Chaturvedi, Ashok K.; Rozental, Sonia

2015-01-01

The generation of a new antifungal against Candida albicans biofilms has become a major priority, since biofilm formation by this opportunistic pathogenic fungus is usually associated with an increased resistance to azole antifungal drugs and treatment failures. Miltefosine is an alkyl phospholipid with promising antifungal activity. Here, we report that, when tested under planktonic conditions, miltefosine displays potent in vitro activity against multiple fluconazole-susceptible and -resistant C. albicans clinical isolates, including isolates overexpressing efflux pumps and/or with well-characterized Erg11 mutations. Moreover, miltefosine inhibits C. albicans biofilm formation and displays activity against preformed biofilms. Serial passage experiments confirmed that miltefosine has a reduced potential to elicit resistance, and screening of a library of C. albicans transcription factor mutants provided additional insight into the activity of miltefosine against C. albicans growing under planktonic and biofilm conditions. Finally, we demonstrate the in vivo efficacy of topical treatment with miltefosine in the murine model of oropharyngeal candidiasis. Overall, our results confirm the potential of miltefosine as a promising antifungal drug candidate, in particular for the treatment of azole-resistant and biofilm-associated superficial candidiasis. PMID:26416861

Saracatinib Impairs Head and Neck Squamous Cell Carcinoma Invasion by Disrupting Invadopodia Function

PubMed Central

Ammer, Amanda Gatesman; Kelley, Laura C.; Hayes, Karen E.; Evans, Jason V.; Lopez-Skinner, Lesly Ann; Martin, Karen H.; Frederick, Barbara; Rothschild, Brian L.; Raben, David; Elvin, Paul; Green, Tim P.; Weed, Scott A.

2010-01-01

Elevated Src kinase activity is linked to the progression of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Src regulates HNSCC proliferation and tumor invasion, with the Src-targeted small molecule inhibitor saracatinib displaying potent anti-invasive effects in preclinical studies. However, the pro-invasive cellular mechanism(s) perturbed by saracatinib are unclear. The anti-proliferative and anti-invasive effects of saracatinib on HNSCC cell lines were therefore investigated in pre-clinical cell and mouse model systems. Saracatinib treatment inhibited growth, cell cycle progression and transwell Matrigel invasion in HNSCC cell lines. Dose-dependent decreases in Src activation and phosphorylation of the invasion-associated substrates focal adhesion kinase, p130 CAS and cortactin were also observed. While saracatinib did not significantly impact HNSCC tumor growth in a mouse orthotopic model of tongue squamous cell carcinoma, impaired perineural invasion and cervical lymph node metastasis was observed. Accordingly, saracatinib treatment displayed a dose-dependent inhibitory effect on invadopodia formation, extracellular matrix degradation and matrix metalloprotease 9 activation. These results suggest that inhibition of Src kinase by saracatinib impairs the pro-invasive activity of HNSCC by inhibiting Src substrate phosphorylation important for invadopodia formation and associated matrix metalloprotease activity. PMID:20505783

Oscillations and uniaxial mechanochemical waves in a model of an active poroelastic medium: Application to deformation patterns in protoplasmic droplets of Physarum polycephalum

NASA Astrophysics Data System (ADS)

Alonso, Sergio; Strachauer, Ulrike; Radszuweit, Markus; Bär, Markus; Hauser, Marcus J. B.

2016-04-01

Self-organization in cells often manifests itself in oscillations and waves. Here, we address deformation waves in protoplasmic droplets of the plasmodial slime mould Physarum polycephalum by modelling and experiments. In particular, we extend a one-dimensional model that considered the cell as a poroelastic medium, where active tension caused mechanochemical waves that were regulated by an inhibitor (Radszuweit et al., 2013). Our extension consists of a simple, qualitative chemical reaction-diffusion model (Brusselator) that describes the regulation of the inhibitor by another biochemical species. The biochemical reaction enhances the formation of mechanochemical waves if the reaction rates and input concentrations are near or inside an oscillatory regime. The period of the waves is found to be controlled by the characteristic oscillation period, whereas their wavelength is set by mechanical parameters. The model also allows for a systematic study of the chemical activity at the onset of mechanochemical waves. We also present examples for pattern formation in protoplasmic droplets of Physarum polycephalum including global oscillations where the central region of the droplets is in antiphase to the boundary zone, as well as travelling and standing wave-like uniaxial patterns. Finally, we apply our model to reproduce these experimental results by identifying the active tension inhibitor with the intracellular calcium concentration in the Physarum droplets and by using parameter values from mechanical experiments, respectively knowledge about the properties of calcium oscillations in Physarum. The simulation results are then found to be in good agreement with the experimental observations.

Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and facilitates HPV-8- and UV-light induced skin carcinogenesis

PubMed Central

Deshmukh, Jayesh; Pofahl, Ruth; Pfister, Herbert; Haase, Ingo

2016-01-01

Overexpression and increased activity of the small Rho GTPase Rac1 has been linked to squamous cell carcinoma of the epidermis and mucosa in humans. Targeted deletion of Rac1 or inhibition of Rac1 activity in epidermal keratinocytes reduced papilloma formation in a chemical skin carcinogenesis mouse model. However, a potential role of Rac1 in HPV- and UV-light induced skin carcinogenesis has not been investigated so far, solar UV radiation being an important carcinogen to the skin. To investigate this, we deleted Rac1 or modulated its activity in mice with transgenic expression of Human papilloma virus type-8 (HPV-8) in epidermal keratinocytes. Our data show that inhibition or deletion of Rac1 results in reduced papilloma formation upon UV-irradiation with a single dose, whereas constitutive activation of Rac1 strongly increases papilloma frequency in these mice. Surprisingly, we observed that, upon chronic UV-irradiation, the majority of mice with transgenic expression of HPV-8 and epidermis specific Rac1 deletion developed squamous cell carcinomas. Taken together, our data show that Rac1 exerts a dual role in skin carcinogenesis: its activation is, on one hand, required for HPV-8- and UV-light induced papilloma formation but, on the other, suppresses the development of squamous cell carcinomas. PMID:27506937

Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and facilitates HPV-8- and UV-light induced skin carcinogenesis.

PubMed

Deshmukh, Jayesh; Pofahl, Ruth; Pfister, Herbert; Haase, Ingo

2016-09-06

Overexpression and increased activity of the small Rho GTPase Rac1 has been linked to squamous cell carcinoma of the epidermis and mucosa in humans. Targeted deletion of Rac1 or inhibition of Rac1 activity in epidermal keratinocytes reduced papilloma formation in a chemical skin carcinogenesis mouse model. However, a potential role of Rac1 in HPV- and UV-light induced skin carcinogenesis has not been investigated so far, solar UV radiation being an important carcinogen to the skin.To investigate this, we deleted Rac1 or modulated its activity in mice with transgenic expression of Human papilloma virus type-8 (HPV-8) in epidermal keratinocytes. Our data show that inhibition or deletion of Rac1 results in reduced papilloma formation upon UV-irradiation with a single dose, whereas constitutive activation of Rac1 strongly increases papilloma frequency in these mice. Surprisingly, we observed that, upon chronic UV-irradiation, the majority of mice with transgenic expression of HPV-8 and epidermis specific Rac1 deletion developed squamous cell carcinomas. Taken together, our data show that Rac1 exerts a dual role in skin carcinogenesis: its activation is, on one hand, required for HPV-8- and UV-light induced papilloma formation but, on the other, suppresses the development of squamous cell carcinomas.

Scaling Relations for Intercalation Induced Damage in Electrodes

DOE PAGES

Chen, Chien-Fan; Barai, Pallab; Smith, Kandler; ...

2016-04-02

Mechanical degradation, owing to intercalation induced stress and microcrack formation, is a key contributor to the electrode performance decay in lithium-ion batteries (LIBs). The stress generation and formation of microcracks are caused by the solid state diffusion of lithium in the active particles. Here in this work, scaling relations are constructed for diffusion induced damage in intercalation electrodes based on an extensive set of numerical experiments with a particle-level description of microcrack formation under disparate operating and cycling conditions, such as temperature, particle size, C-rate, and drive cycle. The microcrack formation and evolution in active particles is simulated based onmore » a stochastic methodology. A reduced order scaling law is constructed based on an extensive set of data from the numerical experiments. The scaling relations include combinatorial constructs of concentration gradient, cumulative strain energy, and microcrack formation. Lastly, the reduced order relations are further employed to study the influence of mechanical degradation on cell performance and validated against the high order model for the case of damage evolution during variable current vehicle drive cycle profiles.« less

Gallium diffusion in zinc oxide via the paired dopant-vacancy mechanism

NASA Astrophysics Data System (ADS)

Sky, T. N.; Johansen, K. M.; Riise, H. N.; Svensson, B. G.; Vines, L.

2018-02-01

Isochronal and isothermal diffusion experiments of gallium (Ga) in zinc oxide (ZnO) have been performed in the temperature range of 900-1050 °C. The samples used consisted of a sputter-deposited and highly Ga-doped ZnO film at the surface of a single-crystal bulk material. We use a novel reaction diffusion (RD) approach to demonstrate that the diffusion behavior of Ga in ZnO is consistent with zinc vacancy (VZn) mediation via the formation and dissociation of GaZnVZn complexes. In the RD modeling, experimental diffusion data are fitted utilizing recent density-functional-theory estimates of the VZn formation energy and the binding energy of GaZnVZn. From the RD modeling, a migration energy of 2.3 eV is deduced for GaZnVZn, and a total/effective activation energy of 3.0 eV is obtained for the Ga diffusion. Furthermore, and for comparison, employing the so-called Fair model, a total/effective activation energy of 2.7 eV is obtained for the Ga diffusion, reasonably close to the total value extracted from the RD-modeling.

Starless Clumps and the Earliest Phases of High-mass Star Formation in the Milky Way

NASA Astrophysics Data System (ADS)

Svoboda, Brian

2018-01-01

High-mass stars are key to regulating the interstellar medium, star formation activity, and overall evolution of galaxies, but their formation remains an open problem in astrophysics. In order to understand the physical conditions during the earliest phases of high-mass star formation, I report on observational studies of dense starless clump candidates (SCCs) that show no signatures of star formation activity. I identify 2223 SCCs from the 1.1 mm Bolocam Galactic Plane Survey, systematically analyze their physical properties, and show that the starless phase is not represented by a single timescale, but evolves more rapidly with increasing clump mass. To investigate the sub-structure in SCCs at high spatial resolution, I study the 12 most high-mass SCCs within 5 kpc using ALMA. I report previously undetected low-luminosity protostars in 11 out of 12 SCCs, fragmentation equal to the thermal Jeans length of the clump, and no starless cores exceeding 30 solar masses. While uncertainties remain concerning the star formation effeciency in this sample, these observational facts are consistent with models where high-mass stars form from intially low- to intermediate-mass protostars that accrete most of their mass from the surrounding clump.

Self-organization principles of intracellular pattern formation.

PubMed

Halatek, J; Brauns, F; Frey, E

2018-05-26

Dynamic patterning of specific proteins is essential for the spatio-temporal regulation of many important intracellular processes in prokaryotes, eukaryotes and multicellular organisms. The emergence of patterns generated by interactions of diffusing proteins is a paradigmatic example for self-organization. In this article, we review quantitative models for intracellular Min protein patterns in Escherichia coli , Cdc42 polarization in Saccharomyces cerevisiae and the bipolar PAR protein patterns found in Caenorhabditis elegans By analysing the molecular processes driving these systems we derive a theoretical perspective on general principles underlying self-organized pattern formation. We argue that intracellular pattern formation is not captured by concepts such as 'activators', 'inhibitors' or 'substrate depletion'. Instead, intracellular pattern formation is based on the redistribution of proteins by cytosolic diffusion, and the cycling of proteins between distinct conformational states. Therefore, mass-conserving reaction-diffusion equations provide the most appropriate framework to study intracellular pattern formation. We conclude that directed transport, e.g. cytosolic diffusion along an actively maintained cytosolic gradient, is the key process underlying pattern formation. Thus the basic principle of self-organization is the establishment and maintenance of directed transport by intracellular protein dynamics.This article is part of the theme issue 'Self-organization in cell biology'. © 2018 The Authors.

Smad4 is required to inhibit osteoclastogenesis and maintain bone mass.

PubMed

Morita, Mayu; Yoshida, Shigeyuki; Iwasaki, Ryotaro; Yasui, Tetsuro; Sato, Yuiko; Kobayashi, Tami; Watanabe, Ryuichi; Oike, Takatsugu; Miyamoto, Kana; Takami, Masamichi; Ozato, Keiko; Deng, Chu-Xia; Aburatani, Hiroyuki; Tanaka, Sakae; Yoshimura, Akihiko; Toyama, Yoshiaki; Matsumoto, Morio; Nakamura, Masaya; Kawana, Hiromasa; Nakagawa, Taneaki; Miyamoto, Takeshi

2016-10-12

Bone homeostasis is maintained as a delicate balance between bone-resorption and bone-formation, which are coupled to maintain appropriate bone mass. A critical question is how bone-resorption is terminated to allow bone-formation to occur. Here, we show that TGFβs inhibit osteoclastogenesis and maintain bone-mass through Smad4 activity in osteoclasts. We found that latent-TGFβ1 was activated by osteoclasts to inhibit osteoclastogenesis. Osteoclast-specific Smad4 conditional knockout mice (Smad4-cKO) exhibited significantly reduced bone-mass and elevated osteoclast formation relative to controls. TGFβ1-activation induced expression of Irf8 and Bcl6, both of which encode factors inhibiting osteoclastogenesis, by blocking their negative regulator, Prdm1, in osteoclasts in a Smad4-dependent manner. Reduced bone-mass and accelerated osteoclastogenesis seen in Smad4-cKO were abrogated by Prdm1 deletion. Administration of latent-TGFβ1-Fc to wild-type mice antagonized LPS-induced bone destruction in a model of activated osteoclast-mediated bone destruction. Thus, latent-TGFβ1-Fc could serve as a promising new therapeutic agent in bone diseases marked by excessive resorption.

HMEC-1 adopt the mixed amoeboid-mesenchymal migration type during EndMT.

PubMed

Kryczka, Jakub; Przygodzka, Patrycja; Bogusz, Helena; Boncela, Joanna

2017-06-01

The contribution of endothelial cells to scar and fibrotic tissue formation is undisputedly connected to their ability to undergo the endothelial-to-mesenchymal transition (EndMT) towards fibroblast phenotype-resembling cells. The migration model of fibroblasts and fibroblast-resembling cells is still not fully understood. It may be either a Rho/ROCK-independent, an integrin- and MMP-correlated ECM degradation-dependent, a mesenchymal model or Rho/ROCK-dependent, integrin adhesion- and MMP activity-independent, an amoeboid model. Here, we hypothesized that microvascular endothelial cells (HMEC-1) undergoing EndMT adopt an intermediate state of drifting migration model between the mesenchymal and amoeboid protrusive types in the early stages of fibrosis. We characterized the response of HMEC-1 to TGF-β2, a well-known mediator of EndMT within the microvasculature. We observed that TGF-β2 induces up to an intermediate mesenchymal phenotype in HMEC-1. In parallel, MMP-2 is upregulated and is responsible for most proteolytic activity. Interestingly, the migration of HMEC-1 undergoing EndMT is dependent on both ECM degradation and invadosome formation associated with MMP-2 proteolytic activity and Rho/ROCK cytoskeleton contraction. In conclusion, the transition from mesenchymal towards amoeboid movement highlights a molecular plasticity mechanism in endothelial cell migration in skin fibrosis. Copyright © 2017 Elsevier GmbH. All rights reserved.

Effects of an Inverted Instructional Delivery Model on Achievement of Ninth-Grade Physical Science Honors Students

NASA Astrophysics Data System (ADS)

Howell, Donna

This mixed-methods action research study was designed to assess the achievement of ninth-grade Physical Science Honors students by analysis of pre and posttest data. In addition, perceptual data from students, parents, and the researcher were collected to form a complete picture of the flipped lecture format versus the traditional lecture format. The researcher utilized a 4MAT learning cycle in two Physical Science Honors classes. One of these classes was traditionally delivered with lecture-type activities taking place inside the classroom and homework-type activities taking place at home; the other inverted, or flipped, delivered with lecture-type activities taking place outside the classroom and homework-type activities taking place inside the classroom. Existing unit pre and posttests for both classes were analyzed for differences in academic achievement. At the completion of the units, the flipped class students and parents were surveyed, and student focus groups were convened to ascertain their perceptions of the flipped classroom delivery model. Statistical analysis of posttest data revealed that there is no significant difference between the traditional lecture delivery format and the flipped delivery format. Analysis of perceptual data revealed six themes that must be considered when deciding to flip the classroom: how to hold students accountable for viewing the at-home videos, accessibility of students to the required technology, technical considerations relating to the video production, comprehension of the material both during and after viewing the videos, pedagogy of the overall flipped method, and preference for the flipped method overall. Findings revealed that students, parents, and the researcher all had a preference for the flipped class format, provided the above issues are addressed. The flipped class format encourages students to become more responsible for their learning, and, in addition, students reported that the hands-on inquiry activities done in class aided them in learning the subject matter. It is recommended, however, that before instructors decide to flip the classroom, they ensure that all students have access to needed technology, that there is a plan in place for ensuring that the students actually view the assigned videos, that they have a way to create the videos and ensure adequate quality, and that some discussion is held in class after each assigned video to ensure comprehension of the material.

Process-driven bacterial community dynamics are key to cured meat colour formation by coagulase-negative staphylococci via nitrate reductase or nitric oxide synthase activities.

PubMed

Sánchez Mainar, María; Leroy, Frédéric

2015-11-06

The cured colour of European raw fermented meats is usually achieved by nitrate-into-nitrite reduction by coagulase-negative staphylococci (CNS), subsequently generating nitric oxide to form the relatively stable nitrosomyoglobin pigment. The present study aimed at comparing this classical curing procedure, based on nitrate reductase activity, with a potential alternative colour formation mechanism, based on nitric oxide synthase (NOS) activity, under different acidification profiles. To this end, meat models with and without added nitrate were fermented with cultures of an acidifying strain (Lactobacillus sakei CTC 494) and either a nitrate-reducing Staphylococcus carnosus strain or a rare NOS-positive CNS strain (Staphylococcus haemolyticus G110), or by relying on the background microbiota. Satisfactory colour was obtained in the models prepared with added nitrate and S. carnosus. In the presence of nitrate but absence of added CNS, however, cured colour was only obtained when L. sakei CTC 494 was also omitted. This was ascribed to the pH dependency of the emerging CNS background microbiota, selecting for nitrate-reducing Staphylococcus equorum strains at mild acidification conditions but for Staphylococcus saprophyticus strains with poor colour formation capability when the pH decrease was more rapid. This reliance of colour formation on the composition of the background microbiota was further explored by a side experiment, demonstrating the heterogeneity in nitrate reduction of a set of 88 CNS strains from different species. Finally, in all batches prepared with S. haemolyticus G110, colour generation failed as the strain was systematically outcompeted by the background microbiota, even when imposing milder acidification profiles. Thus, when aiming at colour formation through CNS metabolism, technological processing can severely interfere with the composition and functionality of the meat-associated CNS communities, for both nitrate reductase and NOS activities. Several major bottlenecks, among which the rareness of phenotypic NOS activity in meat-compatible CNS, need to be considered, which is seriously questioning the relevance of this pathway in fermented meats. Copyright © 2015 Elsevier B.V. All rights reserved.

Building Reliable Forecasts of Solar Activity

NASA Technical Reports Server (NTRS)

Kitiashvili, Irina; Wray, Alan; Mansour, Nagi

2017-01-01

Solar ionizing radiation critically depends on the level of the Sun’s magnetic activity. For robust physics-based forecasts, we employ the procedure of data assimilation, which combines theoretical modeling and observational data such that uncertainties in both the model and the observations are taken into account. Currently we are working in two major directions: 1) development of a new long-term forecast procedure on time-scales of the 11-year solar cycle, using a 2-dimensional mean-field dynamo model and synoptic magnetograms; 2) development of 3-dimensional radiative MHD (Magnetohydrodynamic) simulations to investigate the origin and precursors of local manifestations of magnetic activity, such as the formation of magnetic structures and eruptive dynamics.

Antimalarial Pyrido[1,2-a]benzimidazoles: Lead Optimization, Parasite Life Cycle Stage Profile, Mechanistic Evaluation, Killing Kinetics, and in Vivo Oral Efficacy in a Mouse Model.

PubMed

Singh, Kawaljit; Okombo, John; Brunschwig, Christel; Ndubi, Ferdinand; Barnard, Linley; Wilkinson, Chad; Njogu, Peter M; Njoroge, Mathew; Laing, Lizahn; Machado, Marta; Prudêncio, Miguel; Reader, Janette; Botha, Mariette; Nondaba, Sindisiwe; Birkholtz, Lyn-Marie; Lauterbach, Sonja; Churchyard, Alisje; Coetzer, Theresa L; Burrows, Jeremy N; Yeates, Clive; Denti, Paolo; Wiesner, Lubbe; Egan, Timothy J; Wittlin, Sergio; Chibale, Kelly

2017-02-23

Further structure-activity relationship (SAR) studies on the recently identified pyrido[1,2-a]benzimidazole (PBI) antimalarials have led to the identification of potent, metabolically stable compounds with improved in vivo oral efficacy in the P. berghei mouse model and additional activity against parasite liver and gametocyte stages, making them potential candidates for preclinical development. Inhibition of hemozoin formation possibly contributes to the mechanism of action.

Monitoring the apple polyphenol oxidase-modulated adduct formation of phenolic and amino compounds.

PubMed

Reinkensmeier, Annika; Steinbrenner, Katrin; Homann, Thomas; Bußler, Sara; Rohn, Sascha; Rawel, Hashadrai M

2016-03-01

Minimally processed fruit products such as smoothies are increasingly coming into demand. However, they are often combined with dairy ingredients. In this combination, phenolic compounds, polyphenoloxidases, and amino compounds could interact. In this work, a model approach is presented where apple serves as a source for a high polyphenoloxidase activity for modulating the reactions. The polyphenoloxidase activity ranged from 128 to 333nakt/mL in different apple varieties. From these, 'Braeburn' was found to provide the highest enzymatic activity. The formation and stability of resulting chromogenic conjugates was investigated. The results show that such adducts are not stable and possible degradation mechanisms leading to follow-up products formed are proposed. Finally, apple extracts were used to modify proteins and their functional properties characterized. There were retaining antioxidant properties inherent to phenolic compounds after adduct formation. Consequently, such interactions may also be utilized to improve the textural quality of food products. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antiangiogenic effects and mechanisms of trans-ethyl p-methoxycinnamate from Kaempferia galanga L.

PubMed

He, Zhi-Heng; Yue, Grace Gar-Lee; Lau, Clara Bik-San; Ge, Wei; But, Paul Pui-Hay

2012-11-14

Kaempferia galanga L. (Zingiberaceae) is an aromatic herb and a popular spice used as a condiment in Asian cuisine. The ethanol extract of the dried plant and its successive four subfractions were investigated on zebrafish model by quantitative endogenous alkaline phosphatase assay. Both n-hexane and ethyl acetate fractions had antiangiogenic activity, and two major active components (trans-ethyl p-methoxycinnamate and kaempferol) showed potent antiangiogenic effects on wild-type zebrafish. Because of its much stronger effect and no antiangiogenic activity reported, trans-ethyl p-methoxycinnamate was further investigated for its action mechanism. It dose dependently inhibited vessel formation on both wild- and Tg(fli1a:EGFP)y1-type zebrafish embryos. The semiquantitative reverse transcription polymerase chain reaction assay suggested that trans-ethyl p-methoxycinnamate affects multiple molecular targets related to angiogenesis. In vitro, it specifically inhibited the migration and tube formation of human umbilical vein endothelial cells. In vivo, it could block bFGF-induced vessel formation on Matrigel plug assay.

In situ formation of the active sites in Pd-Au bimetallic nanocatalysts for CO oxidation: NAP (near ambient pressure) XPS and MS study.

PubMed

Bukhtiyarov, A V; Prosvirin, I P; Saraev, A A; Klyushin, A Yu; Knop-Gericke, A; Bukhtiyarov, V I

2018-06-07

Model bimetallic Pd-Au/HOPG catalysts have been investigated in the CO oxidation reaction using a combination of NAP XPS and MS techniques. The samples have shown catalytic activity at temperatures above 150 °C. The redistribution of Au and Pd on the surface depending on the reaction conditions has been demonstrated using NAP XPS. The Pd enrichment of the bimetallic particles' surface under reaction gas mixture has been shown. Apparently, CO adsorption induces Pd segregation on the surface. Heating the sample under reaction conditions above 150 °C decomposes the Pd-CO state due to CO desorption and reaction and simultaneous Pd-Au alloy formation on the surface takes place. Cooling back down to RT results in reversible Pd segregation due to Pd-CO formation and the sample becomes inactive. It has been shown that in situ studies are necessary for investigation of the active sites in Pd-Au bimetallic systems.

The stratigraphic sequence of Scafati (Italy) - An archive of 10,000 years of volcanism, soil formation and land use in the shade of Mount Vesuvius

NASA Astrophysics Data System (ADS)

Maerker, Michael; Vogel, Sebastian; Hoelzmann, Phillip; Rellini, Ivano

2014-05-01

In this study we carried out a detailed lithostratigraphic, pedological and micromorphological analysis at a stratigraphic sequence close to Scafati, about 3 km east of ancient Pompeii. It consists of a multilayered succession of repeated volcanic deposition and pedogenesis caused by several phases of volcanic activity of Somma-Vesuvius and volcanic quiescence. This comprises, at least, the last 10,000 years of sedimentation history, on one hand, reflecting the entire spectrum of eruption types of Somma-Vesuvius from Plinian, sub-Plinian, rather small eruptions to effusive volcanic events and, on the other hand, soil formations of different durations, intensities and soil-forming environments. Furthermore, the paleosols repeatedly reveal clear evidence of anthropogenic activity by means of agriculture. Hence, a landscape evolution model was developed trying to reconstruct the last 10,000 years of volcanic activity, soil formation and land use in the hinterland of Pompeii.

Ran-dependent TPX2 activation promotes acentrosomal microtubule nucleation in neurons

PubMed Central

Chen, Wen-Shin; Chen, Yi-Ju; Huang, Yung-An; Hsieh, Bing-Yuan; Chiu, Ho-Chieh; Kao, Pei-Ying; Chao, Chih-Yuan; Hwang, Eric

2017-01-01

The microtubule (MT) cytoskeleton is essential for the formation of morphologically appropriate neurons. The existence of the acentrosomal MT organizing center in neurons has been proposed but its identity remained elusive. Here we provide evidence showing that TPX2 is an important component of this acentrosomal MT organizing center. First, neurite elongation is compromised in TPX2-depleted neurons. In addition, TPX2 localizes to the centrosome and along the neurite shaft bound to MTs. Depleting TPX2 decreases MT formation frequency specifically at the tip and the base of the neurite, and these correlate precisely with the regions where active GTP-bound Ran proteins are enriched. Furthermore, overexpressing the downstream effector of Ran, importin, compromises MT formation and neuronal morphogenesis. Finally, applying a Ran-importin signaling interfering compound phenocopies the effect of TPX2 depletion on MT dynamics. Together, these data suggest a model in which Ran-dependent TPX2 activation promotes acentrosomal MT nucleation in neurons. PMID:28205572

Inhibition of Steptococcus mutans biofilm formation by extracts of Tenacibaculum sp. 20J, a bacterium with wide-spectrum quorum quenching activity.

PubMed

Muras, Andrea; Mayer, Celia; Romero, Manuel; Camino, Tamara; Ferrer, Maria D; Mira, Alex; Otero, Ana

2018-01-01

Background : Previous studies have suggested the quorum sensing signal AI-2 as a potential target to prevent the biofilm formation by Streptococcus mutans , a pathogen involved in tooth decay. Objective : To obtain inhibition of biofilm formation by S. mutans by extracts obtained from the marine bacterium Tenacibaculum sp. 20J interfering with the AI-2 quorum sensing system. Design : The AI-2 inhibitory activity was tested with the biosensors Vibrio harveyi BB170 and JMH597. S. mutans ATCC25175 biofilm formation was monitored using impedance real-time measurements with the xCELLigence system®, confocal laser microscopy, and the crystal violet quantification method. Results : The addition of the cell extract from Tenacibaculum sp. 20J reduced biofilm formation in S. mutans ATCC25175 by 40-50% compared to the control without significantly affecting growth. A decrease of almost 40% was also observed in S. oralis DSM20627 and S. dentisani 7747 biofilms. Conclusions : The ability of Tenacibaculum sp. 20J to interfere with AI-2 and inhibit biofilm formation in S. mutans was demonstrated. The results indicate that the inhibition of quorum sensing processes may constitute a suitable strategy for inhibiting dental plaque formation, although additional experiments using mixed biofilm models would be required.

Inhibition of Steptococcus mutans biofilm formation by extracts of Tenacibaculum sp. 20J, a bacterium with wide-spectrum quorum quenching activity

PubMed Central

Muras, Andrea; Mayer, Celia; Romero, Manuel; Camino, Tamara; Ferrer, Maria D.; Mira, Alex; Otero, Ana

2018-01-01

ABSTRACT Background: Previous studies have suggested the quorum sensing signal AI-2 as a potential target to prevent the biofilm formation by Streptococcus mutans, a pathogen involved in tooth decay. Objective: To obtain inhibition of biofilm formation by S. mutans by extracts obtained from the marine bacterium Tenacibaculum sp. 20J interfering with the AI-2 quorum sensing system. Design: The AI-2 inhibitory activity was tested with the biosensors Vibrio harveyi BB170 and JMH597. S. mutans ATCC25175 biofilm formation was monitored using impedance real-time measurements with the xCELLigence system®, confocal laser microscopy, and the crystal violet quantification method. Results: The addition of the cell extract from Tenacibaculum sp. 20J reduced biofilm formation in S. mutans ATCC25175 by 40–50% compared to the control without significantly affecting growth. A decrease of almost 40% was also observed in S. oralis DSM20627 and S. dentisani 7747 biofilms. Conclusions: The ability of Tenacibaculum sp. 20J to interfere with AI-2 and inhibit biofilm formation in S. mutans was demonstrated. The results indicate that the inhibition of quorum sensing processes may constitute a suitable strategy for inhibiting dental plaque formation, although additional experiments using mixed biofilm models would be required. PMID:29410771

Pyruvate formate-lyase interacts directly with the formate channel FocA to regulate formate translocation.

PubMed

Doberenz, Claudia; Zorn, Michael; Falke, Dörte; Nannemann, David; Hunger, Doreen; Beyer, Lydia; Ihling, Christian H; Meiler, Jens; Sinz, Andrea; Sawers, R Gary

2014-07-29

The FNT (formate-nitrite transporters) form a superfamily of pentameric membrane channels that translocate monovalent anions across biological membranes. FocA (formate channel A) translocates formate bidirectionally but the mechanism underlying how translocation of formate is controlled and what governs substrate specificity remains unclear. Here we demonstrate that the normally soluble dimeric enzyme pyruvate formate-lyase (PflB), which is responsible for intracellular formate generation in enterobacteria and other microbes, interacts specifically with FocA. Association of PflB with the cytoplasmic membrane was shown to be FocA dependent and purified, Strep-tagged FocA specifically retrieved PflB from Escherichia coli crude extracts. Using a bacterial two-hybrid system, it could be shown that the N-terminus of FocA and the central domain of PflB were involved in the interaction. This finding was confirmed by chemical cross-linking experiments. Using constraints imposed by the amino acid residues identified in the cross-linking study, we provide for the first time a model for the FocA-PflB complex. The model suggests that the N-terminus of FocA is important for interaction with PflB. An in vivo assay developed to monitor changes in formate levels in the cytoplasm revealed the importance of the interaction with PflB for optimal translocation of formate by FocA. This system represents a paradigm for the control of activity of FNT channel proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evidence for Ongoing Modeling-Based Bone Formation in Human Femoral Head Trabeculae via Forming Minimodeling Structures: A Study in Patients with Fractures and Arthritis.

PubMed

Sano, Hiroshige; Kondo, Naoki; Shimakura, Taketoshi; Fujisawa, Junichi; Kijima, Yasufumi; Kanai, Tomotake; Poole, Kenneth E S; Yamamoto, Noriaki; Takahashi, Hideaki E; Endo, Naoto

2018-01-01

Bone modeling is a biological process of bone formation that adapts bone size and shape to mechanical loads, especially during childhood and adolescence. Bone modeling in cortical bone can be easily detected using sequential radiographic images, while its assessment in trabecular bone is challenging. Here, we performed histomorphometric analysis in 21 bone specimens from biopsies collected during hip arthroplasty, and we proposed the criteria for histologically identifying an active modeling-based bone formation, which we call a "forming minimodeling structure" (FMiS). Evidence of FMiSs was found in 9 of 20 specimens (45%). In histomorphometric analysis, bone volume was significant higher in specimens displaying FMiSs compared with the specimens without these structures (BV/TV, 31.7 ± 10.2 vs. 23.1 ± 3.9%; p  < 0.05). Osteoid parameters were raised in FMiS-containing bone specimens (OV/BV, 2.1 ± 1.6 vs. 0.6 ± 0.3%; p  < 0.001, OS/BS, 23.6 ± 15.5 vs. 7.6 ± 4.2%; p  < 0.001, and O.Th, 7.4 µm ± 2.0 vs. 5.2 ± 1.0; p  < 0.05). Our results showed that the modeling-based bone formation on trabecular bone surfaces occurs even during adulthood. As FMiSs can represent histological evidence of modeling-based bone formation, understanding of this physiology in relation to bone homeostasis is crucial.

Immediate Remote Ischemic Postconditioning Reduces Brain Nitrotyrosine Formation in a Piglet Asphyxia Model.

PubMed

Rocha-Ferreira, Eridan; Rudge, Brogan; Hughes, Michael P; Rahim, Ahad A; Hristova, Mariya; Robertson, Nicola J

2016-01-01

Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention that could be administered as an alternative to cooling in cases of perinatal hypoxia-ischemia (HI). In the current study we hypothesized that RIPostC in the piglet model of birth asphyxia confers protection by reducing nitrosative stress and subsequent nitrotyrosine formation, as well as having an effect on glial immunoreactivity. Postnatal day 1 (P1) piglets underwent HI brain injury and were randomised to HI (control) or HI + RIPostC. Immunohistochemistry assessment 48 hours after HI revealed a significant decrease in brain nitrotyrosine deposits in the RIPostC-treated group (p = 0.02). This was accompanied by a significant increase in eNOS expression (p < 0.0001) and decrease in iNOS (p = 0.010), with no alteration in nNOS activity. Interestingly, RIPostC treatment was associated with a significant increase in GFAP (p = 0.002) and IBA1 (p = 0.006), markers of astroglial and microglial activity, respectively. The current study demonstrates a beneficial effect of RIPostC therapy in the preclinical piglet model of neonatal asphyxia, which appears to be mediated by modulation of nitrosative stress, despite glial activation.

Discovery of a new metal and NAD+-dependent formate dehydrogenase from Clostridium ljungdahlii.

PubMed

Çakar, M Mervan; Mangas-Sanchez, Juan; Birmingham, William R; Turner, Nicholas J; Binay, Barış

2018-04-21

Over the next decades, with the growing concern of rising atmospheric carbon dioxide (CO 2 ) levels, the importance of investigating new approaches for its reduction becomes crucial. Reclamation of CO 2 for conversion into biofuels represents an alternative and attractive production method that has been studied in recent years, now with enzymatic methods gaining more attention. Formate dehydrogenases (FDHs) are NAD(P)H-dependent oxidoreductases that catalyze the conversion of formate into CO 2 and have been extensively used for cofactor recycling in chemoenzymatic processes. A new FDH from Clostridium ljungdahlii (ClFDH) has been recently shown to possess activity in the reverse reaction: the mineralization of CO 2 into formate. In this study, we show the successful homologous expression of ClFDH in Escherichia coli. Biochemical and kinetic characterization of the enzyme revealed that this homologue also demonstrates activity toward CO 2 reduction. Structural analysis of the enzyme through homology modeling is also presented.

["Active in rehab": development and formative evaluation of a patient education program to increase health literacy of patients with chronic illness].

PubMed

Ullrich, A; Schöpf, A C; Nagl, M; Farin, E

2015-04-01

The aim of the article is to describe the development, the process of manualisation and results from the formative evaluation of a patient-oriented patient education program to increase health literacy of patients with chronic illness ("Active in rehab"). Themes of the patient education program were extracted from 17 focus groups. An expert meeting was conducted to validate the content of the patient education program. The formative evaluation was based on a questionnaire (N(max) = 295 patients and N(max) = 39 trainers). The patient education program includes 4 modules with 3 themes (bio-psycho-social model, rehabilitation goals, communication competencies). The evaluation of the modules was good to very good. An analysis of free texts and a follow-up survey among trainers helped us to infer important improvements to the patient education program. RESULTS from the formative evaluation show that the patient education program meets patients and trainers needs and is accepted. © Georg Thieme Verlag KG Stuttgart · New York.

Quenching or Bursting: Star Formation Acceleration—A New Methodology for Tracing Galaxy Evolution

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

Martin, D. Christopher; Darvish, Behnam; Seibert, Mark

We introduce a new methodology for the direct extraction of galaxy physical parameters from multiwavelength photometry and spectroscopy. We use semianalytic models that describe galaxy evolution in the context of large-scale cosmological simulation to provide a catalog of galaxies, star formation histories, and physical parameters. We then apply models of stellar population synthesis and a simple extinction model to calculate the observable broadband fluxes and spectral indices for these galaxies. We use a linear regression analysis to relate physical parameters to observed colors and spectral indices. The result is a set of coefficients that can be used to translate observedmore » colors and indices into stellar mass, star formation rate, and many other parameters, including the instantaneous time derivative of the star formation rate, which we denote the Star Formation Acceleration (SFA), We apply the method to a test sample of galaxies with GALEX photometry and SDSS spectroscopy, deriving relationships between stellar mass, specific star formation rate, and SFA. We find evidence for a mass-dependent SFA in the green valley, with low-mass galaxies showing greater quenching and higher-mass galaxies greater bursting. We also find evidence for an increase in average quenching in galaxies hosting an active galactic nucleus. A simple scenario in which lower-mass galaxies accrete and become satellite galaxies, having their star-forming gas tidally and/or ram-pressure stripped, while higher-mass galaxies receive this gas and react with new star formation, can qualitatively explain our results.« less

Quenching or Bursting: Star Formation Acceleration—A New Methodology for Tracing Galaxy Evolution

NASA Astrophysics Data System (ADS)

Martin, D. Christopher; Gonçalves, Thiago S.; Darvish, Behnam; Seibert, Mark; Schiminovich, David

2017-06-01

We introduce a new methodology for the direct extraction of galaxy physical parameters from multiwavelength photometry and spectroscopy. We use semianalytic models that describe galaxy evolution in the context of large-scale cosmological simulation to provide a catalog of galaxies, star formation histories, and physical parameters. We then apply models of stellar population synthesis and a simple extinction model to calculate the observable broadband fluxes and spectral indices for these galaxies. We use a linear regression analysis to relate physical parameters to observed colors and spectral indices. The result is a set of coefficients that can be used to translate observed colors and indices into stellar mass, star formation rate, and many other parameters, including the instantaneous time derivative of the star formation rate, which we denote the Star Formation Acceleration (SFA), We apply the method to a test sample of galaxies with GALEX photometry and SDSS spectroscopy, deriving relationships between stellar mass, specific star formation rate, and SFA. We find evidence for a mass-dependent SFA in the green valley, with low-mass galaxies showing greater quenching and higher-mass galaxies greater bursting. We also find evidence for an increase in average quenching in galaxies hosting an active galactic nucleus. A simple scenario in which lower-mass galaxies accrete and become satellite galaxies, having their star-forming gas tidally and/or ram-pressure stripped, while higher-mass galaxies receive this gas and react with new star formation, can qualitatively explain our results.

Star formation in simulated galaxies: understanding the transition to quiescence at 3 × 1010 M⊙

NASA Astrophysics Data System (ADS)

Taylor, Philip; Federrath, Christoph; Kobayashi, Chiaki

2017-08-01

Star formation in galaxies relies on the availability of cold, dense gas, which, in turn, relies on factors internal and external to the galaxies. In order to provide a simple model for how star formation is regulated by various physical processes in galaxies, we analyse data at redshift z = 0 from a hydrodynamical cosmological simulation that includes prescriptions for star formation and stellar evolution, active galactic nuclei, and their associated feedback processes. This model can determine the star formation rate (SFR) as a function of galaxy stellar mass, gas mass, black hole mass, and environment. We find that gas mass is the most important quantity controlling star formation in low-mass galaxies, and star-forming galaxies in dense environments have higher SFR than their counterparts in the field. In high-mass galaxies, we find that black holes more massive than ˜ 107.5 M⊙ can be triggered to quench star formation in their host; this mass scale is emergent in our simulations. Furthermore, this black hole mass corresponds to a galaxy bulge mass ˜ 2 × 1010 M⊙, consistent with the mass at which galaxies start to become dominated by early types ( ˜ 3 × 1010 M⊙, as previously shown in observations by Kauffmann et al.). Finally, we demonstrate that our model can reproduce well the SFR measured from observations of galaxies in the Galaxy And Mass Assembly and Arecibo Legacy Fast ALFA surveys.

Evaluation of immunomodulatory activity of "Shirishavaleha"-An Ayurvedic compound formulation in albino rats.

PubMed

Yadav, Shyamlal Singh; Galib; Prajapati, P K; Ashok, B K; Ravishankar, B

2011-10-01

The immunomodulatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth), i.e., Twak (Bark) and Sara (Heartwood) as main ingredients was evaluated for humoral antibody formation and cell-mediated immunity in established experimental models. The study used Wistar rats of either sex weighing 200 ± 40 g, while the test drug was administered orally at a dose of 1.8 g/kg. Hemagglutination titer and body weight were recorded to assess effects on humoral immunity; immunological paw edema was assessed for cell-mediated immunity. Shirishavaleha prepared from heartwood shows significant enhancement in antibody formation, attenuation of body weight changes, and suppression of immunological paw edema, while Shirishavaleha prepared from bark shows weak immunomodulatory activity. The study therefore concludes that Shirishavaleha prepared from heartwood has significant immunomodulatory activity.

Evaluation of immunomodulatory activity of “Shirishavaleha”–An Ayurvedic compound formulation in albino rats

PubMed Central

Yadav, Shyamlal Singh; Galib; Prajapati, P. K.; Ashok, B. K.; Ravishankar, B.

2011-01-01

The immunomodulatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth), i.e., Twak (Bark) and Sara (Heartwood) as main ingredients was evaluated for humoral antibody formation and cell-mediated immunity in established experimental models. The study used Wistar rats of either sex weighing 200 ± 40 g, while the test drug was administered orally at a dose of 1.8 g/kg. Hemagglutination titer and body weight were recorded to assess effects on humoral immunity; immunological paw edema was assessed for cell-mediated immunity. Shirishavaleha prepared from heartwood shows significant enhancement in antibody formation, attenuation of body weight changes, and suppression of immunological paw edema, while Shirishavaleha prepared from bark shows weak immunomodulatory activity. The study therefore concludes that Shirishavaleha prepared from heartwood has significant immunomodulatory activity. PMID:22253509

How Object, Situation and Personality Shape Human Attitude in Learning: An Activity Perspective and a Multilevel Modeling Approach

ERIC Educational Resources Information Center

Sun, Jun

2009-01-01

Based on Activity Theory, this article examines attitude formation in human learning as shaped by the experiences of individual learners with various learning objects in particular learning contexts. It hypothesizes that a learner's object-related perceptions, personality traits and situational perceptions may have different relationships with the…

Going Underground: A Field Investigation and Lab Activity on Karst Topography and Water Systems

ERIC Educational Resources Information Center

O'Dell, Gary; Gonzalez-Espada, Wilson

2011-01-01

Students learn science best with activities that mirror the way scientists work. This article describes how geologists investigate groundwater flow systems in areas of karst topography--geologic formations shaped by dissolving bedrock--and provides a way for students to replicate this research. Students also use electric current to model water…

A model and simulation of fast space charge pulses in polymers

NASA Astrophysics Data System (ADS)

Lv, Zepeng; Rowland, Simon M.; Wu, Kai

2017-11-01

The transport of space charge packets across polyethylene and epoxy resin in high electric fields has been characterized as fast or slow depending on packet mobility. Several explanations for the formation and transport of slow space charge packets have been proposed, but the origins of fast space charge pulses, with mobilities above 10-11 m2 V-1 s-1, are unclear. In one suggested model, it is assumed that the formation of fast charge pulses is due to discontinuous electromechanical compression and charge injection at the electrode-insulation interface, and their transport is related to corresponding relaxation processes. In that model, charges travel as a pulse because of group polarization. This paper provides an alternative model based on the reduction of charge carrier activation energy due to charge density triggered polymer chain movement and subsequent chain relaxation times. The generation and transport of fast charge pulses are readily simulated by a bipolar charge transport model with three additional parameters: reduced activation energy, charge density threshold, and chain relaxation time. Such a model is shown to reproduce key features of fast space charge pulses including speed, duration, repetition rate and pulse size. This model provides the basis for a deep understanding of the physical origins of fast space charge pulses in polymers.

Trivalent methylated arsenical-induced phosphatidylserine exposure and apoptosis in platelets may lead to increased thrombus formation

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

Bae, Ok-Nam; Lim, Kyung-Min; AMOREPACIFIC CO/R and D Center, Gyeonggi-do 446-729

2009-09-01

Trivalent methylated metabolites of arsenic, monomethylarsonous acid (MMA{sup III}) and dimethylarsinous acid (DMA{sup III}), have been found highly reactive and toxic in various cells and in vivo animal models, suggesting their roles in the arsenic-associated toxicity. However, their effects on cardiovascular system including blood cells, one of the most important targets for arsenic toxicity, remain poorly understood. Here we found that MMA{sup III} and DMA{sup III} could induce procoagulant activity and apoptosis in platelets, which play key roles in the development of various cardiovascular diseases (CVDs) through excessive thrombus formation. In freshly isolated human platelets, treatment of MMA{sup III} resultedmore » in phosphatidylserine (PS) exposure, a hallmark of procoagulant activation, accompanied by distinctive apoptotic features including mitochondrial membrane potential disruption, cytochrome c release, and caspase-3 activation. These procoagulant activation and apoptotic features were found to be mediated by the depletion of protein thiol and intracellular ATP, and flippase inhibition by MMA{sup III}, while the intracellular calcium increase or reactive oxygen species generation was not involved. Importantly, increased platelet procoagulant activity by MMA{sup III} resulted in enhanced blood coagulation and excessive thrombus formation in a rat in vivo venous thrombosis model. DMA{sup III} also induced PS-exposure with apoptotic features mediated by protein thiol depletion, which resulted in enhanced thrombin generation. In summary, we believe that this study provides an important evidence for the role of trivalent methylated arsenic metabolites in arsenic-associated CVDs, giving a novel insight into the role of platelet apoptosis in toxicant-induced cardiovascular toxicity.« less

A zebrafish model of chordoma initiated by notochord-driven expression of HRASV12

PubMed Central

Burger, Alexa; Vasilyev, Aleksandr; Tomar, Ritu; Selig, Martin K.; Nielsen, G. Petur; Peterson, Randall T.; Drummond, Iain A.; Haber, Daniel A.

2014-01-01

Chordoma is a malignant tumor thought to arise from remnants of the embryonic notochord, with its origin in the bones of the axial skeleton. Surgical resection is the standard treatment, usually in combination with radiation therapy, but neither chemotherapeutic nor targeted therapeutic approaches have demonstrated success. No animal model and only few chordoma cell lines are available for preclinical drug testing, and, although no druggable genetic drivers have been identified, activation of EGFR and downstream AKT-PI3K pathways have been described. Here, we report a zebrafish model of chordoma, based on stable transgene-driven expression of HRASV12 in notochord cells during development. Extensive intra-notochordal tumor formation is evident within days of transgene expression, ultimately leading to larval death. The zebrafish tumors share characteristics of human chordoma as demonstrated by immunohistochemistry and electron microscopy. The mTORC1 inhibitor rapamycin, which has some demonstrated activity in a chordoma cell line, delays the onset of tumor formation in our zebrafish model, and improves survival of tumor-bearing fish. Consequently, the HRASV12-driven zebrafish model of chordoma could enable high-throughput screening of potential therapeutic agents for the treatment of this refractory cancer. PMID:24311731

Effect of electrical polarization of hydroxyapatite ceramics on new bone formation.

PubMed

Itoh, S; Nakamura, S; Kobayashi, T; Shinomiya, K; Yamashita, K; Itoh, S

2006-03-01

Large surface charges can be induced on hydroxyapatite (HAp) ceramics by proton transport polarization, but this does not affect beta-tricalcium phosphate (TCP) because of its low polarizability. We wished to examine differences in osteogenic cell activity and new bone growth between positively or negatively surface-charged HAp and HAp/TCP plates using a calvarial bone defect model. In the first group of rats, test pieces were placed with their positively charged surfaces face down on the dura mater. In the second group, test pieces were placed with their negatively charged surfaces face down on the dura mater. A third group received noncharged test pieces. Histological examination, including enzymatic staining for osteoblasts and osteoclasts, was carried out. While no bone formation was observed at the pericranium, direct bone formation on the cranial bone debris and new bone growth expanded from the margins of the sites of injury to bridge across both the positively and negatively charged surfaces of HAp and HAp/TCP plates occurred. Electrical polarization of implanted plates, including positive charge, led to enhanced osteoblast activity, though decreased osteoclast activity was seen on the positively charged plate surface. Thus, polarization of HAp ceramics may modulate new bone formation and resorption.

Electrocatalytic Oxidation of Ammonia on Transition-Metal Surfaces: A First-Principles Study

DOE PAGES

Herron, Jeffrey A.; Ferrin, Peter; Mavrikakis, Manos

2015-02-20

Here, we investigate the catalytic electro-oxidation of ammonia on model close-packed surfaces of Au, Ag, Cu, Pd, Pt, Ni, Ir, Co, Rh, Ru, Os, and Re to derive insights for the reaction mechanism and evaluate the catalysts based on their energy efficiency and activity in the context of their application in fuel cells. Two mechanisms, which are differentiated by their N–N bond formation step, are compared: (1) a mechanism proposed by Gerischer and Mauerer, whereby the N–N bond formation occurs between hydrogenated NH x adsorbed species, and (2) a mechanism in which N–N bond formation occurs between N adatoms. Themore » results of our study show that the mechanism proposed by Gerischer and Mauerer is kinetically preferred and that the formation of N adatoms poisons the surface of the catalyst. On the basis of a simple Sabatier analysis, we predict that Pt is the most active monometallic catalyst followed by Ir and Cu, whereas all other metal surfaces studied here have significantly lower activity. We conclude by outlining some design principles for bimetallic alloy catalysts for NH 3 electro-oxidation.« less

Stochastic phase of ventral furrow formation in the Drosophila embryo: cellular constriction chains, mechanical feedback, and robustness

NASA Astrophysics Data System (ADS)

Blawzdziewicz, Jerzy; Gao, Guo-Jie J.; Holcomb, Michael C.; Thomas, Jeffrey H.

The key process giving rise to ventral furrow formation (VFF) in Drosophila embryo is apical constriction of cells in the ventral region. The constriction produces negative spontaneous curvature of the cell layer. During the initial slower phase of VFF approximately 40% of cells constrict in a seemingly random order. We show that this initial phase of VFF does not depend on random uncorrelated events. Instead, constricted cell apices form well-defined correlated structures, i.e., cellular constriction chains (CCCs), indicative of strong spatial and directional correlations between the constriction events. We argue that this chain formation is a signature of mechanical signaling that coordinates apical constrictions through tensile stress. To gain insights into the mechanisms involved in this correlated constriction process, we propose an active granular fluid (AGF) model which considers a tissue as a collection of mechanically active, stress-responsive objects. Our AGF molecular dynamics simulations show that cell constriction sensitivity to tensile stress results in formation of CCCs whereas compressive-stress sensitivity leads to compact constricted cell clusters; the CCCs, which can penetrate less-active regions, increase the robustness of the VFF process.

Floral homeotic proteins modulate the genetic program for leaf development to suppress trichome formation in flowers.

PubMed

Ó'Maoiléidigh, Diarmuid S; Stewart, Darragh; Zheng, Beibei; Coupland, George; Wellmer, Frank

2018-02-13

As originally proposed by Goethe in 1790, floral organs are derived from leaf-like structures. The conversion of leaves into different types of floral organ is mediated by floral homeotic proteins, which, as described by the ABCE model of flower development, act in a combinatorial manner. However, how these transcription factors bring about this transformation process is not well understood. We have previously shown that floral homeotic proteins are involved in suppressing the formation of branched trichomes, a hallmark of leaf development, on reproductive floral organs of Arabidopsis Here, we present evidence that the activities of the C function gene AGAMOUS ( AG ) and the related SHATTERPROOF1 / 2 genes are superimposed onto the regulatory network that controls the distribution of trichome formation in an age-dependent manner. We show that AG regulates cytokinin responses and genetically interacts with the organ polarity gene KANADI1 to suppress trichome initiation on gynoecia. Thus, our results show that parts of the genetic program for leaf development remain active during flower formation but have been partially rewired through the activities of the floral homeotic proteins. © 2018. Published by The Company of Biologists Ltd.

Molecular Genetics of Supernumerary Tooth Formation

PubMed Central

Wang, Xiu-Ping; Fan, Jiabing

2011-01-01

Summary Despite advances in the knowledge of tooth morphogenesis and differentiation, relatively little is known about the aetiology and molecular mechanisms underlying supernumerary tooth formation. A small number of supernumerary teeth may be a common developmental dental anomaly, while multiple supernumerary teeth usually have a genetic component and they are sometimes thought to represent a partial third dentition in humans. Mice, which are commonly used for studying tooth development, only exhibit one dentition, with very few mouse models exhibiting supernumerary teeth similar to those in humans. Inactivation of Apc or forced activation of Wnt/β(catenin signalling results in multiple supernumerary tooth formation in both humans and in mice, but the key genes in these pathways are not very clear. Analysis of other model systems with continuous tooth replacement or secondary tooth formation, such as fish, snake, lizard, and ferret, is providing insights into the molecular and cellular mechanisms underlying succesional tooth development, and will assist in the studies on supernumerary tooth formation in humans. This information, together with the advances in stem cell biology and tissue engineering, will pave ways for the tooth regeneration and tooth bioengineering. PMID:21309064

Alternative complement pathway activation increases mortality in a model of burn injury in mice.

PubMed Central

Gelfand, J A; Donelan, M; Hawiger, A; Burke, J F

1982-01-01

We have studied the role of the complement system in burn injury in an experimental model in mice. A 25% body surface area, full-thickness scald wound was produced in anesthetized animals. Massive activation of the alternative complement pathway, but not the classical pathway, was seen. This activation was associated with the generation of neutrophil aggregating activity in the plasma, neutrophil aggregates in the lungs, increased pulmonary vascular permeability, and increased lung edema formation. Decomplementation with cobra venom factor (CVF) or genetic C5 deficiency diminished these pathologic changes, and CVF pretreatment substantially reduced burn mortality in the first 24 h. Preliminary data show that human burn patients have a similar pattern of complement activation involving predominantly the alternative pathway, indicating the possible relevance of the murine model to human disease. Images PMID:7174787

Quantum chemical studies of a model for peptide bond formation. 3. Role of magnesium cation in formation of amide and water from ammonia and glycine

NASA Technical Reports Server (NTRS)

Oie, T.; Loew, G. H.; Burt, S. K.; MacElroy, R. D.

1984-01-01

The SN2 reaction between glycine and ammonia molecules with magnesium cation Mg2+ as a catalyst has been studied as a model reaction for Mg(2+)-catalyzed peptide bond formation using the ab initio Hartree-Fock molecular orbital method. As in previous studies of the uncatalyzed and amine-catalyzed reactions between glycine and ammonia, two reaction mechanisms have been examined, i.e., a two-step and a concerted reaction. The stationary points of each reaction including intermediate and transition states have been identified and free energies calculated for all geometry-optimized reaction species to determine the thermodynamics and kinetics of each reaction. Substantial decreases in free energies of activation were found for both reaction mechanisms in the Mg(2+)-catalyzed amide bond formation compared with those in the uncatalyzed and amine-catalyzed amide bond formation. The catalytic effect of the Mg2+ cation is to stabilize both the transition states and intermediate, and it is attributed to the neutralization of the developing negative charge on the electrophile and formation of a conformationally flexible nonplanar five-membered chelate ring structure.

Chemically-Deduced Star Formation Histories Of Dwarf Galaxies Using Barium

NASA Astrophysics Data System (ADS)

Duggan, Gina; Kirby, Evan

2017-06-01

Dwarf galaxies offer a unique opportunity to study the competing forces of galaxy evolution. Their simpler history (i.e., small size, fewer major mergers, and lack of active galactic nuclei) enables us to isolate different physical mechanisms more easily. The effects of these mechanisms are imprinted on the galaxy's star formation history. Traditionally, star formation histories are determined from color-magnitude diagrams. However, chemical abundances can increase the precision of this measurement. Here we present a simplistic galactic chemical evolution model to infer the star formation history. Chemical abundances are measured from spectra obtained with Keck/DEIMOS medium-resolution spectroscopy for over a hundred red giant stars from several satellite dwarf spheroidal galaxies and globular clusters. We focus our work on iron and barium abundances because they predominantly trace Type Ia supernovae and asymptotic giant branch stars, respectively. The different timescales of these two nucleosynthetic sources can be used to measure a finely resolved star formation history, especially when combined with existing [α/Fe] measurements. These models will inform the details of early star formation in dwarf galaxies and how it is affected by various physical processes, such as reionization and tidal stripping.

Patterns formation in ferrofluids and solid dissolutions using stochastic models with dissipative dynamics

NASA Astrophysics Data System (ADS)

Morales, Marco A.; Fernández-Cervantes, Irving; Agustín-Serrano, Ricardo; Anzo, Andrés; Sampedro, Mercedes P.

2016-08-01

A functional with interactions short-range and long-range low coarse-grained approximation is proposed. This functional satisfies models with dissipative dynamics A, B and the stochastic Swift-Hohenberg equation. Furthermore, terms associated with multiplicative noise source are added in these models. These models are solved numerically using the method known as fast Fourier transform. Results of the spatio-temporal dynamic show similarity with respect to patterns behaviour in ferrofluids phases subject to external fields (magnetic, electric and temperature), as well as with the nucleation and growth phenomena present in some solid dissolutions. As a result of the multiplicative noise effect over the dynamic, some microstructures formed by changing solid phase and composed by binary alloys of Pb-Sn, Fe-C and Cu-Ni, as well as a NiAl-Cr(Mo) eutectic composite material. The model A for active-particles with a non-potential term in form of quadratic gradient explain the formation of nanostructured particles of silver phosphate. With these models is shown that the underlying mechanisms in the patterns formation in all these systems depends of: (a) dissipative dynamics; (b) the short-range and long-range interactions and (c) the appropiate combination of quadratic and multiplicative noise terms.

Discovery of extreme [O III] λ5007 Å outflows in high-redshift red quasars

NASA Astrophysics Data System (ADS)

Zakamska, Nadia L.; Hamann, Fred; Pâris, Isabelle; Brandt, W. N.; Greene, Jenny E.; Strauss, Michael A.; Villforth, Carolin; Wylezalek, Dominika; Alexandroff, Rachael M.; Ross, Nicholas P.

2016-07-01

Black hole feedback is now a standard component of galaxy formation models. These models predict that the impact of black hole activity on its host galaxy likely peaked at z = 2-3, the epoch of strongest star formation activity and black hole accretion activity in the Universe. We used XSHOOTER on the Very Large Telescope to measure rest-frame optical spectra of four z ˜ 2.5 extremely red quasars with infrared luminosities ˜1047 erg s-1. We present the discovery of very broad (full width at half max = 2600-5000 km s-1), strongly blueshifted (by up to 1500 km s-1) [O III] λ5007 Å emission lines in these objects. In a large sample of type 2 and red quasars, [O III] kinematics are positively correlated with infrared luminosity, and the four objects in our sample are on the extreme end in both [O III] kinematics and infrared luminosity. We estimate that at least 3 per cent of the bolometric luminosity in these objects is being converted into the kinetic power of the observed wind. Photo-ionization estimates suggest that the [O III] emission might be extended on a few kpc scales, which would suggest that the extreme outflow is affecting the entire host galaxy of the quasar. These sources may be the signposts of the most extreme form of quasar feedback at the peak epoch of galaxy formation, and may represent an active `blow-out' phase of quasar evolution.

MHD and Reconnection Activity During Local Helicity Injection

NASA Astrophysics Data System (ADS)

Barr, J. L.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Reusch, J. A.; Richner, N. J.

2016-10-01

Scaling local helicity injection (LHI) to larger devices requires a validated, predictive model of its current drive mechanism. NIMROD simulations predict the injected helical current streams persist in the edge and periodically reconnect to form axisymmetric current rings that travel into the bulk plasma to grow Ip and poloidal flux. In simulation, these events result in discrete bursts of Alfvénic-frequency MHD activity and jumps in Ip of order ΔIp Iinj , in qualitative agreement with large n = 1 activity found in experiment. Fast imaging prior to tokamak formation supports the instability of, and apparent reconnection between, adjacent helical streams. The bursts exhibit toroidal amplitude asymmetries consistent with a kink structure singly line-tied to the injectors. Internal measurements localize this activity to the injector radial location. Pairwise correlations of poloidal Mirnov coil amplitude and phase match expectations of an edge-localized current stream carrying Iinj. Prior to tokamak formation, reconnection from both adjacent helical windings and co-injected current streams are shown to strongly heat impurity ions. After tokamak formation, strong anomalous ion heating in the plasma edge is attributed to continuous reconnection between colinear streams. The n = 1 bursts occur less frequently as Ip rises, likely caused by increased stream stability as Bv rises and qedge drops. This evidence supports the general NIMROD model of LHI, confirms the persistence and role of the edge current streams, and motivates experiments at higher Iinj and BT. Supported by US DOE Grants DE-FG02-96ER54375, DE-SC0006928.

Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis.

PubMed

Sprong, Tom; Brandtzaeg, Petter; Fung, Michael; Pharo, Anne M; Høiby, E Arne; Michaelsen, Terje E; Aase, Audun; van der Meer, Jos W M; van Deuren, Marcel; Mollnes, Tom E

2003-11-15

The complement system plays an important role in the initial defense against Neisseria meningitidis. In contrast, uncontrolled activation in meningococcal sepsis contributes to the development of tissue damage and shock. In a novel human whole blood model of meningococcal sepsis, we studied the effect of complement inhibition on inflammation and bacterial killing. Monoclonal antibodies (mAbs) blocking lectin and alternative pathways inhibited complement activation by N meningitidis and oxidative burst induced in granulocytes and monocytes. Oxidative burst was critically dependent on CD11b/CD18 (CR3) expression but not on Fc gamma-receptors. Specific inhibition of C5a using mAb 137-26 binding the C5a moiety of C5 before cleavage prohibited CR3 up-regulation, phagocytosis, and oxidative burst but had no effect on C5b-9 (TCC) formation, lysis, and bacterial killing. An mAb-blocking cleavage of C5, preventing C5a and TCC formation, showed the same effect on CR3, phagocytosis, and oxidative burst as the anti-C5a mAb but additionally inhibited TCC formation, lysis, and bacterial killing, consistent with a C5b-9-dependent killing mechanism. In conclusion, the anti-C5a mAb 137-26 inhibits the potentially harmful effects of N meningitidis-induced C5a formation while preserving complement-mediated bacterial killing. We suggest that this may be an attractive approach for the treatment of meningococcal sepsis.

Parietal Epithelial Cells Participate in the Formation of Sclerotic Lesions in Focal Segmental Glomerulosclerosis

PubMed Central

Smeets, Bart; Kuppe, Christoph; Sicking, Eva-Maria; Fuss, Astrid; Jirak, Peggy; van Kuppevelt, Toin H.; Endlich, Karlhans; Wetzels, Jack F.M.; Gröne, Hermann-Josef; Floege, Jürgen

2011-01-01

The pathogenesis of the development of sclerotic lesions in focal segmental glomerulosclerosis (FSGS) remains unknown. Here, we selectively tagged podocytes or parietal epithelial cells (PECs) to determine whether PECs contribute to sclerosis. In three distinct models of FSGS (5/6-nephrectomy + DOCA-salt; the murine transgenic chronic Thy1.1 model; or the MWF rat) and in human biopsies, the primary injury to induce FSGS associated with focal activation of PECs and the formation of cellular adhesions to the capillary tuft. From this entry site, activated PECs invaded the affected segment of the glomerular tuft and deposited extracellular matrix. Within the affected segment, podocytes were lost and mesangial sclerosis developed within the endocapillary compartment. In conclusion, these results demonstrate that PECs contribute to the development and progression of the sclerotic lesions that define FSGS, but this pathogenesis may be relevant to all etiologies of glomerulosclerosis. PMID:21719782

Osteogenic Activity of Locally Applied Small Molecule Drugs in a Rat Femur Defect Model

PubMed Central

Cottrell, Jessica A.; Vales, Francis M.; Schachter, Deborah; Wadsworth, Scott; Gundlapalli, Rama; Kapadia, Rasesh; O'Connor, J. Patrick

2010-01-01

The long-term success of arthroplastic joints is dependent on the stabilization of the implant within the skeletal site. Movement of the arthroplastic implant within the bone can stimulate osteolysis, and therefore methods which promote rigid fixation or bone growth are expected to enhance implant stability and the long-term success of joint arthroplasty. In the present study, we used a simple bilateral bone defect model to analyze the osteogenic activity of three small-molecule drug implants via microcomputerized tomography (micro-CT) and histomorphometry. In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts. PMID:20625499

Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation

PubMed Central

Yost, Christian C.; Schwertz, Hansjörg; Cody, Mark J.; Wallace, Jared A.; Campbell, Robert A.; Vieira-de-Abreu, Adriana; Araujo, Claudia V.; Schubert, Sebastian; Harris, Estelle S.; Rowley, Jesse W.; Rondina, Matthew T.; Koening, Curry L.; Weyrich, Andrew S.; Zimmerman, Guy A.

2016-01-01

Neutrophil granulocytes, also called polymorphonuclear leukocytes (PMNs), extrude molecular lattices of decondensed chromatin studded with histones, granule enzymes, and antimicrobial peptides that are referred to as neutrophil extracellular traps (NETs). NETs capture and contain bacteria, viruses, and other pathogens. Nevertheless, experimental evidence indicates that NETs also cause inflammatory vascular and tissue damage, suggesting that identifying pathways that inhibit NET formation may have therapeutic implications. Here, we determined that neonatal NET-inhibitory factor (nNIF) is an inhibitor of NET formation in umbilical cord blood. In human neonatal and adult neutrophils, nNIF inhibits key terminal events in NET formation, including peptidyl arginine deiminase 4 (PAD4) activity, neutrophil nuclear histone citrullination, and nuclear decondensation. We also identified additional nNIF-related peptides (NRPs) that inhibit NET formation. nNIFs and NRPs blocked NET formation induced by pathogens, microbial toxins, and pharmacologic agonists in vitro and in mouse models of infection and systemic inflammation, and they improved mortality in murine models of systemic inflammation, which are associated with NET-induced collateral tissue injury. The identification of NRPs as neutrophil modulators that selectively interrupt NET generation at critical steps suggests their potential as therapeutic agents. Furthermore, our results indicate that nNIF may be an important regulator of NET formation in fetal and neonatal inflammation. PMID:27599294

Coiled-coil forming peptides for the induction of silver nanoparticles

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

Božič Abram, Sabina; Graduate School of Biomedicine, University of Ljubljana, Ljubljana 1000; Aupič, Jana

Biopolymers with defined sequence patterns offer an attractive alternative for the formation of silver nanoparticle (AgNP). A set of coiled-coil dimer forming peptides was tested for their AgNP formation ability. Seventeen of those peptides mediated the formation of AgNPs in aqueous solution at neutral pH, while the formation of a coiled-coil dimer inhibited the nanoparticle generation. A QSAR regression model on the relationship between sequence and function suggests that in this peptide type the patterns KXQQ and KXEE are favorable, whereas Ala residues appear to have an inhibitory effect. UV–VIS spectra of the obtained nanoparticles gave a peak at aroundmore » 420 nm, typical for AgNPs in the size range around 40 nm, which was confirmed by dynamic light scattering and transmission electron microscopy. Peptide-induced AgNPs exhibited good antibacterial activity, even after a 15 min contact time, while they had low toxicity to human cells at the same concentrations. These results show that our designed peptides generate AgNPs with antibacterial activity at mild conditions and might be used for antibacterial coatings. - Highlights: • 17 of the 30 tested coiled-coil forming peptides induce AgNP formation. • Coiled-coil dimer formation suppresses AgNP generation of individual peptides. • Size of the peptide-induced silver nanoparticles is around 40 nm. • QSAR analysis points to the importance of KXQQ and KXEE motifs for AgNP generation. • Peptide-induced silver nanoparticles exhibit antibacterial activity.« less

Active Galactic Nuclei, Host Star Formation, and the Far Infrared

NASA Astrophysics Data System (ADS)

Draper, Aden R.; Ballantyne, D. R.

2011-05-01

Telescopes like Herschel and the Atacama Large Millimeter/submillimeter Array (ALMA) are creating new opportunities to study sources in the far infrared (FIR), a wavelength region dominated by cold dust emission. Probing cold dust in active galaxies allows for study of the star formation history of active galactic nuclei (AGN) hosts. The FIR is also an important spectral region for observing AGN which are heavily enshrouded by dust, such as Compton thick (CT) AGN. By using information from deep X-ray surveys and cosmic X-ray background synthesis models, we compute Cloudy photoionization simulations which are used to predict the spectral energy distribution (SED) of AGN in the FIR. Expected differential number counts of AGN and their host galaxies are calculated in the Herschel bands. The expected contribution of AGN and their hosts to the cosmic infrared background (CIRB) is also computed. Multiple star formation scenarios are investigated using a modified blackbody star formation SED. It is found that FIR observations at 350 and 500 um are an excellent tool in determining the star formation history of AGN hosts. Additionally, the AGN contribution to the CIRB can be used to determine whether star formation in AGN hosts evolves differently than in normal galaxies. AGN and host differential number counts are dominated by CT AGN in the Herschel-SPIRE bands. Therefore, X-ray stacking of bright SPIRE sources is likely to disclose a large fraction of the CT AGN population.

A non-canonical role for Rgnef in promoting integrin-stimulated focal adhesion kinase activation

PubMed Central

Miller, Nichol L. G.; Lawson, Christine; Kleinschmidt, Elizabeth G.; Tancioni, Isabelle; Uryu, Sean; Schlaepfer, David D.

2013-01-01

Summary Rgnef (also known as p190RhoGEF or ARHGEF28) is a Rho guanine-nucleotide-exchange factor (GEF) that binds focal adhesion kinase (FAK). FAK is recruited to adhesions and activated by integrin receptors binding to matrix proteins, such as fibronectin (FN). Canonical models place Rgnef downstream of integrin–FAK signaling in regulating Rho GTPase activity and cell movement. Herein, we establish a new, upstream role for Rgnef in enhancing FAK localization to early peripheral adhesions and promoting FAK activation upon FN binding. Rgnef-null mouse embryo fibroblasts (MEFs) exhibit defects in adhesion formation, levels of FAK phosphotyrosine (pY)-397 and FAK localization to peripheral adhesions upon re-plating on FN. Rgnef re-expression rescues these defects, but requires Rgnef–FAK binding. A mutation in the Rgnef pleckstrin homology (PH) domain inhibits adhesion formation, FAK localization, and FAK-Y397 and paxillin-Y118 phosphorylation without disrupting the Rgnef–FAK interaction. A GEF-inactive Rgnef mutant rescues FAK-Y397 phosphorylation and early adhesion localization, but not paxillin-Y118 phosphorylation. This suggests that, downstream of FN binding, paxillin-pY118 requires Rgnef GEF activity through a mechanism distinct from adhesion formation and FAK activation. These results support a scaffolding role for Rgnef in FAK localization and activation at early adhesions in a PH-domain-dependent but GEF-activity-independent manner. PMID:24006257

Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis.

PubMed

Ma, Ruishuang; Xie, Rui; Yu, Chengyuan; Si, Yu; Wu, Xiaoming; Zhao, Lu; Yao, Zhipeng; Fang, Shaohong; Chen, He; Novakovic, Valerie; Gao, Chunyan; Kou, Junjie; Bi, Yayan; Thatte, Hemant S; Yu, Bo; Yang, Shufen; Zhou, Jin; Shi, Jialan

2017-07-10

The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes. Activated platelets adhered were and ultimately digested by ECs in vivo and in vitro. Blocking PS on platelets or αvβ3 integrin on ECs attenuated platelet clearance resulting in increased platelet count in a mouse model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding decrease in platelet-leukocyte complex formation and markedly reduced generation of factor Xa and thrombin on platelets. Pretreatment with lactadherin significantly increased phagocytosis of platelets by approximately 2-fold, diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin formation by 50%. Our results suggest that PS-mediated clearance of activated platelets by the endothelium results in an anti-inflammatory, anticoagulant, and antithrombotic effect that contribute to maintaining platelet homeostasis during acute inflammation. These results suggest a new therapeutic target for impeding the development of DIC.

The Dynamics and Cold Gas Content of Luminous Infrared Galaxy Mergers in the Local Universe

NASA Astrophysics Data System (ADS)

Privon, G. C.

2014-08-01

Luminous Infrared Galaxies (LIRGs; 10^11 ≤ L_IR [8 - 1000 μm]/L_sun < 10^12) and Ultraluminous Infrared Galaxies (ULIRGS; L_IR [8 - 1000 μm]/L_sun ≥ 10^12) are the most extreme star forming systems in the local universe, both in terms of their absolute star formation rates—ten to several hundred times that of ``normal'' galaxies—and their star formation rate densities. Many U/LIRGs are interacting or merging disk galaxies undergoing enhanced star formation and/or nuclear activity, likely triggered as the objects transform into massive S0 and elliptical merger remnants. The LIRG population also contains a significant number of apparently isolated disk galaxies which are undergoing enhanced star formation, providing a window on secular galaxy evolution. This work examines nearby U/LIRGs chosen from the Great Observatories All-sky LIRG Survey (GOALS), an infrared flux and luminosity selected sample. The proximity of these systems enables high spatial resolution study of active galactic nuclei (AGN) and extreme star formation in these objects. New maps of the neutral hydrogen (HI) emission are presented for systems morphologically classified in the optical and mid-infrared as non-merging or pre-merger systems. The results of this study suggests that some infrared-selected galaxies may be minor mergers or interactions which are being viewed so soon after first pass that the stellar disk has not yet been significantly disturbed. Galaxy mergers appear to drive much of the enhanced activity observed in U/LIRGs; understanding the merger state of these systems provides a context for observations of star formation and AGN properties. In order to constrain the merger stage, dynamical models for a sample of nine systems were matched to the observed kinematics and morphology as obtained from optical imaging and interferometric HI maps. The resulting models are used not only to constrain the merger stage, but also the encounter geometry of the precursor. Based on these dynamical models a new merger stage classification is presented, which re-scales objects to a common timeline is used to place the observations in context. Applications of this dynamical merger stage to the study of star formation rates and indicators of AGN activity are presented. Finally, newly obtained measurements of the galaxy-integrated 1-0 rotational transitions of hydrogen cyanide (HCN) and formylium (HCO^+) in a sample of U/LIRGs are used to investigate the ratio of HCN (1-0) to HCO (1-0) and its dependence on mid-infrared indicators of AGN strength. In contrast to previous claims, it is demonstrated that high values of this ratio are not uniquely linked to the presence of an AGN, but can be achieved in systems dominated by star formation. This suggests the excitation of these high critical density molecular gas tracers is determined by the complex interplay of radiation field, gas density, and gas column.

Simulating the formation of Hurricane Isabel (2003) with AIRS data

NASA Astrophysics Data System (ADS)

Wu, Liguang; Braun, Scott A.; Qu, John J.; Hao, Xianjun

2006-02-01

Using the AIRS retrieved temperature and humidity profiles, the Saharan Air Layer (SAL) influence on the formation of Hurricane Isabel (2003) is simulated numerically with the MM5 model. The warmth and dryness of the SAL (the thermodynamic effect) is assimilated by use of the nudging technique, which enables the model thermodynamic state to be relaxed to the profiles of the AIRS retrieved data for the regions without cloud contamination. By incorporating the AIRS data, MM5 better simulates the large-scale flow patterns and the timing and location of the formation of Hurricane Isabel and its subsequent track. By comparing with an experiment without nudging of the AIRS data, it is shown that the SAL may have delayed the formation of Hurricane Isabel and inhibited the development of another tropical disturbance to the east. This case study confirms the argument by Dunion and Velden (2004) that the SAL can suppress Atlantic tropical cyclone activity by increasing the vertical wind shear, reducing the mean relative humidity, and stabilizing the environment at lower levels.

The role of protease-activated receptors PAR-1 and PAR-2 in the repair of 16HBE 14o(-) epithelial cell monolayers in vitro.

PubMed

Ewen, D; Clarke, S L; Smith, J R; Berger, C; Salmon, G; Trevethick, M; Shute, J K

2010-03-01

We recently reported that repair following mechanical wounding of epithelial cell layers in vitro is dependent on fibrin formation and the activity of locally expressed coagulation cascade proteins. Serine proteases of the coagulation cascade are an important group of protease-activated receptor (PAR) activators and PAR-1 to 4 are expressed by the normal bronchial epithelium. We tested the hypothesis that activation of PAR-1 and PAR-2 by coagulation cascade proteases stimulates epithelial repair via effects on fibrin formation. Using mechanically wounded 16HBE 14o(-) epithelial cell layers in culture, we investigated the effect of PAR-1 and PAR-2 agonist peptides, control partially scrambled peptides and PAR-neutralizing antibodies on the rate of repair and fibrin formation. Coagulation factors in culture supernatants were measured by immunoblot. RT-PCR was used to investigate PAR-1, PAR-2 and PGE2 receptor (EP-1 to EP-4) expression in this model and qRT-PCR to quantify responses to wounding. Additionally, we investigated the effect of exogenously added factor Xa (FXa) and neutrophil elastase and the influence of PGE2 and indomethacin on the repair response. PAR-1 and PAR-2 peptide agonists stimulated the rate of repair and enhanced the formation of a fibrin provisional matrix to support the repair process. Conversely, PAR-neutralizing antibodies inhibited repair. Under serum-free culture conditions, 16HBE 14o(-) cells expressed EP-2 and EP-3, but not EP-1 or EP-4, receptors. Wounding induced an increased expression of EP-3 but did not alter EP-2, PAR-1 or PAR-2 expression. In the absence of PAR agonists, there was no evidence for a role for PGE2 in fibrin formation or the repair process. Indomethacin attenuated fibrin formation in wounded cultures only in the presence of the PAR-2 peptide. FXa stimulated epithelial repair while neutrophil elastase reduced the levels of coagulation factors and inhibited repair. Locally expressed serine proteases of the coagulation cascade activate PAR-1 and PAR-2 to enhance fibrin formation and bronchial epithelial repair.

Testing the Role of p21-Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease

DTIC Science & Technology

2015-06-01

preclinical models of NF1? Can whole kinome analysis predict pathways for drug resistance in treated mice? Procuring Contracting/Grants Officer: Emily...cells. b) Evaluate transduction of hydroxyethyl starch (HES)-processed hematopoietic cells. c) Monitor gene transfer in primary FANCC-/- progenitors

How Do Communities Act? Unique Events and Purposeful Strategies in the Formation of an Industrial Base in Rivertown. [Revised].

ERIC Educational Resources Information Center

Brown, Ralph B.

Effective rural education depends on active community involvement. This ethnographic case study examines three models of community organization as an explanation of how community action occurs. The three models are: (1) individuals interacting in formal and informal groups; (2) networks of "weak ties" effective for diffusing information and…

Evidence Evaluation: Measure "Z" Corresponds to Human Utility Judgments Better than Measure "L" and Optimal-Experimental-Design Models

ERIC Educational Resources Information Center

Rusconi, Patrice; Marelli, Marco; D'Addario, Marco; Russo, Selena; Cherubini, Paolo

2014-01-01

Evidence evaluation is a crucial process in many human activities, spanning from medical diagnosis to impression formation. The present experiments investigated which, if any, normative model best conforms to people's intuition about the value of the obtained evidence. Psychologists, epistemologists, and philosophers of science have proposed…

Formation and evolution of Lakshmi Planum, Venus: Assessment of models using observations from geological mapping

NASA Astrophysics Data System (ADS)

Ivanov, M. A.; Head, J. W.

2008-12-01

Detailed geological analysis of the Lakshmi Planum region of western Ishtar Terra results in the establishment of the sequence of major events during the formation and evolution of western Ishtar Terra, an important and somewhat unique area on Venus characterized by a raised volcanic plateau surrounded by distinctive folded mountain belts, such as Maxwell Montes. These mapping results and the stratigraphic and structural relationships provide a basis for addressing the complicated problem of Lakshmi Planum formation and for testing the suite of models previously proposed to explain this structure. We review and classify previous models of formation for western Ishtar Terra into "downwelling" models (generally involving convergence and underthrusting) and "upwelling" models (generally involving plume-like upwelling and divergence). The interpreted nature of units and the sequence of events derived from geological mapping are in contrast to the predictions of the divergent models. The major contradictions are as follows: (1) The very likely presence of an ancient (craton-like) tessera massif in the core of Lakshmi, which is inconsistent with the model of formation of Lakshmi due to rise and collapse of a mantle diapir; (2) The absence of rift zones in the interior of Lakshmi that are predicted by the divergent models; (3) The apparent migration of volcanic activity toward the center of Lakshmi, whereas divergent models predict the opposite trend; (4) The abrupt cessation of ridges of the mountain ranges at the edge of Lakshmi Planum and propagation of these ridges over hundreds of kilometers outside Lakshmi; the divergent models predict the opposite progression in the development of major contractional features. In contrast, convergent models of formation and evolution of Lakshmi Planum appear to be more consistent with the observations and explain this structure by collision and underthrusting/subduction of lower-lying plains with the elevated and rigid block of tessera. These models are capable of explaining formation of the major features of western Ishtar (for example, the mountain belts), the sequences of events, and principal volcanic and tectonic trends during the evolution of Lakshmi. To explain the pronounced north-south asymmetry of Lakshmi these models need to consider the likelihood that the major focal points of collision are at the north and north-west margins of the plateau. We note that pure downwelling models, however, face three important difficulties: (1) The possibly unrealistically long time span that appears to be required to produce the major features of Lakshmi; (2) The strong north-south asymmetry of the Planum; the pure downwelling models predict the formation of a more symmetrical structure; and (3) The absence of radial contractional structures (arches and ridges) in the interior of Lakshmi that would represent the predictions of the downwelling models.

An integrated QSAR-PBK/D modelling approach for predicting detoxification and DNA adduct formation of 18 acyclic food-borne α,β-unsaturated aldehydes

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

Kiwamoto, R., E-mail: reiko.kiwamoto@wur.nl; Spenkelink, A.; Rietjens, I.M.C.M.

Acyclic α,β-unsaturated aldehydes present in food raise a concern because the α,β-unsaturated aldehyde moiety is considered a structural alert for genotoxicity. However, controversy remains on whether in vivo at realistic dietary exposure DNA adduct formation is significant. The aim of the present study was to develop physiologically based kinetic/dynamic (PBK/D) models to examine dose-dependent detoxification and DNA adduct formation of a group of 18 food-borne acyclic α,β-unsaturated aldehydes without 2- or 3-alkylation, and with no more than one conjugated double bond. Parameters for the PBK/D models were obtained using quantitative structure–activity relationships (QSARs) defined with a training set of sixmore » selected aldehydes. Using the QSARs, PBK/D models for the other 12 aldehydes were defined. Results revealed that DNA adduct formation in the liver increases with decreasing bulkiness of the molecule especially due to less efficient detoxification. 2-Propenal (acrolein) was identified to induce the highest DNA adduct levels. At realistic dietary intake, the predicted DNA adduct levels for all aldehydes were two orders of magnitude lower than endogenous background levels observed in disease free human liver, suggesting that for all 18 aldehydes DNA adduct formation is negligible at the relevant levels of dietary intake. The present study provides a proof of principle for the use of QSAR-based PBK/D modelling to facilitate group evaluations and read-across in risk assessment. - Highlights: • Physiologically based in silico models were made for 18 α,β-unsaturated aldehydes. • Kinetic parameters were determined by in vitro incubations and a QSAR approach. • DNA adduct formation was negligible at levels relevant for dietary intake. • The use of QSAR-based PBK/D modelling facilitates group evaluations and read-across.« less

A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models.

PubMed

Huang, Shiu-Wen; Kuo, Heng-Lan; Hsu, Ming-Tsung; Tseng, Yufeng Jane; Lin, Shu-Wha; Kuo, Sheng-Chu; Peng, Hui-Chin; Lien, Jin-Cherng; Huang, Tur-Fu

2016-08-01

A novel benzimidazole derivative, nstpbp5185, was discovered through in vitro and in vivo evaluations for antiplatelet activity. Thromaboxane receptor (TP) is important in vascular physiology, haemostasis and pathophysiological thrombosis. Nstpbp5185 concentration-dependently inhibited human platelet aggregation caused by collagen, arachidonic acid and U46619. Nstpbp5185 caused a right-shift of the concentration-response curve of U46619 and competitively inhibited the binding of 3H-SQ-29548 to TP receptor expressed on HEK-293 cells, with an IC50 of 0.1 µM, indicating that nstpbp5185 is a TP antagonist. In murine thrombosis models, nstpbp5185 significantly prolonged the latent period in triggering platelet plug formation in mesenteric and FeCl3-induced thrombi formation, and increased the survival rate in pulmonary embolism model with less bleeding than aspirin. This study suggests nstpbp5185, an orally selective anti-thrombotic agent, acting through blockade of TXA2 receptor, may be efficacious for prevention or treatment of pathologic thrombosis.

Mesoscopic Modeling of Blood Clotting: Coagulation Cascade and Platelets Adhesion

NASA Astrophysics Data System (ADS)

Yazdani, Alireza; Li, Zhen; Karniadakis, George

2015-11-01

The process of clot formation and growth at a site on a blood vessel wall involve a number of multi-scale simultaneous processes including: multiple chemical reactions in the coagulation cascade, species transport and flow. To model these processes we have incorporated advection-diffusion-reaction (ADR) of multiple species into an extended version of Dissipative Particle Dynamics (DPD) method which is considered as a coarse-grained Molecular Dynamics method. At the continuum level this is equivalent to the Navier-Stokes equation plus one advection-diffusion equation for each specie. The chemistry of clot formation is now understood to be determined by mechanisms involving reactions among many species in dilute solution, where reaction rate constants and species diffusion coefficients in plasma are known. The role of blood particulates, i.e. red cells and platelets, in the clotting process is studied by including them separately and together in the simulations. An agonist-induced platelet activation mechanism is presented, while platelets adhesive dynamics based on a stochastic bond formation/dissociation process is included in the model.

Fueling nuclear activity in disk galaxies: Starbursts and monsters

NASA Astrophysics Data System (ADS)

Heller, Clayton H.; Shlosman, Isaac

1994-03-01

We study the evolution of the gas distribution in a globally unstable galactic disk with a particular emphasis on the gasdynamics in the central kiloparsec and the fueling activity there. The two-component self-gravitating disk is embedded in a responsive halo of comparable mass. The gas and stars are evolved using a three-dimensional hybrid smoothed particle hydrodynamics/N-body code and the gravitational interactions are calculated using a hierarchical TREE algorithm. A massive 'star formation' is introduced when the gas becomes Jeans unstable and locally exceeds the critical density of approximately 100 solar mass pc-3. The newly formed OB stars deposit energy in the gas by means of radiation-driven winds and supernovae. This energy is partially thermalized (efficiency of a few percent); the rest is radiated away. Models without star formation are evolved for a comparison. The effect of a massive object at the disk center is studied by placing a 'seed' black hole (BH) of 5 x 107 solar mass with an accretion radius of 20 pc. The tendency of the system to form a massive object 'spontaneously' is tested in models without the BH. We find that for models without star formation the bar- or dynamical friction-driven inflows lead to (1) domination of the central kpc by a few massive clouds that evolve into a single object probably via a cloud binary system, with and without a 'seed' BH, (2) accretion onto the BH which has a sporadic character, and (3) formation of remnant disks around the BH with a radius of 60-80 pc which result from the capture and digestion of clouds. For models with star formation, we find that (1) the enrgy input into the gas induces angular momentum loss and inflow rates by a factor less than 3, (2) the star formation is concentrated mainly at the apocenters of the gaseous circulation in the stellar bar and in the nuclear region, (3) the nuclear starburst phase appears to be very luminous approximately 1045-1046 erg/s and episodic with a typical single burst duration of aproximately 107 yr, and (4) the starburst phase coincides with both the gas becoming dynamically important and the catastrophic growth of the BH. It ends with the formation of cold residual less than 1 kpc radius gas disks. Models without the 'seed' BH form less than 1 kpc radius fat disks which dominate the dynamics. Gaseous bars follow, drive further inflow, and may fission into a massive cloud binary system at the center.

Production of furfural from palm oil empty fruit bunches: kinetic model comparation

NASA Astrophysics Data System (ADS)

Panjaitan, J. R. H.; Monica, S.; Gozan, M.

2017-05-01

Furfural is a chemical compound that can be applied to pharmaceuticals, cosmetics, resins and cleaning compound which can be produced by acid hydrolysis of biomass. Indonesia’s demand for furfural in 2010 reached 790 tons that still imported mostly 72% from China. In this study, reaction kinetic models of furfural production from oil palm empty fruit bunches with submitting acid catalyst at the beginning of the experiment will be determine. Kinetic data will be obtained from hydrolysis of empty oil palm bunches using sulfuric acid catalyst 3% at temperature 170°C, 180°C and 190°C for 20 minutes. From this study, the kinetic model to describe the production of furfural is the kinetic model where generally hydrolysis reaction with an acid catalyst in hemicellulose and furfural will produce the same decomposition product which is formic acid with different reaction pathways. The activation energy obtained for the formation of furfural, the formation of decomposition products from furfural and the formation of decomposition products from hemicellulose is 8.240 kJ/mol, 19.912 kJ/mol and -39.267 kJ / mol.

The prostaglandin receptor EP2 activates multiple signaling pathways and β-arrestin1 complex formation during mouse skin papilloma development

PubMed Central

Chun, Kyung-Soo; Lao, Huei-Chen; Trempus, Carol S.; Okada, Manabu; Langenbach, Robert

2009-01-01

Prostaglandin E2 (PGE2) is elevated in many tumor types, but PGE2's contributions to tumor growth are largely unknown. To investigate PGE2's roles, the contributions of one of its receptors, EP2, were studied using the mouse skin initiation/promotion model. Initial studies indicated that protein kinase A (PKA), epidermal growth factor receptor (EGFR) and several effectors—cyclic adenosine 3′,5′-monophosphate response element-binding protein (CREB), H-Ras, Src, protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2—were activated in 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas and that PKA and EGFR inhibition (H89 and AG1478, respectively) decreased papilloma formation. EP2's contributions to the activation of these pathways and papilloma development were determined by inhibiting endogenous TPA-induced PGE2 production with indomethacin (Indo) and concomitantly treating with the EP2 agonist, CAY10399 (CAY). CAY treatment restored papilloma formation in TPA/Indo-treated mice and increased cyclic adenosine 3′,5′-monophosphate and PKA activation as measured by p-CREB formation. CAY treatment also increased EGFR and Src activation and their inhibition by AG1478 and PP2 indicated that Src was upstream of EGFR. CAY also increased H-Ras, ERK1/2 and AKT activation, and AG1478 decreased their activation indicating EGFR being upstream. Supporting EP2's contribution, EP2−/− mice exhibited 65% fewer papillomas and reduced Src, EGFR, H-Ras, AKT and ERK1/2 activation. G protein-coupled receptor (GPCR) activation of EGFR has been reported to involve Src's activation via a GPCR–β-arrestin–Src complex. Indeed, immunoprecipitation of β-arrestin1 or p-Src indicated the presence of an EP2–β-arrestin1–p-Src complex in papillomas. The data indicated that EP2 contributed to tumor formation via activation of PKA and EGFR and that EP2 formed a complex with β-arrestin1 and Src that contributed to signaling and/or EP2 desensitization. PMID:19587094

Remediating lapses in professionalism among undergraduate pre-clinical medical students in an Asian Institution: a multimodal approach.

PubMed

Findyartini, Ardi; Sudarsono, Nani Cahyani

2018-05-02

Fostering personal identity formation and professional development among undergraduate medical students is challenging. Based on situated learning, experiential learning and role-modelling frameworks, a six-week course was developed to remediate lapses in professionalism among undergraduate medical students. This study aims to explore the students' perceptions of their personal identity formation and professional development following completion of the course. This qualitative study, adopting a phenomenological design, uses the participants' reflective diaries as primary data sources. In the pilot course, field work, role-model shadowing and discussions with resource personnel were conducted. A total of 14 students were asked to provide written self-reflections. Consistent, multi-source feedback was provided throughout the course. A thematic analysis was conducted to identify the key processes of personal and professional development among the students during remediation. Three main themes were revealed. First, students highlighted the strength of small group activities in helping them 'internalise the essential concepts'. Second, the role-model shadowing supported their understanding of 'what kind of medical doctors they would become'. Third, the field work allowed them to identify 'what the "noble values" are and how to implement them in daily practice'. By implementing multimodal activities, the course has high potential in supporting personal identity formation and professional development among undergraduate pre-clinical medical students, as well as remediating their lapses in professionalism. However, there are challenges in implementing the model among a larger student population and in documenting the long-term impact of the course.

Inducible nitric oxide synthase is key to peroxynitrite-mediated, LPS-induced protein radical formation in murine microglial BV2 cells

PubMed Central

Kumar, Ashutosh; Chen, Shih-Heng; Kadiiska, Maria B.; Hong, Jau-Shyong; Zielonka, Jacek; Kalyanaraman, Balaraman; Mason, Ronald P.

2014-01-01

Microglia are the resident immune cells in the brain. Microglial activation is characteristic of several inflammatory and neurodegenerative diseases including Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. Though LPS-induced microglial activation in models of Parkinson’s disease (PD) is well documented, the free radical-mediated protein radical formation and its underlying mechanism during LPS-induced microglial activation is not known. Here we have used immuno-spin trapping and RNA interference to investigate the role of inducible nitric oxide synthase (iNOS) in peroxynitrite-mediated protein radical formation in murine microglial BV2 cells treated with LPS. Treatment of BV2 cells with LPS resulted in morphological changes, induction of iNOS and increased protein radical formation. Pretreatments with FeTPPS (a peroxynitrite decomposition catalyst), L-NAME (total NOS inhibitor), 1400W (iNOS inhibitor) and apocynin significantly attenuated LPS-induced protein radical formation and tyrosine nitration. Results obtained with coumarin-7-boronic acid, a highly specific probe for peroxynitrite detection, correlated with LPS-induced tyrosine nitration, which demonstrated involvement of peroxynitrite in protein radical formation. A similar degree of protection conferred by 1400W and L-NAME led us to conclude that only iNOS, and no other forms of NOS, are involved in LPS-induced peroxynitrite formation. Subsequently, siRNA for iNOS, the iNOS-specific inhibitor 1400W, the NF-kB inhibitor PDTC and the P38 MAPK inhibitor SB202190 were used to inhibit iNOS directly or indirectly. Inhibition of iNOS precisely correlated with decreased protein radical formation in LPS-treated BV2 cells. The time course of protein radical formation also matched the time course of iNOS expression. Taken together, these results prove the role of iNOS in peroxynitrite-mediated protein radical formation in LPS-treated microglial BV2 cells. PMID:24746617

Large-Scale Patterns in a Minimal Cognitive Flocking Model: Incidental Leaders, Nematic Patterns, and Aggregates

NASA Astrophysics Data System (ADS)

Barberis, Lucas; Peruani, Fernando

2016-12-01

We study a minimal cognitive flocking model, which assumes that the moving entities navigate using the available instantaneous visual information exclusively. The model consists of active particles, with no memory, that interact by a short-ranged, position-based, attractive force, which acts inside a vision cone (VC), and lack velocity-velocity alignment. We show that this active system can exhibit—due to the VC that breaks Newton's third law—various complex, large-scale, self-organized patterns. Depending on parameter values, we observe the emergence of aggregates or millinglike patterns, the formation of moving—locally polar—files with particles at the front of these structures acting as effective leaders, and the self-organization of particles into macroscopic nematic structures leading to long-ranged nematic order. Combining simulations and nonlinear field equations, we show that position-based active models, as the one analyzed here, represent a new class of active systems fundamentally different from other active systems, including velocity-alignment-based flocking systems. The reported results are of prime importance in the study, interpretation, and modeling of collective motion patterns in living and nonliving active systems.

Large-Scale Patterns in a Minimal Cognitive Flocking Model: Incidental Leaders, Nematic Patterns, and Aggregates.

PubMed

Barberis, Lucas; Peruani, Fernando

2016-12-09

We study a minimal cognitive flocking model, which assumes that the moving entities navigate using the available instantaneous visual information exclusively. The model consists of active particles, with no memory, that interact by a short-ranged, position-based, attractive force, which acts inside a vision cone (VC), and lack velocity-velocity alignment. We show that this active system can exhibit-due to the VC that breaks Newton's third law-various complex, large-scale, self-organized patterns. Depending on parameter values, we observe the emergence of aggregates or millinglike patterns, the formation of moving-locally polar-files with particles at the front of these structures acting as effective leaders, and the self-organization of particles into macroscopic nematic structures leading to long-ranged nematic order. Combining simulations and nonlinear field equations, we show that position-based active models, as the one analyzed here, represent a new class of active systems fundamentally different from other active systems, including velocity-alignment-based flocking systems. The reported results are of prime importance in the study, interpretation, and modeling of collective motion patterns in living and nonliving active systems.

Xylem formation can be modeled statistically as a function of primary growth and cambium activity.

PubMed

Huang, Jian-Guo; Deslauriers, Annie; Rossi, Sergio

2014-08-01

Primary (budburst, foliage and shoot) growth and secondary (cambium and xylem) growth of plants play a vital role in sequestering atmospheric carbon. However, their potential relationships have never been mathematically quantified and the underlying physiological mechanisms are unclear. We monitored primary and secondary growth in Picea mariana and Abies balsamea on a weekly basis from 2010 to 2013 at four sites over an altitudinal gradient (25-900 m) in the eastern Canadian boreal forest. We determined the timings of onset and termination through the fitted functions and their first derivative. We quantified the potential relationships between primary growth and secondary growth using the mixed-effects model. We found that xylem formation of boreal conifers can be modeled as a function of cambium activity, bud phenology, and shoot and needle growth, as well as species- and site-specific factors. Our model reveals that there may be an optimal mechanism to simultaneously allocate the photosynthetic products and stored nonstructural carbon to growth of different organs at different times in the growing season. This mathematical link can bridge phenological modeling, forest ecosystem productivity and carbon cycle modeling, which will certainly contribute to an improved prediction of ecosystem productivity and carbon equilibrium. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Moist Thermodynamics of Tropical Cyclone Formation and Intensification in High-Resolution Climate Models

NASA Astrophysics Data System (ADS)

Wing, A. A.; Camargo, S. J.; Sobel, A. H.; Kim, D.; Moon, Y.; Bosilovich, M. G.; Murakami, H.; Reed, K. A.; Vecchi, G. A.; Wehner, M. F.; Zarzycki, C. M.; Zhao, M.

2017-12-01

In recent years, climate models have improved such that high-resolution simulations are able to reproduce the climatology of tropical cyclone activity with some fidelity and show some skill in seasonal forecasting. However, biases remain in many models, motivating a better understanding of what factors control the representation of tropical cyclone activity in climate models. We explore tropical cyclogenesis and intensification processes in six high-resolution climate models from NOAA/GFDL, NCAR, and NASA, including both coupled and uncoupled configurations. Our analysis framework focuses on how convection, moisture, clouds and related processes are coupled and employs budgets of column moist static energy and the spatial variance of column moist static energy. The latter allows us to quantify the different feedback processes responsible for the amplification of moist static energy anomalies associated with the organization of convection and cyclogenesis, including surface flux feedbacks and cloud-radiative feedbacks. We track the formation and evolution of tropical cyclones in the climate model simulations and apply our analysis along the individual tracks and composited over many tropical cyclones. We use two methods of compositing: a composite over all TC track points in a given intensity range, and a composite relative to the time of lifetime maximum intensity for each storm (at the same stage in the TC life cycle).

Improved Characterization and Modeling of Tight Oil Formations for CO 2 Enhanced Oil Recovery Potential and Storage Capacity Estimation

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

Sorensen, James; Smith, Steven; Kurz, Bethany

Tight oil formations such as those in the Bakken petroleum system are known to hold hundreds of billions of barrels of oil in place; however, the primary recovery factor for these plays is typically less than 10%. Tight oil formations, including the Bakken Formation, therefore, may be attractive candidates for enhanced oil recovery (EOR) using CO 2. Multiphase fluid behavior and flow in fluid-rich shales can vary substantially depending on the size of pore throats, and properties such as fluid viscosity and density are much different in nanoscale pores than in macroscale pores. Thus it is critical to understand themore » nature and distribution of nano-, micro-, and macroscale pores and fracture networks. To address these issues, the Energy & Environmental Research Center (EERC) has been conducting a research program entitled “Improved Characterization and Modeling of Tight Oil Formations for CO 2 Enhanced Oil Recovery Potential and Storage Capacity Estimation.” The objectives of the project are 1) the use of advanced characterization methods to better understand and quantify the petrophysical and geomechanical factors that control CO 2 and oil mobility within tight oil formation samples, 2) the determination of CO 2 permeation and oil extraction rates in tight reservoir rocks and organic-rich shales of the Bakken, and 3) the integration of the laboratory-based CO 2 permeation and oil extraction data and the characterization data into geologic models and dynamic simulations to develop predictions of CO 2 storage resource and EOR in the Bakken tight oil formation. A combination of standard and advanced petrophysical characterization techniques were applied to characterize samples of Bakken Formation tight reservoir rock and shales from multiple wells. Techniques included advanced computer tomography (CT) imaging, scanning electron microscopy (SEM) techniques, whole-core and micro x-ray CT imaging, field emission (FE) SEM, and focused ion beam (FIB) SEM. Selected samples were also analyzed for geomechanical properties. X-ray CT imaging yielded information on the occurrence of fractures, bedding planes, fossils, and bioturbation in core, as well as data on bulk density and photoelectric factor logs, which were used to interpret porosity, organic content, and mineralogy. FESEM was used for characterization of nano- and microscale features, including nanoscale pore visualization and micropore and pore throat mineralogy. FIBSEM yielded micro- to nanoscale visualization of fracture networks, porosity and pore-size distribution, connected versus isolated porosity, and distribution of organics. Results from the characterization activities provide insight on nanoscale fracture properties, pore throat mineralogy and connectivity, rock matrix characteristics, mineralogy, and organic content. Laboratory experiments demonstrated that CO 2 can permeate the tight matrix of Bakken shale and nonshale reservoir samples and mobilize oil from those samples. Geologic models were created at scales ranging from the core plug to the reservoir, and dynamic simulations were conducted. The data from the characterization and laboratory-based activities were integrated into modeling research activities to determine the fundamental mechanisms controlling fluid transport in the Bakken, which support EOR scheme design and estimation of CO 2 storage potential in tight oil formations. Simulation results suggest a CO 2 storage resource estimate range of 169 million to 1.5 billion tonnes for the Bakken in North Dakota, possibly resulting in 1.8 billion to 16 billion barrels of incremental oil.« less

A Constructivist Cloud Lab.

ERIC Educational Resources Information Center

Emery, Dave

1996-01-01

Describes a lab involving a cloud formation activity that uses the constructivist learning model to get students more involved in creating the lab. Enables students to develop a greater understanding of the concepts involved and more interest in the lab's outcomes. (JRH)

TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation

PubMed Central

Chen, Guiqian; Deng, Chuxia; Li, Yi-Ping

2012-01-01

Transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-β/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-β/BMPs is specifically through both canonical Smad-dependent pathways (TGF-β/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-β/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-β/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-β/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-β/BMP signaling. This review also highlights the different modes of cross-talk between TGF-β/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation. PMID:22298955

The chromogranin A peptide vasostatin-I inhibits gap formation and signal transduction mediated by inflammatory agents in cultured bovine pulmonary and coronary arterial endothelial cells.

PubMed

Blois, Anna; Srebro, Boleslaw; Mandalà, Maurizio; Corti, Angelo; Helle, Karen B; Serck-Hanssen, Guldborg

2006-07-15

The proinflammatory agent tumour necrosis factor alpha (TNFalpha) is one of several agents causing vascular leakage. The N-terminal domain of CgA, vasostatin-I (CgA1-76), has recently been reported to inhibit TNFalpha induced gap formation in human umbilical venous endothelial cells. Here we report on the effect of recombinant human CgA1-78, vasostatin-I, on TNFalpha induced gap formation in two model systems of vascular leakage in arterial endothelial cells of bovine pulmonary (BPAEC) and coronary (BCAEC) origin. Vasostatin-I inhibited the TNFalpha induced gap formation in both models, being inactive in the unstimulated cells. The phosphorylation of p38MAP kinase in TNFalpha activated BPAEC was markedly attenuated in the presence of vasostatin-I and the inhibitory effect corresponded to that of the specific p38MAPK inhibitor SB203580. Vasostatin-I also inhibited the phosphorylation of p38MAPK induced by both thrombin and pertussis toxin in these cells. The results demonstrate that vasostatin-I has inhibitory effects on TNFalpha-induced disruption of confluent layers of cultured pulmonary and coronary arterial endothelial cells. This suggests that vasostatin-I may affect endothelial barrier dysfunction also in arterial vascular beds. Furthermore, the inhibitory activity of vasostatin-I may be associated with the p38MAPK signalling cascade via a pertussis toxin sensitive, presumably Galphai coupled mechanism.

Saponin Interactions with Model Membrane Systems - Langmuir Monolayer Studies, Hemolysis and Formation of ISCOMs.

PubMed

de Groot, Carolin; Müller-Goymann, Christel C

2016-12-01

Saponins are used in medicine due to their pharmacological and immunological effects. To better understand interactions of saponins with model membranes and natural membranes of, for example, erythrocytes, Langmuir film balance experiments are well established. For most saponins, a strong interaction with cholesterol was demonstrated in dependence of both the aglycone part and the sugar moieties and is suggested to be correlated with a strong hemolytic activity, high toxicity, and high surface activity, as was demonstrated for the steroid saponin digitonin. In general, changes in the sugar chain or in substituents of the aglycone result in a modification of the saponin properties. A promising saponin with regard to fairly low hemolytic activity and high adjuvant effect is α -tomatine, which still shows a high affinity for cholesterol. An interaction with cholesterol and lipids has also been proven for the Quillaja saponin from the bark of Quillaja saponaria Molina. This triterpene saponin was approved in marketed vaccines as an adjuvant due to the formation of immunostimulating complexes. Immunostimulating complexes consist of a Quillaja saponin, cholesterol, phospholipids, and a corresponding antigen. Recently, another saponin from Quillaja brasiliensis was successfully tested in immunostimulating complexes, too. Based on the results of interaction studies, the formation of drug delivery systems such as immunostimulating complexes or similar self-assembled colloids is postulated for a variety of saponins. Georg Thieme Verlag KG Stuttgart · New York.

BrainLiner: A Neuroinformatics Platform for Sharing Time-Aligned Brain-Behavior Data

PubMed Central

Takemiya, Makoto; Majima, Kei; Tsukamoto, Mitsuaki; Kamitani, Yukiyasu

2016-01-01

Data-driven neuroscience aims to find statistical relationships between brain activity and task behavior from large-scale datasets. To facilitate high-throughput data processing and modeling, we created BrainLiner as a web platform for sharing time-aligned, brain-behavior data. Using an HDF5-based data format, BrainLiner treats brain activity and data related to behavior with the same salience, aligning both behavioral and brain activity data on a common time axis. This facilitates learning the relationship between behavior and brain activity. Using a common data file format also simplifies data processing and analyses. Properties describing data are unambiguously defined using a schema, allowing machine-readable definition of data. The BrainLiner platform allows users to upload and download data, as well as to explore and search for data from the web platform. A WebGL-based data explorer can visualize highly detailed neurophysiological data from within the web browser, and a data-driven search feature allows users to search for similar time windows of data. This increases transparency, and allows for visual inspection of neural coding. BrainLiner thus provides an essential set of tools for data sharing and data-driven modeling. PMID:26858636

Vector Data Model: A New Model of HDF-EOS to Support GIS Applications in EOS

NASA Astrophysics Data System (ADS)

Chi, E.; Edmonds, R d

2001-05-01

NASA's Earth Science Data Information System (ESDIS) project has an active program of research and development of systems for the storage and management of Earth science data for Earth Observation System (EOS) mission, a key program of NASA Earth Science Enterprise. EOS has adopted an extension of the Hierarchical Data Format (HDF) as the format of choice for standard product distribution. Three new EOS specific datatypes - point, swath and grid - have been defined within the HDF framework. The enhanced data format is named HDF-EOS. Geographic Information Systems (GIS) are used by Earth scientists in EOS data product generation, visualization, and analysis. There are two major data types in GIS applications, raster and vector. The current HDF-EOS handles only raster type in the swath data model. The vector data model is identified and developed as a new HDFEOS format to meet the requirements of scientists working with EOS data products in vector format. The vector model is designed using a topological data structure, which defines the spatial relationships among points, lines, and polygons. The three major topological concepts that the vector model adopts are: a) lines connect to each other at nodes (connectivity), b) lines that connect to surround an area define a polygon (area definition), and c) lines have direction and left and right sides (contiguity). The vector model is implemented in HDF by mapping the conceptual model to HDF internal data models and structures, viz. Vdata, Vgroup, and their associated attribute structures. The point, line, and polygon geometry and attribute data are stored in similar tables. Further, the vector model utilizes the structure and product metadata, which characterize the HDF-EOS. Both types of metadata are stored as attributes in HDF-EOS files, and are encoded in text format by using Object Description Language (ODL) and stored as global attributes in HDF-EOS files. EOS has developed a series of routines for storing, retrieving, and manipulating vector data in category of access, definition, basic I/O, inquiry, and subsetting. The routines are tested and form a package, HDF-EOS/Vector. The alpha version of HDFEOS/Vector has been distributed through the HDF-EOS project web site at http://hdfeos.gsfc.nasa.gov. We are also developing translators between HDF-EOS vector format and variety of GIS formats, such as Shapefile. The HDF-EOS vector model enables EOS scientists to deliver EOS data in a way ready for Earth scientists to analyze using GIS software, and also provides EOS project a mechanism to store GIS data product in meaningful vector format with significant economy in storage.

An integrated QSAR-PBK/D modelling approach for predicting detoxification and DNA adduct formation of 18 acyclic food-borne α,β-unsaturated aldehydes.

PubMed

Kiwamoto, R; Spenkelink, A; Rietjens, I M C M; Punt, A

2015-01-01

Acyclic α,β-unsaturated aldehydes present in food raise a concern because the α,β-unsaturated aldehyde moiety is considered a structural alert for genotoxicity. However, controversy remains on whether in vivo at realistic dietary exposure DNA adduct formation is significant. The aim of the present study was to develop physiologically based kinetic/dynamic (PBK/D) models to examine dose-dependent detoxification and DNA adduct formation of a group of 18 food-borne acyclic α,β-unsaturated aldehydes without 2- or 3-alkylation, and with no more than one conjugated double bond. Parameters for the PBK/D models were obtained using quantitative structure-activity relationships (QSARs) defined with a training set of six selected aldehydes. Using the QSARs, PBK/D models for the other 12 aldehydes were defined. Results revealed that DNA adduct formation in the liver increases with decreasing bulkiness of the molecule especially due to less efficient detoxification. 2-Propenal (acrolein) was identified to induce the highest DNA adduct levels. At realistic dietary intake, the predicted DNA adduct levels for all aldehydes were two orders of magnitude lower than endogenous background levels observed in disease free human liver, suggesting that for all 18 aldehydes DNA adduct formation is negligible at the relevant levels of dietary intake. The present study provides a proof of principle for the use of QSAR-based PBK/D modelling to facilitate group evaluations and read-across in risk assessment. Copyright © 2014 Elsevier Inc. All rights reserved.

Methylene blue prevents surgery-induced peritoneal adhesions but impairs the early phase of anastomotic wound healing

PubMed Central

Dinc, Soykan; Ozaslan, Cihangir; Kuru, Bekir; Karaca, Sefa; Ustun, Huseyin; Alagol, Haluk; Renda, Nurten; Oz, Murat

2006-01-01

Objectives Adhesion formation continues to be an important problem in gastrointestinal surgery. In recent years, methylene blue (MB) has been reported to be an effective agent for preventing peritoneal adhesions. However, its effects on the wound healing process are unknown. In the present study, we investigated the effects of MB on the early and late phases of anastomotic wound healing and on adhesion formation. Methods We randomly categorized 92 rats into 2 groups in bursting pressure measurements and 50 rats into 3 groups in the adhesion model. We divided the animals into saline-treated (n = 46) or MB-treated (n = 46) groups. Bursting pressures of the anastomoses were measured on postoperative days 3 and 7. In biochemical studies, tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity were measured on postoperative days 3 and 7. In the adhesion model, we randomly categorized rats into sham (n = 10), saline-treated (n = 20) and MB-treated (n = 20) groups, and the formation of intraperitoneal adhesions was scored on postoperative day 14. We compared the measurement of bursting pressure and biochemical measurements of tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity. Histopathological findings of specimens were presented. Results During the early phase of wound healing (postoperative day 3), bursting pressures, tissue hydroxyproline, total nitrite/nitrate levels and nitric oxide synthase activity in the MB-treated group were significantly lower than those of the saline-treated group. On postoperative day 7, there was no significant difference in these parameters between MB and saline-treated groups. In the adhesion model, MB caused a significant reduction in the formation of peritoneal adhesions. Conclusion MB prevents peritoneal adhesions but causes a significant impairment of anastomotic bursting pressure during the early phase of the wound healing process by its transient inhibitory effect on the nitric oxide pathway. PMID:17152569

Using SDO/AIA to Understand the Thermal Evolution of Solar Prominence Formation

NASA Astrophysics Data System (ADS)

Viall, Nicholeen; M.; Kucera, Therese T.; Karpen, Judith

2016-10-01

In this study, we investigate prominence formation using time series analysis of Solar Dynamics Observatory's Atmospheric Imaging Assembly (SDO/AIA) data. We investigate the thermal properties of forming prominences by analyzing observed light curves using the same technique that we have already successfully applied to active regions to diagnose heating and cooling cycles. This technique tracks the thermal evolution using emission formed at different temperatures, made possible by AIA's different wavebands and high time resolution. We also compute the predicted light curves in the same SDO/AIA channels of a hydrodynamic model of thermal nonequilibrium formation of prominence material, an evaporation-condensation model. In these models of prominence formation, heating at the foot-points of sheared coronal flux-tubes results in evaporation of material of a few MK into the corona followed by catastrophic cooling of the hot material to form cool ( 10,000 K) prominence material. We demonstrate that the SDO/AIA light curves for flux tubes undergoing thermal nonequilibrium vary at different locations along the flux tube, especially in the region where the condensate forms, and we compare the predicted light curves with those observed. Supported by NASA's Living with a Star program.

Hierarchical Modeling of Activation Mechanisms in the ABL and EGFR Kinase Domains: Thermodynamic and Mechanistic Catalysts of Kinase Activation by Cancer Mutations

PubMed Central

Dixit, Anshuman; Verkhivker, Gennady M.

2009-01-01

Structural and functional studies of the ABL and EGFR kinase domains have recently suggested a common mechanism of activation by cancer-causing mutations. However, dynamics and mechanistic aspects of kinase activation by cancer mutations that stimulate conformational transitions and thermodynamic stabilization of the constitutively active kinase form remain elusive. We present a large-scale computational investigation of activation mechanisms in the ABL and EGFR kinase domains by a panel of clinically important cancer mutants ABL-T315I, ABL-L387M, EGFR-T790M, and EGFR-L858R. We have also simulated the activating effect of the gatekeeper mutation on conformational dynamics and allosteric interactions in functional states of the ABL-SH2-SH3 regulatory complexes. A comprehensive analysis was conducted using a hierarchy of computational approaches that included homology modeling, molecular dynamics simulations, protein stability analysis, targeted molecular dynamics, and molecular docking. Collectively, the results of this study have revealed thermodynamic and mechanistic catalysts of kinase activation by major cancer-causing mutations in the ABL and EGFR kinase domains. By using multiple crystallographic states of ABL and EGFR, computer simulations have allowed one to map dynamics of conformational fluctuations and transitions in the normal (wild-type) and oncogenic kinase forms. A proposed multi-stage mechanistic model of activation involves a series of cooperative transitions between different conformational states, including assembly of the hydrophobic spine, the formation of the Src-like intermediate structure, and a cooperative breakage and formation of characteristic salt bridges, which signify transition to the active kinase form. We suggest that molecular mechanisms of activation by cancer mutations could mimic the activation process of the normal kinase, yet exploiting conserved structural catalysts to accelerate a conformational transition and the enhanced stabilization of the active kinase form. The results of this study reconcile current experimental data with insights from theoretical approaches, pointing to general mechanistic aspects of activating transitions in protein kinases. PMID:19714203

Investigation of flavonoid influence on peroxidation processes intensity in the blood

NASA Astrophysics Data System (ADS)

Navolokin, N. A.; Mudrak, D. A.; Plastun, I. L.; Bucharskaya, A. B.; Agandeeva, K. E.; Ivlichev, A. V.; Tychina, S. A.; Afanasyeva, G. A.; Polukonova, N. V.; Maslyakova, G. N.

2017-03-01

Influence of flavonoids on the intensity of peroxidation processes in the blood is investigated by numerical modeling and by experiment in vivo. As an example we consider the effects of flavonoid-containing extract of Helichrysum arenarium L. with antitumor activity on serum of rats with transplanted liver cancer PC-1. It was found that the content of malondialdehyde, lipid hydroperoxides and average mass molecules were decreased in animals with transplanted liver cancer after intramuscular and oral administration of Helichrysum arenarium L extract in a dose of 1000 mg/mL. The extract reduces the intensity of lipid peroxidation processes in animals. The compound formation possibility of flavonoids and products of lipid peroxidation is investigated by numerical simulations. Using the density functional theory method of molecular modeling, we analyze hydrogen bonds formation and their influence on IR - spectra and structure of molecular complex which is formed due to interaction between flavonoids and products of lipid peroxidation processes on example of naringine and malondialdehyde. We have found that naringine can form a steady molecular complex with malondialdehyde by hydrogen bonds formation. Thus, the application of Helichrysum arenarium L. extract for suppression processes of lipid peroxidation and activation of enzymatic and non-enzymatic antioxidant systems is promising.

Spontaneous membrane formation and self-encapsulation of active rods in an inhomogeneous motility field

NASA Astrophysics Data System (ADS)

Grauer, Jens; Löwen, Hartmut; Janssen, Liesbeth M. C.

2018-02-01

We study the collective dynamics of self-propelled rods in an inhomogeneous motility field. At the interface between two regions of constant but different motility, a smectic rod layer is spontaneously created through aligning interactions between the active rods, reminiscent of an artificial, semipermeable membrane. This "active membrane" engulfes rods which are locally trapped in low-motility regions and thereby further enhances the trapping efficiency by self-organization, an effect which we call "self-encapsulation." Our results are gained by computer simulations of self-propelled rod models confined on a two-dimensional planar or spherical surface with a stepwise constant motility field, but the phenomenon should be observable in any geometry with sufficiently large spatial inhomogeneity. We also discuss possibilities to verify our predictions of active-membrane formation in experiments of self-propelled colloidal rods and vibrated granular matter.

Nonrandom γ-TuNA-dependent spatial pattern of microtubule nucleation at the Golgi.

PubMed

Sanders, Anna A W M; Chang, Kevin; Zhu, Xiaodong; Thoppil, Roslin J; Holmes, William R; Kaverina, Irina

2017-11-07

Noncentrosomal microtubule (MT) nucleation at the Golgi generates MT network asymmetry in motile vertebrate cells. Investigating the Golgi-derived MT (GDMT) distribution, we find that MT asymmetry arises from nonrandom nucleation sites at the Golgi (hotspots). Using computational simulations, we propose two plausible mechanistic models of GDMT nucleation leading to this phenotype. In the "cooperativity" model, formation of a single GDMT promotes further nucleation at the same site. In the "heterogeneous Golgi" model, MT nucleation is dramatically up-regulated at discrete and sparse locations within the Golgi. While MT clustering in hotspots is equally well described by both models, simulating MT length distributions within the cooperativity model fits the data better. Investigating the molecular mechanism underlying hotspot formation, we have found that hotspots are significantly smaller than a Golgi subdomain positive for scaffolding protein AKAP450, which is thought to recruit GDMT nucleation factors. We have further probed potential roles of known GDMT-promoting molecules, including γ-TuRC-mediated nucleation activator (γ-TuNA) domain-containing proteins and MT stabilizer CLASPs. While both γ-TuNA inhibition and lack of CLASPs resulted in drastically decreased GDMT nucleation, computational modeling revealed that only γ-TuNA inhibition suppressed hotspot formation. We conclude that hotspots require γ-TuNA activity, which facilitates clustered GDMT nucleation at distinct Golgi sites. © 2017 Sanders et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Quenching of the star formation activity in cluster galaxies

NASA Astrophysics Data System (ADS)

Boselli, A.; Roehlly, Y.; Fossati, M.; Buat, V.; Boissier, S.; Boquien, M.; Burgarella, D.; Ciesla, L.; Gavazzi, G.; Serra, P.

2016-11-01

We study the star formation quenching mechanism in cluster galaxies by fitting the spectral energy distribution (SED) of the Herschel Reference Survey, a complete volume-limited K-band-selected sample of nearby galaxies including objects in different density regions, from the core of the Virgo cluster to the general field. The SEDs of the target galaxies were fitted using the CIGALE SED modelling code. The truncated activity of cluster galaxies was parametrised using a specific star formation history with two free parameters, the quenching age QA and the quenching factor QF. These two parameters are crucial for the identification of the quenching mechanism, which acts on long timescales when starvation processes are at work, but is rapid and efficient when ram pressure occurs. To be sensitive to an abrupt and recent variation of the star formation activity, we combined twenty photometric bands in the UV to far-infrared in a new way with three age-sensitive Balmer line absorption indices extracted from available medium-resolution (R 1000) integrated spectroscopy and with Hα narrow-band imaging data. The use of a truncated star formation history significantly increases the quality of the fit in HI-deficient galaxies of the sample, that is to say, in those objects whose atomic gas content has been removed during the interaction with the hostile cluster environment. The typical quenching age of the perturbed late-type galaxies is QA ≲ 300 Myr whenever the activity of star formation is reduced by 50% < QF ≤ 80% and QA ≲ 500 Myr for QF > 80%, while that of the quiescent early-type objects is QA ≃ 1-3 Gyr. The fraction of late-type galaxies with a star formation activity reduced by QF > 80% and with an HI-deficiency parameter HI-def > 0.4 drops by a factor of 5 from the inner half virial radius of the Virgo cluster (R/Rvir < 0.5), where the hot diffuse X-ray emitting gas of the cluster is located, to the outer regions (R/Rvir > 4). The efficient quenching of the star formation activity observed in Virgo suggests that the dominant stripping process is ram pressure. We discuss the implication of this result in the cosmological context of galaxy evolution.

Habitat Suitability Index Models: Eastern meadowlark

USGS Publications Warehouse

Schroeder, Richard L.; Sousa, Patrick J.

1982-01-01

Habitat preferences of the eastern meadowlark (Sturnella magna) are described in this publication, which is one of a series of Habitat Suitability Index (HSI) models. Habitat use information is presented in a synthesis of the literature on the species-habitat requirements of the eastern meadowlark, followed by the development of the HSI model. The model is presented in three formats: graphic, word, and mathematical, and is designed to provide information for use in impact assessment and habitat management activities.

Habitat Suitability Index Models: Pine warbler

USGS Publications Warehouse

Schroeder, Richard L.

1982-01-01

Habitat preferences of the pine warbler (Dendroica pinus) are described in this publication, which is one of a series of Habitat Suitability Index (HSI) models. Habitat use information is presented in a synthesis of the literature on the species-habitat requirements of the pine warbler, followed by the development of the HSI model. The model is presented in three formats: graphic, word, and mathematical, and is designed to provide information for use in impact assessment and habitat management activities.

On the mechanism of pattern formation in glow dielectric barrier discharge

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

Qiao, Yajun; Li, Ben; Ouyang, Jiting, E-mail: jtouyang@bit.edu.cn

2016-01-15

The formation mechanism of pattern in glow dielectric barrier discharge is investigated by two-dimensional fluid modeling. Experimental results are shown for comparison. The simulation results show that the non-uniform distribution of space charges makes the discharge be enhanced in the high-density region but weakened in its neighborhood, which is considered as an activation-inhibition effect. This effect shows through during a current pulse (one discharge event) but also in a certain period of time after discharge that determines a driving frequency range for the non-uniformity of space charges to be enhanced. The effects of applied voltage, surface charge, electrode boundary, andmore » external field are also discussed. All these factors affect the formation of dielectric-barrier-discharge pattern by changing the distribution or the dynamics of space charges and hence the activation-inhibition effect of non-uniform space charges.« less

A central role for S-nitrosothiols in plant disease resistance

PubMed Central

Feechan, Angela; Kwon, Eunjung; Yun, Byung-Wook; Wang, Yiqin; Pallas, Jacqueline A.; Loake, Gary J.

2005-01-01

Animal S-nitrosoglutathione reductase (GSNOR) governs the extent of cellular S-nitrosylation, a key redox-based posttranslational modification. Mutations in AtGSNOR1, an Arabidopsis thaliana GSNOR, modulate the extent of cellular S-nitrosothiol (SNO) formation in this model plant species. Loss of AtGSNOR1 function increased SNO levels, disabling plant defense responses conferred by distinct resistance (R) gene subclasses. Furthermore, in the absence of AtGSNOR1, both basal and nonhost disease resistance are also compromised. Conversely, increased AtGSNOR1 activity reduced SNO formation, enhancing protection against ordinarily virulent microbial pathogens. Here we demonstrate that AtGSNOR1 positively regulates the signaling network controlled by the plant immune system activator, salicylic acid. This contrasts with the function of this enzyme in mice during endotoxic shock, where GSNOR antagonizes inflammatory responses. Our data imply SNO formation and turnover regulate multiple modes of plant disease resistance. PMID:15911759

The structure and formation of natural categories

NASA Technical Reports Server (NTRS)

Fisher, Douglas; Langley, Pat

1990-01-01

Categorization and concept formation are critical activities of intelligence. These processes and the conceptual structures that support them raise important issues at the interface of cognitive psychology and artificial intelligence. The work presumes that advances in these and other areas are best facilitated by research methodologies that reward interdisciplinary interaction. In particular, a computational model is described of concept formation and categorization that exploits a rational analysis of basic level effects by Gluck and Corter. Their work provides a clean prescription of human category preferences that is adapted to the task of concept learning. Also, their analysis was extended to account for typicality and fan effects, and speculate on how the concept formation strategies might be extended to other facets of intelligence, such as problem solving.

Refining Inquiry with Multi-Form Assessment: Formative and summative assessment functions for flexible inquiry

NASA Astrophysics Data System (ADS)

Zuiker, Steven; Reid Whitaker, J.

2014-04-01

This paper describes the 5E+I/A inquiry model and reports a case study of one curricular enactment by a US fifth-grade classroom. A literature review establishes the model's conceptual adequacy with respect to longstanding research related to both the 5E inquiry model and multiple, incremental innovations of it. As a collective line of research, the review highlights a common emphasis on formative assessment, at times coupled either with differentiated instruction strategies or with activities that target the generalization of learning. The 5E+I/A model contributes a multi-level assessment strategy that balances formative and summative functions of multiple forms of assessment in order to support classroom participation while still attending to individual achievement. The case report documents the enactment of a weeklong 5E+I/A curricular design as a preliminary account of the model's empirical adequacy. A descriptive and analytical narrative illustrates variable ways that multi-level assessment makes student thinking visible and pedagogical decision-making more powerful. In light of both, it also documents productive adaptations to a flexible curricular design and considers future research to advance this collective line of inquiry.

SEMI-ANALYTIC GALAXY EVOLUTION (SAGE): MODEL CALIBRATION AND BASIC RESULTS

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

Croton, Darren J.; Stevens, Adam R. H.; Tonini, Chiara

2016-02-15

This paper describes a new publicly available codebase for modeling galaxy formation in a cosmological context, the “Semi-Analytic Galaxy Evolution” model, or sage for short.{sup 5} sage is a significant update to the 2006 model of Croton et al. and has been rebuilt to be modular and customizable. The model will run on any N-body simulation whose trees are organized in a supported format and contain a minimum set of basic halo properties. In this work, we present the baryonic prescriptions implemented in sage to describe the formation and evolution of galaxies, and their calibration for three N-body simulations: Millennium,more » Bolshoi, and GiggleZ. Updated physics include the following: gas accretion, ejection due to feedback, and reincorporation via the galactic fountain; a new gas cooling–radio mode active galactic nucleus (AGN) heating cycle; AGN feedback in the quasar mode; a new treatment of gas in satellite galaxies; and galaxy mergers, disruption, and the build-up of intra-cluster stars. Throughout, we show the results of a common default parameterization on each simulation, with a focus on the local galaxy population.« less

Simulating the Effects of Semivolatile Compounds on Cloud Processing of Aerosol

NASA Astrophysics Data System (ADS)

Kokkola, H.; Kudzotsa, I.; Tonttila, J.; Raatikainen, T.; Romakkaniemi, S.

2017-12-01

Aerosol removal processes largely dictate how well aerosol is transported in the atmosphere and thus the aerosol load over remote regions depends on how effectively aerosol is removed during its transport from the source regions. This means that in order to model the global distribution aerosol, both in vertical and horizontal, wet deposition processes have to be properly modelled. However, in large scale models, the description of wet removal and the vertical redistribution of aerosol by cloud processes is often extremely simplified.Here we present a novel aerosol-cloud model SALSA, where the aerosol properties are tracked through different cloud processes. These processes include: cloud droplet activation, precipitation formation, ice nucleation, melting, and evaporation. It is a sectional model that includes separate size sections for non-activated aerosol, cloud droplets, precipitation droplets, and ice crystals. The aerosol-cloud model was coupled to a large eddy model UCLALES which simulates the boundary-layer dynamics. In this study, the model has been applied in studying the wet removal as well as interactions between aerosol, clouds, and semi-volatile compounds, ammonia and nitric acid. These semi-volative compounds are special in the sense that they co-condense together with water during cloud activation and have been suggested to form droplets that can be considered cloud-droplet-like already in subsaturated conditions. In our model, we calculate the kinetic partitioning of ammonia and sulfate thus explicitly taking into account the effect of ammonia and nitric acid in the cloud formation. Our simulations indicate that especially in polluted conditions, these compounds significantly affect the properties of cloud droplets thus significantly affecting the lifecycle of different aerosol compounds.

Mechanochemical pattern formation in simple models of active viscoelastic fluids and solids

NASA Astrophysics Data System (ADS)

Alonso, Sergio; Radszuweit, Markus; Engel, Harald; Bär, Markus

2017-11-01

The cytoskeleton of the organism Physarum polycephalum is a prominent example of a complex active viscoelastic material wherein stresses induce flows along the organism as a result of the action of molecular motors and their regulation by calcium ions. Experiments in Physarum polycephalum have revealed a rich variety of mechanochemical patterns including standing, traveling and rotating waves that arise from instabilities of spatially homogeneous states without gradients in stresses and resulting flows. Herein, we investigate simple models where an active stress induced by molecular motors is coupled to a model describing the passive viscoelastic properties of the cellular material. Specifically, two models for viscoelastic fluids (Maxwell and Jeffrey model) and two models for viscoelastic solids (Kelvin-Voigt and Standard model) are investigated. Our focus is on the analysis of the conditions that cause destabilization of spatially homogeneous states and the related onset of mechano-chemical waves and patterns. We carry out linear stability analyses and numerical simulations in one spatial dimension for different models. In general, sufficiently strong activity leads to waves and patterns. The primary instability is stationary for all active fluids considered, whereas all active solids have an oscillatory primary instability. All instabilities found are of long-wavelength nature reflecting the conservation of the total calcium concentration in the models studied.

Raindrops of synaptic noise on dual excitability landscape: an approach to astrocyte network modelling

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Yu.; Postnov, Dmitry E.; Verveyko, Darya V.; Brazhe, Alexey R.

2018-04-01

The most abundant non-neuronal cells in the brain, astrocytes, populate all parts of the central nervous system (CNS). Astrocytic calcium activity ranging from subcellular sparkles to intercellular waves is believed to be the key to a plethora of regulatory pathways in the central nervous system from synaptic plasticity to blood flow regulation. Modeling of the calcium wave initiation and transmission and their spatiotemporal dynamics is therefore an important step stone in understanding the crucial cogs of cognition. Astrocytes are active sensors of ongoing neuronal and synaptic activity, and neurotransmitters diffusing from the synaptic cleft make a strong impact on the astrocytic activity. Here we propose a model describing the patterns of calcium wave formation at a single cell level and discuss the interplay between astrocyte shape the calcium waves dynamics driven by local stochastic surges of glutamate simulating synaptic activity.

A study of aluminum-lithium alloy solidification using acoustic emission techniques. Ph.D. Thesis, 1991

NASA Technical Reports Server (NTRS)

Henkel, Daniel P.

1992-01-01

Physical phenomena associated with the solidification of an aluminum lithium alloy was characterized using acoustic emission (AE) techniques. It is shown that repeatable patterns of AE activity may be correlated to microstructural changes that occur during solidification. The influence of the experimental system on generated signals was examined in the time and frequency domains. The analysis was used to show how an AE signal from solidifying aluminum is changed by each component in the detection system to produce a complex waveform. Conventional AE analysis has shown that a period of high AE activity occurs in pure aluminum, an Al-Cu alloy, and the Al-Li alloy, as the last fraction of solid forms. A model attributes this to the internal stresses of grain boundary formation. An additional period of activity occurs as the last fraction of solid forms, but only in the two alloys. A model attributes this to the formation of interdendritic porosity which was not present in the pure aluminum. The AE waveforms were dominated by resonant effects of the waveguide and the transducer.

Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase in Angiogenesis: Isoform-Specific Effects

PubMed Central

Wang, Haibo; Hartnett, M. Elizabeth

2017-01-01

Angiogenesis is the formation of new blood vessels from preexisting ones and is implicated in physiologic vascular development, pathologic blood vessel growth, and vascular restoration. This is in contrast to vasculogenesis, which is de novo growth of vessels from vascular precursors, or from vascular repair that occurs when circulating endothelial progenitor cells home into an area and develop into blood vessels. The objective of this review is to discuss the isoform-specific role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in physiologic and pathologic angiogenesis and vascular repair, but will not specifically address vasculogenesis. As the major source of reactive oxygen species (ROS) in vascular endothelial cells (ECs), NOX has gained increasing attention in angiogenesis. Activation of NOX leads to events necessary for physiologic and pathologic angiogenesis, including EC migration, proliferation and tube formation. However, activation of different NOX isoforms has different effects in angiogenesis. Activation of NOX2 promotes pathologic angiogenesis and vascular inflammation, but may be beneficial in revascularization in the hindlimb ischemic model. In contrast, activation of NOX4 appears to promote physiologic angiogenesis mainly by protecting the vasculature during ischemia, hypoxia and inflammation and by restoring vascularization, except in models of oxygen-induced retinopathy and diabetes where NOX4 activation leads to pathologic angiogenesis. PMID:28587189

Phytochemicals prevent mitochondrial membrane permeabilization and protect SH-SY5Y cells against apoptosis induced by PK11195, a ligand for outer membrane translocator protein.

PubMed

Wu, Yuqiu; Shamoto-Nagai, Masayo; Maruyama, Wakako; Osawa, Toshihiko; Naoi, Makoto

2017-01-01

Epidemiological studies present the beneficial effects of dietary habits on prevention of aging-associated decline of brain function. Phytochemicals, the second metabolites of food, protect neuronal cells from cell death in cellular models of neurodegenerative disorders, and the neuroprotective activity has been ascribed to the anti-oxidant and anti-inflammatory functions. In this paper, the cellular mechanism of neuroprotection by phytochemicals was investigated, using the cellular model of mitochondrial apoptosis induced by PK11195, a ligand of outer membrane translocator protein, in SH-SY5Y cells. PK11195 induced mitochondrial membrane permeabilization with rapid transit production of superoxide (superoxide flashes) and calcium release from mitochondria, and activated apoptosis signal pathway. Study on the structure-activity relationship of astaxanthin, ferulic acid derivatives, and sesame lignans revealed that these phytochemicals inhibited mitochondrial membrane permeabilization and protected cells from apoptosis. Ferulic acid derivatives and sesame lignans inhibited or enhanced the mitochondrial pore formation and cell death by PK11195 according to their amphiphilic properties, not directly depending on the antioxidant activity. Regulation of pore formation at mitochondrial membrane is discussed as a novel mechanism behind neuroprotective activity of phytochemicals in aging and age-associated neurodegenerative disorders, and also behind dual functions of phytochemicals in neuronal and cancer cells.

Thermal And Dynamical Histories Of Saturn's Satellites: Evidence For The Presence Of Short Lived Radioactive Isotopes

NASA Astrophysics Data System (ADS)

Johnson, Torrence V.; Castillo-Rogez, Julie C.; Matson, Dennis L.

2008-04-01

Recent observations of Saturn's satellite system from the Cassini/Huygens mission present serious challenges to understanding the current dynamical states and thermal histories of these icy bodies using conventional thermal models that use long lived radioactive isotopes (LLRI) as the primary heat sources. In particular, the most distant of the regular satellites, Iapetus, is in synchronous rotation about Saturn, implying relatively high levels of dissipation of tidal energy. However, it retains a highly non-equilibrium, oblate spheroid, shape, implying a thick, cold, mechanically rigid outer layer or lithosphere. Thermal history models of Iapetus that successfully explain these apparently contradictory characteristics require significant heating early in the satellite's history from short lived radioactive isotopes (SRLI), particularly Al, implying a formation time for Iapetus of between 2.5 and 5 Myr after the formation of Calcium26 Aluminum Inclusions (CAIs) [l]. The characteristics of the other icy satellites in the system are consistent with this formation time, and the current thermal geyser activity on the more silicate-rich satellite Enceladus may be related to such an early heating event. A consequence of these early formation time models is that the early crust of Iapetus is too thin and weak to retain large impact basin topography until about 100 Myr after formation, and despinning to synchronous rotation might have occurred from 200-900 Myr after formation. This chronology is consistent with the formation of the large impact basins observed on Iapetus' surface by the `late heavy bombardment' or `lunar cataclysm' event recorded in the dating of samples from the Moon at 3900 Ma.

Antibody neutralization of cell-surface gC1qR/HABP1/SF2-p32 prevents lamellipodia formation and tumorigenesis

PubMed Central

Kim, Beom-Chan; Hwang, Hyun-Jung; An, Hyoung-Tae; Lee, Hyun; Park, Jun-Sub; Hong, Jin; Ko, Jesang; Kim, Chungho; Lee, Jae-Seon; Ko, Young-Gyu

2016-01-01

We previously demonstrated that cell-surface gC1qR is a key regulator of lamellipodia formation and cancer metastasis. Here, we screened a monoclonal mouse antibody against gC1qR to prevent cell migration by neutralizing cell-surface gC1qR. The anti-gC1qR antibody prevented growth factor-stimulated lamellipodia formation, cell migration and focal adhesion kinase activation by inactivating receptor tyrosine kinases (RTKs) in various cancer cells such as A549, MDA-MB-231, MCF7 and HeLa cells. The antibody neutralization of cell-surface gC1qR also inhibited angiogenesis because the anti-gC1qR antibody prevented growth factor-stimulated RTK activation, lamellipodia formation, cell migration and tube formation in HUVEC. In addition, we found that A549 tumorigenesis was reduced in a xenograft mouse model by following the administration of the anti-gC1qR antibody. With these data, we can conclude that the antibody neutralization of cell-surface gC1qR could be a good therapeutic strategy for cancer treatment. PMID:27363031

Supermassive Black Holes as the Regulators of Star Formation in Central Galaxies

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

Terrazas, Bryan A.; Bell, Eric F.; Woo, Joanna

We present the relationship between the black hole mass, stellar mass, and star formation rate (SFR) of a diverse group of 91 galaxies with dynamically measured black hole masses. For our sample of galaxies with a variety of morphologies and other galactic properties, we find that the specific SFR is a smoothly decreasing function of the ratio between black hole mass and stellar mass, or what we call the specific black hole mass. In order to explain this relation, we propose a physical framework where the gradual suppression of a galaxy’s star formation activity results from the adjustment to anmore » increase in specific black hole mass, and accordingly, an increase in the amount of heating. From this framework, it follows that at least some galaxies with intermediate specific black hole masses are in a steady state of partial quiescence with intermediate specific SFRs, implying that both transitioning and steady-state galaxies live within this region that is known as the “green valley.” With respect to galaxy formation models, our results present an important diagnostic with which to test various prescriptions of black hole feedback and its effects on star formation activity.« less

Inhibitory activities of some vitamins on the formation of cholesterol oxidation products in beef patties.

PubMed

Wong, Daniel; Wang, Mingfu

2013-09-04

The capacities of 15 vitamins to inhibit the formation of 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 7-ketocholesterol were examined in beef patties. Their inhibitory activities were tested at a concentration of 0.4 mmol in 30 g of beef. Among them, L-ascorbic acid, retinoic acid, and α-(±)-tocopherol were found to exert a potent inhibitory effect (30-50%) on 7-ketocholesterol formation and (~20%) on 7α-hydroxycholesterol and 7β-hydroxycholesterol formations. Pyridoxamine inhibited 7-ketocholesterol formation by 60% with a statistically significant difference (p < 0.05) from that achieved in the control setup. To further elucidate the possible inhibitory mechanism of pyridoxamine against cholesterol oxidation, a chemical model with pyridoxamine added in the cholesterol oxidation system (heated at 140 °C for 240 min in dimethyl sulfoxide) was employed. It was demonstrated that pyridoxamine could directly react with 7-ketocholesterol via the addition reaction. The reaction involved a nucleophilic attack of the free amine group of pyridoxamine on 7-ketocholesterol (an α,β-unsaturated carbonyl compound). This type of reaction was also found to occur in beef patties by chromatographic and spectral analyses.

Willingness to pay for improved respiratory and cardiovascular health: a multiple-format, stated-preference approach.

PubMed

Johnson, F R; Banzhaf, M R; Desvousges, W H

2000-06-01

This study uses stated-preference (SP) analysis to measure willingness to pay (WTP) to reduce acute episodes of respiratory and cardiovascular ill health. The SP survey employs a modified version of the health state descriptions used in the Quality of Well Being (QWB) Index. The four health state attributes are symptom, episode duration, activity restrictions and cost. Preferences are elicited using two different SP formats: graded-pair and discrete-choice. The different formats cause subjects to focus on different evaluation strategies. Combining two elicitation formats yields more valid and robust estimates than using only one approach. Estimates of indirect utility function parameters are obtained using advanced panel econometrics for each format separately and jointly. Socio-economic differences in health preferences are modelled by allowing the marginal utility of money relative to health attributes to vary across respondents. Because the joint model captures the combined preference information provided by both elicitation formats, these model estimates are used to calculate WTP. The results demonstrate the feasibility of estimating meaningful WTP values for policy-relevant respiratory and cardiac symptoms, even from subjects who never have personally experienced these conditions. Furthermore, because WTP estimates are for individual components of health improvements, estimates can be aggregated in various ways depending upon policy needs. Thus, using generic health attributes facilitates transferring WTP estimates for benefit-cost analysis of a variety of potential health interventions. Copyright 2000 John Wiley & Sons, Ltd.

Treatment of collagenase-induced osteoarthritis with a viral vector encoding TSG-6 results in ectopic bone formation.

PubMed

Broeren, Mathijs G A; Di Ceglie, Irene; Bennink, Miranda B; van Lent, Peter L E M; van den Berg, Wim B; Koenders, Marije I; Blaney Davidson, Esmeralda N; van der Kraan, Peter M; van de Loo, Fons A J

2018-01-01

Tumor necrosis factor-inducible gene 6 (TSG-6) has anti-inflammatory and chondroprotective effects in mouse models of inflammatory arthritis. Because cartilage damage and inflammation are also observed in osteoarthritis (OA), we determined the effect of viral overexpression of TSG-6 in experimental osteoarthritis. Bone marrow-derived cells were differentiated to multinucleated osteoclasts in the presence of recombinant TSG-6 or after transduction with a lentiviral TSG-6 expression vector. Multi-nucleated osteoclasts were analyzed after tartrate resistant acid phosphatase staining and resorption activity was determined on dentin slices. Collagenase-induced osteoarthritis (CIOA) was induced in C57BL/6 mice after intra-articular injection of an adenoviral TSG-6 or control luciferase expression vector. Inflammation-related protease activity was measured using bioluminescent Prosense probes. After a second adenovirus injection, cartilage damage was assessed in histological sections stained with Safranin-O. Ectopic bone formation was scored in X-ray images of the affected knees. TSG-6 did not inhibit the formation of multi-nucleated osteoclasts, but caused a significant reduction in the resorption activity on dentin slices. Adenoviral TSG-6 gene therapy in CIOA could not reduce the cartilage damage compared to the luciferase control virus and no significant difference in inflammation-related protease activity was noted between the TSG-6 and control treated group. Instead, X-ray analysis and histological analysis revealed the presence of ectopic bone formation in the TSG-6 treated group. Gene therapy based on the expression of TSG-6 could not provide cartilage protection in experimental osteoarthritis, but instead resulted in increased ectopic bone formation.

Mycobacterium tuberculosis-Induced Polarization of Human Macrophage Orchestrates the Formation and Development of Tuberculous Granulomas In Vitro

PubMed Central

Guo, Yang; Chen, Jie; Xiong, Guoliang; Peng, Yiping; Ye, Jianqing; Li, Junming

2015-01-01

The tuberculous granuloma is an elaborately organized structure and one of the main histological hallmarks of tuberculosis. Macrophages, which are important immunologic effector and antigen-presenting cells, are the main cell type found in the tuberculous granuloma and have high plasticity. Macrophage polarization during bacterial infection has been elucidated in numerous recent studies; however, macrophage polarization during tuberculous granuloma formation and development has rarely been reported. It remains to be clarified whether differences in the activation status of macrophages affect granuloma formation. In this study, the variation in macrophage polarization during the formation and development of tuberculous granulomas was investigated in both sections of lung tissues from tuberculosis patients and an in vitro tuberculous granuloma model. The roles of macrophage polarization in this process were also investigated. Mycobacterium tuberculosis (M. tuberculosis) infection was found to induce monocyte-derived macrophage polarization. In the in vitro tuberculous granuloma model, macrophage transformation from M1 to M2 was observed over time following M. tuberculosis infection. M2 macrophages were found to predominate in both necrotic and non-necrotic granulomas from tuberculosis patients, while both M1 and M2 polarized macrophages were found in the non-granulomatous lung tissues. Furthermore, it was found that M1 macrophages promote granuloma formation and macrophage bactericidal activity in vitro, while M2 macrophages inhibit these effects. The findings of this study provide insights into the mechanism by which M. tuberculosis circumvents the host immune system as well as a theoretical foundation for the development of novel tuberculosis therapies based on reprogramming macrophage polarization. PMID:26091535

Mycobacterium tuberculosis-Induced Polarization of Human Macrophage Orchestrates the Formation and Development of Tuberculous Granulomas In Vitro.

PubMed

Huang, Zikun; Luo, Qing; Guo, Yang; Chen, Jie; Xiong, Guoliang; Peng, Yiping; Ye, Jianqing; Li, Junming

2015-01-01

The tuberculous granuloma is an elaborately organized structure and one of the main histological hallmarks of tuberculosis. Macrophages, which are important immunologic effector and antigen-presenting cells, are the main cell type found in the tuberculous granuloma and have high plasticity. Macrophage polarization during bacterial infection has been elucidated in numerous recent studies; however, macrophage polarization during tuberculous granuloma formation and development has rarely been reported. It remains to be clarified whether differences in the activation status of macrophages affect granuloma formation. In this study, the variation in macrophage polarization during the formation and development of tuberculous granulomas was investigated in both sections of lung tissues from tuberculosis patients and an in vitro tuberculous granuloma model. The roles of macrophage polarization in this process were also investigated. Mycobacterium tuberculosis (M. tuberculosis) infection was found to induce monocyte-derived macrophage polarization. In the in vitro tuberculous granuloma model, macrophage transformation from M1 to M2 was observed over time following M. tuberculosis infection. M2 macrophages were found to predominate in both necrotic and non-necrotic granulomas from tuberculosis patients, while both M1 and M2 polarized macrophages were found in the non-granulomatous lung tissues. Furthermore, it was found that M1 macrophages promote granuloma formation and macrophage bactericidal activity in vitro, while M2 macrophages inhibit these effects. The findings of this study provide insights into the mechanism by which M. tuberculosis circumvents the host immune system as well as a theoretical foundation for the development of novel tuberculosis therapies based on reprogramming macrophage polarization.

A novel antiangiogenic peptide derived from hepatocyte growth factor inhibits neovascularization in vitro and in vivo

PubMed Central

Xu, Yi; Zhao, Hui; Zheng, Ying; Gu, Qing; Ma, Jianxing

2010-01-01

Purpose To study the antiangiogenic activity of two small peptides (H-RN and H-FT) derived from the hepatocyte growth factor kringle 1 domain (HGF K1) using in vitro and in vivo assays. Methods RF/6A rhesus macaque choroid-retina endothelial cells were used for in vitro studies. The inhibiting effect of two peptides on a vascular endothelial growth factor (VEGF)-stimulated cell proliferation, cell migration, and endothelial cell tube formation were investigated. For in vivo assays, the antiangiogenic activity of H-RN and H-FT in the chick chorioallantoic membrane model (CAM) and a mice oxygen-induced retinopathy model (OIR) were studied. A recombinant mouse VEGF-neutralizing antibody, bevacizumab, and a scrambled peptide were used as two control groups in separate studies. Results H-RN effectively inhibited VEGF-stimulated RF/6A cell proliferation, migration, and tube formation on Matrigel™, while H-FT did not. H-RN was also able to inhibit angiogenesis when applied to the CAM, and had antineovascularization activity in the retinal neovascularization of a mouse OIR model when administrated as an intravitreous injection. The antiangiogenic activity of H-RN was not as strong as that of VEGF antibodies. The H-FT and scrambled peptide had no such activity. Conclusions H-RN, a new peptide derived from the HGF K1 domain, was shown to have antiangiogenic activity in vitro and in vivo. It may lead to new potential drug discoveries and the development of new treatments for pathological retinal angiogenesis. PMID:21031024

STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX

PubMed Central

Willey, Christopher D.; Palanisamy, Arun P.; Johnston, Rebecca K.; Mani, Santhosh K.; Shiraishi, Hirokazu; Tuxworth, William J.; Zile, Michael R.; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani

2008-01-01

Growth, survival and cytoskeletal rearrangement of cardiomyocytes are critical for cardiac hypertrophy. Signal transducer and activator of transcription-3 (STAT3) activation is an important cardioprotective factor associated with cardiac hypertrophy. Although STAT3 activation has been reported via signaling through Janus Kinase 2 (JAK2) in several cardiac models of hypertrophy, the importance of other nonreceptor tyrosine kinases (NTKs) has not been explored. Utilizing an in vivo feline right ventricular pressure-overload (RVPO) model of hypertrophy, we demonstrate that in 48 h pressure-overload (PO) myocardium, STAT3 becomes phosphorylated and redistributed to detergent-insoluble fractions with no accompanying JAK2 activation. PO also caused increased levels of phosphorylated STAT3 in both cytoplasmic and nuclear fractions. To investigate the role of other NTKs, we used our established in vitro cell culture model of hypertrophy where adult feline cardiomyocytes are embedded three-dimensionally (3D) in type-I collagen and stimulated with an integrin binding peptide containing an Arg-Gly-Asp (RGD) motif that we have previously shown to recapitulate the focal adhesion complex (FAC) formation of 48 h RVPO. RGD stimulation of adult cardiomyocytes in vitro caused both STAT3 redistribution and activation that were accompanied by the activation and redistribution of c-Src and the TEC family kinase, BMX, but not JAK2. However, infection with dominant negative c-Src adenovirus was unable to block RGD-stimulated changes on either STAT3 or BMX. Further analysis in vivo in 48 h PO myocardium showed the presence of both STAT3 and BMX in the detergent-insoluble fraction with their complex formation and phosphorylation. Therefore, these studies indicate a novel mechanism of BMX-mediated STAT3 activation within a PO model of cardiac hypertrophy that might contribute to cardiomyocyte growth and survival. PMID:18612371

Mobile Voting Systems for Creating Collaboration Environments and Getting Immediate Feedback: A New Curriculum Model of a University Lecture

ERIC Educational Resources Information Center

Titova, Svetlana; Talmo, Tord

2014-01-01

Mobile devices can enhance learning and teaching by providing instant feedback and better diagnosis of learning problems, helping design new assessment models, enhancing learner autonomy and creating new formats of enquiry-based activities. The objective of this paper is to investigate the pedagogical impact of mobile voting tools. The authors'…

Do You See What I See? Exploring the Consequences of Luminosity Limits in Black Hole-Galaxy Evolution Studies

NASA Astrophysics Data System (ADS)

Jones, Mackenzie L.; Hickox, Ryan C.; Mutch, Simon J.; Croton, Darren J.; Ptak, Andrew F.; DiPompeo, Michael A.

2017-07-01

In studies of the connection between active galactic nuclei (AGNs) and their host galaxies, there is widespread disagreement on some key aspects of the connection. These disagreements largely stem from a lack of understanding of the nature of the full underlying AGN population. Recent attempts to probe this connection utilize both observations and simulations to correct for a missed population, but presently are limited by intrinsic biases and complicated models. We take a simple simulation for galaxy evolution and add a new prescription for AGN activity to connect galaxy growth to dark matter halo properties and AGN activity to star formation. We explicitly model selection effects to produce an “observed” AGN population for comparison with observations and empirically motivated models of the local universe. This allows us to bypass the difficulties inherent in models that attempt to infer the AGN population by inverting selection effects. We investigate the impact of selecting AGNs based on thresholds in luminosity or Eddington ratio on the “observed” AGN population. By limiting our model AGN sample in luminosity, we are able to recreate the observed local AGN luminosity function and specific star formation-stellar mass distribution, and show that using an Eddington ratio threshold introduces less bias into the sample by selecting the full range of growing black holes, despite the challenge of selecting low-mass black holes. We find that selecting AGNs using these various thresholds yield samples with different AGN host galaxy properties.

Native and hydrogen-containing point defects in Mg3N2 : A density functional theory study

NASA Astrophysics Data System (ADS)

Lange, Björn; Freysoldt, Christoph; Neugebauer, Jörg

2010-06-01

The formation energy and solubility of hydrogen in magnesium nitride bulk (antibixbyite Mg3N2 ) have been studied employing density functional theory in the generalized gradient approximation. The effect of doping and the presence of native defects and complex formation have been taken into account. Our results show that magnesium nitride is a nearly defect-free insulator with insignificant hydrogen-storage capacity. Based on this insight we derive a model that highlights the role of the formation and presence of the parasitic Mg3N2 inclusions in the activation of p -doped GaN in optoelectronic devices.

The standard model and some new directions. [for scientific theory of Active Galactic Nuclei

NASA Technical Reports Server (NTRS)

Blandford, R. D.; Rees, M. J.

1992-01-01

A 'standard' model of Active Galactic Nuclei (AGN), based upon a massive black hole surrounded by a thin accretion disk, is defined. It is argued that, although there is good evidence for the presence of black holes and orbiting gas, most of the details of this model are either inadequate or controversial. Magnetic field may be responsible for the confinement of continuum and line-emitting gas, for the dynamical evolution of accretion disks and for the formation of jets. It is further argued that gaseous fuel is supplied in molecular form and that this is responsible for thermal re-radiation, equatorial obscuration and, perhaps, the broad line gas clouds. Stars may also supply gas close to the black hole, especially in low power AGN and they may be observable in discrete orbits as probes of the gravitational field. Recent observations suggest that magnetic field, stars, dusty molecular gas and orientation effects must be essential components of a complete description of AGN. The discovery of quasars with redshifts approaching 5 is an important clue to the mechanism of galaxy formation.

Reaction-diffusion systems and external morphogen gradients: the two-dimensional case, with an application to skeletal pattern formation.

PubMed

Glimm, Tilmann; Zhang, Jianying; Shen, Yun-Qiu; Newman, Stuart A

2012-03-01

We investigate a reaction-diffusion system consisting of an activator and an inhibitor in a two-dimensional domain. There is a morphogen gradient in the domain. The production of the activator depends on the concentration of the morphogen. Mathematically, this leads to reaction-diffusion equations with explicitly space-dependent terms. It is well known that in the absence of an external morphogen, the system can produce either spots or stripes via the Turing bifurcation. We derive first-order expansions for the possible patterns in the presence of an external morphogen and show how both stripes and spots are affected. This work generalizes previous one-dimensional results to two dimensions. Specifically, we consider the quasi-one-dimensional case of a thin rectangular domain and the case of a square domain. We apply the results to a model of skeletal pattern formation in vertebrate limbs. In the framework of reaction-diffusion models, our results suggest a simple explanation for some recent experimental findings in the mouse limb which are much harder to explain in positional-information-type models.

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation.

PubMed

Bonnet, Amandine; Randrianarison-Huetz, Voahangy; Nzounza, Patrycja; Nedelec, Martine; Chazal, Maxime; Waast, Laetitia; Pene, Sabrina; Bazarbachi, Ali; Mahieux, Renaud; Bénit, Laurence; Pique, Claudine

2012-09-25

The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4⁺ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4⁺ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation. These data reveal that the formation of Tax nuclear bodies, previously associated to transcriptional activities in Tax-transfected cells, is dispensable for NF-κB promoter activation, notably in CD4⁺ T cells. They also provide the first evidence that Tax SUMOylation is not a key determinant for Tax-induced NF-κB activation.

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation

PubMed Central

2012-01-01

Background The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. Results In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation. Conclusions These data reveal that the formation of Tax nuclear bodies, previously associated to transcriptional activities in Tax-transfected cells, is dispensable for NF-κB promoter activation, notably in CD4+ T cells. They also provide the first evidence that Tax SUMOylation is not a key determinant for Tax-induced NF-κB activation. PMID:23009398

Photo-Activated Psoralen Binds the ErbB2 Catalytic Kinase Domain, Blocking ErbB2 Signaling and Triggering Tumor Cell Apoptosis

PubMed Central

Xia, Wenle; Gooden, David; Liu, Leihua; Zhao, Sumin; Soderblom, Erik J.; Toone, Eric J.; Beyer, Wayne F.; Walder, Harold; Spector, Neil L.

2014-01-01

Photo-activation of psoralen with UVA irradiation, referred to as PUVA, is used in the treatment of proliferative skin disorders. The anti-proliferative effects of PUVA have been largely attributed to psoralen intercalation of DNA, which upon UV treatment, triggers the formation of interstrand DNA crosslinks (ICL) that inhibit transcription and DNA replication. Here, we show that PUVA exerts antitumor effects in models of human breast cancer that overexpress the ErbB2 receptor tyrosine kinase oncogene, through a new mechanism. Independent of ICL formation, the antitumor effects of PUVA in ErbB2+ breast cancer models can instead be mediated through inhibition of ErbB2 activation and signaling. Using a mass spectroscopy-based approach, we show for the first time that photo-activated 8MOP (8-methoxypsoralen) interacts with the ErbB2 catalytic autokinase domain. Furthermore, PUVA can reverse therapeutic resistance to lapatinib and other ErbB2 targeted therapies, including resistance mediated via expression of a phosphorylated, truncated form of ErbB2 (p85ErbB2) that is preferentially expressed in tumor cell nuclei. Current ErbB2 targeted therapies, small molecule kinase inhibitors or antibodies, do not block the phosphorylated, activated state of p85ErbB2. Here we show that PUVA reduced p85ErbB2 phosphorylation leading to tumor cell apoptosis. Thus, in addition to its effects on DNA and the formation of ICL, PUVA represents a novel ErbB2 targeted therapy for the treatment of ErbB2+ breast cancers, including those that have developed resistance to other ErbB2 targeted therapies. PMID:24551203

Structural and Biochemical Characterization of Spa47 Provides Mechanistic Insight into Type III Secretion System ATPase Activation and Shigella Virulence Regulation.

PubMed

Burgess, Jamie L; Burgess, R Alan; Morales, Yalemi; Bouvang, Jenna M; Johnson, Sean J; Dickenson, Nicholas E

2016-12-09

Like many Gram-negative pathogens, Shigella rely on a complex type III secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific side chain contributions from adjacent protomers within the complex. Follow-up mutagenesis experiments targeting the predicted active site residues validate the oligomeric model and determined that each of the tested residues are essential for Spa47 ATPase activity, although they are not directly responsible for stable oligomer formation. Although N-terminal domain truncation was necessary for crystal formation, it resulted in strictly monomeric Spa47 that is unable to hydrolyze ATP, despite maintaining the canonical ATPase core structure and active site residues. Coupled with studies of ATPase inactive full-length Spa47 point mutants, we find that Spa47 oligomerization and ATP hydrolysis are needed for complete T3SS apparatus formation, a proper translocator secretion profile, and Shigella virulence. This work represents the first structure-function characterization of Spa47, uniquely complementing the multitude of included Shigella T3SS phenotype assays and providing a more complete understanding of T3SS ATPase-mediated pathogen virulence. Additionally, these findings provide a strong platform for follow-up studies evaluating regulation of Spa47 oligomerization in vivo as a much needed means of treating and perhaps preventing shigellosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Systemically administered rhBMP-2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice.

PubMed

Turgeman, Gadi; Zilberman, Yoram; Zhou, Shuanhu; Kelly, Pam; Moutsatsos, Ioannis K; Kharode, Yogendra P; Borella, Luis E; Bex, Frederick J; Komm, Barry S; Bodine, Peter V N; Gazit, Dan

2002-01-01

Osteoporosis is a disease manifested in drastic bone loss resulting in osteopenia and high risk for fractures. This disease is generally divided into two subtypes. The first, post-menopausal (type I) osteoporosis, is primarily related to estrogen deficiency. The second, senile (type II) osteoporosis, is mostly related to aging. Decreased bone formation, as well as increased bone resorption and turnover, are thought to play roles in the pathophysiology of both types of osteoporosis. In this study, we demonstrate in murine models for both type I (estrogen deficiency) and type II (senile) osteopenia/osteoporosis that reduced bone formation is related to a decrease in adult mesenchymal stem cell (AMSC) number, osteogenic activity, and proliferation. Decreased proliferation is coupled with increased apoptosis in AMSC cultures obtained from osteopenic mice. Recombinant human bone morphogenetic protein (rhBMP-2) is a highly osteoinductive protein, promoting osteogenic differentiation of AMSCs. Systemic intra-peritoneal (i.p.) injections of rhBMP-2 into osteopenic mice were able to reverse this phenotype in the bones of these animals. Moreover, this change in bone mass was coupled to an increase in AMSCs numbers, osteogenic activity, and proliferation as well as a decrease in apoptosis. Bone formation activity was increased as well. However, the magnitude of this response to rhBMP-2 varied among different stains of mice. In old osteopenic BALB/c male mice (type II osteoporosis model), rhBMP-2 systemic treatment also restored both articular and epiphyseal cartilage width to the levels seen in young mice. In summary, our study shows that AMSCs are a good target for systemically active anabolic compounds like rhBMP-2. Copyright 2002 Wiley-Liss, Inc.

Structural and Biochemical Characterization of Spa47 Provides Mechanistic Insight into Type III Secretion System ATPase Activation and Shigella Virulence Regulation*

PubMed Central

Burgess, Jamie L.; Burgess, R. Alan; Morales, Yalemi; Bouvang, Jenna M.; Johnson, Sean J.; Dickenson, Nicholas E.

2016-01-01

Like many Gram-negative pathogens, Shigella rely on a complex type III secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific side chain contributions from adjacent protomers within the complex. Follow-up mutagenesis experiments targeting the predicted active site residues validate the oligomeric model and determined that each of the tested residues are essential for Spa47 ATPase activity, although they are not directly responsible for stable oligomer formation. Although N-terminal domain truncation was necessary for crystal formation, it resulted in strictly monomeric Spa47 that is unable to hydrolyze ATP, despite maintaining the canonical ATPase core structure and active site residues. Coupled with studies of ATPase inactive full-length Spa47 point mutants, we find that Spa47 oligomerization and ATP hydrolysis are needed for complete T3SS apparatus formation, a proper translocator secretion profile, and Shigella virulence. This work represents the first structure-function characterization of Spa47, uniquely complementing the multitude of included Shigella T3SS phenotype assays and providing a more complete understanding of T3SS ATPase-mediated pathogen virulence. Additionally, these findings provide a strong platform for follow-up studies evaluating regulation of Spa47 oligomerization in vivo as a much needed means of treating and perhaps preventing shigellosis. PMID:27770024

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

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

Son, Dong Ju; Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA; Kim, Soo Yeon

2012-10-19

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murinemore » model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.« less

Ground-water flow model of the Boone formation at the Tar Creek superfund site, Oklahoma and Kansas

USGS Publications Warehouse

Reed, T.B.; Czarnecki, John B.

2006-01-01

Extensive mining activities conducted at the Tar Creek Superfund site, one of the largest Superfund sites in the United States, pose substantial health and safety risks. Mining activities removed a total of about 6,000,000 tons of lead and zinc by 1949. To evaluate the effect of this mining on the ground-water flow, a MODFLOW 2000 digital model has been developed to simulate ground-water flow in the carbonate formations of Mississippian age underlying the Tar Creek Superfund site. The model consists of three layers of variable thickness and a grid of 580 rows by 680 columns of cells 164 feet (50 meters) on a side. Model flux boundary conditions are specified for rivers and general head boundaries along the northern boundary of the Boone Formation. Selected cells in layer 1 are simulated as drain cells. Model calibration has been performed to minimize the difference between simulated and observed water levels in the Boone Formation. Hydraulic conductivity values specified during calibration range from 1.3 to 35 feet per day for the Boone Formation with the larger values occurring along the axis of the Miami Syncline where horizontal anisotropy is specified as 10 to 1. Hydraulic conductivity associated with the mine void is set at 50,000 feet per day and a specific yield of 1.0 is specified to represent that the mine void is filled completely with water. Residuals (the difference between measured and simulated ground-water altitudes) has a root-mean-squared value of 8.53 feet and an absolute mean value of 7.29 feet for 17 observed values of water levels in the Boone Formation. The utility of the model for simulating and evaluating the possible consequences of remediation activities has been demonstrated. The model was used to simulate the emplacement of chat (mine waste consisting of fines and fragments of chert) back into the mine. Scenarios using 1,800,000 and 6,500,000 tons of chat were run. Hydraulic conductivity was reduced from 50,000 feet per day to 35 feet per day in the model cells corresponding to chat emplacement locations. A comparison of the simulated baseline conditions and conditions after simulated chat emplacement revealed little change in water levels, drainage and stream flux, and ground-water flow velocity. Using the calibrated flow model, particle tracks were simulated using MODPATH to evaluate the simultaneous movement of particles with water in the vicinity of four potential sites at which various volumes of chat might be emplaced in the underground mine workings as part of potential remediation efforts at the site. Particle tracks were generated to follow the rate and direction of water movement for a simulated period of 100 years. In general, chat emplacement had minimal effect on the direction and rate of movement when compared to baseline (current) flow conditions. Water-level differences between baseline and chat-emplacement scenarios showed declines as much as 2 to 3 feet in areas immediately downgradient from the chat emplacement cells and little or no head change upgradient. Chat emplacements had minimal effect on changes in surfacewater flux with the largest simulated difference in one cell between baseline and chat emplacement scenarios being about 3.5 gallons per minute.

Does active ageing contribute to life satisfaction for older people? Testing a new model of active ageing.

PubMed

Marsillas, Sara; De Donder, Liesbeth; Kardol, Tinie; van Regenmortel, Sofie; Dury, Sarah; Brosens, Dorien; Smetcoren, An-Sofie; Braña, Teresa; Varela, Jesús

2017-09-01

Several debates have emerged across the literature about the conceptualisation of active ageing. The aim of this study is to develop a model of the construct that is focused on the individual, including different elements of people's lives that have the potential to be modified by intervention programs. Moreover, the paper examines the contributions of active ageing to life satisfaction, as well as the possible predictive role of coping styles on active ageing. For this purpose, a representative sample of 404 Galician (Spain) community-dwelling older adults (aged ≥60 years) were interviewed using a structured survey. The results demonstrate that the proposed model composed of two broad categories is valid. The model comprises status variables (related to physical, psychological, and social health) as well as different types of activities, called processual variables. This model is tested using partial least squares (PLS) regression. The findings show that active ageing is a fourth-order, formative construct. In addition, PLS analyses indicate that active ageing has a moderate and positive path on life satisfaction and that coping styles may predict active ageing. The discussion highlights the potential of active ageing as a relevant concept for people's lives, drawing out policy implications and suggestions for further research.

Stellar Mass Function of Active and Quiescent Galaxies via the Continuity Equation

NASA Astrophysics Data System (ADS)

Lapi, A.; Mancuso, C.; Bressan, A.; Danese, L.

2017-09-01

The continuity equation is developed for the stellar mass content of galaxies and exploited to derive the stellar mass function of active and quiescent galaxies over the redshift range z˜ 0{--}8. The continuity equation requires two specific inputs gauged from observations: (I) the star formation rate functions determined on the basis of the latest UV+far-IR/submillimeter/radio measurements and (II) average star formation histories for individual galaxies, with different prescriptions for disks and spheroids. The continuity equation also includes a source term taking into account (dry) mergers, based on recent numerical simulations and consistent with observations. The stellar mass function derived from the continuity equation is coupled with the halo mass function and with the SFR functions to derive the star formation efficiency and the main sequence of star-forming galaxies via the abundance-matching technique. A remarkable agreement of the resulting stellar mass functions for active and quiescent galaxies of the galaxy main sequence, and of the star formation efficiency with current observations is found; the comparison with data also allows the characteristic timescales for star formation and quiescence of massive galaxies, the star formation history of their progenitors, and the amount of stellar mass added by in situ star formation versus that contributed by external merger events to be robustly constrained. The continuity equation is shown to yield quantitative outcomes that detailed physical models must comply with, that can provide a basis for improving the (subgrid) physical recipes implemented in theoretical approaches and numerical simulations, and that can offer a benchmark for forecasts on future observations with multiband coverage, as will become routinely achievable in the era of JWST.

Meeting report from the first meetings of the Computational Modeling in Biology Network (COMBINE)

PubMed Central

Le Novère, Nicolas; Hucka, Michael; Anwar, Nadia; Bader, Gary D; Demir, Emek; Moodie, Stuart; Sorokin, Anatoly

2011-01-01

The Computational Modeling in Biology Network (COMBINE), is an initiative to coordinate the development of the various community standards and formats in computational systems biology and related fields. This report summarizes the activities pursued at the first annual COMBINE meeting held in Edinburgh on October 6-9 2010 and the first HARMONY hackathon, held in New York on April 18-22 2011. The first of those meetings hosted 81 attendees. Discussions covered both official COMBINE standards-(BioPAX, SBGN and SBML), as well as emerging efforts and interoperability between different formats. The second meeting, oriented towards software developers, welcomed 59 participants and witnessed many technical discussions, development of improved standards support in community software systems and conversion between the standards. Both meetings were resounding successes and showed that the field is now mature enough to develop representation formats and related standards in a coordinated manner. PMID:22180826

Meeting report from the first meetings of the Computational Modeling in Biology Network (COMBINE).

PubMed

Le Novère, Nicolas; Hucka, Michael; Anwar, Nadia; Bader, Gary D; Demir, Emek; Moodie, Stuart; Sorokin, Anatoly

2011-11-30

The Computational Modeling in Biology Network (COMBINE), is an initiative to coordinate the development of the various community standards and formats in computational systems biology and related fields. This report summarizes the activities pursued at the first annual COMBINE meeting held in Edinburgh on October 6-9 2010 and the first HARMONY hackathon, held in New York on April 18-22 2011. The first of those meetings hosted 81 attendees. Discussions covered both official COMBINE standards-(BioPAX, SBGN and SBML), as well as emerging efforts and interoperability between different formats. The second meeting, oriented towards software developers, welcomed 59 participants and witnessed many technical discussions, development of improved standards support in community software systems and conversion between the standards. Both meetings were resounding successes and showed that the field is now mature enough to develop representation formats and related standards in a coordinated manner.

Formation and implications of alpha-synuclein radical in Maneb- and paraquat-induced models of Parkinson’s disease

PubMed Central

Kumar, Ashutosh; Leinisch, Fabian; Kadiiska, Maria B.; Corbett, Jean; Mason, Ronald P.

2015-01-01

Parkinson’s disease (PD) is a debilitating, progressive, neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and motor deficits. Alpha-synuclein-containing aggregates represent a feature of a variety of neurodegenerative disorders, including PD; however, the mechanism that initiates and promotes intraneuronal alpha-synuclein aggregation remains unknown. We hypothesized protein radical formation as an initiating mechanism for alpha-synuclein aggregation. Therefore, we used the highly sensitive immuno-spin trapping technique to investigate protein radical formation as a possible mechanism of alpha-synuclein aggregation as well as to investigate the source of protein radical formation in the midbrains of Maneb and paraquat coexposed mice. Coexposure to Maneb and paraquat for 6 weeks resulted in active microgliosis, NADPH oxidase activation, and inducible nitric oxide synthase (iNOS) induction, which culminated in protein radical formation in the midbrains of mice. Results obtained with immuno-spin trapping and immunoprecipitation experiments confirmed formation of alpha-synuclein radicals in dopaminergic neurons of exposed mice. Free radical formation requires NADPH oxidase and iNOS, as indicated by decreased protein radical formation in knockout mice (P47phox−/− and iNOS−/−) and in mice treated with inhibitors such as FeTPPS (a peroxynitrite decomposition catalyst), 1400W (an iNOS inhibitor), or apocynin (a NADPH oxidase inhibitor). Concurrence of protein radical formation with dopaminergic neuronal death indicated a link between protein radicals and disease progression. Taken together, these results show for the first time the formation and detection of the alpha-synuclein radical and suggest that NADPH oxidase and iNOS play roles in peroxynitrite-mediated protein radical formation and subsequent neuronal death in the midbrains of Maneb and paraquat coexposed mice. PMID:25952542

Service and education share responsibility for nurses' value development.

PubMed

Schank, M J; Weis, D

2001-01-01

This article examines professional values of senior baccalaureate nursing students and practicing nurses. An important finding was that practicing nurses rated behaviors reflecting values in the American Nurses Association (ANA) Code for Nurses as more important than did senior students, thereby supporting the notion that practice contributes to value formation. The ongoing development and internalization of the nursing professions' values requires active involvement by staff development educators. The phenomena of value formation and development of professional values appear to mirror the novice to expert model.

Wound healing effects of deoxyshikonin isolated from Jawoongo: In vitro and in vivo studies.

PubMed

Park, Jun Yeon; Kwak, Jin Ho; Kang, Ki Sung; Jung, Eun Bee; Lee, Dong-Soo; Lee, Sanghyun; Jung, Yujung; Kim, Ki Hyun; Hwang, Gwi Seo; Lee, Hye Lim; Yamabe, Noriko; Kim, Su-Nam

2017-03-06

Jawoongo is a traditional drug ointment (with a traditional botanic formula) used for the treatment of burns and wounds in Korea. One of the components of Jawoongo is Lithospermi Radix (LR, the dried root of Lithospermum erythrorhizon Siebold & Zucc., also known as Zicao or Gromwell), which contains deoxyshikonin and its derivatives. The aim of the present study was to investigate the effects of deoxyshikonin on wound healing. The effects of LR extract and deoxyshikonin on tube formation and migration were measured in human umbilical vein vascular endothelial cells (HUVEC) and HaCaT cells, respectively. We evaluated protein expression of mitogen-activated protein kinase (MAPK) activation by Western blotting. The wound healing effects of deoxyshikonin was assessed in a mouse model of cutaneous wounds. The results showed that deoxyshikonin enhanced tube formation in HUVEC and migration in HaCaT cells. From the western blot analysis, we found that deoxyshikonin stimulated the phosphorylation of p38 and extracellular signal-regulated kinase (ERK) in HaCaT cells. Moreover, 20µm deoxyshikonin-treated groups showed accelerated wound closure compared with the controls in a mouse model of cutaneous wounds. In conclusion, the current data indicate that deoxyshikonin treatment elevated tube formation in HUVECs, and that deoxyshikonin-induced proliferation and migration in HaCaT cells were mediated by the activation of ERK and p38 MAPKs, respectively. Collectively, these data suggest that deoxyshikonin in Jawoongo must be an active compound for may be wound healing. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity

PubMed Central

Bennett, James E. M.; Bair, Wyeth

2015-01-01

Traveling waves in the developing brain are a prominent source of highly correlated spiking activity that may instruct the refinement of neural circuits. A candidate mechanism for mediating such refinement is spike-timing dependent plasticity (STDP), which translates correlated activity patterns into changes in synaptic strength. To assess the potential of these phenomena to build useful structure in developing neural circuits, we examined the interaction of wave activity with STDP rules in simple, biologically plausible models of spiking neurons. We derive an expression for the synaptic strength dynamics showing that, by mapping the time dependence of STDP into spatial interactions, traveling waves can build periodic synaptic connectivity patterns into feedforward circuits with a broad class of experimentally observed STDP rules. The spatial scale of the connectivity patterns increases with wave speed and STDP time constants. We verify these results with simulations and demonstrate their robustness to likely sources of noise. We show how this pattern formation ability, which is analogous to solutions of reaction-diffusion systems that have been widely applied to biological pattern formation, can be harnessed to instruct the refinement of postsynaptic receptive fields. Our results hold for rich, complex wave patterns in two dimensions and over several orders of magnitude in wave speeds and STDP time constants, and they provide predictions that can be tested under existing experimental paradigms. Our model generalizes across brain areas and STDP rules, allowing broad application to the ubiquitous occurrence of traveling waves and to wave-like activity patterns induced by moving stimuli. PMID:26308406

Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity.

PubMed

Bennett, James E M; Bair, Wyeth

2015-08-01

Traveling waves in the developing brain are a prominent source of highly correlated spiking activity that may instruct the refinement of neural circuits. A candidate mechanism for mediating such refinement is spike-timing dependent plasticity (STDP), which translates correlated activity patterns into changes in synaptic strength. To assess the potential of these phenomena to build useful structure in developing neural circuits, we examined the interaction of wave activity with STDP rules in simple, biologically plausible models of spiking neurons. We derive an expression for the synaptic strength dynamics showing that, by mapping the time dependence of STDP into spatial interactions, traveling waves can build periodic synaptic connectivity patterns into feedforward circuits with a broad class of experimentally observed STDP rules. The spatial scale of the connectivity patterns increases with wave speed and STDP time constants. We verify these results with simulations and demonstrate their robustness to likely sources of noise. We show how this pattern formation ability, which is analogous to solutions of reaction-diffusion systems that have been widely applied to biological pattern formation, can be harnessed to instruct the refinement of postsynaptic receptive fields. Our results hold for rich, complex wave patterns in two dimensions and over several orders of magnitude in wave speeds and STDP time constants, and they provide predictions that can be tested under existing experimental paradigms. Our model generalizes across brain areas and STDP rules, allowing broad application to the ubiquitous occurrence of traveling waves and to wave-like activity patterns induced by moving stimuli.

The Impact of Dopant Segregation on the Maximum Carrier Density in Si:P Multilayers.

PubMed

Keizer, Joris G; McKibbin, Sarah R; Simmons, Michelle Y

2015-07-28

Abrupt dopant profiles and low resistivity are highly sought after qualities in the silicon microelectronics industry and, more recently, in the development of an all epitaxial Si:P based quantum computer. If we increase the active carrier density in silicon to the point where the material becomes superconducting, while maintaining a low thermal budget, it will be possible to fabricate nanoscale superconducting devices using the highly successful technique of depassivation lithography. In this work, we investigate the dopant profile and activation in multiple high density Si:P δ-layers fabricated by stacking individual layers with intervening silicon growth. We determine that dopant activation is ultimately limited by the formation of P-P dimers due to the segregation of dopants between multilayers. By increasing the encapsulation thickness between subsequent layers, thereby minimizing the formation of these deactivating defects, we are able to achieve an active carrier density of ns = 4.5 ×10(14) cm(-2) for a triple layer. The results of electrical characterization are combined with those of secondary ion mass spectroscopy to construct a model that accurately describes the impact of P segregation on the final active carrier density in Si:P multilayers. Our model predicts that a 3D active carrier density of 8.5 × 10(20) cm(-3) (1.7 atom %) can be achieved.

Modulation of type II TGF-β receptor degradation by integrin-linked kinase.

PubMed

Vi, Linda; Boo, Stellar; Sayedyahossein, Samar; Singh, Randeep K; McLean, Sarah; Di Guglielmo, Gianni M; Dagnino, Lina

2015-03-01

Cutaneous responses to injury, infection, and tumor formation involve the activation of resident dermal fibroblasts and subsequent transition to myofibroblasts. The key for induction of myofibroblast differentiation is the activation of transforming growth factor-β (TGF-β) receptors and stimulation of integrins and their associated proteins, including integrin-linked kinase (ILK). Cross-talk processes between TGF-β and ILK are crucial for myofibroblast formation, as ILK-deficient dermal fibroblasts exhibit impaired responses to TGF-β receptor stimulation. We now show that ILK associates with type II TGF-β receptors (TβRII) in ligand- and receptor kinase activity-independent manners. In cells with targeted Ilk gene inactivation, cellular levels of TβRII are decreased, through mechanisms that involve enhanced ubiquitination and proteasomal degradation. Partitioning of TGF-β receptors into membrane has been linked to proteasome-dependent receptor degradation. We found that interfering with membrane raft formation in ILK-deficient cells restored TβRII levels and signaling. These observations support a model whereby ILK functions in fibroblasts to direct TβRII away from degradative pathways during their differentiation into myofibroblasts.

Rasch analyses of the Activities-specific Balance Confidence Scale with individuals 50 years and older with lower limb amputations

PubMed Central

Sakakibara, Brodie M.; Miller, William C.; Backman, Catherine L.

2012-01-01

Objective To explore shortened response formats for use with the Activities-specific Balance Confidence scale and then: 1) evaluate the unidimensionality of the scale; 2) evaluate the item difficulty; 3) evaluate the scale for redundancy and content gaps; and 4) evaluate the item standard error of measurement (SEM) and internal consistency reliability among aging individuals (≥50 years) with a lower-limb amputation living in the community. Design Secondary analysis of cross-sectional survey and chart review data. Setting Out-patient amputee clinics, Ontario, Canada. Participants Four hundred forty eight community living adults, at least 50 years old (mean = 68 years), who have used a prosthesis for at least 6 months for a major unilateral lower limb amputation. Three hundred twenty five (72.5%) were men. Intervention N/a Main Outcome Measure(s) Activities-specific Balance Confidence Scale. Results A 5-option response format outperformed 4- and 6-option formats. Factor analyses confirmed a unidimensional scale. The distance between response options is not the same for all items on the scale, evident by the Partial Credit Model (PCM) having a better fit to the data than the Rating Scale Model. Two items, however, did not fit the PCM within statistical reason. Revising the wording of the two items may resolve the misfit, and improve the construct validity and lower the SEM. Overall, the difficulty of the scale’s items is appropriate for use with aging individuals with lower-limb amputation, and is most reliable (Cronbach ∝ = 0.94) for use with individuals with moderately low balance confidence levels. Conclusions The ABC-scale with a simplified 5-option response format is a valid and reliable measure of balance confidence for use with individuals aging with a lower limb amputation. PMID:21704978

Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition.

PubMed

Fumoto, Katsumi; Takigawa-Imamura, Hisako; Sumiyama, Kenta; Kaneiwa, Tomoyuki; Kikuchi, Akira

2017-01-01

In lung development, the apically constricted columnar epithelium forms numerous buds during the pseudoglandular stage. Subsequently, these epithelial cells change shape into the flat or cuboidal pneumocytes that form the air sacs during the canalicular and saccular (canalicular-saccular) stages, yet the impact of cell shape on tissue morphogenesis remains unclear. Here, we show that the expression of Wnt components is decreased in the canalicular-saccular stages, and that genetically constitutive activation of Wnt signaling impairs air sac formation by inducing apical constriction in the epithelium as seen in the pseudoglandular stage. Organ culture models also demonstrate that Wnt signaling induces apical constriction through apical actomyosin cytoskeletal organization. Mathematical modeling reveals that apical constriction induces bud formation and that loss of apical constriction is required for the formation of an air sac-like structure. We identify MAP/microtubule affinity-regulating kinase 1 (Mark1) as a downstream molecule of Wnt signaling and show that it is required for apical cytoskeletal organization and bud formation. These results suggest that Wnt signaling is required for bud formation by inducing apical constriction during the pseudoglandular stage, whereas loss of Wnt signaling is necessary for air sac formation in the canalicular-saccular stages. © 2017. Published by The Company of Biologists Ltd.

The Route to Raindrop Formation in a Shallow Cumulus Cloud Simulated by a Lagrangian Cloud Model

NASA Astrophysics Data System (ADS)

Noh, Yign; Hoffmann, Fabian; Raasch, Siegfried

2017-11-01

The mechanism of raindrop formation in a shallow cumulus cloud is investigated using a Lagrangian cloud model (LCM). The analysis is focused on how and under which conditions a cloud droplet grows to a raindrop by tracking the history of individual Lagrangian droplets. It is found that the rapid collisional growth, leading to raindrop formation, is triggered when single droplets with a radius of 20 μm appear in the region near the cloud top, characterized by a large liquid water content, strong turbulence, large mean droplet size, a broad drop size distribution (DSD), and high supersaturations. Raindrop formation easily occurs when turbulence-induced collision enhancement(TICE) is considered, with or without any extra broadening of the DSD by another mechanism (such as entrainment and mixing). In contrast, when TICE is not considered, raindrop formation is severely delayed if no other broadening mechanism is active. The reason leading to the difference is clarified by the additional analysis of idealized box-simulations of the collisional growth process for different DSDs in varied turbulent environments. It is found that TICE does not accelerate the timing of the raindrop formation for individual droplets, but it enhances the collisional growth rate significantly afterward. KMA R & D Program (Korea), DFG (Germany).

A novel taspine analog, HMQ1611, inhibits growth of non-small cell lung cancer by inhibiting angiogenesis

PubMed Central

LU, WEN; DAI, BINGLING; MA, WEINA; ZHANG, YANMIN

2012-01-01

In the present study, we investigated the antitumor activity of HMQ1611, a novel synthetic taspine derivative, in vivo and evaluated associated potential antiangiogenesis mechanisms. The proliferation of A549 cells was examined by WST-1 assay in vitro. Tube formation and lung tissue vessel models were used to observe the antiangiogenic activity of HMQ1611. In addition, vascular enodthelial growth factor (VEGF) secretion and KDR kinase activities were measured by ELISA and the HTRF®KinEASE™-TK assay. In vivo, the antitumor activity was assessed by implantation of A549 cells in athymic mice. The results showed that HMQ1611 inhibited A549 cell proliferation and VEGF secretion, while it significantly inhibited tube formation and tissue vascularization. Furthermore, HMQ1611 inhibited A549 xenograft tumor growth. In conclusion, the results of our study suggest that HMQ1611 has latent properties for the inhibition of angiogenesis which are involved in its antitumor activity. PMID:23162661

A novel taspine analog, HMQ1611, inhibits growth of non-small cell lung cancer by inhibiting angiogenesis.

PubMed

Lu, Wen; Dai, Bingling; Ma, Weina; Zhang, Yanmin

2012-11-01

In the present study, we investigated the antitumor activity of HMQ1611, a novel synthetic taspine derivative, in vivo and evaluated associated potential antiangiogenesis mechanisms. The proliferation of A549 cells was examined by WST-1 assay in vitro. Tube formation and lung tissue vessel models were used to observe the antiangiogenic activity of HMQ1611. In addition, vascular enodthelial growth factor (VEGF) secretion and KDR kinase activities were measured by ELISA and the HTRF(®)KinEASE(™)-TK assay. In vivo, the antitumor activity was assessed by implantation of A549 cells in athymic mice. The results showed that HMQ1611 inhibited A549 cell proliferation and VEGF secretion, while it significantly inhibited tube formation and tissue vascularization. Furthermore, HMQ1611 inhibited A549 xenograft tumor growth. In conclusion, the results of our study suggest that HMQ1611 has latent properties for the inhibition of angiogenesis which are involved in its antitumor activity.

Using an ACTIVE teaching format versus a standard lecture format for increasing resident interaction and knowledge achievement during noon conference: a prospective, controlled study.

PubMed

Sawatsky, Adam P; Berlacher, Kathryn; Granieri, Rosanne

2014-07-01

The traditional lecture is used by many residency programs to fulfill the mandate for regular didactic sessions, despite limited evidence to demonstrate its effectiveness. Active teaching strategies have shown promise in improving medical knowledge but have been challenging to implement within the constraints of residency training. We developed and evaluated an innovative structured format for interactive teaching within the residency noon conference. We developed an ACTIVE teaching format structured around the following steps: assemble (A) into groups, convey (C) learning objectives, teach (T) background information, inquire (I) through cases and questions, verify (V) understanding, and explain (E) answer choices and educate on the learning points. We conducted a prospective, controlled study of the ACTIVE teaching format versus the standard lecture format, comparing resident satisfaction, immediate knowledge achievement and long-term knowledge retention. We qualitatively assessed participating faculty members' perspectives on the faculty development efforts and the feasibility of teaching using the ACTIVE format. Sixty-nine internal medicine residents participated in the study. Overall, there was an improvement in perceived engagement using the ACTIVE teaching format (4.78 vs. 3.80, P < 0.01), with no increase in stress or decrement in break time. There was an improvement in initial knowledge achievement with the ACTIVE teaching format (overall absolute score increase of 11%, P = 0.04) and a trend toward improvement in long-term knowledge retention. Faculty members felt adequately prepared to use the ACTIVE teaching format, and enjoyed teaching with the ACTIVE teaching format more than the standard lecture. A structured ACTIVE teaching format improved resident engagement and initial knowledge, and required minimal resources. The ACTIVE teaching format offers an exciting alternative to the standard lecture for resident noon conference and is easy to implement.

Critical role of FcR gamma-chain, LAT, PLCgamma2 and thrombin in arteriolar thrombus formation upon mild, laser-induced endothelial injury in vivo.

PubMed

Kalia, Neena; Auger, Jocelyn M; Atkinson, Ben; Watson, Steve P

2008-05-01

The role of collagen receptor complex GPVI-FcR gamma-chain, PLCgamma2 and LAT in laser-induced thrombosis is unclear. Controversy surrounds whether collagen is exposed in this model or whether thrombosis is dependent on thrombin. This study hypothesized that collagen exposure plays a critical role in thrombus formation in this model, which was tested by investigating contributions of FcR gamma-chain, LAT, PLCgamma2 and thrombin. Thrombi were monitored using intravital microscopy in anesthetized wild-type and FcR gamma-chain, LAT and PLCgamma2 knockout mice. Hirudin (thrombin inhibitor) was administered to wild-type and FcR gamma-chain knockout mice. Significantly reduced thrombus formation was observed in FcR gamma-chain and PLCgamma2 knockouts with a greater decrease observed in LAT knockouts. Dramatic reduction was observed in wild-types treated with hirudin, with abolished thrombus formation only observed in FcR gamma-chain knockouts treated with hirudin. GPVI-FcR gamma-chain, LAT and PLCgamma2 are essential for thrombus generation and stability in this laser-induced model of injury. More importantly, a greater role for LAT was identified, which may reflect a role for it downstream of a second matrix protein receptor. However, inhibition of platelet activation by matrix proteins and thrombin generation are both required to maximally prevent thrombus formation.

Two Distinct Coagulase-Dependent Barriers Protect Staphylococcus aureus from Neutrophils in a Three Dimensional in vitro Infection Model

PubMed Central

Guggenberger, Christoph; Wolz, Christiane; Morrissey, Julie A.; Heesemann, Jürgen

2012-01-01

Staphylococcus aureus is a pyogenic abscess-forming facultative pathogenic microorganism expressing a large set of virulence-associated factors. Among these, secreted proteins with binding capacity to plasma proteins (e.g. fibrinogen binding proteins Eap and Emp) and prothrombin activators such as Coagulase (Coa) and vWbp are involved in abscess formation. By using a three-dimensional collagen gel (3D-CoG) supplemented with fibrinogen (Fib) we studied the growth behavior of S. aureus strain Newman and a set of mutants as well as their interaction with mouse neutrophils by real-time confocal microscopy. In 3D-CoG/Fib, S. aureus forms microcolonies which are surrounded by an inner pseudocapsule and an extended outer dense microcolony-associated meshwork (MAM) containing fibrin. Coa is involved in formation of the pseudocapsule whereas MAM formation depends on vWbp. Moreover, agr-dependent dispersal of late stage microcolonies could be observed. Furthermore, we demonstrate that the pseudocapsule and the MAM act as mechanical barriers against neutrophils attracted to the microcolony. The thrombin inhibitor argatroban is able to prevent formation of both pseudocapsule and MAM and supports access of neutrophils to staphylococci. Taken together, this model can simulate specific stages of S. aureus abscess formation by temporal dissection of bacterial growth and recruitment of immune cells. It can complement established animal infection models in the development of new treatment options. PMID:22253592

Antioxidant Compounds in Traditional Indian Pickles May Prevent the Process-Induced Formation of Benzene.

PubMed

Kharat, Mahesh M; Adiani, Vanshika; Variyar, Prasad; Sharma, Arun; Singhal, Rekha S

2016-01-01

Pickles in the Indian market contain ascorbic acid from the raw material used and benzoate as an added preservative that are involved in the formation of benzene in soft drinks. In this work, 24 market pickle samples were surveyed for benzene content, as well as its precursors and other constituents that influence its formation. The analysis showed that pickle samples were high in acid content (low pH) and showed significant amount of ascorbic acid, minerals (Cu and Fe), and benzoic acid present in them. Also, most samples exhibited high antioxidant activity that might be attributed to the ingredients used, such as fruits and spices. The solid-phase microextraction headspace gas chromatography-mass spectrometry method was developed in-house for benzene analysis. Eleven of 24 samples had benzene, with the highest concentration of 4.36 ± 0.82 μg of benzene per kg of pickle for a lime pickle that was also reported to have highest benzoic acid and considerably less hydroxyl radical ((•)OH) scavenging activity. However, benzene levels for all 11 samples were considerably below the World Health Organization regulatory limit of 10 μg/kg for benzene in mineral water. Studies on model systems revealed that the high antioxidant activity of Indian pickles may have had a strong inhibitory effect on benzene formation.

A Quantitative Model for the Prediction of Sooting Tendency from Molecular Structure

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

St. John, Peter C.; Kairys, Paul; Das, Dhrubajyoti D.

Particulate matter emissions negatively affect public health and global climate, yet newer fuel-efficient gasoline direct injection engines tend to produce more soot than their port-fuel injection counterparts. Fortunately, the search for sustainable biomass-based fuel blendstocks provides an opportunity to develop fuels that suppress soot formation in more efficient engine designs. However, as emissions tests are experimentally cumbersome and the search space for potential bioblendstocks is vast, new techniques are needed to estimate the sooting tendency of a diverse range of compounds. In this study, we develop a quantitative structure-activity relationship (QSAR) model of sooting tendency based on the experimental yieldmore » sooting index (YSI), which ranks molecules on a scale from n-hexane, 0, to benzene, 100. The model includes a rigorously defined applicability domain, and the predictive performance is checked using both internal and external validation. Model predictions for compounds in the external test set had a median absolute error of ~3 YSI units. An investigation of compounds that are poorly predicted by the model lends new insight into the complex mechanisms governing soot formation. Predictive models of soot formation can therefore be expected to play an increasingly important role in the screening and development of next-generation biofuels.« less

A Quantitative Model for the Prediction of Sooting Tendency from Molecular Structure

DOE PAGES

St. John, Peter C.; Kairys, Paul; Das, Dhrubajyoti D.; ...

2017-07-24

Particulate matter emissions negatively affect public health and global climate, yet newer fuel-efficient gasoline direct injection engines tend to produce more soot than their port-fuel injection counterparts. Fortunately, the search for sustainable biomass-based fuel blendstocks provides an opportunity to develop fuels that suppress soot formation in more efficient engine designs. However, as emissions tests are experimentally cumbersome and the search space for potential bioblendstocks is vast, new techniques are needed to estimate the sooting tendency of a diverse range of compounds. In this study, we develop a quantitative structure-activity relationship (QSAR) model of sooting tendency based on the experimental yieldmore » sooting index (YSI), which ranks molecules on a scale from n-hexane, 0, to benzene, 100. The model includes a rigorously defined applicability domain, and the predictive performance is checked using both internal and external validation. Model predictions for compounds in the external test set had a median absolute error of ~3 YSI units. An investigation of compounds that are poorly predicted by the model lends new insight into the complex mechanisms governing soot formation. Predictive models of soot formation can therefore be expected to play an increasingly important role in the screening and development of next-generation biofuels.« less

Planetesimal formation during protoplanetary disk buildup

NASA Astrophysics Data System (ADS)

Drążkowska, J.; Dullemond, C. P.

2018-06-01

Context. Models of dust coagulation and subsequent planetesimal formation are usually computed on the backdrop of an already fully formed protoplanetary disk model. At the same time, observational studies suggest that planetesimal formation should start early, possibly even before the protoplanetary disk is fully formed. Aims: In this paper we investigate under which conditions planetesimals already form during the disk buildup stage, in which gas and dust fall onto the disk from its parent molecular cloud. Methods: We couple our earlier planetesimal formation model at the water snow line to a simple model of disk formation and evolution. Results: We find that under most conditions planetesimals only form after the buildup stage, when the disk becomes less massive and less hot. However, there are parameters for which planetesimals already form during the disk buildup. This occurs when the viscosity driving the disk evolution is intermediate (αv 10-3-10-2) while the turbulent mixing of the dust is reduced compared to that (αt ≲ 10-4), and with the assumption that the water vapor is vertically well-mixed with the gas. Such a αt ≪ αv scenario could be expected for layered accretion, where the gas flow is mostly driven by the active surface layers, while the midplane layers, where most of the dust resides, are quiescent. Conclusions: In the standard picture where protoplanetary disk accretion is driven by global turbulence, we find that no planetesimals form during the disk buildup stage. Planetesimal formation during the buildup stage is only possible in scenarios in which pebbles reside in a quiescent midplane while the gas and water vapor are diffused at a higher rate.

CREB and the discovery of cognitive enhancers.

PubMed

Scott, Roderick; Bourtchuladze, Rusiko; Gossweiler, Scott; Dubnau, Josh; Tully, Tim

2002-01-01

In the past few years, a series of molecular-genetic, biochemical, cellular and behavioral studies in fruit flies, sea slugs and mice have confirmed a long-standing notion that long-term memory formation depends on the synthesis of new proteins. Experiments focused on the cAMP-responsive transcription factor, CREB, have established that neural activity-induced regulation of gene transcription promotes a synaptic growth process that strengthens the connections among active neurons. This process constitutes a physical basis for the engram--and CREB is a "molecular switch" to produce the engram. Helicon Therapeutics has been formed to identify drug compounds that enhance memory formation via augmentation of CREB biochemistry. Candidate compounds have been identified from a high throughput cell-based screen and are being evaluated in animal models of memory formation. A gene discovery program also seeks to identify new genes, which function downstream of CREB during memory formation, as a source for new drug discoveries in the future. Together, these drug and gene discovery efforts promise new class of pharmaceutical therapies for the treatment of various forms of cognitive dysfunction.

Disrupting a key hydrophobic pair in the oligomerization interface of the actinoporins impairs their pore‐forming activity

PubMed Central

Mesa‐Galloso, Haydeé; Delgado‐Magnero, Karelia H.; Cabezas, Sheila; López‐Castilla, Aracelys; Hernández‐González, Jorge E.; Pedrera, Lohans; Alvarez, Carlos; Peter Tieleman, D.; García‐Sáez, Ana J.; Lanio, Maria E.; Valiente, Pedro A.

2017-01-01

Abstract Crystallographic data of the dimeric and octameric forms of fragaceatoxin C (FraC) suggested the key role of a small hydrophobic protein–protein interaction surface for actinoporins oligomerization and pore formation in membranes. However, site‐directed mutagenesis studies supporting this hypothesis for others actinoporins are still lacking. Here, we demonstrate that disrupting the key hydrophobic interaction between V60 and F163 (FraC numbering scheme) in the oligomerization interface of FraC, equinatoxin II (EqtII), and sticholysin II (StII) impairs the pore formation activity of these proteins. Our results allow for the extension of the importance of FraC protein–protein interactions in the stabilization of the oligomeric intermediates of StII and EqtII pointing out that all of these proteins follow a similar pathway of membrane disruption. These findings support the hybrid pore proposal as the universal model of actinoporins pore formation. Moreover, we reinforce the relevance of dimer formation, which appears to be a functional intermediate in the assembly pathway of some different pore‐forming proteins. PMID:28000294

Learning and Transition of Symbols: Towards a Dynamical Model of a Symbolic Individual

NASA Astrophysics Data System (ADS)

Hashimoto, Takashi; Masumi, Akira

The remarkable feature of linguistic communications is the use of symbols for transmitting information and mutual understanding. Deacon (1997) pointed out that humans are symbolic species, namely, we show symbolic cognitive activities such as learning, formation, and manipulation of symbols. In research into the origin and the evolution of language, we should elucidate the emerging process of such symbolic cognitive activities.

Recursive Model of a Methodical Competency Formation of a High School Teacher in the Context of Competency-Based Education

ERIC Educational Resources Information Center

??lekhina, ??rina Borisovna

2015-01-01

The present study examines the professional development problems of a high school teacher. A high school teacher is both a scientist and a teacher. Teaching and research activities are integrated by using methodical activity. Methodical competency of a teacher is defined as a basis in the context of Competence-based Education. The methodical…

A zebrafish model of chordoma initiated by notochord-driven expression of HRASV12.

PubMed

Burger, Alexa; Vasilyev, Aleksandr; Tomar, Ritu; Selig, Martin K; Nielsen, G Petur; Peterson, Randall T; Drummond, Iain A; Haber, Daniel A

2014-07-01

Chordoma is a malignant tumor thought to arise from remnants of the embryonic notochord, with its origin in the bones of the axial skeleton. Surgical resection is the standard treatment, usually in combination with radiation therapy, but neither chemotherapeutic nor targeted therapeutic approaches have demonstrated success. No animal model and only few chordoma cell lines are available for preclinical drug testing, and, although no druggable genetic drivers have been identified, activation of EGFR and downstream AKT-PI3K pathways have been described. Here, we report a zebrafish model of chordoma, based on stable transgene-driven expression of HRASV12 in notochord cells during development. Extensive intra-notochordal tumor formation is evident within days of transgene expression, ultimately leading to larval death. The zebrafish tumors share characteristics of human chordoma as demonstrated by immunohistochemistry and electron microscopy. The mTORC1 inhibitor rapamycin, which has some demonstrated activity in a chordoma cell line, delays the onset of tumor formation in our zebrafish model, and improves survival of tumor-bearing fish. Consequently, the HRASV12-driven zebrafish model of chordoma could enable high-throughput screening of potential therapeutic agents for the treatment of this refractory cancer. © 2014. Published by The Company of Biologists Ltd.

NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation

PubMed Central

Yao, Zhenqiang; Li, Yanyun; Yin, Xiaoxiang; Dong, Yufeng; Xing, Lianping; Boyce, Brendan F.

2013-01-01

RelA-mediated NF-κB canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-κB RelB may also negatively regulate bone formation through non-canonical signaling, but they involved a complex knockout mouse model and the molecular mechanisms involved were not investigated. Here, we report that RelB−/− mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB−/− bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runx2. In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB−/− bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair. PMID:24115294

High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

PubMed Central

Larmonier, C. B.; McFadden, R.-M. T.; Hill, F. M.; Schreiner, R.; Ramalingam, R.; Besselsen, D. G.; Ghishan, F. K.

2013-01-01

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D3 has been considered a viable adjunctive therapy in IBD. However, vitamin D3 plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D3 supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10−/− CD4+ T cell transfer model of chronic colitis. High-dose vitamin D3 supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D3 metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D3 supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D3 diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D3 group. Our data suggest that vitamin D3, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D3 supplementation in patients with active IBD. PMID:23639807

High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model.

PubMed

Larmonier, C B; McFadden, R-M T; Hill, F M; Schreiner, R; Ramalingam, R; Besselsen, D G; Ghishan, F K; Kiela, P R

2013-07-01

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D₃ has been considered a viable adjunctive therapy in IBD. However, vitamin D₃ plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D₃ supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10-/- CD4⁺ T cell transfer model of chronic colitis. High-dose vitamin D₃ supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D₃ metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D₃ supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D₃ diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D₃ group. Our data suggest that vitamin D₃, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D₃ supplementation in patients with active IBD.

Pharmacological studies on Buchanania lanzan Spreng.-A focus on wound healing with particular reference to anti-biofilm properties

PubMed Central

Pattnaik, Ashok; Sarkar, Ratul; Sharma, Amrita; Yadav, Kirendra Kumar; Kumar, Alekh; Roy, Paramita; Mazumder, Avijit; Karmakar, Sanmoy; Sen, Tuhinadri

2013-01-01

Objective To evaluate the wound healing activity of the methanolic root extract of Buchanania lanzan Spreng. (B. lanzan), with a focus on antimicrobial and anti-biofilm properties. Methods The extract was evaluated for its wound healing properties (excision and incision models) as evident from the analysis of tensile strength and wound contraction. The extract was also screened for antibacterial properties against different Gram positive and Gram negative bacterial strains. B. lanzan was also studied for its effect on biofilm formation and disruption of preformed biofilms. The synergistic effect of B. lanzan was determined in combination with gentamicin. Results Topical application of B. lanzan (10% w/w ointment) significantly increased (40.84%) the tensile strength in the incision wound model. B. lanzan also showed significant wound healing activity in excision model and such significant activity was observed from the 9th day. Whereas Soframycin displayed significant wound healing activity from the 6th day. It was found that root extracts of B. lanzan revealed significant inhibition against all tested pathogens. B. lanzan displayed antimicrobial activity against Gram positive (MIC 0.625 mg/mL) and Gram negative (MIC 0.625–1.25 mg/mL). B. lanzan was able to reduce biofilm formation and also caused disruption of preformed biofilms in a manner similar to ciprofloxacin. However, gentamicin was found to be ineffective against biofilms formed by Gram negative organism. According to the fractional inhibitory concentration index, B. lanzan displayed synergistic activity when it was combined with gentamicin. Conclusions From this study it may be concluded that the root extract of B. lanzan revealed significant wound healing potential, which was supported and well correlated with pronounced antibacterial activity of the tested plant parts. PMID:24093788

Edible Earth and Space Science Activities

NASA Astrophysics Data System (ADS)

Lubowich, D.; Shupla, C.

2014-07-01

In this workshop we describe using Earth and Space Science demonstrations with edible ingredients to increase student interest. We show how to use chocolate, candy, cookies, popcorn, bagels, pastries, Pringles, marshmallows, whipped cream, and Starburst candy for activities such as: plate tectonics, the interior structure of the Earth and Mars, radioactivity/radioactive dating of rocks and stars, formation of the planets, lunar phases, convection, comets, black holes, curvature of space, dark energy, and the expansion of the Universe. In addition to creating an experience that will help students remember specific concepts, edible activities can be used as a formative assessment, providing students with the opportunity to create something that demonstrates their understanding of the model. The students often eat the demonstrations. These demonstrations are an effective teaching tool for all ages, and can be adapted for cultural, culinary, and ethnic differences among the students.

Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation

PubMed Central

den Brok, Martijn H.; Büll, Christian; Wassink, Melissa; de Graaf, Annemarie M.; Wagenaars, Jori A.; Minderman, Marthe; Thakur, Mayank; Amigorena, Sebastian; Rijke, Eric O.; Schrier, Carla C.; Adema, Gosse J.

2016-01-01

Saponin-based adjuvants (SBAs) are being used in animal and human (cancer) vaccines, as they induce protective cellular immunity. Their adjuvant potency is a factor of inflammasome activation and enhanced antigen cross-presentation by dendritic cells (DCs), but how antigen cross-presentation is induced is not clear. Here we show that SBAs uniquely induce intracellular lipid bodies (LBs) in the CD11b+ DC subset in vitro and in vivo. Using genetic and pharmacological interference in models for vaccination and in situ tumour ablation, we demonstrate that LB induction is causally related to the saponin-dependent increase in cross-presentation and T-cell activation. These findings link adjuvant activity to LB formation, aid the application of SBAs as a cancer vaccine component, and will stimulate development of new adjuvants enhancing T-cell-mediated immunity. PMID:27819292

Group Formation in Economics

NASA Astrophysics Data System (ADS)

Demange, Gabrielle; Wooders, Myrna

2005-01-01

Broad and diverse ranges of activities are conducted within and by organized groups of individuals, including political, economic and social activities. These activities have recently become a subject of intense interest in economics and game theory. Some of the topics investigated in this collection are models of networks of power and privilege, trade networks, co-authorship networks, buyer-seller networks with differentiated products, and networks of medical innovation and the adaptation of new information. Other topics are social norms on punctuality, clubs and the provision of club goods and public goods, research and development and collusive alliances among corporations, and international alliances and trading agreements. While relatively recent, the literature on game theoretic studies of group formation in economics is already vast. This volume provides an introduction to this important literature on game-theoretic treatments of situations with networks, clubs, and coalitions, including some applications.

Triterpenoid Saponin W3 from Anemone flaccida Suppresses Osteoclast Differentiation through Inhibiting Activation of MAPKs and NF-κB Pathways.

PubMed

Kong, Xiangying; Yang, Yue; Wu, Wenbin; Wan, Hongye; Li, Xiaomin; Zhong, Michun; Su, Xiaohui; Jia, Shiwei; Lin, Na

2015-01-01

Excessive bone resorption by osteoclasts within inflamed joints is the most specific hallmark of rheumatoid arthritis. A. flaccida has long been used for the treatment of arthritis in folk medicine of China; however, the active ingredients responsible for the anti-arthritis effects of A. flaccida are still elusive. In this study, W3, a saponin isolated from the extract of A. flaccida was identified as the major active ingredient by using an osteoclast formation model induced by receptor activator of nuclear factor kappa-B ligand (RANKL). W3 dose-dependently suppressed the actin ring formation and lacunar resorption. Mechanistic investigation revealed that W3 inhibited the RANKL-induced TRAF6 expression, decreased phosphorylation of mitogen-activated protein kinases (MAPKs) and IκB-α, and suppressed NF-κB p65 DNA binding activity. Furthermore, W3 almost abrogated the expression of c-Fos and nuclear factor of activated T cells (NFATc1). Therefore, our results suggest that W3 is a potential agent for treating lytic bone diseases although further evaluation in vivo and in clinical trials is needed.

Learning about Fossil Formation by Classroom Simulation.

ERIC Educational Resources Information Center

Schlenker, Richard M.; Yoshida, Sarah J.

1991-01-01

Activities in which students build their own simulations of fossils, using seashells, chicken bones, toy dinosaurs, or leaves as models and plaster of paris, sand, mud, clay, or a mixture of gravel and clay as a matrix are presented. Curriculum extensions are included. (KR)

Modeling Trihalomethane Formation Potential from Wastewater Chlorination

DTIC Science & Technology

1994-09-01

Aerated Lagoon Chlor/Dechlor - - - King Salmon River Luke, AZ Tertiary Ultraviolet 1.2 MGD Agua Fria River / Irrigation MacDD, FL Activated Sludge...November 1988). Tchobanoglous, George and Burton, Franklin L. Wastewater engineering: treatment, disposal, and reuse / Metcalf & Eddy, Inc. -3rd ed

A DFT study and micro-kinetic analysis of acetylene selective hydrogenation on Pd-doped Cu(111) surfaces

NASA Astrophysics Data System (ADS)

Ma, Ling-Ling; Lv, Cun-Qin; Wang, Gui-Chang

2017-07-01

Semi-hydrogenation of acetylene in a hydrogen-rich stream is an industrially important process. Inspired by the recent experiments that Cu(111) surface doped by a small number of Pd atoms can exhibit excellent catalytic performance toward the dissociation of H2 molecule as well as the high selective hydrogenation of acetylene as compared with pure Cu and Pd metal alone at low-temperature, here we performed systematic first-principles calculations to investigate the corresponding reaction mechanism related to the acetylene hydrogenation processes on single atom alloys (SAAs) and monolayer Pd/Cu(111) (i.e.,1.00 ML Pd/Cu(111)) model catalysts in detail, and to explore the possible factors controlling the high selectivity on SAAs. Our results clearly demonstrate that the SAA catalyst has higher selectivity for the ethylene formation than that of 1.00 ML Pd/Cu(111), and lower activity for the acetylene conversion compared with that of 1.00 ML Pd/Cu(111). The relatively high selectivity on SAA is mainly due to the facile desorption of ethylene and moderate activity in the dissociation of molecular H2. The main factor which lowers the selectivity towards the ethylene formation on 1.00 ML Pd/Cu(111) is that this system has a higher capacity to promote the breaking of Csbnd H/Csbnd C bonds, which leads to the formation of carbonaceous deposits and polymers such as benzene, and thus reduces the selectivity for the ethylene formation. Meanwhile, it was found that the desorption energy of ethylene on these two surfaces was smaller than the energy barrier of further hydrogenation, which results in the absence of ethane on these two systems. Micro-kinetic model analysis provides a further valuable insight into the evidence for the key factors controlling the catalytic activity and selectivity towards the selective hydrogenation of acetylene. Our findings may help people to design a highly selective hydrogenation catalyst by controlling the balance between the H2 dissociation and Csbnd H/Csbnd C bond broken processes, and a good catalyst should be the one with the modest catalytic activity in the activation of molecular H2. At the same time, the present work provides an extremely significant mechanism of acetylene trimerization to form benzene and carbon formation.

Transgenic medaka fish as models to analyze bone homeostasis under micro-gravity conditions in vivo

NASA Astrophysics Data System (ADS)

Winkler, C.; Wagner, T.; Renn, J.; Goerlich, R.; Schartl, M.

Long-term space flight and microgravity results in bone loss that can be explained by reduced activity of bone-forming osteoblast cells and/or an increase in activity of bone resorbing osteoclast cells. Osteoprotegerin (OPG), a secreted protein of 401 amino acids, has been shown to regulate the balance between osteoblast and osteoclast formation and thereby warrants constant bone mass under normal gravitational conditions. Consistent with this, earlier reports using transgenic mice have shown that increased activation of OPG leads to exc essive bone formation (osteopetrosis), while inactivation of OPG leads to bone loss (osteoporosis). Importantly, it has recently been reported that expression of murine OPG is regulated by vector averaged gravity (Kanematsu et al., 2002, Bone 30, p553). The small bony fish medaka (Oryzias latipes ) has attracted increasing attention as genetic model system to study developmental and pathological processes. To analyze the molecular mechanisms of bone formation in this small vertebrate, we have isolated two related genes, opr-1 and opr -2, from medaka. Our phylogenetic analysis revealed that both genes originated from a common ancestor by fish-specific gene duplication and represent the orthologs of the mammalian OPG gene. Both opr genes are differentially expressed during embryonic and larval development, in adult tissues and in cultured primary osteoblast cells. We have characterized their promoter regions and identified consensus binding sites for transcription factors of the bone-morphogenetic-protein (BMP) p thway and for core-binding-factor-1Aa (cbfa1). Cbfa1 has been shown to be the key regulator of OPG expression during several steps of osteoblast differentiation in mammals. This opens the possibility that the mechanisms controlling bone formation in teleost fish and higher vertebrates are regulated by related mechanisms. We are currently generating transgenic medakafish expressing a GFP reporter gene under control of the teleost OPG promoter in order to visualize osteoblast activity in a living organism under different gravity conditions. This work is supported by the German Aerospace Center, DLR.

The solsticial pause on Mars: 2 modelling and investigation of causes

NASA Astrophysics Data System (ADS)

Mulholland, David P.; Lewis, Stephen R.; Read, Peter L.; Madeleine, Jean-Baptiste; Forget, Francois

2016-01-01

The martian solsticial pause, presented in a companion paper (Lewis et al., 2016), was investigated further through a series of model runs using the UK version of the LMD/UK Mars Global Climate Model. It was found that the pause could not be adequately reproduced if radiatively active water ice clouds were omitted from the model. When clouds were used, along with a realistic time-dependent dust opacity distribution, a substantial minimum in near-surface transient eddy activity formed around solstice in both hemispheres. The net effect of the clouds in the model is, by altering the thermal structure of the atmosphere, to decrease the vertical shear of the westerly jet near the surface around solstice, and thus reduce baroclinic growth rates. A similar effect was seen under conditions of large dust loading, implying that northern midlatitude eddy activity will tend to become suppressed after a period of intense flushing storm formation around the northern cap edge. Suppression of baroclinic eddy generation by the barotropic component of the flow and via diabatic eddy dissipation were also investigated as possible mechanisms leading to the formation of the solsticial pause but were found not to make major contributions. Zonal variations in topography were found to be important, as their presence results in weakened transient eddies around winter solstice in both hemispheres, through modification of the near-surface flow. The zonal topographic asymmetry appears to be the primary reason for the weakness of eddy activity in the southern hemisphere relative to the northern hemisphere, and the ultimate cause of the solsticial pause in both hemispheres. The meridional topographic gradient was found to exert a much weaker influence on near-surface transient eddies.

The effect of the flipped model on achievement in an introductory college physics course

NASA Astrophysics Data System (ADS)

Winter, Joshua Brian

The flipped or inverted classroom model is one in which the time and place for traditional lecture and homework are reversed. Traditional lecture is replaced by online videos assigned as homework. This frees up time in class to be spent with more student centered activities such as discussion based concept questions and group problem solving. While growing in popularity, research on the effectiveness of this format is sparse. In this quasi-experimental study, two sections of an introductory algebra-based college physics course were examined over a five week period. Each section was taught with either the traditional or flipped model and physics knowledge achieved was compared using independent samples t-tests on both the instructor's unit exam and the Mechanics Baseline Test pre/posttest normalized gain. Results indicated that there was no statistically significant difference between the flipped model and the traditional lecture format. Avenues for further research are discussed.

Administration of PDE4 Inhibitors Suppressed the Pannus-Like Inflammation by Inhibition of Cytokine Production by Macrophages and Synovial Fibroblast Proliferation

PubMed Central

Kobayashi, Katsuya; Suda, Toshio; Manabe, Haruhiko; Miki, Ichiro

2007-01-01

A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1β, TNF-α, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-α and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation. PMID:18274640

Administration of PDE4 inhibitors suppressed the pannus-like inflammation by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

PubMed

Kobayashi, Katsuya; Suda, Toshio; Manabe, Haruhiko; Miki, Ichiro

2007-01-01

A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1beta, TNF-alpha, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-alpha and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

Sea anemone actinoporins: the transition from a folded soluble state to a functionally active membrane-bound oligomeric pore.

PubMed

Alegre-Cebollada, J; Oñaderra, M; Gavilanes, J G; del Pozo, A Martínez

2007-12-01

Actinoporins are a family of 20-kDa, basic proteins isolated from sea anemones, whose activity is inhibited by preincubation with sphingomyelin. They are produced in monomeric soluble form but, when binding to the plasma membrane, they oligomerize to produce functional pores which result in cell lysis. Equinatoxin II (EqtII) from Actinia equina and Sticholysin II (StnII) from Stichodactyla helianthus are the actinoporins that have been studied in more detail. Both proteins display a beta-sandwich fold composed of 10 beta-strands flanked on each side by two short alpha-helices. Two-dimensional crystallization on lipid monolayers has allowed the determination of low-resolution models of tetrameric structures distinct from the pore. However, the actual structure of the pore is not known yet. Wild-type EqtII and StnII, as well as a nice collection of natural and artificially made variants of both proteins, have been produced in Escherichia coli and purified. Their characterization has allowed the proposal of a model for the mechanism of pore formation. Four regions of the actinoporins structure seem to play an important role. First, a phosphocholine-binding site and a cluster of exposed aromatic residues, together with a basic region, would be involved in the initial interaction with the membrane, whereas the amphipathic N-terminal region would be essential for oligomerization and pore formation. Accordingly, the model states that pore formation would proceed in at least four steps: Monomer binding to the membrane interface, assembly of four monomers, and at least two distinct conformational changes driving to the final formation of the functional pore.

Evaluating antithrombotic activity of HY023016 on rat hypercoagulable model.

PubMed

Chen, Qiu-Fang; Li, Yun-Zhan; Wang, Xin-Hui; Su, You-Rui; Cui, Shuang; Miao, Ming-Xing; Jiang, Zhen-Zhou; Jiang, Mei-Ling; Jiang, Ai-Dou; Chen, Xiang; Xu, Yun-Gen; Gong, Guo-Qing

2016-06-15

The generation of thrombus is not considered as an isolated progression without other pathologic processes, which may also enhance procoagulant state. The purpose of this study was to assess whether HY023016, a novel dabigatran prodrug and an oral direct thrombin inhibitor, or dabigatran etexilate, another thrombin inhibitor can improve the state of whole blood hypercoagulability in vitro/vivo. By using whole blood flow cytometry we explored the effects of HY023016 and dabigatran etexilate on thrombin and ADP-induced human platelet-leukocyte aggregation generated in vitro. With the method of continuous infusion of thrombin intravenous, we successfully established a rat hypercoagulable model and evaluated the effect of HY023016 or dabigatran etexilate in vivo. HY023016 was able to inhibit thrombin- or ADP-induced platelet P-selectin or CD40L expression, leukocyte CD11b expression and formation of platelet-leukocyte aggregates in dose-dependent manner. Dabigatran etexilate was unable to affect ADP-induced platelet P-selectin or CD40L expression, leukocyte CD11b expression and formation of platelet-leukocyte aggregates. Based on rat hypercoagulable model, dabigatran etexilate could reverse thrombin-induced circulatory system hypercoagulable state in a concentration-dependent manner. Dabigatran etexilate also inhibited electrical stimulation induced formation of arterial thrombus in rat under hypercoagulable state, and extracorporal circulation-induced formation of thrombus in dose-dependent manner. Compared with dabigatran etexilate, HY023016 showed nearly equal or even better antithrombotic activity, regardless of reversing the cycle of rat hypercoagulable state or inhibiting platelet-leukocyte aggregation. In surrmary, HY023016 could effectively improve hypercoagulable state of circulatory system. Copyright © 2016. Published by Elsevier B.V.

Chronic activation of wild-type epidermal growth factor receptor and loss of Cdkn2a cause mouse glioblastoma formation.

PubMed

Acquaviva, Jaime; Jun, Hyun Jung; Lessard, Julie; Ruiz, Rolando; Zhu, Haihao; Donovan, Melissa; Woolfenden, Steve; Boskovitz, Abraham; Raval, Ami; Bronson, Roderick T; Pfannl, Rolf; Whittaker, Charles A; Housman, David E; Charest, Al

2011-12-01

Glioblastoma multiforme (GBM) is characterized by overexpression of epidermal growth factor receptor (EGFR) and loss of the tumor suppressors Ink4a/Arf. Efforts at modeling GBM using wild-type EGFR in mice have proven unsuccessful. Here, we present a unique mouse model of wild-type EGFR-driven gliomagenesis. We used a combination of somatic conditional overexpression and ligand-mediated chronic activation of EGFR in cooperation with Ink4a/Arf loss in the central nervous system of adult mice to generate tumors with the histopathologic and molecular characteristics of human GBMs. Sustained, ligand-mediated activation of EGFR was necessary for gliomagenesis, functionally substantiating the clinical observation that EGFR-positive GBMs from patients express EGFR ligands. To gain a better understanding of the clinically disappointing EGFR-targeted therapies for GBM, we investigated the molecular responses to EGFR tyrosine kinase inhibitor (TKI) treatment in this model. Gefitinib treatment of primary GBM cells resulted in a robust apoptotic response, partially conveyed by mitogen-activated protein kinase (MAPK) signaling attenuation and accompanied by BIM(EL) expression. In human GBMs, loss-of-function mutations in the tumor suppressor PTEN are a common occurrence. Elimination of PTEN expression in GBM cells posttumor formation did not confer resistance to TKI treatment, showing that PTEN status in our model is not predictive. Together, these findings offer important mechanistic insights into the genetic determinants of EGFR gliomagenesis and sensitivity to TKIs and provide a robust discovery platform to better understand the molecular events that are associated with predictive markers of TKI therapy.

Water and complex organic chemistry in the cold dark cloud Barnard 5: Observations and Models

NASA Astrophysics Data System (ADS)

Wirström, Eva; Charnley, Steven B.; Taquet, Vianney; Persson, Carina M.

2015-08-01

Studies of complex organic molecule (COM) formation have traditionally been focused on hot cores in regions of massive star formation, where chemistry is driven by the elevated temperatures - evaporating ices and allowing for endothermic reactions in the gas-phase. As more sensitive instruments have become available, the types of objects known to harbour COMs like acetaldehyde (CH3CHO), dimethyl ether (CH3OCH3), methyl formate (CH3OCHO), and ketene (CH2CO) have expanded to include low mass protostars and, recently, even pre-stellar cores. We here report on the first in a new category of objects harbouring COMs: the cold dark cloud Barnard 5 where non-thermal ice desorption induce complex organic chemistry entirely unrelated to local star-formation.Methanol, which only forms efficiently on the surfaces of dust grains, provide evidence of efficient non-thermal desorption of ices in the form of prominent emission peaks offset from protostellar activity and high density tracers in cold molecular clouds. A study with Herschel targeting such methanol emission peaks resulted in the first ever detection of gas-phase water offset from protostellar activity in a dark cloud, at the so called methanol hotspot in Barnard 5.To model the effect a transient injection of ices into the gas-phase has on the chemistry of a cold, dark cloud we have included gas-grain interactions in an existing gas-phase chemical model and connected it to a chemical reaction network updated and expanded to include the formation and destruction paths of the most common COMs. Results from this model will be presented.Ground-based follow-up studies toward the methanol hotspot in B5 have resulted in the detection of a number of COMs, including CH2CO, CH3CHO, CH3OCH3, and CH3OCHO, as well as deuterated methanol (CH2DOH). Observations have also confirmed that COM emission is extended and not localised to a core structure. The implications of these observational and theoretical studies of B5 will be discussed in the context of the gas-grain interaction in dark clouds and its relation to the chemistry of the earliest phases of low-mass star formation.

Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

PubMed

Chung, Hwa-Jin; Kyung Kim, Won; Joo Park, Hyen; Cho, Lan; Kim, Me-Riong; Kim, Min Jeong; Shin, Joon-Shik; Ho Lee, Jin; Ha, In-Hyuk; Kook Lee, Sang

2016-02-17

Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models. Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model. Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase. Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Unified Model for Methylmercury Formation and Bioaccumulation in the Global Ocean

NASA Astrophysics Data System (ADS)

Zhang, Y.; Schartup, A. T.; Soerensen, A.; Dutkiewicz, S.; Sunderland, E. M.

2017-12-01

Marine fish consumption is the main exposure pathway for methylmercury (MeHg), a neurotoxin, in many countries. The Hg in the ocean is mainly from atmospheric deposition in inorganic forms. How the deposited Hg is methylated and accumulated in biota remain an open question. We develop a 3D model (MITgcm) for MeHg formation and bioaccumulation in the global ocean and evaluate the driving factors. The model is based on a previous published inorganic Hg model and is coupled with the bioaccumulation model for marine methylmercury (BAM3) with ocean biogeochemistry from DARWIN model. We develop a unified scheme that scales methylation by microbe activity and assumes demethylation a function of short wave radiation and temperature. The model result agrees well with currently available observations at the 0-100 m (mod.: 43±52 fM vs obs.: 69±67 fM, 1 fM = 10-15 mol/L), 500 m (360±280 fM vs 340±260 fM), and 1000 m depth (260±170 fM vs 290±210 fM). In the surface ocean, we find the MeHg concentrations are a function of latitude, resulting from photodemethylation. The model reproduces the high concentrations observed over the sub-thermocline of Pacific Subarctic Gyre, which is associated with active microbe activity. On the other hand, both the model and observations suggest low concentrations over oligotrophic regions such as Indian Ocean Gyre. In the tropical oceans, the model predicts the highest MeHg concentrations, consistent with observation, and it is caused by the overlapping high atmospheric deposition and active microbe activities. The model captures the high concentrations in the subsurface of the Arctic and Southern Ocean where low temperature slows down abiotic demethylation. The modeled global average MeHg concentration in phytoplankton is 2.0 ng/g (by wet weight), within the same range of observations. High concentrations are modeled over tropical and high-latitude regions due to the dominance of small sized prochlorococcus and high seawater concentrations, respectively. Due to the different palatability of phytoplankton to zooplankton, the small zooplankton has 96% of MeHg grazed from picoplankton, but the large zooplankton mainly from microplankton (92%). The MeHg concentrations are higher in large zooplankton (9.3 ng/g) than small ones (2.6 ng/g) with spatial patterns influenced by their main food sources.

HOBYS and W43-HERO: Two more steps toward a Galaxy-wide understanding of high-mass star formation

NASA Astrophysics Data System (ADS)

Motte, Frédérique; Bontemps, Sylvain; Tigé, Jérémy

The Herschel/HOBYS key program allows to statistically study the formation of 10-20 M ⊙ stars. The IRAM/W43-HERO large program is itself dedicated to the much more extreme W43 molecular complex, which forms stars up to 50 M ⊙. Both reveal high-density cloud filaments of several pc3, which are forming clusters of OB-type stars. Given their activity, these so-called mini-starburst cloud ridges could be seen as ``miniature and instant models'' of starburst galaxies. Both surveys also strongly suggest that high-mass prestellar cores do not exist, in agreement with the dynamical formation of cloud ridges. The HOBYS and W43 surveys are necessary steps towards Galaxy-wide studies of high-mass star formation.

Determination of Gibbs energies of formation in aqueous solution using chemical engineering tools.

PubMed

Toure, Oumar; Dussap, Claude-Gilles

2016-08-01

Standard Gibbs energies of formation are of primary importance in the field of biothermodynamics. In the absence of any directly measured values, thermodynamic calculations are required to determine the missing data. For several biochemical species, this study shows that the knowledge of the standard Gibbs energy of formation of the pure compounds (in the gaseous, solid or liquid states) enables to determine the corresponding standard Gibbs energies of formation in aqueous solutions. To do so, using chemical engineering tools (thermodynamic tables and a model enabling to predict activity coefficients, solvation Gibbs energies and pKa data), it becomes possible to determine the partial chemical potential of neutral and charged components in real metabolic conditions, even in concentrated mixtures. Copyright © 2016 Elsevier Ltd. All rights reserved.

Radioactive elements on Mercury's surface from MESSENGER: implications for the planet's formation and evolution.

PubMed

Peplowski, Patrick N; Evans, Larry G; Hauck, Steven A; McCoy, Timothy J; Boynton, William V; Gillis-Davis, Jeffery J; Ebel, Denton S; Goldsten, John O; Hamara, David K; Lawrence, David J; McNutt, Ralph L; Nittler, Larry R; Solomon, Sean C; Rhodes, Edgar A; Sprague, Ann L; Starr, Richard D; Stockstill-Cahill, Karen R

2011-09-30

The MESSENGER Gamma-Ray Spectrometer measured the average surface abundances of the radioactive elements potassium (K, 1150 ± 220 parts per million), thorium (Th, 220 ± 60 parts per billion), and uranium (U, 90 ± 20 parts per billion) in Mercury's northern hemisphere. The abundance of the moderately volatile element K, relative to Th and U, is inconsistent with physical models for the formation of Mercury requiring extreme heating of the planet or its precursor materials, and supports formation from volatile-containing material comparable to chondritic meteorites. Abundances of K, Th, and U indicate that internal heat production has declined substantially since Mercury's formation, consistent with widespread volcanism shortly after the end of late heavy bombardment 3.8 billion years ago and limited, isolated volcanic activity since.

Nonlinear Hebbian Learning as a Unifying Principle in Receptive Field Formation.

PubMed

Brito, Carlos S N; Gerstner, Wulfram

2016-09-01

The development of sensory receptive fields has been modeled in the past by a variety of models including normative models such as sparse coding or independent component analysis and bottom-up models such as spike-timing dependent plasticity or the Bienenstock-Cooper-Munro model of synaptic plasticity. Here we show that the above variety of approaches can all be unified into a single common principle, namely nonlinear Hebbian learning. When nonlinear Hebbian learning is applied to natural images, receptive field shapes were strongly constrained by the input statistics and preprocessing, but exhibited only modest variation across different choices of nonlinearities in neuron models or synaptic plasticity rules. Neither overcompleteness nor sparse network activity are necessary for the development of localized receptive fields. The analysis of alternative sensory modalities such as auditory models or V2 development lead to the same conclusions. In all examples, receptive fields can be predicted a priori by reformulating an abstract model as nonlinear Hebbian learning. Thus nonlinear Hebbian learning and natural statistics can account for many aspects of receptive field formation across models and sensory modalities.

Nonlinear Hebbian Learning as a Unifying Principle in Receptive Field Formation

PubMed Central

Gerstner, Wulfram

2016-01-01

The development of sensory receptive fields has been modeled in the past by a variety of models including normative models such as sparse coding or independent component analysis and bottom-up models such as spike-timing dependent plasticity or the Bienenstock-Cooper-Munro model of synaptic plasticity. Here we show that the above variety of approaches can all be unified into a single common principle, namely nonlinear Hebbian learning. When nonlinear Hebbian learning is applied to natural images, receptive field shapes were strongly constrained by the input statistics and preprocessing, but exhibited only modest variation across different choices of nonlinearities in neuron models or synaptic plasticity rules. Neither overcompleteness nor sparse network activity are necessary for the development of localized receptive fields. The analysis of alternative sensory modalities such as auditory models or V2 development lead to the same conclusions. In all examples, receptive fields can be predicted a priori by reformulating an abstract model as nonlinear Hebbian learning. Thus nonlinear Hebbian learning and natural statistics can account for many aspects of receptive field formation across models and sensory modalities. PMID:27690349

Galaxy Formation in Sterile Neutrino Dark Matter Models

NASA Astrophysics Data System (ADS)

Menci, N.; Grazian, A.; Lamastra, A.; Calura, F.; Castellano, M.; Santini, P.

2018-02-01

We investigate galaxy formation in models with dark matter (DM) constituted by sterile neutrinos. Given their large parameter space, defined by the combinations of sterile neutrino mass {m}ν and mixing parameter {\\sin }2(2θ ) with active neutrinos, we focus on models with {m}ν =7 {keV}, consistent with the tentative 3.5 keV line detected in several X-ray spectra of clusters and galaxies. We consider (1) two resonant production models with {\\sin }2(2θ )=5 × {10}-11 and {\\sin }2(2θ )=2 × {10}-10, to cover the range of mixing parameters consistent with the 3.5 keV line; (2) two scalar-decay models, representative of the two possible cases characterizing such a scenario: a freeze-in and a freeze-out case. We also consider thermal warm DM with particle mass {m}X=3 {keV}. Using a semianalytic model, we compare the predictions for the different DM scenarios with a wide set of observables. We find that comparing the predicted evolution of the stellar mass function, the abundance of satellites of Milky Way–like galaxies, and the global star formation history of galaxies with observations does not allow us to disentangle the effects of the baryonic physics from those related to the different DM models. On the other hand, the distribution of the stellar-to-halo mass ratios, the abundance of faint galaxies in the UV luminosity function at z≳ 6, and the specific star formation and age distribution of local, low-mass galaxies constitute potential probes for the DM scenarios considered. We discuss how future observations with upcoming facilities will enable us to rule out or to strongly support DM models based on sterile neutrinos.

Mass distribution in galaxy clusters: the role of Active Galactic Nuclei feedback

NASA Astrophysics Data System (ADS)

Teyssier, Romain; Moore, Ben; Martizzi, Davide; Dubois, Yohan; Mayer, Lucio

2011-06-01

We use 1-kpc resolution cosmological Adaptive Mesh Refinement (AMR) simulations of a Virgo-like galaxy cluster to investigate the effect of feedback from supermassive black holes on the mass distribution of dark matter, gas and stars. We compared three different models: (i) a standard galaxy formation model featuring gas cooling, star formation and supernovae feedback, (ii) a 'quenching' model for which star formation is artificially suppressed in massive haloes and finally (iii) the recently proposed active galactic nucleus (AGN) feedback model of Booth and Schaye. Without AGN feedback (even in the quenching case), our simulated cluster suffers from a strong overcooling problem, with a stellar mass fraction significantly above observed values in M87. The baryon distribution is highly concentrated, resulting in a strong adiabatic contraction (AC) of dark matter. With AGN feedback, on the contrary, the stellar mass in the brightest cluster galaxy (BCG) lies below observational estimates and the overcooling problem disappears. The stellar mass of the BCG is seen to increase with increasing mass resolution, suggesting that our stellar masses converge to the correct value from below. The gas and total mass distributions are in better agreement with observations. We also find a slight deficit (˜10 per cent) of baryons at the virial radius, due to the combined effect of AGN-driven convective motions in the inner parts and shock waves in the outer regions, pushing gas to Mpc scales and beyond. This baryon deficit results in a slight adiabatic expansion of the dark matter distribution that can be explained quantitatively by AC theory.

NDMA formation during drinking water treatment: A multivariate analysis of factors influencing formation.

PubMed

Leavey-Roback, Shannon L; Sugar, Catherine A; Krasner, Stuart W; Suffet, Irwin H Mel

2016-05-15

The formation of the carcinogen N-nitrosodimethylamine (NDMA) during drinking water treatment has raised concerns in the drinking water industry. Many bench-scale laboratory tests and pilot plant studies have been completed to try to determine which factors during water treatment increase or decrease the amount of NDMA formed in drinking water. This study used data from over 20 drinking water treatment plants in the United States and Canada to determine which factors are most highly correlated with the NDMA concentration in delivered water using a mixed effects model with a random intercept. This type of analysis has not been used previously with trihalomethane (THM) models due to the fact that those studies did not sample such a large number and range of plants as was done in this NDMA study. Ultraviolet absorbance at 254 nm (UV254) in the plant influent and pre-chlorination time used at the plant were highly correlated in all models with NDMA concentration in finished water as well as the percentage change between NDMA formation potential in the plant influent and actual formation in the finished water. Specifically, an increase in UV254 absorbance in a model was associated with an increase in NDMA and an increase in pre-chlorination time in a model was associated with a decrease in NDMA. Other water quality parameters including sucralose concentration in the plant influent, polyDADMAC polymer dose, pH, and chlorine-to-ammonia weight ratio used in the plant were also correlated with NDMA concentration in the distribution system. Lastly, NDMA precursor loading was correlated with the use of polyDADMAC (where precursors were added) and the use of ozone and granular activated carbon (GAC) treatment (where precursors were removed). Copyright © 2016 Elsevier Ltd. All rights reserved.

Measuring Star-Formation Rates of AGNs and QSOs using a new calibration from Polycyclic Aromatic Hydrocarbon Emission

NASA Astrophysics Data System (ADS)

Papovich, Casey

Understanding the coevolution of star-formation and supermassive black hole accretion is one of the key questions in galaxy formation theory. This relation is important for understanding why at present the mass in galaxy bulges (on scales of kpc) correlates so tightly with the mass of galaxy central supermassive blackholes (on scales of AU). Feedback from supermassive black hole accretion may also be responsible for heating or expelling cold gas from galaxies, shutting off the fuel for star-formation and additional black hole growth. Did bulges proceed the formation of black holes, or vice versa, or are they contemporaneous? Therefore, understanding the exact rates of star-formation and supermassive black hole growth, and how they evolve with time and galaxy mass has deep implications for how galaxies form. It has previously been nearly impossible to study simultaneously both star-formation and accretion onto supermassive black holes in galaxies because the emission from black hole accretion contaminates nearly all diagnostics of star-formation. The "standard" diagnostics for the star-formation rate (the emission from hydrogen, UV emission, midIR emission, far-IR emission, etc) are not suitable for measuring star-formation rates in galaxies with actively accreting supermassive blackholes. In this proposal, the researchers request NASA/ADP funding for an archival study using spectroscopy with the Spitzer Space Telescope to measure simultaneously the star-formation rate (SFR) and bolometric emission from accreting supermassive blackholes to understand the complex relation between both processes. The key to this study is that they will develop a new calibrator for SFRs in galaxies with active supermassive black holes based on the molecular emission from polycyclic aromatic hydrocarbons (PAHs), which emit strongly in the mid-IR (3 - 20 micron) and are very strong in spectra from the Spitzer Space Telescope. The PAH molecules exist near photo-dissociation regions, and they re-emit a large fraction of the ionization radiation from ongoing star formation. Preliminary work using archival spectra from Spitzer show that the PAH luminosity scales linearly with the SFR with smaller scatter than "gold standard" SFR tracers, such as the (dust corrected) hydrogen emission. The PAH emission becomes important because they are destroyed by the hard UV radiation in the vicinity of accreting supermassive blackholes. Therefore, this makes the PAH emission extremely powerful: it has the unique ability to measure SFRs in galaxies with active supermassive black holes, where every other SFR indicator is contaminated by emission from the supermassive black hole. This objectives for this proposal are to (1) provide a robust recalibration of the SFR from the mid-IR PAH emission features using a large sample of star-forming galaxies in the Spitzer archive; (2) demonstrate the utility of the PAHs to derive valid SFRs from JWST observations, using archival Spitzer spectroscopy for distant galaxies strongly lensed gravitationally; finally, using a large sample of galaxies with Spitzer spectroscopy spanning a large range of total luminosity and AGN activity (from pure starbursts to quasars) to (3) measure the distribution function of the luminosity of star-formation, AGN, and test how these vary with total luminosity and redshift. Theoretical models make strong predictions for this distribution function. Comparing the data to these predictions allows us to test these models directly.

Analysis, modeling, and simulation (AMS) testbed development and evaluation to support dynamic mobility applications (DMA) and active transportation and demand management (ATDM) programs — evaluation report for ATDM program. [supporting datasets - Pasadena Testbed

DOT National Transportation Integrated Search

2017-07-26

This zip file contains POSTDATA.ATT (.ATT); Print to File (.PRN); Portable Document Format (.PDF); and document (.DOCX) files of data to support FHWA-JPO-16-385, Analysis, modeling, and simulation (AMS) testbed development and evaluation to support d...

THE HCN/HNC ABUNDANCE RATIO TOWARD DIFFERENT EVOLUTIONARY PHASES OF MASSIVE STAR FORMATION

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

Jin, Mihwa; Lee, Jeong-Eun; Kim, Kee-Tae, E-mail: mihwajin.sf@gmail.com, E-mail: jeongeun.lee@khu.ac.kr, E-mail: ktkim@kasi.re.kr

2015-07-20

Using the H{sup 13}CN and HN{sup 13}C J = 1–0 line observations, the abundance ratio of HCN/HNC has been estimated for different evolutionary stages of massive star formation: infrared dark clouds (IRDCs), high-mass protostellar objects (HMPOs), and ultracompact H ii regions (UCH iis). IRDCs were divided into “quiescent IRDC cores (qIRDCc)” and “active IRDC cores (aIRDCc),” depending on star formation activity. The HCN/HNC ratio is known to be higher at active and high temperature regions related to ongoing star formation, compared to cold and quiescent regions. Our observations toward 8 qIRDCc, 16 aIRDCc, 23 HMPOs, and 31 UCH iis showmore » consistent results; the ratio is 0.97 (±0.10), 2.65 (±0.88), 4.17 (±1.03), and 8.96 (±3.32) in these respective evolutionary stages, increasing from qIRDCc to UCH iis. The change of the HCN/HNC abundance ratio, therefore, seems directly associated with the evolutionary stages of star formation, which have different temperatures. One suggested explanation for this trend is the conversion of HNC to HCN, which occurs effectively at higher temperatures. To test the explanation, we performed a simple chemical model calculation. In order to fit the observed results, the energy barrier of the conversion must be much lower than the value provided by theoretical calculations.« less

Estimating the kinetic parameters of activated sludge storage using weighted non-linear least-squares and accelerating genetic algorithm.

PubMed

Fang, Fang; Ni, Bing-Jie; Yu, Han-Qing

2009-06-01

In this study, weighted non-linear least-squares analysis and accelerating genetic algorithm are integrated to estimate the kinetic parameters of substrate consumption and storage product formation of activated sludge. A storage product formation equation is developed and used to construct the objective function for the determination of its production kinetics. The weighted least-squares analysis is employed to calculate the differences in the storage product concentration between the model predictions and the experimental data as the sum of squared weighted errors. The kinetic parameters for the substrate consumption and the storage product formation are estimated to be the maximum heterotrophic growth rate of 0.121/h, the yield coefficient of 0.44 mg CODX/mg CODS (COD, chemical oxygen demand) and the substrate half saturation constant of 16.9 mg/L, respectively, by minimizing the objective function using a real-coding-based accelerating genetic algorithm. Also, the fraction of substrate electrons diverted to the storage product formation is estimated to be 0.43 mg CODSTO/mg CODS. The validity of our approach is confirmed by the results of independent tests and the kinetic parameter values reported in literature, suggesting that this approach could be useful to evaluate the product formation kinetics of mixed cultures like activated sludge. More importantly, as this integrated approach could estimate the kinetic parameters rapidly and accurately, it could be applied to other biological processes.

Brains striving for coherence: Long-term cumulative plot formation in the default mode network.

PubMed

Tylén, K; Christensen, P; Roepstorff, A; Lund, T; Østergaard, S; Donald, M

2015-11-01

Many everyday activities, such as engaging in conversation or listening to a story, require us to sustain attention over a prolonged period of time while integrating and synthesizing complex episodic content into a coherent mental model. Humans are remarkably capable of navigating and keeping track of all the parallel social activities of everyday life even when confronted with interruptions or changes in the environment. However, the underlying cognitive and neurocognitive mechanisms of such long-term integration and profiling of information remain a challenge to neuroscience. While brain activity is generally traceable within the short time frame of working memory (milliseconds to seconds), these integrative processes last for minutes, hours or even days. Here we report two experiments on story comprehension. Experiment I establishes a cognitive dissociation between our comprehension of plot and incidental facts in narratives: when episodic material allows for long-term integration in a coherent plot, we recall fewer factual details. However, when plot formation is challenged, we pay more attention to incidental facts. Experiment II investigates the neural underpinnings of plot formation. Results suggest a central role for the brain's default mode network related to comprehension of coherent narratives while incoherent episodes rather activate the frontoparietal control network. Moreover, an analysis of cortical activity as a function of the cumulative integration of narrative material into a coherent story reveals to linear modulations of right hemisphere posterior temporal and parietal regions. Together these findings point to key neural mechanisms involved in the fundamental human capacity for cumulative plot formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Exact solutions to a spatially extended model of kinase-receptor interaction.

PubMed

Szopa, Piotr; Lipniacki, Tomasz; Kazmierczak, Bogdan

2011-10-01

B and Mast cells are activated by the aggregation of the immune receptors. Motivated by this phenomena we consider a simple spatially extended model of mutual interaction of kinases and membrane receptors. It is assumed that kinase activates membrane receptors and in turn the kinase molecules bound to the active receptors are activated by transphosphorylation. Such a type of interaction implies positive feedback and may lead to bistability. In this study we apply the Steklov eigenproblem theory to analyze the linearized model and find exact solutions in the case of non-uniformly distributed membrane receptors. This approach allows us to determine the critical value of receptor dephosphorylation rate at which cell activation (by arbitrary small perturbation of the inactive state) is possible. We found that cell sensitivity grows with decreasing kinase diffusion and increasing anisotropy of the receptor distribution. Moreover, these two effects are cooperating. We showed that the cell activity can be abruptly triggered by the formation of the receptor aggregate. Since the considered activation mechanism is not based on receptor crosslinking by polyvalent antigens, the proposed model can also explain B cell activation due to receptor aggregation following binding of monovalent antigens presented on the antigen presenting cell.

PPAR-gamma pathways attenuate pulmonary granuloma formation in a carbon nanotube induced murine model of sarcoidosis.

PubMed

McPeek, Matthew; Malur, Anagha; Tokarz, Debra A; Murray, Gina; Barna, Barbara P; Thomassen, Mary Jane

2018-06-15

Peroxisome proliferator activated receptor gamma (PPARγ), a ligand activated nuclear transcription factor, is constitutively expressed in alveolar macrophages of healthy individuals. PPARγ deficiencies have been noted in several lung diseases including the alveolar macrophages of pulmonary sarcoidosis patients. We have previously described a murine model of multiwall carbon nanotubes (MWCNT) induced pulmonary granulomatous inflammation which bears striking similarities to pulmonary sarcoidosis, including the deficiency of alveolar macrophage PPARγ. Further studies demonstrate alveolar macrophage PPARγ deficiency exacerbates MWCNT-induced pulmonary granulomas. Based on these observations we hypothesized that activation of PPARγ via administration of the PPARγ-specific ligand rosiglitazone would limit MWCNT-induced granuloma formation and promote PPARγ-dependent pathways. Results presented here show that rosiglitazone significantly limits the frequency and severity of MWCNT-induced pulmonary granulomas. Furthermore, rosiglitazone attenuates alveolar macrophage NF-κB activity and downregulates the expression of the pro-inflammatory mediators, CCL2 and osteopontin. PPARγ activation via rosiglitazone also prevents the MWCNT-induced deficiency of PPARγ-regulated ATP-binding cassette lipid transporter-G1 (ABCG1) expression. ABCG1 is crucial to pulmonary lipid homeostasis. ABCG1 deficiency results in lipid accumulation which promotes pro-inflammatory macrophage activation. Our results indicate that restoration of homeostatic ABCG1 levels by rosiglitazone correlates with both reduced pulmonary lipid accumulation, and decreased alveolar macrophage activation. These data confirm and further support our previous observations that PPARγ pathways are critical in regulating MWCNT-induced pulmonary granulomatous inflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

Simulating Freak Waves in the Ocean with CFD Modeling

NASA Astrophysics Data System (ADS)

Manolidis, M.; Orzech, M.; Simeonov, J.

2017-12-01

Rogue, or freak, waves constitute an active topic of research within the world scientific community, as various maritime authorities around the globe seek to better understand and more accurately assess the risks that the occurrence of such phenomena entail. Several experimental studies have shed some light on the mechanics of rogue wave formation. In our work we numerically simulate the formation of such waves in oceanic conditions by means of Computational Fluid Dynamics (CFD) software. For this purpose we implement the NHWAVE and OpenFOAM software packages. Both are non-hydrostatic, turbulent flow solvers, but NHWAVE implements a shock-capturing scheme at the free surface-interface, while OpenFOAM utilizes the Volume Of Fluid (VOF) method. NHWAVE has been shown to accurately reproduce highly nonlinear surface wave phenomena, such as soliton propagation and wave shoaling. We conducted a range of tests simulating rogue wave formation and horizontally varying currents to evaluate and compare the capabilities of the two software packages. Then we used each model to investigate the effect of ocean currents and current gradients on the formation of rogue waves. We present preliminary results.

The homologous recombination machinery modulates the formation of RNA–DNA hybrids and associated chromosome instability

PubMed Central

Wahba, Lamia; Gore, Steven K; Koshland, Douglas

2013-01-01

Genome instability in yeast and mammals is caused by RNA–DNA hybrids that form as a result of defects in different aspects of RNA biogenesis. We report that in yeast mutants defective for transcription repression and RNA degradation, hybrid formation requires Rad51p and Rad52p. These proteins normally promote DNA–DNA strand exchange in homologous recombination. We suggest they also directly promote the DNA–RNA strand exchange necessary for hybrid formation since we observed accumulation of Rad51p at a model hybrid-forming locus. Furthermore, we provide evidence that Rad51p mediates hybridization of transcripts to homologous chromosomal loci distinct from their site of synthesis. This hybrid formation in trans amplifies the genome-destabilizing potential of RNA and broadens the exclusive co-transcriptional models that pervade the field. The deleterious hybrid-forming activity of Rad51p is counteracted by Srs2p, a known Rad51p antagonist. Thus Srs2p serves as a novel anti-hybrid mechanism in vivo. DOI: http://dx.doi.org/10.7554/eLife.00505.001 PMID:23795288

Vertically uniform formation pathways of tropospheric sulfate aerosols in East China detected from triple stable oxygen and radiogenic sulfur isotopes

NASA Astrophysics Data System (ADS)

Lin, Mang; Biglari, Saman; Zhang, Zhisheng; Crocker, Daniel; Tao, Jun; Su, Binbin; Liu, Lanzhong; Thiemens, Mark H.

2017-05-01

Sulfate aerosols (SO42-) in the continental outflow from East China significantly alter the atmospheric sulfur budget across the Pacific Rim, but its formation pathways, especially in the free troposphere (FT), remain poorly understood. Here we analyze stable oxygen (δ17O and δ18O) and radiogenic sulfur (35S) isotopes in SO42- collected at a mountain site in East China to investigate SO42- formation pathways at varying altitudes. We find that Δ17O (=δ17O-0.52 × δ18O) in SO42- is not correlated with 35S (a direct measure of high-altitude air masses). This pattern notably differs from the currently known 35S-Δ17O relation. The result implies that the formation pathway of tropospheric SO42- in East China is vertically uniform, likely due to large emissions and active convection in this region. Our measurements provide unambiguous isotopic constraints for reducing uncertainties in modeling SO42- in the FT over East China, which greatly affects regional climate but current models fail to accurately estimate.

Interactive educational technologies as a method of communicative competency development of optical and fiber optic communication systems specialists

NASA Astrophysics Data System (ADS)

Matveeva, Tatiana U.; Osadchiy, Igor S.; Husnutdinova, Marina N.

2017-04-01

The article examines the process of formation of communicative competencies of optic and fiber optic communication systems specialists; the role of communicative competencies is examined in the structure of professionally important skills, together with the contents of professional activity. The stages of empirical research into formation of communicative competencies have been presented, and the values of statistical reliability of data have been provided. The model of formation of communicative competency using interactive technology has been developed based on the research done, and main stages of model implementation and motives of formation of communicative competency have been highlighted. A scheme of "Communicative competence as a base of future success" training session has been suggested as one of the basic interactive technologies. Main components of education that are used during the stages of the training cycle have been examined. The statistical data on the effectiveness of use of interactive educational technologies has been presented; it allowed development of communicative competency of specialists in the field of optical and fiber optic communication system.

Groundwater flow with energy transport and water-ice phase change: Numerical simulations, benchmarks, and application to freezing in peat bogs

USGS Publications Warehouse

McKenzie, J.M.; Voss, C.I.; Siegel, D.I.

2007-01-01

In northern peatlands, subsurface ice formation is an important process that can control heat transport, groundwater flow, and biological activity. Temperature was measured over one and a half years in a vertical profile in the Red Lake Bog, Minnesota. To successfully simulate the transport of heat within the peat profile, the U.S. Geological Survey's SUTRA computer code was modified. The modified code simulates fully saturated, coupled porewater-energy transport, with freezing and melting porewater, and includes proportional heat capacity and thermal conductivity of water and ice, decreasing matrix permeability due to ice formation, and latent heat. The model is verified by correctly simulating the Lunardini analytical solution for ice formation in a porous medium with a mixed ice-water zone. The modified SUTRA model correctly simulates the temperature and ice distributions in the peat bog. Two possible benchmark problems for groundwater and energy transport with ice formation and melting are proposed that may be used by other researchers for code comparison. ?? 2006 Elsevier Ltd. All rights reserved.

Origin of the Galaxy Mass-Metallicity-Star Formation Relation

NASA Astrophysics Data System (ADS)

Harwit, Martin; Brisbin, Drew

2015-02-01

We describe an equilibrium model that links the metallicity of low-redshift galaxies to stellar evolution models. It enables the testing of different stellar initial mass functions and metal yields against observed galaxy metallicities. We show that the metallicities of more than 80,000 Sloan Digital Sky Survey galaxies in the low-redshift range 0.07 <= z <= 0.3 considerably constrain stellar evolution models that simultaneously relate galaxy stellar mass, metallicity, and star formation rates to the infall rate of low-metallicity extragalactic gas and outflow of enriched matter. A feature of our model is that it encompasses both the active star forming phases of a galaxy and epochs during which the same galaxy may lie fallow. We show that the galaxy mass-metallicity-star formation relation can be traced to infall of extragalactic gas mixing with native gas from host galaxies to form stars of observed metallicities, the most massive of which eject oxygen into extragalactic space. Most consequential among our findings is that, on average, extragalactic infall accounts for one half of the gas required for star formation, a ratio that is remarkably constant across galaxies with stellar masses ranging at least from M* = 2 × 109 to 6 × 1010 M ⊙. This leads us to propose that star formation is initiated when extragalactic infall roughly doubles the mass of marginally stable interstellar clouds. The processes described may also account quantitatively for the metallicity of extragalactic space, though to check this the fraction of extragalactic baryons will need to be more firmly established.

Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration

NASA Astrophysics Data System (ADS)

Bora, Puran S.; Hu, Zhiwei; Tezel, Tongalp H.; Sohn, Jeong-Hyeon; Kang, Shin Goo; Cruz, Jose M. C.; Bora, Nalini S.; Garen, Alan; Kaplan, Henry J.

2003-03-01

Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.

Active Brownian rods

NASA Astrophysics Data System (ADS)

Peruani, Fernando

2016-11-01

Bacteria, chemically-driven rods, and motility assays are examples of active (i.e. self-propelled) Brownian rods (ABR). The physics of ABR, despite their ubiquity in experimental systems, remains still poorly understood. Here, we review the large-scale properties of collections of ABR moving in a dissipative medium. We address the problem by presenting three different models, of decreasing complexity, which we refer to as model I, II, and III, respectively. Comparing model I, II, and III, we disentangle the role of activity and interactions. In particular, we learn that in two dimensions by ignoring steric or volume exclusion effects, large-scale nematic order seems to be possible, while steric interactions prevent the formation of orientational order at large scales. The macroscopic behavior of ABR results from the interplay between active stresses and local alignment. ABR exhibit, depending on where we locate ourselves in parameter space, a zoology of macroscopic patterns that ranges from polar and nematic bands to dynamic aggregates.

[Psychophysiological aspects of the problem of narcotic dependency].

PubMed

Tursunkhodzhaev, M Kh; Tursunkhodzhaeva, L A

2002-01-01

An attempt has been made at analyzing mechanisms of formation of addiction to narcotics from the standpoint of a systemic approach to a functional organization of psychic activity. A model is proposed of the pathological functional system as the basis of narcodependence, which combines processes of two adjoining levels--those of psychic activity and of higher nervous activity. It is suggested that pathological hyperactivity of the functional structure maintaining the need for a change in the emotional state might be the basis of addiction to narcotic drugs.

ALTERED PHOSPHORYLATION OF MAP KINASE AFTER ACUTE EXPOSURE TO PCB153.

EPA Science Inventory

Long-term potentiation (LTP) is a model of synaptic plasticity believed to encompass the physiological substrate of memory. The mitogen-activated protein kinase (ERK1/2) signalling cascade contributes to synaptic plasticity and to long-term memory formation. Learning and LTP st...

SaeRS Is Responsive to Cellular Respiratory Status and Regulates Fermentative Biofilm Formation in Staphylococcus aureus.

PubMed

Mashruwala, Ameya A; Gries, Casey M; Scherr, Tyler D; Kielian, Tammy; Boyd, Jeffrey M

2017-08-01

Biofilms are multicellular communities of microorganisms living as a quorum rather than as individual cells. The bacterial human pathogen Staphylococcus aureus uses oxygen as a terminal electron acceptor during respiration. Infected human tissues are hypoxic or anoxic. We recently reported that impaired respiration elicits a p rogrammed c ell l ysis (PCL) phenomenon in S. aureus leading to the release of cellular polymers that are utilized to form biofilms. PCL is dependent upon the AtlA murein hydrolase and is regulated, in part, by the SrrAB two-component regulatory system (TCRS). In the current study, we report that the SaeRS TCRS also governs fermentative biofilm formation by positively influencing AtlA activity. The SaeRS-modulated factor fibronectin-binding protein A (FnBPA) also contributed to the fermentative biofilm formation phenotype. SaeRS-dependent biofilm formation occurred in response to changes in cellular respiratory status. Genetic evidence presented suggests that a high cellular titer of phosphorylated SaeR is required for biofilm formation. Epistasis analyses found that SaeRS and SrrAB influence biofilm formation independently of one another. Analyses using a mouse model of orthopedic implant-associated biofilm formation found that both SaeRS and SrrAB govern host colonization. Of these two TCRSs, SrrAB was the dominant system driving biofilm formation in vivo We propose a model wherein impaired cellular respiration stimulates SaeRS via an as yet undefined signal molecule(s), resulting in increasing expression of AtlA and FnBPA and biofilm formation. Copyright © 2017 American Society for Microbiology.

Characterizing the Developmental Trajectory of Sirolimus Clearance in Neonates and Infants

PubMed Central

Emoto, C; Mizuno, T; Schniedewind, B; Christians, Uwe; Adams, DM; Vinks, AA

2016-01-01

Sirolimus is increasingly being used in neonates and infants, but the mechanistic basis of age‐dependent changes in sirolimus disposition has not been fully addressed yet. In order to characterize the age‐dependent changes, serial sirolimus clearance (CL) estimates in individual young pediatric patients were collected and analyzed by population modeling analysis. In addition, sirolimus metabolite formation was also investigated to further substantiate the corresponding age‐dependent change in CYP3A activity. The increasing pattern over time of allometrically size‐normalized sirolimus CL estimates vs. age was well described by a sigmoidal Emax model. This age‐dependent increase was also observed within each individual patient over a 4‐year study period. CYP3A‐dependent sirolimus metabolite formation changed in a similar fashion. This study clearly demonstrates the rapid increase of sirolimus CL over time in neonates and infants, indicating the developmental change. This developmental pattern can be explained by a parallel increase in CYP3A metabolic activity. PMID:27501453

Active cell-matrix coupling regulates cellular force landscapes of cohesive epithelial monolayers

NASA Astrophysics Data System (ADS)

Zhao, Tiankai; Zhang, Yao; Wei, Qiong; Shi, Xuechen; Zhao, Peng; Chen, Long-Qing; Zhang, Sulin

2018-03-01

Epithelial cells can assemble into cohesive monolayers with rich morphologies on substrates due to competition between elastic, edge, and interfacial effects. Here we present a molecularly based thermodynamic model, integrating monolayer and substrate elasticity, and force-mediated focal adhesion formation, to elucidate the active biochemical regulation over the cellular force landscapes in cohesive epithelial monolayers, corroborated by microscopy and immunofluorescence studies. The predicted extracellular traction and intercellular tension are both monolayer size and substrate stiffness dependent, suggestive of cross-talks between intercellular and extracellular activities. Our model sets a firm ground toward a versatile computational framework to uncover the molecular origins of morphogenesis and disease in multicellular epithelia.

Galaxy modelling. II. Multi-wavelength faint counts from a semi-analytic model of galaxy formation

NASA Astrophysics Data System (ADS)

Devriendt, J. E. G.; Guiderdoni, B.

2000-11-01

This paper predicts self-consistent faint galaxy counts from the UV to the submm wavelength range. The stardust spectral energy distributions described in Devriendt et al. \\citeparyear{DGS99} (Paper I) are embedded within the explicit cosmological framework of a simple semi-analytic model of galaxy formation and evolution. We begin with a description of the non-dissipative and dissipative collapses of primordial perturbations, and plug in standard recipes for star formation, stellar evolution and feedback. We also model the absorption of starlight by dust and its re-processing in the IR and submm. We then build a class of models which capture the luminosity budget of the universe through faint galaxy counts and redshift distributions in the whole wavelength range spanned by our spectra. In contrast with a rather stable behaviour in the optical and even in the far-IR, the submm counts are dramatically sensitive to variations in the cosmological parameters and changes in the star formation history. Faint submm counts are more easily accommodated within an open universe with a low value of Omega_0 , or a flat universe with a non-zero cosmological constant. We confirm the suggestion of Guiderdoni et al. \\citeparyear{GHBM98} that matching the current multi-wavelength data requires a population of heavily-extinguished, massive galaxies with large star formation rates ( ~ 500 M_sun yr-1) at intermediate and high redshift (z >= 1.5). Such a population of objects probably is the consequence of an increase of interaction and merging activity at high redshift, but a realistic quantitative description can only be obtained through more detailed modelling of such processes. This study illustrates the implementation of multi-wavelength spectra into a semi-analytic model. In spite of its simplicity, it already provides fair fits of the current data of faint counts, and a physically motivated way of interpolating and extrapolating these data to other wavelengths and fainter flux levels.

Nucleation and growth in alkaline zinc electrodeposition An Experimental and Theoretical study

NASA Astrophysics Data System (ADS)

Desai, Divyaraj

The current work seeks to investigate the nucleation and growth of zinc electrodeposition in alkaline electrolyte, which is of commercial interest to alkaline zinc batteries for energy storage. The morphology of zinc growth places a severe limitation on the typical cycle life of such batteries. The formation of mossy zinc leads to a progressive deterioration of battery performance while zinc dendrites are responsible for sudden catastrophic battery failure. The problems are identified as the nucleation-controlled formation of mossy zinc and the transport-limited formation of dendritic zinc. Consequently, this thesis work seeks to investigate and accurately simulate the conditions under which such morphologies are formed. The nucleation and early-stage growth of Zn electrodeposits is studied on carbon-coated TEM grids. At low overpotentials, the morphology develops by aggregation at two distinct length scales: ~5 nm diameter monocrystalline nanoclusters form ~50nm diameter polycrystalline aggregates, and second, the aggregates form a branched network. Epitaxial (0002) growth above a critical overpotential leads to the formation of hexagonal single-crystals. A kinetic model is provided using the rate equations of vapor solidification to simulate the evolution of the different morphologies. On solving these equations, we show that aggregation is attributed to cluster impingement and cluster diffusion while single-crystal formation is attributed to direct attachment. The formation of dendritic zinc is investigated using in-operando transmission X-ray microscopy which is a unique technique for imaging metal electrodeposits. The nucleation density of zinc nuclei is lowered using polyaniline films to cover the active nucleation sites. The effect of overpotential is investigated and the morphology shows beautiful in-operando formation of symmetric zinc crystals. A linear perturbation model was developed to predict the growth and formation of these crystals to first-order accuracy. Existing phase-field models of solidification and electrodeposition are used to simulate the growth and formation of individual zinc crystals. The driving force for solidification models (i.e. supersaturation) is reinterpreted in terms of overpotential under the assumption of a conductive electrolyte. The final morphologies are astonishingly similar to those observed in dynamical experiments. Further, the phase-field models obey the predictions of the linear perturbation analysis, which gives good credibility to the phase-field approach to simulate electrodeposition processes.

Spiral and never-settling patterns in active systems

NASA Astrophysics Data System (ADS)

Yang, X.; Marenduzzo, D.; Marchetti, M. C.

2014-01-01

We present a combined numerical and analytical study of pattern formation in an active system where particles align, possess a density-dependent motility, and are subject to a logistic reaction. The model can describe suspensions of reproducing bacteria, as well as polymerizing actomyosin gels in vitro or in vivo. In the disordered phase, we find that motility suppression and growth compete to yield stable or blinking patterns, which, when dense enough, acquire internal orientational ordering to give asters or spirals. We predict these may be observed within chemotactic aggregates in bacterial fluids. In the ordered phase, the reaction term leads to previously unobserved never-settling patterns which can provide a simple framework to understand the formation of motile and spiral patterns in intracellular actin systems.

Lecithin:Cholesterol Acyltransferase Activation by Sulfhydryl-Reactive Small Molecules: Role of Cysteine-31

PubMed Central

Freeman, Lita A.; Demosky, Stephen J.; Konaklieva, Monika; Kuskovsky, Rostislav; Aponte, Angel; Ossoli, Alice F.; Gordon, Scott M.; Koby, Ross F.; Manthei, Kelly A.; Shen, Min; Vaisman, Boris L.; Shamburek, Robert D.; Jadhav, Ajit; Calabresi, Laura; Gucek, Marjan; Tesmer, John J.G.; Levine, Rodney L.

2017-01-01

Lecithin:cholesterol acyltransferase (LCAT) catalyzes plasma cholesteryl ester formation and is defective in familial lecithin:cholesterol acyltransferase deficiency (FLD), an autosomal recessive disorder characterized by low high-density lipoprotein, anemia, and renal disease. This study aimed to investigate the mechanism by which compound A [3-(5-(ethylthio)-1,3,4-thiadiazol-2-ylthio)pyrazine-2-carbonitrile], a small heterocyclic amine, activates LCAT. The effect of compound A on LCAT was tested in human plasma and with recombinant LCAT. Mass spectrometry and nuclear magnetic resonance were used to determine compound A adduct formation with LCAT. Molecular modeling was performed to gain insight into the effects of compound A on LCAT structure and activity. Compound A increased LCAT activity in a subset (three of nine) of LCAT mutations to levels comparable to FLD heterozygotes. The site-directed mutation LCAT-Cys31Gly prevented activation by compound A. Substitution of Cys31 with charged residues (Glu, Arg, and Lys) decreased LCAT activity, whereas bulky hydrophobic groups (Trp, Leu, Phe, and Met) increased activity up to 3-fold (P < 0.005). Mass spectrometry of a tryptic digestion of LCAT incubated with compound A revealed a +103.017 m/z adduct on Cys31, consistent with the addition of a single hydrophobic cyanopyrazine ring. Molecular modeling identified potential interactions of compound A near Cys31 and structural changes correlating with enhanced activity. Functional groups important for LCAT activation by compound A were identified by testing compound A derivatives. Finally, sulfhydryl-reactive β-lactams were developed as a new class of LCAT activators. In conclusion, compound A activates LCAT, including some FLD mutations, by forming a hydrophobic adduct with Cys31, thus providing a mechanistic rationale for the design of future LCAT activators. PMID:28576974

Leakage detection of Marcellus Shale natural gas at an Upper Devonian gas monitoring well: a 3-d numerical modeling approach.

PubMed

Zhang, Liwei; Anderson, Nicole; Dilmore, Robert; Soeder, Daniel J; Bromhal, Grant

2014-09-16

Potential natural gas leakage into shallow, overlying formations and aquifers from Marcellus Shale gas drilling operations is a public concern. However, before natural gas could reach underground sources of drinking water (USDW), it must pass through several geologic formations. Tracer and pressure monitoring in formations overlying the Marcellus could help detect natural gas leakage at hydraulic fracturing sites before it reaches USDW. In this study, a numerical simulation code (TOUGH 2) was used to investigate the potential for detecting leaking natural gas in such an overlying geologic formation. The modeled zone was based on a gas field in Greene County, Pennsylvania, undergoing production activities. The model assumed, hypothetically, that methane (CH4), the primary component of natural gas, with some tracer, was leaking around an existing well between the Marcellus Shale and the shallower and lower-pressure Bradford Formation. The leaky well was located 170 m away from a monitoring well, in the Bradford Formation. A simulation study was performed to determine how quickly the tracer monitoring could detect a leak of a known size. Using some typical parameters for the Bradford Formation, model results showed that a detectable tracer volume fraction of 2.0 × 10(-15) would be noted at the monitoring well in 9.8 years. The most rapid detection of tracer for the leak rates simulated was 81 days, but this scenario required that the leakage release point was at the same depth as the perforation zone of the monitoring well and the zones above and below the perforation zone had low permeability, which created a preferred tracer migration pathway along the perforation zone. Sensitivity analysis indicated that the time needed to detect CH4 leakage at the monitoring well was very sensitive to changes in the thickness of the high-permeability zone, CH4 leaking rate, and production rate of the monitoring well.

Differential roles of tissue factor and phosphatidylserine in activation of coagulation.

PubMed

Spronk, Henri M H; ten Cate, Hugo; van der Meijden, Paola E J

2014-05-01

It has been suggested that the main physiological trigger of coagulation, tissue factor, possesses limited procoagulant activity and occurs in an inactive or so-called encrypted state. For the conversion of encrypted into decrypted tissue factor with sufficient procoagulant activity, four distinct models have been proposed: 1; dimer formation, 2; lipid rafts, 3; disulfide bonds, and 4; phosphatidylserine exposure. Pro and cons can be given for each of these mechanisms of tissue factor encryption/decryption, however, it seems most likely that two or more mechanisms act together in activating the procoagulant activity. The exposure of phosphatidylserine in the outer layer of cell membranes supports coagulation through enhanced formation of the tenase (factors IXa, VIIIa and X) and prothrombinase (factors Xa, Va and prothrombin) complexes. The proposed role for phosphatidylserine in decryption of tissue factor could contribute to the correct orientation of the tissue factor - factor VII complex. Overall, the contribution of both tissue factor and phosphatidylserine to coagulation seems distinct with tissue factor being the physiological activator and phosphatidylserine the driving force of propagation of coagulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Galaxy formation in the Planck cosmology - IV. Mass and environmental quenching, conformity and clustering

NASA Astrophysics Data System (ADS)

Henriques, Bruno M. B.; White, Simon D. M.; Thomas, Peter A.; Angulo, Raul E.; Guo, Qi; Lemson, Gerard; Wang, Wenting

2017-08-01

We study the quenching of star formation as a function of redshift, environment and stellar mass in the galaxy formation simulations of Henriques et al. (2015), which implement an updated version of the Munich semi-analytic model (L-GALAXIES) on the two Millennium Simulations after scaling to a Planck cosmology. In this model, massive galaxies are quenched by active galactic nucleus (AGN) feedback depending on both black hole and hot gas mass, and hence indirectly on stellar mass. In addition, satellite galaxies of any mass can be quenched by ram-pressure or tidal stripping of gas and through the suppression of gaseous infall. This combination of processes produces quenching efficiencies which depend on stellar mass, host halo mass, environment density, distance to group centre and group central galaxy properties in ways which agree qualitatively with observation. Some discrepancies remain in dense regions and close to group centres, where quenching still seems too efficient. In addition, although the mean stellar age of massive galaxies agrees with observation, the assumed AGN feedback model allows too much ongoing star formation at late times. The fact that both AGN feedback and environmental effects are stronger in higher density environments leads to a correlation between the quenching of central and satellite galaxies which roughly reproduces observed conformity trends inside haloes.

Staphylococcus aureus β-Toxin Mutants Are Defective in Biofilm Ligase and Sphingomyelinase Activity, and Causation of Infective Endocarditis and Sepsis.

PubMed

Herrera, Alfa; Vu, Bao G; Stach, Christopher S; Merriman, Joseph A; Horswill, Alexander R; Salgado-Pabón, Wilmara; Schlievert, Patrick M

2016-05-03

β-Toxin is an important virulence factor of Staphylococcus aureus, contributing to colonization and development of disease [Salgado-Pabon, W., et al. (2014) J. Infect. Dis. 210, 784-792; Huseby, M. J., et al. (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 14407-14412; Katayama, Y., et al. (2013) J. Bacteriol. 195, 1194-1203]. This cytotoxin has two distinct mechanisms of action: sphingomyelinase activity and DNA biofilm ligase activity. However, the distinct mechanism that is most important for its role in infective endocarditis is unknown. We characterized the active site of β-toxin DNA biofilm ligase activity by examining deficiencies in site-directed mutants through in vitro DNA precipitation and biofilm formation assays. Possible conformational changes in mutant structure compared to that of wild-type toxin were assessed preliminarily by trypsin digestion analysis, retention of sphingomyelinase activity, and predicted structures based on the native toxin structure. We addressed the contribution of each mechanism of action to producing infective endocarditis and sepsis in vivo in a rabbit model. The H289N β-toxin mutant, lacking sphingomyelinase activity, exhibited lower sepsis lethality and infective endocarditis vegetation formation compared to those of the wild-type toxin. β-Toxin mutants with disrupted biofilm ligase activity did not exhibit decreased sepsis lethality but were deficient in infective endocarditis vegetation formation compared to the wild-type protein. Our study begins to characterize the DNA biofilm ligase active site of β-toxin and suggests β-toxin functions importantly in infective endocarditis through both of its mechanisms of action.

Dynamic model based on voltage transfer curve for pattern formation in dielectric barrier glow discharge

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

Li, Ben; He, Feng; Ouyang, Jiting, E-mail: jtouyang@bit.edu.cn

2015-12-15

Simulation work is very important for understanding the formation of self-organized discharge patterns. Previous works have witnessed different models derived from other systems for simulation of discharge pattern, but most of these models are complicated and time-consuming. In this paper, we introduce a convenient phenomenological dynamic model based on the basic dynamic process of glow discharge and the voltage transfer curve (VTC) to study the dielectric barrier glow discharge (DBGD) pattern. VTC is an important characteristic of DBGD, which plots the change of wall voltage after a discharge as a function of the initial total gap voltage. In the modeling,more » the combined effect of the discharge conditions is included in VTC, and the activation-inhibition effect is expressed by a spatial interaction term. Besides, the model reduces the dimensionality of the system by just considering the integration effect of current flow. All these greatly facilitate the construction of this model. Numerical simulations turn out to be in good accordance with our previous fluid modeling and experimental result.« less

Inhibition of Biofilm Formation, Quorum Sensing and Infection in Pseudomonas aeruginosa by Natural Products-Inspired Organosulfur Compounds

PubMed Central

Cady, Nathaniel C.; McKean, Kurt A.; Behnke, Jason; Kubec, Roman; Mosier, Aaron P.; Kasper, Stephen H.; Burz, David S.; Musah, Rabi A.

2012-01-01

Using a microplate-based screening assay, the effects on Pseudomonas aeruginosa PAO1 biofilm formation of several S-substituted cysteine sulfoxides and their corresponding disulfide derivatives were evaluated. From our library of compounds, S-phenyl-L-cysteine sulfoxide and its breakdown product, diphenyl disulfide, significantly reduced the amount of biofilm formation by P. aeruginosa at levels equivalent to the active concentration of 4-nitropyridine-N-oxide (NPO) (1 mM). Unlike NPO, which is an established inhibitor of bacterial biofilms, our active compounds did not reduce planktonic cell growth and only affected biofilm formation. When used in a Drosophila-based infection model, both S-phenyl-L-cysteine sulfoxide and diphenyl disulfide significantly reduced the P. aeruginosa recovered 18 h post infection (relative to the control), and were non-lethal to the fly hosts. The possibility that the observed biofilm inhibitory effects were related to quorum sensing inhibition (QSI) was investigated using Escherichia coli-based reporters expressing P. aeruginosa lasR or rhIR response proteins, as well as an endogenous P. aeruginosa reporter from the lasI/lasR QS system. Inhibition of quorum sensing by S-phenyl-L-cysteine sulfoxide was observed in all of the reporter systems tested, whereas diphenyl disulfide did not exhibit QSI in either of the E. coli reporters, and showed very limited inhibition in the P. aeruginosa reporter. Since both compounds inhibit biofilm formation but do not show similar QSI activity, it is concluded that they may be functioning by different pathways. The hypothesis that biofilm inhibition by the two active compounds discovered in this work occurs through QSI is discussed. PMID:22715388

Inhibitory effects of ethyl acetate extract of Teucrium polium on in vitro protein glycoxidation.

PubMed

Ardestani, Amin; Yazdanparast, Razieh

2007-12-01

Regarding the involvement of free radicals and oxidative reactions in protein glycoxidation processes, compounds with antioxidant activities have been tested in order to reduce or to stop glycoxidation. In this study, we evaluated the antioxidant potential of several organic fractions of Teucrium polium extract using different model systems including total antioxidant capacity by the phosphomolybdenum method, ferric reducing antioxidant power and Trolox equivalent antioxidant capacity assays, antioxidant activity in linoleic acid emulsion system and scavenging of 1,1-diphenyl-2-picrylhydrazyl radical. The results indicated that the ethyl acetate (EtOAc) fraction of T. polium possesses the highest antioxidant activity and total phenolic and flavonoid contents. Given the link between glycation and oxidation, we proposed that the EtOAc fraction might possess significant in vitro antiglycation activities as well. Our data confirmed the inhibitory effect of EtOAc fraction on bovine serum albumin (BSA) glycoxidation measured in terms of advanced glycation end products (AGEs) and pentosidine formation as well as protein oxidation markers including protein carbonyl formation (PCO) and loss of protein thiols. Reducing sugars such as ribose and glucose increase fluorescence intensity of glycated BSA in terms of total AGEs and pentosidine during 21 day of exposure. Moreover, sugars cause more PCO formation and also oxidize thiol groups more in glycated than in native BSA. EtOAc extract at different concentrations (10-100 microg/ml) has significantly quenched the fluorescence intensity of glycated BSA. Furthermore, we demonstrated that the inhibitory effect of EtOAc extract in preventing oxidative protein damages including effect on PCO formation and thiol oxidation which are believe to form under the glycoxidation process. These results clearly demonstrate that, the EtOAc fraction, owning to its antioxidant content, is capable of suppressing the formation of AGEs and protein oxidation in vitro.

Heterologous Expression of sahH Reveals That Biofilm Formation Is Autoinducer-2-independent in Streptococcus sanguinis but Is Associated with an Intact Activated Methionine Cycle*

PubMed Central

Redanz, Sylvio; Standar, Kerstin; Podbielski, Andreas; Kreikemeyer, Bernd

2012-01-01

Numerous studies have claimed deleterious effects of LuxS mutation on many bacterial phenotypes, including bacterial biofilm formation. Genetic complementation mostly restored the observed mutant phenotypes to WT levels, leading to the postulation that quorum sensing via a family of molecules generically termed autoinducer-2 (AI-2) is essential for many phenotypes. Because LuxS mutation has dual effects, this hypothesis needs to be investigated into the details for each bacterial species. In this study we used S. sanguinis SK36 as a model biofilm bacterium and employed physiological characterization and transcriptome approaches on WT and luxS-deficient strains, in combination with chemical, luxS, and sahH complementation experiments. SahH enables a direct conversion of SAH to homocysteine and thereby restores the activated methionine cycle in a luxS-negative background without formation of the AI-2 precursor 4,5-dihydroxy-2,3-pentanedione. With this strategy we were able to dissect the individual contribution of LuxS and AI-2 activity in detail. Our data revealed that S. sanguinis biofilm formation is independent from AI-2 substance pools and is rather supported by an intact activated methyl cycle. Of 216 differentially transcribed genes in the luxS mutant, 209 were restored by complementation with a gene encoding the S-adenosylhomocysteine hydrolase. Only nine genes, mainly involved in natural competence, were directly affected by the AI-2 quorum-sensing substance pool. Cumulatively, this suggested that biofilm formation in S. sanguinis is not under control of AI-2. Our study suggests that previously evaluated LuxS mutants in other species need to be revisited to resolve the precise contribution of AI-2 substance pools and the methionine pathways. PMID:22942290

Hypoxic cell waves around necrotic cores in glioblastoma: a biomathematical model and its therapeutic implications.

PubMed

Martínez-González, Alicia; Calvo, Gabriel F; Pérez Romasanta, Luis A; Pérez-García, Víctor M

2012-12-01

Glioblastoma is a rapidly evolving high-grade astrocytoma that is distinguished pathologically from lower grade gliomas by the presence of necrosis and microvascular hyperplasia. Necrotic areas are typically surrounded by hypercellular regions known as "pseudopalisades" originated by local tumor vessel occlusions that induce collective cellular migration events. This leads to the formation of waves of tumor cells actively migrating away from central hypoxia. We present a mathematical model that incorporates the interplay among two tumor cell phenotypes, a necrotic core and the oxygen distribution. Our simulations reveal the formation of a traveling wave of tumor cells that reproduces the observed histologic patterns of pseudopalisades. Additional simulations of the model equations show that preventing the collapse of tumor microvessels leads to slower glioma invasion, a fact that might be exploited for therapeutic purposes.

Intercentrosomal angular separation during mitosis plays a crucial role for maintaining spindle stability

NASA Astrophysics Data System (ADS)

Sutradhar, S.; Basu, S.; Paul, R.

2015-10-01

Cell division through proper spindle formation is one of the key puzzles in cell biology. In most mammalian cells, chromosomes spontaneously arrange to achieve a stable bipolar spindle during metaphase which eventually ensures proper segregation of the DNA into the daughter cells. In this paper, we present a robust three-dimensional mechanistic model to investigate the formation and maintenance of a bipolar mitotic spindle in mammalian cells under different physiological constraints. Using realistic parameters, we test spindle viability by measuring the spindle length and studying the chromosomal configuration. The model strikingly predicts a feature of the spindle instability arising from the insufficient intercentrosomal angular separation and impaired sliding of the interpolar microtubules. In addition, our model successfully reproduces chromosomal patterns observed in mammalian cells, when activity of different motor proteins is perturbed.

Using an ACTIVE teaching format versus a standard lecture format for increasing resident interaction and knowledge achievement during noon conference: a prospective, controlled study

PubMed Central

2014-01-01

Background The traditional lecture is used by many residency programs to fulfill the mandate for regular didactic sessions, despite limited evidence to demonstrate its effectiveness. Active teaching strategies have shown promise in improving medical knowledge but have been challenging to implement within the constraints of residency training. We developed and evaluated an innovative structured format for interactive teaching within the residency noon conference. Methods We developed an ACTIVE teaching format structured around the following steps: assemble (A) into groups, convey (C) learning objectives, teach (T) background information, inquire (I) through cases and questions, verify (V) understanding, and explain (E) answer choices and educate on the learning points. We conducted a prospective, controlled study of the ACTIVE teaching format versus the standard lecture format, comparing resident satisfaction, immediate knowledge achievement and long-term knowledge retention. We qualitatively assessed participating faculty members’ perspectives on the faculty development efforts and the feasibility of teaching using the ACTIVE format. Results Sixty-nine internal medicine residents participated in the study. Overall, there was an improvement in perceived engagement using the ACTIVE teaching format (4.78 vs. 3.80, P < 0.01), with no increase in stress or decrement in break time. There was an improvement in initial knowledge achievement with the ACTIVE teaching format (overall absolute score increase of 11%, P = 0.04) and a trend toward improvement in long-term knowledge retention. Faculty members felt adequately prepared to use the ACTIVE teaching format, and enjoyed teaching with the ACTIVE teaching format more than the standard lecture. Conclusions A structured ACTIVE teaching format improved resident engagement and initial knowledge, and required minimal resources. The ACTIVE teaching format offers an exciting alternative to the standard lecture for resident noon conference and is easy to implement. PMID:24985781

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

John F. Schabron; A. Troy Pauli; Joseph F. Rovani Jr.

The dispersed particle solution model of petroleum residua structure was used to develop predictors for pyrolytic coke formation. Coking Indexes were developed in prior years that measure how near a pyrolysis system is to coke formation during the coke formation induction period. These have been demonstrated to be universally applicable for residua regardless of the source of the material. Coking onset is coincidental with the destruction of the ordered structure and the formation of a multiphase system. The amount of coke initially formed appears to be a function of the free solvent volume of the original residua. In the currentmore » work, three-dimensional coke make predictability maps were developed at 400 C, 450 C, and 500 C (752 F, 842 F, and 932 F). These relate residence time and free solvent volume to the amount of coke formed at a particular pyrolysis temperature. Activation energies for two apparent types of zero-order coke formation reactions were estimated. The results provide a new tool for ranking residua, gauging proximity to coke formation, and predicting initial coke make tendencies.« less

Mechanisms for the target patterns formation in a stochastic bistable excitable medium

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Yu.; Verveyko, Darya V.; Postnov, Dmitry E.

2018-04-01

We study the features of formation and evolution of spatiotemporal chaotic regime generated by autonomous pacemakers in excitable deterministic and stochastic bistable active media using the example of the FitzHugh - Nagumo biological neuron model under discrete medium conditions. The following possible mechanisms for the formation of autonomous pacemakers have been studied: 1) a temporal external force applied to a small region of the medium, 2) geometry of the solution region (the medium contains regions with Dirichlet or Neumann boundaries). In our work we explore the conditions for the emergence of pacemakers inducing target patterns in a stochastic bistable excitable system and propose the algorithm for their analysis.

Is there any evidence that ionized outflows quench star formation in type 1 quasars at z < 1?

NASA Astrophysics Data System (ADS)

Balmaverde, B.; Marconi, A.; Brusa, M.; Carniani, S.; Cresci, G.; Lusso, E.; Maiolino, R.; Mannucci, F.; Nagao, T.

2016-01-01

Aims: The aim of this paper is to test the basic model of negative active galactic nuclei (AGN) feedback. According to this model, once the central black hole accretes at the Eddington limit and reaches a certain critical mass, AGN driven outflows blow out gas, suppressing star formation in the host galaxy and self-regulating black hole growth. Methods: We consider a sample of 224 quasars selected from the Sloan Digital Sky Survey (SDSS) at z< 1 observed in the infrared band by the Herschel Space Observatory in point source photometry mode. We evaluate the star formation rate in relation to several outflow signatures traced by the [O III] λ4959, 5007 and [O II] λ3726, 3729 emission lines in about half of the sample with high quality spectra. Results: Most of the quasars show asymmetric and broad wings in [O III], which we interpret as outflow signatures. We separate the quasars in two groups, "weakly" and "strongly" outflowing, using three different criteria. When we compare the mean star formation rate in five redshift bins in the two groups, we find that the star formation rate (SFR) are comparable or slightly larger in the strongly outflowing quasars. We estimate the stellar mass from spectral energy distribution (SED) fitting and the quasars are distributed along the star formation main sequence, although with a large scatter. The scatter from this relation is uncorrelated with respect to the kinematic properties of the outflow. Moreover, for quasars dominated in the infrared by starburst or by AGN emission, we do not find any correlation between the star formation rate and the velocity of the outflow, a trend previously reported in the literature for pure starburst galaxies. Conclusions: We conclude that the basic AGN negative feedback scenario seems not to agree with our results. Although we use a large sample of quasars, we did not find any evidence that the star formation rate is suppressed in the presence of AGN driven outflows on large scale. A possibility is that feedback is effective over much longer timescales than those of single episodes of quasar activity.

The Rise and Fall of Star Formation Histories of Blue Galaxies at Redshifts 0.2 < z < 1.4

NASA Technical Reports Server (NTRS)

Pacifici, Camilla; Kassin, Susan A.; Weiner, Benjamin; Charlot, Stephane; Gardner, Jonathan P.

2012-01-01

Popular cosmological scenarios predict that galaxies form hierarchically from the merger of many progenitor, each with their own unique star formation history (SFH). We use the approach recently developed by Pacifici et al. to constrain the SFHs of 4517 blue (presumably star-forming) galaxies with spectroscopic redshifts in the range O.2 < z < 1:4 from the All-Wavelength Extended Groth Strip International Survey (AEGIS). This consists in the Bayesian analysis of the observed galaxy spectral ' energy distributions with a comprehensive library of synthetic spectra assembled using state-of-the-art models of star formation and chemical enrichment histories, stellar population synthesis, nebular emission and attenuation by dust. We constrain the SFH of each galaxy in our sample by comparing the observed fluxes in the B, R,l and K(sub s) bands and rest-frame optical emission-line luminosities with those of one million model spectral energy distributions. We explore the dependence of the resulting SFH on galaxy stellar mass and redshift. We find that the average SFHs of high-mass galaxies rise and fall in a roughly symmetric bell-shaped manner, while those of low-mass galaxies rise progressively in time, consistent with the typically stronger activity of star formation in low-mass compared to high-mass galaxies. For galaxies of all masses, the star formation activity rises more rapidly at high than at low redshift. These findings imply that the standard approximation of exponentially declining SFHs wIdely used to interpret observed galaxy spectral energy distributions is not appropriate to constrain the physical parameters of star-forming galaxies at intermediate redshifts.

STAR FORMATION ACTIVITY IN THE GALACTIC H II COMPLEX S255-S257

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

Ojha, D. K.; Ghosh, S. K.; Samal, M. R.

We present results on the star formation activity of an optically obscured region containing an embedded cluster (S255-IR) and molecular gas between two evolved H II regions, S255 and S257. We have studied the complex using optical and near-infrared (NIR) imaging, optical spectroscopy, and radio continuum mapping at 15 GHz, along with Spitzer-IRAC results. We found that the main exciting sources of the evolved H II regions S255 and S257 and the compact H II regions associated with S255-IR are of O9.5-B3 V nature, consistent with previous observations. Our NIR observations reveal 109 likely young stellar object (YSO) candidates inmore » an area of {approx}4.'9 x 4.'9 centered on S255-IR, which include 69 new YSO candidates. To see the global star formation, we constructed the V - I/V diagram for 51 optically identified IRAC YSOs in an area of {approx}13' x 13' centered on S255-IR. We suggest that these YSOs have an approximate age between 0.1 and 4 Myr, indicating a non-coeval star formation. Using spectral energy distribution models, we constrained physical properties and evolutionary status of 31 and 16 YSO candidates outside and inside the gas ridge, respectively. The models suggest that the sources associated with the gas ridge are younger (mean age {approx}1.2 Myr) than the sources outside the gas ridge (mean age {approx}2.5 Myr). The positions of the young sources inside the gas ridge at the interface of the H II regions S255 and S257 favor a site of induced star formation.« less

Emergent Vortex Patterns in Systems of Self-Propelled, Chiral Particles

NASA Astrophysics Data System (ADS)

Huber, Lorenz; Denk, Jonas; Reithmann, Emanuel; Frey, Erwin

Self-organization of FtsZ polymers is vital for Z-ring assembly during bacterial cell division, and has been studied using reconstituted in vitro model systems. Employing Brownian dynamics simulations and a Boltzmann approach, we model FtsZ polymers as active particles moving along chiral circular paths. With both theoretical approaches we find self-organization into vortex structures and characterize different states in parameter states. Our work demonstrates that these patterns are robust and are generic for active chiral matter. Moreover, we show that the dynamics at the onset of pattern formation is described by a generalized complex Ginzburg-Landau equation.

"ABC's Earthquake" (Experiments and models in seismology)

NASA Astrophysics Data System (ADS)

Almeida, Ana

2017-04-01

Ana Almeida, Portugal Almeida, Ana Escola Básica e Secundária Dr. Vieira de Carvalho Moreira da Maia, Portugal The purpose of this presentation, in poster format, is to disclose an activity which was planned and made by me, in a school on the north of Portugal, using a kit of materials simple and easy to use - the sismo-box. The activity "ABC's Earthquake" was developed under the discipline of Natural Sciences, with students from 7th grade, geosciences teachers and other areas. The possibility of work with the sismo-box was seen as an exciting and promising opportunity to promote science, seismology more specifically, to do science, when using the existing models in the box and with them implement the scientific method, to work and consolidate content and skills in the area of Natural Sciences, to have a time of sharing these materials with classmates, and also with other teachers from the different areas. Throughout the development of the activity, either with students or teachers, it was possible to see the admiration by the models presented in the earthquake-box, as well as, the interest and the enthusiasm in wanting to move and understand what the results after the proposed procedure in the script. With this activity, we managed to promote: - educational success in this subject; a "school culture" with active participation, with quality, rules, discipline and citizenship values; fully integration of students with special educational needs; strengthen the performance of the school as a cultural, informational and formation institution; provide activities to date and innovative; foment knowledge "to be, being and doing" and contribute to a moment of joy and discovery.Learn by doing!

Controlled Delivery of a Focal Adhesion Kinase Inhibitor Results in Accelerated Wound Closure with Decreased Scar Formation.

PubMed

Ma, Kun; Kwon, Sun Hyung; Padmanabhan, Jagannath; Duscher, Dominik; Trotsyuk, Artem A; Dong, Yixiao; Inayathullah, Mohammed; Rajadas, Jayakumar; Gurtner, Geoffrey C

2018-05-15

Formation of scars following wounding or trauma represents a significant healthcare burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, due to the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries. To address this issue, we have developed a pullulan collagen-based hydrogel to deliver FAKI to excisional and burn wounds in mice. Specifically, two distinct drug-laden hydrogels were developed for rapid or sustained release of FAKI for treatment of burn wounds and excisional wounds, respectively. Controlled delivery of FAKI via pullulan collagen hydrogels accelerated wound healing, reduced collagen deposition and activation of scar forming myofibroblasts in both wound healing models. Our study highlights a biomaterial-based drug delivery approach for wound and scar management that has significant translational implications. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Pavement cells: a model system for non-transcriptional auxin signalling and crosstalks

PubMed Central

Chen, Jisheng; Wang, Fei; Zheng, Shiqin; Xu, Tongda; Yang, Zhenbiao

2015-01-01

Auxin (indole acetic acid) is a multifunctional phytohormone controlling various developmental patterns, morphogenetic processes, and growth behaviours in plants. The transcription-based pathway activated by the nuclear TRANSPORT INHIBITOR RESISTANT 1/auxin-related F-box auxin receptors is well established, but the long-sought molecular mechanisms of non-transcriptional auxin signalling remained enigmatic until very recently. Along with the establishment of the Arabidopsis leaf epidermal pavement cell (PC) as an exciting and amenable model system in the past decade, we began to gain insight into non-transcriptional auxin signalling. The puzzle-piece shape of PCs forms from intercalated or interdigitated cell growth, requiring local intra- and inter-cellular coordination of lobe and indent formation. Precise coordination of this interdigitated pattern requires auxin and an extracellular auxin sensing system that activates plasma membrane-associated Rho GTPases from plants and subsequent downstream events regulating cytoskeletal reorganization and PIN polarization. Apart from auxin, mechanical stress and cytokinin have been shown to affect PC interdigitation, possibly by interacting with auxin signals. This review focuses upon signalling mechanisms for cell polarity formation in PCs, with an emphasis on non-transcriptional auxin signalling in polarized cell expansion and pattern formation and how different auxin pathways interplay with each other and with other signals. PMID:26047974

Physical activity interventions using mass media, print media, and information technology.

PubMed

Marcus, B H; Owen, N; Forsyth, L H; Cavill, N A; Fridinger, F

1998-11-01

Media-based physical activity interventions include a variety of print, graphic, audiovisual, and broadcast media programs intended to influence behavior change. New information technology allows print to be delivered in personalized, interactive formats that may enhance efficacy. Media-based interventions have been shaped by conceptual models from health education, Social Cognitive Theory, the Transtheoretical Model, and Social Marketing frameworks. We reviewed 28 studies of media-based interventions of which seven were mass media campaigns at the state or national level and the remaining 21 were delivered through health care, the workplace, or in the community. Recall of mass-media messages generally was high, but mass-media campaigns had very little impact on physical activity behavior. Interventions using print and/or telephone were effective in changing behavior in the short term. Studies in which there were more contacts and interventions tailored to the target audience were most effective. A key issue for research on media-based physical activity interventions is reaching socially disadvantaged groups for whom access, particularly to new forms of communication technology, may be limited. There is a clear need for controlled trials comparing different forms and intensities of media-based physical activity interventions. Controlled studies of personalized print, interactive computer-mediated programs, and web-based formats for program delivery also are needed. The integration of media-based methods into public and private sector service delivery has much potential for innovation.

Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin

PubMed Central

Foley, Jonathan H.; Walton, Bethany L.; Aleman, Maria M.; O'Byrne, Alice M.; Lei, Victor; Harrasser, Micaela; Foley, Kimberley A.; Wolberg, Alisa S.; Conway, Edward M.

2016-01-01

Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied. In a murine venous thrombosis model, levels of thrombin–antithrombin complexes poorly correlated with C3a and C5a, excluding a central role for thrombin in C3a/C5a production. However, clot weight strongly correlated with C5a, suggesting processes triggered during thrombosis promote C5a generation. Since thrombosis elicits fibrinolysis, we hypothesized that plasmin activates C5 during thrombosis. In vitro, the catalytic efficiency of plasmin-mediated C5a generation greatly exceeded that of thrombin or factor Xa, but was similar to the recognized complement C5 convertases. Plasmin-activated C5 yielded a functional membrane attack complex (MAC). In an arterial thrombosis model, plasminogen activator administration increased C5a levels. Overall, these findings suggest plasmin bridges thrombosis and the immune response by liberating C5a and inducing MAC assembly. These new insights may lead to the development of strategies to limit thrombus formation and/or enhance resolution. PMID:27077125

Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms.

PubMed

Wolach, Ofir; Sellar, Rob S; Martinod, Kimberly; Cherpokova, Deya; McConkey, Marie; Chappell, Ryan J; Silver, Alexander J; Adams, Dylan; Castellano, Cecilia A; Schneider, Rebekka K; Padera, Robert F; DeAngelo, Daniel J; Wadleigh, Martha; Steensma, David P; Galinsky, Ilene; Stone, Richard M; Genovese, Giulio; McCarroll, Steven A; Iliadou, Bozenna; Hultman, Christina; Neuberg, Donna; Mullally, Ann; Wagner, Denisa D; Ebert, Benjamin L

2018-04-11

Thrombosis is a major cause of morbidity and mortality in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), clonal disorders of hematopoiesis characterized by activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. Neutrophil extracellular trap (NET) formation, a component of innate immunity, has been linked to thrombosis. We demonstrate that neutrophils from patients with MPNs are primed for NET formation, an effect blunted by pharmacological inhibition of JAK signaling. Mice with conditional knock-in of Jak2 V617F , the most common molecular driver of MPN, have an increased propensity for NET formation and thrombosis. Inhibition of JAK-STAT signaling with the clinically available JAK2 inhibitor ruxolitinib abrogated NET formation and reduced thrombosis in a deep vein stenosis murine model. We further show that expression of PAD4, a protein required for NET formation, is increased in JAK2 V617F -expressing neutrophils and that PAD4 is required for Jak2 V617F -driven NET formation and thrombosis in vivo. Finally, in a population study of more than 10,000 individuals without a known myeloid disorder, JAK2 V617F -positive clonal hematopoiesis was associated with an increased incidence of thrombosis. In aggregate, our results link JAK2 V617F expression to NET formation and thrombosis and suggest that JAK2 inhibition may reduce thrombosis in MPNs through cell-intrinsic effects on neutrophil function. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Anti-atherosclerotic activities of flavonoids from the flowers of Helichrysum arenarium L. MOENCH through the pathway of anti-inflammation.

PubMed

Mao, Zhonghua; Gan, Chunli; Zhu, Jiuxin; Ma, Nan; Wu, Lijun; Wang, Libo; Wang, Xiaobo

2017-06-15

We have successfully established AS model using thoracic aortas vascular ring which evaluated by the morphological changes of blood vessels, the proliferation of VSMC, and the expression of inflammation factors VEGF, CRP, JNK2 and p38. This AS model has the advantages of low cost, convenient and short period of established time. Moreover, we investigated the anti-AS activities of 7 flavonoids Narirutin (1), Naringin (2), Eriodictyol (3), Luteolin (4), Galuteolin (5), Astragalin (6), Kaempferol (7) from flowers of Helichrysum arenarium L. MOENCH by examining the vascular morphology, the inhibition on the expression of inflammation factors CRP, VEGF, JNK2, p38. In addition, we investigated the anti-AS activities of these 7 flavonoids by examining NO secretion of RAW264.7 cells in response to LPS. All above inflammation factors have been proved to be involved in the formation of AS. After comprehensive analysis of all results to discuss the structure-activity relationship, we summarized the conclusions at follow: compounds 1-7 could inhibit the expression of VEGF, CRP, JNK2, p38 and NO at different level, and we evaluated that flavonol aglycone have more significant anti-inflammation than it's glycoside, and the anti-AS activity of flavonols were stronger than flavanones and flavones, which means that 3-group might be the effective group. Eventually, we supposed the main anti-inflammatory mechanism of these compounds was to reduce the expression of CRP, inhibit the kinases activity of JNK2 and p38, and then the MAPK pathway was suppressed, which resulted in the decrease of NO synthesis, VEGF expression and endothelial adhesion factor expression. And eventually, the scar tissue and vascular stenosis formations were prevented. This conclusion suggested flavonoids have the potential of preventing AS formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modelling reveals kinetic advantages of co-transcriptional splicing.

PubMed

Aitken, Stuart; Alexander, Ross D; Beggs, Jean D

2011-10-01

Messenger RNA splicing is an essential and complex process for the removal of intron sequences. Whereas the composition of the splicing machinery is mostly known, the kinetics of splicing, the catalytic activity of splicing factors and the interdependency of transcription, splicing and mRNA 3' end formation are less well understood. We propose a stochastic model of splicing kinetics that explains data obtained from high-resolution kinetic analyses of transcription, splicing and 3' end formation during induction of an intron-containing reporter gene in budding yeast. Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing. Model comparison is used to assess the alternative representations of reactions. Modelling also indicates the functional coupling of transcription and splicing, because both the rate of initiation of transcription and the probability that step one of splicing occurs co-transcriptionally are reduced, when the second step of splicing is abolished in a mutant reporter.

Molecular gas excitation in Kleinmann-Low nebula

NASA Astrophysics Data System (ADS)

Callejo, Gonzague; Lemaire, Jean-Louis; Le Petit, F.; Pineau Des Forets, Guillaume; Field, David

2004-12-01

The Orion molecular cloud OMC-1 is the perfect object for the study of the dense interstellar medium accounting for active star formation; the intrinsic complexity of this region serves as a stallion, both for observing techniques and for interstellar medium modelling. A detailed dynamic and spectroscopic study has been performed using VLT and CFHT observations of the infrared Kleinmann-Low nebula; yielding a complete small-scale structure in velocity and most importantly powerful diagnosis tools in order to put a new light into the gas behaviour. These results allow to build up a consistent model of the gas excitation, and a clear dynamical view of the region. The crucial action of the shock waves is confirmed, and the discrepancies between the observations and the standard models are discussed. The consequences of this modelling will be discussed in terms of extinction, magnetic field, and other quantities related to induced star formation. The goodness of the models used for the interpretations will be also discussed and some future directions of investigation enhanced.

Mast cells mediate malignant pleural effusion formation.

PubMed

Giannou, Anastasios D; Marazioti, Antonia; Spella, Magda; Kanellakis, Nikolaos I; Apostolopoulou, Hara; Psallidas, Ioannis; Prijovich, Zeljko M; Vreka, Malamati; Zazara, Dimitra E; Lilis, Ioannis; Papaleonidopoulos, Vassilios; Kairi, Chrysoula A; Patmanidi, Alexandra L; Giopanou, Ioanna; Spiropoulou, Nikolitsa; Harokopos, Vaggelis; Aidinis, Vassilis; Spyratos, Dionisios; Teliousi, Stamatia; Papadaki, Helen; Taraviras, Stavros; Snyder, Linda A; Eickelberg, Oliver; Kardamakis, Dimitrios; Iwakura, Yoichiro; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Kalomenidis, Ioannis; Blackwell, Timothy S; Agalioti, Theodora; Stathopoulos, Georgios T

2015-06-01

Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1β, which in turn induced pleural vasculature leakiness and triggered NF-κB activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell-induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenocarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable.

Mast cells mediate malignant pleural effusion formation

PubMed Central

Giannou, Anastasios D.; Marazioti, Antonia; Spella, Magda; Kanellakis, Nikolaos I.; Apostolopoulou, Hara; Psallidas, Ioannis; Prijovich, Zeljko M.; Vreka, Malamati; Zazara, Dimitra E.; Lilis, Ioannis; Papaleonidopoulos, Vassilios; Kairi, Chrysoula A.; Patmanidi, Alexandra L.; Giopanou, Ioanna; Spiropoulou, Nikolitsa; Harokopos, Vaggelis; Aidinis, Vassilis; Spyratos, Dionisios; Teliousi, Stamatia; Papadaki, Helen; Taraviras, Stavros; Snyder, Linda A.; Eickelberg, Oliver; Kardamakis, Dimitrios; Iwakura, Yoichiro; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Kalomenidis, Ioannis; Blackwell, Timothy S.; Agalioti, Theodora; Stathopoulos, Georgios T.

2015-01-01

Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1β, which in turn induced pleural vasculature leakiness and triggered NF-κB activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell–induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenocarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable. PMID:25915587

The suppression of star formation by powerful active galactic nuclei.

PubMed

Page, M J; Symeonidis, M; Vieira, J D; Altieri, B; Amblard, A; Arumugam, V; Aussel, H; Babbedge, T; Blain, A; Bock, J; Boselli, A; Buat, V; Castro-Rodríguez, N; Cava, A; Chanial, P; Clements, D L; Conley, A; Conversi, L; Cooray, A; Dowell, C D; Dubois, E N; Dunlop, J S; Dwek, E; Dye, S; Eales, S; Elbaz, D; Farrah, D; Fox, M; Franceschini, A; Gear, W; Glenn, J; Griffin, M; Halpern, M; Hatziminaoglou, E; Ibar, E; Isaak, K; Ivison, R J; Lagache, G; Levenson, L; Lu, N; Madden, S; Maffei, B; Mainetti, G; Marchetti, L; Nguyen, H T; O'Halloran, B; Oliver, S J; Omont, A; Panuzzo, P; Papageorgiou, A; Pearson, C P; Pérez-Fournon, I; Pohlen, M; Rawlings, J I; Rigopoulou, D; Riguccini, L; Rizzo, D; Rodighiero, G; Roseboom, I G; Rowan-Robinson, M; Sánchez Portal, M; Schulz, B; Scott, D; Seymour, N; Shupe, D L; Smith, A J; Stevens, J A; Trichas, M; Tugwell, K E; Vaccari, M; Valtchanov, I; Viero, M; Vigroux, L; Wang, L; Ward, R; Wright, G; Xu, C K; Zemcov, M

2012-05-09

The old, red stars that constitute the bulges of galaxies, and the massive black holes at their centres, are the relics of a period in cosmic history when galaxies formed stars at remarkable rates and active galactic nuclei (AGN) shone brightly as a result of accretion onto black holes. It is widely suspected, but unproved, that the tight correlation between the mass of the black hole and the mass of the stellar bulge results from the AGN quenching the surrounding star formation as it approaches its peak luminosity. X-rays trace emission from AGN unambiguously, whereas powerful star-forming galaxies are usually dust-obscured and are brightest at infrared and submillimetre wavelengths. Here we report submillimetre and X-ray observations that show that rapid star formation was common in the host galaxies of AGN when the Universe was 2-6 billion years old, but that the most vigorous star formation is not observed around black holes above an X-ray luminosity of 10(44) ergs per second. This suppression of star formation in the host galaxy of a powerful AGN is a key prediction of models in which the AGN drives an outflow, expelling the interstellar medium of its host and transforming the galaxy's properties in a brief period of cosmic time.

The Suppression of Star Formation by Powerful Active Galactic Nuclei

NASA Technical Reports Server (NTRS)

Dwek, E.

2012-01-01

The old, red stars that constitute the bulges of galaxies, and the massive black holes at their centres, are the relics of a period in cosmic history when galaxies formed stars at remarkable rates and active galactic nuclei (AGN) shone brightly as a result of accretion onto black holes. It is widely suspected, but unproved, that the tight corre1ation between the mass of the black hole and the mas. of the stellar bulge results from the AGN quenching the surrounding star formation as it approaches its peak luminosity. X-rays trace emission from AGN unambiguously, whereas powerful star-forming ga1axies are usually dust-obscured and are brightest at infrared and submillimeter wavelengths. Here we report submillimetre and X-ray observations that show that rapid star formation was common in the host galaxies of AGN when the Universe was 2-6 billion years old, but that the most vigorous star formation is not observed around black holes above an X-ray luminosity of 10(exp 44) ergs per second. This suppression of star formation in the host galaxy of a powerful AGN is a key prediction of models in which the AGN drives an outflow, expe11ing the interstellar medium of its host and transforming the galaxy's properties in a brief period of cosmic time.

The assessment of a structured online formative assessment program: a randomised controlled trial

PubMed Central

2014-01-01

Background Online formative assessment continues to be an important area of research and methods which actively engage the learner and provide useful learning outcomes are of particular interest. This study reports on the outcomes of a two year study of medical students using formative assessment tools. Method The study was conducted over two consecutive years using two different strategies for engaging students. The Year 1 strategy involved voluntary use of the formative assessment tool by 129 students. In Year 2, a second cohort of 130 students was encouraged to complete the formative assessment by incorporating summative assessment elements into it. Outcomes from pre and post testing students around the formative assessment intervention were used as measures of learning. To compare improvement scores between the two years a two-way Analysis of Variance (ANOVA) model was fitted to the data. Results The ANOVA model showed that there was a significant difference in improvement scores between students in the two years (mean improvement percentage 19% vs. 38.5%, p < 0.0001). Students were more likely to complete formative assessment items if they had a summative component. In Year 2, the time spent using the formative assessment tool had no impact on student improvement, nor did the number of assessment items completed. Conclusion The online medium is a valuable learning resource, capable of providing timely formative feedback and stimulating student-centered learning. However the production of quality content is a time-consuming task and careful consideration must be given to the strategies employed to ensure its efficacy. Course designers should consider the potential positive impact summative components to formative assessment may have on student engagement and outcomes. PMID:24400883

Star formation in galaxy mergers with realistic models of stellar feedback and the interstellar medium

NASA Astrophysics Data System (ADS)

Hopkins, Philip F.; Cox, Thomas J.; Hernquist, Lars; Narayanan, Desika; Hayward, Christopher C.; Murray, Norman

2013-04-01

We use hydrodynamic simulations with detailed, explicit models for stellar feedback to study galaxy mergers. These high-resolution (˜1 pc) simulations follow the formation and destruction of individual giant molecular clouds (GMC) and star clusters. We find that the final starburst is dominated by in situ star formation, fuelled by gas which flows inwards due to global torques. The resulting high gas density results in rapid star formation. The gas is self-gravitating, and forms massive (≲1010 M⊙) GMC and subsequently super star clusters (with masses up to 108 M⊙). However, in contrast to some recent simulations, the bulk of new stars which eventually form the central bulge are not born in super-clusters which then sink to the centre of the galaxy. This is because feedback efficiently disperses GMC after they turn several per cent of their mass into stars. In other words, most of the mass that reaches the nucleus does so in the form of gas. The Kennicutt-Schmidt law emerges naturally as a consequence of feedback balancing gravitational collapse, independent of the small-scale star formation microphysics. The same mechanisms that drive this relation in isolated galaxies, in particular radiation pressure from infrared photons, extend, with no fine-tuning, over seven decades in star formation rate (SFR) to regulate star formation in the most extreme starburst systems with densities ≳104 M⊙ pc-2. This feedback also drives super-winds with large mass-loss rates; however, a significant fraction of the wind material falls back on to the discs at later times, leading to higher post-starburst SFRs in the presence of stellar feedback. This suggests that strong active galactic nucleus feedback may be required to explain the sharp cut-offs in SFR that are observed in post-merger galaxies. We compare the results to those from simulations with no explicit resolution of GMC or feedback [`effective equation-of-state' (EOS) models]. We find that global galaxy properties are similar between EOS and resolved-feedback models. The relic structure and mass profile, and the total mass of stars formed in the nuclear starburst are quite similar, as is the morphological structure during and after mergers (tails, bridges, etc.). Disc survival in sufficiently gas rich mergers is similar in the two cases, and the new models follow the same scalings as derived for the efficiency of disc re-formation after a merger as derived from previous work with the simplified EOS models. While the global galaxy properties are similar between EOS and feedback models, subgalaxy-scale properties and the SFRs can be quite different: the more detailed models exhibit significantly higher star formation in tails and bridges (especially in shocks), and allow us to resolve the formation of super star clusters. In the new models, the star formation is more strongly time-variable and drops more sharply between close passages. The instantaneous burst enhancement can be higher or lower, depending on the details of the orbit and initial structural properties of the galaxies; first-passage bursts are more sensitive to these details than those at the final coalescence.

Prediction of damage formation in hip arthroplasties by finite element analysis using computed tomography images.

PubMed

Abdullah, Abdul Halim; Todo, Mitsugu; Nakashima, Yasuharu

2017-06-01

Femoral bone fracture is one of the main causes for the failure of hip arthroplasties (HA). Being subjected to abrupt and high impact forces in daily activities may lead to complex loading configuration such as bending and sideway falls. The objective of this study is to predict the risk of femoral bone fractures in total hip arthroplasty (THA) and resurfacing hip arthroplasty (RHA). A computed tomography (CT) based on finite element analysis was conducted to demonstrate damage formation in a three dimensional model of HAs. The inhomogeneous model of femoral bone was constructed from a 79 year old female patient with hip osteoarthritis complication. Two different femoral components were modeled with titanium alloy and cobalt chromium and inserted into the femoral bones to present THA and RHA models respectively. The analysis included six configurations, which exhibited various loading and boundary conditions, including axial compression, torsion, lateral bending, stance and two types of falling configurations. The applied hip loadings were normalized to body weight (BW) and accumulated from 1 BW to 3 BW. Predictions of damage formation in the femoral models were discussed as the resulting tensile failure as well as the compressive yielding and failure elements. The results indicate that loading directions can forecast the pattern and location of fractures at varying magnitudes of loading. Lateral bending configuration experienced the highest damage formation in both THA and RHA models. Femoral neck and trochanteric regions were in a common location in the RHA model in most configurations, while the predicted fracture locations in THA differed as per the Vancouver classification. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Do You See What I See? Exploring the Consequences of Luminosity Limits in Black Hole–Galaxy Evolution Studies

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

Jones, Mackenzie L.; Hickox, Ryan C.; DiPompeo, Michael A.

In studies of the connection between active galactic nuclei (AGNs) and their host galaxies, there is widespread disagreement on some key aspects of the connection. These disagreements largely stem from a lack of understanding of the nature of the full underlying AGN population. Recent attempts to probe this connection utilize both observations and simulations to correct for a missed population, but presently are limited by intrinsic biases and complicated models. We take a simple simulation for galaxy evolution and add a new prescription for AGN activity to connect galaxy growth to dark matter halo properties and AGN activity to starmore » formation. We explicitly model selection effects to produce an “observed” AGN population for comparison with observations and empirically motivated models of the local universe. This allows us to bypass the difficulties inherent in models that attempt to infer the AGN population by inverting selection effects. We investigate the impact of selecting AGNs based on thresholds in luminosity or Eddington ratio on the “observed” AGN population. By limiting our model AGN sample in luminosity, we are able to recreate the observed local AGN luminosity function and specific star formation-stellar mass distribution, and show that using an Eddington ratio threshold introduces less bias into the sample by selecting the full range of growing black holes, despite the challenge of selecting low-mass black holes. We find that selecting AGNs using these various thresholds yield samples with different AGN host galaxy properties.« less

BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

PubMed Central

Rosati, Alessandra; Basile, Anna; D'Auria, Raffaella; d'Avenia, Morena; De Marco, Margot; Falco, Antonia; Festa, Michelina; Guerriero, Luana; Iorio, Vittoria; Parente, Roberto; Pascale, Maria; Marzullo, Liberato; Franco, Renato; Arra, Claudio; Barbieri, Antonio; Rea, Domenica; Menichini, Giulio; Hahne, Michael; Bijlsma, Maarten; Barcaroli, Daniela; Sala, Gianluca; di Mola, Fabio Francesco; di Sebastiano, Pierluigi; Todoric, Jelena; Antonucci, Laura; Corvest, Vincent; Jawhari, Anass; Firpo, Matthew A; Tuveson, David A; Capunzo, Mario; Karin, Michael; De Laurenzi, Vincenzo; Turco, Maria Caterina

2015-01-01

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential. PMID:26522614

BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages.

PubMed

Rosati, Alessandra; Basile, Anna; D'Auria, Raffaella; d'Avenia, Morena; De Marco, Margot; Falco, Antonia; Festa, Michelina; Guerriero, Luana; Iorio, Vittoria; Parente, Roberto; Pascale, Maria; Marzullo, Liberato; Franco, Renato; Arra, Claudio; Barbieri, Antonio; Rea, Domenica; Menichini, Giulio; Hahne, Michael; Bijlsma, Maarten; Barcaroli, Daniela; Sala, Gianluca; di Mola, Fabio Francesco; di Sebastiano, Pierluigi; Todoric, Jelena; Antonucci, Laura; Corvest, Vincent; Jawhari, Anass; Firpo, Matthew A; Tuveson, David A; Capunzo, Mario; Karin, Michael; De Laurenzi, Vincenzo; Turco, Maria Caterina

2015-11-02

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential.

[Bone remodeling and modeling/mini-modeling.

PubMed

Hasegawa, Tomoka; Amizuka, Norio

Modeling, adapting structures to loading by changing bone size and shapes, often takes place in bone of the fetal and developmental stages, while bone remodeling-replacement of old bone into new bone-is predominant in the adult stage. Modeling can be divided into macro-modeling(macroscopic modeling)and mini-modeling(microscopic modeling). In the cellular process of mini-modeling, unlike bone remodeling, bone lining cells, i.e., resting flattened osteoblasts covering bone surfaces will become active form of osteoblasts, and then, deposit new bone onto the old bone without mediating osteoclastic bone resorption. Among the drugs for osteoporotic treatment, eldecalcitol(a vitamin D3 analog)and teriparatide(human PTH[1-34])could show mini-modeling based bone formation. Histologically, mature, active form of osteoblasts are localized on the new bone induced by mini-modeling, however, only a few cell layer of preosteoblasts are formed over the newly-formed bone, and accordingly, few osteoclasts are present in the region of mini-modeling. In this review, histological characteristics of bone remodeling and modeling including mini-modeling will be introduced.

Evaluation of Asteraceae herbal extracts in the management of diabetes and obesity. Contribution of caffeoylquinic acids on the inhibition of digestive enzymes activity and formation of advanced glycation end-products (in vitro).

PubMed

Spínola, Vítor; Castilho, Paula C

2017-11-01

The study was performed to assess, for the first time, the in vitro anti-diabetic potential of ten Asteraceae plant extracts to inhibit the activity of digestive enzymes (α-amylase, α-, β-glucosidases and lipase) responsible for hydrolysis/digestion of sugar and lipids. Prevention of advanced glycation end-products (AGEs) formation was evaluated in bovine serum albumin/ribose glycation reaction model. The phytochemical profiles and caffeoylquinic acids (CQAs) contents were determined for the methanolic extract of each plant. Analyzed plant extracts exhibited significant inhibitory activity against key digestive enzymes linked to type II diabetes and obesity. A strong inhibition was observed for glucosidases and mild activity towards amylase and lipase (compared to reference compounds). Moreover, some extracts exhibited potent ability to prevent formation of AGEs, implicated in some diabetic complications. Caffeoylquinic acids were dominant in all plant extracts and findings demonstrate that these compounds are the most relevant hypoglycemic and anti-glycation agents. From the obtained results, Argyranthemum pinnatifidum, Helichrysum melaleucum, and Phagnalon lowei are good candidates for further development of phyto-pharmaceutical preparations as complementary therapy for diabetes and obesity control. Copyright © 2017 Elsevier Ltd. All rights reserved.

β-Escin Effectively Modulates HUVECS Proliferation and Tube Formation.

PubMed

Varinská, Lenka; Fáber, Lenka; Kello, Martin; Petrovová, Eva; Balážová, Ľudmila; Solár, Peter; Čoma, Matúš; Urdzík, Peter; Mojžiš, Ján; Švajdlenka, Emil; Mučaji, Pavel; Gál, Peter

2018-01-17

In the present study we evaluated the anti-angiogenic activities of β-escin (the major active compound of Aesculus hippocastanum L. seeds). Human umbilical-vein endothelial cells (HUVECs) were used as an in vitro model for studying the molecular mechanism underlying the anti-angiogenic effect of β-escin. We investigated the in vitro effects on proliferation, migration, and tube formation of HUVECs and in vivo anti-angiogenic activity was evaluated in a chick chorioallantoic membrane (CAM) angiogenesis assay. Moreover, the effect on gene expressions was determined by the RT2 ProfilerTM human angiogenesis PCR Array. It was found that β-escin exerts inhibitory effect on the basic fibroblast growth factor (bFGF)-induced proliferation, migration and tube formation, as well as CAM angiogenesis in vivo. The inhibition of critical steps of angiogenic process observed with β-escin could be partially explained by suppression of Akt activation in response to bFGF. Moreover, the anti-angiogenic effects of β-escin could also be mediated via inhibition of EFNB2 and FGF-1 gene expressions in endothelial cells. In conclusion, β-escin affects endothelial cells as a negative mediator of angiogenesis in vitro and in vivo and may therefore be considered as a promising candidate for further research elucidating its underlying mechanism of action.

High-efficiency Agrobacterium rhizogenes-mediated transformation of heat inducible sHSP18.2-GUS in Nicotiana tabacum.

PubMed

Chen, Shih-Cheng; Liu, Hui-Wen; Lee, Kung-Ta; Yamakawa, Takashi

2007-01-01

The chimerical gene, Arabidopsis thaliana sHSP18.2 promoter fused to E. coli gusA gene, was Agrobacterium rhizogenes-mediated transformed into Nicotiana tabacum as a heat-regulatable model, and the thermo-inducible expression of GUS activity in N. tabacum transgenic hairy roots was profiled. An activation of A. rhizogenes with acetosyringone (AS) before cocultured with tobacco's leaf disc strongly promoted transgenic hairy roots formation. Transgenic hairy roots formation efficiency of A. rhizogenes precultured with 200 microM AS supplementation was 3.1-fold and 7.5-fold, respectively, compared to the formation efficiency obtained with and without AS supplementation in coculture. Transgenic hairy roots transformed with different AS concentration exhibited a similar pattern of thermo-inducibility after 10 min to 3 h heat treatments detected by GUS expression. The peak of expressed GUS specific activity, 399,530 pmol MUG per mg total protein per min, of the transgenic hairy roots was observed at 48 h after 3 h of 42 degrees C heat treatment, and the expressed GUS specific activity was 7-26 times more than that reported in A. thaliana, tobacco BY-2 cells and Nicotiana plumbaginifolia. Interference caused by AS supplementation on the growth of transgenic hairy roots, time-course of GUS expression and its expression level were not observed.

Bicarbonate-induced activation of H₂O₂ for metal-free oxidative desulfurization.

PubMed

Bokare, Alok D; Choi, Wonyong

2016-03-05

Efficient oxidative desulfurization (ODS) of model oil containing dibenzothiophene (DBT) and aromatic thiophenic derivatives has been achieved at room temperature using hydrogen peroxide activation by inorganic bicarbonate (HCO3(-)). Using in-situ formation of peroxymonocarbonate as oxidant, the transformation of main model substrate DBT to corresponding DBT-sulfone was easily accomplished in biphasic reaction conditions. In the presence of water-acetonitrile polar phase, increasing the water content upto 50% decreased the extraction capacity more than 3 times, but ∼ 90% DBT oxidation was still achieved. The oxidizing capacity of bicarbonate catalyst was maintained during repeated ODS cycles, but DBT removal efficiency was critically dependent on the extraction capacity of the polar phase. Under heterogeneous reaction conditions, bicarbonate-modified ion-exchange resin achieved similar ODS activity compared to the homogeneous catalytic system. Additionally, the efficient formation of peroxymonocarbonate using gaseous CO2 precursor in alkaline conditions was also utilized for DBT oxidation. The present study proposes the NaHCO3/H2O2 catalytic system as an efficient and cheap metal-free alternative for the oxidative removal of aromatic sulfur compounds from fuel oil. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of Recombinant Human Lactoferrin on Osteoblast Growth and Bone Status in Piglets.

PubMed

Li, Qiuling; Zhao, Jie; Hu, Wenping; Wang, Jianwu; Yu, Tian; Dai, Yunping; Li, Ning

2018-04-03

Lactoferrin (LF), an ~80 kDa iron-binding glycoprotein, modulates many biological effects, including antimicrobial and immunomodulatory activities. Recently, it was shown that LF also regulates bone cell activity, suggesting its therapeutic effect on postmenopausal bone loss. However, a minimal amount is known regarding the effects of recombinant human LF (rhLF) supplementation on bone status in young healthy infants. We found osteoblast cell differentiation was significantly promoted in vitro. Furthermore, treatment of human osteoblast cells with rhLF rapidly induced phosphorylation of p44/p42 mitogen-activated protein kinase (p44/p42 MAPK, ERK1/2). In order to investigate the effects of rhLF on bone status in vivo, we used a piglet model, which is a useful model for human infants. Piglets were supplemented with rhLF milk for 30 days. Bone formation markers, Serum calcium concentration, bone mineral density (BMD), bone mineral content (BMC), tibia bone strength, and the overall metabolite profile analysis showed that rhLF was advantageous to the bone growth in piglets. These findings suggest that rhLF supplementation benefits neonate bone health by modulating bone formation.

Methane oxidation and formation of EPS in compost: effect of oxygen concentration.

PubMed

Wilshusen, J H; Hettiaratchi, J P A; De Visscher, A; Saint-Fort, R

2004-05-01

Oxygen concentration plays an important role in the regulation of methane oxidation and the microbial ecology of methanotrophs. However, this effect is still poorly quantified in soil and compost ecosystems. The effect of oxygen on the formation of exopolymeric substances (EPS) is as yet unknown. We studied the effect of oxygen on the evolution of methanotrophic activity. At both high and low oxygen concentrations, peak activity was observed twice within a period of 6 months. Phospholipid fatty acid analysis showed that there was a shift from type I to type II methanotrophs during this period. At high oxygen concentration, EPS production was about 250% of the amount at low oxygen concentration. It is hypothesized that EPS serves as a carbon cycling mechanism for type I methanotrophs when inorganic nitrogen is limiting. Simultaneously, EPS stimulates nitrogenase activity in type II methanotrophs by creating oxygen-depleted zones. The kinetic results were incorporated in a simulation model for gas transport and methane oxidation in a passively aerated biofilter. Comparison between the model and experimental data showed that, besides acting as a micro-scale diffusion barrier, EPS can act as a barrier to macro-scale diffusion, reducing the performance of such biofilters.

Matrix Metalloproteinase 9 in Epilepsy: The Role of Neuroinflammation in Seizure Development

PubMed Central

2016-01-01

Matrix metalloproteinase 9 is a proteolytic enzyme which is recently one of the more often studied biomarkers. Its possible use as a biomarker of neuronal damage in stroke, heart diseases, tumors, multiple sclerosis, and epilepsy is being widely indicated. In epilepsy, MMP-9 is suggested to play a role in epileptic focus formation and in the stimulation of seizures. The increase of MMP-9 activity in the epileptic focus was observed both in animal models and in clinical studies. MMP-9 contributes to formation of epileptic focus, for example, by remodeling of synapses. Its proteolytic action on the elements of blood-brain barrier and activation of chemotactic processes facilitates accumulation of inflammatory cells and induces seizures. Also modification of glutamatergic transmission by MMP-9 is associated with seizures. In this review we will try to recapitulate the results of previous studies about MMP-9 in terms of its association with epilepsy. We will discuss the mechanisms of its actions and present the results revealed in animal models and clinical studies. We will also provide a comparison of the results of various studies on MMP-9 levels in the context of its possible use as a biomarker of the activity of epilepsy. PMID:28104930

Tracing Star Formation Around Quasars With Polycyclic Aromatic Hydrocarbons

NASA Astrophysics Data System (ADS)

Bilton, Lawrence Edward

2016-09-01

The feedback processes linking quasar activity to galaxy stellar mass growth are not well understood. If star formation is closely causally linked to black hole accretion, one may expect star formation confined to nuclear regions rather than extended over several kpc scales. Since Polycyclic Aromatic Hydrocarbon (PAH) emission features are widely used as tracers of stellar formation, it is, therefore, possible to use PAH emission detected around QSOs to help resolve this question. PAH data from a sample of 63 QSOs procured from the Spitzer Space Telescope’s Infrared Spectrograph (IRS) is used, employing the Spectroscopic Modelling Analysis and Reduction Tool’s (SMART) Advanced Optimal (AdOpt) extraction routines. A composite spectrum was also produced to help determine the average conditions and compositions of star forming regions. It is found, from our high redshift (>1) sample of QSOs, there is a marginally significant extended star formation on average of 34 scales. At low redshift, the median extension after deconvolving the instrumental point spread function is 3.2 , potentially showing evolutionary variations in star formation activity. However, limitations of the spatial resolving power constrain the ability to make any absolute conclusive remarks. It is also found that the QSO/AGN composite has more neutral PAHs than the starbursting and the main sequence galaxies, consistent with the AGN having no contribution to heating the PAH emission, and also consistent with the average PAH emission found on scales (i.e. not confined to the nuclear regions). A tentative detection of water vapour emission from the gravitationally lensed Einstein Cross quasar, QSO J2237+0305, is also presented suggesting a strong molecular outflow possibly driven by the active nucleus.

Neuron-specific (pro)renin receptor knockout prevents the development of salt-sensitive hypertension

PubMed Central

Li, Wencheng; Peng, Hua; Mehaffey, Eamonn P.; Kimball, Christie D.; Grobe, Justin L.; van Gool, Jeanette M.G.; Sullivan, Michelle N.; Earley, Scott; Danser, A.H. Jan; Ichihara, Atsuhiro; Feng, Yumei

2013-01-01

The (pro)renin receptor, which binds both renin and prorenin, is a newly discovered component of the renin angiotensin system that is highly expressed in the central nervous system. The significance of brain PRRs in mediating local angiotensin II formation and regulating blood pressure remains unclear. The current study was performed to test the hypothesis that PRR-mediated, non-proteolytic activation of prorenin is the main source of angiotensin II in the brain. Thus, PRR knockout in the brain is expected to prevent angiotensin II formation and development of deoxycorticosterone acetate salt induced hypertension. A neuron-specific PRR (ATP6AP2) knockout mouse model was generated using the Cre-LoxP system. Physiological parameters were recorded by telemetry. (Pro)renin receptor expression, detected by immunostaining and RT-PCR, was significantly decreased in the brains of knockout compared with wide-type mice. Intracerebroventricular infusion of mouse prorenin increased blood pressure and angiotensin II formation in wild type mice. This hypertensive response was abolished in (pro)renin receptor knockout mice in association with a reduction in angiotensin II levels. Deoxycorticosterone acetate salt increased (pro)renin receptor expression and angiotensin II formation in the brains of wild-type mice, an effect that was attenuated in (pro)renin receptor knockout mice. (Pro)renin receptor knockout in neurons prevented the development of Deoxycorticosterone acetate salt-induced hypertension as well as activation of cardiac and vasomotor sympathetic tone. In conclusion, non-proteolytic activation of prorenin through binding to the PRR mediates angiotensin II formation in the brain. Neuron-specific PRR knockout prevents the development of deoxycorticosterone acetate salt-induced hypertension, possibly through diminished angiotensin II formation. PMID:24246383

Inhibition of TGF–β signaling in subchondral bone mesenchymal stem cells attenuates osteoarthritis

PubMed Central

Zhen, Gehua; Wen, Chunyi; Jia, Xiaofeng; Li, Yu; Crane, Janet L.; Mears, Simon C.; Askin, Frederic B.; Frassica, Frank J.; Chang, Weizhong; Yao, Jie; Nayfeh, Tariq; Johnson, Carl; Artemov, Dmitri; Chen, Qianming; Zhao, Zhihe; Zhou, Xuedong; Cosgarea, Andrew; Carrino, John; Riley, Lee; Sponseller, Paul; Wan, Mei; Lu, William Weijia; Cao, Xu

2013-01-01

Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for osteoarthritis due to limited understanding of osteoarthritis pathogenesis. We show that TGF–β1 is activated in the subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) osteoarthritis mouse model. TGF–β1 concentrations also increased in human osteoarthritis subchondral bone. High concentrations of TGF–β1 induced formation of nestin+ mesenchymal stem cell (MSC) clusters leading to aberrant bone formation accompanied by increased angiogenesis. Transgenic expression of active TGF–β1 in osteoblastic cells induced osteoarthritis. Inhibition of TGF–β activity in subchondral bone attenuated degeneration of osteoarthritis articular cartilage. Notably, knockout of the TGF–β type II receptor (TβRII) in nestin+ MSCs reduced development of osteoarthritis in ACLT mice. Thus, high concentrations of active TGF–β1 in the subchondral bone initiated the pathological changes of osteoarthritis, inhibition of which could be a potential therapeutic approach. PMID:23685840

Suppressive activities and mechanisms of ugonin J on vascular smooth muscle cells and balloon angioplasty-induced neointimal hyperplasia.

PubMed

Pan, Chun-Hsu; Li, Pei-Chuan; Chien, Yi-Chung; Yeh, Wan-Ting; Liaw, Chih-Chuang; Sheu, Ming-Jyh; Wu, Chieh-Hsi

2018-02-01

Neointimal hyperplasia (or restenosis) is primarily attributed to excessive proliferation and migration of vascular smooth muscle cells (VSMCs). In this study, we investigated the inhibitory effects and mechanisms of ugonin J on VSMC proliferation and migration as well as neointimal formation. Cell viability and the cell-cycle distribution were, respectively, analyzed using an MTT assay and flow cytometry. Cell migration was examined using a wound-healing analysis and a transwell assay. Protein expressions and gelatinase activities were, respectively, measured using Western blot and gelatin zymography. Balloon angioplasty-induced neointimal formation was induced in a rat carotid artery model and then examined using immunohistochemical staining. Ugonin J induced cell-cycle arrest at the G 0 /G 1 phase and apoptosis to inhibit VSMC growth. Ugonin J also exhibited marked suppressive activity on VSMC migration. Ugonin J significantly reduced activations of focal adhesion kinase, phosphoinositide 3-kinase, v-akt murine thymoma viral oncogene homolog 1, and extracellular signal-regulated kinase 1/2 proteins. Moreover, ugonin J obviously reduced expressions and activity levels of matrix metalloproteinase-2 and matrix metalloproteinase-9. In vivo data indicated that ugonin J prevented balloon angioplasty-induced neointimal hyperplasia. Our study suggested that ugonin J has the potential for application in the prevention of balloon injury-induced neointimal formation. Copyright © 2017 John Wiley & Sons, Ltd.