WorldWideScience

Sample records for model offers insight

  1. New Insights Offered by a Computational Model of Deep Brain Stimulation

    DEFF Research Database (Denmark)

    Modolo, J.; Mosekilde, Erik; Beuter, A.

    2007-01-01

    elucidated. The paper starts with a brief review on the use of DBS to treat PD symptoms. The second section introduces a computational model based on the population density approach and the Izhikevich neuron model. We explain why this model is appropriate for investigating macroscopic network effects...

  2. Predicting Behavior from Normative Influences: What Insights Can the Fishbein Model Offer?

    Science.gov (United States)

    Walster, Dian E.

    The Fishbein Model is an attitude behavior consistency model which is used in both laboratory and field settings for predicting and understanding attitudinal and normative influences on behavior. This paper examines controversy surrounding the Fishbein Model's normative component in the context of a study of library and information science (LIS)…

  3. Multi-level modeling of light-induced stomatal opening offers new insights into its regulation by drought.

    Science.gov (United States)

    Sun, Zhongyao; Jin, Xiaofen; Albert, Réka; Assmann, Sarah M

    2014-11-01

    Plant guard cells gate CO2 uptake and transpirational water loss through stomatal pores. As a result of decades of experimental investigation, there is an abundance of information on the involvement of specific proteins and secondary messengers in the regulation of stomatal movements and on the pairwise relationships between guard cell components. We constructed a multi-level dynamic model of guard cell signal transduction during light-induced stomatal opening and of the effect of the plant hormone abscisic acid (ABA) on this process. The model integrates into a coherent network the direct and indirect biological evidence regarding the regulation of seventy components implicated in stomatal opening. Analysis of this signal transduction network identified robust cross-talk between blue light and ABA, in which [Ca2+]c plays a key role, and indicated an absence of cross-talk between red light and ABA. The dynamic model captured more than 10(31) distinct states for the system and yielded outcomes that were in qualitative agreement with a wide variety of previous experimental results. We obtained novel model predictions by simulating single component knockout phenotypes. We found that under white light or blue light, over 60%, and under red light, over 90% of all simulated knockouts had similar opening responses as wild type, showing that the system is robust against single node loss. The model revealed an open question concerning the effect of ABA on red light-induced stomatal opening. We experimentally showed that ABA is able to inhibit red light-induced stomatal opening, and our model offers possible hypotheses for the underlying mechanism, which point to potential future experiments. Our modelling methodology combines simplicity and flexibility with dynamic richness, making it well suited for a wide class of biological regulatory systems.

  4. Assets and tactics in a mating market: Economic models of negotiation offer insights into animal courtship dynamics on the lek

    Directory of Open Access Journals (Sweden)

    Gail L. PATRICELLI, Alan H. KRAKAUER, Richard MCELREATH

    2011-04-01

    Full Text Available Economists study negotiation as a series of events—partner choice, information gathering, bargaining, etc.—with each step of the process affecting the outcome of the next, and the optimal decision at each stage depending on the player’s bargaining power. The context in which these negotiations occur—the market—is critical, since players can adjust their behaviors in response to outside offers. Animals similarly are faced with sequential decisions regarding courtship: who to court, how to approach a potential mate, at what level to display, when to give up, etc. Thus economic models of negotiation in a market provide a framework in which we can view not just the outcome of courtship (assortative mating, but also the process, where each sex can use tactics to improve their negotiating outcome, using the assets that they have available. Here we propose to use negotiation as a conceptual framework to explore the factors promoting the tactical adjustments during sequential stages of courtship in lekking species. Our goal is to discuss the utility of negotiation as a heuristic tool, as well as the promise and peril of co-opting game theoretic models from economics to understand animal interactions. We will provide a brief overview of a few areas where we see promise for using negotiation as a framework to understand animal courtship dynamics: choice of a display territory, tactical partner choice for negotiation, approaching a potential partner and courtship haggling [Current Zoology 57 (2: 225–236, 2011].

  5. Assets and tactics in a mating market:Economic models of negotiation offer insights into animal courtship dynamics on the lek

    Institute of Scientific and Technical Information of China (English)

    Gail L.PATRICELLI; Alan H.KRAKAUER; Richard MCELREATH

    2011-01-01

    Economists study negotiation as a series of events-partner choice,information gathering,bargaining,etc.-with each step,of the process afffecting the outcome of the next,and the optimal decision at each stage depending on the player's bargaining power.The context in which these negotiations occur-the-market-is critical,since players can adjust their behaviors in response to outside offers.Animals similarly are faced with sequential decisions regarding courtsnip:who to court,how to approaCh a potential mate,at what level to display,when to give up,etc.Thus economic models of negotiation in a market provide a frameword in which we can view not just the outcome of courtship(assortativemating),but also the process,where each sex can use tactics to improve their negotiating outcome,using the assets that they have available.Here we propose to use negotiation as a conceplual framework to explore the factors promoting tactical adjustments during sequential stages of courtship in lekking species.Our goal is to discuss the utility of negotiation as a heuristic tool,as well as the promise and peril of co-opting game theoretic models from economics to understand animal interactions.We will provide a brief overview of a few areas where we see promise for using negotiation as a framework to understand animal courtship dynamics:choice of a display territory,tactical partner choice for negotiation,approaching a potential partner and courtship haggling.

  6. Offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Special offers for our members       Go Sport in Val Thoiry is offering 15% discount on all purchases made in the shop upon presentation of the Staff Association membership card (excluding promotions, sale items and bargain corner, and excluding purchases using Go Sport  and Kadéos gift cards. Only one discount can be applied to each purchase).  

  7. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    L'Occitane en Provence proposes the following offer: 10 % discount on all products in all L'Occitane shops in Metropolitan France upon presentation of your Staff Association membership card and a valid ID. This offer is valid only for one person, is non-transferable and cannot be combined with other promotions.

  8. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

    New offers : Discover the theater Galpon in Geneva. The Staff Association is happy to offer to its members a discount of 8.00 CHF on a full-price ticket (tickets of 15.00 CHF instead of 22.00 CHF) so do not hesitate anymore (mandatory reservation by phone + 4122 321  21 76 as tickets are quickly sold out!). For further information, please see our website: http://staff-association.web.cern.ch/fr/content/th%C3%A9%C3%A2tre-du-galpon  

  9. Offer

    CERN Multimedia

    Staff Association

    2016-01-01

    CERN was selected and participated in the ranking "Best Employers" organized by the magazine Bilan. To thank CERN for its collaboration, the magazine offers a reduction to the subscription fee for all employed members of personnel. 25% off the annual subscription: CHF 149.25 instead of CHF 199 .— The subscription includes the magazine delivered to your home for a year, every other Wednesday, as well as special editions and access to the e-paper. To benefit from this offer, simply fill out the form provided for this purpose. To get the form, please contact the secretariat of the Staff Association (Staff.Association@cern.ch).

  10. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    SPECIAL OFFER FOR OUR MEMBERS Prices Spring and Summer 2013 Day ticket: same price weekends, public holidays and weekdays: Children from 5 to 15 years old: 30 CHF instead of 39 CHF Adults from 16 years old: 36 CHF instead of 49 CHF Bonus! Free for children under 5 Tickets available at the Staff Association Secretariat.

  11. Offers

    CERN Multimedia

    Association du personnel

    2013-01-01

    SPECIAL OFFER FOR OUR MEMBERS Prices Spring and Summer 2013 Day ticket: same price weekends, public holidays and weekdays: – Children from 5 to 15 years old: 30 CHF instead of 39 CHF – Adults from 16 years old: 36 CHF instead of 49 CHF – Bonus! Free for children under 5 Tickets available at the Staff Association Secretariat.

  12. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    The theater season will start again, so do not hesitate to benefit from our discount: Théâtre de Carouge : Discount for all shows and on various season tickets. La Comédie : reduction on various tickets, on annual subscriptions and on discounted card. For further information, see our website: http://staff-association.web.cern.ch/sociocultural/offers

  13. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    proposes the following offer: 15% discount for the Staff Association members who enroll their children in summer FUTUREKIDS activities. Extracurricular Activities For Your Children The FUTUREKIDS Geneva Learning Center is open 6 days a week and offers a selection of after-school extracurricular activities for children and teenagers (ages 5 to 16). In addition to teaching in its Learning Centers, Futurekids collaborates with many private schools in Suisse Romande (Florimont, Moser, Champittet, Ecole Nouvelle, etc.) and with the Département de l'Instruction Publique (DIP) Genève. Courses and camps are usually in French but English groups can be set up on demand. FUTUREKIDS Computer Camps (during school holidays) FUTUREKIDS Computer Camps are a way of having a great time during vacations while learning something useful, possibly discovering a new hobby or even, why not, a future profession. Our computer camps are at the forefront of technology. Themes are diverse and suit all ...

  14. Offers

    CERN Multimedia

    Staff Association

    2015-01-01

    New offer for our members. The Staff Association CERN staff has recently concluded a framework agreement with AXA Insurance Ltd, General-Guisan-Strasse 40, 8401 Winterthur. This contract allows you to benefit from a preferential tariff and conditions for insurances: Motor vehicles for passenger cars and motorcycles of the product line STRADA: 10% discount Household insurance (personal liability and household contents) the product line BOX: 10% discount Travel insurance: 10% discount Buildings: 10% discount Legal protection: 10% discount AXA is number one on the Swiss insurance market. The product range encompasses all non-life insurance such as insurance of persons, property, civil liability, vehicles, credit and travel as well as innovative and comprehensive solutions in the field of occupational benefits insurance for individuals and businesses. Finally, the affiliate AXA-ARAG (legal expenses insurance) completes the offer. Armed with your staff association CERN card, you can always get the offe...

  15. Offer

    CERN Multimedia

    Staff Association

    2010-01-01

      Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 22th to 29th November 2010

  16. Offer

    CERN Multimedia

    Staff Association

    2011-01-01

      Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 25th to 27th March 2011  

  17. Offer

    CERN Multimedia

    CARLSON WAGONLIT TRAVEL

    2011-01-01

    Special offer   From 14th to 28th February 2011: no CWT service fee! For any new reservation of a holiday package (flight + hotel/apartment) from a catalog “summer 2011” For any additional information our staff is at your disposal from Monday – Friday, from 8h30 to 16h30. Phone number 72763 or 72797 Carlson Wagonlit Tavel, Agence du CERN  

  18. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    SPECIAL OFFER FOR OUR MEMBERS Prices Spring and Summer 2012 Half-day ticket: 5 hours, same price weekends, public holidays and weekdays. Children from 5 to 15 years old: 26 CHF instead of 35 CHF Adults from 16 years old: 32 CHF instead of 43 CHF Bonus! Free for children under 5. Aquaparc Les Caraïbes sur Léman 1807 Le Bouveret (VS)

  19. Offers

    CERN Document Server

    Staff Association

    2012-01-01

    SPECIAL OFFER FOR OUR MEMBERS Single tariff Adulte/Enfant Tickets “Zone terrestre” 20 euros instead of 25 euros. Access to Aqualibi: 5 euros instead of 8 euros on presentation of your ticket SA member. Free for children under 3, with limited access to the attractions. More information on our website : http://association.web.cern.ch/association/en/OtherActivities/Walibi.html

  20. Offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Banque cantonale de Genève (BCGE) The BCGE Business partner programme devised for members of the CERN Staff Association offers personalized banking solutions with preferential conditions. The advantages are linked to salary accounts (free account keeping, internet banking, free Maestro and credit cards, etc.), mortgage lending, retirement planning, investment, credit, etc. The details of the programme and the preferential conditions are available on our website: http://association.web.cern.ch/association/en/OtherActivities/BCGE.html.  

  1. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    Special offer for members of the Staff Association and their families 10 % reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20 % reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 11th to 23rd November 2013 Please contact the Staff Association Secretariat to get the discount voucher.  

  2. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 21st to 26th May 2012 Please contact the Staff Association Secretariat to get the discount voucher  

  3. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    Special offer for members of the Staff Association and their families 10 % reduction on all products in the Sephora shop (sells perfume, beauty products etc.) in Val Thoiry all year round. Plus 20 % reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * next “vente privée” from 21st November to 1st December 2012 Please contact the Staff Association Secretariat to get the discount voucher.

  4. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

    Passeport Gourmand   Are you dying for a nice meal? The “Passeport Gourmand” offers discounted prices to the members of the Staff Association (available until April 2015 and on sale in the Staff Association Secretariat): Passeport gourmand Ain / Savoie/ Haute Savoie: 56 CHF instead of 79 CHF. Passeport gourmand Geneva / neighbouring France:72 CHF instead of 95 CHF. To the members of the Staff Association: Benefit of reduced tickets: CHF 10 (instead of  18 CHF at the desk) on sale to the secretariat of the Staff Association, Building 510-R010 (in front of the Printshop).

  5. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

    Special offer for members of the Staff Association and their families 10 % reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Simply present your Staff Association membership card when you make your purchase. Plus 20 % reduction during their “vente privée”* three or four times a year. * Next “vente privée” from 24th September to 6th November 2014 Please contact the Staff Association Secretariat to get the discount voucher.  

  6. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    The « Théâtre de Carouge » offers a 5.- CHF discount for all shows (30.- CHF instead of 35.- CHF) and for the season tickets "Premières représentations" (132.- CHF instead of 162.- CHF) and "Classique" (150.- CHF instead of 180.- CHF). Please send your reservation by email to smills@tcag.ch via your professional email address. Please indicate the date of your reservation, your name and firstname and your telephone number A confirmation will be sent by email. Your membership card will be asked when you collect the tickets. More information on www.tcag.ch and www.tcag.ch/blog/

  7. Big Data Offers Novel Insights for Oncolytic Virus Immunotherapy

    Directory of Open Access Journals (Sweden)

    Stephanie L. Swift

    2016-02-01

    Full Text Available Large-scale assays, such as microarrays, next-generation sequencing and various “omics” technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. Yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (OVIT in the cancer setting. Tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and functionality within global populations or individual cells. Mapping immune changes over the course of oncolytic biotherapy—from initial infection to tumour stabilisation/regression through to long-term cure or escape/relapse—has the potential to generate important therapeutic insights around virus-host interactions. Further, correlating such immune signatures with specific tumour outcomes has significant value for guiding the development of novel oncolytic virus immunotherapy strategies. Here, we provide insights for OVIT from large-scale analyses of immune populations in the infection, vaccination and immunotherapy setting. We analyse several approaches to manipulating immune engagement during OVIT. We further explore immunocentric changes in the tumour tissue following immunotherapy, and compile several immune signatures of therapeutic success. Ultimately, we highlight clinically relevant large-scale approaches with the potential to strengthen future oncolytic strategies to optimally engage the immune system.

  8. Big Data Offers Novel Insights for Oncolytic Virus Immunotherapy

    Science.gov (United States)

    Swift, Stephanie L.; Stojdl, David F.

    2016-01-01

    Large-scale assays, such as microarrays, next-generation sequencing and various “omics” technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. Yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (OVIT) in the cancer setting. Tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and functionality within global populations or individual cells. Mapping immune changes over the course of oncolytic biotherapy—from initial infection to tumour stabilisation/regression through to long-term cure or escape/relapse—has the potential to generate important therapeutic insights around virus-host interactions. Further, correlating such immune signatures with specific tumour outcomes has significant value for guiding the development of novel oncolytic virus immunotherapy strategies. Here, we provide insights for OVIT from large-scale analyses of immune populations in the infection, vaccination and immunotherapy setting. We analyse several approaches to manipulating immune engagement during OVIT. We further explore immunocentric changes in the tumour tissue following immunotherapy, and compile several immune signatures of therapeutic success. Ultimately, we highlight clinically relevant large-scale approaches with the potential to strengthen future oncolytic strategies to optimally engage the immune system. PMID:26861383

  9. Offers

    CERN Multimedia

    Staff Association

    2015-01-01

    New season 2015-2016 The new season was revealed in May, and was warmly welcomed by the press, which is especially enthusiastic about the exceptional arrival of Fanny Ardand in September in the framework of Cassandre show. Discover the programme 2015-2016. The theatre La Comédie proposes different offers to our members Benefit from a reduction of 20 % on a full price ticket during all the season: from 38 CHF to 23 CHF ticket instead of 50 CHF to 30 CHF depending on the show. Buy two seasonal tickets at the price of one (offers valid upon availability, and until 30 september 2015) 2 Cards Libertà for 240 CHF instead of 480 CHF. Cruise freely through the season with 8 perfomances of your choice per season. These cards are transferrable, and can be shared with one or more accompanying persons. 2 Abo Piccolo for 120 CHF instead of 240 CHF. Let yourself be surprised a theatre performance with our discovery seasonal tickets, which includes 4 flagship perfomances for the season. ...

  10. Offer

    CERN Multimedia

    Staff Association

    2015-01-01

    RRP Communication organizes cultural events such as concerts, shows, sporting events. The members of the Staff Association profits from a reduction of 10 CHF per ticket. How to proceed: The ticket reservation is made by mail info@rrp.ch. You need to give the following information: Name of the show, and which date chosen Number of tickets, and category Name and surname Address Telephone number Mention “offer CERN”, and attach a photocopy of your Staff Association member card. After your reservation, you will be sent a copy with a payslip to the address mentioned above. Once paid, the members have the possibility to: pick up their ticket(s) from the cash register the evening of the show (opens 1 hour before the show) by showing their member card; receive the ticket(s) to the address indicated above, by registered mail, subject to an extra cost of 10CHF. Next show : More information at http://www.rrp.ch/

  11. Offers

    CERN Document Server

    Staff Association

    2013-01-01

    FUTUREKIDS proposes 15% discount for the Staff Association members who enroll their children in FUTUREKIDS activities. New workshop for 12-15 year olds, on how to develop applications for Android phones. Easter activities calendar Extracurricular Activities For Your Children The FUTUREKIDS Geneva Learning Center is open 6 days a week and offers a selection of after-school extracurricular activities for children and teenagers (ages 5 to 16). In addition to teaching in its Learning Centers, Futurekids collaborates with many private schools in Suisse Romande (Florimont, Moser, Champittet, Ecole Nouvelle, etc.) and with the Département de l'Instruction Publique (DIP) Genève. Courses and camps are usually in French but English groups can be set up on demand. FUTUREKIDS Computer Camps (during school holidays) FUTUREKIDS Computer Camps are a way of having a great time during vacations while learning something useful, possibly discovering a new hobby or even, why not, a fut...

  12. Offers

    CERN Multimedia

    Association du personnel

    2010-01-01

    THEATRE FORUM DE MEYRIN 1, place des Cinq-Continents 1217 Meyrin    Special offer for members of the Staff Association: Reduced ticket prices for the play Love is my sin (in English) from 15 to 17 March at 8.30pm http://www.forum-meyrin.ch/main.php?page=119&s=12   First category: 37 CHF instead of 46 CHF Second category (seats towards the sides): 30 CHF instead of 38 CHF Please present your CERN card and your Staff Association membership card at the ticket office. Ticket reservation: tel. 022 989 34 34 (from Monday to Friday 2pm to 6pm) or e-mail : billetterie@forum-meyrin.ch  

  13. Offer

    CERN Multimedia

    Staff Association

    2011-01-01

    DETAILS OF THE AGREEMENT WITH BCGE The BCGE Business partner programme devised for members of the CERN Staff Association offers personalized banking solutions with preferential conditions. The advantages are linked to salary accounts (free account keeping, internet banking, free Maestro and credit cards, etc.), mortgage lending, retirement planning, investment, credit, etc. The details of the programme and the preferential conditions are available on the Staff Association web site and from the secretariat (http://cern.ch/association/en/OtherActivities/BCGE.html). To benefit from these advantages, you will need to fill in the form available on our site, which must then be stamped by the Staff Association as proof that you are a paid-up member.  

  14. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    Do not hesitate to benefit of our offers in our partners: Théâtre de Carouge Discount of 5 CHF for all shows (30 CHF instead of 35 CHF) and on season tickets « first performance » ( 132 CHF instead 162 CHF) and also on « classical » ( 150 CHF instead of 180 CHF) upon presentation of your Staff Association membership card before payment. Théâtre La Comédie de Genève  20% off on tickets (full price – also available for partner): from 24 to 32 CHF a ticket instead of 30 to 40 CHF depending on the shows. 40% off on annual subscriptions (access to the best seats, pick up tickets at the last minute): 200 CHF for 9 shows (about 22 CHF a ticket instead of 30 to 40 CHF. Discounted card: 60 CHF and single price ticket of 16 CHF.

  15. Offers

    CERN Document Server

    Staff Association

    2011-01-01

    At the UN Cultural kiosk (door C6) This offer is meant for international civil servants, members of diplomatic missions as well as official delegates under presentation of their accreditation card. Matthew Lee & 5 musiciens Du Blues, du Boogie, du Rock’n’Roll 28 octobre 2011 à 20h30 Théâtre du Léman Quai du Mont-Blanc 19 Hôtel Kempinski Genève Matthew Lee is an exciting pianist singer combining classic Rock’n’Roll with timeless ballads. He revisits the standards, being alternately Jerry Lee Lewis, Chuck Berry, Little Richards and many others... He is a showman with a soulful voice and displays virtuosity during his piano solos. Simply amazing! 20 % reduction Tickets from 32 to 68 CHF Kiosque Culturel ONU Palais des Nations Porte 6 Avenue de la Paix 8-14 1211 Genève 10 Tél. 022 917 11 11 info@kiosqueonu.ch

  16. Offer

    CERN Multimedia

    Staff Association

    2016-01-01

    The “La Comédie” theatre unveiled its programme for the season 2016–2017 in late May, and it was met with great enthusiasm by the press. Leading names of the European and Swiss theatre scenes, such as director Joël Pommerat who recently won four Molière awards, will make an appearance! We are delighted to share this brand new, rich and varied programme with you. The “La Comédie” theatre has various discounts for our members Buy 2 subscriptions for the price of 1 : 2 cards “Libertà” for CHF 240.- instead of CHF 480.- Cruise freely through the season with an 8-entry card valid for the shows of your choice. These cards are transferable and can be shared with one or more accompanying persons. 2 cards “Piccolo” for CHF 120 instead of CHF 240.- This card lets you discover 4 shows which are suitable for all audiences (offers valid while stock lasts and until October 31, 201...

  17. Offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 21st to 26th November 2011 New BCGE Business partner benefits As you may remember thanks to our BCGE business partner agreement you benefit from various advantages such as free annual subscription on your Silver or Gold credit card both for yourself and your partner (joint account). Please be informed that as of October 1st  2011 the below mentioned features will be added to your annual credit card subscription : MasterCard/Visa Silver and Gold: travel cancellation as well as related services such as holiday interruption best guaranteed price Only for Ma...

  18. Radar interferometry offers new insights into threats to the Angkor site

    Science.gov (United States)

    Chen, Fulong; Guo, Huadong; Ma, Peifeng; Lin, Hui; Wang, Cheng; Ishwaran, Natarajan; Hang, Peou

    2017-01-01

    The conservation of World Heritage is critical to the cultural and social sustainability of regions and nations. Risk monitoring and preventive diagnosis of threats to heritage sites in any given ecosystem are a complex and challenging task. Taking advantage of the performance of Earth Observation technologies, we measured the impacts of hitherto imperceptible and poorly understood factors of groundwater and temperature variations on the monuments in the Angkor World Heritage site (400 km2). We developed a two-scale synthetic aperture radar interferometry (InSAR) approach. We describe spatial-temporal displacements (at millimeter-level accuracy), as measured by high-resolution TerraSAR/TanDEM-X satellite images, to provide a new solution to resolve the current controversy surrounding the potential structural collapse of monuments in Angkor. Multidisciplinary analysis in conjunction with a deterioration kinetics model offers new insights into the causes that trigger the potential decline of Angkor monuments. Our results show that pumping groundwater for residential and touristic establishments did not threaten the sustainability of monuments during 2011 to 2013; however, seasonal variations of the groundwater table and the thermodynamics of stone materials are factors that could trigger and/or aggravate the deterioration of monuments. These factors amplify known impacts of chemical weathering and biological alteration of temple materials. The InSAR solution reported in this study could have implications for monitoring and sustainable conservation of monuments in World Heritage sites elsewhere. PMID:28275729

  19. Modeling for Insights

    Energy Technology Data Exchange (ETDEWEB)

    Jacob J. Jacobson; Gretchen Matthern

    2007-04-01

    System Dynamics is a computer-aided approach to evaluating the interrelationships of different components and activities within complex systems. Recently, System Dynamics models have been developed in areas such as policy design, biological and medical modeling, energy and the environmental analysis, and in various other areas in the natural and social sciences. The real power of System Dynamic modeling is gaining insights into total system behavior as time, and system parameters are adjusted and the effects are visualized in real time. System Dynamic models allow decision makers and stakeholders to explore long-term behavior and performance of complex systems, especially in the context of dynamic processes and changing scenarios without having to wait decades to obtain field data or risk failure if a poor management or design approach is used. The Idaho National Laboratory recently has been developing a System Dynamic model of the US Nuclear Fuel Cycle. The model is intended to be used to identify and understand interactions throughout the entire nuclear fuel cycle and suggest sustainable development strategies. This paper describes the basic framework of the current model and presents examples of useful insights gained from the model thus far with respect to sustainable development of nuclear power.

  20. Novel Insights Into Causes of Scleroderma Offer Potential New Treatment Strategies

    Science.gov (United States)

    ... Into Causes of Scleroderma Offer Potential New Treatment Strategies Integrins, a large class of cell surface molecules, ... that targeting integrins could be a promising treatment strategy for scleroderma. The scientists were also curious about ...

  1. Offering architects insights into experiences of living with dementia: A case study on orientation in space, time, and identity.

    Science.gov (United States)

    Van Steenwinkel, Iris; Van Audenhove, Chantal; Heylighen, Ann

    2017-01-01

    Due to memory loss, people with dementia are increasingly disorientated in space, time, and identity, which causes profound experiences of insecurity, anxiety, and homesickness. In the case study presented in this article, we explored how architecture can support people in coping with this challenge. We took a novel approach to offer architects insights into experiences of living with dementia. Starting from a critical realist and constructionist approach, we combined ethnographic techniques with an architectural analysis. This case study offers insights into the experiences and activities of a woman living with dementia within the architectural context of her home. We describe how the physical and social environment provided her guidance through sequences of day-to-day activities. This study highlights how architecture can support people with dementia in orientating by accommodating places for (1) everyday activities and (2) privacy and togetherness.

  2. Genomic analysis offers insights into the evolution of the bovine TRA/TRD locus.

    Science.gov (United States)

    Connelley, Timothy K; Degnan, Kathryn; Longhi, Cassandra W; Morrison, W Ivan

    2014-11-19

    The TRA/TRD locus contains the genes for V(D)J somatic rearrangement of TRA and TRD chains expressed by αβ and γδ T cells respectively. Previous studies have demonstrated that the bovine TRA/TRD locus contains an exceptionally large number of TRAV/TRDV genes. In this study we combine genomic and transcript analysis to provide insights into the evolutionary development of the bovine TRA/TRD locus and the remarkable TRAV/TRDV gene repertoire. Annotation of the UMD3.1 assembly identified 371 TRAV/TRDV genes (distributed in 42 subgroups), 3 TRDJ, 6 TRDD, 62 TRAJ and single TRAC and TRDC genes, most of which were located within a 3.5 Mb region of chromosome 10. Most of the TRAV/TRDV subgroups have multiple members and several have undergone dramatic expansion, most notably TRDV1 (60 genes). Wide variation in the proportion of pseudogenes within individual subgroups, suggest that differential 'birth' and 'death' rates have been used to form a functional bovine TRAV/TRDV repertoire which is phylogenetically distinct from that of humans and mice. The expansion of the bovine TRAV/TRDV gene repertoire has predominantly been achieved through a complex series of homology unit (regions of DNA containing multiple gene) replications. Frequent co-localisation within homology units of genes from subgroups with low and high pseudogene proportions suggest that replication of homology units driven by evolutionary selection for the former may have led to a 'collateral' expansion of the latter. Transcript analysis was used to define the TRAV/TRDV subgroups available for recombination of TRA and TRD chains and demonstrated preferential usage of different subgroups by the expressed TRA and TRD repertoires, indicating that TRA and TRD selection have had distinct impacts on the evolution of the TRAV/TRDV repertoire. Both TRA and TRD selection have contributed to the evolution of the bovine TRAV/TRDV repertoire. However, our data suggest that due to homology unit duplication TRD

  3. What Can Human Geography Offer Climate Change Modelling?

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2014-01-01

    The discipline of Geography may be one of the most prominent and oldest disciplines in the conceptualization of human–environment interactions that integrates elements from both natural and social sciences. Yet, much research on society–environment interactions on climate change reduces human...... conceptual modelling of climate change adaption and mitigation. In other words, geographical representations do matter. In the following we will first reflect upon what I shall call spatio-temporal tides and waves of the human environment theme to examine the methodological grounds on which climate change...

  4. Two New Complete Genome Sequences Offer Insight into Host and Tissue Specificity of Plant Pathogenic Xanthomonas spp.▿†

    Science.gov (United States)

    Bogdanove, Adam J.; Koebnik, Ralf; Lu, Hong; Furutani, Ayako; Angiuoli, Samuel V.; Patil, Prabhu B.; Van Sluys, Marie-Anne; Ryan, Robert P.; Meyer, Damien F.; Han, Sang-Wook; Aparna, Gudlur; Rajaram, Misha; Delcher, Arthur L.; Phillippy, Adam M.; Puiu, Daniela; Schatz, Michael C.; Shumway, Martin; Sommer, Daniel D.; Trapnell, Cole; Benahmed, Faiza; Dimitrov, George; Madupu, Ramana; Radune, Diana; Sullivan, Steven; Jha, Gopaljee; Ishihara, Hiromichi; Lee, Sang-Won; Pandey, Alok; Sharma, Vikas; Sriariyanun, Malinee; Szurek, Boris; Vera-Cruz, Casiana M.; Dorman, Karin S.; Ronald, Pamela C.; Verdier, Valérie; Dow, J. Maxwell; Sonti, Ramesh V.; Tsuge, Seiji; Brendel, Volker P.; Rabinowicz, Pablo D.; Leach, Jan E.; White, Frank F.; Salzberg, Steven L.

    2011-01-01

    Xanthomonas is a large genus of bacteria that collectively cause disease on more than 300 plant species. The broad host range of the genus contrasts with stringent host and tissue specificity for individual species and pathovars. Whole-genome sequences of Xanthomonas campestris pv. raphani strain 756C and X. oryzae pv. oryzicola strain BLS256, pathogens that infect the mesophyll tissue of the leading models for plant biology, Arabidopsis thaliana and rice, respectively, were determined and provided insight into the genetic determinants of host and tissue specificity. Comparisons were made with genomes of closely related strains that infect the vascular tissue of the same hosts and across a larger collection of complete Xanthomonas genomes. The results suggest a model in which complex sets of adaptations at the level of gene content account for host specificity and subtler adaptations at the level of amino acid or noncoding regulatory nucleotide sequence determine tissue specificity. PMID:21784931

  5. Two new complete genome sequences offer insight into host and tissue specificity of plant pathogenic Xanthomonas spp.

    Science.gov (United States)

    Bogdanove, Adam J; Koebnik, Ralf; Lu, Hong; Furutani, Ayako; Angiuoli, Samuel V; Patil, Prabhu B; Van Sluys, Marie-Anne; Ryan, Robert P; Meyer, Damien F; Han, Sang-Wook; Aparna, Gudlur; Rajaram, Misha; Delcher, Arthur L; Phillippy, Adam M; Puiu, Daniela; Schatz, Michael C; Shumway, Martin; Sommer, Daniel D; Trapnell, Cole; Benahmed, Faiza; Dimitrov, George; Madupu, Ramana; Radune, Diana; Sullivan, Steven; Jha, Gopaljee; Ishihara, Hiromichi; Lee, Sang-Won; Pandey, Alok; Sharma, Vikas; Sriariyanun, Malinee; Szurek, Boris; Vera-Cruz, Casiana M; Dorman, Karin S; Ronald, Pamela C; Verdier, Valérie; Dow, J Maxwell; Sonti, Ramesh V; Tsuge, Seiji; Brendel, Volker P; Rabinowicz, Pablo D; Leach, Jan E; White, Frank F; Salzberg, Steven L

    2011-10-01

    Xanthomonas is a large genus of bacteria that collectively cause disease on more than 300 plant species. The broad host range of the genus contrasts with stringent host and tissue specificity for individual species and pathovars. Whole-genome sequences of Xanthomonas campestris pv. raphani strain 756C and X. oryzae pv. oryzicola strain BLS256, pathogens that infect the mesophyll tissue of the leading models for plant biology, Arabidopsis thaliana and rice, respectively, were determined and provided insight into the genetic determinants of host and tissue specificity. Comparisons were made with genomes of closely related strains that infect the vascular tissue of the same hosts and across a larger collection of complete Xanthomonas genomes. The results suggest a model in which complex sets of adaptations at the level of gene content account for host specificity and subtler adaptations at the level of amino acid or noncoding regulatory nucleotide sequence determine tissue specificity.

  6. The physiological resilience of fern sporophytes and gametophytes: advances in water relations offer new insights into an old lineage

    Directory of Open Access Journals (Sweden)

    Jarmila ePittermann

    2013-08-01

    Full Text Available Ferns are some of the oldest vascular plants in existence and they are the second most diverse lineage of tracheophytes next to angiosperms. Recent efforts to understand fern success have fo-cused on the physiological capacity and stress tolerance of both the sporophyte and the gameto-phyte generations. In this review, we examine these insights through the lens of plant water rela-tions, focusing primarily on the form and function of xylem tissue in the sporophyte, as well as the tolerance to and recovery from drought and desiccation stress in both stages of the fern life cycle. The absence of secondary xylem in ferns is compensated by selection for efficient primary xylem composed of large, closely arranged tracheids with permeable pit membranes. Protection from drought-induced hydraulic failure appears to arise from a combination of pit membrane traits and the arrangement of vascular bundles. Features such as tracheid-based xylem and vari-ously sized megaphylls are shared between ferns and more derived lineages, and offer an oppor-tunity to compare convergent and divergent hydraulic strategies critical to the success of xylem-bearing plants. Fern gametophytes show a high degree of desiccation tolerance but new evidence shows that morphological attributes in the gametophytes may facilitate water retention, though little work has addressed the ecological significance of this variation. We conclude with an emergent hypothesis that selection acted on the physiology of both the sporophyte and gameto-phyte generations in a synchronous manner that is consistent with selection for drought tolerance in the epiphytic niche, and the increasingly diverse habitats of the mid to late Cenozoic.

  7. The ratio of cholesterol 5,6-secosterols formed from ozone and singlet oxygen offers insight into the oxidation of cholesterol in vivo

    Science.gov (United States)

    Wentworth, Anita D.; Song, Byeong-Doo; Nieva, Jorge; Shafton, Asher; Tripurenani, Sangeetha; Wentworth, Paul

    2010-01-01

    Ongoing efforts to unravel the origins of the cholesterol 5,6-secosterols (1a and 1b) in biological systems have revealed that the two known chemical routes to these oxysterols; ozonolysis of cholesterol (3) and Hock-cleavage of 5-α-hydroperoxycholesterol (4a), are distinguishable based upon the ratio of the hydrazone derivatives (2a–b) formed in each case and this ratio offers an insight into the chemical origin of the secosterols in vivo. PMID:19462099

  8. New insights in permafrost modelling

    Science.gov (United States)

    Tubini, Niccolò; Serafin, Francesco; Gruber, Stephan; Casulli, Vincenzo; Rigon, Riccardo

    2017-04-01

    Simulating freezing soil has ignored for long time in mainstream surface hydrology. However, it has indubitably a large influence on soil infiltrability and an even larger influence on the soil energy budget, and, over large spatial scales, a considerable feedback on climate. The topic is difficult because it involves concepts of disequilibrium Thermodynamics and also because, once solved the theoretical problem, integration of the resulting partial differential equations in a robust manner, is not trivial at all. In this abstract, we are presenting a new algorithm to estimate the water and energy budget in freezing soils. The first step is a derivation of a new equation for freezing soil mass budget (called generalized Richards equation) based on the freezing equals drying hypothesis (Miller 1965). The second step is the re-derivation of the energy budget. Finally there is the application of new techniques based on the double nested Newton algorithm (Casulli and Zanolli, 2010) to integrate the coupled equations. Some examples of the freezing dynamics and comparison with the Dall'Amico et al. (2011) algorithm are also shown. References Casulli, V., & Zanolli,P. (2010). A nested newton-type algorithm for finite colume methods solving Richards' equation in mixed form. SIAM J. SCI. Comput., 32(4), 2225-2273. Dall'Amico, M., Endrizzi, S., Gruber, S., & Rigon, R. (2011). A robust and energy-conserving model of freezing variably-saturated soil. The Cryosphere, 5(2), 469-484. http://doi.org/10.5194/tc-5-469-2011 Miller, R.: Phase equilibria and soil freezing, in: Permafrost: Proceedings of the Second International Conference. Washington DC: National Academy of Science-National Research Council, 287, 193-197, 1965.

  9. Prescriptive Statements and Educational Practice: What Can Structural Equation Modeling (SEM) Offer?

    Science.gov (United States)

    Martin, Andrew J.

    2011-01-01

    Longitudinal structural equation modeling (SEM) can be a basis for making prescriptive statements on educational practice and offers yields over "traditional" statistical techniques under the general linear model. The extent to which prescriptive statements can be made will rely on the appropriate accommodation of key elements of research design,…

  10. Quantitative 31P NMR analysis of solid wood offers an insight into the acetylation of its components.

    Science.gov (United States)

    Sadeghifar, Hasan; Dickerson, James P; Argyropoulos, Dimitris S

    2014-11-26

    As a solid substrate, wood and its components are almost invariably examined via spectroscopic or indirect methods of analysis. Unlike earlier approaches, in this effort we dissolve pulverized wood in ionic liquid and then directly derive its functional group contents by quantitative (31)P NMR. As such, this novel analytical methodology is thoroughly examined and an insight into the detailed way acetylation proceeds on solid wood and its components is provided as a function of wood density and within its various anatomical features. As anticipated, the efficiency of acetylation was found to be greater within low density wood than in high density wood. The lignin, the cellulose and the hemicelluloses of the low density wood was found to be acetylated nearly twice as fast with remarkable differences in their quantitative degree of acetylation amongst them. This direct analytical data validates the applied methodology and confirms, for the first time, that the order of acetylation in solid wood is lignin>hemicellulose>cellulose and no reactivity differences exist between early wood and late wood.

  11. An Inventory Model with Finite Replenishment Rate, Trade Credit Policy and Price-Discount Offer

    Directory of Open Access Journals (Sweden)

    Biswajit Sarkar

    2013-01-01

    Full Text Available When some suppliers offer trade credit periods and price discounts to retailers in order to increase the demand of their products, retailers have to face different types of discount offers and credits within which they have to take a decision which is the best offer for them to make more profit. The retailers try to buy perfect-quality items at a reasonable price, and also they try to invest returns obtained by selling those items in such a manner that their business is not hampered. In this point of view, we consider an economic order quantity (EOQ model for various types of time-dependent demand when delay in payment and price discount are permitted by suppliers to retailers. The models of various demand patterns are discussed analytically. Some numerical examples and graphical representations are considered to illustrate the model.

  12. Modelling marine protected areas: insights and hurdles

    OpenAIRE

    Elizabeth A Fulton; Bax, Nicholas J.; Bustamante, Rodrigo H.; Jeffrey M. Dambacher; Dichmont, Catherine; Dunstan, Piers K.; Hayes, Keith R.; Hobday, Alistair J.; Pitcher, Roland; Plagányi, Éva E.; Punt, André E; Savina-rolland, Marie; Anthony D M Smith; David C. Smith

    2015-01-01

    Models provide useful insights into conservation and resource management issues and solutions. Their use to date has highlighted conditions under which no-take marine protected areas (MPAs) may help us to achieve the goals of ecosystem-based management by reducing pressures, and where they might fail to achieve desired goals. For example, static reserve designs are unlikely to achieve desired objectives when applied to mobile species or when compromised by climate-related ecosystem restructur...

  13. Quantitative model validation techniques: new insights

    CERN Document Server

    Ling, You

    2012-01-01

    This paper develops new insights into quantitative methods for the validation of computational model prediction. Four types of methods are investigated, namely classical and Bayesian hypothesis testing, a reliability-based method, and an area metric-based method. Traditional Bayesian hypothesis testing is extended based on interval hypotheses on distribution parameters and equality hypotheses on probability distributions, in order to validate models with deterministic/stochastic output for given inputs. Two types of validation experiments are considered - fully characterized (all the model/experimental inputs are measured and reported as point values) and partially characterized (some of the model/experimental inputs are not measured or are reported as intervals). Bayesian hypothesis testing can minimize the risk in model selection by properly choosing the model acceptance threshold, and its results can be used in model averaging to avoid Type I/II errors. It is shown that Bayesian interval hypothesis testing...

  14. Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.

    Science.gov (United States)

    Warren, Helen R; Evangelou, Evangelos; Cabrera, Claudia P; Gao, He; Ren, Meixia; Mifsud, Borbala; Ntalla, Ioanna; Surendran, Praveen; Liu, Chunyu; Cook, James P; Kraja, Aldi T; Drenos, Fotios; Loh, Marie; Verweij, Niek; Marten, Jonathan; Karaman, Ibrahim; Lepe, Marcelo P Segura; O'Reilly, Paul F; Knight, Joanne; Snieder, Harold; Kato, Norihiro; He, Jiang; Tai, E Shyong; Said, M Abdullah; Porteous, David; Alver, Maris; Poulter, Neil; Farrall, Martin; Gansevoort, Ron T; Padmanabhan, Sandosh; Mägi, Reedik; Stanton, Alice; Connell, John; Bakker, Stephan J L; Metspalu, Andres; Shields, Denis C; Thom, Simon; Brown, Morris; Sever, Peter; Esko, Tõnu; Hayward, Caroline; van der Harst, Pim; Saleheen, Danish; Chowdhury, Rajiv; Chambers, John C; Chasman, Daniel I; Chakravarti, Aravinda; Newton-Cheh, Christopher; Lindgren, Cecilia M; Levy, Daniel; Kooner, Jaspal S; Keavney, Bernard; Tomaszewski, Maciej; Samani, Nilesh J; Howson, Joanna M M; Tobin, Martin D; Munroe, Patricia B; Ehret, Georg B; Wain, Louise V

    2017-03-01

    Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

  15. Genome-wide expression analysis offers new insights into the origin and evolution of Physcomitrella patens stress response

    KAUST Repository

    Khraiwesh, Basel

    2015-11-30

    Changes in the environment, such as those caused by climate change, can exert stress on plant growth, diversity and ultimately global food security. Thus, focused efforts to fully understand plant response to stress are urgently needed in order to develop strategies to cope with the effects of climate change. Because Physcomitrella patens holds a key evolutionary position bridging the gap between green algae and higher plants, and because it exhibits a well-developed stress tolerance, it is an excellent model for such exploration. Here, we have used Physcomitrella patens to study genome-wide responses to abiotic stress through transcriptomic analysis by a high-throughput sequencing platform. We report a comprehensive analysis of transcriptome dynamics, defining profiles of elicited gene regulation responses to abiotic stress-associated hormone Abscisic Acid (ABA), cold, drought, and salt treatments. We identified more than 20,000 genes expressed under each aforementioned stress treatments, of which 9,668 display differential expression in response to stress. The comparison of Physcomitrella patens stress regulated genes with unicellular algae, vascular and flowering plants revealed genomic delineation concomitant with the evolutionary movement to land, including a general gene family complexity and loss of genes associated with different functional groups.

  16. Offering model for a virtual power plant based on stochastic programming

    DEFF Research Database (Denmark)

    PandŽić, Hrvoje; Morales González, Juan Miguel; Conejo, Antonio J.

    2013-01-01

    electricity in both the day-ahead and the balancing markets seeking to maximize its expected profit. Such model is mathematically rigorous, yet computationally efficient.The offering problem is cast as a two-stage stochastic mixed-integer linear programming model which maximizes the virtual power plant......A virtual power plant aggregates various local production/consumption units that act in the market as a single entity. This paper considers a virtual power plant consisting of an intermittent source, a storage facility, and a dispatchable power plant. The virtual power plant sells and purchases...

  17. Modelling marine protected areas: insights and hurdles.

    Science.gov (United States)

    Fulton, Elizabeth A; Bax, Nicholas J; Bustamante, Rodrigo H; Dambacher, Jeffrey M; Dichmont, Catherine; Dunstan, Piers K; Hayes, Keith R; Hobday, Alistair J; Pitcher, Roland; Plagányi, Éva E; Punt, André E; Savina-Rolland, Marie; Smith, Anthony D M; Smith, David C

    2015-11-05

    Models provide useful insights into conservation and resource management issues and solutions. Their use to date has highlighted conditions under which no-take marine protected areas (MPAs) may help us to achieve the goals of ecosystem-based management by reducing pressures, and where they might fail to achieve desired goals. For example, static reserve designs are unlikely to achieve desired objectives when applied to mobile species or when compromised by climate-related ecosystem restructuring and range shifts. Modelling tools allow planners to explore a range of options, such as basing MPAs on the presence of dynamic oceanic features, and to evaluate the potential future impacts of alternative interventions compared with 'no-action' counterfactuals, under a range of environmental and development scenarios. The modelling environment allows the analyst to test if indicators and management strategies are robust to uncertainties in how the ecosystem (and the broader human-ecosystem combination) operates, including the direct and indirect ecological effects of protection. Moreover, modelling results can be presented at multiple spatial and temporal scales, and relative to ecological, economic and social objectives. This helps to reveal potential 'surprises', such as regime shifts, trophic cascades and bottlenecks in human responses. Using illustrative examples, this paper briefly covers the history of the use of simulation models for evaluating MPA options, and discusses their utility and limitations for informing protected area management in the marine realm. © 2015 The Author(s).

  18. New insight on petroleum system modeling of Ghadames basin, Libya

    Science.gov (United States)

    Bora, Deepender; Dubey, Siddharth

    2015-12-01

    Underdown and Redfern (2008) performed a detailed petroleum system modeling of the Ghadames basin along an E-W section. However, hydrocarbon generation, migration and accumulation changes significantly across the basin due to complex geological history. Therefore, a single section can't be considered representative for the whole basin. This study aims at bridging this gap by performing petroleum system modeling along a N-S section and provides new insights on source rock maturation, generation and migration of the hydrocarbons using 2D basin modeling. This study in conjunction with earlier work provides a 3D context of petroleum system modeling in the Ghadames basin. Hydrocarbon generation from the lower Silurian Tanezzuft formation and the Upper Devonian Aouinet Ouenine started during the late Carboniferous. However, high subsidence rate during middle to late Cretaceous and elevated heat flow in Cenozoic had maximum impact on source rock transformation and hydrocarbon generation whereas large-scale uplift and erosion during Alpine orogeny has significant impact on migration and accumulation. Visible migration observed along faults, which reactivated during Austrian unconformity. Peak hydrocarbon expulsion reached during Oligocene for both the Tanezzuft and the Aouinet Ouenine source rocks. Based on modeling results, capillary entry pressure driven downward expulsion of hydrocarbons from the lower Silurian Tanezzuft formation to the underlying Bir Tlacsin formation observed during middle Cretaceous. Kinetic modeling has helped to model hydrocarbon composition and distribution of generated hydrocarbons from both the source rocks. Application of source to reservoir tracking technology suggest some accumulations at shallow stratigraphic level has received hydrocarbons from both the Tanezzuft and Aouinet Ouenine source rocks, implying charge mixing. Five petroleum systems identified based on source to reservoir correlation technology in Petromod*. This Study builds

  19. Offering solutions of sustainable urban tourism by the use of SWOT model, case study Isfahan city

    Directory of Open Access Journals (Sweden)

    Monireh Roustazadeh Sheikh Yousefi

    2014-08-01

    Full Text Available Tourism phenomenon has been spread world wildtoday. It's because of technological innovation development and overallcapitalism expansion in current age. Tourism in this situation has caused humanbeing relocation and mobility and in worldwide level, has created concept ofrelationship with other cultures in different locations, as socio-geographicalphenomenon. In this case cities includes important scientific, recreational,sport, shrine, historical, culture, medical, centers, etc., in addition to thiscases, also utilities natural attraction, etc., can play vole as touristic cityin the center of the country. in this research discursive- analysis method hasbeen used for collecting data and proceed to identify tourism potentials ,abilities, limitations and inadequacy of Isfahan by documental and librarydeliberations and field studies, SWOT model has been used for analyzing data.Then, offering solutions for sustainable urban development and eventuallymovement toward tourism development have been emphasized on.

  20. Special Offers

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    Association du personnel

    2011-01-01

    Walibi Rhône-Alpes is open until 31 October. Reduced prices for children and adults at this French attraction park in Les Avenières. For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  1. Special offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Are you a member of the Staff Association? Did you know that as a member you can benefit from the following special offers: BCGE (Banque Cantonale de Genève): personalized banking solutions with preferential conditions. TPG: reduced rates on annual transport passes for active and retired staff. Aquaparc: reduced ticket prices for children and adults at this Swiss waterpark in Le Bouveret. FNAC: 5% reduction on FNAC vouchers. For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  2. Special Offers

    CERN Multimedia

    Association du personnel

    2011-01-01

    Are you a member of the Staff Association? Did you know that as a member you can benefit from the following special offers: BCGE (Banque Cantonale de Genève): personalized banking solutions with preferential conditions. TPG: reduced rates on annual transport passes for active and retired staff. Aquaparc: reduced ticket prices for children and adults at this Swiss waterpark in Le Bouveret. Walibi: reduced prices for children and adults at this French attraction park in Les Avenières. FNAC: 5% reduction on FNAC vouchers. For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  3. Offers INTERSOCCER

    CERN Document Server

    Staff Association

    2014-01-01

      Summer Football camps   New offer to the members of the Staff Association – INTERSOCCER: 12% discount on summer football camps and courses for children (bilingual) so do not hesitate anymore!    

  4. A Dynamic Web Page Prediction Model Based on Access Patterns to Offer Better User Latency

    CERN Document Server

    Mukhopadhyay, Debajyoti; Saha, Dwaipayan; Kim, Young-Chon

    2011-01-01

    The growth of the World Wide Web has emphasized the need for improvement in user latency. One of the techniques that are used for improving user latency is Caching and another is Web Prefetching. Approaches that bank solely on caching offer limited performance improvement because it is difficult for caching to handle the large number of increasingly diverse files. Studies have been conducted on prefetching models based on decision trees, Markov chains, and path analysis. However, the increased uses of dynamic pages, frequent changes in site structure and user access patterns have limited the efficacy of these static techniques. In this paper, we have proposed a methodology to cluster related pages into different categories based on the access patterns. Additionally we use page ranking to build up our prediction model at the initial stages when users haven't already started sending requests. This way we have tried to overcome the problems of maintaining huge databases which is needed in case of log based techn...

  5. Special Offers

    CERN Multimedia

    Association du personnel

    2011-01-01

    Are you a member of the Staff Association? Did you know that as a member you can benefit from the following special offers: BCGE (Banque Cantonale de Genève): personalized banking solutions with preferential conditions.     TPG: reduced rates on annual transport passes for active and retired staff.     Aquaparc: reduced ticket prices for children and adults at this Swiss waterpark in Le Bouveret.     Walibi: reduced prices for children and adults at this French attraction park in Les Avenières.       FNAC: 5% reduction on FNAC vouchers.       For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  6. Special Offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Are you a member of the Staff Association? Did you know that as a member you can benefit from the following special offers: BCGE (Banque Cantonale de Genève): personalized banking solutions with preferential conditions.     TPG: reduced rates on annual transport passes for all active and retired staff.     Aquaparc: reduced ticket prices for children and adults at this Swiss waterpark in Le Bouveret.     Walibi: reduced prices for children and adults at this French attraction park in Les Avenières.       FNAC: 5% reduction on FNAC vouchers.       For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  7. Special offer

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    Staff Association

    2010-01-01

    Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * next “vente privée” from 24th to 29th May 2010  

  8. Special offer

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    SPECIAL OFFER FOR OUR MEMBERS Tarif unique Adulte/Enfant Entrée Zone terrestre 19 euros instead of 23 euros Entrée “Zone terrestre + aquatique” 24 euros instead of 31 euros Free for children under 3, with limited access to the attractions. Walibi Rhône-Alpes is open daily from 22 June to 31 August, and every week end from 3 September until 31 October. Closing of the “zone aquatique” 11 September.

  9. Special offer

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    Staff Association

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    SPECIAL OFFER FOR OUR MEMBERS Tarif unique Adulte/Enfant Entrée Zone terrestre 19 euros instead of 23 euros Entrée “Zone terrestre + aquatique” 24 euros instead of 31 euros Free for children under 3, with limited access to the attractions. Walibi Rhône-Alpes is open daily from 22 June to 31 August, and every week end from 3 September until 31 October. Closing of the “zone aquatique” 11 September.

  10. Cameroon mid-level providers offer a promising public health dentistry model

    Directory of Open Access Journals (Sweden)

    Achembong Leo

    2012-11-01

    Full Text Available Background Oral health services are inadequate and unevenly distributed in many developing countries, particularly those in sub-Saharan Africa. Rural areas in these countries and poorer sections of the population in urban areas often do not have access to oral health services mainly because of a significant shortage of dentists and the high costs of care. We reviewed Cameroon’s experience with deploying a mid-level cadre of oral health professionals and the feasibility of establishing a more formal and predictable role for these health workers. We anticipate that a task-shifting approach in the provision of dental care will significantly improve the uneven distribution of oral health services particularly in the rural areas of Cameroon, which is currently served by only 3% of the total number of dentists. Methods The setting of this study was the Cameroon Baptist Convention Health Board (BCHB, which has four dentists and 42 mid-level providers. De-identified data were collected manually from the registries of 10 Baptist Convention clinics located in six of Cameroon’s 10 regions and then entered into an Excel format before importing into STATA. A retrospective abstraction of all entries for patient visits starting October 2010, and going back in time until 1500 visits were extracted from each clinic. Results This study showed that mid-level providers in BCHB clinics are offering a full scope of dental work across the 10 clinics, with the exception of treatment for major facial injuries. Mid-level providers alone performed 93.5% of all extractions, 87.5% of all fillings, 96.5% of all root canals, 97.5% of all cleanings, and 98.1% of all dentures. The dentists also typically played a teaching role in training the mid-level providers. Conclusions The Ministry of Health in Cameroon has an opportunity to learn from the BCHB model to expand access to oral health care across the country. This study shows the benefits of using a simple, workable, low

  11. Offering an Anatomy and Physiology Course through a High School-University Partnership: The Minnesota Model

    Science.gov (United States)

    Jensen, Murray; Mattheis, Allison; Loyle, Anne

    2013-01-01

    This article describes a one-semester anatomy and physiology course that is currently offered through the concurrent enrollment program at the University of Minnesota. The article explains how high school teachers are prepared to teach the course and describes efforts to promote program quality, student inquiry, and experiential learning.…

  12. Hmong Cosmology: Proposed Model, Preliminary Insights

    Directory of Open Access Journals (Sweden)

    Vincent K. Her

    2006-01-01

    Full Text Available Is there an underlying structure to Hmong cosmology? What are its components? And how might these interrelate? In this paper, I will show that the Hmong cosmos consists of three separate realms and that these are connected together by the cycle of the human soul. Using zaaj qhuabke, I will trace the journey of the deceased and look at how ritual movement is expressive of human agency, narrative experience and community history. My insights are based on primary fieldwork research carried out for a doctoral dissertation on Hmong funeral rites in the Midwest.

  13. Corvid Caching : Insights From a Cognitive Model

    NARCIS (Netherlands)

    van der Vaart, Elske; Verbrugge, Rineke; Hemelrijk, Charlotte K.

    2011-01-01

    Caching and recovery of food by corvids is well-studied, but some ambiguous results remain. To help clarify these, we built a computational cognitive model. It is inspired by similar models built for humans, and it assumes that memory strength depends on frequency and recency of use. We compared our

  14. Could a new ice core offer an insight into the stability of the West Antarctic Ice Sheet during the last interglacial?

    Science.gov (United States)

    Mulvaney, R.; Hindmarsh, R. C.

    2013-12-01

    Vaughan et al., in their 2011 paper 'Potential Seaways across West Antarctica' (Geochem. Geophys. Geosyst., 12, Q10004, doi:10.1029/2011GC003688), offer the intriguing prospect that substantial ice loss from the West Antarctic Ice Sheet during the previous interglacial period might have resulted in the opening of a seaway between the Weddell Sea and the Amundsen Sea. One of their potential seaways passes between the south western corner of the present Ronne Ice Shelf and the Pine Island Bay, through what is currently the course of the Rutford Ice Stream, between the Ellsworth Mountains and the Fletcher Promontory. To investigate whether this seaway could have existed (and to recover a paleoclimate and ice sheet history from the Weddell Sea), a team from the British Antarctic Survey and the Laboratoire de Glaciologie et Géophysique de l'Environnement drilled an ice core from a close to a topographic dome in the ice surface on the Fletcher Promontory in January 2012, reaching the bedrock at 654.3m depth from the surface. The site was selected to penetrate directly through the centre of a Raymond cupola observed in internal radar reflections from the ice sheet, with the intention that this would ensure we obtained the oldest ice available from the Fletcher Promontory. The basal ice sheet temperature measured was -18°C, implying the oldest ice would not have melted away from the base, while the configuration of the Raymond cupola in the radar horizons suggested stability in the ice dome topography during the majority of the Holocene. Our hypothesis is that chemical analysis of the ice core will reveal whether the site was ever relatively close to open sea water or ice shelf in the Rutford channel 20 km distant, rather than the current 700 km distance to sea ice/open water in either the Weddell Sea or the Amundsen Sea. While we do not yet have the chemistry data to test this hypothesis, in this poster we will discuss whether there is in reality any potential local

  15. Mathematical model insights into arsenic detoxification

    Directory of Open Access Journals (Sweden)

    Nijhout H Frederik

    2011-08-01

    Full Text Available Abstract Background Arsenic in drinking water, a major health hazard to millions of people in South and East Asia and in other parts of the world, is ingested primarily as trivalent inorganic arsenic (iAs, which then undergoes hepatic methylation to methylarsonic acid (MMAs and a second methylation to dimethylarsinic acid (DMAs. Although MMAs and DMAs are also known to be toxic, DMAs is more easily excreted in the urine and therefore methylation has generally been considered a detoxification pathway. A collaborative modeling project between epidemiologists, biologists, and mathematicians has the purpose of explaining existing data on methylation in human studies in Bangladesh and also testing, by mathematical modeling, effects of nutritional supplements that could increase As methylation. Methods We develop a whole body mathematical model of arsenic metabolism including arsenic absorption, storage, methylation, and excretion. The parameters for arsenic methylation in the liver were taken from the biochemical literature. The transport parameters between compartments are largely unknown, so we adjust them so that the model accurately predicts the urine excretion rates of time for the iAs, MMAs, and DMAs in single dose experiments on human subjects. Results We test the model by showing that, with no changes in parameters, it predicts accurately the time courses of urinary excretion in mutiple dose experiments conducted on human subjects. Our main purpose is to use the model to study and interpret the data on the effects of folate supplementation on arsenic methylation and excretion in clinical trials in Bangladesh. Folate supplementation of folate-deficient individuals resulted in a 14% decrease in arsenicals in the blood. This is confirmed by the model and the model predicts that arsenicals in the liver will decrease by 19% and arsenicals in other body stores by 26% in these same individuals. In addition, the model predicts that arsenic

  16. Cancer immunotherapy : insights from transgenic animal models

    NARCIS (Netherlands)

    McLaughlin, PMJ; Kroesen, BJ; Harmsen, MC; de Leij, LFMH

    2001-01-01

    A wide range of strategies in cancer immunotherapy has been developed in the last decade, some of which are currently being used in clinical settings. The development of these immunotherapeutical strategies has been facilitated by the generation of relevant transgenic animal models. Since the

  17. Cancer immunotherapy : insights from transgenic animal models

    NARCIS (Netherlands)

    McLaughlin, PMJ; Kroesen, BJ; Harmsen, MC; de Leij, LFMH

    2001-01-01

    A wide range of strategies in cancer immunotherapy has been developed in the last decade, some of which are currently being used in clinical settings. The development of these immunotherapeutical strategies has been facilitated by the generation of relevant transgenic animal models. Since the differ

  18. New insights in portfolio selection modeling

    OpenAIRE

    Zareei, Abalfazl

    2016-01-01

    Recent advancements in the field of network theory commence a new line of developments in portfolio selection techniques that stands on the ground of perceiving financial market as a network with assets as nodes and links accounting for various types of relationships among financial assets. In the first chapter, we model the shock propagation mechanism among assets via network theory and provide an approach to construct well-diversified portfolios that are resilient to shock propagation and c...

  19. New macrophage models of Gaucher disease offer new tools for drug development.

    Science.gov (United States)

    Borger, Daniel K; Sidransky, Ellen; Aflaki, Elma

    Gaucher disease is an inherited enzyme deficiency resulting in the lysosomal accumulation of specific glycolipids in macrophages and, in some cases, neurons. While current treatments are effective at reducing this glycolipid storage in macrophages, they are expensive and ineffective in treating neurological manifestations of the disease, driving the search for novel therapeutics. Moreover, mutations in GBA1, the gene implicated in Gaucher disease, are an important risk factor for the development of Parkinson disease and related disorders, an association that has further heightened interest in Gaucher disease research. However, the development of therapeutic strategies has been hampered by a shortage of appropriate cellular models of Gaucher disease. We have generated two novel macrophage models of Gaucher disease, one through the differentiation of peripheral blood monocytes from patients with Gaucher disease and the other through the differentiation of induced pluripotent stem cells derived from patient fibroblasts. Both disease models demonstrate similar cellular phenotypes and exhibit extensive glycolipid storage when exposed to exogenous lipid sources such as erythrocyte membranes. Furthermore, we have used these models to confirm the efficacy of a novel small molecule in clearing glycolipid storage and restoring normal macrophage function. These results demonstrate the usefulness of these models in exploring new therapeutics for Gaucher disease and related disorders.

  20. A Model of Sustainability for Professional Organizations: Using a Learning Management System to Offer Continuing Education

    Science.gov (United States)

    Sparrow, Gregory S.

    2017-01-01

    Professional membership organizations have long maintained their exposure and revenue stream through a variety of traditional avenues, most notably memberships, sponsored conferences, and professional journals. The synergy of this three-tiered model has depended on a certain enhanced status derived from membership benefits and proprietary…

  1. Variations in offer arrival rates in a stationary search model : a note

    NARCIS (Netherlands)

    Rao Sahib, Padma

    2001-01-01

    The standard search model predicts that the hazard and the expected accepted wage should be constant over an unemployment spell. This note shows that heterogeneity in job o®er arrival rates can generate declining hazards and declining accepted wages, results in conformity with the empirical evidence

  2. Terrane accretion: Insights from numerical modelling

    Science.gov (United States)

    Vogt, Katharina; Gerya, Taras

    2016-04-01

    The oceanic crust is not homogenous, but contains significantly thicker crust than norm, i.e. extinct arcs, spreading ridges, detached continental fragments, volcanic piles or oceanic swells. These (crustal) fragments may collide with continental crust and form accretionary complexes, contributing to its growth. We analyse this process using a thermo-mechanical computer model (i2vis) of an ocean-continent subduction zone. In this model the oceanic plate can bend spontaneously under the control of visco-plastic rheologies. It moreover incorporates effects such as mineralogical phase changes, fluid release and consumption, partial melting and melt extraction. Based on our 2-D experiments we suggest that the lithospheric buoyancy of the downgoing slab and the rheological strength of crustal material may result in a variety of accretionary processes. In addition to terrane subduction, we are able to identify three distinct modes of terrane accretion: frontal accretion, basal accretion and underplating plateaus. We show that crustal fragments may dock onto continental crust and cease subduction, be scrapped off the downgoing plate, or subduct to greater depth prior to slab break off and subsequent exhumation. Direct consequences of these processes include slab break off, subduction zone transference, structural reworking, formation of high-pressure terranes, partial melting and crustal growth.

  3. Describing dengue epidemics: Insights from simple mechanistic models

    Science.gov (United States)

    Aguiar, Maíra; Stollenwerk, Nico; Kooi, Bob W.

    2012-09-01

    We present a set of nested models to be applied to dengue fever epidemiology. We perform a qualitative study in order to show how much complexity we really need to add into epidemiological models to be able to describe the fluctuations observed in empirical dengue hemorrhagic fever incidence data offering a promising perspective on inference of parameter values from dengue case notifications.

  4. Dynamic statistical models of biological cognition: insights from communications theory

    Science.gov (United States)

    Wallace, Rodrick

    2014-10-01

    Maturana's cognitive perspective on the living state, Dretske's insight on how information theory constrains cognition, the Atlan/Cohen cognitive paradigm, and models of intelligence without representation, permit construction of a spectrum of dynamic necessary conditions statistical models of signal transduction, regulation, and metabolism at and across the many scales and levels of organisation of an organism and its context. Nonequilibrium critical phenomena analogous to physical phase transitions, driven by crosstalk, will be ubiquitous, representing not only signal switching, but the recruitment of underlying cognitive modules into tunable dynamic coalitions that address changing patterns of need and opportunity at all scales and levels of organisation. The models proposed here, while certainly providing much conceptual insight, should be most useful in the analysis of empirical data, much as are fitted regression equations.

  5. Expression of Hox, Cdx, and Six3/6 genes in the hoplonemertean Pantinonemertes californiensis offers insight into the evolution of maximally indirect development in the phylum Nemertea.

    Science.gov (United States)

    Hiebert, Laurel S; Maslakova, Svetlana A

    2015-01-01

    Maximally indirect development via a pilidium larva is unique to the pilidiophoran clade of phylum Nemertea. All other nemerteans have more or less direct development. The origin of pilidial development with disjunct invaginated juvenile rudiments and catastrophic metamorphosis remains poorly understood. While basal members of the phylum, the Palaeonemertea, do not appear to have ever had a pilidium, certain similarity exists in the development of the Pilidiophora and the sister clade, the Hoplonemertea. It is unclear whether this similarity represents the homology and whether pilidial development evolved before or after pilidiophorans diverged from hoplonemerteans. To gain insight into these questions, we examined the expression of Hox, Cdx, and Six3/6 genes in the development of the hoplonemertean Pantinonemertes californiensis and expression of Six3/6 in the pilidium of Micrura alaskensis. To further characterize the function of larval structures showing expression of these genes, we examined the serotonergic nervous system and cell proliferation in P. californiensis. We show that Hox and Cdx genes, which pattern the pilidial imaginal discs giving rise to the juvenile trunk, are expressed in paired posterior epidermal invaginations in P. californiensis larvae. We also show that Six3/6 patterns both the pilidial cephalic discs, which give rise to the juvenile head, and a pair of anterior epidermal invaginations in hoplonemertean development. We show that anterior invaginations in larval P. californiensis are associated with a pair of serotonergic neurons, and thus may have a role in the development of the juvenile nervous system. This is similar to the role of cephalic discs in pilidiophoran development. Finally, we show that four zones of high cell proliferation correspond to the paired invaginations in P. californiensis, suggesting that these invaginations may play a similar role in the development of the hoplonemertean juvenile to the role of imaginal discs in

  6. Hydrologic impacts of past shifts of Earth's thermal equator offer insight into those to be produced by fossil fuel CO2.

    Science.gov (United States)

    Broecker, Wallace S; Putnam, Aaron E

    2013-10-15

    Major changes in global rainfall patterns accompanied a northward shift of Earth's thermal equator at the onset of an abrupt climate change 14.6 kya. This northward pull of Earth's wind and rain belts stemmed from disintegration of North Atlantic winter sea ice cover, which steepened the interhemispheric meridional temperature gradient. A southward migration of Earth's thermal equator may have accompanied the more recent Medieval Warm to Little Ice Age climate transition in the Northern Hemisphere. As fossil fuel CO2 warms the planet, the continents of the Northern Hemisphere are expected to warm faster than the Southern Hemisphere oceans. Therefore, we predict that a northward shift of Earth's thermal equator, initiated by an increased interhemispheric temperature contrast, may well produce hydrologic changes similar to those that occurred during past Northern Hemisphere warm periods. If so, the American West, the Middle East, and southern Amazonia will become drier, and monsoonal Asia, Venezuela, and equatorial Africa will become wetter. Additional paleoclimate data should be acquired and model simulations should be conducted to evaluate the reliability of this analog.

  7. Subcellular localization of a fluorescent derivative of CuII(atsm) offers insight into the neuroprotective action of CuII(atsm).

    Science.gov (United States)

    Price, Katherine Ann; Crouch, Peter J; Lim, SinChun; Paterson, Brett M; Liddell, Jeffrey R; Donnelly, Paul S; White, Anthony R

    2011-12-01

    Copper complexes of bis(thiosemicarbazone) (Cu(II)(btsc)s) have been studied as potential anti-cancer agents and hypoxia imaging agents. More recently, Cu(II)(btsc)s have been identified as possessing potent neuroprotective properties in cell and animal models of neurodegenerative disease. Despite their broad range of pharmacological activity little is known about how cells traffic Cu(II)(btsc)s and how this relates to potential anti-cancer or neuroprotective outcomes. One method of investigating sub-cellular localization of metal complexes is through confocal fluorescence imaging of the compounds in cells. Previously we harnessed the fluorescence of a pyrene group attached to diacetyl-bis(N4-methylthiosemicarbazonato)copper(ii)) (Cu(II)(atsm)), (Cu(II)L(1)). We demonstrated that Cu(II)L(1) was partially localized to lysosomes in HeLa cancer epithelial cells. Here we extend these studies to map the sub-cellular localization of Cu(II)L(1) in M17 neuroblastoma cells. Treatment of M17 or HeLa cells led to rapid association of the Cu-complex into distinct punctate structures that partially co-localized with lysosomes as assessed by co-localization with Lysotracker and acridine orange. No localization to early or late endosomes, the nucleus or mitochondria was observed. We also found evidence for a limited association of Cu(II)L(1) with autophagic structures, however, this did not account for the majority of the punctate localization of Cu(II)L(1). In addition, Cu(II)L(1) revealed partial localization with ER Tracker and was found to inhibit ER stress induced by tunicamycin. This is the first report to comprehensively characterize the sub-cellular localization of a Cu(II)(atsm) derivative in cells of a neuronal origin and the partial association with lysosome/autophagic structures and the ER may have a potential role in neuroprotection.

  8. Offering a model for measuring service brand equity in the field of services : Testing and implementation in a virtual university.

    Directory of Open Access Journals (Sweden)

    Mehdi Giahchin

    2013-09-01

    Full Text Available Nowadays brand in businesses around the world including service provider companies, has a special role and a great importance.Brand equity is also a powerful tool in the marketing competitionthus managing the brand equity measurement is consequential. In this study we are trying to find some effective dimensions of the brand equity in the service firms and companies and after that we are going to offer some significant dimensions as a comprehensive model in education and e-learning at the level of higher education with considering different aspects of the products and services and also with considering the different aspects of service businesses on the services spectrumthen test the model statistically in a virtual university. Data collection was done through a questionnaire distributed to all 1031 faculty, students and staff of Mehralborz university and 300 responses were received. Sampling was done through random method and the sample volume based on Cochran's formula was 280 persons. Cronbach's alpha was used to ensure the reliability of the questionnaire and structural equation modeling was used to test the model. The consequences of statistical analysis showed that among the factors related to the customers, just experiences and psychological characteristics of faculty, students and staff are effective on the service brand equity of Mehralborz university.And also among the factors related to the brand awareness,just marketing activities are effective on the service brand equity of Mehralborz uiversity. Among the characteristics offered for the brand image,just symbolic characteristics and servicescape and also servise provider characteristics are effective on the service brand equity of Mehralborz university.

  9. Insights into pre-reversal paleosecular variation from stochastic models

    Science.gov (United States)

    Peqini, Klaudio; Duka, Bejo; De Santis, Angelo

    2015-09-01

    To provide insights on the paleosecular variation of the geomagnetic field and the mechanism of reversals, long time series of the dipolar magnetic moment are generated by two different stochastic models, known as the “domino” model and the inhomogeneous Lebovitz disk dynamo model, with initial values taken from the from paleomagnetic data. The former model considers mutual interactions of N macrospins embedded in a uniformly rotating medium, where random forcing and dissipation act on each macrospin. With an appropriate set of the model’s parameters values, the series generated by this model have similar statistical behaviour to the time series of the SHA.DIF.14K model. The latter model is an extension of the classical two-disk Rikitake model, considering N dynamo elements with appropriate interactions between them. We varied the parameters set of both models aiming at generating suitable time series with behaviour similar to the long time series of recent secular variation (SV). Such series are then extended to the near future, obtaining reversals in both cases of models. The analysis of the time series generated by simulating the models show that the reversals appears after a persistent period of low intensity geomagnetic field, as it is occurring in the present times.

  10. Insights into pre-reversal paleosecular variation from stochastic models

    Directory of Open Access Journals (Sweden)

    Klaudio ePeqini

    2015-09-01

    Full Text Available To provide insights on the paleosecular variation of the geomagnetic field and the mechanism of reversals, long time series of the dipolar magnetic moment are generated by two different stochastic models, known as the domino model and the inhomogeneous Lebovitz disk dynamo model, with initial values taken from the from paleomagnetic data. The former model considers mutual interactions of N macrospins embedded in a uniformly rotating medium, where random forcing and dissipation act on each macrospin. With an appropriate set of the model’s parameters values, the series generated by this model have similar statistical behaviour to the time series of the SHA.DIF.14K model. The latter model is an extension of the classical two-disk Rikitake model, considering N dynamo elements with appropriate interactions between them.We varied the parameters set of both models aiming at generating suitable time series with behaviour similar to the long time series of recent secular variation (SV. Such series are then extended to the near future, obtaining reversals in both cases of models. The analysis of the time series generated by simulating the models show that the reversals appears after a persistent period of low intensity geomagnetic field, as it is occurring in the present times.

  11. Study Offers New Insights into Triassic Protorosaurs

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ The novel discovery of a longnecked marine reptile fossil in southwest China's Guizhou Province sheds new light on the evolution, diversity and hunting strategies of protorosaurid that lived before the dinosaur, about 230 million years ago.

  12. Insights from Development of Regulatory PSA Model for SMART

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang Ju; Cho, Nam Chul [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of); Kim, Inn Seock [ISSA Technology, Maryland (United States); Lee, Yong Suk [Seoul National University, Seoul (Korea, Republic of)

    2010-10-15

    SMART (System-Integrated Modular Advanced Reactor) is a first-of-the-kind integral reactor with 330 MW thermal power under active development by Korea Atomic Energy Research Institute (KAERI) for power generation and seawater desalination. SMART employs various design features that are not typically found in other nuclear power plants. Examples include a unique passive residual heat removal system (PRHRS), and enclosure of a pressurizer, eight helical steam generators, and eight canned reactor coolant pumps inside the reactor pressure vessel. This paper presents risk insights on the SMART reactor gained during the development of a regulatory PSA model by Korea Institute of Nuclear Safety (KINS)

  13. Insights on PRA Review Practices: Necessity for Model Shaking

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Inn Seock; Jang, Mi suk; Kim, Seoung Rae [NESS, Daejeon (Korea, Republic of)

    2016-05-15

    Probabilistic risk assessment (PRA) is increasingly used as a technique to help ensure design and operational safety of nuclear power plants (NPPs) in the nuclear industry. Hence, there is considerable interest in the PRA quality, and as a result, a peer review of the PRA model is typically performed to ensure its technical adequacy as part of the PRA development process or for any other reason (e.g., regulatory requirement). For the PRA model to be used as a valuable vehicle for risk-informed applications, it is essential that the PRA model must yield correct and physically meaningful accident sequences and minimal cutsets for specific plant configurations or conditions relating to the applications. Hence, the existing peer review guidelines need to be updated to reflect these insights so that risk-informed applications could be more actively pursued with confidence.

  14. Insights revealed by rodent models of sugar binge eating.

    Science.gov (United States)

    Murray, Susan M; Tulloch, Alastair J; Chen, Eunice Y; Avena, Nicole M

    2015-12-01

    Binge eating is seen across the spectrum of eating disorder diagnoses as well as among individuals who do not meet diagnostic criteria. Analyses of the specific types of foods that are frequently binged upon reveal that sugar-rich items feature prominently in binge-type meals, making the effects of binge consumption of sugar an important focus of study. One avenue to do this involves the use of animal models. Foundational and recent studies of animal models of sugar bingeing, both outlined here, lend insight into the various neurotransmitters and neuropeptides that may participate in or be altered by this behavior. Further, several preclinical studies incorporating sugar bingeing paradigms have explored the utility of pharmacological agents that target such neural systems for reducing sugar bingeing in an effort to enhance clinical treatment. Indeed, the translational implications of findings generated using animal models of sugar bingeing are considered here, along with potential avenues for further study.

  15. Model year 2010 Honda insight level-1 testing report.

    Energy Technology Data Exchange (ETDEWEB)

    Rask, E.; Bocci, D.; Duoba, M.; Lohse-Busch, H. (Energy Systems)

    2011-03-22

    As a part of the US Department of Energy's Advanced Vehicle Testing Activity (AVTA), a model year 2010 Honda Insight was procured by eTec (Phoenix, AZ) and sent to ANL's Advanced Powertrain Research Facility for the purposes of vehicle-level testing in support of the Advanced Vehicle Testing Activity (AVTA). Data was acquired during testing using non-intrusive sensors, vehicle network information, and facilities equipment (emissions and dynamometer data). Standard drive cycles, performance cycles, steady-state cycles and A/C usage cycles were tested. Much of this data is openly available for download in ANL's Downloadable Dynamometer Database (D3). The major results are shown here in this report. Given the preliminary nature of this assessment, the majority of the testing was done over standard regulatory cycles and seeks to obtain a general overview of how the vehicle performs. These cycles include the US FTP cycle (Urban) and Highway Fuel Economy Test cycle as well as the US06, a more aggressive supplemental regulatory cycle. Data collection for this testing was kept at a fairly high level and includes emissions and fuel measurements from an exhaust emissions bench, high-voltage and accessory current and voltage from a DC power analyzer, and CAN bus data such as engine speed, engine load, and electric machine operation when available. The following sections will seek to explain some of the basic operating characteristics of the MY2010 Insight and provide insight into unique features of its operation and design.

  16. APP physiological and pathophysiological functions:insights from animal models

    Institute of Scientific and Technical Information of China (English)

    Qinxi Guo; Zilai Wang; Hongmei Li; Mary Wiese; Hui Zheng

    2012-01-01

    The amyloid precursor protein (APP) has been under intensive study in recent years,mainly due to its critical role in the pathogenesis of Alzheimer's disease (AD).β-Amyloid (Aβ) peptides generated from APP proteolytic cleavage can aggregate,leading to plaque formation in human AD brains.Point mutations of APP affecting Aβ production are found to be causal for hereditary early onset familial AD.It is very likely that elucidating the physiological properties of APP will greatly facilitate the understanding of its role in AD pathogenesis.A number of APP loss- and gainof-function models have been established in model organisms including Caenorhabditis elegans,Drosophila,zebrafish and mouse.These in vivo models provide us valuable insights into APP physiological functions.In addition,several knock-in mouse models expressing mutant APP at a physiological level are available to allow us to study AD pathogenesis without APP overexpression.This article will review the current physiological and pathophysiological animal models of APP.

  17. Preventing clonal evolutionary processes in cancer: Insights from mathematical models.

    Science.gov (United States)

    Rodriguez-Brenes, Ignacio A; Wodarz, Dominik

    2015-07-21

    Clonal evolutionary processes can drive pathogenesis in human diseases, with cancer being a prominent example. To prevent or treat cancer, mechanisms that can potentially interfere with clonal evolutionary processes need to be understood better. Mathematical modeling is an important research tool that plays an ever-increasing role in cancer research. This paper discusses how mathematical models can be useful to gain insights into mechanisms that can prevent disease initiation, help analyze treatment responses, and aid in the design of treatment strategies to combat the emergence of drug-resistant cells. The discussion will be done in the context of specific examples. Among defense mechanisms, we explore how replicative limits and cellular senescence induced by telomere shortening can influence the emergence and evolution of tumors. Among treatment approaches, we consider the targeted treatment of chronic lymphocytic leukemia (CLL) with tyrosine kinase inhibitors. We illustrate how basic evolutionary mathematical models have the potential to make patient-specific predictions about disease and treatment outcome, and argue that evolutionary models could become important clinical tools in the field of personalized medicine.

  18. Cholinergic modulation of cognitive processing: insights drawn from computational models

    Directory of Open Access Journals (Sweden)

    Ehren L Newman

    2012-06-01

    Full Text Available Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm play a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers.

  19. Neural circuit dysfunction in schizophrenia: Insights from animal models.

    Science.gov (United States)

    Sigurdsson, T

    2016-05-03

    Despite decades of research, the neural circuit abnormalities underlying schizophrenia remain elusive. Although studies on schizophrenia patients have yielded important insights they have not been able to fully reveal the details of how neural circuits are disrupted in the disease, which is essential for understanding its pathophysiology and developing new treatment strategies. Animal models of schizophrenia are likely to play an important role in this effort. Such models allow neural circuit dysfunction to be investigated in detail and the role of risk factors and pathophysiological mechanisms to be experimentally assessed. The goal of this review is to summarize what we have learned from electrophysiological studies that have examined neural circuit function in animal models of schizophrenia. Although these studies have revealed diverse manifestations of neural circuit dysfunction spanning multiple levels of analysis, common themes have nevertheless emerged across different studies and animal models, revealing a core set of neural circuit abnormalities. These include an imbalance between excitation and inhibition, deficits in synaptic plasticity, disruptions in local and long-range synchrony and abnormalities in dopaminergic signaling. The relevance of these findings to the pathophysiology of the disease is discussed, as well as outstanding questions for future research.

  20. Genetic Aspects of Autism Spectrum Disorders: Insights from Animal Models

    Directory of Open Access Journals (Sweden)

    Swati eBanerjee

    2014-02-01

    Full Text Available Autism spectrum disorders (ASD are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute towards the formation, stabilization and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD.

  1. Zebrafish Models of Human Leukemia: Technological Advances and Mechanistic Insights.

    Science.gov (United States)

    Harrison, Nicholas R; Laroche, Fabrice J F; Gutierrez, Alejandro; Feng, Hui

    2016-01-01

    Insights concerning leukemic pathophysiology have been acquired in various animal models and further efforts to understand the mechanisms underlying leukemic treatment resistance and disease relapse promise to improve therapeutic strategies. The zebrafish (Danio rerio) is a vertebrate organism with a conserved hematopoietic program and unique experimental strengths suiting it for the investigation of human leukemia. Recent technological advances in zebrafish research including efficient transgenesis, precise genome editing, and straightforward transplantation techniques have led to the generation of a number of leukemia models. The transparency of the zebrafish when coupled with improved lineage-tracing and imaging techniques has revealed exquisite details of leukemic initiation, progression, and regression. With these advantages, the zebrafish represents a unique experimental system for leukemic research and additionally, advances in zebrafish-based high-throughput drug screening promise to hasten the discovery of novel leukemia therapeutics. To date, investigators have accumulated knowledge of the genetic underpinnings critical to leukemic transformation and treatment resistance and without doubt, zebrafish are rapidly expanding our understanding of disease mechanisms and helping to shape therapeutic strategies for improved outcomes in leukemic patients.

  2. UV damage of collagen: insights from model collagen peptides.

    Science.gov (United States)

    Jariashvili, Ketevan; Madhan, Balaraman; Brodsky, Barbara; Kuchava, Ana; Namicheishvili, Louisa; Metreveli, Nunu

    2012-03-01

    Fibrils of Type I collagen in the skin are exposed to ultraviolet (UV) light and there have been claims that collagen photo-degradation leads to wrinkles and may contribute to skin cancers. To understand the effects of UV radiation on collagen, Type I collagen solutions were exposed to the UV-C wavelength of 254 nm for defined lengths of time at 4°C. Circular dichroism (CD) experiments show that irradiation of collagen leads to high loss of triple helical content with a new lower thermal stability peak and SDS-gel electrophoresis indicates breakdown of collagen chains. To better define the effects of UV radiation on the collagen triple-helix, the studies were extended to peptides which model the collagen sequence and conformation. CD studies showed irradiation for days led to lower magnitudes of the triple-helix maximum at 225 nm and lower thermal stabilities for two peptides containing multiple Gly-Pro-Hyp triplets. In contrast, the highest radiation exposure led to little change in the T(m) values of (Gly-Pro-Pro)(10) and (Ala-Hyp-Gly)(10) , although (Gly-Pro-Pro)(10) did show a significant decrease in triple helix intensity. Mass spectroscopy indicated preferential cleavage sites within the peptides, and identification of some of the most susceptible sites of cleavage. The effect of radiation on these well defined peptides gives insight into the sequence and conformational specificity of photo-degradation of collagen.

  3. Stents: Biomechanics, Biomaterials, and Insights from Computational Modeling.

    Science.gov (United States)

    Karanasiou, Georgia S; Papafaklis, Michail I; Conway, Claire; Michalis, Lampros K; Tzafriri, Rami; Edelman, Elazer R; Fotiadis, Dimitrios I

    2017-04-01

    Coronary stents have revolutionized the treatment of coronary artery disease. Improvement in clinical outcomes requires detailed evaluation of the performance of stent biomechanics and the effectiveness as well as safety of biomaterials aiming at optimization of endovascular devices. Stents need to harmonize the hemodynamic environment and promote beneficial vessel healing processes with decreased thrombogenicity. Stent design variables and expansion properties are critical for vessel scaffolding. Drug-elution from stents, can help inhibit in-stent restenosis, but adds further complexity as drug release kinetics and coating formulations can dominate tissue responses. Biodegradable and bioabsorbable stents go one step further providing complete absorption over time governed by corrosion and erosion mechanisms. The advances in computing power and computational methods have enabled the application of numerical simulations and the in silico evaluation of the performance of stent devices made up of complex alloys and bioerodible materials in a range of dimensions and designs and with the capacity to retain and elute bioactive agents. This review presents the current knowledge on stent biomechanics, stent fatigue as well as drug release and mechanisms governing biodegradability focusing on the insights from computational modeling approaches.

  4. Genetic rodent models of obesity-associated ovarian dysfunction and subfertility: insights into polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Isabel eHuang-Doran

    2016-06-01

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrinopathy affecting women, and a leading cause of female infertility worldwide. Defined clinically by the presence of hyperandrogenemia and oligomenorrhoea, PCOS represents a state of hormonal dysregulation, disrupted ovarian follicle dynamics, and subsequent oligo- or anovulation. The syndrome’s prevalence is attributed at least partly to a well-established association with obesity and insulin resistance (IR. Indeed, the presence of severe PCOS in human genetic obesity and IR syndromes supports a causal role for IR in the pathogenesis of PCOS. The molecular mechanisms underlying this causality, however, as well as the important role of hyperandrogenemia, remain poorly elucidated. As such, treatment of PCOS is necessarily empirical, focusing on symptom alleviation. The generation of knockout and transgenic rodent models of obesity and IR offer a promising platform in which to address mechanistic questions about reproductive dysfunction in the context of metabolic disease. The impact of primary perturbations in rodent gonadotrophin or androgen signaling has been similarly interrogated. The insights gained from such models, however, have been limited by the relatively poor fidelity of rodent models to human PCOS. In this minireview we evaluate the ovarian phenotypes associated with rodent models of obesity and IR, including the extent of endocrine disturbance, ovarian dysmorphology and subfertility. We compare them to both human PCOS and other animal models of the syndrome (genetic and hormonal, explore reasons for their discordance and consider the new opportunities that are emerging to better understand and treat this important condition.

  5. Genetic Rodent Models of Obesity-Associated Ovarian Dysfunction and Subfertility: Insights into Polycystic Ovary Syndrome

    Science.gov (United States)

    Huang-Doran, Isabel; Franks, Stephen

    2016-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women and a leading cause of female infertility worldwide. Defined clinically by the presence of hyperandrogenemia and oligomenorrhoea, PCOS represents a state of hormonal dysregulation, disrupted ovarian follicle dynamics, and subsequent oligo- or anovulation. The syndrome’s prevalence is attributed, at least partly, to a well-established association with obesity and insulin resistance (IR). Indeed, the presence of severe PCOS in human genetic obesity and IR syndromes supports a causal role for IR in the pathogenesis of PCOS. However, the molecular mechanisms underlying this causality, as well as the important role of hyperandrogenemia, remain poorly elucidated. As such, treatment of PCOS is necessarily empirical, focusing on symptom alleviation. The generation of knockout and transgenic rodent models of obesity and IR offers a promising platform in which to address mechanistic questions about reproductive dysfunction in the context of metabolic disease. Similarly, the impact of primary perturbations in rodent gonadotrophin or androgen signaling has been interrogated. However, the insights gained from such models have been limited by the relatively poor fidelity of rodent models to human PCOS. In this mini review, we evaluate the ovarian phenotypes associated with rodent models of obesity and IR, including the extent of endocrine disturbance, ovarian dysmorphology, and subfertility. We compare them to both human PCOS and other animal models of the syndrome (genetic and hormonal), explore reasons for their discordance, and consider the new opportunities that are emerging to better understand and treat this important condition. PMID:27375552

  6. Modelling insights on the partition of evapotranspiration components across biomes

    Science.gov (United States)

    Fatichi, Simone; Pappas, Christoforos

    2017-04-01

    Recent studies using various methodologies have found a large variability (from 35 to 90%) in the ratio of transpiration to total evapotranspiration (denoted as T:ET) across biomes or even at the global scale. Concurrently, previous results suggest that T:ET is independent of mean precipitation and has a positive correlation with Leaf Area Index (LAI). We used the mechanistic ecohydrological model, T&C, with a refined process-based description of soil resistance and a detailed treatment of canopy biophysics and ecophysiology, to investigate T:ET across multiple biomes. Contrary to observation-based estimates, simulation results highlight a well-constrained range of mean T:ET across biomes that is also robust to perturbations of the most sensitive parameters. Simulated T:ET was confirmed to be independent of average precipitation, while it was found to be uncorrelated with LAI across biomes. Higher values of LAI increase evaporation from interception but suppress ground evaporation with the two effects largely cancelling each other in many sites. These results offer mechanistic, model-based, evidence to the ongoing research about the range of T:ET and the factors affecting its magnitude across biomes.

  7. Fracture development around deep underground excavations: Insights from FDEM modelling

    Directory of Open Access Journals (Sweden)

    Andrea Lisjak

    2014-12-01

    Full Text Available Over the past twenty years, there has been a growing interest in the development of numerical models that can realistically capture the progressive failure of rock masses. In particular, the investigation of damage development around underground excavations represents a key issue in several rock engineering applications, including tunnelling, mining, drilling, hydroelectric power generation, and the deep geological disposal of nuclear waste. The goal of this paper is to show the effectiveness of a hybrid finite-discrete element method (FDEM code to simulate the fracturing mechanisms associated with the excavation of underground openings in brittle rock formations. A brief review of the current state-of-the-art modelling approaches is initially provided, including the description of selecting continuum- and discontinuum-based techniques. Then, the influence of a number of factors, including mechanical and in situ stress anisotropy, as well as excavation geometry, on the simulated damage is analysed for three different geomechanical scenarios. Firstly, the fracture nucleation and growth process under isotropic rock mass conditions is simulated for a circular shaft. Secondly, the influence of mechanical anisotropy on the development of an excavation damaged zone (EDZ around a tunnel excavated in a layered rock formation is considered. Finally, the interaction mechanisms between two large caverns of an underground hydroelectric power station are investigated, with particular emphasis on the rock mass response sensitivity to the pillar width and excavation sequence. Overall, the numerical results indicate that FDEM simulations can provide unique geomechanical insights in cases where an explicit consideration of fracture and fragmentation processes is of paramount importance.

  8. Preliminary insights into a model for mafic magma fragmentation

    Science.gov (United States)

    Edwards, Matt; Pioli, Laura; Andronico, Daniele; Cristaldi, Antonio; Scollo, Simona

    2017-04-01

    phase durations obtained from the network of fixed INGV cameras, early insight into possible links between fragmentation and eruption conditions are identified. A link between fragmentation and magma properties is also examined. We discuss the relationship between the conventional and new analytical methods and their potential in unraveling key information on the fragmentation process and analyse how the dataset on the May eruption can be modelled with the current fragmentation theories. Finally, we suggest the systematic use of a comprehensive TGSD dataset to develop a fragmentation model for mafic eruptions.

  9. GSK-3: functional insights from cell biology and animal models

    Directory of Open Access Journals (Sweden)

    Oksana eKaidanovich-Beilin

    2011-11-01

    Full Text Available Glycogen synthase kinase-3 (GSK-3 is a widely expressed and highly conserved serine/threonine protein kinase encoded in mammals by two genes that generate two related proteins: GSK-3α and GSK-3β. GSK-3 is active in cells under resting conditions and is primarily regulated through inhibition or diversion of its activity. While GSK-3 is one of the few protein kinases that can be inactivated by phosphorylation, the mechanisms of GSK-3 regulation are more varied and not fully understood. Precise control appears to be achieved by a combination of phosphorylation, localization, and sequestration by a number of GSK-3-binding proteins. GSK-3 lies downstream of several major signaling pathways including the phosphatidylinositol 3’ kinase pathway, the Wnt pathway, Hedgehog signaling and Notch. Specific pools of GSK-3, which differ in intracellular localization, binding partner affinity and relative amount are differentially sensitized to several distinct signaling pathways and these sequestration mechanisms contribute to pathway insulation and signal specificity. Dysregulation of signaling pathways involving GSK-3 is associated with the pathogenesis of numerous neurological and psychiatric disorders and there are data suggesting GSK-3 isoform-selective roles in several of these. Here, we review the current knowledge of GSK-3 regulation and targets and discuss the various animal models that have been employed to dissect the functions of GSK-3 in brain development and function through the use of conventional or conditional knock-out mice as well as transgenic mice. These studies have revealed fundamental roles for these protein kinases in memory, behavior and neuronal fate determination and provide insights into possible therapeutic interventions.

  10. Offer/Acceptance Ratio.

    Science.gov (United States)

    Collins, Mimi

    1997-01-01

    Explores how human resource professionals, with above average offer/acceptance ratios, streamline their recruitment efforts. Profiles company strategies with internships, internal promotion, cooperative education programs, and how to get candidates to accept offers. Also discusses how to use the offer/acceptance ratio as a measure of program…

  11. Breaching the skin barrier--insights from molecular simulation of model membranes.

    Science.gov (United States)

    Notman, Rebecca; Anwar, Jamshed

    2013-02-01

    Breaching the skin's barrier function by design is an important strategy for delivering drugs and vaccines to the body. However, while there are many proposed approaches for reversibly breaching the skin barrier, our understanding of the molecular processes involved is still rudimentary. Molecular simulation offers an unprecedented molecular-level resolution with an ability to reproduce molecular and bulk level properties. We review the basis of the molecular simulation methodology and give applications of relevance to the skin lipid barrier, focusing on permeation of molecules and chemical approaches for breaching the lipid barrier by design. The bulk kinetic model based on Fick's Law describing absorption of a drug through skin has been reconciled with statistical mechanical quantities such as the local excess chemical potential and local diffusion coefficient within the membrane structure. Applications of molecular simulation reviewed include investigations of the structure and dynamics of simple models of skin lipids, calculation of the permeability of molecules in simple model membranes, and mechanisms of action of the penetration enhancers, DMSO, ethanol and oleic acid. The studies reviewed illustrate the power and potential of molecular simulation to yield important physical insights, inform and rationalize experimental studies, and to predict structural changes, and kinetic and thermodynamic quantities. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Insight, psychopathology, explanatory models and outcome of schizophrenia in India: a prospective 5-year cohort study

    Directory of Open Access Journals (Sweden)

    Johnson Shanthi

    2012-09-01

    Full Text Available Abstract Background The sole focus of models of insight on bio-medical perspectives to the complete exclusion of local, non-medical and cultural constructs mandates review. This study attempted to investigate the impact of insight, psychopathology, explanatory models of illness on outcome of first episode schizophrenia. Method Patients diagnosed to have DSM IV schizophrenia (n = 131 were assessed prospectively for insight, psychopathology, explanatory models of illness at baseline, 6, 12 and 60 months using standard instruments. Multiple linear and logistic regression and generalized estimating equations (GEE were employed to assess predictors of outcome. Results We could follow up 95 (72.5% patients. Sixty-five of these patients (68.4% achieved remission. There was a negative relationship between psychosis rating and insight scores. Urban residence, fluctuating course of the initial illness, and improvement in global functioning at 6 months and lower psychosis rating at 12 months were significantly related to remission at 5 years. Insight scores, number of non-medical explanatory models and individual explanatory models held during the later course of the illness were significantly associated with outcome. Analysis of longitudinal data using GEE showed that women, rural residence, insight scores and number of non-medical explanatory models of illness held were significantly associated with BPRS scores during the study period. Conclusions Insight, the disease model and the number of non-medical model positively correlated with improvement in psychosis arguing for a complex interaction between the culture, context and illness variables. These finding argue that insight and explanatory models are secondary to psychopathology, course and outcome of the illness. The awareness of mental illness is a narrative act in which people make personal sense of the many challenges they face. The course and outcome of the illness, cultural context

  13. Photosynthetic water oxidation: insights from manganese model chemistry.

    Science.gov (United States)

    Young, Karin J; Brennan, Bradley J; Tagore, Ranitendranath; Brudvig, Gary W

    2015-03-17

    Catalysts for light-driven water oxidation are a critical component for development of solar fuels technology. The multielectron redox chemistry required for this process has been successfully deployed on a global scale in natural photosynthesis by green plants and cyanobacteria using photosystem II (PSII). PSII employs a conserved, cuboidal Mn4CaOX cluster called the O2-evolving complex (OEC) that offers inspiration for artificial O2-evolution catalysts. In this Account, we describe our work on manganese model chemistry relevant to PSII, particularly the functional model [Mn(III/IV)2(terpy)2(μ-O)2(OH2)2](NO3)3 complex (terpy = 2,2';6',2″-terpyridine), a mixed-valent di-μ-oxo Mn dimer with two terminal aqua ligands. In the presence of oxo-donor oxidants such as HSO5(-), this complex evolves O2 by two pathways, one of which incorporates solvent water in an O-O bond-forming reaction. Deactivation pathways of this catalyst include comproportionation to form an inactive Mn(IV)Mn(IV) dimer and also degradation to MnO2, a consequence of ligand loss when the oxidation state of the complex is reduced to labile Mn(II) upon release of O2. The catalyst's versatility has been shown by its continued catalytic activity after direct binding to the semiconductor titanium dioxide. In addition, after binding to the surface of TiO2 via a chromophoric linker, the catalyst can be oxidized by a photoinduced electron-transfer mechanism, mimicking the natural PSII process. Model oxomanganese complexes have also aided in interpreting biophysical and computational studies on PSII. In particular, the μ-oxo exchange rates of the Mn-terpy dimer have been instrumental in establishing that the time scale for μ-oxo exchange of high-valent oxomanganese complexes with terminal water ligands is slower than O2 evolution in the natural photosynthetic system. Furthermore, computational studies on the Mn-terpy dimer and the OEC point to similar Mn(IV)-oxyl intermediates in the O-O bond

  14. Exotic models may offer unique opportunities to decipher specific scientific question: the case of Xenopus olfactory system.

    Science.gov (United States)

    Gascuel, Jean; Amano, Tosikazu

    2013-09-01

    The fact that olfactory systems are highly conserved in all animal species from insects to mammals allow the generalization of findings from one species to another. Most of our knowledge about the anatomy and physiology of the olfactory system comes from data obtained in a very limited number of biological models such as rodents, Zebrafish, Drosophila, and a worm, Caenorhabditis elegans. These models have proved useful to answer most questions in the field of olfaction, and thus concentrating on these few models appear to be a pragmatic strategy. However, the diversity of the organization and physiology of the olfactory system amongst phyla appear to be greater than generally assumed and the four models alone may not be sufficient to address all the questions arising from the study of olfaction. In this article, we will illustrate the idea that we should take advantage of biological diversity to address specific scientific questions and will show that the Xenopus olfactory system is a very good model to investigate: first, olfaction in aerial versus aquatic conditions and second, mechanisms underlying postnatal reorganization of the olfactory system especially those controlled by tyroxine hormone.

  15. An educational model for preparing Christian nurses and church congregations to offer local whole-person health programmes

    Directory of Open Access Journals (Sweden)

    Helen Anne Wordsworth

    2016-01-01

    Full Text Available The implications of the Tübingen declarations for congregational involvement in health provide the setting for this commentary. Using an example from the United Kingdom, where government health provision has become economically challenging and largely disease focused, the author demonstrates how it is possible to introduce the kind of education for nurses and congregations that will lead to them becoming important sources of whole-person health promotion. In this way, parish nurses and church congregations may make a distinctive contribution that will complement state and private health provision. This model has relevance across all Christian denominations. It is already being followed in 28 different countries, and with appropriate respect to culture, language and health policy, could be globally transferable.

  16. A three-dimensional model of thoughts: insight into depression.

    Science.gov (United States)

    Desseilles, Martin; Chang, Trina; Piguet, Camille; Bertschy, Gilles; Dayer, Alexandre G

    2012-01-01

    Thought processing and mood regulation are closely linked, but existing classifications of mood disorders fail to recognize the complex interplay between these two clinical dimensions. Furthermore, existing classifications fail to account for the possibility that depression might be associated with an increased frequency of self-referential thoughts that could in some circumstances be related to creativity processes. Based on recent evidence from clinical phenomenology, experimental psychology and affective neuroscience, we propose a novel comprehensive theoretical framework that incorporates thought processing and emotional valence. This new taxonomy provides insights into the clinical understanding of the spectrum of mood disorders and accounts for the possibility of increased creativity in altered mood states.

  17. Insights into pulverized rock formation from dynamic rupture models of earthquakes

    Science.gov (United States)

    Payne, R. M.; Duan, B.

    2017-02-01

    Pulverized rocks (PR) are extremely incohesive and highly fractured rocks found within the damage zones of several large strike-slip faults around the world. They maintain their crystal structure, show little evidence of shearing or chemical alteration, and are believed to be produced by strong tensile forces. Several mechanisms for pulverization have been proposed based on simple qualitative analyses or laboratory experiments under simplified loading conditions. Numerical modelling, however, can offer new insights into what is needed to produce PR and likely conditions of formation. We perform dynamic rupture simulations of different earthquakes, varying the magnitude, the slip distribution, and the rupture speed (supershear and subshear), while measuring the stresses produced away from the fault. To contextualize our results, a basic threshold of 10 MPa is set as the tensile strength of the rock mass and recordings are made of where, when, and by how much this threshold is exceeded for each earthquake type. Guided by field observations, we discern that a large (>Mw 7.1) subshear earthquake along a bimaterial fault produces a pulverized rock distribution most consistent with observations. The damage is asymmetric with the majority on the stiffer side of the fault extending out for several hundred metres. Within this zone there is a large and sudden volumetric expansion in all directions as the rupture passes. We propose that such an extreme tensile stress state, repeated for every earthquake, eventually produces the PR seen in the field.

  18. Insights: Simple Models for Teaching Equilibrium and Le Chatelier's Principle.

    Science.gov (United States)

    Russell, Joan M.

    1988-01-01

    Presents three models that have been effective for teaching chemical equilibrium and Le Chatelier's principle: (1) the liquid transfer model, (2) the fish model, and (3) the teeter-totter model. Explains each model and its relation to Le Chatelier's principle. (MVL)

  19. What One Physicist Has to Offer

    Science.gov (United States)

    Ross, Marc

    2004-05-01

    I was a particle theorist. In the early 1970s I began to analyze energy and its use in society. My theme is: What can physicists offer on a societal issue like energy? I have four topics: 1) Traffic safety and vehicle mass. The measurements are the record of some 40,000 deaths per year, vehicle characterizations and registrations. The statistical record is good, but information is lacking on physical processes in serious crashes. Our insight: while driver behavior is critical to safety, so is vehicle quality and design. Although one cannot definitively separate the injury impacts associated with momentum transfer from those due to intrusion, mass as such is not critical to safety. 2) Prospects for improving the energy efficiency of industrial processes. Our "measurements" were planning documents and interviews enabling us to analyze which "energy projects" were undertaken and which not. Insight: capital for projects was not allocated according to textbook economics; instead it was rationed. 3) Energy use by cars. Based on dynamometer studies motivated by the 1990 Clean Air Act Amendments, we created models of energy consumption that enable evaluation of modifications such as adopting a small engine while supplementing its capability for power. Insight: Vehicles could be designed to use much less fuel; but the gain for society is offset by low interest by new-car-buyers and manufacturers. 4) The effectiveness of automotive emissions controls. In addition to laboratory studies, we had surveys in "non-attainment" areas. Insight: Controls installed by original manufacturers are more robust and effective than repairs. Of the four, this is the one success for society. Conclusions: There are fascinating and solvable analytical challenges everywhere you look. But applications are hampered by the lack of a heritage and the close coupling between theorists and experimenters we know in physics.

  20. The mechanism of forearc basement subduction in eastern Taiwan: Insights from sandbox modeling: Insight from Sandbox

    Science.gov (United States)

    Lu, Chia-Yu

    2015-04-01

    In Taiwan today, the subduction of the Chinese continental margin under the Philippine Sea plate results in the progressive growth of an active orogenic wedge. It is one of the best places to study the complex relationships that occur between the tectono-metamorphic processes controlling deformation (plate rheology and kinematics) and surface processes (erosion and sedimentation). In the Central Range of Taiwan, foliation and lineation traces outline the geometry and kinematics of deformation in both, the foreland and hinterland of the orogenic wedge. The foliation dip and the strain ellipsoids distribution show the fan shape of a large pop-up structure characterizing the effects of oblique plate convergence. On the eastern flank, regionally developed penetrative cleavage dips, isotope data and sedimentary structures demonstrating regional overturned structures. Two mélange units, the Kenting and Lichi mélange are exposed at the south and east of the Central Range respectively. Experiments allow the study of interactions between tectonics and surface processes. Accounting for various boundary conditions and parameters such as sedimentation, erosion, basal friction, and décollement level. We present the results of 2D and 3D sandbox models designed to investigate the complex deformation characterizing the active Taiwan orogenic wedge and to demonstrate the development of those mélanges, overturned structures and mountain frontal thrusts. Models are analyzed using pictures, movies and PIV (Particle Image Velocimetry software). We then characterize the exhumation patterns, the mode of fault propagation and displacement patterns by strain partitioning of those mélanges and overturned structures.

  1. 土木工程投标报价模型研究(英)%An Offer Model for Civil Engineering Construction

    Institute of Scientific and Technical Information of China (English)

    卢德林; 章祥荪; 糜莺英

    2001-01-01

    本文主要研究单一不可分土木工程的n人投标报价模型.报价高低不是是否中标的唯一决定性因素,施工方案和工程报价为赢得工程施工合同共同发挥组合效应,并且在一定条件下,通过工程竞标,中标价会趋于Nash平衡.%In this paper,we consider an offer model in which one indivisible civil-engineering project of unknown construction cost is tendered to n tenders.The offer is not the sole decisive factor which decides who will get the contract,the tendering plan and the offer can play an important combinatorial role in the competition,and the winner's final offer via the procedure of competitive bidding tends to the symmetric Nash equilibrium in both the probabilistic sense and the economic sense.

  2. The Role of Serotype Interactions and Seasonality in Dengue Model Selection and Control: Insights from a Pattern Matching Approach.

    Science.gov (United States)

    Ten Bosch, Quirine A; Singh, Brajendra K; Hassan, Muhammad R A; Chadee, Dave D; Michael, Edwin

    2016-05-01

    The epidemiology of dengue fever is characterized by highly seasonal, multi-annual fluctuations, and the irregular circulation of its four serotypes. It is believed that this behaviour arises from the interplay between environmental drivers and serotype interactions. The exact mechanism, however, is uncertain. Constraining mathematical models to patterns characteristic to dengue epidemiology offers a means for detecting such mechanisms. Here, we used a pattern-oriented modelling (POM) strategy to fit and assess a range of dengue models, driven by combinations of temporary cross protective-immunity, cross-enhancement, and seasonal forcing, on their ability to capture the main characteristics of dengue dynamics. We show that all proposed models reproduce the observed dengue patterns across some part of the parameter space. Which model best supports the dengue dynamics is determined by the level of seasonal forcing. Further, when tertiary and quaternary infections are allowed, the inclusion of temporary cross-immunity alone is strongly supported, but the addition of cross-enhancement markedly reduces the parameter range at which dengue dynamics are produced, irrespective of the strength of seasonal forcing. The implication of these structural uncertainties on predicted vulnerability to control is also discussed. With ever expanding spread of dengue, greater understanding of dengue dynamics and control efforts (e.g. a near-future vaccine introduction) has become critically important. This study highlights the capacity of multi-level pattern-matching modelling approaches to offer an analytic tool for deeper insights into dengue epidemiology and control.

  3. Initial Public Offering

    OpenAIRE

    Veselý, Marek

    2009-01-01

    Thesis describes initial public offering on the stock markets. There are mentioned basic phases of this process. In this thesis is named pros & cons of this source of financing. Recommends also other ways how to gain capital for own company business acitivities. Thesis is interested about main conditions for successfull "going public". Initial Public Offering of bonds is described too. Practical part of this thesis is concern IPO in the Czech Republic -- historical data, IPO in the past on Pr...

  4. Despite the minimalist approach of Grameen Bank training program, similarities may be drawn between its practice and the models offered by Kirkpatrick and others

    Directory of Open Access Journals (Sweden)

    Kazi Abdur Rouf

    2017-01-01

    Full Text Available This paper compares and contrasts training evaluation different models and theories specially applies Kirkpatrick’s (K & K training evaluation model: four levels of measurement and their application in the Gramen Bank (GB training program. The objective of the paper is to know training evaluation models offered by Kirkpatrick and others, and their applications and usefulness to Grameen Bank and other microfinance institutions (MFIs. The paper uses literature review for analyzing of different models of training evaluation. Although K & K how training evaluation model of measuring training depend upon the training program and the demands of top management including stakeholders and donors, this K & K training evaluation model’s four-level training evaluation steps are simple enough that Grameen Bank Bangladesh and other micro-financing institutions (MFIs can adopt it in GB training evaluation process, which can assist GB and other micro-credit micro-management processes in monitoring employees’ performances.

  5. Using Models to Inform Policy: Insights from Modeling the Complexities of Global Polio Eradication

    Science.gov (United States)

    Thompson, Kimberly M.

    Drawing on over 20 years of experience modeling risks in complex systems, this talk will challenge SBP participants to develop models that provide timely and useful answers to critical policy questions when decision makers need them. The talk will include reflections on the opportunities and challenges associated with developing integrated models for complex problems and communicating their results effectively. Dr. Thompson will focus the talk largely on collaborative modeling related to global polio eradication and the application of system dynamics tools. After successful global eradication of wild polioviruses, live polioviruses will still present risks that could potentially lead to paralytic polio cases. This talk will present the insights of efforts to use integrated dynamic, probabilistic risk, decision, and economic models to address critical policy questions related to managing global polio risks. Using a dynamic disease transmission model combined with probabilistic model inputs that characterize uncertainty for a stratified world to account for variability, we find that global health leaders will face some difficult choices, but that they can take actions that will manage the risks effectively. The talk will emphasize the need for true collaboration between modelers and subject matter experts, and the importance of working with decision makers as partners to ensure the development of useful models that actually get used.

  6. Insight, self-stigma and psychosocial outcomes in Schizophrenia: a structural equation modelling approach.

    Science.gov (United States)

    Lien, Y-J; Chang, H-A; Kao, Y-C; Tzeng, N-S; Lu, C-W; Loh, C-H

    2016-12-15

    Poor insight is prevalent in patients with schizophrenia and has been associated with acute illness severity, medication non-adherence and poor treatment outcomes. Paradoxically, high insight has been associated with various undesirable outcomes, including low self-esteem, depression and low subjective quality of life (QoL) in patients with schizophrenia. Despite the growing body of studies conducted in Western countries supporting the pernicious effects of improved insight in psychosis, which bases on the level of self-stigma, the effects are unclear in non-Western societies. The current study examined the role of self-stigma in the relationship between insight and psychosocial outcomes in a Chinese population. A total of 170 outpatients with schizophrenia spectrum disorders were recruited from two general university hospitals. Sociodemographic data and clinical variables were recorded and self-report scales were employed to measure self-stigma, depression, insight, self-esteem and subjective QoL. Structural equation modelling (SEM) was used to analyse the cross-sectional data. High levels of self-stigma were reported by 39% of the participants (n = 67). The influences of insight, self-stigma, self-esteem and depression on subjective QoL were confirmed by the SEM results. Our model with the closest fit to the data (χ 2 = 33.28; df = 20; p = 0.03; χ 2/df = 1.66; CFI = 0.98; TLI = 0.97; RMSEA = 0.06) demonstrated that self-stigma might fully mediate the association of insight with low self-esteem, depression and poor subjective QoL. High insight into illness contributed to self-stigma, which caused low self-esteem and depression and, consequently, low QoL. Notably, insight did not directly affect self-esteem, depression or QoL. Furthermore, the association of insight with poor psychosocial outcomes was not moderated by self-stigma. Our findings support the mediating model of insight relevant to the poor psychosocial outcomes of individuals diagnosed with

  7. Pathogenesis of ANCA-associated vasculitis : recent insights from animal models

    NARCIS (Netherlands)

    van Timmeren, Mirjan M.; Heeringa, Peter

    2012-01-01

    Purpose of review To provide an update on animal models of antineutrophil cytoplasmic autoantibody (ANCA)-mediated vasculitis and highlight recent insights gained from studies in these models pertaining to immunopathogenesis. Recent findings Animal models support the pathogenic potential of myeloper

  8. Insights about data assimilation frameworks for integrating GRACE with hydrological models

    Science.gov (United States)

    Schumacher, Maike; Kusche, Jürgen; Van Dijk, Albert I. J. M.; Döll, Petra; Schuh, Wolf-Dieter

    2016-04-01

    Improving the understanding of changes in the water cycle represents a challenging objective that requires merging information from various disciplines. Debates exist on selecting an appropriate assimilation technique to integrate GRACE-derived terrestrial water storage changes (TWSC) into hydrological models in order to downscale and disaggregate GRACE TWSC, overcome model limitations, and improve monitoring and forecast skills. Yet, the effect of the specific data assimilation technique in conjunction with ill-conditioning, colored noise, resolution mismatch between GRACE and model, and other complications is still unclear. Due to its simplicity, ensemble Kalman filters or smoothers (EnKF/S) are often applied. In this study, we show that modification of the filter approach might open new avenues to improve the integration process. Particularly, we discuss an improved calibration and data assimilation (C/DA) framework (Schumacher et al., 2016), which is based on the EnKF and was extended by the square root analysis scheme (SQRA) and the singular evolutive interpolated Kalman (SEIK) filter. In addition, we discuss an off-line data blending approach (Van Dijk et al., 2014) that offers the chance to merge multi-model ensembles with GRACE observations. The investigations include: (i) a theoretical comparison, focusing on similarities and differences of the conceptual formulation of the filter algorithms, (ii) a practical comparison, for which the approaches were applied to an ensemble of runs of the WaterGAP Global Hydrology Model (WGHM), as well as (iii) an impact assessment of the GRACE error structure on C/DA results. First, a synthetic experiment over the Mississippi River Basin (USA) was used to gain insights about the C/DA set-up before applying it to real data. The results indicated promising performances when considering alternative methods, e.g. applying the SEIK algorithm improved the correlation coefficient and root mean square error (RMSE) of TWSC by 0

  9. Comparative Election Forecasting: Further Insights from Synthetic Models

    OpenAIRE

    Michael S. Lewis-Beck; Dassonneville, Ruth

    2015-01-01

    As an enterprise, election forecasting has spread and grown. Initial work began in the 1980s in the United States, eventually travelling to Western Europe, where it finds a current outlet in the most of the region’s democracies. However, that work has been confined to traditional approaches – statistical modeling or poll-watching. We import a new approach, which we call synthetic modeling. These forecasts come from hybrid models blending structural knowledge with contemporary p...

  10. VIP Programs Offer More

    Institute of Scientific and Technical Information of China (English)

    ISABELDING

    2005-01-01

    When choosing a hotel, service standards are a high priority for customers, with the quality of service often reflecting a hotel's standing.While most hotels try to provide the beststandard possible to their guest, many also offer special VIP programs that provide vale-added service and reward customer loyalty.

  11. Genetic models of absence epilepsy: New concepts and insights

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Coenen, A.M.L.

    2009-01-01

    The discovery, development, and use of genetic rodent models of absence epilepsy have led to a new theory about the origin of absence seizures. A focal zone has been identified in the peri-oral region of the somatosensory cortex in WAG/Rij and GAERS – the two most commonly used models – from which

  12. Partition function of nearest neighbour Ising models: Some new insights

    Indian Academy of Sciences (India)

    G Nandhini; M V Sangaranarayanan

    2009-09-01

    The partition function for one-dimensional nearest neighbour Ising models is estimated by summing all the energy terms in the Hamiltonian for N sites. The algebraic expression for the partition function is then employed to deduce the eigenvalues of the basic 2 × 2 matrix and the corresponding Hermitian Toeplitz matrix is derived using the Discrete Fourier Transform. A new recurrence relation pertaining to the partition function for two-dimensional Ising models in zero magnetic field is also proposed.

  13. OBESITY AND CRITICAL ILLNESS: INSIGHTS FROM ANIMAL MODELS.

    Science.gov (United States)

    Mittwede, Peter N; Clemmer, John S; Bergin, Patrick F; Xiang, Lusha

    2016-04-01

    Critical illness is a major cause of morbidity and mortality around the world. While obesity is often detrimental in the context of trauma, it is paradoxically associated with improved outcomes in some septic patients. The reasons for these disparate outcomes are not well understood. A number of animal models have been used to study the obese response to various forms of critical illness. Just as there have been many animal models that have attempted to mimic clinical conditions, there are many clinical scenarios that can occur in the highly heterogeneous critically ill patient population that occupies hospitals and intensive care units. This poses a formidable challenge for clinicians and researchers attempting to understand the mechanisms of disease and develop appropriate therapies and treatment algorithms for specific subsets of patients, including the obese. The development of new, and the modification of existing animal models, is important in order to bring effective treatments to a wide range of patients. Not only do experimental variables need to be matched as closely as possible to clinical scenarios, but animal models with pre-existing comorbid conditions need to be studied. This review briefly summarizes animal models of hemorrhage, blunt trauma, traumatic brain injury, and sepsis. It also discusses what has been learned through the use of obese models to study the pathophysiology of critical illness in light of what has been demonstrated in the clinical literature.

  14. The Manifest Association Structure of the Single-Factor Model: Insights from Partial Correlations

    Science.gov (United States)

    Salgueiro, Maria de Fatima; Smith, Peter W. F.; McDonald, John W.

    2008-01-01

    The association structure between manifest variables arising from the single-factor model is investigated using partial correlations. The additional insights to the practitioner provided by partial correlations for detecting a single-factor model are discussed. The parameter space for the partial correlations is presented, as are the patterns of…

  15. Offers for our members

    CERN Multimedia

    Staff Association

    2013-01-01

    The Courir shops propose the following offer: 15% discount on all articles (not on sales) in the Courir shops (Val Thoiry, Annemasse and Neydens) and 5% discount on sales upon presentation of your Staff Association membership card and an identity card before payment. Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 21 € instead of 26 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 30 CHF instead of 39 CHF – Adults : 36 CHF instead of 49 CHF Bonus! Free for children under 5.

  16. Offers for our members

    CERN Multimedia

    Staff Association

    2017-01-01

    Summer is coming, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 24 € instead of 30 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children under 100 cm. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  17. Offers for our members

    CERN Multimedia

    Staff Association

    2017-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 24 € instead of 30 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children under 100 cm. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  18. How to produce flat slabs: insights from numeric modeling

    Science.gov (United States)

    Constantin Manea, Vlad; Perez-Gussinye, Marta; Manea, Marina

    2010-05-01

    Flat slab subduction occurs at ~10% of the active convergent margins and it is assumed that subduction of oceanic aseismic ridges or seamount chains is the main mechanism to produce very low angle subduction slabs. However, recent numeric and analog modeling showed that ridges alone of moderate dimensions subducted perpendicular to the trench are not sufficient to produce flat-slab geometries. Therefore an alternative mechanism able to produce flat-slabs is required. In this paper we present dynamic numeric modeling results of subduction in the vicinity of thick continental lithosphere, as a craton for example. We tailored our modeling setup for the Chilean margins at ~31° and our models are integrated back in time 30 Myr. Modeling results show that a craton thickness of 200 km or more when approaching the trench is capable of blocking the asthenospheric flow in the mantle wedge and increasing considerably the suction force. We were able to produce a flat slab that fits well the flat slab geometry in Chile (based on seismicity) and stress distribution. We conclude that thick cratons located in the vicinity of subduction zones, are capable to produce very low angle slabs, and probable a combination of buoyant ridge subduction with a neighbor thick craton represent a better mechanism to produce flat slabs.

  19. New insights into autoimmune cholangitis through animal models.

    Science.gov (United States)

    Trauner, Michael; Fickert, Peter; Baghdasaryan, Anna; Claudel, Thierry; Halilbasic, Emina; Moustafa, Tarek; Wagner, Martin; Zollner, Gernot

    2010-01-01

    Improving our understanding of the pathogenesis of chronic immune-mediated cholangiopathies such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), as well as the development of novel diagnostic, prognostic and therapeutic tools for these disorders critically depends on easily reproducible animal models. Recently, several spontaneous mouse models for PBC (not requiring previous manipulations for breakdown of immunotolerance) have been reported, including NOD.c3c4 and NOD.c3c4-derived mice, IL-2Ralpha(-/-) mice, dominant negative TGF-beta receptor II mice and Ae2(a,b)(-/-) mice. To date, no animal model exhibits all of the attributes of PSC. Rodent models induced by bacterial cell components or colitis may help to explain the strong association between PSC and inflammatory bowel disease. Other models include direct injury to biliary epithelia, peribiliary vascular endothelia or portal venous endothelia. Mice with targeted disruption of the Mdr2 (Abcb4) gene encoding a canalicular phospholipid flippase (Mdr2(-/-) mice) spontaneously develop sclerosing cholangitis with macroscopic and microscopic features of human PSC. Another example for a transporter involved in the pathogenesis of sclerosing cholangitis is the cystic fibrosis transmembrane conductance regulator (CFTR/ABCC7). Xenobiotics and drugs may also lead to bile duct injury and biliary fibrosis via direct toxic and indirect immune-mediated injury. Hydrophobic bile acids, such as lithocholic acid, cause bile duct injury and destructive cholangitis with periductal fibrosis resembling sclerosing cholangitis. These models have enhanced our understanding of the pathogenesis of PBC and PSC and will hopefully result in improved treatment of these disorders.

  20. Giant Glial Cell: New Insight Through Mechanism-Based Modeling

    DEFF Research Database (Denmark)

    Postnov, D. E.; Ryazanova, L. S.; Brazhe, Nadezda;

    2008-01-01

    The paper describes a detailed mechanism-based model of a tripartite synapse consisting of P- and R-neurons together with a giant glial cell in the ganglia of the medical leech (Hirudo medicinalis), which is a useful object for experimental studies in situ. We describe the two main pathways of th...

  1. Insights on protein-DNA recognition by coarse grain modelling

    Science.gov (United States)

    Poulain, Pierre; Saladin, Adrien; Hartmann, Brigitte; Prévost, Chantal

    2008-01-01

    Coarse grain modelling of macromolecules is a new approach potentially well adapted to answer numerous issues, ranging from physics to biology. We propose here an original DNA coarse grain model specifically dedicated to protein–DNA docking, a crucial, but still largely unresolved, question in molecular biology. Using a representative set of protein–DNA complexes, we first show that our model is able to predict the interaction surface between the macromolecular partners taken in their bound form. In a second part, the impact of the DNA sequence and electrostatics, together with the DNA and protein conformations on docking is investigated. Our results strongly suggest that the overall DNA structure mainly contributes in discriminating the interaction site on cognate proteins. Direct electrostatic interactions between phosphate groups and amino acids side chains strengthen the binding. Overall, this work demonstrates that coarse grain modelling can reveal itself a precious auxiliary for a general and complete description and understanding of protein–DNA association mechanisms. PMID:18478582

  2. Modeling the mammalian locomotor CPG: insights from mistakes and perturbations.

    Science.gov (United States)

    McCrea, David A; Rybak, Ilya A

    2007-01-01

    A computational model of the mammalian spinal cord circuitry incorporating a two-level central pattern generator (CPG) with separate half-center rhythm generator (RG) and pattern formation (PF) networks is reviewed. The model consists of interacting populations of interneurons and motoneurons described in the Hodgkin-Huxley style. Locomotor rhythm generation is based on a combination of intrinsic (persistent sodium current dependent) properties of excitatory RG neurons and reciprocal inhibition between the two half-centers comprising the RG. The two-level architecture of the CPG was suggested from an analysis of deletions (spontaneous omissions of activity) and the effects of afferent stimulation on the locomotor pattern and rhythm observed during fictive locomotion in the cat. The RG controls the activity of the PF network that in turn defines the rhythmic pattern of motoneuron activity. The model produces realistic firing patterns of two antagonist motoneuron populations and generates locomotor oscillations encompassing the range of cycle periods and phase durations observed during cat locomotion. A number of features of the real CPG operation can be reproduced with separate RG and PF networks, which would be difficult if not impossible to demonstrate with a classical single-level CPG. The two-level architecture allows the CPG to maintain the phase of locomotor oscillations and cycle timing during deletions and during sensory stimulation. The model provides a basis for functional identification of spinal interneurons involved in generation and control of the locomotor pattern.

  3. Improving Perovskite Solar Cells: Insights From a Validated Device Model

    NARCIS (Netherlands)

    Sherkar, Tejas S.; Momblona, Cristina; Gil-Escrig, Lidon; Bolink, Henk J.; Koster, L. Jan Anton

    2017-01-01

    To improve the efficiency of existing perovskite solar cells (PSCs), a detailed understanding of the underlying device physics during their operation is essential. Here, a device model has been developed and validated that describes the operation of PSCs and quantitatively explains the role of conta

  4. Insights on non-perturbative aspects of TMDs from models

    Energy Technology Data Exchange (ETDEWEB)

    H. Avakian, A. Efremov, P. Schweitzer, O. Teryaev, F. Yuan, P. Zavada

    2009-12-01

    Transverse momentum dependent parton distribution functions are a key ingredient in the description of spin and azimuthal asymmetries in deep-inelastic scattering processes. Recent results from non-perturbative calculations in effective approaches are reviewed, with focus on relations among different parton distribution functions in QCD and models.

  5. Managing Dog Waste: Campaign Insights from the Health Belief Model

    Science.gov (United States)

    Typhina, Eli; Yan, Changmin

    2014-01-01

    Aiming to help municipalities develop effective education and outreach campaigns to reduce stormwater pollutants, such as pet waste, this study applied the Health Belief Model (HBM) to identify perceptions of dog waste and corresponding collection behaviors from dog owners living in a small U.S. city. Results of 455 online survey responses…

  6. Improving Perovskite Solar Cells: Insights From a Validated Device Model

    NARCIS (Netherlands)

    Sherkar, Tejas S.; Momblona, Cristina; Gil-Escrig, Lidon; Bolink, Henk J.; Koster, L. Jan Anton

    2017-01-01

    To improve the efficiency of existing perovskite solar cells (PSCs), a detailed understanding of the underlying device physics during their operation is essential. Here, a device model has been developed and validated that describes the operation of PSCs and quantitatively explains the role of conta

  7. The microbiota and inflammatory bowel disease: insights from animal models.

    Science.gov (United States)

    Peloquin, Joanna M; Nguyen, Deanna D

    2013-12-01

    Inflammatory bowel disease (IBD) is thought to result from a dysregulated immune response to intestinal microbial flora in individuals with genetic predisposition(s). Genome-wide association studies (GWAS) in human IBD have identified more than 150 associated loci, some of which are key players in innate immunity and bacterial handling, reflecting the importance of the microbiota in disease pathogenesis. In fact, the presence of a microbial flora is not only crucial to the development of a normal murine immune system but also critical for the development of disease in the majority of animal models of IBD. Although animal models do not perfectly recapitulate human IBD, they have led to the discovery of important concepts in IBD pathogenesis, such as the central role of microbiota in disease development and perpetuation. Many genetically susceptible models do not develop colitis when raised in a germ-free or Helicobacter-free environment. In fact, disease in most models can be attenuated or completely abolished with antibiotic treatment. Moreover, an interplay between intestinal microbiota and mucosal immune activation is suggested by the presence of serum antibodies against the Cbir1 flagellin, an immunodominant antigen that activates TLR5, in certain models of spontaneous colitis as well as in human patients. Furthermore, T cells reactive to Cbir1 are able to induce disease in recipient mice upon adoptive cell transfer, demonstrating the pro-inflammatory properties of certain bacterial products. In fact, it has been shown that transfer of certain intestinal bacteria from a specific genetically altered mouse model with spontaneous colitis can induce disease in wild-type mice upon co-housing or direct feeding. These observations demonstrate the pathogenic potential of intestinal microbiota in IBD. However, intestinal bacteria are not always maladaptive in mucosal homeostasis. Both Bacteroides fragilis and Clostridium species promote the number and function of a

  8. Rock Burst Mechanics: Insight from Physical and Mathematical Modelling

    Directory of Open Access Journals (Sweden)

    J. Vacek

    2008-01-01

    Full Text Available Rock burst processes in mines are studied by many groups active in the field of geomechanics. Physical and mathematical modelling can be used to better understand the phenomena and mechanisms involved in the bursts. In the present paper we describe both physical and mathematical models of a rock burst occurring in a gallery of a coal mine.For rock bursts (also called bumps to occur, the rock has to possess certain particular rock burst properties leading to accumulation of energy and the potential to release this energy. Such materials may be brittle, or the rock burst may arise at the interfacial zones of two parts of the rock, which have principally different material properties (e.g. in the Poíbram uranium mines.The solution is based on experimental and mathematical modelling. These two methods have to allow the problem to be studied on the basis of three presumptions:· the solution must be time dependent,· the solution must allow the creation of cracks in the rock mass,· the solution must allow an extrusion of rock into an open space (bump effect. 

  9. Insights from simple models for surface states in nanostructures

    Science.gov (United States)

    Boykin, Timothy B.; Klimeck, Gerhard

    2017-03-01

    Surface passivation is of great technological importance due to the increasing miniaturisation of electronic devices. It has been known for many years that under certain conditions surface states can form; when they do so in a quantum well (QW) the result is an unbound (i.e., evanescent) state in the QW. Such surface states are generally undesirable, so a good physical understanding of them is important. A simple single-p-orbital valence band model is used with two types of surface passivation to examine surface states in a QW: (1) an energy upshift added to the terminal atoms; and (2) explicit passivation by an s-orbital on each end of the QW. These models show these unbound/evanescent QW states can occur in both models; that in them the wavefunction is bound to the terminal atoms; and that the existence of these states is connected to the effective valence-band offset between the terminal atoms and the bulk QW.

  10. Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models

    Directory of Open Access Journals (Sweden)

    Lois Choy

    2016-09-01

    Full Text Available The mouse is the second mammalian species, after the human, in which substantial amount of the genomic information has been analyzed. With advances in transgenic technology, mutagenesis is now much easier to carry out in mice. Consequently, an increasing number of transgenic mouse systems have been generated for the study of cardiac arrhythmias in ion channelopathies and cardiomyopathies. Mouse hearts are also amenable to physical manipulation such as coronary artery ligation and transverse aortic constriction to induce heart failure, radiofrequency ablation of the AV node to model complete AV block and even implantation of a miniature pacemaker to induce cardiac dyssynchrony. Last but not least, pharmacological models, despite being simplistic, have enabled us to understand the physiological mechanisms of arrhythmias and evaluate the anti-arrhythmic properties of experimental agents, such as gap junction modulators, that may be exert therapeutic effects in other cardiac diseases. In this article, we examine these in turn, demonstrating that primary inherited arrhythmic syndromes are now recognized to be more complex than abnormality in a particular ion channel, involving alterations in gene expression and structural remodelling. Conversely, in cardiomyopathies and heart failure, mutations in ion channels and proteins have been identified as underlying causes, and electrophysiological remodelling are recognized pathological features. Transgenic techniques causing mutagenesis in mice are extremely powerful in dissecting the relative contributions of different genes play in producing disease phenotypes. Mouse models can serve as useful systems in which to explore how protein defects contribute to arrhythmias and direct future therapy.

  11. How craton margins are preserved: Insights from geodynamic models

    Science.gov (United States)

    Currie, Claire A.; van Wijk, Jolante

    2016-10-01

    Lateral variations in lithosphere thickness are observed in many continental regions, especially at the boundary between the ancient cratonic core and the adjacent more juvenile lithosphere. In some places, such as the North America craton margin in western Canada and the Sorgenfrei-Tornquist Zone in northern Europe, the transition in lithosphere thickness has a steep gradient (>45°) and it appears to be a long-lived feature (at least 50 Ma). We use thermal-mechanical numerical models to address the dynamics of lithospheric thickness changes on timescales of 100 Ma. Models start with the juxtaposition of 60 km thick lithosphere ("mobile belt") and 160 km thick lithosphere ("craton"). In the reference model, all mantle materials have a damp olivine rheology and a density comparable to primitive mantle. With this configuration, edge-driven mantle convection occurs at the craton boundary, resulting in a lateral smoothing of the thickness transition. The density and rheology of the craton mantle lithosphere are then varied to approximate changes in composition and water content. For all densities, a steep transition is maintained only if the craton strength is 5-50 times stronger than the reference damp olivine. If dry olivine is an upper limit on strength, only cratonic mantle with moderate compositional buoyancy (20-40 kg/m3 less dense than primitive mantle) remains stable. At higher densities, the thick lithosphere is eroded through downwellings, and the craton margin migrates inboard. Conversely, a compositionally buoyant craton destabilises through lateral spreading below the mobile belt.

  12. Offers for our members

    CERN Multimedia

    Staff Association

    2017-01-01

    Summer is here, enjoy our offers for the water parks! Walibi: Tickets "Zone terrestre": 24 € instead of 30 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your ticket purchased at the Staff Association. Bonus! Free for children under 100 cm, with limited access to the attractions. Free car park. *  *  *  *  *  *  *  * Aquaparc: Day ticket: -  Children: 33 CHF instead of 39 CHF -  Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5 years old.

  13. Offers for our members

    CERN Multimedia

    Staff Association

    2016-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 23 € instead of 29 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12:00 p.m. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  14. Offers for our members

    CERN Multimedia

    Staff Association

    2016-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 23 € instead of 29 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12:00 p.m. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  15. Offers for our members

    CERN Multimedia

    Staff Association

    2015-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 21,50 € instead of 27 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12:00 p.m. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  16. Offers for our members

    CERN Multimedia

    Staff Association

    2013-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 21 € instead of 26 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 30 CHF instead of 39 CHF – Adults : 36 CHF instead of 49 CHF Bonus! Free for children under 5.

  17. Hair-offerings: an enigmatic Egyptian custom

    Directory of Open Access Journals (Sweden)

    G. J. Tassie

    1996-11-01

    Full Text Available The Egyptians did not record the reasons that lay behind the offering of hair. Using an holistic approach, which combines both ethnographic and ethnohistoric evidence, insights may be gained into the ancient remains of these rituals and practices.

  18. Ambient vibrations of unstable rock slopes - insights from numerical modeling

    Science.gov (United States)

    Burjanek, Jan; Kleinbrod, Ulrike; Fäh, Donat

    2017-04-01

    The recent events in Nepal (2015 M7.8 Gorkha) and New Zealand (2016 M7.8 Kaikoura) highlighted the importance of earthquake-induced landslides, which caused significant damages. Moreover, landslide created dams present a potential developing hazard. In order to reduce the costly consequences of such events it is important to detect and characterize earthquake susceptible rock slope instabilities before an event, and to take mitigation measures. For the characterisation of instable slopes, acquisition of ambient vibrations might be a new alternative to the already existing methods. We present both observations and 3D numerical simulations of the ambient vibrations of unstable slopes. In particular, models of representative real sites have been developed based on detailed terrain mapping and used for the comparison between synthetics and observations. A finite-difference code has been adopted for the seismic wave propagation in a 3D inhomogeneous visco-elastic media with irregular free surface. It utilizes a curvilinear grid for a precise modeling of curved topography and local mesh refinement to make computational mesh finer near the free surface. Topographic site effects, controlled merely by the shape of the topography, do not explain the observed seismic response. In contrast, steeply-dipping compliant fractures have been found to play a key role in fitting observations. Notably, the synthetized response is controlled by inertial mass of the unstable rock, and by stiffness, depth and network density of the fractures. The developed models fit observed extreme amplification levels (factors of 70!) and show directionality as well. This represents a possibility to characterize slope structure and infer depth or volume of the slope instability from the ambient noise recordings in the future.

  19. Neural network models: Insights and prescriptions from practical applications

    Energy Technology Data Exchange (ETDEWEB)

    Samad, T. [Honeywell Technology Center, Minneapolis, MN (United States)

    1995-12-31

    Neural networks are no longer just a research topic; numerous applications are now testament to their practical utility. In the course of developing these applications, researchers and practitioners have been faced with a variety of issues. This paper briefly discusses several of these, noting in particular the rich connections between neural networks and other, more conventional technologies. A more comprehensive version of this paper is under preparation that will include illustrations on real examples. Neural networks are being applied in several different ways. Our focus here is on neural networks as modeling technology. However, much of the discussion is also relevant to other types of applications such as classification, control, and optimization.

  20. New insights from the use of pilocarpine and kainate models.

    Science.gov (United States)

    Leite, J P; Garcia-Cairasco, N; Cavalheiro, E A

    2002-06-01

    Local or systemic administration of pilocarpine and kainate in rodents leads to a pattern of repetitive limbic seizures and status epilepticus, which can last for several hours. A latent period follows status epilepticus and precedes a chronic phase, which is characterized by the occurrence of spontaneous limbic seizures. These distinct features, in a single animal preparation, of an acute damage induced by status epilepticus, a silent interval between injury and the onset of spontaneous seizures, and a chronic epileptic state have allowed antiepileptic drug (AED) studies with different purposes, (a) in the acute phase, identification of compounds with efficacy against refractory status epilepticus and/or neuroprotection against damage induced by sustained seizures; (b) in the latent period, identification of agents with a potential for preventing epileptogenesis and/or against seizure-induced long-term behavioral deficits and (c) in the chronic phase, testing drugs effective against partial and secondarily generalized seizures. Studies on pilocarpine and kainate models have pointed out that some AEDs or other compounds exert an antiepileptogenic effect. The analogy of the latent phase of pilocarpine and kainate models with the acquisition of amygdala kindling should encourage testing of drugs that have proved to suppress the evolution of amygdala kindling. Drug testing in the chronic phase should not address only the suppression of secondarily generalized motor seizures. Most of current tools used to quantify spontaneous seizure events need to be coupled to electrophysiology and more sophisticated systems for recording and analyzing behavior.

  1. Subduction initiation and Obduction: insights from analog models

    Science.gov (United States)

    Agard, P.; Zuo, X.; Funiciello, F.; Bellahsen, N.; Faccenna, C.; Savva, D.

    2013-12-01

    Subduction initiation and obduction are two poorly constrained geodynamic processes which are interrelated in a number of natural settings. Subduction initiation can be viewed as the result of a regional-scale change in plate convergence partitioning between the set of existing subduction (and collision or obduction) zones worldwide. Intraoceanic subduction initiation may also ultimately lead to obduction of dense oceanic "ophiolites" atop light continental plates. A classic example is the short-lived Peri-Arabic obduction, which took place along thousands of km almost synchronously (within ~5-10 myr), from Turkey to Oman, while the subduction zone beneath Eurasia became temporarily jammed. We herein present analog models designed to study both processes and more specifically (1) subduction initiation through the partitioning of deformation between two convergent zones (a preexisting and a potential one) and, as a consequence, (2) the possible development of obduction, which has so far never been modeled. These models explore the mechanisms of subduction initiation and obduction and test various triggering hypotheses (i.e., plate acceleration, slab crossing the 660 km discontinuity, ridge subduction; Agard et al., 2007). The experimental setup comprises an upper mantle modelled as a low-viscosity transparent Newtonian glucose syrup filling a rigid Plexiglas tank and high-viscosity silicone plates. Convergence is simulated by pushing on a piston at one end of the model with plate tectonics like velocities (1-10 cm/yr) onto (i) a continental margin, (ii) a weakness zone with variable resistance and dip (W), (iii) an oceanic plate - with or without a spreading ridge, (iv) a subduction zone (S) dipping away from the piston and (v) an upper active continental margin, below which the oceanic plate is being subducted at the start of the experiment (as for the Oman case). Several configurations were tested over thirty-five parametric experiments. Special emphasis was

  2. Coupling between mantle and surface processes: Insights from analogue modelling

    Science.gov (United States)

    Király, Ágnes; Sembroni, Andrea; Faccenna, Claudio; Funiciello, Francesca

    2014-05-01

    Thermal or density anomalies located beneath the lithosphere are thought to generate dynamic topography. Such a topographic signal compensates the viscous stresses originating from the anomaly driven mantle flow. It has been demonstrated that the erosion modulates the dynamic signal of topography changing the uplift rate by unload. The characteristic time for adjustments of dynamic topography due to surface erosion is likely similar to post-glacial rebound time (10000 - 50000 years). Here we present preliminary results of a new set of analogue models realized to study and quantify the contribution given by erosion to dynamic topography, during a process specifically driven by a positively buoyant deep anomaly. The adopted set up consists of a Plexiglas box (40x40x50 cm3) filled with glucose syrup as analogue upper mantle. A silicon plate positioned on the top of the syrup simulates the lithosphere. On the silicone plate is placed a thin layer of a high viscous glucose syrup which reproduces the upper, erodible layer of the crust. To simulate the positively buoyant anomaly we used an elastic, undeformable silicon ball free to rise by buoyancy in the syrup until the floating silicone plate is hit. The changes in topography have been monitored by using a 3D laser scan, while a side-view camera recorded the position of the rising ball in time. Data have been post-processed with image analysis techniques (e.g., Particle Image Velocimetry) in order to obtain the evolution of topography, uplift rate, erosion patterns of the top layer, bulge width and mantle circulation during the experiment. We ran experiments with and without the shallow, erodible crustal layer in order to quantify the effect of erosion on dynamic topography. Preliminary results showed that both the maximum topography and uplift rate are inversely proportional to the lithospheric thickness. The maximum uplift rate and the deformation of the lithospheric plate occurred just before the arrival of the

  3. Newest insights from MHD numerical modeling of Pulsar Wind Nebulae

    Science.gov (United States)

    Olmi, B.; Del Zanna, L.; Amato, E.; Bucciantini, N.; Bandiera, R.

    2016-06-01

    Numerical MHD models are considered very successful in accounting for many of the observed properties of Pulsar Wind Nebulae (PWNe), especially those concerning the high energy emission morphology and the inner nebula dynamics. Although PWNe are known to be among the most powerful accelerators in nature, producing particles up to PeV energies, the mechanisms responsible of such an efficient acceleration are still a deep mystery. Indeed, these processes take place in one of the most hostile environment for particle acceleration: the relativistic and highly magnetized termination shock of the pulsar wind. The newest results from numerical simulations of the Crab Nebula, the PWN prototype, will be presented, with special attention to the problem of particle acceleration. In particular it will be shown how a multi-wavelengths analysis of the wisps properties can be used to constrain the particle acceleration mechanisms working at the Crab's termination shock, by identifying the particle acceleration site at the shock front.

  4. New insights into continental rifting from a damage rheology modeling

    Science.gov (United States)

    Lyakhovsky, Vladimir; Segev, Amit; Weinberger, Ram; Schattner, Uri

    2010-05-01

    Previous studies have discussed how tectonic processes could produce relative tension to initiate and propagate rift zones and estimated the magnitude of the rift-driving forces. Both analytic and semi-analytic models as well as numerical simulations assume that the tectonic force required to initiate rifting is available. However, Buck (2004, 2006) estimated the minimum tectonic force to allow passive rifting and concluded that the available forces are probably not large enough for rifting of thick and strong lithosphere in the absence of basaltic magmatism (the "Tectonic Force" Paradox). The integral of the yielding stress needed for rifting over the thickness of the normal or thicker continental lithosphere are well above the available tectonic forces and tectonic rifting cannot happen (Buck, 2006). This conclusion is based on the assumption that the tectonic stress has to overcome simultaneously the yielding stress over the whole lithosphere thickness and ignore gradual weakening of the brittle rocks under long-term loading. In this study we demonstrate that the rifting process under moderate tectonic stretching is feasible due to gradual weakening and "long-term memory" of the heavily fractured brittle rocks, which makes it significantly weaker than the surrounding intact rock. This process provides a possible solution for the tectonic force paradox. We address these questions utilizing 3-D lithosphere-scale numerical simulations of the plate motion and faulting process base on the damage mechanics. The 3-D modeled volume consists of three main lithospheric layers: an upper layer of weak sediments, middle layer of crystalline crust and lower layer of the lithosphere mantle. Results of the modeling demonstrate gradual formation of the rift zone in the continental lithosphere with the flat layered structure. Successive formation of the rift system and associated seismicity pattern strongly depend not only on the applied tectonic force, but also on the healing

  5. Fetal developmental programing: insights from human studies and experimental models.

    Science.gov (United States)

    Lopes, Gisele Aparecida Dionísio; Ribeiro, Vinícius Luís Bertotti; Barbisan, Luís Fernando; Marchesan Rodrigues, Maria Aparecida

    2017-03-01

    Environmental factors, particularly nutrition during pregnancy and early life can influence the risk of chronic diseases in later life. The underlying mechanism, termed "programing", postulates that an environmental stimulus during a critical window of time, early in life, has a permanent effect on subsequent structure and function of the organism. In this study we review the concept of fetal programing on chronic diseases and the proposed hypotheses for the association between early development and later disease, including epigenetic variation. We concentrate on specific aspects of maternal nutrition, particularly under-nutrition and over-nutrition, in humans and animal models. An adequate maternal nutrition during pregnancy is crucial for the health outcome of the offspring at adulthood.

  6. Botulinum Neurotoxin for Pain Management: Insights from Animal Models

    Directory of Open Access Journals (Sweden)

    Siro Luvisetto

    2010-12-01

    Full Text Available The action of botulinum neurotoxins (BoNTs at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models.

  7. Botulinum neurotoxin for pain management: insights from animal models.

    Science.gov (United States)

    Pavone, Flaminia; Luvisetto, Siro

    2010-12-01

    The action of botulinum neurotoxins (BoNTs) at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models.

  8. An insight into DVB-T system using formal modelling in Event-B

    Science.gov (United States)

    Krayem, Said; Pátíková, Zuzana

    2017-07-01

    Digital Video Broadcast - Terrestrial (DVB-T) can be seen as a complex system with many concrete features and aspects. This paper presents a simplified model and the first insight into this system from point of view of formal modelling methods. Using Event-B a start-up model concerning relations between signals, multiplexes and channels is introduced. As a background the standards for DVB-T in the Czech Republic are taken.

  9. Flood damage modeling based on expert knowledge: Insights from French damage model for agricultural sector

    Science.gov (United States)

    Grelot, Frédéric; Agenais, Anne-Laurence; Brémond, Pauline

    2015-04-01

    damage in euros by hectare for 14 agricultural lands categories. As a conclusion, we will discuss the validation step of the model. Although the model was validated by experts, we analyse how it could gain insight from comparison with past events.

  10. Lithospheric Architecture, Heterogenities, Instabilities, Melting - insight form numerical modelling

    Science.gov (United States)

    Gorczyk, Weronika; Hobbs, Bruce; Ord, Alison; Gessner, Klaus; Gerya, Taras V.

    2010-05-01

    The seismological structure of the Earth's lithosphere is identified to be strongly heterogeneous in terms of thermal and rheological structures. Lithospheric discontinuities (sharp changes in the thermal and/or compositional structure) are thought to be long lived and are mostly correlated with major tectonic boundaries that commonly have been reactivated and which subsequently are the foci of magma intrusion and major mineralization. Resent studies have shown that mantle metasomatism is also controlled by such boundaries. This paper explores the control that lithospheric heterogeneity exerts on the thermal and chemical evolution during deformation subsequent to the development of the heterogeneity. We explore the behaviour of the rheological heterogeneous lithosphere in a compressional regime. The occurrence of such variations may be caused for instance by amalgamation of micro-continents such as is thought to be characteristic of the Yilgarn, Western Australia or South Africa. Theses micro-continents, due to diverse histories may be characterised by various thermal and rheological structures. The models are simplistic but illustrate the basic principles. The code used in this study is based on a conservative finite-difference, multi-grid, marker in cell method. Devolatilisation reactions and melting can affect the physical properties of rocks and are incorporated in a self-consistent manner. We use a petrological-thermomechanical modelling approach with all rock properties including mechanical properties calculated in the Lagrangian scheme for rock markers at every time step based on Gibbs free energy minimization as a function of the local pressure, temperature and rock composition. The results illustrate that initial structural complexity is necessary for and has a dramatic effect on fault and development, the growth of deep basins, core complex formation, melting and devolatilisation within the lithosphere. The horizontal and vertical variation in plastic

  11. Insights into magma depth under resurgent domes from analogue modelling

    Science.gov (United States)

    Brothelande, Elodie; Merle, Olivier

    2014-05-01

    Post-collapse resurgence is a common process observed in many calderas, yet the mechanisms of this phenomenon are still poorly known. Whereas most models account for circular doming, deviations from circular shape is common in nature, reflecting either the shape of the underlying reservoir or the influence of regional structures. We conducted a series of scaled experiments to investigate the structural evolution of a resurgent dome in response to an elongated source. A sand-plaster mixture was chosen as the analogue for the brittle pile of volcanic rocks and silicone putty simulates the ductile behavior of the intruding magma. The uplift of the intrusion roof drives the resurgence. A set of 21 experiments have been conducted varying the thickness of the brittle overburden and the width of the silicone intrusion. Three types of extensional patterns associated with doming are observed: two lateral grabens, a single axial graben, and no graben. In the third type, the shape of the dome is significantly less elongated and extension is accommodated by two sets of normal faults, which are roughly concentric and radial from the center of the dome. These three extension modes are strongly related to the thickness of the brittle overburden. The "single axial graben" type, frequently observed in nature, corresponds to intermediate thicknesses. Results of experiments with a single graben show that the dome width is dependent on both tested parameters. In contrast, the graben width is strongly dependent on the overburden thickness whereas the intrusion width is of limited importance. As a significant result, the graben width shows an almost perfectly linear dependency upon the brittle overburden thickness. A simple geometrical model of the analogue system can be proposed, in which opposite master faults of the graben intersect at depth at the junction with the rising viscous intrusion. Geometric constants, or nearly so, such as the slope of the dome flanks and the dip of the

  12. New insights on geomagnetic storms from observations and modeling

    Energy Technology Data Exchange (ETDEWEB)

    Jordanova, Vania K [Los Alamos National Laboratory

    2009-01-01

    Understanding the response at Earth of the Sun's varying energy output and forecasting geomagnetic activity is of central interest to space science, since intense geomagnetic storms may cause severe damages on technological systems and affect communications. Episodes of southward (Bzmodel (RAM), and investigate the mechanisms responsible for trapping particles and for causing their loss. We find that periods of increased magnetospheric convection coinciding with enhancements of plasma sheet density are needed for strong ring current buildup. During the HSS-driven storm the convection potential is highly variable and causes small sporadic injections into the ring current. The long period of enhanced convection during the CME-driven storm causes a continuous ring current injection penetrating to lower L shells and stronger ring current buildup.

  13. Tracking Strains in the Microbiome: Insights from Metagenomics and Models.

    Science.gov (United States)

    Brito, Ilana L; Alm, Eric J

    2016-01-01

    Transmission usually refers to the movement of pathogenic organisms. Yet, commensal microbes that inhabit the human body also move between individuals and environments. Surprisingly little is known about the transmission of these endogenous microbes, despite increasing realizations of their importance for human health. The health impacts arising from the transmission of commensal bacteria range widely, from the prevention of autoimmune disorders to the spread of antibiotic resistance genes. Despite this importance, there are outstanding basic questions: what is the fraction of the microbiome that is transmissible? What are the primary mechanisms of transmission? Which organisms are the most highly transmissible? Higher resolution genomic data is required to accurately link microbial sources (such as environmental reservoirs or other individuals) with sinks (such as a single person's microbiome). New computational advances enable strain-level resolution of organisms from shotgun metagenomic data, allowing the transmission of strains to be followed over time and after discrete exposure events. Here, we highlight the latest techniques that reveal strain-level resolution from raw metagenomic reads and new studies that are tracking strains across people and environments. We also propose how models of pathogenic transmission may be applied to study the movement of commensals between microbial communities.

  14. Dynamos at extreme magnetic Prandtl numbers: insights from shell models

    Science.gov (United States)

    Verma, Mahendra K.; Kumar, Rohit

    2016-12-01

    We present an MHD shell model suitable for computation of various energy fluxes of magnetohydrodynamic turbulence for very small and very large magnetic Prandtl numbers $\\mathrm{Pm}$; such computations are inaccessible to direct numerical simulations. For small $\\mathrm{Pm}$, we observe that both kinetic and magnetic energy spectra scale as $k^{-5/3}$ in the inertial range, but the dissipative magnetic energy scales as $k^{-11/3}\\exp(-k/k_\\eta)$. Here, the kinetic energy at large length scale feeds the large-scale magnetic field that cascades to small-scale magnetic field, which gets dissipated by Joule heating. The large-$\\mathrm{Pm}$ dynamo has a similar behaviour except that the dissipative kinetic energy scales as $k^{-13/3}$. For this case, the large-scale velocity field transfers energy to the large-scale magnetic field, which gets transferred to small-scale velocity and magnetic fields; the energy of the small-scale magnetic field also gets transferred to the small-scale velocity field, and the energy thus accumulated is dissipated by the viscous force.

  15. Rehabilitation and plasticity following stroke: Insights from rodent models.

    Science.gov (United States)

    Caleo, M

    2015-12-17

    Ischemic injuries within the motor cortex result in functional deficits that may profoundly impact activities of daily living in patients. Current rehabilitation protocols achieve only limited recovery of motor abilities. The brain reorganizes spontaneously after injury, and it is believed that appropriately boosting these neuroplastic processes may restore function via recruitment of spared areas and pathways. Here I review studies on circuit reorganization, neuronal and glial plasticity and axonal sprouting following ischemic damage to the forelimb motor cortex, with a particular focus on rodent models. I discuss evidence pointing to compensatory take-over of lost functions by adjacent peri-lesional areas and the role of the contralesional hemisphere in recovery. One key issue is the need to distinguish "true" recovery (i.e. re-establishment of original movement patterns) from compensation in the assessment of post-stroke functional gains. I also consider the effects of physical rehabilitation, including robot-assisted therapy, and the potential mechanisms by which motor training induces recovery. Finally, I describe experimental approaches in which training is coupled with delivery of plasticizing drugs that render the remaining, undamaged pathways more sensitive to experience-dependent modifications. These combinatorial strategies hold promise for the definition of more effective rehabilitation paradigms that can be translated into clinical practice.

  16. Defective membrane remodeling in neuromuscular diseases: insights from animal models.

    Directory of Open Access Journals (Sweden)

    Belinda S Cowling

    Full Text Available Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1, and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1 a common molecular pathway underlying these different neuromuscular diseases, and (2 tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches.

  17. Offers for our members

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    2013-01-01

    The warm weather arrives, it's time to take advantage of our offers Walibi and Aquapark! Walibi : Tickets "Zone terrestre": 21 € instead of 26 € Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Half-day ticket (5 hours): – Children: 26 CHF instead of 35 CHF – Adults : 32 CHF instead of 43 CHF Day ticket: – Children: 30 CHF instead of 39 CHF – Adults : 36 CHF instead of 49 CHF Free for children under 5.

  18. Offers for our members

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    2013-01-01

    La banque LCL propose aux membres de l’Association du personnel les avantages suivants : – Un barème Privilège sur le Prêt immobilier – Des avantages tarifaires sur l’épargne, notamment l’assurance-vie. – Un taux préférentiel de prêt à la consommation. En outre, jusqu’au 30 septembre 2013, elle offre 50€ à tous les nouveaux clients, membres de l'Association du personnel. Summer is here, enjoy our offers for the aquatic parcs! Tickets "Zone terrestre" : 21 € instead of de 26 €. Access to Aqualibi : 5 euros instead of 8 euros on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Free car park. * * * * * * * Full day ticket: – Children : 30 CHF instead of 39 CHF &...

  19. Subduction and exhumation of continental crust: insights from laboratory models

    Science.gov (United States)

    Bialas, Robert W.; Funiciello, Francesca; Faccenna, Claudio

    2011-01-01

    When slivers of continental crust and sediment overlying oceanic lithosphere enter a subduction zone, they may be scraped off at shallow levels, subducted to depths of up to 100-200 km and then exhumed as high pressure (HP) and ultra-high pressure (UHP) rocks, or subducted and recycled in the mantle. To investigate the factors that influence the behaviour of subducting slivers of continental material, we use 3-D dynamically consistent laboratory models. A laboratory analogue of a slab-upper mantle system is set up with two linearly viscous layers of silicone putty and glucose syrup in a tank. A sliver of continental material, also composed of silicone putty, overlies the subducting lithosphere, separated by a syrup detachment. The density of the sliver, viscosity of the detachment, geometry of the subducting system (attached plate versus free ridge) and dimensions of the sliver are varied in 34 experiments. By varying the density of the sliver and viscosity of the detachment, we can reproduce a range of sliver behaviour, including subduction, subduction and exhumation from various depths and offscraping. Sliver subduction and exhumation requires sufficient sliver buoyancy and a detachment that is strong enough to hold the sliver during initial subduction, but weak enough to allow adequate sliver displacement or detachment for exhumation. Changes to the system geometry alter the slab dip, subduction velocity, pattern of mantle flow and amount of rollback. Shallower slab dips with more trench rollback produce a mantle flow pattern that aids exhumation. Steeper slab dips allow more buoyancy force to be directed in the up-dip direction of the plane of the plate, and aide exhumation of subducted slivers. Slower subduction can also aide exhumation, but if slab dip is too steep or subduction too slow, the sliver will subduct to only shallow levels and not exhume. Smaller slivers are most easily subducted and exhumed and influenced by the mantle flow.

  20. Behavioral and cognitive impact of early life stress: Insights from an animal model.

    Science.gov (United States)

    Liu, Hesong; Atrooz, Fatin; Salvi, Ankita; Salim, Samina

    2017-08-01

    Children subjected to traumatic events during childhood are reported to exhibit behavioral and cognitive deficits later in life, often leading to post-traumatic stress disorder (PTSD) and major depression. Interestingly, some children continue to remain normal despite being exposed to the same risk factors. These trauma-related behavioral and cognitive profiles across different stages of life are not well understood. Animal studies can offer useful insights. The goal of this study was to determine the impact of early life exposure to traumatic events on behavioral and cognitive profile in rats by tracking the behavior of each rat at different ages. We utilized the single prolonged stress (SPS), a rodent model of PTSD, to study the effects of early life stress. Male Sprague-Dawley rats were exposed to SPS on post-natal day (PND) 25. Tests to assess anxiety- and depression-like behavior, as well as learning and memory function were performed at PND32, 60 and 90. Rats exposed to SPS exhibited both anxiety- and depression-like behavior at PND32. And, short-term (STM) but not long-term memory (LTM) was impaired. Rats exposed to SPS at PND60 exhibited anxiety- but not depression-like behavior. STM but not LTM was impaired. Rats exposed to SPS at PND90 exhibited fearful (as indicated by elevated plus maze test) but not an overall anxiety-like behavior (in light and dark test). These rats also displayed significant depression-like behavior with no changes in STM or LTM. Interestingly, when data was further analyzed, two subsets of PND90 rats exposed to SPS were identified, "susceptible": with depression-like behavior and "resilient": without depression-like behavior. Importantly, while resilient group expressed early signs of anxiety- (at PND32 and PND60) and depression-like behavior (at PND32), these behavioral deficits were absent at PND90. On the other hand, susceptible PND90 rats exposed to SPS expressed later onset of anxiety-like behavior (at PND60), while depression

  1. Using genetic mouse models to gain insight into glaucoma: Past results and future possibilities.

    Science.gov (United States)

    Fernandes, Kimberly A; Harder, Jeffrey M; Williams, Pete A; Rausch, Rebecca L; Kiernan, Amy E; Nair, K Saidas; Anderson, Michael G; John, Simon W M; Howell, Gareth R; Libby, Richard T

    2015-12-01

    While all forms of glaucoma are characterized by a specific pattern of retinal ganglion cell death, they are clinically divided into several distinct subclasses, including normal tension glaucoma, primary open angle glaucoma, congenital glaucoma, and secondary glaucoma. For each type of glaucoma there are likely numerous molecular pathways that control susceptibility to the disease. Given this complexity, a single animal model will never precisely model all aspects of all the different types of human glaucoma. Therefore, multiple animal models have been utilized to study glaucoma but more are needed. Because of the powerful genetic tools available to use in the laboratory mouse, it has proven to be a highly useful mammalian system for studying the pathophysiology of human disease. The similarity between human and mouse eyes coupled with the ability to use a combination of advanced cell biological and genetic tools in mice have led to a large increase in the number of studies using mice to model specific glaucoma phenotypes. Over the last decade, numerous new mouse models and genetic tools have emerged, providing important insight into the cell biology and genetics of glaucoma. In this review, we describe available mouse genetic models that can be used to study glaucoma-relevant disease/pathobiology. Furthermore, we discuss how these models have been used to gain insights into ocular hypertension (a major risk factor for glaucoma) and glaucomatous retinal ganglion cell death. Finally, the potential for developing new mouse models and using advanced genetic tools and resources for studying glaucoma are discussed.

  2. Parameter sensitivity analysis of stochastic models provides insights into cardiac calcium sparks.

    Science.gov (United States)

    Lee, Young-Seon; Liu, Ona Z; Hwang, Hyun Seok; Knollmann, Bjorn C; Sobie, Eric A

    2013-03-05

    We present a parameter sensitivity analysis method that is appropriate for stochastic models, and we demonstrate how this analysis generates experimentally testable predictions about the factors that influence local Ca(2+) release in heart cells. The method involves randomly varying all parameters, running a single simulation with each set of parameters, running simulations with hundreds of model variants, then statistically relating the parameters to the simulation results using regression methods. We tested this method on a stochastic model, containing 18 parameters, of the cardiac Ca(2+) spark. Results show that multivariable linear regression can successfully relate parameters to continuous model outputs such as Ca(2+) spark amplitude and duration, and multivariable logistic regression can provide insight into how parameters affect Ca(2+) spark triggering (a probabilistic process that is all-or-none in a single simulation). Benchmark studies demonstrate that this method is less computationally intensive than standard methods by a factor of 16. Importantly, predictions were tested experimentally by measuring Ca(2+) sparks in mice with knockout of the sarcoplasmic reticulum protein triadin. These mice exhibit multiple changes in Ca(2+) release unit structures, and the regression model both accurately predicts changes in Ca(2+) spark amplitude (30% decrease in model, 29% decrease in experiments) and provides an intuitive and quantitative understanding of how much each alteration contributes to the result. This approach is therefore an effective, efficient, and predictive method for analyzing stochastic mathematical models to gain biological insight.

  3. ISLAND DESTINATIONS' TOURISM OFFER - TOURISTS' VS. RESIDENTS' ATTITUDES

    National Research Council Canada - National Science Library

    Daniela Soldic Frleta

    2014-01-01

      The intent of this paper is to provide empirical insights into the tourists' and residents' attitudes regarding islands tourism and its offer, using the Kvarner Bay islands (Losinj and Rab) as a case study...

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    To our members 5% discount on Fnac vouchers Vouchers of 50.-, 100.- et 200. - CHF Valid in the 4 shops in Switzerland without restriction on purchases. On sale in the office of Secretariat of the staff Association.

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    12 % discount on football camps and courses for children from 3 to 13 years old, with bilingual coaches.   Now also courses during the autumn holidays! In order to get the discount you need to register online, then send a mail to info@intersoccer.ch with a scan of your membership card to recieve a refund of the discount.

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    Découvrez les plus belles tables de Suisse romande et de France voisine en bénéficiant des réductions suivantes sur chaque repas, pendant une année : 50 % pour 2 personnes / 40 % pour 3 personnes / 30 % pour 4 personnes / 20 % pour 5 à 6 personnes. Comment ça marche ? Faites votre choix parmi les 110 restaurants de votre région et réservez votre table pour 2, 3, 4, 5 ou 6 personnes. Présentez votre Passeport Gourmand dès votre arrivée. Savourez votre repas et profitez d’une réduction exceptionnelle sur votre addition (hors boissons, menu du jour et business lunch). Quels sont vos avantages ? Profitez du prix préférentiel pour les membres de l’association du CERN : – Passeport Gourmand Genève : CHF 75.- (au lieu de CHF 95.-) – Passeport Gourmand Ain/Savoie/Haute-Savoie : CHF 59.- (au lieu de...

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    Découvrez les plus belles tables de Suisse romande et de France voisine en bénéficiant des réductions suivantes sur chaque repas, pendant une année : 50 % pour 2 personnes, 40 % pour 3 personnes, 30 % pour 4 personnes, 20 % pour 5 à 6 personnes. Comment ça marche ? Faites votre choix parmi les 110 restaurants de votre région et réservez votre table pour 2, 3, 4, 5 ou 6 personnes. Présentez votre Passeport Gourmand dès votre arrivée. Savourez votre repas et profitez d’une réduction exceptionnelle sur votre addition (hors boissons, menu du jour et business lunch). Quels sont vos avantages ? Profitez du prix préférentiel pour les membres de l’association du CERN : – Passeport Gourmand Genève : CHF 75.- (au lieu de CHF 95.-) – Passeport Gourmand Ain/Savoie/Haute-Savoie : CHF 59.- (au lieu de CH...

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    Concert Scoop music tour sur le parc Walibi ! Vendredi 12 Juillet Vous trouverez la présentation de l’événement et les vidéos des artistes attendus avec leurs titres faisant vibrer les radios en ce moment sur le site internet http://www.walibi.com/rhone-alpes/fr-fr/evenements/scoop-music-tour. Le concert est gratuit et débute à la fermeture du parc avec une première partie surprise. Profitez donc d’une belle journée sur le parc et finissez en beauté avec le concert de l’été !

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    LA BÂTIE-FESTIVAL DE GENEVE Offre pour les membres de l'association du personnel du CERN   P r é s e n t a t i o n L a B â t i e-F e s t i v a l d e G e n è v e : Festival pluridisciplinaire et contemporain, souvent qualifié de «tête chercheuse», La Bâtie-Festival de Genève permet durant deux semaines de découvrir plus de 40 spectacles d’artistes emblématiques d’ici ou d’ailleurs, aussi bien pour les grands que les petits (mini-Bâtie). De la danse, du théâtre, de la musique, du 3 au 18 septembre 2010 nous recevrons près de 300 artistes dans une vingtaine de salles à Genève et en France voisine (Annemasse et Divonne). La Bâtie c’est aussi deux lieux de rencontre et d’échange, Le Tampopo, notre restaurant-l...

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        Envie de soirée au théâtre, n’hésitez pas à bénéficier de nos offres pour nos membres ! Théâtre de Carouge : Réduction de 5 CHF pour tous les spectacles (30 CHF au lieu de 35 CHF) Le théâtre de Carouge vous présente sa nouvelle pièce : La double insconstance Du vedredi 21 mars au dimanche 6 avril 2014 De Marivaux Mise en scène de Philippe Mentha Audio-description le mardi 1er avril et le samedi 5 avril 2014 Il règne un doux mélange de révoltes et de séductions, de ruses et de fatalité dans cette Double Inconstance de Marivaux que met en scène Philippe Mentha, membre fondateur du Théâtre de Carouge et directeur depuis plus de trente ans du Théâtre Kléber-Méleau. L’allure d...

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      Bénéficiez du tarif spécial de 35 CHF/personne + 1 accompagnant au Théâtre de Carouge  en étant membre de l’Association du personnel.  Envoyez votre réservation par mail à smills@tcag.ch via votre adresse mail professionnelle. Indiquez la date de votre réservation, votre nom, prénom et numéro de téléphone. Une confirmation de réservation vous sera retournée par mail. La présentation de votre carte de membre sera demandée lors du retrait des billets.   De Molière – Mise en scène de Jean Liermier Argan, veuf, remarié avec Béline qui n’attend que la mort de son mari pour hériter, multiplie saignées, purges et autres ingestions de remèdes. Angélique, sa fille, vuet &a...

  12. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    Tickets "Zone terrestre": 21.50 € instead of 27 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free.

  13. Offer

    CERN Multimedia

    Staff Association

    2015-01-01

    Le parc ouvre ses portes le samedi 4 avril 2015!   La Chasse aux Oeufs du 4 au 26 avril En plus de ses 25 attractions et spectacles, le parc proposera aux enfants de 3 à 12 ans de relever le challenge d’une course aux oeufs dans un jardin de Pâques reconstitué ! Autant de petits oeufs à trouver dans un temps limite ; tout cela au milieu de lapins, poules, fleurs et autres oeufs géants pour repartir avec des gourmandises en chocolat de la marque Revillon Chocolatier.   Profitez de notre offre spéciale pour nos membres : Tarif unique Adulte/Enfant Entrée Zone terrestre 21,50 euros au lieu de 27 euros Accès à l’Aqualibi : 5 euros au lieu de 8 euros sur présentation du billet d’entrée au tarif membre AP. Entrée gratuite pour les enfants de moins de 3 ans, avec accès limité aux attractions. Les billet...

  14. Offers

    CERN Multimedia

    Staff Association

    2015-01-01

    Tickets "Zone terrestre": 21 € instead of 27 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free.

  15. OFFERS

    CERN Multimedia

    Staff Association

    2014-01-01

    Nouveau partenaire - Joy’s Club   Venez profiter des remises au Joy’s Club / Minigolf à Divonne-les-bains en tant que membre de l’Association ! Sur présentation de votre carte membre, vous bénéficierez d’une remise immédiate telle que : - Pour une partie adulte : 6 euros au lieu de 7 euros - Pour une partie enfant : 4 euros au lieu de 5 euros - Pour le mini Park : 6 euros au lieu de 7 euros Pour plus de renseignements, n’hésitez pas à demander au Secrétariat de l’Association ou à consulter notre site web: http://staff-association.web.cern.ch/fr/socioculturel/offres  

  16. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    Si cette offre vous intéresse, merci d’envoyer un mail à mh.boulanger@comedie.ch avec le détail de votre réservation via votre adresse mail professionnelle. Le retrait des places se fait à la billetterie sur présentation de votre carte de membre de l’Association du personnel. Pour toute commande d’abonnement ou de carte de réduction par courrier ou internet, cocher le tarif collectif en indiquant le nom de l’entreprise et en joignant un justificatif nominatif. Pour tout renseignement, n’hésitez pas à contacter Marie-Hélène Boulanger : –  Tel. : 022 809 60 86 –  email : mh.boulanger@comedie.ch

  17. CO2 conversion by plasma technology: insights from modeling the plasma chemistry and plasma reactor design

    Science.gov (United States)

    Bogaerts, A.; Berthelot, A.; Heijkers, S.; Kolev, St.; Snoeckx, R.; Sun, S.; Trenchev, G.; Van Laer, K.; Wang, W.

    2017-06-01

    In recent years there has been growing interest in the use of plasma technology for CO2 conversion. To improve this application, a good insight into the underlying mechanisms is of great importance. This can be obtained from modeling the detailed plasma chemistry in order to understand the chemical reaction pathways leading to CO2 conversion (either in pure form or mixed with another gas). Moreover, in practice, several plasma reactor types are being investigated for CO2 conversion, so in addition it is essential to be able to model these reactor geometries so that their design can be improved, and the most energy efficient CO2 conversion can be achieved. Modeling the detailed plasma chemistry of CO2 conversion in complex reactors is, however, very time-consuming. This problem can be overcome by using a combination of two different types of model: 0D chemical reaction kinetics models are very suitable for describing the detailed plasma chemistry, while the characteristic features of different reactor geometries can be studied by 2D or 3D fluid models. In the first instance the latter can be developed in argon or helium with a simple chemistry to limit the calculation time; however, the ultimate aim is to implement the more complex CO2 chemistry in these models. In the present paper, examples will be given of both the 0D plasma chemistry models and the 2D and 3D fluid models for the most common plasma reactors used for CO2 conversion in order to emphasize the complementarity of both approaches. Furthermore, based on the modeling insights, the paper discusses the possibilities and limitations of plasma-based CO2 conversion in different types of plasma reactors, as well as what is needed to make further progress in this field.

  18. Studies offer insight into the formative mechanism of "red tides"

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Harmful algal blooms (HABs) in coastal waters, popularly known as "red tides" in China, have become a serious marine environmental problem and an ecological disaster, arousing grave concern of governments, the public and scientists worldwide.

  19. Why Do Markets Crash? Bitcoin Data Offers Unprecedented Insights.

    Science.gov (United States)

    Donier, Jonathan; Bouchaud, Jean-Philippe

    2015-01-01

    Crashes have fascinated and baffled many canny observers of financial markets. In the strict orthodoxy of the efficient market theory, crashes must be due to sudden changes of the fundamental valuation of assets. However, detailed empirical studies suggest that large price jumps cannot be explained by news and are the result of endogenous feedback loops. Although plausible, a clear-cut empirical evidence for such a scenario is still lacking. Here we show how crashes are conditioned by the market liquidity, for which we propose a new measure inspired by recent theories of market impact and based on readily available, public information. Our results open the possibility of a dynamical evaluation of liquidity risk and early warning signs of market instabilities, and could lead to a quantitative description of the mechanisms leading to market crashes.

  20. Does a Spatial Perspective Offer New Insights into Inclusive Organizing?

    DEFF Research Database (Denmark)

    Holck, Lotte

    -scape (Taylor & Spicer 2007, Clegg & Kornberger 2006, Foucault 1984, Soja 1996, Lefebvre 1991, Butler 1990, Acker 2006, 2009, 1990, Ashcraft 2013, 2001). Counter intuitively my research shows how the allegedly borderless, flat, free seating open office space does not a priory convey membership inclusion...

  1. Communication Theory Offers Insight into Mathematics Teachers' Talk

    Science.gov (United States)

    Forrest, Denise B.

    2008-01-01

    This article discusses how communication theory is used to understand the thoughts mathematics teachers employ when creating messages intended for students. According to communication theory, individuals have different premises about the act of communicating, and these thoughts, called message design logics, guide the process of reasoning from…

  2. Why Do Markets Crash? Bitcoin Data Offers Unprecedented Insights

    Science.gov (United States)

    Donier, Jonathan; Bouchaud, Jean-Philippe

    2015-01-01

    Crashes have fascinated and baffled many canny observers of financial markets. In the strict orthodoxy of the efficient market theory, crashes must be due to sudden changes of the fundamental valuation of assets. However, detailed empirical studies suggest that large price jumps cannot be explained by news and are the result of endogenous feedback loops. Although plausible, a clear-cut empirical evidence for such a scenario is still lacking. Here we show how crashes are conditioned by the market liquidity, for which we propose a new measure inspired by recent theories of market impact and based on readily available, public information. Our results open the possibility of a dynamical evaluation of liquidity risk and early warning signs of market instabilities, and could lead to a quantitative description of the mechanisms leading to market crashes. PMID:26448333

  3. Next-generation sequencing offers new insights into DNA degradation

    DEFF Research Database (Denmark)

    Overballe-Petersen, Søren; Orlando, Ludovic Antoine Alexandre; Willerslev, Eske

    2012-01-01

    The processes underlying DNA degradation are central to various disciplines, including cancer research, forensics and archaeology. The sequencing of ancient DNA molecules on next-generation sequencing platforms provides direct measurements of cytosine deamination, depurination and fragmentation r...

  4. Why Do Markets Crash? Bitcoin Data Offers Unprecedented Insights.

    Directory of Open Access Journals (Sweden)

    Jonathan Donier

    Full Text Available Crashes have fascinated and baffled many canny observers of financial markets. In the strict orthodoxy of the efficient market theory, crashes must be due to sudden changes of the fundamental valuation of assets. However, detailed empirical studies suggest that large price jumps cannot be explained by news and are the result of endogenous feedback loops. Although plausible, a clear-cut empirical evidence for such a scenario is still lacking. Here we show how crashes are conditioned by the market liquidity, for which we propose a new measure inspired by recent theories of market impact and based on readily available, public information. Our results open the possibility of a dynamical evaluation of liquidity risk and early warning signs of market instabilities, and could lead to a quantitative description of the mechanisms leading to market crashes.

  5. Insights into thermophilic archaebacterial membrane stability from simplified models of lipid membranes

    Science.gov (United States)

    Davis, Charles H.; Nie, Huifen; Dokholyan, Nikolay V.

    2007-05-01

    Lipid aggregation into fluid bilayers is an essential process for sustaining life. Simplified models of lipid structure, which allow for long time scales or large length scales not obtainable with all-atom simulations, have recently been developed and show promise for describing lipid dynamics in biological systems. Here, we describe two simplified models, a reduced-lipid model and a bola-lipid model for thermophilic bacterial membranes, developed for use with the rapid discrete molecular dynamics simulation method. In the reduced-lipid model, we represent the lipid chain by a series of three beads interacting through pairwise discrete potentials that model hydrophobic attractions between hydrocarbon tails in implicit solvent. Our phase diagram recapitulates those produced by continuous potential models with similar coarse-grained lipid representations. We also find that phase transition temperatures for our reduced-lipid model are dependent upon the flexibility of the lipid chain, giving an insight into archaebacterial membrane stability and prompting development of a bola-lipid model specific for archaebacteria lipids. With both the reduced-lipid and bola-lipid model, we find that the reduced flexibility inherent in archaebacteria lipids yields more stable bilayers as manifested by increased phase transition temperatures. The results of these studies provide a simulation methodology for lipid molecules in biological systems and show that discrete molecular dynamics is applicable to lipid aggregation and dynamics.

  6. Business Model Innovation: Insights from a Multiple Case Study of Slovenian SMEs

    Directory of Open Access Journals (Sweden)

    Marolt Marjeta

    2016-08-01

    Full Text Available Background and Purpose: Business model innovation (BMI has become increasingly important, especially in the fast changing business environment. While large enterprises approach these changes systematically, small and medium sized enterprises (SMEs are left to their own resourcefulness. For the purpose of developing dedicated methods and tools to support different SMEs in addressing these challenges, we have conducted a multiple case study to gain insights into factors that drive SMEs to innovate their BM, how they approach BMI and what changes they made to their BM.

  7. Insight in Psychosis: An Indicator of Severity of Psychosis, an Explanatory Model of Illness, and a Coping Strategy.

    Science.gov (United States)

    Jacob, K S

    2016-01-01

    Recent studies related to insight, explanatory models (EMs) of illness and their relationship to outcome of psychosis are reviewed. The traditional argument that insight predicts outcome in psychosis is not supported by recent longitudinal data, which has been analyzed using multivariable statistics that adjust for severity and quality of illness. While all cognition will have a neurobiological representation, if "insight" is related to the primary psychotic process, then insight cannot be seen as an independent predictor of outcome but a part of the progression of illness. The evidence suggests insight, like all EMs, is belief which interacts with the trajectory of the person's illness and the local culture to produce a unique understanding of the illness for the particular individual and his/her family.

  8. Neurocognition, insight and medication nonadherence in schizophrenia: a structural equation modeling approach.

    Directory of Open Access Journals (Sweden)

    Laurent Boyer

    Full Text Available OBJECTIVE: The aim of this study was to examine the complex relationships among neurocognition, insight and nonadherence in patients with schizophrenia. METHODS: DESIGN: Cross-sectional study. INCLUSION CRITERIA: Diagnosis of schizophrenia according to the DSM-IV-TR criteria. DATA COLLECTION: Neurocognition was assessed using a global approach that addressed memory, attention, and executive functions; insight was analyzed using the multidimensional 'Scale to assess Unawareness of Mental Disorder;' and nonadherence was measured using the multidimensional 'Medication Adherence Rating Scale.' ANALYSIS: Structural equation modeling (SEM was applied to examine the non-straightforward relationships among the following latent variables: neurocognition, 'awareness of positive symptoms' and 'negative symptoms', 'awareness of mental disorder' and nonadherence. RESULTS: One hundred and sixty-nine patients were enrolled. The final testing model showed good fit, with normed χ(2 = 1.67, RMSEA = 0.063, CFI = 0.94, and SRMR = 0.092. The SEM revealed significant associations between (1 neurocognition and 'awareness of symptoms,' (2 'awareness of symptoms' and 'awareness of mental disorder' and (3 'awareness of mental disorder' and nonadherence, mainly in the 'attitude toward taking medication' dimension. In contrast, there were no significant links between neurocognition and nonadherence, neurocognition and 'awareness of mental disorder,' and 'awareness of symptoms' and nonadherence. CONCLUSIONS: Our findings support the hypothesis that neurocognition influences 'awareness of symptoms,' which must be integrated into a higher level of insight (i.e., the 'awareness of mental disorder' to have an impact on nonadherence. These findings have important implications for the development of effective strategies to enhance medication adherence.

  9. Evolution of mammal tooth patterns: new insights from a developmental prediction model.

    Science.gov (United States)

    Renvoisé, Elodie; Evans, Alistair R; Jebrane, Ahmad; Labruère, Catherine; Laffont, Rémi; Montuire, Sophie

    2009-05-01

    The study of mammalian evolution is often based on insights into the evolution of teeth. Developmental studies may attempt to address the mechanisms that guide evolutionary changes. One example is the new developmental model proposed by Kavanagh et al. (2007), which provides a high-level testable model to predict mammalian tooth evolution. It is constructed on an inhibitory cascade model based on a dynamic balance of activators and inhibitors, regulating differences in molar size along the lower dental row. Nevertheless, molar sizes in some mammals differ from this inhibitory cascade model, in particular in voles. The aim of this study is to point out arvicoline and murine differences within this model and to suggest an alternative model. Here we demonstrate that the inhibitory cascade is not followed, due to the arvicoline's greatly elongated first lower molar. We broaden the scope of the macroevolutionary model by projecting a time scale onto the developmental model. We demonstrate that arvicoline evolution is rather characterized by a large gap from the oldest vole to more recent genera, with the rapid acquisition of a large first lower molar contemporaneous to their radiation. Our study provides alternative evolutionary hypotheses for mammals with different trajectories of development.

  10. Modeling the Fluid Dynamics in a Human Stomach to Gain Insight of Food Digestion

    Science.gov (United States)

    Ferrua, MJ; Singh, RP

    2010-01-01

    During gastric digestion, food is disintegrated by a complex interaction of chemical and mechanical effects. Although the mechanisms of chemical digestion are usually characterized by using in vitro analysis, the difficulty in reproducing the stomach geometry and motility has prevented a good understanding of the local fluid dynamics of gastric contents. The goal of this study was to use computational fluid dynamics (CFD) to develop a 3-D model of the shape and motility pattern of the stomach wall during digestion, and use it to characterize the fluid dynamics of gastric contents of different viscosities. A geometrical model of an averaged-sized human stomach was created, and its motility was characterized by a series of antral-contraction waves of up to 80% relative occlusion. The flow field within the model (predicted using the software Fluent™) strongly depended on the viscosity of gastric contents. By increasing the viscosity, the formation of the 2 flow patterns commonly regarded as the main mechanisms driving digestion (i.e., the retropulsive jet-like motion and eddy structures) was significantly diminished, while a significant increase of the pressure field was predicted. These results were in good agreement with experimental data previously reported in the literature, and suggest that, contrary to the traditional idea of a rapid and complete homogenization of the meal, gastric contents associated with high viscous meals are poorly mixed. This study illustrates the capability of CFD to provide a unique insight into the fluid dynamics of the gastric contents, and points out its potential to develop a fundamental understanding and modeling of the mechanisms involved in the digestion process. Practical Application This study illustrates the capability of computational fluid dynamic techniques to provide a unique insight into the dynamics of the gastric contents, pointing out its potential to develop a fundamental understanding and modeling of the human

  11. Averaged model for probabilistic coalescence avalanches in two-dimensional emulsions: Insights into uncertainty propagation

    Science.gov (United States)

    Danny Raj, M.; Rengaswamy, R.

    2017-03-01

    A two-dimensional concentrated emulsion exhibits spontaneous rapid destabilization through an avalanche of coalescence events which propagate through the assembly stochastically. We propose a deterministic model to explain the average dynamics of the avalanching process. The dynamics of the avalanche phenomenon is studied as a function of a composite parameter, the decay time ratio, which characterizes the ratio of the propensity of coalescence to cease propagation to that of propagation. When this ratio is small, the avalanche grows autocatalytically to destabilize the emulsion. Using a scaling analysis, we unravel the relation between a local characteristic of the system and a global system wide effect. The anisotropic nature of local coalescence results in a system size dependent transition from nonautocatalytic to autocatalytic behavior. By incorporating uncertainty into the parameters in the model, several possible realizations of the coalescence avalanche are generated. The results are compared with the Monte Carlo simulations to derive insights into how the uncertainty propagates in the system.

  12. Genome-Scale Metabolic Modeling of Archaea Lends Insight into Diversity of Metabolic Function

    Science.gov (United States)

    2017-01-01

    Decades of biochemical, bioinformatic, and sequencing data are currently being systematically compiled into genome-scale metabolic reconstructions (GEMs). Such reconstructions are knowledge-bases useful for engineering, modeling, and comparative analysis. Here we review the fifteen GEMs of archaeal species that have been constructed to date. They represent primarily members of the Euryarchaeota with three-quarters comprising representative of methanogens. Unlike other reviews on GEMs, we specially focus on archaea. We briefly review the GEM construction process and the genealogy of the archaeal models. The major insights gained during the construction of these models are then reviewed with specific focus on novel metabolic pathway predictions and growth characteristics. Metabolic pathway usage is discussed in the context of the composition of each organism's biomass and their specific energy and growth requirements. We show how the metabolic models can be used to study the evolution of metabolism in archaea. Conservation of particular metabolic pathways can be studied by comparing reactions using the genes associated with their enzymes. This demonstrates the utility of GEMs to evolutionary studies, far beyond their original purpose of metabolic modeling; however, much needs to be done before archaeal models are as extensively complete as those for bacteria. PMID:28133437

  13. Resilience offers escape from trapped thinking on poverty alleviation.

    Science.gov (United States)

    Lade, Steven J; Haider, L Jamila; Engström, Gustav; Schlüter, Maja

    2017-05-01

    The poverty trap concept strongly influences current research and policy on poverty alleviation. Financial or technological inputs intended to "push" the rural poor out of a poverty trap have had many successes but have also failed unexpectedly with serious ecological and social consequences that can reinforce poverty. Resilience thinking can help to (i) understand how these failures emerge from the complex relationships between humans and the ecosystems on which they depend and (ii) navigate diverse poverty alleviation strategies, such as transformative change, that may instead be required. First, we review commonly observed or assumed social-ecological relationships in rural development contexts, focusing on economic, biophysical, and cultural aspects of poverty. Second, we develop a classification of poverty alleviation strategies using insights from resilience research on social-ecological change. Last, we use these advances to develop stylized, multidimensional poverty trap models. The models show that (i) interventions that ignore nature and culture can reinforce poverty (particularly in agrobiodiverse landscapes), (ii) transformative change can instead open new pathways for poverty alleviation, and (iii) asset inputs may be effective in other contexts (for example, where resource degradation and poverty are tightly interlinked). Our model-based approach and insights offer a systematic way to review the consequences of the causal mechanisms that characterize poverty traps in different agricultural contexts and identify appropriate strategies for rural development challenges.

  14. Resilience offers escape from trapped thinking on poverty alleviation

    Science.gov (United States)

    Lade, Steven J.; Haider, L. Jamila; Engström, Gustav; Schlüter, Maja

    2017-01-01

    The poverty trap concept strongly influences current research and policy on poverty alleviation. Financial or technological inputs intended to “push” the rural poor out of a poverty trap have had many successes but have also failed unexpectedly with serious ecological and social consequences that can reinforce poverty. Resilience thinking can help to (i) understand how these failures emerge from the complex relationships between humans and the ecosystems on which they depend and (ii) navigate diverse poverty alleviation strategies, such as transformative change, that may instead be required. First, we review commonly observed or assumed social-ecological relationships in rural development contexts, focusing on economic, biophysical, and cultural aspects of poverty. Second, we develop a classification of poverty alleviation strategies using insights from resilience research on social-ecological change. Last, we use these advances to develop stylized, multidimensional poverty trap models. The models show that (i) interventions that ignore nature and culture can reinforce poverty (particularly in agrobiodiverse landscapes), (ii) transformative change can instead open new pathways for poverty alleviation, and (iii) asset inputs may be effective in other contexts (for example, where resource degradation and poverty are tightly interlinked). Our model-based approach and insights offer a systematic way to review the consequences of the causal mechanisms that characterize poverty traps in different agricultural contexts and identify appropriate strategies for rural development challenges. PMID:28508077

  15. Plant Metabolic Modeling: Achieving New Insight into Metabolism and Metabolic Engineering

    Science.gov (United States)

    Baghalian, Kambiz; Hajirezaei, Mohammad-Reza; Schreiber, Falk

    2014-01-01

    Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology. PMID:25344492

  16. Child Disruptive Behavior and Parenting Efficacy: A Comparison of the Effects of Two Models of Insights

    Science.gov (United States)

    O'Connor, Erin; Rodriguez, Eileen; Cappella, Elise; Morris, Jordan; McClowry, Sandee

    2012-01-01

    In this article, we investigate the effectiveness of INSIGHTS into Children's Temperament (INSIGHTS), a temperament-based preventive intervention, in reducing the disruptive behavior problems of young children from low-income, urban families. Results indicate that children enrolled in INSIGHTS evidenced a decrease in disruptive behavior problems…

  17. Child Disruptive Behavior and Parenting Efficacy: A Comparison of the Effects of Two Models of Insights

    Science.gov (United States)

    O'Connor, Erin; Rodriguez, Eileen; Cappella, Elise; Morris, Jordan; McClowry, Sandee

    2012-01-01

    In this article, we investigate the effectiveness of INSIGHTS into Children's Temperament (INSIGHTS), a temperament-based preventive intervention, in reducing the disruptive behavior problems of young children from low-income, urban families. Results indicate that children enrolled in INSIGHTS evidenced a decrease in disruptive behavior problems…

  18. [Insight into tuberculosis pathogenic mechanism from the zebra fish-Mycobacterium marinum model--a review].

    Science.gov (United States)

    Hou, Manmei; Xie, Jianping

    2010-01-01

    Tuberculosis remains a major global health threat. Nearly one-third of the world population infected with Mycobacterium tuberculosis, the etiologic agent of tuberculosis. M. tuberculosis is a typical and most successful intracellular pathogen. The pathogen can evade and manipulate the host immune response. Insights into the interplays between the pathogen and the host was pivotal to develop more sophisticated diagnosis methods and control measures to tuberculosis. No single model can address the full spectrum of this extraordinarily successful pathogen. Multiple models are urgently needed to explore diverse facets of this human being scourge. Zebrafish-M. marinum model was increasingly recognized as an ideal system for preliminary studies. Some key findings emerging from this model were summarized in this paper, such as the interactions between host and M. marinum when the bacterium invades and the contribution of the virulence determinants of M. marinum such as Erp, Esx-1, pmiA, Mel and KasB. Discoveries from different models will be complementary and conducive to find clues to eradicate Mycobacterium tuberculosis.

  19. Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus

    Science.gov (United States)

    da Fontoura Budaszewski, Renata; von Messling, Veronika

    2016-01-01

    Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development. PMID:27727184

  20. Etiology of phantom limb syndrome: Insights from a 3D default space consciousness model.

    Science.gov (United States)

    Jerath, Ravinder; Crawford, Molly W; Jensen, Mike

    2015-08-01

    In this article, we examine phantom limb syndrome to gain insights into how the brain functions as the mind and how consciousness arises. We further explore our previously proposed consciousness model in which consciousness and body schema arise when information from throughout the body is processed by corticothalamic feedback loops and integrated by the thalamus. The parietal lobe spatially maps visual and non-visual information and the thalamus integrates and recreates this processed sensory information within a three-dimensional space termed the "3D default space." We propose that phantom limb syndrome and phantom limb pain arise when the afferent signaling from the amputated limb is lost but the neural circuits remain intact. In addition, integration of conflicting sensory information within the default 3D space and the loss of inhibitory afferent feedback to efferent motor activity from the amputated limb may underlie phantom limb pain.

  1. Insights and models from medical anthropology for understanding the healing activity of the Historical Jesus

    Directory of Open Access Journals (Sweden)

    John J. Pilch

    1995-01-01

    Full Text Available This essay sketches a basic introdution to medical anthropology as a key to understanding and interpreting  the healing activity of the historical Jesus described in the gospels. It presents select literature, leading experts, fundamental concepts, and insights and models of special value to biblical specialists. Only a cross-cultural discipline like medical anthropology allows the investigator to  interpret texts and events from other cultures with respect for their distinctive cultural contexts in order to draw more appropriate conclusions and applications in other cultures. Applications to biblical texts are not included in this essay but may be found in other articles published by the author and listed in the bibliography.

  2. Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus

    Directory of Open Access Journals (Sweden)

    Renata da Fontoura Budaszewski

    2016-10-01

    Full Text Available Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development.

  3. Consumer Insights

    Institute of Scientific and Technical Information of China (English)

    JANKOT

    2004-01-01

    Fang Jun, the head of consumer and market insights of Unilever Shanghai, has summarized his early life as a market in two sentences: rush about to study market changes;act all day to observe consumer behavior. And now?"Tell stories, conduct interviews and piece together different data; calculate numbers,build models and write reports."

  4. Analysis and insights from a dynamical model of nuclear plant safety risk

    Energy Technology Data Exchange (ETDEWEB)

    Hess, Stephen M. [Electric Power Research Institute, 30 Bethel Road, Glen Mills, PA 19342 (United States)]. E-mail: shess@epri.com; Albano, Alfonso M. [School of Economics and Social Sciences, Singapore Management University, 90 Stamford Road, Singapore 178903 (Singapore); Gaertner, John P. [Electric Power Research Institute, 1300 Harris Boulevard, Charlotte, NC 28262 (United States)

    2007-01-15

    In this paper, we expand upon previously reported results of a dynamical systems model for the impact of plant processes and programmatic performance on nuclear plant safety risk. We utilize both analytical techniques and numerical simulations typical of the analysis of nonlinear dynamical systems to obtain insights important for effective risk management. This includes use of bifurcation diagrams to show that period doubling bifurcations and regions of chaotic dynamics can occur. We also investigate the impact of risk mitigating functions (equipment reliability and loss prevention) on plant safety risk and demonstrate that these functions are capable of improving risk to levels that are better than those that are represented in a traditional risk assessment. Next, we analyze the system response to the presence of external noise and obtain some conclusions with respect to the allocation of resources to ensure that safety is maintained at optimal levels. In particular, we demonstrate that the model supports the importance of management and regulator attention to plants that have demonstrated poor performance by providing an external stimulus to obtain desired improvements. Equally important, the model suggests that excessive intervention, by either plant management or regulatory authorities, can have a deleterious impact on safety for plants that are operating with very effective programs and processes. Finally, we propose a modification to the model that accounts for the impact of plant risk culture on process performance and plant safety risk. We then use numerical simulations to demonstrate the important safety benefits of a strong risk culture.

  5. Insights into the genetic basis of systemic sclerosis: immunity in human disease and in mouse models

    Directory of Open Access Journals (Sweden)

    Wu M

    2014-09-01

    Full Text Available Minghua Wu, Maureen D Mayes Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX, USA Abstract: Systemic sclerosis (SSc; scleroderma is a chronic, multisystem autoimmune disease characterized by vasculopathy, fibrosis, and autoantibodies. In the past decade, great efforts have been made to investigate genetic susceptibility for SSc. To date, over 20 gene loci have been identified as risk factors for SSc in large genome-wide association studies and confirmed by independent replication studies. However, the biological relevance of these genetic associations is still largely unknown. Exploring the mechanism behind these risk loci is essential to better understand disease pathogenesis and to identify novel therapeutic targets. Mouse model studies including knockout, knockin and knockdown of these genes can advance our understanding of pathogenic cellular and molecular mechanisms in human disease. Although such mouse model systems do not exactly correspond to human disease, they can provide insight into pathological mechanisms that influence disease pathways. In this review, we discuss recent findings regarding the genetic basis of SSc in the setting of genetic manipulation of these pathways in murine models. Keywords: GWAS, Immunochip study, type I interferon pathway, genetic mutation animal models

  6. First Versus Second Order Latent Growth Curve Models: Some Insights From Latent State-Trait Theory.

    Science.gov (United States)

    Geiser, Christian; Keller, Brian; Lockhart, Ginger

    2013-07-01

    First order latent growth curve models (FGMs) estimate change based on a single observed variable and are widely used in longitudinal research. Despite significant advantages, second order latent growth curve models (SGMs), which use multiple indicators, are rarely used in practice, and not all aspects of these models are widely understood. In this article, our goal is to contribute to a deeper understanding of theoretical and practical differences between FGMs and SGMs. We define the latent variables in FGMs and SGMs explicitly on the basis of latent state-trait (LST) theory and discuss insights that arise from this approach. We show that FGMs imply a strict trait-like conception of the construct under study, whereas SGMs allow for both trait and state components. Based on a simulation study and empirical applications to the CES-D depression scale (Radloff, 1977) we illustrate that, as an important practical consequence, FGMs yield biased reliability estimates whenever constructs contain state components, whereas reliability estimates based on SGMs were found to be accurate. Implications of the state-trait distinction for the measurement of change via latent growth curve models are discussed.

  7. Couples Counseling Directive Technique: A (Mis)communication Model to Promote Insight, Catharsis, Disclosure, and Problem Resolution

    Science.gov (United States)

    Mahaffey, Barbara A.

    2010-01-01

    A psychoeducational model for improving couple communication is proposed. An important goal in couples counseling is to assist couples in resolving communication conflicts. The proposed communication model helps to establish a therapeutic environment that encourages insight, therapeutic alliance formation, catharsis, self-disclosure, symptom…

  8. Hydroclimatology of Dual-Peak Annual Cholera Incidence: Insights from a Spatially Explicit Model

    Science.gov (United States)

    Bertuzzo, E.; Mari, L.; Righetto, L.; Gatto, M.; Casagrandi, R.; Rodriguez-Iturbe, I.; Rinaldo, A.

    2012-12-01

    modeling framework suggests insights on how environmental drivers concert the generation of complex spatiotemporal infections and proposes an explanation for the different cholera patterns (dual or single annual peaks) exhibited by regions that share similar hydroclimatological forcings.

  9. Vacancy Duration, Wage Offers, and Job Requirements

    DEFF Research Database (Denmark)

    Eriksson, Tor Viking; Chen, Long-Hwa

    is concerned with how vacancy durations vary with firms' minimum wage offers and minimum job requirements (regarding education, skills, age, gender and earlier work experience). The empirical analysis is based on ten employer surveys carried out by the DGBAS on Taiwan during the period 1996-2006. We estimate......Besides wage offers, credentials like education, work experience and skill requirements are key screening tools for firms in their recruitment of new employees. This paper adds some new evidence to a relatively tiny literature on firms' recruitment behaviour. In particular, our analysis...... logistic discrete hazard models with a rich set of job and firm characteristics as explanatory variables. The results show that vacancies associated with higher wage offers take, ceteris paribus, longer to be filled. The impact of firms' wage offers and credential requirements does not vary over...

  10. Breaking the entry barriers of startup companies to offer AAL services through integrated eHealth solutions based on a hybrid business model

    DEFF Research Database (Denmark)

    Kyriazakos, Sofoklis

    Healthcare sector is one of the main pillars of the economy at a global level that involves patients, physicians, National Health Systems, insurance companies, pharmaceuticals, vendors, researchers and providers. Healthcare sector represents a good portion of the GDP of any Government and attract...... Organizations (CRO). The full paper will elaborate on the hybrid business model and present how a multi-million € research project has applied this model in order to encounter the challenges and create a solid startup....

  11. Insight into the Functionality of Microbial Exopolysaccharides by NMR Spectroscopy and Molecular Modeling.

    Science.gov (United States)

    Larsen, Flemming H; Engelsen, Søren B

    2015-01-01

    Microbial polysaccharides represent an important class of microbial polymers with diverse functions such as biofilm formation, thickening, and gelling properties as well as health-promoting properties. The broad range of exopolysaccharide (EPS) functionalities has sparked a renewed interest in this class of molecules. Chemical, enzymatic as well as genetic modifications by metabolic engineering can be used to create large numbers of analogous EPS variants with respect to EPS functionality. While this top-down approach is effective in finding new candidates for desired functionality, there seems to be a lack of the corresponding bottom-up approach. The molecular mechanisms of the desired functionalities can be established from Nuclear Magnetic Resonance (NMR) and molecular models and it is proposed that these models can be fed back into the biotechnology by using a quantitative structure-property approach. In this way it will be possible to tailor specific functionality within a given design space. This perspective will include two well-known commercial microbial EPS examples namely gellan and diutan and show how even a limited use of multiphase NMR and molecular modeling can increase the insight into their different properties, which are based on only minor structural differences.

  12. Insight into the functionality of microbioal exo-polysaccharides by NMR and molecular modelling

    Directory of Open Access Journals (Sweden)

    Flemming Hofmann Larsen

    2015-12-01

    Full Text Available Microbial polysaccharides represent an important class of microbial polymers with diverse functions such as biofilm formation, thickening and gelling properties as well as health-promoting properties.The broad range of exopolysaccharide functionalities has sparked a renewed interest in this class of molecules. Chemical, enzymatic as well as genetic modifications by metabolic engineering can be used to create large numbers of analogous exopolysaccharide variants with respect to exopolysaccharide functionality. While this top-down approach is effective in finding new candidates for desired functionality, there seems to be a lack of the corresponding bottom-up approach. The molecular mechanisms of the desired functionalities can be established from NMR and molecular models and it is proposed that these models can be fed back into the biotechnology by using a quantitative structure-property approach. In this way it will be possible to tailor specific functionality within a given design space.This perspective will include two well-known commercial microbial exopolysaccharide examples namely gellan and diutan and show how even a limited use of multiphase NMR and molecular modelling can increase the insight into their different properties, which are based on only minor structural differences.

  13. Business Model Design from an ANT Perspective: Contributions and Insights of an Open and Living Theory

    Science.gov (United States)

    Costa, Cristina Chuva; da Cunha, Paulo Rupino

    The way the Internet has connected millions of users at negligible costs has changed playing field for companies. Several stakeholders can now come together in virtual networks to create innovative business models that would be unfeasible in the physical world. However, the more radical the departure from the established models of value creation, the bigger the complexity in ensuring the sustained interest of the involved parties and the stability of the bonds. To address this problem, we sought inspiration in the Actor-Network Theory (ANT), which is capable of providing insights into socio-technical settings where human and non-human agents interact. We describe how several of its principles, ideas, and concepts were adapted and embedded in our approach for complex business model design or analysis. A simple illustration is provided. Our iterative approach helps systematically scrutinize and tune the contributions and returns of the various actors, ensuring that all end up with an attractive value proposal, thus promoting the robustness of the network. Guidelines for the services that an underlying information system must provide are also derived from the results.

  14. Direct numerical simulation of turbulent combustion: fundamental insights towards predictive models

    Science.gov (United States)

    Hawkes, Evatt R.; Sankaran, Ramanan; Sutherland, James C.; Chen, Jacqueline H.

    2005-01-01

    The advancement of our basic understanding of turbulent combustion processes and the development of physics-based predictive tools for design and optimization of the next generation of combustion devices are strategic areas of research for the development of a secure, environmentally sound energy infrastructure. In direct numerical simulation (DNS) approaches, all scales of the reacting flow problem are resolved. However, because of the magnitude of this task, DNS of practical high Reynolds number turbulent hydrocarbon flames is out of reach of even terascale computing. For the foreseeable future, the approach to this complex multi-scale problem is to employ distinct but synergistic approaches to tackle smaller sub-ranges of the complete problem, which then require models for the small scale interactions. With full access to the spatially and temporally resolved fields, DNS can play a major role in the development of these models and in the development of fundamental understanding of the micro-physics of turbulence-chemistry interactions. Two examples, from simulations performed at terascale Office of Science computing facilities, are presented to illustrate the role of DNS in delivering new insights to advance the predictive capability of models. Results are presented from new three-dimensional DNS with detailed chemistry of turbulent non-premixed jet flames, revealing the differences between mixing of passive and reacting scalars, and determining an optimal lower dimensional representation of the full thermochemical state space.

  15. Insights into the variability of nucleated amyloid polymerization by a minimalistic model of stochastic protein assembly

    Science.gov (United States)

    Eugène, Sarah; Xue, Wei-Feng; Robert, Philippe; Doumic, Marie

    2016-05-01

    Self-assembly of proteins into amyloid aggregates is an important biological phenomenon associated with human diseases such as Alzheimer's disease. Amyloid fibrils also have potential applications in nano-engineering of biomaterials. The kinetics of amyloid assembly show an exponential growth phase preceded by a lag phase, variable in duration as seen in bulk experiments and experiments that mimic the small volumes of cells. Here, to investigate the origins and the properties of the observed variability in the lag phase of amyloid assembly currently not accounted for by deterministic nucleation dependent mechanisms, we formulate a new stochastic minimal model that is capable of describing the characteristics of amyloid growth curves despite its simplicity. We then solve the stochastic differential equations of our model and give mathematical proof of a central limit theorem for the sample growth trajectories of the nucleated aggregation process. These results give an asymptotic description for our simple model, from which closed form analytical results capable of describing and predicting the variability of nucleated amyloid assembly were derived. We also demonstrate the application of our results to inform experiments in a conceptually friendly and clear fashion. Our model offers a new perspective and paves the way for a new and efficient approach on extracting vital information regarding the key initial events of amyloid formation.

  16. The ultimatum game: Discrete vs. continuous offers

    Science.gov (United States)

    Dishon-Berkovits, Miriam; Berkovits, Richard

    2014-09-01

    In many experimental setups in social-sciences, psychology and economy the subjects are requested to accept or dispense monetary compensation which is usually given in discrete units. Using computer and mathematical modeling we show that in the framework of studying the dynamics of acceptance of proposals in the ultimatum game, the long time dynamics of acceptance of offers in the game are completely different for discrete vs. continuous offers. For discrete values the dynamics follow an exponential behavior. However, for continuous offers the dynamics are described by a power-law. This is shown using an agent based computer simulation as well as by utilizing an analytical solution of a mean-field equation describing the model. These findings have implications to the design and interpretation of socio-economical experiments beyond the ultimatum game.

  17. Postgraduates courses offered to nursing

    Directory of Open Access Journals (Sweden)

    Pedro Jorge Araujo

    2011-07-01

    Full Text Available Aim: To know the official masters that the Spanish Universities have offered during the academic course 2010/2011.Material and methods: Descriptive observational and transversal court study, in which it has analysed 170 university official masters and in which it has used a questionnaire with a total of 15 questions elaborated for this work.Results: 52 Spanish Universities of the 75 that there is have offered during the academic course 2010/2011 official masters that can realise for graduated in infirmary. By areas, the official masters more offered have been the ones of nutrition and alimentary security. 76,33% of the official masters have a length of 1 academic year. Almost the half of the official masters have an orientation researcher-professional and almost 40% researcher. 62,65% of the masters give of face-to-face way. In 52,1% of the official masters do not realise external practices and 86,2% has continuity with the doctorate.Conclusions: It has seen that it is necessary that expand the number of masters including other fields of study that contribute to a main specialisation of the professionals of the infirmary. An important percentage of official masters give in face-to-face modality, and there is very few offered on-line or to distance.

  18. Where Health and Death Intersect: Insights from a Terror Management Health Model.

    Science.gov (United States)

    Arndt, Jamie; Goldenberg, Jamie L

    2017-01-01

    This paper offers an integrative understanding of the intersection between "health" and "death" from the perspective of the terror management health model. After highlighting the potential for health-related situations to elicit concerns about mortality, we turn to the question, how do thoughts of death influence health decision-making? Across varied health domains, the answer depends on whether these cognitions are in conscious awareness or not. When mortality concerns are conscious, people engage in healthy intentions and behavior if efficacy and coping resources are present. In contrast, when contending with accessible but non-conscious thoughts of death, health relevant decisions are guided more by esteem implications of the behavior. Lastly, we present research suggesting how these processes can be leveraged to facilitate health promotion and reduce health risk.

  19. Comparative Study of Lectin Domains in Model Species: New Insights into Evolutionary Dynamics

    Directory of Open Access Journals (Sweden)

    Sofie Van Holle

    2017-05-01

    Full Text Available Lectins are present throughout the plant kingdom and are reported to be involved in diverse biological processes. In this study, we provide a comparative analysis of the lectin families from model species in a phylogenetic framework. The analysis focuses on the different plant lectin domains identified in five representative core angiosperm genomes (Arabidopsis thaliana, Glycine max, Cucumis sativus, Oryza sativa ssp. japonica and Oryza sativa ssp. indica. The genomes were screened for genes encoding lectin domains using a combination of Basic Local Alignment Search Tool (BLAST, hidden Markov models, and InterProScan analysis. Additionally, phylogenetic relationships were investigated by constructing maximum likelihood phylogenetic trees. The results demonstrate that the majority of the lectin families are present in each of the species under study. Domain organization analysis showed that most identified proteins are multi-domain proteins, owing to the modular rearrangement of protein domains during evolution. Most of these multi-domain proteins are widespread, while others display a lineage-specific distribution. Furthermore, the phylogenetic analyses reveal that some lectin families evolved to be similar to the phylogeny of the plant species, while others share a closer evolutionary history based on the corresponding protein domain architecture. Our results yield insights into the evolutionary relationships and functional divergence of plant lectins.

  20. Conformity, anticonformity and polarization of opinions: insights from a mathematical model of opinion dynamics

    CERN Document Server

    Krüger, Tyll; Weron, Tomasz

    2016-01-01

    Understanding and quantifying polarization in social systems is important because of many reasons. It could for instance help to avoid segregation and conflicts in the society (DiMaggio et al. 1996) or to control polarized debates and predict their outcomes (Walton 1991). In a recent paper (Siedlecki et al. 2016) we used an agent-based model of a segmented society to check if the polarization may be induced by a competition between conformity and anticonformity. Among other things we have shown that the interplay of intra-clique conformity and inter-clique anticonformity may indeed lead to a bi-polarized state of the system. This paper is a continuation of the work done in (Siedlecki et al. 2016). We consider here a slightly modified version of the model that allows for mathematical treatment and gives more insight into the dynamics of the system. We determine conditions needed to arrive at consensus in a double-clique network with conformity and anticonformity as types of social influence and find regimes, i...

  1. Mechanism for cocaine blocking the transport of dopamine: insights from molecular modeling and dynamics simulations.

    Science.gov (United States)

    Huang, Xiaoqin; Gu, Howard H; Zhan, Chang-Guo

    2009-11-12

    Molecular modeling and dynamics simulations have been performed to study how cocaine inhibits dopamine transporter (DAT) for the transport of dopamine. The computationally determined DAT-ligand binding mode is totally different from the previously proposed overlap binding mode in which cocaine- and dopamine-binding sites are the same (Beuming, T.; et al. Nat. Neurosci. 2008, 11, 780-789). The new cocaine-binding site does not overlap with, but is close to, the dopamine-binding site. Analysis of all results reveals that when cocaine binds to DAT, the initial binding site is likely the one modeled in this study because this binding site can naturally accommodate cocaine. Then cocaine may move to the dopamine-binding site after DAT makes some necessary conformational change and expands the binding site cavity. It has been demonstrated that cocaine may inhibit the transport of dopamine through both blocking the initial DAT-dopamine binding and reducing the kinetic turnover of the transporter following the DAT-dopamine binding. The relative contributions to the phenomenological inhibition of the transport of dopamine from blocking the initial binding and reducing the kinetic turnover can be different in different types of assays. The obtained general structural and mechanistic insights are consistent with available experimental data and could be valuable for guiding future studies toward understanding cocaine's inhibiting of other transporters.

  2. Policy insights from the nutritional food market transformation model: the case of obesity prevention.

    Science.gov (United States)

    Struben, Jeroen; Chan, Derek; Dubé, Laurette

    2014-12-01

    This paper presents a system dynamics policy model of nutritional food market transformation, tracing over-time interactions between the nutritional quality of supply, consumer food choice, population health, and governmental policy. Applied to the Canadian context and with body mass index as the primary outcome, we examine policy portfolios for obesity prevention, including (1) industry self-regulation efforts, (2) health- and nutrition-sensitive governmental policy, and (3) efforts to foster health- and nutrition-sensitive innovation. This work provides novel theoretical and practical insights on drivers of nutritional market transformations, highlighting the importance of integrative policy portfolios to simultaneously shift food demand and supply for successful and self-sustaining nutrition and health sensitivity. We discuss model extensions for deeper and more comprehensive linkages of nutritional food market transformation with supply, demand, and policy in agrifood and health/health care. These aim toward system design and policy that can proactively, and with greater impact, scale, and resilience, address single as well as double malnutrition in varying country settings. © 2014 New York Academy of Sciences.

  3. Toward a model of cognitive insight in first-episode psychosis: verbal memory and hippocampal structure.

    Science.gov (United States)

    Buchy, L; Czechowska, Y; Chochol, C; Malla, A; Joober, R; Pruessner, J; Lepage, M

    2010-09-01

    Our previous work has linked verbal learning and memory with cognitive insight, but not clinical insight, in individuals with a first-episode psychosis (FEP). The current study reassessed the neurocognitive basis of cognitive and clinical insight and explored their neural basis in 61 FEP patients. Cognitive insight was measured with the Beck Cognitive Insight Scale (BCIS) and clinical insight with the Scale to assess Unawareness of Mental Disorder (SUMD). Global measures for 7 domains of cognition were examined. Hippocampi were manually segmented in to 3 parts: the body, head, and tail. Verbal learning and memory significantly correlated with the BCIS composite index. Composite index scores were significantly associated with total left hippocampal (HC) volume; partial correlations, however, revealed that this relationship was attributable largely to verbal memory performance. The BCIS self-certainty subscale significantly and inversely correlated with bilateral HC volumes, and these associations were independent of verbal learning and memory performance. The BCIS self-reflectiveness subscale significantly correlated with verbal learning and memory but not with HC volume. No significant correlations emerged between the SUMD and verbal memory or HC volume. These results strengthen our previous assertion that in individuals with an FEP cognitive insight may rely on memory whereby current experiences are appraised based on previous ones. The HC may be a viable location among others for the brain system that underlies aspects of cognitive insight in individuals with an FEP.

  4. Robust determinants of OECD FDI in developing countries: Insights from Bayesian model averaging

    Directory of Open Access Journals (Sweden)

    Nikolaos Antonakakis

    2015-12-01

    Full Text Available In this paper, we examine the determinants of outward FDI from four major OECD investors, namely, the US, Germany, France, and the Netherlands, to 129 developing countries classified under five regions over the period 1995–2008. Our goal is to distinguish whether the motivation for FDI differs among these investors in developing countries. Rather than relying on specific theories of FDI determinants, we examine them all simultaneously by employing Bayesian model averaging (BMA. This approach permits us to select the most appropriate model (or combination of models that governs FDI allocation and to distinguish robust FDI determinants. We find that no single theory governs the decision of OECD FDI in developing countries but a combination of theories. In particular, OECD investors search for destinations with whom they have established intensive trade relations and that offer a qualified labor force. Low wages and attractive tax rates are robust investment criteria too, and a considerable share of FDI is still resource-driven. Overall, investors show fairly similar strategies in the five developing regions.

  5. A model for the implementation of a two-shift municipal solid waste and recyclable material collection plan that offers greater convenience to residents.

    Science.gov (United States)

    Lin, Hung-Yueh; Tsai, Zong-Pei; Chen, Guan-Hwa; Kao, Jehng-Jung

    2011-01-01

    Separating recyclables from municipal solid waste (MSW) before collection reduces not only the quantity of MSW that needs to be treated but also the depletion of resources. However, the participation of residents is essential for a successful recycling program, and the level of participation usually depends on the degree of convenience associated with accessing recycling collection points. The residential accessing convenience (RAC) of a collection plan is determined by the proximity of its collection points to all residents and its temporal flexibility in response to resident requirements. The degree of proximity to all residents is determined by using a coverage radius that represents the maximum distance residents need to travel to access a recycling point. The temporal flexibility is assessed by the availability of proximal recycling points at times suitable to the lifestyles of all residents concerned. In Taiwan, the MSW collection is implemented at fixed locations and at fixed times. Residents must deposit their garbage directly into the collection vehicle. To facilitate the assignment of collection vehicles and to encourage residents to thoroughly separate their recyclables, in Taiwan MSW and recyclable materials are usually collected at the same time by different vehicles. A heuristic procedure including an integer programming (IP) model and ant colony optimization (ACO) is explored in this study to determine an efficient two-shift collection plan that takes into account RAC factors. The IP model has been developed to determine convenient collection points in each shift on the basis of proximity, and then the ACO algorithm is applied to determine the most effective routing plan of each shift. With the use of a case study involving a city in Taiwan, this study has demonstrated that collection plans generated using the above procedure are superior to current collection plans on the basis of proximity and total collection distance.

  6. Is human Type 2 diabetes maternally inherited? Insights from an animal model.

    Science.gov (United States)

    Gill-Randall, R J; Adams, D; Ollerton, R L; Alcolado, J C

    2004-07-01

    Patients with Type 2 diabetes mellitus more often report a history of an affected mother than father. However, in the few studies where both parents and offspring have been directly tested, this apparent maternal excess has not been confirmed. Rodent models of diabetes have the advantage that all parents and offspring can undergo glucose tolerance testing at a specific age in adult life. The aim of this study was to gain insights into the inheritance of human Type 2 diabetes by using a rat model. Goto Kakizaki (GK) rats (a model of Type 2 diabetes) were mated with non-diabetic Wistar rats. Offspring were produced from 20 GK female vs. Wistar male and 20 Wistar female vs. GK male crosses. Fasting blood glucose was measured at 6 weeks and 3 months of age and an intravenous glucose tolerance test (0.8 g/kg) performed at 6 months of age. Wistar mothers produced litters with almost twice as many viable offspring as GK mothers (14.1 vs. 7.4, P < 0.001). Despite the larger litter size, offspring in the two groups were of comparable weight at 6 weeks and 6 months of age. At 3 months of age, male offspring of Wistar mothers were heavier than offspring of GK mothers (415.7 g vs. 379.5 g, P = 0.016) but this difference was not sustained at 6 months of age. Fasting blood glucose at all ages and average blood glucose during the glucose tolerance test were similar in both groups. We therefore conclude that there is no evidence for maternal transmission of diabetes in the GK rat. Mothers were able to adjust their supply of milk so that offspring attained similar weights independent of litter size. The weight of the offspring remained independent of litter size into adult life.

  7. Sources of Sahelian-Sudan moisture: Insights from a moisture-tracing atmospheric model

    Science.gov (United States)

    Salih, Abubakr A. M.; Zhang, Qiong; Pausata, Francesco S. R.; Tjernström, Michael

    2016-07-01

    The summer rainfall across Sahelian-Sudan is one of the main sources of water for agriculture, human, and animal needs. However, the rainfall is characterized by large interannual variability, which has attracted extensive scientific efforts to understand it. This study attempts to identify the source regions that contribute to the Sahelian-Sudan moisture budget during July through September. We have used an atmospheric general circulation model with an embedded moisture-tracing module (Community Atmosphere Model version 3), forced by observed (1979-2013) sea-surface temperatures. The result suggests that about 40% of the moisture comes with the moisture flow associated with the seasonal migration of the Intertropical Convergence Zone (ITCZ) and originates from Guinea Coast, central Africa, and the Western Sahel. The Mediterranean Sea, Arabian Peninsula, and South Indian Ocean regions account for 10.2%, 8.1%, and 6.4%, respectively. Local evaporation and the rest of the globe supply the region with 20.3% and 13.2%, respectively. We also compared the result from this study to a previous analysis that used the Lagrangian model FLEXPART forced by ERA-Interim. The two approaches differ when comparing individual regions, but are in better agreement when neighboring regions of similar atmospheric flow features are grouped together. Interannual variability with the rainfall over the region is highly correlated with contributions from regions that are associated with the ITCZ movement, which is in turn linked to the Atlantic Multidecadal Oscillation. Our result is expected to provide insights for the effort on seasonal forecasting of the rainy season over Sahelian Sudan.

  8. Dynamic mechanisms of cell rigidity sensing: insights from a computational model of actomyosin networks.

    Directory of Open Access Journals (Sweden)

    Carlos Borau

    Full Text Available Cells modulate themselves in response to the surrounding environment like substrate elasticity, exhibiting structural reorganization driven by the contractility of cytoskeleton. The cytoskeleton is the scaffolding structure of eukaryotic cells, playing a central role in many mechanical and biological functions. It is composed of a network of actins, actin cross-linking proteins (ACPs, and molecular motors. The motors generate contractile forces by sliding couples of actin filaments in a polar fashion, and the contractile response of the cytoskeleton network is known to be modulated also by external stimuli, such as substrate stiffness. This implies an important role of actomyosin contractility in the cell mechano-sensing. However, how cells sense matrix stiffness via the contractility remains an open question. Here, we present a 3-D Brownian dynamics computational model of a cross-linked actin network including the dynamics of molecular motors and ACPs. The mechano-sensing properties of this active network are investigated by evaluating contraction and stress in response to different substrate stiffness. Results demonstrate two mechanisms that act to limit internal stress: (i In stiff substrates, motors walk until they exert their maximum force, leading to a plateau stress that is independent of substrate stiffness, whereas (ii in soft substrates, motors walk until they become blocked by other motors or ACPs, leading to submaximal stress levels. Therefore, this study provides new insights into the role of molecular motors in the contraction and rigidity sensing of cells.

  9. Eliminating bovine tuberculosis in cattle and badgers: insight from a dynamic model.

    Science.gov (United States)

    Brooks-Pollock, Ellen; Wood, James L N

    2015-06-01

    Bovine tuberculosis (BTB) is a multi-species infection that commonly affects cattle and badgers in Great Britain. Despite years of study, the impact of badgers on BTB incidence in cattle is poorly understood. Using a two-host transmission model of BTB in cattle and badgers, we find that published data and parameter estimates are most consistent with a system at the threshold of control. The most consistent explanation for data obtained from cattle and badger populations includes within-host reproduction numbers close to 1 and between-host reproduction numbers of approximately 0.05. In terms of controlling infection in cattle, reducing cattle-to-cattle transmission is essential. In some regions, even large reductions in badger prevalence can have a modest impact on cattle infection and a multi-stranded approach is necessary that also targets badger-to-cattle transmission directly. The new perspective highlighted by this two-host approach provides insight into the control of BTB in Great Britain.

  10. Understanding the causes and prevention of neural tube defects: Insights from the splotch mouse model.

    Science.gov (United States)

    Greene, Nicholas D E; Massa, Valentina; Copp, Andrew J

    2009-04-01

    Splotch mutant mice develop neural tube defects (NTDs), comprising exencephaly and/or spina bifida, as well as neural crest-related defects and abnormalities of limb musculature. Defects in splotch mice result from mutations in Pax3, and some human NTDs may also result from mutations in the human PAX3 gene. Pax3 encodes a transcription factor whose function may influence expression of multiple downstream genes associated with a variety of cellular properties (including apoptosis, adhesion, proliferation, and differentiation), that could be important for neural tube closure. The frequency of NTDs varies between mutant alleles and is also influenced by genetic background and environmental factors. Notably, splotch provides a model for folic acid-preventable NTDs, and conversely, dietary folate deficiency exacerbates NTDs. Understanding the molecular and cellular basis of splotch NTDs, as well as the mechanisms by which the frequency of defects is influenced by genetic and environmental factors (such as sub-optimal folate status), may provide insight into the causation of these severe congenital malformations in humans.

  11. How is visual salience computed in the brain? Insights from behaviour, neurobiology and modelling

    Science.gov (United States)

    Veale, Richard; Hafed, Ziad M.

    2017-01-01

    Inherent in visual scene analysis is a bottleneck associated with the need to sequentially sample locations with foveating eye movements. The concept of a ‘saliency map’ topographically encoding stimulus conspicuity over the visual scene has proven to be an efficient predictor of eye movements. Our work reviews insights into the neurobiological implementation of visual salience computation. We start by summarizing the role that different visual brain areas play in salience computation, whether at the level of feature analysis for bottom-up salience or at the level of goal-directed priority maps for output behaviour. We then delve into how a subcortical structure, the superior colliculus (SC), participates in salience computation. The SC represents a visual saliency map via a centre-surround inhibition mechanism in the superficial layers, which feeds into priority selection mechanisms in the deeper layers, thereby affecting saccadic and microsaccadic eye movements. Lateral interactions in the local SC circuit are particularly important for controlling active populations of neurons. This, in turn, might help explain long-range effects, such as those of peripheral cues on tiny microsaccades. Finally, we show how a combination of in vitro neurophysiology and large-scale computational modelling is able to clarify how salience computation is implemented in the local circuit of the SC. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044023

  12. On the Modelling of Biological Patterns with Mechanochemical Models: Insights from Analysis and Computation

    KAUST Repository

    Moreo, P.

    2009-11-14

    The diversity of biological form is generated by a relatively small number of underlying mechanisms. Consequently, mathematical and computational modelling can, and does, provide insight into how cellular level interactions ultimately give rise to higher level structure. Given cells respond to mechanical stimuli, it is therefore important to consider the effects of these responses within biological self-organisation models. Here, we consider the self-organisation properties of a mechanochemical model previously developed by three of the authors in Acta Biomater. 4, 613-621 (2008), which is capable of reproducing the behaviour of a population of cells cultured on an elastic substrate in response to a variety of stimuli. In particular, we examine the conditions under which stable spatial patterns can emerge with this model, focusing on the influence of mechanical stimuli and the interplay of non-local phenomena. To this end, we have performed a linear stability analysis and numerical simulations based on a mixed finite element formulation, which have allowed us to study the dynamical behaviour of the system in terms of the qualitative shape of the dispersion relation. We show that the consideration of mechanotaxis, namely changes in migration speeds and directions in response to mechanical stimuli alters the conditions for pattern formation in a singular manner. Furthermore without non-local effects, responses to mechanical stimuli are observed to result in dispersion relations with positive growth rates at arbitrarily large wavenumbers, in turn yielding heterogeneity at the cellular level in model predictions. This highlights the sensitivity and necessity of non-local effects in mechanically influenced biological pattern formation models and the ultimate failure of the continuum approximation in their absence. © 2009 Society for Mathematical Biology.

  13. Computational modeling of electric imaging in weakly electric fish: insights for physiology, behavior and evolution.

    Science.gov (United States)

    Gómez-Sena, Leonel; Pedraja, Federico; Sanguinetti-Scheck, Juan I; Budelli, Ruben

    2014-01-01

    Weakly electric fish can sense electric signals produced by other animals whether they are conspecifics, preys or predators. These signals, sensed by passive electroreception, sustain electrocommunication, mating and agonistic behavior. Weakly electric fish can also generate a weak electrical discharge with which they can actively sense the animate and inanimate objects in their surroundings. Understanding both sensory modalities depends on our knowledge of how pre-receptorial electric images are formed and how movements modify them during behavior. The inability of effectively measuring pre-receptorial fields at the level of the skin contrasts with the amount of knowledge on electric fields and the availability of computational methods for estimating them. In this work we review past work on modeling of electric organ discharge and electric images, showing the usefulness of these methods to calculate the field and providing a brief explanation of their principles. In addition, we focus on recent work demonstrating the potential of electric image modeling and what the method has to offer for experimentalists studying sensory physiology, behavior and evolution.

  14. Phosphorus dynamics in lake sediments: Insights from field study and reactive-transport modeling

    Science.gov (United States)

    Dittrich, Maria; Markovic, Stefan; Cadena, Sandra; Doan, Phuong T. K.; Watson, Sue; Mugalingam, Shan

    2016-04-01

    Phosphorus is an indispensable nutrient for organisms in aquatic systems and its availability often controls primary productivity. At the sediment-water interface, intensive microbiological, geochemical and physical processes determine the fraction of organic matter, nutrients and pollutants released into the overlying water. Therefore, detailed understanding of the processes occurring in the top centimeters of the sediment is essential for the assessment of water quality and the management of surface waters. In cases where measurements are impossible or expensive, diagenetic modelling is required to investigate the interplay among the processes, verify concepts and predict potential system behavior. The main aims of this study are to identify and predict the dynamics of phosphorus (P) in sediments and gain insight into the mechanism of P release from sediments under varying environmental conditions. We measured redox, O2 and pH profiles with micro-sensors at the sediment-water interface; analyzed phosphate and metals (Fe, Mn, Al, Ca) content in pore waters collected using in situ samplers, so called "peepers"; determined P binding forms using sequential extraction and analyzed metals associated with each fraction. Following the sediment analysis, P binding forms were divided in five groups: inert, carbonate-bound, organic, redox-sensitive, and labile P. Using the flux of organic and inorganic matter as dynamic boundary conditions, the diagenetic model simulates P internal loading and predicts P retention. This presentation will discuss the results of two years studies on P dynamics at the sediment-water interface in three different lakes ranging from heavy-polluted Hamilton Harbor and Bay of Quinte to pristine Georgian Bay in Ontario, Canada.

  15. New insights into chromatin folding and dynamics from multi-scale modeling

    Science.gov (United States)

    Olson, Wilma

    The dynamic organization of chromatin plays an essential role in the regulation of gene expression and in other fundamental cellular processes. The underlying physical basis of these activities lies in the sequential positioning, chemical composition, and intermolecular interactions of the nucleosomes-the familiar assemblies of roughly 150 DNA base pairs and eight histone proteins-found on chromatin fibers. We have developed a mesoscale model of short nucleosomal arrays and a computational framework that make it possible to incorporate detailed structural features of DNA and histones in simulations of short chromatin constructs with 3-25 evenly spaced nucleosomes. The correspondence between the predicted and observed effects of nucleosome composition, spacing, and numbers on long-range communication between regulatory proteins bound to the ends of designed nucleosome arrays lends credence to the model and to the molecular insights gleaned from the simulated structures. We have extracted effective nucleosome-nucleosome potentials from the mesoscale simulations and introduced the potentials in a larger scale computational treatment of regularly repeating chromatin fibers. Our results reveal a remarkable influence of nucleosome spacing on chromatin flexibility. Small changes in the length of the DNA fragments linking successive nucleosomes introduce marked changes in the local interactions of the nucleosomes and in the spatial configurations of the fiber as a whole. The changes in nucleosome positioning influence the statistical properties of longer chromatin constructs with 100-10,000 nucleosomes. We are investigating the extent to which the `local' interactions of regularly spaced nucleosomes contribute to the corresponding interactions in chains with mixed spacings as a step toward the treatment of fibers with nucleosomes positioned at the sites mapped at base-pair resolution on genomic sequences. Support of the work by USPHS R01 GM 34809 is gratefully acknowledged.

  16. Introductory lecture: atmospheric organic aerosols: insights from the combination of measurements and chemical transport models.

    Science.gov (United States)

    Pandis, Spyros N; Donahue, Neil M; Murphy, Benjamin N; Riipinen, Ilona; Fountoukis, Christos; Karnezi, Eleni; Patoulias, David; Skyllakou, Ksakousti

    2013-01-01

    The formation, atmospheric evolution, properties, and removal of organic particulate matter remain some of the least understood aspects of atmospheric chemistry despite the importance of organic aerosol (OA) for both human health and climate change. Here, we summarize our recent efforts to deal with the chemical complexity of the tens of thousands of organic compounds in the atmosphere using the volatility-oxygen content framework (often called the 2D-Volatility Basis Set, 2D-VBS). Our current ability to measure the ambient OA concentration as a function of its volatility and oxygen to carbon (O:C) ratio is evaluated. The combination of a thermodenuder, isothermal dilution and Aerosol Mass Spectrometry (AMS) together with a mathematical aerosol dynamics model is a promising approach. The development of computational modules based on the 2D-VBS that can be used in chemical transport models (CTMs) is described. Approaches of different complexity are tested against ambient observations, showing the challenge of simulating the complex chemical evolution of atmospheric OA. The results of the simplest approach describing the net change due to functionalization and fragmentation are quite encouraging, reproducing both the observed OA levels and O : C in a variety of conditions. The same CTM coupled with source-apportionment algorithms can be used to gain insights into the travel distances and age of atmospheric OA. We estimate that the average age of OA near the ground in continental locations is 1-2 days and most of it was emitted (either as precursor vapors or particles) hundreds of kilometers away. Condensation of organic vapors on fresh particles is critical for the growth of these new particles to larger sizes and eventually to cloud condensation nuclei (CCN) sizes. The semivolatile organics currently simulated by CTMs are too volatile to condense on these tiny particles with high curvature. We show that chemical aging reactions converting these semivolatile

  17. Evolution of stress-induced borehole breakout in inherently anisotropic rock: Insights from discrete element modeling

    Science.gov (United States)

    Duan, K.; Kwok, C. Y.

    2016-04-01

    The aim of this study is to better understand the mechanisms controlling the initiation, propagation, and ultimate pattern of borehole breakouts in shale formation when drilled parallel with and perpendicular to beddings. A two-dimensional discrete element model is constructed to explicitly represent the microstructure of inherently anisotropic rocks by inserting a series of individual smooth joints into an assembly of bonded rigid discs. Both isotropic and anisotropic hollow square-shaped samples are generated to represent the wellbores drilled perpendicular to and parallel with beddings at reduced scale. The isotropic model is validated by comparing the stress distribution around borehole wall and along X axis direction with analytical solutions. Effects of different factors including the particle size distribution, borehole diameter, far-field stress anisotropy, and rock anisotropy are systematically evaluated on the stress distribution and borehole breakout propagation. Simulation results reveal that wider particle size distribution results in the local stress perturbations which cause localization of cracks. Reduction of borehole diameter significantly alters the crack failure from tensile to shear and raises the critical pressure. Rock anisotropy plays an important role on the stress state around wellbore which lead to the formation of preferred cracks under hydrostatic stress. Far-field stress anisotropy plays a dominant role in the shape of borehole breakout when drilled perpendicular to beddings while a secondary role when drilled parallel with beddings. Results from this study can provide fundamental insights on the underlying particle-scale mechanisms for previous findings in laboratory and field on borehole stability in anisotropic rock.

  18. The Spin-Charge-Family theory offers the explanation for all the assumptions of the Standard model, for the Dark matter, for the Matter-antimatter asymmetry, making several predictions

    CERN Document Server

    Borštnik, Norma Susana Mankoč

    2016-01-01

    The spin-charge-family theory, which is a kind of the Kaluza-Klein theories but with fermions carrying two kinds of spins (no charges), offers the explanation for all the assumptions of the standard model, with the origin of families, the higgs and the Yukawa couplings included. It offers the explanation also for other phenomena, like the origin of the dark matter and of the matter/antimatter asymmetry in the universe. It predicts the existence of the fourth family to the observed three, as well as several scalar fields with the weak and the hyper charge of the standard model higgs ($\\pm \\frac{1}{2}, \\mp \\frac{1}{2}$, respectively), which determine the mass matrices of family members, offering an explanation, why the fourth family with the masses above $1$ TeV contributes weakly to the gluon-fusion production of the observed higgs and to its decay into two photons, and predicting that the two photons events, observed at the LHC at $\\approx 750$ GeV, might be an indication for the existence of one of several s...

  19. Using economic instruments to develop effective management of invasive species: insights from a bioeconomic model.

    Science.gov (United States)

    McDermott, Shana M; Irwin, Rebecca E; Taylor, Brad W

    2013-07-01

    Economic growth is recognized as an important factor associated with species invasions. Consequently, there is increasing need to develop solutions that combine economics and ecology to inform invasive species management. We developed a model combining economic, ecological, and sociological factors to assess the degree to which economic policies can be used to control invasive plants. Because invasive plants often spread across numerous properties, we explored whether property owners should manage invaders cooperatively as a group by incorporating the negative effects of invader spread in management decisions (collective management) or independently, whereby the negative effects of invasive plant spread are ignored (independent management). Our modeling approach used a dynamic optimization framework, and we applied the model to invader spread using Linaria vulgaris. Model simulations allowed us to determine the optimal management strategy based on net benefits for a range of invader densities. We found that optimal management strategies varied as a function of initial plant densities. At low densities, net benefits were high for both collective and independent management to eradicate the invader, suggesting the importance of early detection and eradication. At moderate densities, collective management led to faster and more frequent invader eradication compared to independent management. When we used a financial penalty to ensure that independent properties were managed collectively, we found that the penalty would be most feasible when levied on a property's perimeter boundary to control spread among properties. At the highest densities, the optimal management strategy was "do nothing" because the economic costs of removal were too high relative to the benefits of removal. Spatial variation in L. vulgaris densities resulted in different optimal management strategies for neighboring properties, making a formal economic policy to encourage invasive species removal

  20. Alluvial fan response to climatic change: Insights from numerical modeling (Invited)

    Science.gov (United States)

    Pelletier, J. D.

    2009-12-01

    Alluvial fans in the western U.S. exhibit a regionally correlative sequence of Plio-Quaternary deposits. Cosmogenic and U-series dating has greatly improved the age control on these deposits and their associated terraces and generally strengthened the case for aggradation during humid-to-arid transitions. Still, the linkages between climate change, upland basin response, and alluvial fan response are not well constrained. Fans may fill and cut as a result of autogenetic processes/internal adjustments, changes in regional temperature (which controls snowmelt-induced flooding), changes in the frequency-size distribution of rainfall events, and/or changes in upslope vegetation. Here I describe the results of a numerical modeling study designed to better constrain the relationships between different end-member forcing mechanisms and the geologic record of alluvial fan deposits and terraces. The model solves the evolution of the fan topography using Exner's equation (conservation of mass) coupled with a nonlinear, threshold-controlled transport relation for sand and gravel. Bank retreat is modeled using an advection equation with a rate proportional to bank shear stress. I begin by considering the building of a fan under conditions of constant water and sediment supply. This simple system exhibits all of the complexity of fans developed under experimental conditions, and it provides insights into the mechanisms that control avulsions and it provides a baseline estimate for the within-fan relief that can result from autogenetic processes. Relationships between the magnitude and period of variations in the sediment-to-water ratio and the geomorphic response of fans are then discussed. I also consider the response of a coupled drainage basin-fan system to changes in climate, including the hydrologic and vegetation response of upland hillslopes. Fans can aggrade or incise in response to the same climatic event depending on the relief of the upstream drainage basin, which

  1. The Growth Entrapment Model (GEM): New Insights from Molecular-Scale Simulations of Ti in Quartz

    Science.gov (United States)

    Watson, E. B.; Lanzillo, N. A.; Nayak, S. K.

    2011-12-01

    The growth entrapment model (GEM) put forth by Watson and Liang (Am. Min. 80, 1170-1187) and Watson (GCA 68, 1473-1488) offers a mechanism by which crystals can acquire non-equilibrium chemical or isotopic properties during growth from a uniform fluid medium. The GEM is based on the premise that the equilibrium properties of the near-surface region of a crystal differ from those of the bulk, much as the properties of nanocrystals differ from those of larger crystals of the same phase. In the GEM model, "capture" of the near-surface composition within a growing crystal-creating a non-equilibrium condition-depends upon the outcome of the competition between growth (which buries near-surface atoms) and diffusion (which attempts to restore equilibrium). In any application of the GEM model, the most uncertain input parameters are the near-surface diffusivity (D) and the equilibrium partition coefficient (F) between the near-surface region and the bulk lattice. Experimental measurement of these quantities is elusive because the relevant length scales are small (1-5 nm). However, molecular-scale simulations hold some promise for deducing relative values, as we illustrate here using Ti uptake in quartz as an example. We undertook ab initio molecular dynamics simulations based on a supercell approach to show that the binding energy of Ti^{4+} in quartz is a function of depth in the crystal within a few nanometers of the surface, confirming that F in the GEM model must differ from unity. We also show, using the meta-dynamics method to compute the unbiased diffusion path and corresponding energy barrier, that the activation energy for Ti^{4+} diffusion in the near-surface (2-3 nm deep) is substantially lower than that pertaining to the "deep" lattice diffusivity that is typically measured in diffusion experiments (which we also reproduced computationally). These findings substantiate the underlying phenomena upon which the GEM model is based, in addition to providing

  2. How to Improve Adolescent Stress Responses: Insights From Integrating Implicit Theories of Personality and Biopsychosocial Models.

    Science.gov (United States)

    Yeager, David S; Lee, Hae Yeon; Jamieson, Jeremy P

    2016-08-01

    This research integrated implicit theories of personality and the biopsychosocial model of challenge and threat, hypothesizing that adolescents would be more likely to conclude that they can meet the demands of an evaluative social situation when they were taught that people have the potential to change their socially relevant traits. In Study 1 (N = 60), high school students were assigned to an incremental-theory-of-personality or a control condition and then given a social-stress task. Relative to control participants, incremental-theory participants exhibited improved stress appraisals, more adaptive neuroendocrine and cardiovascular responses, and better performance outcomes. In Study 2 (N = 205), we used a daily-diary intervention to test high school students' stress reactivity outside the laboratory. Threat appraisals (Days 5-9 after intervention) and neuroendocrine responses (Days 8 and 9 after intervention only) were unrelated to the intensity of daily stressors when adolescents received the incremental-theory intervention. Students who received the intervention also had better grades over freshman year than those who did not. These findings offer new avenues for improving theories of adolescent stress and coping.

  3. Optimal drug cocktail design: methods for targeting molecular ensembles and insights from theoretical model systems.

    Science.gov (United States)

    Radhakrishnan, Mala L; Tidor, Bruce

    2008-05-01

    required. We also treated cases in which a subset of target variants was to be avoided, modeling the common challenge of closely related host molecules that may be implicated in drug toxicity. Such decoys generally increased the size of the required cocktail and more often resulted in infeasible optimizations. Taken together, this work provides practical optimization methods for the design of drug cocktails and a theoretical, physics-based framework through which useful insights can be achieved.

  4. An integrated Biophysical CGE model to provide Sustainable Development Goal insights

    Science.gov (United States)

    Sanchez, Marko; Cicowiez, Martin; Howells, Mark; Zepeda, Eduardo

    2016-04-01

    Future projected changes in the energy system will inevitably result in changes to the level of appropriation of environmental resources, particularly land and water, and this will have wider implications for environmental sustainability, and may affect other sectors of the economy. An integrated climate, land, energy and water (CLEW) system will provide useful insights, particularly with regard to the environmental sustainability. However, it will require adequate integration with other tools to detect economic impacts and broaden the scope for policy analysis. A computable general equilibrium (CGE) model is a well suited tool to channel impacts, as detected in a CLEW analysis, onto all sectors of the economy, and evaluate trade-offs and synergies, including those of possible policy responses. This paper will show an application of such integration in a single-country CGE model with the following key characteristics. Climate is partly exogenous (as proxied by temperature and rainfall) and partly endogenous (as proxied by emissions generated by different sectors) and has an impact on endogenous variables such as land productivity and labor productivity. Land is a factor of production used in agricultural and forestry activities which can be of various types if land use alternatives (e.g., deforestation) are to be considered. Energy is an input to the production process of all economic sectors and a consumption good for households. Because it is possible to allow for substitution among different energy sources (e.g. renewable vs non-renewable) in the generation of electricity, the production process of energy products can consider the use of natural resources such as oil and water. Water, data permitting, can be considered as an input into the production process of agricultural sectors, which is particularly relevant in case of irrigation. It can also be considered as a determinant of total factor productivity in hydro-power generation. The integration of a CLEW

  5. Growth plate regulation and osteochondroma formation: insights from tracing proteoglycans in zebrafish models and human cartilage.

    Science.gov (United States)

    de Andrea, Carlos E; Prins, Frans A; Wiweger, Malgorzata I; Hogendoorn, Pancras C W

    2011-06-01

    Proteoglycans are secreted into the extracellular matrix of virtually all cell types and function in several cellular processes. They consist of a core protein onto which glycosaminoglycans (e.g., heparan or chondroitin sulphates), are attached. Proteoglycans are important modulators of gradient formation and signal transduction. Impaired biosynthesis of heparan sulphate glycosaminoglycans causes osteochondroma, the most common bone tumour to occur during adolescence. Cytochemical staining with positively charged dyes (e.g., polyethyleneimine-PEI) allows, visualisation of proteoglycans and provides a detailed description of how proteoglycans are distributed throughout the cartilage matrix. PEI staining was studied by electron and reflection contrast microscopy in human growth plates, osteochondromas and five different proteoglycan-deficient zebrafish mutants displaying one of the following skeletal phenotypes: dackel (dak/ext2), lacking heparan sulphate and identified as a model for human multiple osteochondromas; hi307 (β3gat3), deficient for most glycosaminoglycans; pinscher (pic/slc35b2), presenting with defective sulphation of glycosaminoglycans; hi954 (uxs1), lacking most glycosaminoglycans; and knypek (kny/gpc4), missing the protein core of the glypican-4 proteoglycan. The panel of genetically well-characterized proteoglycan-deficient zebrafish mutants serves as a convincing and comprehensive study model to investigate proteoglycan distribution and the relation of this distribution to the model mutation status. They also provide insight into the distributions and gradients that can be expected in the human homologue. Human growth plate, wild-type zebrafish and fish mutants with mild proteoglycan defects (hi307 and kny) displayed proteoglycans distributed in a gradient throughout the matrix. Although the mutants pic and hi954, which had severely impaired proteoglycan biosynthesis, showed no PEI staining, dak mutants demonstrated reduced PEI staining and no

  6. Ionian Paterae: New Insights from Observations, Numerical Modeling and Laboratory Simulations

    Science.gov (United States)

    Gregg, T. K.; Lopes, R. M.; Black, S. M.; Lougen, J.

    2006-12-01

    To constrain the behavior of Ionian volcanic paterae in general, and Loki Patera in particular, we have used the following techniques in concert: 1) geologic mapping and analyses; 2) laboratory simulations; and 3) mathematical modeling. Here, we present preliminary results from the synthesis of these data. Loki Patera (310°W, 12°°N) is significantly different from the rest of the Ionian paterae for the following reasons: 1) its surface area falls 6 s outside the range for other Ionian paterae; 2) it is the only patera containing a bright "island" that is cut by dark lineaments; 3) at times of a thermal brightening event, it emits up to 15% of Io's global heat flux. Debate continues over whether Loki Paterae is an overturning lava lake, or a depression whose floor is periodically resurfaced by lava flows. Laboratory simulations, in which corn syrup or polyethylene glycol wax (PEG) were extruded into a square tank through 1 or 2 floor vents at a constant rate, were conducted to provide insight into Loki Patera's behavior. Results from both sets of experiments suggest that a single convection cell would be difficult to establish at Loki Patera. Crustal foundering of a lava lake may be possible under special conditions. Given the unique nature of Loki Patera and its island, we propose that the island may be similar to a resurgent dome in a terrestrial caldera complex composed primarily of evolved lavas, such as Long Valley Caldera, California. We examined other paterae that contain bright "islands" on their floors in an effort to constrain their origins. Geologic mapping, and shape analyses of the paterae and the islands they contain, suggest that most paterae islands are patches of cooled lava on the paterae floor. Only about 8% of paterae islands have morphologies and geologic relations that are consistent with a tectonic origin.

  7. What's statistical about learning? Insights from modelling statistical learning as a set of memory processes.

    Science.gov (United States)

    Thiessen, Erik D

    2017-01-05

    Statistical learning has been studied in a variety of different tasks, including word segmentation, object identification, category learning, artificial grammar learning and serial reaction time tasks (e.g. Saffran et al. 1996 Science 274: , 1926-1928; Orban et al. 2008 Proceedings of the National Academy of Sciences 105: , 2745-2750; Thiessen & Yee 2010 Child Development 81: , 1287-1303; Saffran 2002 Journal of Memory and Language 47: , 172-196; Misyak & Christiansen 2012 Language Learning 62: , 302-331). The difference among these tasks raises questions about whether they all depend on the same kinds of underlying processes and computations, or whether they are tapping into different underlying mechanisms. Prior theoretical approaches to statistical learning have often tried to explain or model learning in a single task. However, in many cases these approaches appear inadequate to explain performance in multiple tasks. For example, explaining word segmentation via the computation of sequential statistics (such as transitional probability) provides little insight into the nature of sensitivity to regularities among simultaneously presented features. In this article, we will present a formal computational approach that we believe is a good candidate to provide a unifying framework to explore and explain learning in a wide variety of statistical learning tasks. This framework suggests that statistical learning arises from a set of processes that are inherent in memory systems, including activation, interference, integration of information and forgetting (e.g. Perruchet & Vinter 1998 Journal of Memory and Language 39: , 246-263; Thiessen et al. 2013 Psychological Bulletin 139: , 792-814). From this perspective, statistical learning does not involve explicit computation of statistics, but rather the extraction of elements of the input into memory traces, and subsequent integration across those memory traces that emphasize consistent information (Thiessen and Pavlik

  8. Underperformance of African protected area networks and the case for new conservation models: insights from Zambia.

    Science.gov (United States)

    Lindsey, Peter A; Nyirenda, Vincent R; Barnes, Jonathan I; Becker, Matthew S; McRobb, Rachel; Tambling, Craig J; Taylor, W Andrew; Watson, Frederick G; t'Sas-Rolfes, Michael

    2014-01-01

    Many African protected areas (PAs) are not functioning effectively. We reviewed the performance of Zambia's PA network and provide insights into how their effectiveness might be improved. Zambia's PAs are under-performing in ecological, economic and social terms. Reasons include: a) rapidly expanding human populations, poverty and open-access systems in Game Management Areas (GMAs) resulting in widespread bushmeat poaching and habitat encroachment; b) underfunding of the Zambia Wildlife Authority (ZAWA) resulting in inadequate law enforcement; c) reliance of ZAWA on extracting revenues from GMAs to cover operational costs which has prevented proper devolution of user-rights over wildlife to communities; d) on-going marginalization of communities from legal benefits from wildlife; e) under-development of the photo-tourism industry with the effect that earnings are limited to a fraction of the PA network; f) unfavourable terms and corruption which discourage good practice and adequate investment by hunting operators in GMAs; g) blurred responsibilities regarding anti-poaching in GMAs resulting in under-investment by all stakeholders. The combined effect of these challenges has been a major reduction in wildlife densities in most PAs and the loss of habitat in GMAs. Wildlife fares better in areas with investment from the private and/or NGO sector and where human settlement is absent. There is a need for: elevated government funding for ZAWA; greater international donor investment in protected area management; a shift in the role of ZAWA such that they focus primarily on national parks while facilitating the development of wildlife-based land uses by other stakeholders elsewhere; and new models for the functioning of GMAs based on joint-ventures between communities and the private and/or NGO sector. Such joint-ventures should provide defined communities with ownership of land, user-rights over wildlife and aim to attract long-term private/donor investment. These

  9. High pressure thermal inactivation of Clostridium botulinum type E endospores – kinetic modeling and mechanistic insights

    Directory of Open Access Journals (Sweden)

    Christian Andreas Lenz

    2015-07-01

    Full Text Available Cold-tolerant, neurotoxigenic, endospore forming Clostridium (C. botulinum type E belongs to the non-proteolytic physiological C. botulinum group II, is primarily associated with aquatic environments, and presents a safety risk for seafood. High pressure thermal (HPT processing exploiting the synergistic effect of pressure and temperature can be used to inactivate bacterial endospores.We investigated the inactivation of C. botulinum type E spores by (near isothermal HPT treatments at 300 – 1200 MPa at 30 – 75 °C for 1 s – 10 min. The occurrence of heat and lysozyme susceptible spore fractions after such treatments was determined. The experimental data were modeled to obtain kinetic parameters and represented graphically by isoeffect lines. In contrast to findings for spores of other species and within the range of treatment parameters applied, zones of spore stabilization (lower inactivation than heat treatments alone, large heat susceptible (HPT-induced germinated or lysozyme-dependently germinable (damaged coat layer spore fractions were not detected. Inactivation followed 1st order kinetics. DPA release kinetics allowed for insights into possible inactivation mechanisms suggesting a (poorly effective physiologic-like (similar to nutrient-induced germination at ≤ 450 MPa/≤ 45 °C and non-physiological germination at >500 MPa/>60 – 70 °C.Results of this study support the existence of some commonalities in the HPT inactivation mechanism of C. botulinum type E spores and Bacillus spores although both organisms have significantly different HPT resistance properties. The information presented here contributes to closing the gap in knowledge regarding the HPT inactivation of spore formers relevant to food safety and may help industrial implementation of HPT processing. The markedly lower HPT resistance of C. botulinum type E spores than spores from other C. botulinum types, could allow for the implementation of milder processes without

  10. Quantitative Hydraulic Models Of Early Land Plants Provide Insight Into Middle Paleozoic Terrestrial Paleoenvironmental Conditions

    Science.gov (United States)

    Wilson, J. P.; Fischer, W. W.

    2010-12-01

    Fossil plants provide useful proxies of Earth’s climate because plants are closely connected, through physiology and morphology, to the environments in which they lived. Recent advances in quantitative hydraulic models of plant water transport provide new insight into the history of climate by allowing fossils to speak directly to environmental conditions based on preserved internal anatomy. We report results of a quantitative hydraulic model applied to one of the earliest terrestrial plants preserved in three dimensions, the ~396 million-year-old vascular plant Asteroxylon mackei. This model combines equations describing the rate of fluid flow through plant tissues with detailed observations of plant anatomy; this allows quantitative estimates of two critical aspects of plant function. First and foremost, results from these models quantify the supply of water to evaporative surfaces; second, results describe the ability of plant vascular systems to resist tensile damage from extreme environmental events, such as drought or frost. This approach permits quantitative comparisons of functional aspects of Asteroxylon with other extinct and extant plants, informs the quality of plant-based environmental proxies, and provides concrete data that can be input into climate models. Results indicate that despite their small size, water transport cells in Asteroxylon could supply a large volume of water to the plant's leaves--even greater than cells from some later-evolved seed plants. The smallest Asteroxylon tracheids have conductivities exceeding 0.015 m^2 / MPa * s, whereas Paleozoic conifer tracheids do not reach this threshold until they are three times wider. However, this increase in conductivity came at the cost of little to no adaptations for transport safety, placing the plant’s vegetative organs in jeopardy during drought events. Analysis of the thickness-to-span ratio of Asteroxylon’s tracheids suggests that environmental conditions of reduced relative

  11. Galaxy Evolution Insights from Spectral Modeling of Large Data Sets from the Sloan Digital Sky Survey

    Energy Technology Data Exchange (ETDEWEB)

    Hoversten, Erik A. [Johns Hopkins Univ., Baltimore, MD (United States)

    2007-10-01

    This thesis centers on the use of spectral modeling techniques on data from the Sloan Digital Sky Survey (SDSS) to gain new insights into current questions in galaxy evolution. The SDSS provides a large, uniform, high quality data set which can be exploited in a number of ways. One avenue pursued here is to use the large sample size to measure precisely the mean properties of galaxies of increasingly narrow parameter ranges. The other route taken is to look for rare objects which open up for exploration new areas in galaxy parameter space. The crux of this thesis is revisiting the classical Kennicutt method for inferring the stellar initial mass function (IMF) from the integrated light properties of galaxies. A large data set (~ 105 galaxies) from the SDSS DR4 is combined with more in-depth modeling and quantitative statistical analysis to search for systematic IMF variations as a function of galaxy luminosity. Galaxy Hα equivalent widths are compared to a broadband color index to constrain the IMF. It is found that for the sample as a whole the best fitting IMF power law slope above 0.5 M is Γ = 1.5 ± 0.1 with the error dominated by systematics. Galaxies brighter than around Mr,0.1 = -20 (including galaxies like the Milky Way which has Mr,0.1 ~ -21) are well fit by a universal Γ ~ 1.4 IMF, similar to the classical Salpeter slope, and smooth, exponential star formation histories (SFH). Fainter galaxies prefer steeper IMFs and the quality of the fits reveal that for these galaxies a universal IMF with smooth SFHs is actually a poor assumption. Related projects are also pursued. A targeted photometric search is conducted for strongly lensed Lyman break galaxies (LBG) similar to MS1512-cB58. The evolution of the photometric selection technique is described as are the results of spectroscopic follow-up of the best targets. The serendipitous discovery of two interesting blue compact dwarf galaxies is reported. These

  12. Informing energy and climate policies using energy systems models insights from scenario analysis increasing the evidence base

    CERN Document Server

    Giannakidis, George; Ó Gallachóir, Brian; Tosato, GianCarlo

    2015-01-01

    This book highlights how energy-system models are used to underpin and support energy and climate mitigation policy decisions at national, multi-country and global levels. It brings together, for the first time in one volume, a range of methodological approaches and case studies of good modeling practice on a national and international scale from the IEA-ETSAP energy technology initiative. It provides insights for the reader into the rich and varied applications of energy-system models and the underlying methodologies and policy questions they can address. The book demonstrates how these mode

  13. Clinical picture of obsessive-compulsive disorder with poor insight: a regression model.

    Science.gov (United States)

    Bellino, Silvio; Patria, Luca; Ziero, Simona; Bogetto, Filippo

    2005-09-15

    DSM-IV included a type of obsessive-compulsive disorder (OCD) with poor insight in the official classification. The present study was performed using a continuous measure of the level of insight to analyze the association between this variable and characteristics of the disorder. Seventy-four consecutive OCD outpatients (DSM-IV criteria) were assessed using: a semistructured interview for sociodemographic and clinical features, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the National Institute of Mental Health Obsessive-Compulsive Scale (NIMH-OCS), the Hamilton Depression and Anxiety Rating Scales (HDRS, HARS), and the Overvalued Ideas Scale (OVIS) as a continuous measure of the level of insight. Stepwise multiple regression analysis revealed that demographic and clinical factors were related to the OVIS score. The following four factors were found to be significantly related to the OVIS score: the Y-BOCS score for compulsions, OCD chronic course, and family history of OCD were positively related, while obsessive-compulsive personality disorder was negatively related. These results suggest that poor insight identifies a group of OCD patients with distinct clinical characteristics.

  14. Metaproteomics of our microbiome - Developing insight in function and activity in man and model systems

    NARCIS (Netherlands)

    Kolmeder, C.; Vos, de W.M.

    2014-01-01

    We are all colonized by a large microbiome, a complex set of microbes that have intimate associations with us. Culture-based approaches have provided insights in the complexity of the microbial communities living on surfaces inside and outside the body. However, the application of high-throughput se

  15. Investigating small scale transient deformation features in convergent settings- Insights from analogue modeling

    Science.gov (United States)

    Santimano, T. N.; Rosenau, M.; Oncken, O.

    2013-12-01

    The evolution of a convergent orogenic belt can be dissected into a combination of small scale events. Deformation in the orogenic belts can range in a timescale from earthquake cycle to millions of years. Moreover, long term deformation trends are a composition of the smaller events that together create the final geometry of an orogen. Therefore, it is important to understand the complexity of these events in order to further understand large scale mechanics of deformation. In this study, we employ analogue models of sand wedges representing the brittle upper crust to visualize temporal and spatial deformation in a convergent setting. The time-series evolution of these convergent sand wedges is monitored by Particle Image Velocimetry (PIV). In addition, the stress change within the wedge, especially at the localization of strain i.e. faulting events and between fault events is monitored by a force sensor. The sensor is attached to the back wall, in the experimental setup and against which the sand wedge grows. In these experiments the effect of basal friction on the final geometry of the wedge is tested. This parameter is varied twice. Results show that displacement data from the PIV system, analyzed in the form of strain correlates well with data from the force sensor. On a larger scale, force increases (indicating a linear trend) until strain is localized and a fault is formed causing a sudden drop in force and a release of stress. The magnitude of the force drop after a fault has occurred is related mainly to the horizontal length of the fault. However between fault events, recordings of the force measurements show a cyclic pattern with a decreasing frequency towards a fault event. Over time and as the wedge grows and matures, this intra fault frequency decreases as well. Varying basal friction demonstrates a cutoff in the maximum stress a wedge can handle due to the strength of its base. Time-series image analysis of strain combined with stress analysis

  16. Dynamics of Mantle Circulation Associated with Slab Window Formation: Insights from 3D Laboratory Models

    Science.gov (United States)

    Guillaume, B.; Funiciello, F.; Moroni, M.; Faccenna, C.; Martinod, J.

    2009-12-01

    Slab window can form either by the intersection of a spreading ridge with a subduction zone or because of internal deformation of the slab that leads to its disruption. The main consequences of this phenomenon are the modifications of the physical, chemical and thermal conditions in the backarc mantle that in turn affect the tectonic and magmatic evolution of the overriding plate. We performed laboratory models of a two-layer linear viscous slab (silicone putty)-upper mantle (glucose syrup) system to quantitatively investigate the pattern of mantle circulation within the slab window (using Feature Tracking image analysis technique) and its influence on the kinematics of the system. Two different geometries have been tested considering a window located (a) at slab edges or (b) within the slab. Kinematic consequences of slab window have been explored to understand the dynamics of the mantle-slab interaction. Configuration (a) implies a reduction of the slab width (W) during subduction and is characterized by toroidal fluxes around the slab edges. The abrupt opening of lateral slab windows produces an acceleration of the trench retreat and subduction velocity, such as 40% for a three-fold width reduction. We interpret this behavior as mostly due to the decrease in the toroidal flow inside subduction windows, scaling with W2. Configuration (b) has been designed to explore the pattern of mantle flow within the window in the case of a laterally constrained subduction system. Slab window, which had a width (Ww) fixed to 15 % of the slab width, opened in the trench-perpendicular direction. It produced the formation of two toroidal mantle cells, centered on the slab midpoint and laterally growing as the slab window enlarged. Particles extruded through the slab window did not mix with particles located in the mantle wedge, the boundary between both reaching distances from the trench up to 3×Ww in the trench-perpendicular direction, and up to 1.5×Ww from the window edge in

  17. Underperformance of African protected area networks and the case for new conservation models: insights from Zambia.

    Directory of Open Access Journals (Sweden)

    Peter A Lindsey

    Full Text Available Many African protected areas (PAs are not functioning effectively. We reviewed the performance of Zambia's PA network and provide insights into how their effectiveness might be improved. Zambia's PAs are under-performing in ecological, economic and social terms. Reasons include: a rapidly expanding human populations, poverty and open-access systems in Game Management Areas (GMAs resulting in widespread bushmeat poaching and habitat encroachment; b underfunding of the Zambia Wildlife Authority (ZAWA resulting in inadequate law enforcement; c reliance of ZAWA on extracting revenues from GMAs to cover operational costs which has prevented proper devolution of user-rights over wildlife to communities; d on-going marginalization of communities from legal benefits from wildlife; e under-development of the photo-tourism industry with the effect that earnings are limited to a fraction of the PA network; f unfavourable terms and corruption which discourage good practice and adequate investment by hunting operators in GMAs; g blurred responsibilities regarding anti-poaching in GMAs resulting in under-investment by all stakeholders. The combined effect of these challenges has been a major reduction in wildlife densities in most PAs and the loss of habitat in GMAs. Wildlife fares better in areas with investment from the private and/or NGO sector and where human settlement is absent. There is a need for: elevated government funding for ZAWA; greater international donor investment in protected area management; a shift in the role of ZAWA such that they focus primarily on national parks while facilitating the development of wildlife-based land uses by other stakeholders elsewhere; and new models for the functioning of GMAs based on joint-ventures between communities and the private and/or NGO sector. Such joint-ventures should provide defined communities with ownership of land, user-rights over wildlife and aim to attract long-term private/donor investment

  18. Social deprivation and burden of influenza: Testing hypotheses and gaining insights from a simulation model for the spread of influenza.

    Science.gov (United States)

    Hyder, Ayaz; Leung, Brian

    2015-06-01

    Factors associated with the burden of influenza among vulnerable populations have mainly been identified using statistical methodologies. Complex simulation models provide mechanistic explanations, in terms of spatial heterogeneity and contact rates, while controlling other factors and may be used to better understand statistical patterns and, ultimately, design optimal population-level interventions. We extended a sophisticated simulation model, which was applied to forecast epidemics and validated for predictive ability, to identify mechanisms for the empirical relationship between social deprivation and the burden of influenza. Our modeled scenarios and associated epidemic metrics systematically assessed whether neighborhood composition and/or spatial arrangement could qualitatively replicate this empirical relationship. We further used the model to determine consequences of local-scale heterogeneities on larger scale disease spread. Our findings indicated that both neighborhood composition and spatial arrangement were critical to qualitatively match the empirical relationship of interest. Also, when social deprivation was fully included in the model, we observed lower age-based attack rates and greater delay in epidemic peak week in the most socially deprived neighborhoods. Insights from simulation models complement current understandings from statistical-based association studies. Additional insights from our study are: (1) heterogeneous spatial arrangement of neighborhoods is a necessary condition for simulating observed disparities in the burden of influenza and (2) unmeasured factors may lead to a better quantitative match between simulated and observed rate ratio in the burden of influenza between the most and least socially deprived populations.

  19. Social deprivation and burden of influenza: Testing hypotheses and gaining insights from a simulation model for the spread of influenza

    Directory of Open Access Journals (Sweden)

    Ayaz Hyder

    2015-06-01

    Full Text Available Factors associated with the burden of influenza among vulnerable populations have mainly been identified using statistical methodologies. Complex simulation models provide mechanistic explanations, in terms of spatial heterogeneity and contact rates, while controlling other factors and may be used to better understand statistical patterns and, ultimately, design optimal population-level interventions. We extended a sophisticated simulation model, which was applied to forecast epidemics and validated for predictive ability, to identify mechanisms for the empirical relationship between social deprivation and the burden of influenza. Our modeled scenarios and associated epidemic metrics systematically assessed whether neighborhood composition and/or spatial arrangement could qualitatively replicate this empirical relationship. We further used the model to determine consequences of local-scale heterogeneities on larger scale disease spread. Our findings indicated that both neighborhood composition and spatial arrangement were critical to qualitatively match the empirical relationship of interest. Also, when social deprivation was fully included in the model, we observed lower age-based attack rates and greater delay in epidemic peak week in the most socially deprived neighborhoods. Insights from simulation models complement current understandings from statistical-based association studies. Additional insights from our study are: (1 heterogeneous spatial arrangement of neighborhoods is a necessary condition for simulating observed disparities in the burden of influenza and (2 unmeasured factors may lead to a better quantitative match between simulated and observed rate ratio in the burden of influenza between the most and least socially deprived populations.

  20. Marketing Digital Offerings Is Different: Strategies for Teaching about Digital Offerings in the Marketing Classroom

    Science.gov (United States)

    Roberts, Scott D.; Micken, Kathleen S.

    2015-01-01

    Digital offerings represent different challenges for marketers than do traditional goods and services. After reviewing the literature, the authors suggest ways that the marketing of digital goods and services might be better presented to and better understood by students. The well-known four challenges of services marketing model (e.g.,…

  1. Marketing Digital Offerings Is Different: Strategies for Teaching about Digital Offerings in the Marketing Classroom

    Science.gov (United States)

    Roberts, Scott D.; Micken, Kathleen S.

    2015-01-01

    Digital offerings represent different challenges for marketers than do traditional goods and services. After reviewing the literature, the authors suggest ways that the marketing of digital goods and services might be better presented to and better understood by students. The well-known four challenges of services marketing model (e.g.,…

  2. An Extended, Boolean Model of the Septation Initiation Network in S.Pombe Provides Insights into Its Regulation.

    Science.gov (United States)

    Chasapi, Anastasia; Wachowicz, Paulina; Niknejad, Anne; Collin, Philippe; Krapp, Andrea; Cano, Elena; Simanis, Viesturs; Xenarios, Ioannis

    2015-01-01

    Cytokinesis in fission yeast is controlled by the Septation Initiation Network (SIN), a protein kinase signaling network using the spindle pole body as scaffold. In order to describe the qualitative behavior of the system and predict unknown mutant behaviors we decided to adopt a Boolean modeling approach. In this paper, we report the construction of an extended, Boolean model of the SIN, comprising most SIN components and regulators as individual, experimentally testable nodes. The model uses CDK activity levels as control nodes for the simulation of SIN related events in different stages of the cell cycle. The model was optimized using single knock-out experiments of known phenotypic effect as a training set, and was able to correctly predict a double knock-out test set. Moreover, the model has made in silico predictions that have been validated in vivo, providing new insights into the regulation and hierarchical organization of the SIN.

  3. 重度残障学生实施园区送教教学模式的探究%Exploration of a new teaching model of offering education services in living quarter for the students with severe disabilities

    Institute of Scientific and Technical Information of China (English)

    凌伟; 曾佳金; 张瑾; 冯莉青

    2015-01-01

    Objective:To research effectiveness of the teaching model of offering education services in living quarters, through implementing it to special children to ensure their educational rights in the compulsory education stage and improve their living abili-ties. Methods:The teaching forms like team intervention, group teaching, and individualized training were used to do the teaching study, and different teaching methods as guided teaching, games activities act, demonstration and operation and behavior modification were implied to offer the education services for the students in the living quarter. Before and after the teaching process, these students were evaluated. Results:After receiving the education in the living quarter for one semester, 22. 7 percent of the students were im-proved significantly in varying degrees, especially on movement ability, social skills and self-care ability. Conclusions:The teaching mode of offering the education services in the living quarters enables the students with severe disabilities to receive compulsory educa-tion, and to improve the survival and life quality.%目的::通过实施园区送教,保障义务教育阶段特殊儿童接受教育,提高生活能力,探究园区送教教学模式的有效性。方法:采用集体干预、小组教学及个别化训练的送教教学形式,运用引导式教学法、游戏活动法、演示与操作法和行为矫正法对园区送教的学生进行教学研究,并且在教学前后进行测评。结果:经过一学期的教学,22.7%学生在不同程度上有所提高,特别在运动能力、社会交往能力及生活自理能力上有较为显著的效果。结论:园区送教教学模式能使重度残障学生接受义务教育,较大限度地提高生存和生活质量。

  4. Extended Pile Driving Model to Predict the Penetration of the Insight/HP3 Mole into the Martian Soil

    Science.gov (United States)

    Poganski, Joshua; Kömle, Norbert I.; Kargl, Günter; Schweiger, Helmut F.; Grott, Matthias; Spohn, Tilman; Krömer, Olaf; Krause, Christian; Wippermann, Torben; Tsakyridis, Georgios; Fittock, Mark; Lichtenheldt, Roy; Vrettos, Christos; Anrade, Jose E.

    2016-11-01

    The NASA InSight mission will provide an opportunity for soil investigations using the penetration data of the heat flow probe built by the German Aerospace Center DLR. The Heat flow and Physical Properties Probe (HP3) will penetrate 3 to 5 meter into the Martian subsurface to investigate the planetary heat flow. The measurement of the penetration rate during the insertion of the HP3 will be used to determine the physical properties of the soil at the landing site. For this purpose, numerical simulations of the penetration process were performed to get a better understanding of the soil properties influencing the penetration performance of HP3. A pile driving model has been developed considering all masses of the hammering mechanism of HP3. By cumulative application of individual stroke cycles it is now able to describe the penetration of the Mole into the Martian soil as a function of time, assuming that the soil parameters of the material through which it penetrates are known. We are using calibrated materials similar to those expected to be encountered by the InSight/HP3 Mole when it will be operated on the surface of Mars after the landing of the InSight spacecraft. We consider various possible scenarios, among them a more or less homogeneous material down to a depth of 3-5 m as well as a layered ground, consisting of layers with different soil parameters. Finally we describe some experimental tests performed with the latest prototype of the InSight Mole at DLR Bremen and compare the measured penetration performance in sand with our modeling results. Furthermore, results from a 3D DEM simulation are presented to get a better understanding of the soil response.

  5. Governance arrangements for IT project portfolio management qualitative insights and a quantitative modeling approach

    CERN Document Server

    Frey, Thorsten

    2014-01-01

    Due to the growing importance of IT-based innovations, contemporary firms face an excessive number of proposals for IT projects. As typically only a fraction of these projects can be implemented with the given capacity, IT project portfolio management as a relatively new discipline has received growing attention in research and practice in recent years.?Thorsten Frey demonstrates how companies are struggling to find the right balance between local autonomy and central overview about all projects in the organization. In this context, impacts of different contextual factors on the design of governance arrangements for IT project portfolio management are demonstrated. Moreover, consequences of the use of different organizational designs are analyzed. The author presents insights from a qualitative empirical study as well as a simulative approach.

  6. Multi-Layered Stratification in the Baltic Sea: Insight from a Modeling Study with Reference to Environmental Conditions

    Directory of Open Access Journals (Sweden)

    Bijan Dargahi

    2017-01-01

    Full Text Available The hydrodynamic and transport characteristics of the Baltic Sea in the period 2000–2009 were studied using a fully calibrated and validated 3D hydrodynamic model with a horizontal resolution of 4.8 km. This study provided new insight into the type and dynamics of vertical structure in the Baltic Sea, not considered in previous studies. Thermal and salinity stratification are both addressed, with a focus on the structural properties of the layers. The detection of cooler regions (dicothermal within the layer structure is an important finding. The detailed investigation of thermal stratification for a 10-year period (i.e., 2000–2009 revealed some new features. A multilayered structure that contains several thermocline and dicothermal layers was identified from this study. Statistical analysis of the simulation results made it possible to derive the mean thermal stratification properties, expressed as mean temperatures and the normalized layer thicknesses. The three-layered model proposed by previous investigators appears to be valid only during the winter periods; for other periods, a multi-layered structure with more than five layers has been identified during this investigation. This study provides detailed insight into thermal and salinity stratification in the Baltic Sea during a recent decade that can be used as a basis for diverse environmental assessments. It extends previous studies on stratification in the Baltic Sea regarding both the extent and the nature of stratification.

  7. Integrating economic and psychological insights in binary choice models with social interactions

    CERN Document Server

    Ostasiewicz, K; Magnuszewski, P; Radosz, A; Sendzimir, J; Tyc, M H; Goliczewski, Piotr; Magnuszewski, Piotr; Ostasiewicz, Katarzyna; Radosz, Andrzej; Sendzimir, Jan; Tyc, Michal H.

    2006-01-01

    We investigate a class of binary choice models with social interactions. We propose a unifying perspective that integrates economic models using a utility function and psychological models using an impact function. A general approach for analyzing the equilibrium structure of these models within mean-field approximation is developed. It is shown that within a mean-field approach both the utility function and the impact function models are equivalent to threshold models. The interplay between heterogeneity and randomness in model formulation is discussed. A general framework is applied in a number of examples leading to some well-known models but also showing the possibility of more complex dynamics related to multiple equilibria. Our synthesis can provide a basis for many practical applications extending the scope of binary choice models.

  8. THE ACCOUNTANT INFORMATION. DEMAND AND OFFER

    OpenAIRE

    Irina CHIRITA; Ioana ZAHEU

    2008-01-01

    The present paper is trying to correlate what Demand and Offer mean, from the economical point of view, which in the end tends towards the demand and offer of the accountant information. The objective of the demand and offer of accountant information is to promo te an efficient financial communication, objective that might be reached through the confrontation of the informational offer with the user’s demand. The information given by the enterprises are the basis of numerous economical and po...

  9. Connectivity of Caribbean coral populations: complementary insights from empirical and modelled gene flow

    NARCIS (Netherlands)

    Foster, N.L.; Paris, C.B.; Kool, J.T.; Baums, I.B.; Stevens, J.R.; Sanchez, J.A.; Bastidas, C.; Agudelo, C.; Bush, P.; Day, O.; Ferrari, R.; Gonzalez, P.; Gore, S.; Guppy, R.; McCartney, M.A.; McCoy, C.; Mendes, J.; Srinivasan, A.; Steiner, S.; Vermeij, M.J.A.; Weil, E.; Mumby, P.J.

    2012-01-01

    Understanding patterns of connectivity among populations of marine organisms is essential for the development of realistic, spatially explicit models of population dynamics. Two approaches, empirical genetic patterns and oceanographic dispersal modelling, have been used to estimate levels of

  10. Elements of a flexible approach for conceptual hydrological modeling: 2. Application and experimental insights

    NARCIS (Netherlands)

    Kavetski, D.; Fenicia, F.

    2011-01-01

    In this article's companion paper, flexible approaches for conceptual hydrological modeling at the catchment scale were motivated, and the SUPERFLEX framework, based on generic model components, was introduced. In this article, the SUPERFLEX framework and the “fixed structure” GR4H model (an hourly

  11. Fitting Item Response Theory Models to Two Personality Inventories: Issues and Insights.

    Science.gov (United States)

    Chernyshenko, Oleksandr S.; Stark, Stephen; Chan, Kim-Yin; Drasgow, Fritz; Williams, Bruce

    2001-01-01

    Compared the fit of several Item Response Theory (IRT) models to two personality assessment instruments using data from 13,059 individuals responding to one instrument and 1,770 individuals responding to the other. Two- and three-parameter logistic models fit some scales reasonably well, but not others, and the graded response model generally did…

  12. Some insights in novel risk modeling of liquefied natural gas carrier maintenance operations

    Science.gov (United States)

    Nwaoha, T. C.; John, Andrew

    2016-06-01

    This study discusses the analysis of various modeling approaches and maintenance techniques applicable to the Liquefied Natural Gas (LNG) carrier operations in the maritime environment. Various novel modeling techniques are discussed; including genetic algorithms, fuzzy logic and evidential reasoning. We also identify the usefulness of these algorithms in the LNG carrier industry in the areas of risk assessment and maintenance modeling.

  13. Control of crystallite and particle size in the synthesis of layered double hydroxides: Macromolecular insights and a complementary modeling tool.

    Science.gov (United States)

    Galvão, Tiago L P; Neves, Cristina S; Caetano, Ana P F; Maia, Frederico; Mata, Diogo; Malheiro, Eliana; Ferreira, Maria J; Bastos, Alexandre C; Salak, Andrei N; Gomes, José R B; Tedim, João; Ferreira, Mário G S

    2016-04-15

    Zinc-aluminum layered double hydroxides with nitrate intercalated (Zn(n)Al-NO3, n=Zn/Al) is an intermediate material for the intercalation of different functional molecules used in a wide range of industrial applications. The synthesis of Zn(2)Al-NO3 was investigated considering the time and temperature of hydrothermal treatment. By examining the crystallite size in two different directions, hydrodynamic particle size, morphology, crystal structure and chemical species in solution, it was possible to understand the crystallization and dissolution processes involved in the mechanisms of crystallite and particle growth. In addition, hydrogeochemical modeling rendered insights on the speciation of different metal cations in solution. Therefore, this tool can be a promising solution to model and optimize the synthesis of layered double hydroxide-based materials for industrial applications.

  14. Determinants of High Schools' Advanced Course Offerings

    Science.gov (United States)

    Iatarola, Patrice; Conger, Dylan; Long, Mark C.

    2011-01-01

    This article examines the factors that determine a high school's probability of offering Advanced Placement (AP) and International Baccalaureate (IB) courses. The likelihood that a school offers advanced courses, and the number of sections that it offers, is largely driven by having a critical mass of students who enter high school with…

  15. The primary relevance of subconsciously offered attitudes

    DEFF Research Database (Denmark)

    Kristiansen, Tore

    2015-01-01

    ) and subconsciously (covertly) offered attitudes – because subconsciously offered attitudes appear to be a driving force in linguistic variation and change in a way that consciously offered attitudes are not. The argument is based on evidence from empirical investigations of attitudes and use in the ‘...

  16. Insights into the softening of chaotic statistical models by quantum considerations

    Science.gov (United States)

    Cafaro, C.; Giffin, A.; Lupo, C.; Mancini, S.

    2012-05-01

    We analyze the information geometry and the entropic dynamics of a 3D Gaussian statistical model and compare our analysis to that of a 2D Gaussian statistical model obtained from the higher-dimensional model via introduction of an additional information constraint that resembles the quantum mechanical canonical minimum uncertainty relation. We uncover that the chaoticity of the 2D Gaussian statistical model, quantified by means of the Information Geometric Entropy (IGE), is softened with respect to the chaoticity of the 3D Gaussian statistical model.

  17. Uppermost mantle (Pn) velocity model for the Afar region, Ethiopia: an insight into rifting processes

    Science.gov (United States)

    Stork, A. L.; Stuart, G. W.; Henderson, C. M.; Keir, D.; Hammond, J. O. S.

    2013-04-01

    The Afar Depression, Ethiopia, offers unique opportunities to study the transition from continental rifting to oceanic spreading because the process is occurring onland. Using traveltime tomography and data from a temporary seismic deployment, we describe the first regional study of uppermost mantle P-wave velocities (VPn). We find two separate low VPn zones (as low as 7.2 km s-1) beneath regions of localized thinned crust in northern Afar, indicating the existence of high temperatures and, potentially, partial melt. The zones are beneath and off-axis from, contemporary crustal magma intrusions in active magmatic segments, the Dabbahu-Manda-Hararo and Erta'Ale segments. This suggests that these intrusions can be fed by off-axis delivery of melt in the uppermost mantle and that discrete areas of mantle upwelling and partial melting, thought to characterize segmentation of the uppermost mantle at seafloor spreading centres, are initiated during the final stages of break-up.

  18. Better Insight Into Water Resources Management With Integrated Hydrodynamic And Water Quality Models

    Science.gov (United States)

    Debele, B.; Srinivasan, R.; Parlange, J.

    2004-12-01

    Models have long been used in water resources management to guide decision making and improve understanding of the system. Numerous models of different scales -spatial and temporal - are available. Yet, very few models manage to bridge simulations of hydrological and water quality parameters from both upland watershed and riverine system. Most water quality models, such as QUAL2E and EPD-RIV1 concentrate on the riverine system while CE-QUAL-W2 and WASP models focus on larger waterbodies, such as lakes and reservoirs. On the other hand, the original SWAT model, HSPF and other upland watershed hydrological models simulate agricultural (diffuse) pollution sources with limited number of processes incorporated to handle point source pollutions that emanate from industrial sectors. Such limitations, which are common in most hydrodynamic and water quality models undermine better understanding that otherwise could be uncovered by employing integrated hydrological and water quality models for both upland watershed and riverine system. The SWAT model is a well documented and verified hydrological and water quality model that has been developed to simulate the effects of various management scenarios on the health of the environment in terms of water quantity and quality. Recently, the SWAT model has been extended to include the simulation of hydrodynamic and water quality parameters in the river system. The extended SWAT model (ESWAT) has been further extended to run using diurnally varying (hourly) weather data and produce outputs at hourly timescales. This and other improvements in the ESWAT model have been documented in the current work. Besides, the results from two case studies in Texas will be reported.

  19. Initial insights from 2.5D hydraulic modeling of floods in Athabasca Valles, Mars

    Science.gov (United States)

    Keszthelyi, L.P.; Denlinger, R.P.; O'Connell, D. R. H.; Burr, D.M.

    2007-01-01

    We present the first application of a 2.5D hydraulic model to catastrophic floods on Mars. This model simulates flow over complex topography and incorporates flood dynamics that could not be modeled in the earlier 1D models. We apply this model to Athabasca Valles, the youngest outflow channel on Mars, investigating previous bank-full discharge estimates and utilizing the interpolated Mars Orbiter Laser Altimeter elevation map as input. We confirm that the bank-full assumption does not fit the observed landforms. Instead, the channel appears more deeply incised near the source. Flow modeling also identifies several areas of special interest, including a dry cataract that coincides with a region of predicted high erosion. However, artifacts in the elevation data strongly impacted estimated stages and velocities in other areas. More extensive connection between the flood hydraulics and observed landforms awaits improved topographic data.

  20. A quantitative model of human DNA base excision repair. I. mechanistic insights

    OpenAIRE

    Sokhansanj, Bahrad A.; Rodrigue, Garry R.; Fitch, J. Patrick; David M Wilson

    2002-01-01

    Base excision repair (BER) is a multistep process involving the sequential activity of several proteins that cope with spontaneous and environmentally induced mutagenic and cytotoxic DNA damage. Quantitative kinetic data on single proteins of BER have been used here to develop a mathematical model of the BER pathway. This model was then employed to evaluate mechanistic issues and to determine the sensitivity of pathway throughput to altered enzyme kinetics. Notably, the model predicts conside...

  1. First Versus Second Order Latent Growth Curve Models: Some Insights From Latent State-Trait Theory

    OpenAIRE

    Geiser, Christian; Keller, Brian; Lockhart, Ginger

    2013-01-01

    First order latent growth curve models (FGMs) estimate change based on a single observed variable and are widely used in longitudinal research. Despite significant advantages, second order latent growth curve models (SGMs), which use multiple indicators, are rarely used in practice, and not all aspects of these models are widely understood. In this article, our goal is to contribute to a deeper understanding of theoretical and practical differences between FGMs and SGMs. We define the latent ...

  2. Insights into granulosa cell tumors using spontaneous or genetically engineered mouse models.

    Science.gov (United States)

    Kim, So-Youn

    2016-03-01

    Granulosa cell tumors (GCTs) are rare sex cord-stromal tumors that have been studied for decades. However, their infrequency has delayed efforts to research their etiology. Recently, mutations in human GCTs have been discovered, which has led to further research aimed at determining the molecular mechanisms underlying the disease. Mouse models have been important tools for studying GCTs, and have provided means to develop and improve diagnostics and therapeutics. Thus far, several genetically modified mouse models, along with one spontaneous mouse model, have been reported. This review summarizes the phenotypes of these mouse models and their applicability in elucidating the mechanisms of granulosa cell tumor development.

  3. Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model.

    Science.gov (United States)

    Kim, Ji-Ae; Park, Seul-Ki; Kumar, Mukesh; Lee, Chan-Hee; Shin, Ok Sarah

    2015-11-03

    Varicella zoster virus (VZV) is the etiological agent of shingles, a painful skin rash that affects a significant proportion of the elderly population. In the present study, we used two aging cell models, Hutchinson-Gilford progeria syndrome (HGPS) fibroblasts and stress or replicative senescence-induced normal human dermal fibroblasts (NHDFs), to investigate age-associated susceptibility to VZV infection. VZV infectivity titers were significantly associated with donor age in HGPS fibroblasts and senescence induction in NHDFs. High throughput RNA-sequencing (RNA-seq) analysis was performed to assess global and dynamic changes in the host transcriptomes of VZV-infected aging cells. Analysis of differentially expressed genes (DEGs) indicated that VZV infection in aged HGPS fibroblasts resembled that in senescent NHDFs, particularly in terms of genes associated with pattern recognition receptors in virus sensing network, providing novel insights into the mechanisms of senescence-associated susceptibility to VZV infection. Additionally, we identified stimulator of interferon genes (STING) as a potential VZV sensing receptor. Knockdown of STING expression resulted in increased viral replication in primary fibroblasts, whereas STING overexpression led to suppression of VZV plaque formation. In conclusion, our findings highlight the important role of immunosenescence following VZV infection and provide significant insights into the mechanisms underlying cellular sensing of VZV infection and the induction of immune responses in aged skin cells.

  4. Quaternary association in -prism I fold plant lectins: Insights from X-ray crystallography, modelling and molecular dynamics

    Indian Academy of Sciences (India)

    Alok Sharma; Mamannamana Vijayan

    2011-12-01

    Dimeric banana lectin and calsepa, tetrameric artocarpin and octameric heltuba are mannose-specific -prism I fold lectins of nearly the same tertiary structure. MD simulations on individual subunits and the oligomers provide insights into the changes in the structure brought about in the protomers on oligomerization, including swapping of the N-terminal stretch in one instance. The regions that undergo changes also tend to exhibit dynamic flexibility during MD simulations. The internal symmetries of individual oligomers are substantially retained during the calculations. Energy minimization and simulations were also carried out on models using all possible oligomers by employing the four different protomers. The unique dimerization pattern observed in calsepa could be traced to unique substitutions in a peptide stretch involved in dimerization. The impossibility of a specific mode of oligomerization involving a particular protomer is often expressed in terms of unacceptable steric contacts or dissociation of the oligomer during simulations. The calculations also led to a rationale for the observation of a heltuba tetramer in solution although the lectin exists as an octamer in the crystal, in addition to providing insights into relations among evolution, oligomerization and ligand binding.

  5. Insights on the Subduction Process from High-Resolution 3D Models

    Science.gov (United States)

    Jadamec, Margarete

    2015-04-01

    This is an exciting time in geodynamics as the use of unprecedented high-resolution 3D modeling allows us to ask new questions that were previously unattainable. It is now relatively straightforward to run 3D numerical simulations, with local mesh refinement to ~1 km, input data mapped onto over 100 million finite element nodes, and using tens of thousands of compute hours per model, e.g. Jadamec et al. [2012]. With the additional computational resources, comes a new approach to modeling the tectonic problem. For example, mapping tectonic plates onto a high-resolution 3D geodynamic model grid forces the modeler to ask questions much as a field geologist would ask when constructing a geologic map. In this process of moving from textbook models of subduction to using models based on observation, the modeler is forced to explain the more complicated geometries and features in the Earth, allowing for the new computational approaches to be powerful tools for scientific discovery. Subduction modeling of this kind has expanded the classical view of two-dimensional corner flow, e.g. McKenzie [1969], to a slab driven flow that can be quite complex with predictions for upper mantle flow rates that can be over ten times surface plate motions, e.g. Jadamec et al. [2010] and others. In this talk, I will investigate the role of the third-dimension and non-linearity in plate boundary deformation. I will present high-resolution 3D numerical models that examine the effect of observationally based slab geometry, multiple subducting plates, non-linear rheology, and variations in overriding plate thickness on the subduction related deformation of plate margins. Specific examples include the Alaska and Central America subduction systems. In addition, I will highlight future directions in subduction modeling, and how these can be advanced by the increased incorporation of observational data, high-performance computing, focused numerical algorithms, and 3D interactive data visualization.

  6. Neuroinflammation in epileptogenesis: Insights and translational perspectives from new models of epilepsy.

    Science.gov (United States)

    Barker-Haliski, Melissa L; Löscher, Wolfgang; White, H Steve; Galanopoulou, Aristea S

    2017-07-01

    Animal models have provided a wealth of information on mechanisms of epileptogenesis and comorbidogenesis, and have significantly advanced our ability to investigate the potential of new therapies. Processes implicating brain inflammation have been increasingly observed in epilepsy research. Herein we discuss the progress on animal models of epilepsy and comorbidities that inform us on the potential role of inflammation in epileptogenesis and comorbidity pathogenesis in rodent models of West syndrome and the Theiler's murine encephalomyelitis virus (TMEV) mouse model of viral encephalitis-induced epilepsy. Rat models of infantile spasms were generated in rat pups after right intracerebral injections of proinflammatory compounds (lipopolysaccharides with or without doxorubicin, or cytokines) and were longitudinally monitored for epileptic spasms and neurodevelopmental and cognitive deficits. Anti-inflammatory treatments were tested after the onset of spasms. The TMEV mouse model was induced with intracerebral administration of TMEV and prospective monitoring for handling-induced seizures or seizure susceptibility, as well as long-term evaluations of behavioral comorbidities of epilepsy. Inflammatory processes are evident in both models and are implicated in the pathogenesis of the observed seizures and comorbidities. A common feature of these models, based on the data so far available, is their pharmacoresistant profile. The presented data support the role of inflammatory pathways in epileptogenesis and comorbidities in two distinct epilepsy models. Pharmacoresistance is a common feature of both inflammation-based models. Utilization of these models may facilitate the identification of age-specific, syndrome- or etiology-specific therapies for the epilepsies and attendant comorbidities, including the drug-resistant forms. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  7. Exploring business model innovation in professional service firms: Insights from architecture

    NARCIS (Netherlands)

    Lieftink, B.; Bos-de Vos, M.; Lauche, K.; Smits, A.

    2014-01-01

    Business model innovation may be a significant source of competitive advantage and firm performance. New ways of doing business have become increasingly important in the professional service sector. This research specifically focuses on business model innovation by architecture firms, which are

  8. Which insights have we gained from the kindling and post-status epilepticus models?

    NARCIS (Netherlands)

    Gorter, J.A.; van Vliet, E.A.; Lopes da Silva, F.H.

    2016-01-01

    Experimental animal epilepsy research got a big boost since the discovery that daily mild and short (seconds) tetanic stimulations in selected brain regions led to seizures with increasing duration and severity. This model that was developed by Goddard (1967) became known as the kindling model for e

  9. Homology modeling of the serotonin transporter: Insights into the primary escitalopram-binding Site

    DEFF Research Database (Denmark)

    Jørgensen, Anne Marie; Tagmose, L.; Jørgensen, A.M.M.

    2007-01-01

    -ray structure of the closely related amino acid transporter, Aquifex aeolicus leucine transporter (LeuT), provides an opportunity to develop a three-dimensional model of the structure of SERT. We present herein a homology model of SERT using LeuT as the template and containing escitalopram as a bound ligand...

  10. Understanding Chinese American Adolescents' Developmental Outcomes: Insights from the Family Stress Model

    Science.gov (United States)

    Benner, Aprile D.; Kim, Su Yeong

    2010-01-01

    In this brief report, we investigated whether the Family Stress Model could be replicated with a sample of Chinese American families. Path analyses with 444 adolescents and their parents provided support for the model's generalizability. Specifically, mothers' and fathers' reports of economic status (i.e., income, financial, and job instability)…

  11. Which insights have we gained from the kindling and post-status epilepticus models?

    NARCIS (Netherlands)

    J.A. Gorter; E.A. van Vliet; F.H. Lopes da Silva

    2015-01-01

    Experimental animal epilepsy research got a big boost since the discovery that daily mild and short (seconds) tetanic stimulations in selected brain regions led to seizures with increasing duration and severity. This model that was developed by Goddard (1967) became known as the kindling model for e

  12. Understanding Chinese American Adolescents' Developmental Outcomes: Insights from the Family Stress Model

    Science.gov (United States)

    Benner, Aprile D.; Kim, Su Yeong

    2010-01-01

    In this brief report, we investigated whether the Family Stress Model could be replicated with a sample of Chinese American families. Path analyses with 444 adolescents and their parents provided support for the model's generalizability. Specifically, mothers' and fathers' reports of economic status (i.e., income, financial, and job instability)…

  13. Exploring business model innovation in professional service firms: Insights from architecture

    NARCIS (Netherlands)

    Lieftink, B.; Bos-de Vos, M.; Lauche, K.; Smits, A.

    2014-01-01

    Business model innovation may be a significant source of competitive advantage and firm performance. New ways of doing business have become increasingly important in the professional service sector. This research specifically focuses on business model innovation by architecture firms, which are suff

  14. Modelling the Cooling of Coffee: Insights from a Preliminary Study in Indonesia

    Science.gov (United States)

    Widjaja, Wanty

    2010-01-01

    This paper discusses an attempt to examine pre-service teachers' mathematical modelling skills. A modelling project investigating relationships between temperature and time in the process of cooling of coffee was chosen. The analysis was based on group written reports of the cooling of coffee project and observation of classroom discussion.…

  15. Neuregulin 1: a prime candidate for research into gene-environment interactions in schizophrenia? Insights from genetic rodent models

    Directory of Open Access Journals (Sweden)

    Tim eKarl

    2013-08-01

    Full Text Available Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors. In recent years, an increasing number of researchers worldwide have started investigating the ‘two-hit hypothesis’ of schizophrenia predicting that genetic and environmental risk factors (GxE interactively cause the development of the disorder. This work is starting to produce valuable new animal models and reveal novel insights into the pathophysiology of schizophrenia. This mini review will focus on recent advancements in the field made by challenging mutant and transgenic rodent models for the schizophrenia candidate gene neuregulin 1 (NRG1 with particular environmental factors. It will outline results obtained from mouse and rat models for various Nrg1 isoforms/isoform types (e.g. transmembrane domain Nrg1, Type II Nrg1, which have been exposed to different forms of stress (acute versus chronic, restraint versus social and housing conditions (standard laboratory versus minimally enriched housing. These studies suggest Nrg1 as a prime candidate for GxE interactions in schizophrenia rodent models and that the use of rodent models will enable a better understanding of GxE interactions and the underlying mechanisms.

  16. Ocean (de)oxygenation from the Last Glacial Maximum to the twenty-first century: insights from Earth System models.

    Science.gov (United States)

    Bopp, L; Resplandy, L; Untersee, A; Le Mezo, P; Kageyama, M

    2017-09-13

    All Earth System models project a consistent decrease in the oxygen content of oceans for the coming decades because of ocean warming, reduced ventilation and increased stratification. But large uncertainties for these future projections of ocean deoxygenation remain for the subsurface tropical oceans where the major oxygen minimum zones are located. Here, we combine global warming projections, model-based estimates of natural short-term variability, as well as data and model estimates of the Last Glacial Maximum (LGM) ocean oxygenation to gain some insights into the major mechanisms of oxygenation changes across these different time scales. We show that the primary uncertainty on future ocean deoxygenation in the subsurface tropical oceans is in fact controlled by a robust compensation between decreasing oxygen saturation (O2sat) due to warming and decreasing apparent oxygen utilization (AOU) due to increased ventilation of the corresponding water masses. Modelled short-term natural variability in subsurface oxygen levels also reveals a compensation between O2sat and AOU, controlled by the latter. Finally, using a model simulation of the LGM, reproducing data-based reconstructions of past ocean (de)oxygenation, we show that the deoxygenation trend of the subsurface ocean during deglaciation was controlled by a combination of warming-induced decreasing O2sat and increasing AOU driven by a reduced ventilation of tropical subsurface waters.This article is part of the themed issue 'Ocean ventilation and deoxygenation in a warming world'. © 2017 The Author(s).

  17. Recent advances in biosynthetic modeling of nitric oxide reductases and insights gained from nuclear resonance vibrational and other spectroscopic studies

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Saumen; Reed, Julian; Sage, Timothy; Branagan, Nicole C.; Petrik, Igor D.; Miner, Kyle D.; Hu, Michael Y.; Zhao, Jiyong; Alp, E. Ercan; Lu, Yi

    2015-10-05

    This Forum Article focuses on recent advances in structural and spectroscopic studies of biosynthetic models of nitric oxide reductases (NORs). NORs are complex metalloenzymes found in the denitrification pathway of Earth's nitrogen cycle where they catalyze the proton-dependent twoelectron reduction of nitric oxide (NO) to nitrous oxide (N2O). While much progress has been made in biochemical and biophysical studies of native NORs and their variants, a. clear mechanistic understanding of this important metalloenzyme related to its function is still elusive. We report herein UV vis and nuclear resonance vibrational spectroscopy (NRVS) studies of mononitrosylated intermediates of the NOR reaction of a biosynthetic model. The ability to selectively substitute metals at either heme or nonheme metal sites allows the introduction of independent 57Fe probe atoms at either site, as well as allowing the preparation of analogues of stable reaction intermediates by replacing either metal with a redox inactive metal. Together with previous structural and spectroscopic results, we summarize insights gained from studying these biosynthetic models toward understanding structural features responsible for the NOR activity and its mechanism. As a result, the outlook on NOR modeling is also discussed, with an emphasis on the design of models capable of catalytic turnovers designed based on close mimics of the secondary coordination sphere of native NORs.

  18. Insights into the mutation-induced HHH syndrome from modeling human mitochondrial ornithine transporter-1.

    Directory of Open Access Journals (Sweden)

    Jing-Fang Wang

    Full Text Available Human mitochondrial ornithine transporter-1 is reported in coupling with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH syndrome, which is a rare autosomal recessive disorder. For in-depth understanding of the molecular mechanism of the disease, it is crucially important to acquire the 3D structure of human mitochondrial ornithine transporter-1. Since no such structure is available in the current protein structure database, we have developed it via computational approaches based on the recent NMR structure of human mitochondrial uncoupling protein (Berardi MJ, Chou JJ, et al. Nature 2011, 476:109-113. Subsequently, we docked the ligand L-ornithine into the computational structure to search for the favorable binding mode. It was observed that the binding interaction for the most favorable binding mode is featured by six remarkable hydrogen bonds between the receptor and ligand, and that the most favorable binding mode shared the same ligand-binding site with most of the homologous mitochondrial carriers from different organisms, implying that the ligand-binding sites are quite conservative in the mitochondrial carriers family although their sequences similarity is very low with 20% or so. Moreover, according to our structural analysis, the relationship between the disease-causing mutations of human mitochondrial ornithine transporter-1 and the HHH syndrome can be classified into the following three categories: (i the mutation occurs in the pseudo-repeat regions so as to change the region of the protein closer to the mitochondrial matrix; (ii the mutation is directly affecting the substrate binding pocket so as to reduce the substrate binding affinity; (iii the mutation is located in the structural region closer to the intermembrane space that can significantly break the salt bridge networks of the protein. These findings may provide useful insights for in-depth understanding of the molecular mechanism of the HHH syndrome and

  19. Insights into the mutation-induced HHH syndrome from modeling human mitochondrial ornithine transporter-1.

    Science.gov (United States)

    Wang, Jing-Fang; Chou, Kuo-Chen

    2012-01-01

    Human mitochondrial ornithine transporter-1 is reported in coupling with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, which is a rare autosomal recessive disorder. For in-depth understanding of the molecular mechanism of the disease, it is crucially important to acquire the 3D structure of human mitochondrial ornithine transporter-1. Since no such structure is available in the current protein structure database, we have developed it via computational approaches based on the recent NMR structure of human mitochondrial uncoupling protein (Berardi MJ, Chou JJ, et al. Nature 2011, 476:109-113). Subsequently, we docked the ligand L-ornithine into the computational structure to search for the favorable binding mode. It was observed that the binding interaction for the most favorable binding mode is featured by six remarkable hydrogen bonds between the receptor and ligand, and that the most favorable binding mode shared the same ligand-binding site with most of the homologous mitochondrial carriers from different organisms, implying that the ligand-binding sites are quite conservative in the mitochondrial carriers family although their sequences similarity is very low with 20% or so. Moreover, according to our structural analysis, the relationship between the disease-causing mutations of human mitochondrial ornithine transporter-1 and the HHH syndrome can be classified into the following three categories: (i) the mutation occurs in the pseudo-repeat regions so as to change the region of the protein closer to the mitochondrial matrix; (ii) the mutation is directly affecting the substrate binding pocket so as to reduce the substrate binding affinity; (iii) the mutation is located in the structural region closer to the intermembrane space that can significantly break the salt bridge networks of the protein. These findings may provide useful insights for in-depth understanding of the molecular mechanism of the HHH syndrome and developing effective

  20. A quantitative model of human DNA base excision repair. I. Mechanistic insights.

    Science.gov (United States)

    Sokhansanj, Bahrad A; Rodrigue, Garry R; Fitch, J Patrick; Wilson, David M

    2002-04-15

    Base excision repair (BER) is a multistep process involving the sequential activity of several proteins that cope with spontaneous and environmentally induced mutagenic and cytotoxic DNA damage. Quantitative kinetic data on single proteins of BER have been used here to develop a mathematical model of the BER pathway. This model was then employed to evaluate mechanistic issues and to determine the sensitivity of pathway throughput to altered enzyme kinetics. Notably, the model predicts considerably less pathway throughput than observed in experimental in vitro assays. This finding, in combination with the effects of pathway cooperativity on model throughput, supports the hypothesis of cooperation during abasic site repair and between the apurinic/apyrimidinic (AP) endonuclease, Ape1, and the 8-oxoguanine DNA glycosylase, Ogg1. The quantitative model also predicts that for 8-oxoguanine and hydrolytic AP site damage, short-patch Polbeta-mediated BER dominates, with minimal switching to the long-patch subpathway. Sensitivity analysis of the model indicates that the Polbeta-catalyzed reactions have the most control over pathway throughput, although other BER reactions contribute to pathway efficiency as well. The studies within represent a first step in a developing effort to create a predictive model for BER cellular capacity.

  1. An improved dust emission model with insights into the global dust cycle's climate sensitivity

    Science.gov (United States)

    Kok, J. F.; Mahowald, N. M.; Albani, S.; Fratini, G.; Gillies, J. A.; Ishizuka, M.; Leys, J. F.; Mikami, M.; Park, M.-S.; Park, S.-U.; Van Pelt, R. S.; Ward, D. S.; Zobeck, T. M.

    2014-03-01

    Simulations of the global dust cycle and its interactions with a changing Earth system are hindered by the empirical nature of dust emission parameterizations in climate models. Here we take a step towards improving global dust cycle simulations by presenting a physically-based dust emission model. The resulting dust flux parameterization depends only on the wind friction speed and the soil's threshold friction speed, and can therefore be readily implemented into climate models. We show that our parameterization's functional form is supported by a compilation of quality-controlled vertical dust flux measurements, and that it better reproduces these measurements than existing parameterizations. Both our theory and measurements indicate that many climate models underestimate the dust flux's sensitivity to soil erodibility. This finding can explain why dust cycle simulations in many models are improved by using an empirical preferential sources function that shifts dust emissions towards the most erodible regions. In fact, implementing our parameterization in a climate model produces even better agreement against aerosol optical depth measurements than simulations that use such a source function. These results indicate that the need to use a source function is at least partially eliminated by the additional physics accounted for by our parameterization. Since soil erodibility is affected by climate changes, our results further suggest that many models have underestimated the climate sensitivity of the global dust cycle.

  2. Dynamics of the HPA axis and inflammatory cytokines: Insights from mathematical modeling.

    Science.gov (United States)

    Malek, Hamed; Ebadzadeh, Mohammad Mehdi; Safabakhsh, Reza; Razavi, Alireza; Zaringhalam, Jalal

    2015-12-01

    In the work presented here, a novel mathematical model was developed to explore the bi-directional communication between the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory cytokines in acute inflammation. The dynamic model consists of five delay differential equations 5D for two main pro-inflammatory cytokines (TNF-α and IL-6) and two hormones of the HPA axis (ACTH and cortisol) and LPS endotoxin. The model is an attempt to increase the understanding of the role of primary hormones and cytokines in this complex relationship by demonstrating the influence of different organs and hormones in the regulation of the inflammatory response. The model captures the main qualitative features of cytokine and hormone dynamics when a toxic challenge is introduced. Moreover, in this work a new simple delayed model of the HPA axis is introduced which supports the understanding of the ultradian rhythm of HPA hormones both in normal and infection conditions. Through simulations using the model, the role of key inflammatory cytokines and cortisol in transition from acute to persistent inflammation through stability analysis is investigated. Also, by employing a Markov chain Monte Carlo (MCMC) method, parameter uncertainty and the effects of parameter variations on each other are analyzed. This model confirms the important role of the HPA axis in acute and prolonged inflammation and can be a useful tool in further investigation of the role of stress on the immune response to infectious diseases.

  3. Simplified three-dimensional model provides anatomical insights in lizards' caudal autotomy as printed illustration

    Directory of Open Access Journals (Sweden)

    JOANA D.C.G. DE AMORIM

    2015-03-01

    Full Text Available Lizards' caudal autotomy is a complex and vastly employed antipredator mechanism, with thorough anatomic adaptations involved. Due to its diminished size and intricate structures, vertebral anatomy is hard to be clearly conveyed to students and researchers of other areas. Three-dimensional models are prodigious tools in unveiling anatomical nuances. Some of the techniques used to create them can produce irregular and complicated forms, which despite being very accurate, lack didactical uniformity and simplicity. Since both are considered fundamental characteristics for comprehension, a simplified model could be the key to improve learning. The model here presented depicts the caudal osteology of Tropidurus itambere, and was designed to be concise, in order to be easily assimilated, yet complete, not to compromise the informative aspect. The creation process requires only basic skills in manipulating polygons in 3D modeling softwares, in addition to the appropriate knowledge of the structure to be modeled. As reference for the modeling, we used microscopic observation and a photograph database of the caudal structures. This way, no advanced laboratory equipment was needed and all biological materials were preserved for future research. Therefore, we propose a wider usage of simplified 3D models both in the classroom and as illustrations for scientific publications.

  4. Water Management in the Camargue Biosphere Reserve: Insights from Comparative Mental Models Analysis

    Directory of Open Access Journals (Sweden)

    Raphael Mathevet

    2011-03-01

    Full Text Available Mental models are the cognitive representations of the world that frame how people interact with the world. Learning implies changing these mental models. The successful management of complex social-ecological systems requires the coordination of actions to achieve shared goals. The coordination of actions requires a level of shared understanding of the system or situation; a shared or common mental model. We first describe the elicitation and analysis of mental models of different stakeholder groups associated with water management in the Camargue Biosphere Reserve in the Rhône River delta on the French Mediterranean coast. We use cultural consensus analysis to explore the degree to which different groups shared mental models of the whole system, of stakeholders, of resources, of processes, and of interactions among these last three. The analysis of the elicited data from this group structure enabled us to tentatively explore the evidence for learning in the nonstatute Water Board; comprising important stakeholders related to the management of the central Rhône delta. The results indicate that learning does occur and results in richer mental models that are more likely to be shared among group members. However, the results also show lower than expected levels of agreement with these consensual mental models. Based on this result, we argue that a careful process and facilitation design can greatly enhance the functioning of the participatory process in the Water Board. We conclude that this methodology holds promise for eliciting and comparing mental models. It enriches group-model building and participatory approaches with a broader view of social learning and knowledge-sharing issues.

  5. Current crisis or artifact of surveillance: insights into rebound chlamydia rates from dynamic modelling

    Directory of Open Access Journals (Sweden)

    Vickers David M

    2010-03-01

    Full Text Available Abstract Background After initially falling in the face of intensified control efforts, reported rates of sexually transmitted chlamydia in many developed countries are rising. Recent hypotheses for this phenomenon have broadly focused on improved case finding or an increase in the prevalence. Because of many complex interactions behind the spread of infectious diseases, dynamic models of infection transmission are an effective means to guide learning, and assess quantitative conjectures of epidemiological processes. The objective of this paper is to bring a unique and robust perspective to observed chlamydial patterns through analyzing surveillance data with mathematical models of infection transmission. Methods This study integrated 25-year testing volume data from the Canadian province of Saskatchewan with one susceptible-infected-treated-susceptible and three susceptible-infected-treated-removed compartmental models. Calibration of model parameters to fit observed 25-year case notification data, after being combined with testing records, placed constraints on model behaviour and allowed for an approximation of chlamydia prevalence to be estimated. Model predictions were compared to observed case notification trends, and extensive sensitivity analyses were performed to confirm the robustness of model results. Results Model predictions accurately mirrored historic chlamydial trends including an observed rebound in the mid 1990s. For all models examined, the results repeatedly highlighted that increased testing volumes, rather than changes in the sensitivity and specificity of testing technologies, sexual behaviour, or truncated immunological responses brought about by treatment can, explain the increase in observed chlamydia case notifications. Conclusions Our results highlight the significant impact testing volume can have on observed incidence rates, and that simple explanations for these observed increases appear to have been dismissed in

  6. Funny current and cardiac rhythm: insights from HCN knockout mouse models

    Directory of Open Access Journals (Sweden)

    Mirko eBaruscotti

    2012-07-01

    Full Text Available In the adult animal the sinoatrial node (SAN rhythmically generates a depolarizing wave that propagates to the rest of the heart. However, the SAN is more than a simple clock; it is a clock that adjusts its pace according to the metabolic requirements of the organism. The Hyperpolarization-activated Cyclic Nucleotide-gated channels (HCN1-4 are the structural component of the funny (If channels; in the SAN the If current is the main driving electrical force of the diastolic depolarization and the HCN4 is the most abundant isoform. The generation of HCN KO mouse models has advanced the understanding of the role of these channels in cardiac excitability. The HCN4 KO models that were first developed allowed either global or cardiac-specific constitutive ablation of HCN4 channels, and resulted in embryonic lethality. A further progress was made with the development of three separate inducible HCN4 KO models; in one model KO was induced globally in the entire organism, in a second, ablation occurred only in HCN4-expressing cells, and finally in a third model KO was confined to cardiac cells. Unexpectedly, the three models yielded different results; similarities and differences among these models will be presented and discussed. The functional effects of HCN2 and HCN3 knockout models and transgenic HCN4 mouse models will also be discussed.In conclusion, HCN KO/transgenic models have allowed to evaluate the functional role of the If currents in intact animals as well as in single SAN cells isolated from the same animals. This opportunity is therefore unique since it allows to 1 verify the contribution of specific HCN isoforms to cardiac activity in intact animals, and 2 to compare these results to those obtained in single cell experiments. These combined studies were not possible prior to the development of KO models. Finally, these models represent critical tools to improve our understanding of the molecular basis of some inheritable arrhythmic human

  7. When Should Nintendo Launch its Wii? Insights From a Bivariate Successive Generation Model

    OpenAIRE

    Franses, Philip Hans; Hernández-Mireles, Carlos

    2006-01-01

    textabstractNovember 2006 most likely marks the launch of Sony’s PS3, the successor to PS2. Later, Nintendo is expected to launch the Wii, the successor to the GameCube. We answer the question in the title by analyzing the diffusion of the earlier generations of these consoles, and by using a new model that extends the successive-generations model of Norton and Bass (1987) by introducing two market players. Based on interviews with consumers and with retailers, we calibrate part of this model...

  8. Modeling of Learners’ Interest in Blended Learning: Insights from Emotional Cognition

    Directory of Open Access Journals (Sweden)

    Chen Hai-Jian

    2016-01-01

    Full Text Available In blended learning, how to explore and evaluate the learner’s interest is very important. In this paper, we study on modeling of learners’ interest from the perspective of cognitive neuroscience. Emotional cognitive theory and brain cognitive process for situational learning interest were introduced. In addition, in order to solve the problem of quantitative assessment of interest, learner’s online operation behaviour was summarized through data mining methods, and the learners' interest regression model was built. Experimental results show that the accuracy of the model is more than 91% and it has good applicability in blended learning.

  9. Risk Measurement about Shanghai Interbank Offered Rate Based on GARCH Models%基于GARCH模型的上海同业拆借利率风险度量

    Institute of Scientific and Technical Information of China (English)

    房小定; 吕鹏

    2013-01-01

    In this paper, we make the overnight lending rate data of SHIBOR from October 8, 2006 to September 29, 2012 as an object for our study, useing VaR model to measure the Shanghai Interbank Offered Rate.We find GARCH (1,2)-GED distribution could characterize SHIBOR logarithmic distribution of daily return series betterly, in considering asymmetric rates tested, the EGARCH (1,2)-GED distribution can best portray SHIBOR logarithmic the distribution of daily return series and the estimated value of the asymmetric term is greater than zero and significant, indicating the presence of"anti-leverage effect", that is the impact of a negative impact for the interbank interest rate markets will cause greater volatility. Finally, we use the GARCH (1,2)-GED and EGARCH (1,2)-GED, respectively 95% and 99% confidence level to get VaR values about Shanghai interbank interest rate. Both models have passed the test back to test, and the models can be used to measure VaR values about the Shanghai interbank offered rate market.%  本文采用2006年10月8日至2012年9月29日的上海银行间同业拆借利率(SHIBOR)中的隔夜拆借利率数据作为研究对象,利用VaR模型对上海同业拆借利率进行度量,得出GARCH(1,2)-GED分布较好地刻画SHIBOR对数日收益率序列的分布,在考虑利率非对称性进行检验时,得出EGARCH(1,2)-GED分布最能刻画SHIBOR对数日收益率序列的分布,且非对称项的估计值为大于零且显著,表明存在“反杠杆效应”,即正的冲击比负的冲击会引起同业拆借利率市场更大的波动性。最后对GARCH(1,2)-GED与EGARCH(1,2)-GED分别在95%与99%的置信水平下得出上海同业拆借利率的VaR值。这两个模型都通过了模型回测检验,可用于测算上海银行间同业拆借利率市场对数收益率的风险价值。

  10. Modelling auditory attention: Insights from the Theory of Visual Attention (TVA)

    DEFF Research Database (Denmark)

    Roberts, K. L.; Andersen, Tobias; Kyllingsbæk, Søren

    , and that there is a ‘race’ for selection and representation in visual short term memory (VSTM). In the basic TVA task, participants view a brief display of letters and are asked to report either all of the letters (whole report) or a subset of the letters (e.g., the red letters; partial report). Fitting the model......We report initial progress towards creating an auditory analogue of a mathematical model of visual attention: the ‘Theory of Visual Attention’ (TVA; Bundesen, 1990). TVA is one of the best established models of visual attention. It assumes that visual stimuli are initially processed in parallel...... been used to model normal visual attention, as well as identifying how the different parameters are affected by changes across the lifespan (McAvinue et al., 2012) and by attentional deficits such as neglect (Duncan et al., 1999). An auditory analogue would allow these same parameters to be measured...

  11. Unraveling the sub-processes of selective attention: insights from dynamic modeling and continuous behavior.

    Science.gov (United States)

    Frisch, Simon; Dshemuchadse, Maja; Görner, Max; Goschke, Thomas; Scherbaum, Stefan

    2015-11-01

    Selective attention biases information processing toward stimuli that are relevant for achieving our goals. However, the nature of this bias is under debate: Does it solely rely on the amplification of goal-relevant information or is there a need for additional inhibitory processes that selectively suppress currently distracting information? Here, we explored the processes underlying selective attention with a dynamic, modeling-based approach that focuses on the continuous evolution of behavior over time. We present two dynamic neural field models incorporating the diverging theoretical assumptions. Simulations with both models showed that they make similar predictions with regard to response times but differ markedly with regard to their continuous behavior. Human data observed via mouse tracking as a continuous measure of performance revealed evidence for the model solely based on amplification but no indication of persisting selective distracter inhibition.

  12. Mechanisms of cigarette smoke-induced COPD: insights from animal models

    National Research Council Canada - National Science Library

    Andrew Churg; Manuel Cosio; Joanne L. Wright

    2008-01-01

    Cigarette smoke-induced animal models of chronic obstructive pulmonary disease support the protease-antiprotease hypothesis of emphysema, although which cells and proteases are the crucial actors remains controversial...

  13. Ice age distriutions of European small mammals: insights from species distribution modelling

    DEFF Research Database (Denmark)

    Fløjgaard, Camilla; Normand, Signe; Skov, Flemming

    2009-01-01

    evidence. Our aim was to investigate the potential refuge locations using species distribution modelling to estimate the geographical distribution of suitable climatic conditions for selected rodent species during the LGM. Location Eurasia. Methods Presence/absence data for seven rodent species with range...... limits corresponding to the limits of temperate or boreal forest or arctic tundra were used in the analysis. We developed predictive distribution models based on the species present-day European distributions and validated these against their present-day Siberian ranges. The models with the best...... predictors of the species distributions across Siberia were projected onto LGM climate simulations to assess the distribution of climatically suitable areas. Results.The best distribution models provided good predictions of the present-day Siberian ranges of the study species. Their LGM projections showed...

  14. Structure-function relationships in hardwood--insight from micromechanical modelling.

    Science.gov (United States)

    de Borst, K; Bader, T K

    2014-03-21

    A micromechanical model is presented that predicts the stiffness of wood tissues in their three principal anatomical directions, across various hardwood species. The wood polymers cellulose, hemicellulose, and lignin, common to all wood tissues, serve as the starting point. In seven homogenisation steps, the stiffnesses of these polymers are linked to the macroscopic stiffness. The good agreement of model predictions and corresponding experimental data for ten different European and tropical species confirms the functionality and accuracy of the model. The model enables investigating the influence of individual microstructural features on the overall stiffness. This is exploited to elucidate the mechanical effects of vessels and ray cells. Vessels are shown to reduce the stiffness of wood at constant overall density. This supports that a trade-off exists between the hydraulic efficiency and the mechanical support in relation to the anatomical design of wood. Ray cells are shown to act as reinforcing elements in the radial direction.

  15. Further insights on the French WISC-IV factor structure through Bayesian structural equation modeling.

    Science.gov (United States)

    Golay, Philippe; Reverte, Isabelle; Rossier, Jérôme; Favez, Nicolas; Lecerf, Thierry

    2013-06-01

    The interpretation of the Wechsler Intelligence Scale for Children--Fourth Edition (WISC-IV) is based on a 4-factor model, which is only partially compatible with the mainstream Cattell-Horn-Carroll (CHC) model of intelligence measurement. The structure of cognitive batteries is frequently analyzed via exploratory factor analysis and/or confirmatory factor analysis. With classical confirmatory factor analysis, almost all cross-loadings between latent variables and measures are fixed to zero in order to allow the model to be identified. However, inappropriate zero cross-loadings can contribute to poor model fit, distorted factors, and biased factor correlations; most important, they do not necessarily faithfully reflect theory. To deal with these methodological and theoretical limitations, we used a new statistical approach, Bayesian structural equation modeling (BSEM), among a sample of 249 French-speaking Swiss children (8-12 years). With BSEM, zero-fixed cross-loadings between latent variables and measures are replaced by approximate zeros, based on informative, small-variance priors. Results indicated that a direct hierarchical CHC-based model with 5 factors plus a general intelligence factor better represented the structure of the WISC-IV than did the 4-factor structure and the higher order models. Because a direct hierarchical CHC model was more adequate, it was concluded that the general factor should be considered as a breadth rather than a superordinate factor. Because it was possible for us to estimate the influence of each of the latent variables on the 15 subtest scores, BSEM allowed improvement of the understanding of the structure of intelligence tests and the clinical interpretation of the subtest scores. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  16. Using Genetic Mouse Models to Gain Insight into Glaucoma: Past Results and Future Possibilities

    OpenAIRE

    Fernandes, Kimberly A; Harder, Jeffrey M.; Williams, Pete A.; Rausch, Rebecca L.; Kiernan, Amy E.; Nair, K. Saidas; Anderson, Michael G; John, Simon W.; Howell, Gareth R.; Libby, Richard T.

    2015-01-01

    While all forms of glaucoma are characterized by a specific pattern of retinal ganglion cell death, they are clinically divided into several distinct subclasses, including normal tension glaucoma, primary open angle glaucoma, congenital glaucoma, and secondary glaucoma. For each type of glaucoma there are likely numerous molecular pathways that control susceptibility to the disease. Given this complexity, a single animal model will never precisely model all aspects of all the different types ...

  17. Some insights for a relationship marketing model integrating SERVQUAL and customer loyalty in dental clinics

    OpenAIRE

    Vargas Perez, Ana Maria; Grijalvo Martin, Maria Mercedes; Mercado Idoeta, Carmelo

    2012-01-01

    The demand of new services, the emergence of new business models, insufficient innovation, underestimation of customer loyalty and reluctance to adopt new management are evidence of the deficiencies and the lack of research about the relations between patients and dental clinics. In this article we propose the structure of a model of Relationship Marketing (RM) in the dental clinic that integrates information from SERVQUAL, Customer Loyalty (CL) and activities of RM and combines the vision of...

  18. Role of body stiffness in undulatory swimming: Insights from robotic and computational models

    Science.gov (United States)

    Tytell, Eric D.; Leftwich, Megan C.; Hsu, Chia-Yu; Griffith, Boyce E.; Cohen, Avis H.; Smits, Alexander J.; Hamlet, Christina; Fauci, Lisa J.

    2016-11-01

    In an effort to understand the locomotion dynamics of a simple vertebrate, the lamprey, both physical and computational models have been developed. A key feature of these models is the ability to vary the passive stiffness of portions of the swimmer, focusing on highly flexible models similar in material properties to lampreys and other anguilliform fishes. The physical model is a robotic lampreylike swimmer that is actuated along most of its length but has passively flexible tails of different stiffnesses. The computational model is a two-dimensional model that captures fluid-structure interactions using an immersed boundary framework. This simulated lamprey is passively flexible throughout its length and is also actuated along most of its length by the activation of muscle forces. Although the three-dimensional robot and the two-dimensional computational swimmer are such different constructs, we demonstrate that the wake structures generated by these models share many features and we examine how flexibility affects these features. Both models produce wakes with two or more same-sign vortices shed each time the tail changes direction (a "2P" or higher-order wake). In general, wakes become less coherent as tail flexibility increases. We examine the pressure distribution near the tail tip and the timing of vortex formation in both cases and find good agreement. Because we include flexibility, we are able to estimate resonant frequencies for several of the robotic and computational swimmers. We find that actuation at the resonant frequency dramatically increases the distance traveled per tail-beat cycle with only a small increase in the lost kinetic energy in the wake, suggesting that the resonant swimmers are more efficient.

  19. Modeling X-Ray Binary Evolution in Normal Galaxies: Insights from SINGS

    Science.gov (United States)

    Tzanavaris, P.; Fragos, T.; Tremmel, M.; Jenkins, L.; Zezas, A.; Lehmer, B. D.; Hornschemeier, A.; Kalogera, V.; Ptak, A; Basu-Zych, A.

    2013-01-01

    We present the largest-scale comparison to date between observed extragalactic X-ray binary (XRB) populations and theoretical models of their production. We construct observational X-ray luminosity functions (oXLFs) using Chandra observations of 12 late-type galaxies from the Spitzer Infrared Nearby Galaxy Survey (SINGS). For each galaxy, we obtain theoretical XLFs (tXLFs) by combining XRB synthetic models, constructed with the population synthesis code StarTrack, with observational star formation histories (SFHs). We identify highest-likelihood models both for individual galaxies and globally, averaged over the full galaxy sample. Individual tXLFs successfully reproduce about half of oXLFs, but for some galaxies we are unable to find underlying source populations, indicating that galaxy SFHs and metallicities are not well matched and/or XRB modeling requires calibration on larger observational samples. Given these limitations, we find that best models are consistent with a product of common envelope ejection efficiency and central donor concentration approx.. = 0.1, and a 50% uniform - 50% "twins" initial mass-ratio distribution. We present and discuss constituent subpopulations of tXLFs according to donor, accretor and stellar population characteristics. The galaxy-wide X-ray luminosity due to low-mass and high-mass XRBs, estimated via our best global model tXLF, follows the general trend expected from the L(sub X) - star formation rate and L(sub X) - stellar mass relations of Lehmer et al. Our best models are also in agreement with modeling of the evolution both of XRBs over cosmic time and of the galaxy X-ray luminosity with redshift.

  20. Modelling of Thyroid Peroxidase Reveals Insights into Its Enzyme Function and Autoantigenicity.

    Science.gov (United States)

    Le, Sarah N; Porebski, Benjamin T; McCoey, Julia; Fodor, James; Riley, Blake; Godlewska, Marlena; Góra, Monika; Czarnocka, Barbara; Banga, J Paul; Hoke, David E; Kass, Itamar; Buckle, Ashley M

    2015-01-01

    Thyroid peroxidase (TPO) catalyses the biosynthesis of thyroid hormones and is a major autoantigen in Hashimoto's disease--the most common organ-specific autoimmune disease. Epitope mapping studies have shown that the autoimmune response to TPO is directed mainly at two surface regions on the molecule: immunodominant regions A and B (IDR-A, and IDR-B). TPO has been a major target for structural studies for over 20 years; however, to date, the structure of TPO remains to be determined. We have used a molecular modelling approach to investigate plausible modes of TPO structure and dimer organisation. Sequence features of the C-terminus are consistent with a coiled-coil dimerization motif that most likely anchors the TPO dimer in the apical membrane of thyroid follicular cells. Two contrasting models of TPO were produced, differing in the orientation and exposure of their active sites relative to the membrane. Both models are equally plausible based upon the known enzymatic function of TPO. The "trans" model places IDR-B on the membrane-facing side of the myeloperoxidase (MPO)-like domain, potentially hindering access of autoantibodies, necessitating considerable conformational change, and perhaps even dissociation of the dimer into monomers. IDR-A spans MPO- and CCP-like domains and is relatively fragmented compared to IDR-B, therefore most likely requiring domain rearrangements in order to coalesce into one compact epitope. Less epitope fragmentation and higher solvent accessibility of the "cis" model favours it slightly over the "trans" model. Here, IDR-B clusters towards the surface of the MPO-like domain facing the thyroid follicular lumen preventing steric hindrance of autoantibodies. However, conformational rearrangements may still be necessary to allow full engagement with autoantibodies, with IDR-B on both models being close to the dimer interface. Taken together, the modelling highlights the need to consider the oligomeric state of TPO, its conformational

  1. Lateral spreading processes in mountain ranges: Insights from an analogue modelling experiment

    Science.gov (United States)

    Bozzano, Francesca; Bretschneider, Alberto; Esposito, C.; Martino, Salvatore; Prestininzi, Alberto; Scarascia Mugnozza, Gabriele

    2013-10-01

    The results of a study on gravitational induced lateral spreading phenomena are here reported. The lateral spreading processes are widely represented in the Italian Apennines due to the widespread overlapping of stiff rock masses on more ductile ones. The stress-strain evolution of these processes was investigated by combining an analogical and a numerical modelling approach. The analogue modelling reproduced the evolution of a carbonate ridge thrust over a clayey flysch with reference to the case-study of Mt. Roccatagliata-Mt. Sant'Angelo ridge. The rock mass juxtaposition was reproduced in a laboratory experiment by overlapping a brittle concrete on a viscous ductile material; these materials were selected with rheological properties, physically scaled with respect to the natural rock mass prototypes. The spreading phenomenon was modelled by opening horizontal panels in sequential stages and monitoring the resulting stresses within the ductile material during the experiment. A stress-strain modelling was also performed by an FDM numerical solution; this modelling replied the laboratory experiment by testing the use of different rheological constitutive laws. The resulting stresses and morphological evolutions are comparable with the analogical laboratory experiment only if a time-dependent rheological behaviour is assumed for the ductile material. The results show that lateral spreading processes can be properly investigated by combining analogue and numerical modelling techniques which take into account the viscous-plastic behaviour of the used materials.

  2. Insights on in vitro models for safety and toxicity assessment of cosmetic ingredients.

    Science.gov (United States)

    Almeida, Andreia; Sarmento, Bruno; Rodrigues, Francisca

    2017-03-15

    According to the current European legislation, the safety assessment of each individual cosmetic ingredient of any formulation is the basis for the safety evaluation of a cosmetic product. Also, animal testing in the European Union is prohibited for cosmetic ingredients and products since 2004 and 2009, respectively. Additionally, the commercialization of any cosmetic products containing ingredients tested on animal models was forbidden in 2009. In consequence of these boundaries, the European Centre for the Validation of Alternative Methods (ECVAM) proposes a list of validated cell-based in vitro models for predicting the safety and toxicity of cosmetic ingredients. These models have been demonstrated as valuable and effective tools to overcome the limitations of animal in vivo studies. Although the use of in vitro cell-based models for the evaluation of absorption and permeability of cosmetic ingredients is widespread, a detailed study on the properties of these platforms and the in vitro-in vivo correlation compared with human data are required. Moreover, additional efforts must be taken to develop in vitro models to predict carcinogenicity, repeat dose toxicity and reproductive toxicity, for which no alternative in vitro methods are currently available. This review paper summarizes and characterizes the most relevant in vitro models validated by ECVAM employed to predict the safety and toxicology of cosmetic ingredients. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Animal models of post-traumatic stress disorder and recent neurobiological insights.

    Science.gov (United States)

    Whitaker, Annie M; Gilpin, Nicholas W; Edwards, Scott

    2014-09-01

    Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder characterized by the intrusive re-experiencing of past trauma, avoidant behavior, enhanced fear, and hyperarousal following a traumatic event in vulnerable populations. Preclinical animal models do not replicate the human condition in its entirety, but seek to mimic symptoms or endophenotypes associated with PTSD. Although many models of traumatic stress exist, few adequately capture the complex nature of the disorder and the observed individual variability in susceptibility of humans to PTSD. In addition, various types of stressors may produce different molecular neuroadaptations that likely contribute to the various behavioral disruptions produced by each model, although certain consistent neurobiological themes related to PTSD have emerged. For example, animal models report traumatic stress-induced and trauma reminder-induced alterations in neuronal activity in the amygdala and prefrontal cortex, in agreement with the human PTSD literature. Models have also provided a conceptual framework for the often-observed combination of PTSD and comorbid conditions such as alcohol use disorder. Future studies will continue to refine preclinical PTSD models in hope of capitalizing on their potential to deliver new and more efficacious treatments for PTSD and associated psychiatric disorders.

  4. Opsins have evolved under the permanent heterozygote model: insights from phylotranscriptomics of Odonata.

    Science.gov (United States)

    Suvorov, Anton; Jensen, Nicholas O; Sharkey, Camilla R; Fujimoto, M Stanley; Bodily, Paul; Wightman, Haley M Cahill; Ogden, T Heath; Clement, Mark J; Bybee, Seth M

    2017-03-01

    Gene duplication plays a central role in adaptation to novel environments by providing new genetic material for functional divergence and evolution of biological complexity. Several evolutionary models have been proposed for gene duplication to explain how new gene copies are preserved by natural selection, but these models have rarely been tested using empirical data. Opsin proteins, when combined with a chromophore, form a photopigment that is responsible for the absorption of light, the first step in the phototransduction cascade. Adaptive gene duplications have occurred many times within the animal opsins' gene family, leading to novel wavelength sensitivities. Consequently, opsins are an attractive choice for the study of gene duplication evolutionary models. Odonata (dragonflies and damselflies) have the largest opsin repertoire of any insect currently known. Additionally, there is tremendous variation in opsin copy number between species, particularly in the long-wavelength-sensitive (LWS) class. Using comprehensive phylotranscriptomic and statistical approaches, we tested various evolutionary models of gene duplication. Our results suggest that both the blue-sensitive (BS) and LWS opsin classes were subjected to strong positive selection that greatly weakens after multiple duplication events, a pattern that is consistent with the permanent heterozygote model. Due to the immense interspecific variation and duplicability potential of opsin genes among odonates, they represent a unique model system to test hypotheses regarding opsin gene duplication and diversification at the molecular level.

  5. Swelling in light water reactor internal components: Insights from computational modeling

    Energy Technology Data Exchange (ETDEWEB)

    Stoller, Roger E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Barashev, Alexander V. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States); Golubov, Stanislav I. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-08-01

    A modern cluster dynamics model has been used to investigate the materials and irradiation parameters that control microstructural evolution under the relatively low-temperature exposure conditions that are representative of the operating environment for in-core light water reactor components. The focus is on components fabricated from austenitic stainless steel. The model accounts for the synergistic interaction between radiation-produced vacancies and the helium that is produced by nuclear transmutation reactions. Cavity nucleation rates are shown to be relatively high in this temperature regime (275 to 325°C), but are sensitive to assumptions about the fine scale microstructure produced under low-temperature irradiation. The cavity nucleation rates observed run counter to the expectation that void swelling would not occur under these conditions. This expectation was based on previous research on void swelling in austenitic steels in fast reactors. This misleading impression arose primarily from an absence of relevant data. The results of the computational modeling are generally consistent with recent data obtained by examining ex-service components. However, it has been shown that the sensitivity of the model s predictions of low-temperature swelling behavior to assumptions about the primary damage source term and specification of the mean-field sink strengths is somewhat greater that that observed at higher temperatures. Further assessment of the mathematical model is underway to meet the long-term objective of this research, which is to provide a predictive model of void swelling at relevant lifetime exposures to support extended reactor operations.

  6. Quantitative strain analysis in analogue modelling experiments: insights from X-ray computed tomography and tomographic image correlation

    Science.gov (United States)

    Adam, J.; Klinkmueller, M.; Schreurs, G.; Wieneke, B.

    2009-04-01

    deformation. We have adapted our analogue modelling setups for optimal analysis of complex deformation processes using leading-edge volumetric strain monitoring techniques (3D volume DIC, Tomographic DIC). In this study, we apply DIC on X-ray CT images of analogue models. Our first results indicate that DIC can successfully be applied to quantify the 2D and 3D spatial and temporal patterns of strain accumulation. REFERENCES Adam, J., Urai, J.L, Wieneke, B., Oncken, O., Pfeiffer, K., Kukowski, N., Lohrmann, J., Hoth, S. van der Zee, W., and Schmatz, J.; 2005: Shear localisation and strain distribution during tectonic faulting - new insights from granular-flow experiments and high-resolution optical image correlation techniques. Journal of Structural Geology, 27, 283-301. Lohrmann, J., Kukowski, N., Adam, J. & Oncken, O.; 2003: The control of sand wedges by material properties: sensitivity analyses and application to convergent margin mechanics. - Journal of Structural Geology, 25, 1691-1711 Panien, M., Schreurs, G., and Pfiffner, A.; 2006. Mechanical behaviour of granular materials used in analogue modelling: insights from grain characterisation, ring-shear tests and analogue experiments. Journal of Structural Geology, 28, 1710-1724. Schreurs, G., Hänni, R, and Vock, P.; 2002: Analogue modelling of transfer zones in fold and thrust belts: a 4-D analysis. In: Schellart, W.P. and Passchier, C. (eds). Analogue modelling of large-scale tectonic processes. Journal of the Virtual Explorer, 7, 67-73. Schreurs, G., Hänni, R, Panien, M. and Vock, P.; 2003: Analysis of analogue models by helical X-ray computed tomography. In: Mees, F., Swennen, R., Van Geet, M. and Jacobs, P. (eds). Applications of X-ray Computed Tomogaphy in Earth Sciences. Geological Society, London, Special Publications, 215, 213-223.

  7. A Carbon Flux Super Site. New Insights and Innovative Atmosphere-Terrestrial Carbon Exchange Measurements and Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Leclerc, Monique Y. [The University of Georgia Research Foundation, Athens, GA (United States)

    2014-11-17

    This final report presents the main activities and results of the project “A Carbon Flux Super Site: New Insights and Innovative Atmosphere-Terrestrial Carbon Exchange Measurements and Modeling” from 10/1/2006 to 9/30/2014. It describes the new AmeriFlux tower site (Aiken) at Savanna River Site (SC) and instrumentation, long term eddy-covariance, sodar, microbarograph, soil and other measurements at the site, and intensive field campaigns of tracer experiment at the Carbon Flux Super Site, SC, in 2009 and at ARM-CF site, Lamont, OK, and experiments in Plains, GA. The main results on tracer experiment and modeling, on low-level jet characteristics and their impact on fluxes, on gravity waves and their influence on eddy fluxes, and other results are briefly described in the report.

  8. Insights on slab-driven mantle flow from advances in three-dimensional modelling

    Science.gov (United States)

    Jadamec, Margarete A.

    2016-10-01

    The wealth of seismic observations collected over the past 20 years has raised intriguing questions about the three-dimensional (3D) nature of the mantle flow field close to subduction zones and provided a valuable constraint for how the plate geometry may influence mantle flow proximal to the slab. In geodynamics, there has been a new direction of subduction zone modelling that has explored the 3D nature of slab-driven mantle flow, motivated in part by the observations from shear wave splitting, but also by the observed variations in slab geometries worldwide. Advances in high-performance computing are now allowing for an unprecedented level of detail to be incorporated into numerical models of subduction. This paper summarizes recent advances from 3D geodynamic models that reveal the complex nature of slab-driven mantle flow, including trench parallel flow, toroidal flow around slab edges, mantle upwelling at lateral slab edges, and small scale convection within the mantle wedge. This implies slab-driven mantle deformation zones occur in the asthenosphere proximal to the slab, wherein the mantle may commonly flow in a different direction and rate than the surface plates, implying laterally variable plate-mantle coupling. The 3D slab-driven mantle flow can explain, in part, the lateral transport of geochemical signatures in subduction zones. In addition, high-resolution geographically referenced models can inform the interpretation of slab structure, where seismic data are lacking. The incorporation of complex plate boundaries into high-resolution, 3D numerical models opens the door to a new avenue of research in model construction, data assimilation, and modelling workflows, and gives 3D immersive visualization a new role in scientific discovery.

  9. Marketing strategy to differentiate the offer

    OpenAIRE

    Miceski, Trajko; Pasovska, Silvana

    2013-01-01

    The marketing strategy for differentiation of the offers is important and accepted strategy especially by the bigger legal entities. The differentiation of the offers leads to bigger profit and bigger profitability in operation, through targeting of the demand towards the product of the enterprise. The vertical differentiation of the offers is directed towards the quality of the product itself which is observed as a something superior despite the competitive product which is observed as somet...

  10. Geochemical Modeling of Evaporation Processes on Mars: Insight From the Sedimentary Record at Meridiani Planum

    Science.gov (United States)

    Tosca, N. J.; McLennan, S. M.

    2004-12-01

    The Opportunity rover's analysis of an impure evaporite component present in the Martian sedimentary record reveals a unique geochemical system. The evaporation of basaltic weathering fluids is a process which is rare on Earth, but is likely to have played a major role in the formation of sedimentary rocks at Meridiani Planum. Adequately modeling the evaporation processes in this system must involve adding additional components to current thermodynamic models, namely Fe(II) and Fe(III). The goals of this study are to: (1) develop a thermodynamic database suitable for modeling evaporation of basaltic weathering fluids in the Meridiani system and (2) to apply the model to experimental fluid data obtained in our laboratory from weathering synthetic Martian basalt, which will allow for the testing of hypotheses related to the geochemical evolution of the Meridiani site. The evaporation of these fluids is simulated using an expanded version of the Harvie-Moller-Weare model which employs Pitzer's ion interaction approach in calculating activity coefficients in high ionic strength solutions. This model has been expanded using recent data to include Fe(II) and Fe(III). Although a full set of experimentally-derived data allowing the inclusion of Fe(III) into such models is not yet available, an adequate set of interaction parameters was built, based on viable assumptions and substitutions using analog data (e.g., Al3+, Ga3+, Cr3+). The accuracy of the thermodynamic model in predicting Fe(II) and Fe(III) activities in a multi-component system can be assessed. This is accomplished by comparing calculated Eh values (proportional to aFe2+/aFe3+) to those measured in the field from high ionic strength acid mine waters containing all of the relevant components of the model. The agreement between calculated and observed values suggests that the model calculations are adequate for reaction path calculations. New thermodynamic data for several Fe(II) and/or Fe(III) containing

  11. Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Inflammatory bowel disease (IBD), the most important being Crohn's disease and ulcerative colitis, results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract. Although the pathogenesis of IBD remains unclear, it is widely accepted that genetic, environmental, and immunological factors are involved. Recent studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative stresses. To investigate the etiology of IBD, animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for IBD. Several models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been described. In this manuscript, we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis (e.g. dextran sodium sulfate-, 2,4,6-trinitrobenzene sulfonic acid-, oxazolone-, acetic acid-, and indomethacin-induced models). We also summarize some regulatory and pathogenic factors demonstrated by these models that can, hopefully, be exploited to develop future therapeutic strategies against IBD.

  12. Insights into the molecular interactions between aminopeptidase and amyloid beta peptide using molecular modeling techniques.

    Science.gov (United States)

    Dhanavade, Maruti J; Sonawane, Kailas D

    2014-08-01

    Amyloid beta (Aβ) peptides play a central role in the pathogenesis of Alzheimer's disease. The accumulation of Aβ peptides in AD brain was caused due to overproduction or insufficient clearance and defects in the proteolytic degradation of Aβ peptides. Hence, Aβ peptide degradation could be a promising therapeutic approach in AD treatment. Recent experimental report suggests that aminopeptidase from Streptomyces griseus KK565 (SGAK) can degrade Aβ peptides but the interactive residues are yet to be known in detail at the atomic level. Hence, we developed the three-dimensional model of aminopeptidase (SGAK) using SWISS-MODEL, Geno3D and MODELLER. Model built by MODELLER was used for further studies. Molecular docking was performed between aminopeptidase (SGAK) with wild-type and mutated Aβ peptides. The docked complex of aminopeptidase (SGAK) and wild-type Aβ peptide (1IYT.pdb) shows more stability than the other complexes. Molecular docking and MD simulation results revealed that the residues His93, Asp105, Glu139, Glu140, Asp168 and His255 are involved in the hydrogen bonding with Aβ peptide and zinc ions. The interactions between carboxyl oxygen atoms of Glu139 of aminopeptidase (SGAK) with water molecule suggest that the Glu139 may be involved in the nucleophilic attack on Ala2-Glu3 peptide bond of Aβ peptide. Hence, amino acid Glu139 of aminopeptidase (SGAK) might play an important role to degrade Aβ peptides, a causative agent of Alzheimer's disease.

  13. Formal modeling and analysis of the MAL-associated biological regulatory network: insight into cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Jamil Ahmad

    Full Text Available The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs. This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL--a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis.

  14. Propagated rifting in the Southwest Sub-basin, South China Sea: Insights from analogue modelling

    Science.gov (United States)

    Ding, Weiwei; Li, Jiabiao

    2016-10-01

    How the South China Sea rifted has long been a puzzling question that is still debated, particularly with reference to the Southwest Sub-basin (SWSB). Analogue modelling remains one of the most useful tools for testing rift models and processes. Here, we present and discuss a series of analogue modelling experiments designed to investigate the rifting process of the SWSB. Convincing geophysical results were compiled to provide realistic constraints to test the experimental results and interpretations. A heterogeneous lithosphere model with a varied lithospheric structure showed tectono-morphological features similar to the natural case of the SWSB, indicating that the initial thermal condition and rheological stratification of the lithosphere should have a dominant effect on the rifting process of the SWSB. Rigid tectonic blocks existed in the continental margin, such as the Macclesfield Bank and the Reed Bank, and they played important roles in both the shaping of the continent-ocean boundary and the coupling between the crust and mantle. The initial thermal condition and rheological stratification of the lithosphere under the South China Sea controlled the propagated rifting process of the SWSB. Extension was centred on the deep troughs between the rigid blocks, and the break-up occurred in these areas between them. The westward rifting propagation is best explained with a heterogeneous lithosphere model characterized by varied lithospheric structure, and it was responsible for producing the V-shaped configuration of the SWSB.

  15. Constrained solution scattering modelling of human antibodies and complement proteins reveals novel biological insights.

    Science.gov (United States)

    Perkins, Stephen J; Okemefuna, Azubuike I; Nan, Ruodan; Li, Keying; Bonner, Alexandra

    2009-10-06

    X-ray and neutron-scattering techniques characterize proteins in solution and complement high-resolution structural studies. They are useful when either a large protein cannot be crystallized, in which case scattering yields a solution structure, or a crystal structure has been determined and requires validation in solution. These solution structures are determined by the application of constrained modelling methods based on known subunit structures. First, an appropriate starting model is generated. Next, its conformation is randomized to generate thousands of models for trial-and-error fits. Comparison with the experimental data identifies a small family of best-fit models. Finally, their significance for biological function is assessed. We illustrate this in application to structure determinations for secretory immunoglobulin A, the most prevalent antibody in the human body and a first line of defence in mucosal immunity. We also discuss the applications to the large multi-domain proteins of the complement system, most notably its major regulator factor H, which is important in age-related macular degeneration and renal diseases. We discuss the importance of complementary data from analytical ultracentrifugation, and structural studies of protein-protein complexes. We conclude that constrained scattering modelling makes useful contributions to our understanding of antibody and complement structure and function.

  16. Tourists’ expectations towards the agritourism farms’ offer

    Directory of Open Access Journals (Sweden)

    Iwona Wilk

    2013-06-01

    Full Text Available Agritourism plays an important role in multifunctional agriculture. Its development depends on agritourists’ needs identification in relation to the desired agritourism offer components which contributes to their improvement within agritourism farms market activity. The aim of the study was to determine customers preferences towards the agritourism farms offer in the Lodz region. The study was carried out on a sample of 120 respondents in 2011 (July-August and revealed that agritourists expect an offer, consisting of the components of various options offered by agritourism farm, matching their individual needs.

  17. Insights from Thermo-Mechanically Coupled Modeling of High-Elevation Regions of the Greenland Ice Sheet

    Science.gov (United States)

    Sommers, A. N.; Rajaram, H.; Colgan, W. T.

    2014-12-01

    As observations become more plentiful through remote sensing and numerical models become increasingly sophisticated, a clear priority of the ice sheet modeling community is to compare model simulations with observations. Temperature and velocity conditions within the Greenland ice sheet and at the bed remain largely unknown with the exception of sparse borehole measurements, but much can be inferred from rigorous thermo-mechanically coupled modeling. Surface velocities on the Greenland ice sheet are well constrained, both from satellite imagery and field observations. We take advantage of the observed surface velocities at the PARCA stakes around the 2,000m elevation contour of the ice sheet as modeling targets that represent a broad range of flow characteristics in different regions. Prescribing ice geometry, we use a two-dimensional thermo-mechanically coupled model to calculate 'steady-state' velocity and temperature profiles throughout the depth of the ice along flowlines from the main divide to the 2,000m elevation contour. Vertical velocity calculations are based on first principles of mass conservation, accounting for convergence and divergence of the streamtube width, and the enthalpy-based temperature calculations also incorporate the effects of liquid water content in temperate ice through the flow law parameter. Numerous insights from our simulations are presented for different regions, such as the influence of variable geothermal heat flux, the treatment of basal boundary conditions, and appropriate enhancement factors based on the age of ice. Results indicate that areas of temperate bed do exist in the high-elevation interior in certain sections of Greenland. Also highlighted is the importance of including temperature calculations in ice sheet modeling, particularly in regions with a temperate bed. For example, on the west coast, computations assuming a constant temperature of -5°C result in a 41% underestimation of the surface velocity at the 2,000m

  18. Is pertussis actually reemerging? Insights from an individual-based model.

    Science.gov (United States)

    Codeço, C T; Luz, P M

    2001-01-01

    In this paper, we introduce a spatially explicit, individual-based model developed to simulate the dynamics of pertussis in a small population. With this simulation approach, complex epidemic systems can be built using information on parasite population structure (strain diversity, virulence diversity, etc.), human population structure (individual risk, age structure, interaction matrices, immune response, etc.), as well as mechanisms of evolution and learning. We parameterized our model to describe pertussis in an age-structured community. Pertussis or whooping cough is an acute infection of the respiratory tract caused by Bordetella pertussis. Despite wide-scale vaccination in many countries, this disease is reemerging throughout the world in both adults and children. Emergence has been explained by many factors: wane of vaccine and natural immunity, increase of asymptomatic carriers, and/or natural selection of non-vaccine strains. Here, we model these hypotheses and analyze their potential impact on the observed increase of pertussis notification.

  19. Is pertussis actually reemerging? Insights from an individual-based model

    Directory of Open Access Journals (Sweden)

    Codeço Cláudia Torres

    2001-01-01

    Full Text Available In this paper, we introduce a spatially explicit, individual-based model developed to simulate the dynamics of pertussis in a small population. With this simulation approach, complex epidemic systems can be built using information on parasite population structure (strain diversity, virulence diversity, etc., human population structure (individual risk, age structure, interaction matrices, immune response, etc., as well as mechanisms of evolution and learning. We parameterized our model to describe pertussis in an age-structured community. Pertussis or whooping cough is an acute infection of the respiratory tract caused by Bordetella pertussis. Despite wide-scale vaccination in many countries, this disease is reemerging throughout the world in both adults and children. Emergence has been explained by many factors: wane of vaccine and natural immunity, increase of asymptomatic carriers, and/or natural selection of non-vaccine strains. Here, we model these hypotheses and analyze their potential impact on the observed increase of pertussis notification.

  20. Understanding melatonin receptor pharmacology: latest insights from mouse models, and their relevance to human disease.

    Science.gov (United States)

    Tosini, Gianluca; Owino, Sharon; Guillaume, Jean-Luc; Jockers, Ralf

    2014-08-01

    Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications toward type 2 diabetes development, visual functions, sleep disturbances, and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2 , which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1 /MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models.

  1. Information Processing in Single Cells and Small Networks: Insights from Compartmental Models

    Science.gov (United States)

    Poirazi, Panayiota

    2009-03-01

    The goal of this paper is to present a set of predictions generated by detailed compartmental models regarding the ways in which information may be processed, encoded and propagated by single cells and neural assemblies. Towards this goal, I will review a number of modelling studies from our lab that investigate how single pyramidal neurons and small neural networks in different brain regions process incoming signals that are associated with learning and memory. I will first discuss the computational capabilities of individual pyramidal neurons in the hippocampus [1-3] and how these properties may allow a single cell to discriminate between different memories [4]. I will then present biophysical models of prefrontal layer V neurons and small networks that exhibit sustained activity under realistic synaptic stimulation and discuss their potential role in working memory [5].

  2. Mode specificity and product energy disposal in unimolecular reactions: insights from the sudden vector projection model.

    Science.gov (United States)

    Li, Jun; Guo, Hua

    2014-04-03

    A simple model is proposed to predict mode specificity and product energy disposal in unimolecular dissociation reactions. This so-called Sudden Vector Projection (SVP) model quantifies the coupling of a reactant or product mode with the reaction coordinate at the transition state by projecting the corresponding normal mode vector onto the imaginary frequency mode at the saddle point. Due to the sudden assumption, SVP predictions for mode specificity are expected to be valid only when the reactant molecule has weak intermodal coupling. On the other hand, the sudden limit is generally satisfied for its predictions of product energy disposal in unimolecular reactions with a tight barrier. The SVP model is applied to several prototypical systems and the agreement with available experimental and theoretical results is satisfactory.

  3. Is pertussis actually reemerging? Insights from an individual-based model

    Directory of Open Access Journals (Sweden)

    Cláudia Torres Codeço

    2001-06-01

    Full Text Available In this paper, we introduce a spatially explicit, individual-based model developed to simulate the dynamics of pertussis in a small population. With this simulation approach, complex epidemic systems can be built using information on parasite population structure (strain diversity, virulence diversity, etc., human population structure (individual risk, age structure, interaction matrices, immune response, etc., as well as mechanisms of evolution and learning. We parameterized our model to describe pertussis in an age-structured community. Pertussis or whooping cough is an acute infection of the respiratory tract caused by Bordetella pertussis. Despite wide-scale vaccination in many countries, this disease is reemerging throughout the world in both adults and children. Emergence has been explained by many factors: wane of vaccine and natural immunity, increase of asymptomatic carriers, and/or natural selection of non-vaccine strains. Here, we model these hypotheses and analyze their potential impact on the observed increase of pertussis notification.

  4. Multiscaling in Hall-magnetohydrodynamic turbulence: insights from a shell model.

    Science.gov (United States)

    Banerjee, Debarghya; Ray, Samriddhi Sankar; Sahoo, Ganapati; Pandit, Rahul

    2013-10-25

    We show that a shell-model version of the three-dimensional Hall-magnetohydrodynamic (3D Hall-MHD) equations provides a natural theoretical model for investigating the multiscaling behaviors of velocity and magnetic structure functions. We carry out extensive numerical studies of this shell model, obtain the scaling exponents for its structure functions, in both the low-k and high-k power-law ranges of three-dimensional Hall-magnetohydrodynamic, and find that the extended-self-similarity procedure is helpful in extracting the multiscaling nature of structure functions in the high-k regime, which otherwise appears to display simple scaling. Our results shed light on intriguing solar-wind measurements.

  5. Time-resolved spectroscopy at surfaces and adsorbate dynamics: Insights from a model-system approach

    Science.gov (United States)

    Boström, Emil; Mikkelsen, Anders; Verdozzi, Claudio

    2016-05-01

    We introduce a model description of femtosecond laser induced desorption at surfaces. The substrate part of the system is taken into account as a (possibly semi-infinite) linear chain. Here, being especially interested in the early stages of dissociation, we consider a finite-size implementation of the model (i.e., a finite substrate), for which an exact numerical solution is possible. By time-evolving the many-body wave function, and also using results from a time-dependent density functional theory description for electron-nuclear systems, we analyze the competition between several surface-response mechanisms and electronic correlations in the transient and longer time dynamics under the influence of dipole-coupled fields. Our model allows us to explore how coherent multiple-pulse protocols can impact desorption in a variety of prototypical experiments.

  6. An insight into chemical kinetics and turbulence-chemistry interaction modeling in flameless combustion

    Directory of Open Access Journals (Sweden)

    Amir Azimi, Javad Aminian

    2015-01-01

    Full Text Available Computational Fluid Dynamics (CFD study of flameless combustion condition is carried out by solving the Reynolds-Averaged Navier-Stokes (RANS equations in the open-source CFD package of OpenFOAM 2.1.0. Particular attention is devoted to the comparison of three global and detailed chemical mechanisms using the Partially Stirred Reactor (PaSR combustion model for the turbulence-chemistry interaction treatment. The OpenFOAM simulations are assessed against previously published CFD results using the Eddy Dissipation Concept (EDC combustion model as well as the experimental data available in the literature. Results show that global chemical mechanisms provide acceptable predictions of temperature and major species fields in flameless mode with much lower computational costs comparing with the detailed chemical mechanisms. However, incorporation of detailed chemical mechanisms with proper combustion models is crucial to account for finite-rate chemistry effects and accurately predict net production of minor species.

  7. Mathematical modeling of cancer cell invasion of tissue: biological insight from mathematical analysis and computational simulation.

    Science.gov (United States)

    Andasari, Vivi; Gerisch, Alf; Lolas, Georgios; South, Andrew P; Chaplain, Mark A J

    2011-07-01

    The ability of cancer cells to break out of tissue compartments and invade locally gives solid tumours a defining deadly characteristic. One of the first steps of invasion is the remodelling of the surrounding tissue or extracellular matrix (ECM) and a major part of this process is the over-expression of proteolytic enzymes, such as the urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), by the cancer cells to break down ECM proteins. Degradation of the matrix enables the cancer cells to migrate through the tissue and subsequently to spread to secondary sites in the body, a process known as metastasis. In this paper we undertake an analysis of a mathematical model of cancer cell invasion of tissue, or ECM, which focuses on the role of the urokinase plasminogen activation system. The model consists of a system of five reaction-diffusion-taxis partial differential equations describing the interactions between cancer cells, uPA, uPA inhibitors, plasmin and the host tissue. Cancer cells react chemotactically and haptotactically to the spatio-temporal effects of the uPA system. The results obtained from computational simulations carried out on the model equations produce dynamic heterogeneous spatio-temporal solutions and using linear stability analysis we show that this is caused by a taxis-driven instability of a spatially homogeneous steady-state. Finally we consider the biological implications of the model results, draw parallels with clinical samples and laboratory based models of cancer cell invasion using three-dimensional invasion assay, and go on to discuss future development of the model.

  8. Dispersal patterns in the North Sea, insights from a high resolution model

    Science.gov (United States)

    Mayorga Adame, Claudia Gabriela; Polton, Jeff; Holt, Jason; Graham, Jennifer; Henry, Lea-Anne

    2017-04-01

    Lagrangian particle tracking simulations are useful to elucidate the fate of materials transported by ocean currents ( i.e. larvae, pollutants, debris, drifters), and can therefore be useful to study important process in coastal seas. Dispersal patterns should be improved by the new generation of high horizontal resolution (ocean circulation models which provide an improved, more dynamic representation of the coastal ocean. We used the new high resolution Northwest European Shelf NEMO ocean circulation model and LTRANS, a particle tracking code, to study the effects of the increased resolution on the dispersion of Lagrangian particles in the North Sea. Particles were released at the locations of offshore oil and gas platforms in the North Sea and tracked for periods similar to the larval duration of benthic organisms that have colonized the subsea platforms. Dispersal patterns and spatio-temporal scales are identified for the summer (stratified) and winter (mixed) oceanographic regimes. The high resolution of the new NEMO model allows for fine scale detail of flow speed and variability. The small scale features (i.e. eddies and fronts) now represented in the model trap particles, decreasing their dispersal and increasing retention times in comparison to simulations done on a previous coarser resolution NEMO version (7 km AMM7). We isolated the effects of resolution from those due to different representations of the circulation in the different versions of the ocean circulation model by averaging the high resolution model velocity fields to the coarser (7 km) grid, and comparing the results of identical particle tracking experiments using these two flow fields. Our results provide a measure of the importance of high resolution flow fields when estimating transport of materials in an enclosed sea and provide a more realistic characterisation of dispersion in the North Sea.

  9. Monte-Carlo modeling of the central carbon metabolism of Lactococcus lactis: insights into metabolic regulation.

    Science.gov (United States)

    Murabito, Ettore; Verma, Malkhey; Bekker, Martijn; Bellomo, Domenico; Westerhoff, Hans V; Teusink, Bas; Steuer, Ralf

    2014-01-01

    Metabolic pathways are complex dynamic systems whose response to perturbations and environmental challenges are governed by multiple interdependencies between enzyme properties, reactions rates, and substrate levels. Understanding the dynamics arising from such a network can be greatly enhanced by the construction of a computational model that embodies the properties of the respective system. Such models aim to incorporate mechanistic details of cellular interactions to mimic the temporal behavior of the biochemical reaction system and usually require substantial knowledge of kinetic parameters to allow meaningful conclusions. Several approaches have been suggested to overcome the severe data requirements of kinetic modeling, including the use of approximative kinetics and Monte-Carlo sampling of reaction parameters. In this work, we employ a probabilistic approach to study the response of a complex metabolic system, the central metabolism of the lactic acid bacterium Lactococcus lactis, subject to perturbations and brief periods of starvation. Supplementing existing methodologies, we show that it is possible to acquire a detailed understanding of the control properties of a corresponding metabolic pathway model that is directly based on experimental observations. In particular, we delineate the role of enzymatic regulation to maintain metabolic stability and metabolic recovery after periods of starvation. It is shown that the feedforward activation of the pyruvate kinase by fructose-1,6-bisphosphate qualitatively alters the bifurcation structure of the corresponding pathway model, indicating a crucial role of enzymatic regulation to prevent metabolic collapse for low external concentrations of glucose. We argue that similar probabilistic methodologies will help our understanding of dynamic properties of small-, medium- and large-scale metabolic networks models.

  10. Phylogeographic model selection leads to insight into the evolutionary history of four-eyed frogs

    Science.gov (United States)

    Thomé, Maria Tereza C.; Carstens, Bryan C.

    2016-01-01

    Phylogeographic research investigates biodiversity at the interface between populations and species, in a temporal and geographic context. Phylogeography has benefited from analytical approaches that allow empiricists to estimate parameters of interest from the genetic data (e.g., θ = 4Neμ, population divergence, gene flow), and the widespread availability of genomic data allow such parameters to be estimated with greater precision. However, the actual inferences made by phylogeographers remain dependent on qualitative interpretations derived from these parameters’ values and as such may be subject to overinterpretation and confirmation bias. Here we argue in favor of using an objective approach to phylogeographic inference that proceeds by calculating the probability of multiple demographic models given the data and the subsequent ranking of these models using information theory. We illustrate this approach by investigating the diversification of two sister species of four-eyed frogs of northeastern Brazil using single nucleotide polymorphisms obtained via restriction-associated digest sequencing. We estimate the composite likelihood of the observed data given nine demographic models and then rank these models using Akaike information criterion. We demonstrate that estimating parameters under a model that is a poor fit to the data is likely to produce values that lead to spurious phylogeographic inferences. Our results strongly imply that identifying which parameters to estimate from a given system is a key step in the process of phylogeographic inference and is at least as important as being able to generate precise estimates of these parameters. They also illustrate that the incorporation of model uncertainty should be a component of phylogeographic hypothesis tests. PMID:27432969

  11. Soil carbonyl sulfide fluxes in a Mediterranean ecosystem: insights from model-data fusion analysis

    Science.gov (United States)

    Sun, W.; Seibt, U. H.; Maseyk, K. S.; Lett, C.

    2013-12-01

    Carbonyl sulfide (COS) is linked to biosphere components of the carbon cycle, due in large part to its hydrolysis by the enzyme carbonic anhydrase (CA). Stomatal diffusion models and observations at leaf and ecosystem scales have demonstrated the potential of COS as a tracer for Gross Primary Production (GPP). Although considered small relative to canopy COS fluxes, accurate knowledge of soil COS fluxes is required for the use of net ecosystem COS fluxes in carbon flux partitioning. However, extensive field measurements of soil COS fluxes are rare and process-based modeling is limited. Here we report continuous chamber measurements of soil COS fluxes in a Mediterranean ecosystem in the Santa Monica Mountains, California during April and early May 2013. Both COS uptake and emissions were observed, but the soil acted as a net sink in most conditions and was a net source only when soil temperatures were above 22 C. COS sink fluxes were positively correlated with soil water content and CO2 fluxes. COS uptake had a maximum at a temperature around 15 C. However, no single environmental variable could be correlated to COS fluxes with an r-square > 0.6. COS fluxes from soil chambers ranged from -9 to 2.5 pmol m-2 s-1. Leaf litter appeared to increase soil COS metabolic activity. We observed huge bursts of soil COS uptake induced by a precipitation event, probably due to enhanced soil microbial activity resulting from alleviated water limitation and a decrease in soil temperature towards the optimum. We used a soil gas exchange model coupled with CA enzyme kinetics to simulate the soil COS fluxes. Micrometeorological and soil data were used to drive the soil flux model. Model simulations indicated that diurnal and synoptic variations of COS fluxes were driven by soil temperature and water content, controlling both CA activity and diffusion. We suggest that multiple parameters need to be optimized to reduce uncertainties in models of soil COS fluxes at larger scales.

  12. Coseismic and Post-seismic landsliding: insights from seismological modeling and landslide map time series.

    Science.gov (United States)

    Marc, Odin; Hovius, Niels; Meunier, Patrick; Uchida, Taro; Gorum, Tolga

    2016-04-01

    Earthquakes impart a catastrophic forcing on hillslopes, that often lead to widespread landsliding and can contribute significantly to sedimentary and organic matter fluxes. We present a new expression for the total area and volume of populations of earthquake-induced landslides.This model builds on a set of scaling relationships between key parameters, such as landslide density, ground acceleration, fault size, earthquake source depth and seismic moment, derived from geomorphological and seismological observations. To assess the model we have assembled and normalized a catalogue of landslide inventories for 40 earthquakes. We have found that low landscape steepness systematically leads to over-prediction of the total area and volume of landslides.When this effect is accounted for, the model is able to predict within a factor of 2 the landslide areas and associated volumes for about two thirds of the cases in our databases. This is a significant improvement on a previously published empirical expression based only on earthquake moment. This model is suitable for integration into landscape evolution models, and application to the assessment of secondary hazards and risks associated with earthquakes. However, it only models landslides associated to the strong ground shaking and neglects the intrinsic permanent damage that also occurred on hillslopes and persist for longer period. With time series of landslide maps we have constrained the magnitude of the change in landslide susceptibility in the epicentral areas of 4 intermediate to large earthquakes. We propose likely causes for this transient ground strength perturbations and compare our observations to other observations of transient perturbations in epicentral areas, such as suspended sediment transport increases, seismic velocity reductions and hydrological perturbations. We conclude with some preliminary observations on the coseismic mass wasting and post-seismic landslide enhancement caused by the 2015 Mw.7

  13. Modelling of Thyroid Peroxidase Reveals Insights into Its Enzyme Function and Autoantigenicity.

    Directory of Open Access Journals (Sweden)

    Sarah N Le

    Full Text Available Thyroid peroxidase (TPO catalyses the biosynthesis of thyroid hormones and is a major autoantigen in Hashimoto's disease--the most common organ-specific autoimmune disease. Epitope mapping studies have shown that the autoimmune response to TPO is directed mainly at two surface regions on the molecule: immunodominant regions A and B (IDR-A, and IDR-B. TPO has been a major target for structural studies for over 20 years; however, to date, the structure of TPO remains to be determined. We have used a molecular modelling approach to investigate plausible modes of TPO structure and dimer organisation. Sequence features of the C-terminus are consistent with a coiled-coil dimerization motif that most likely anchors the TPO dimer in the apical membrane of thyroid follicular cells. Two contrasting models of TPO were produced, differing in the orientation and exposure of their active sites relative to the membrane. Both models are equally plausible based upon the known enzymatic function of TPO. The "trans" model places IDR-B on the membrane-facing side of the myeloperoxidase (MPO-like domain, potentially hindering access of autoantibodies, necessitating considerable conformational change, and perhaps even dissociation of the dimer into monomers. IDR-A spans MPO- and CCP-like domains and is relatively fragmented compared to IDR-B, therefore most likely requiring domain rearrangements in order to coalesce into one compact epitope. Less epitope fragmentation and higher solvent accessibility of the "cis" model favours it slightly over the "trans" model. Here, IDR-B clusters towards the surface of the MPO-like domain facing the thyroid follicular lumen preventing steric hindrance of autoantibodies. However, conformational rearrangements may still be necessary to allow full engagement with autoantibodies, with IDR-B on both models being close to the dimer interface. Taken together, the modelling highlights the need to consider the oligomeric state of TPO, its

  14. WE-F-304-05: Cranial TCP/NTCP Modeling Insights and Caveats

    Energy Technology Data Exchange (ETDEWEB)

    El Naqa, I. [University of Michigan (United States)

    2015-06-15

    Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT’s work for cranial sites, and recurrent head and neck cancer. From literature-based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear-quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer-reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes. 1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60. Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear-quadratic model

  15. What moves the European carbon market? Insights from conditional jump models

    Energy Technology Data Exchange (ETDEWEB)

    Gronwald, Marc; Ketterer, Janina [Munich Univ. (Germany). Ifo Institute - Leibniz Institute for Economic Research

    2012-04-15

    This paper is concerned with carbon price volatility and the underlying causes of large price movements in the European emissions trading market. Based on the application of a combined jump-GARCH model the behavior of EUA prices is characterized. The jump- GARCH model explains the unsteady carbon price movement well and, moreover, shows that between 40 and 60 percent of the carbon price variance are triggered by jumps. Information regarding EUA supply and news from international carbon markets are identified as important drivers of these price spikes. These results can lead regulators the way if smoother carbon prices are desired.

  16. Internal deformation within an unstable granular slope: insights from physical modeling

    Science.gov (United States)

    Liu, Z.; Koyi, H.; Nilfouroushan, F.; Swantesson, J.; Reshetyuk, Y.

    2012-04-01

    The collapses of granular materials frequently occur in nature in the form of, for example, rock avalanches, debris avalanches and debris flow. In previous studies of collapses of a granular material, most of the focus has been on the effect of initial geometry and mechanical properties of the granular materials, the run-out distance, and the topography of final deposit. In this study, results of analogue models and scanned natural failed slopes are used to outline the mode of failure of an unstable slope. Model results and field observations are used to argue that a granular mass moves downslope in a wavy pattern resulting in its intensive deformation. In the models, we mainly investigated the internal deformation of collapses of granular slopes in terms of their internal structures and the spatial and temporal distribution of the latter. Model results showed that a displaced mass of the granular slope has the following two features: (1) Initial collapse resulted in a series of normal faults, where hanging-wall blocks were slightly deformed, like the slump-shear structures in nature; (2) With further collapse, a set of secondary structures, such as deformed/folded fault surfaces, faulted folds, displaced inclined folds, and overturned folds formed near the slope surface. The occurrence of these structures reflects the failure process of the granular mass in space and time. In addition, our model results show that the nature of basal friction has a significant influence on the geometry and kinematics of these structures at the slope toe. Model results show also that the mass does not glide downslope along only one surface, but includes several gliding surfaces each of which take part of the sliding. These gliding surfaces become steeper deeper in the sliding mass. Some of these features observed in the models are also detected in the field. Scanned failed slope surfaces show a wavy pattern similar to that in the models, reflecting the presence of normal faults at

  17. Decision support for organ offers in liver transplantation.

    Science.gov (United States)

    Volk, Michael L; Goodrich, Nathan; Lai, Jennifer C; Sonnenday, Christopher; Shedden, Kerby

    2015-06-01

    Organ offers in liver transplantation are high-risk medical decisions with a low certainty of whether a better liver offer will come along before death. We hypothesized that decision support could improve the decision to accept or decline. With data from the Scientific Registry of Transplant Recipients, survival models were constructed for 42,857 waiting-list patients and 28,653 posttransplant patients from 2002 to 2008. Daily covariate-adjusted survival probabilities from these 2 models were combined into a 5-year area under the curve to create an individualized prediction of whether an organ offer should be accepted for a given patient. Among 650,832 organ offers from 2008 to 2013, patient survival was compared by whether the clinical decision was concordant or discordant with model predictions. The acceptance benefit (AB)--the predicted gain or loss of life by accepting a given organ versus waiting for the next organ--ranged from 3 to -22 years (harm) and varied geographically; for example, the average benefit of accepting a donation after cardiac death organ ranged from 0.47 to -0.71 years by donation service area. Among organ offers, even when AB was >1 year, the offer was only accepted 10% of the time. Patient survival from the time of the organ offer was better if the model recommendations and the clinical decision were concordant: for offers with AB > 0, the 3-year survival was 80% if the offer was accepted and 66% if it was declined (P decision support may improve patient survival in liver transplantation. © 2015 American Association for the Study of Liver Diseases.

  18. Evolving dynamical regimes during secular cooling of terrestrial planets : insights and inferences from numerical models

    NARCIS (Netherlands)

    Thienen, Peter van

    2003-01-01

    Although plate tectonics is the present-day mode of geodynamics on Earth, it is not so on Mars and Venus, and probably also not during the early history of the Earth. In this thesis, the conditions under which plate tectonics may operate on terrestrial planets are investigated. Numerical model studi

  19. 9.7 um Silicate Features in AGNs: New Insights into Unification Models

    CERN Document Server

    Shi, Y; Hines, D C; Gorjian, V; Werner, M W; Cleary, K; Low, F J; Smith, P S; Bouwman, J

    2006-01-01

    We describe observations of 9.7 um silicate features in 97 AGNs, exhibiting a wide range of AGN types and of X-ray extinction toward the central nuclei. We find that the strength of the silicate feature correlates with the HI column density estimated from fitting the X-ray data, such that low HI columns correspond to silicate emission while high columns correspond to silicate absorption. The behavior is generally consistent with unification models where the large diversity in AGN properties is caused by viewing-angle-dependent obscuration of the nucleus. Radio-loud AGNs and radio-quiet quasars follow roughly the correlation between HI columns and the strength of the silicate feature defined by Seyfert galaxies. The agreement among AGN types suggests a high-level unification with similar characteristics for the structure of the obscuring material. We demonstrate the implications for unification models qualitatively with a conceptual disk model. The model includes an inner accretion disk (< 0.1 pc in radius)...

  20. MicroRNAs and Alzheimer's Disease Mouse Models: Current Insights and Future Research Avenues

    Directory of Open Access Journals (Sweden)

    Charlotte Delay

    2011-01-01

    Full Text Available Evidence from clinical trials as well as from studies performed in animal models suggest that both amyloid and tau pathologies function in concert with other factors to cause the severe neurodegeneration and dementia in Alzheimer’s disease (AD patients. Accumulating data in the literature suggest that microRNAs (miRNAs could be such factors. These conserved, small nonprotein-coding RNAs are essential for neuronal function and survival and have been implicated in the regulation of key genes involved in genetic and sporadic AD. The study of miRNA changes in AD mouse models provides an appealing approach to address the cause-consequence relationship between miRNA dysfunction and AD pathology in humans. Mouse models also provide attractive tools to validate miRNA targets in vivo and provide unique platforms to study the role of specific miRNA-dependent gene pathways in disease. Finally, mouse models may be exploited for miRNA diagnostics in the fight against AD.

  1. Evaluating Topographic Effects on Ground Deformation: Insights from Finite Element Modeling

    Science.gov (United States)

    Ronchin, Erika; Geyer, Adelina; Martí, Joan

    2015-07-01

    Ground deformation has been demonstrated to be one of the most common signals of volcanic unrest. Although volcanoes are commonly associated with significant topographic relief, most analytical models assume the Earth's surface as flat. However, it has been confirmed that this approximation can lead to important misinterpretations of the recorded surface deformation data. Here we perform a systematic and quantitative analysis of how topography may influence ground deformation signals generated by a spherical pressure source embedded in an elastic homogeneous media and how these variations correlate with the different topographic parameters characterizing the terrain form (e.g., slope, aspect, curvature). For this, we bring together the results presented in previous published papers and complement them with new axisymmetric and 3D finite element (FE) model results. First, we study, in a parametric way, the influence of a volcanic edifice centered above the pressure source axis. Second, we carry out new 3D FE models simulating the real topography of three different volcanic areas representative of topographic scenarios common in volcanic regions: Rabaul caldera (Papua New Guinea) and the volcanic islands of Tenerife and El Hierro (Canary Islands). The calculated differences are then correlated with a series of topographic parameters. The final aim is to investigate the artifacts that might arise from the use of half-space models at volcanic areas due to diverse topographic features (e.g., collapse caldera structures, prominent central edifices, large landslide scars).

  2. Insights into the damage zones in fault-bend folds from geomechanical models and field data

    Science.gov (United States)

    Ju, Wei; Hou, Guiting; Zhang, Bo

    2014-01-01

    Understanding the rock mass deformation and stress states, the fracture development and distribution are critical to a range of endeavors including oil and gas exploration and development, and geothermal reservoir characterization and management. Geomechanical modeling can be used to simulate the forming processes of faults and folds, and predict the onset of failure and the type and abundance of deformation features along with the orientations and magnitudes of stresses. This approach enables the development of forward models that incorporate realistic mechanical stratigraphy (e.g., the bed thickness, bedding planes and competence contrasts), include faults and bedding-slip surfaces as frictional sliding interfaces, reproduce the geometry of the fold structures, and allow tracking strain and stress through the whole deformation process. In this present study, we combine field observations and finite element models to calibrate the development and distribution of fractures in the fault-bend folds, and discuss the mechanical controls (e.g., the slip displacement, ramp cutoff angle, frictional coefficient of interlayers and faults) that are able to influence the development and distribution of fractures during fault-bend folding. A linear relationship between the slip displacement and the fracture damage zone, the ramp cutoff angle and the fracture damage zone, and the frictional coefficient of interlayers and faults and the fracture damage zone was established respectively based on the geomechanical modeling results. These mechanical controls mentioned above altogether contribute to influence and control the development and distribution of fractures in the fault-bend folds.

  3. Evolving dynamical regimes during secular cooling of terrestrial planets : insights and inferences from numerical models

    NARCIS (Netherlands)

    Thienen, Peter van

    2003-01-01

    Although plate tectonics is the present-day mode of geodynamics on Earth, it is not so on Mars and Venus, and probably also not during the early history of the Earth. In this thesis, the conditions under which plate tectonics may operate on terrestrial planets are investigated. Numerical model

  4. Microsolvated transition state models for improved insight into chemical properties and reaction mechanisms.

    Science.gov (United States)

    Sunoj, Raghavan B; Anand, Megha

    2012-10-05

    Over the years, several methods have been developed to effectively represent the chemical behavior of solutes in solvents. The environmental effects arising due to solvation can generally be achieved either through inclusion of discrete solvent molecules or by inscribing into a cavity in a homogeneous and continuum dielectric medium. In both these approaches of computational origin, the perturbations on the solute induced by the surrounding solvent are at the focus of the problem. While the rigor and method of inclusion of solvent effects vary, such solvation models have found widespread applications, as evident from modern chemical literature. A hybrid method, commonly referred to as cluster-continuum model (CCM), brings together the key advantages of discrete and continuum models. In this perspective, we intend to highlight the latent potential of CCM toward obtaining accurate estimates on a number of properties as well as reactions of contemporary significance. The objective has generally been achieved by choosing illustrative examples from the literature, besides expending efforts to bring out the complementary advantages of CCM as compared to continuum or discrete solvation models. The majority of examples emanate from the prevalent applications of CCM to organic reactions, although a handful of interesting organometallic reactions have also been discussed. In addition, increasingly accurate computations of properties like pK(a) and solvation of ions obtained using the CCM protocol are also presented.

  5. Fundulus as the Premier Teleost Model in Environmental Biology: Opportunities for New Insights Using Genomics

    Science.gov (United States)

    A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an ex...

  6. Modeling, Analysis, and Design Insights for Shuttle-based Compact Storage Systems

    NARCIS (Netherlands)

    E. Tappia (Elena); D. Roy (Debjit); M.B.M. de Koster (René); M. Melacini (Marco)

    2015-01-01

    textabstractShuttle-based compact systems are new automated multi-deep unit-load storage systems with lifts that promise both low operational cost and large volume flexibility. In this paper, we develop novel queuing network models to estimate the performance of both single-tier and multi-tier shutt

  7. Modelling long term biodenitrification processes from column experiments: Insight in how feeding strategy affect hydraulic properties

    Science.gov (United States)

    Rodríguez-Escales, Paula; Folch, Albert; van Breukelen, Boris; Vidal-Gavilan, Georgina; Sanchez-Vila, Xavier

    2015-04-01

    We developed a reactive transport model that reproduced a 342 days long laboratory column experiment of biodenitrification processes with different injection strategies in terms of frequency (daily, weekly) and C:N ratio. Furthermore, we evaluated changes in hydraulic properties as result of biodenitrification. It was found that biodenitrification promoted the transition from normal to anomalous (non-Fickian) transport due to the increase of heterogeneity in hydraulic parameters. Comparing the breakthrough curves from two conservative bromide tracer tests performed at the beginning and at the end of the experiment, two significant features were observed: first, an increase in dispersivity, and second, a transition from a curve that can be modeled with an advection-dispersion equation to a different one that can be modeled using a dual domain mass transfer model. This behavior is associated to the presence of a diffusive layer promoted by biofilm growth during the last 100 days of the experiment. Regarding the injection conditions, it was found that besides other parameters described in the literature (nutrient loading, flow rate, and grain size), injection frequency significantly modifies dispersivity, being largest for continuous injection. Moreover, reducing the C:N ratio for optimizing costs was possible after a substantial biomass developed. A careful design of injection conditions and substrate rates can then be devised in specific cases to promote biodenitrification.

  8. The Extended Perturbation Method: New Insights on the New Keynesian Model

    DEFF Research Database (Denmark)

    Andreasen, Martin Møller; Kronborg, Anders Farver

    bound on inflation as implied by Calvo pricing. In contrast, extended perturbation generates stable dynamics as it enforces this bound. Extended perturbation also adds to existing evidence on downward nominal wage rigidities in the New Keynesian model, as we only find support for this friction when...

  9. 3D Modeling and Printing in History/Social Studies Classrooms: Initial Lessons and Insights

    Science.gov (United States)

    Maloy, Robert; Trust, Torrey; Kommers, Suzan; Malinowski, Allison; LaRoche, Irene

    2017-01-01

    This exploratory study examines the use of 3D technology by teachers and students in four middle school history/social studies classrooms. As part of a university-developed 3D Printing 4 Teaching & Learning project, teachers integrated 3D modeling and printing into curriculum topics in world geography, U.S. history, and government/civics.…

  10. Evolving dynamical regimes during secular cooling of terrestrial planets : insights and inferences from numerical models

    NARCIS (Netherlands)

    Thienen, Peter van

    2003-01-01

    Although plate tectonics is the present-day mode of geodynamics on Earth, it is not so on Mars and Venus, and probably also not during the early history of the Earth. In this thesis, the conditions under which plate tectonics may operate on terrestrial planets are investigated. Numerical model studi

  11. Controls on Yardang Morphology: Insights from Field Measurements, Lidar Topographic Analyses, and Numerical Modeling

    Science.gov (United States)

    Pelletier, J. D.; Kapp, P. A.

    2014-12-01

    Yardangs are streamlined bedforms sculpted by the wind and wind-blown sand. They can form as relatively resistant exposed rocks erode more slowly than surrounding exposed rocks, thus causing the more resistant rocks to stand higher in the landscape and deflect the wind and wind-blown sand into adjacent troughs in a positive feedback. How this feedback gives rise to streamlined forms that locally have a consistent size is not well understood theoretically. In this study we combine field measurements in the yardangs of Ocotillo Wells SVRA with analyses of airborne and terrestrial lidar datasets and numerical modeling to quantify and understand the controls on yardang morphology. The classic model for yardang morphology is that they evolve to an ideal 4:1 length-to-width aspect ratio that minimizes aerodynamic drag. We show using computational fluid dynamics (CFD) modeling that this model is incorrect: the 4:1 aspect ratio is the value corresponding to minimum drag for free bodies, i.e. obstacles around which air flows on all sides. Yardangs, in contrast, are embedded in Earth's surface. For such rough streamlined half-bodies, the aspect ratio corresponding to minimum drag is larger than 20:1. As an alternative to the minimum-drag model, we propose that the aspect ratio of yardangs not significantly influenced by structural controls is controlled by the angle of dispersion of the aerodynamic jet created as deflected wind and wind-blown sand exits the troughs between incipient yardang noses. Aerodynamic jets have a universal dispersion angle of 11.8 degrees, thus predicting a yardang aspect ratio of ~5:1. We developed a landscape evolution model that combines the physics of boundary layer flow with aeolian saltation and bedrock erosion to form yardangs with a range of sizes and aspect ratios similar to those observed in nature. Yardangs with aspect ratios both larger and smaller than 5:1 occur in the model since the strike and dip of the resistant rock unit also exerts

  12. Predicting hunter behavior of indigenous communities in the Ecuadorian Amazon: insights from a household production model

    Directory of Open Access Journals (Sweden)

    Enrique de la Montaña

    2015-12-01

    Full Text Available Many indigenous communities living in the Amazon rely on hunting and fishing to meet the majority of their protein needs. Despite the importance of these practices, few studies from the region have analyzed the socioeconomic drivers of hunting and fishing at the household level. We propose a household production model to assess the effect of key economic parameters on hunting and fishing in small indigenous communities located in the Ecuadorian Amazon, whose principal source of protein is derived from hunting and fishing. The model was validated using empirical data from two communities that reflect different levels of market integration and forest conservation. Demand and supply functions were generated from household data gathered over 19 months. Elasticities were derived to determine the sensitivity of the decision to engage in hunting to exogenous parameters such as off-farm wages, hunting costs, bushmeat price, penalties for the illegal sale of bushmeat, and biological characteristics of the game species. After calibrating the model, we simulated changes in the key economic parameters. The parameter that most directly affected hunting activity in both communities was off-farm wages. Simulating a 10% wage increase resulted in a 16-20% reduction in harvested biomass, while a 50% increase diminished harvested biomass by > 50%. Model simulations revealed that bushmeat price and penalties for illegal trade also had important effects on hunter behavior in terms of amount of bushmeat sold, but not in terms of total harvest. As a tool for understanding hunters' economic decision-making, the model provides a basis for developing strategies that promote sustainable hunting and wildlife conservation while protecting indigenous livelihoods.

  13. Random-field Ising model: Insight from zero-temperature simulations

    Directory of Open Access Journals (Sweden)

    P.E. Theodorakis

    2014-12-01

    Full Text Available We enlighten some critical aspects of the three-dimensional (d=3 random-field Ising model (RFIM from simulations performed at zero temperature. We consider two different, in terms of the field distribution, versions of model, namely a Gaussian RFIM and an equal-weight trimodal RFIM. By implementing a computational approach that maps the ground-state of the system to the maximum-flow optimization problem of a network, we employ the most up-to-date version of the push-relabel algorithm and simulate large ensembles of disorder realizations of both models for a broad range of random-field values and systems sizes V=LxLxL, where L denotes linear lattice size and Lmax=156. Using as finite-size measures the sample-to-sample fluctuations of various quantities of physical and technical origin, and the primitive operations of the push-relabel algorithm, we propose, for both types of distributions, estimates of the critical field hmax and the critical exponent ν of the correlation length, the latter clearly suggesting that both models share the same universality class. Additional simulations of the Gaussian RFIM at the best-known value of the critical field provide the magnetic exponent ratio β/ν with high accuracy and clear out the controversial issue of the critical exponent α of the specific heat. Finally, we discuss the infinite-limit size extrapolation of energy- and order-parameter-based noise to signal ratios related to the self-averaging properties of the model, as well as the critical slowing down aspects of the algorithm.

  14. New insights into the organic carbon export in the Mediterranean Sea from 3-D modeling

    Directory of Open Access Journals (Sweden)

    A. Guyennon

    2015-04-01

    Full Text Available The Mediterranean Sea is one of the most oligotrophic regions of the oceans, and nutrients have been shown to limit both phytoplankton and bacterial activities. This has direct implications on the stock of dissolved organic carbon (DOC, whose high variability has already been well-documented even if measurements are still sparse and are associated with important uncertainties. We here propose a Mediterranean Basin-scale view of the export of organic carbon, under its dissolved and particulate forms. For this purpose, we have used a coupled model combining a mechanistic biogeochemical model (Eco3M-MED and a high-resolution (eddy-resolving hydrodynamic simulation (NEMO-MED12. This is the first Basin-scale application of the biogeochemical model Eco3M-MED and is shown to reproduce the main spatial and seasonal biogeochemical characteristics of the Mediterranean Sea. Model estimations of carbon export are of the same order of magnitude as estimations from in situ observations, and their respective spatial patterns are consistent with each other. As for surface chlorophyll, nutrient concentrations, and productivity, strong differences between the Western and Eastern Basins are evidenced by the model for organic carbon export, with only 39% of organic carbon (particulate and dissolved export taking place in the Western Basin. The major result is that except for the Alboran Sea, dissolved organic carbon (DOC contribution to organic carbon export is higher than that of particulate (POC in the whole Basin, especially in the Eastern Basin. This paper also investigates the seasonality of DOC and POC exports as well as the differences in the processes involved in DOC and POC exports.

  15. Biogenic silica dissolution in diatom aggregates: insights from reactive transport modelling

    KAUST Repository

    Moriceau, B

    2014-12-15

    © Inter-Research 2014. Diatom aggregates contribute significantly to the vertical sinking flux of particulate matter in the ocean. These fragile structures form a specific microhabitat for the aggregated cells, but their internal chemical and physical characteristics remain largely unknown. Studies on the impact of aggregation on the Si cycle led to apparent inconsistency. Despite a lower biogenic silica (bSiO2) dissolution rate and diffusion of the silicic acid (dSi) being similar in aggregates and in sea-water, dSi surprisingly accumulates in aggregates. A reaction-diffusion model helps to clarify this incoherence by reconstructing dSi accumulation measured during batch experiments with aggregated and non-aggregated Skeletonema marinoi and Chaetoceros decipiens. The model calculates the effective bSiO2 dissolution rate as opposed to the experimental apparent bSiO2 dissolution rate, which is the results of the effective dissolution of bSiO2 and transport of dSi out of the aggregate. In the model, dSi transport out of the aggregate is modulated by alternatively considering retention (decrease of the dSi diffusion constant) and adsorption (reversible chemical bonds between dSi and the aggregate matrix) processes. Modelled bSiO2 dissolution is modulated by the impact of dSi concentration inside aggregates and diatom viability, as enhanced persistence of metabolically active diatoms has been observed in aggregates. Adsorption better explains dSi accumulation within and outside aggregates, raising the possible importance of dSi travelling within aggregates to the deep sea (potentially representing 20% of the total silica flux). The model indicates that bSiO2 dissolution is effectively decreased in aggregates mainly due to higher diatom viability but also to other parameters discussed herein.

  16. Characterizing mercury concentrations and fluxes in a Coastal Plain watershed: Insights from dynamic modeling and data

    Science.gov (United States)

    Golden, H.E.; Knightes, C.D.; Conrads, P.A.; Davis, G.M.; Feaster, T.D.; Journey, C.A.; Benedict, S.T.; Brigham, M.E.; Bradley, P.M.

    2012-01-01

    Mercury (Hg) is one of the leading water quality concerns in surface waters of the United States. Although watershed-scale Hg cycling research has increased in the past two decades, advances in modeling watershed Hg processes in diverse physiographic regions, spatial scales, and land cover types are needed. The goal of this study was to assess Hg cycling in a Coastal Plain system using concentrations and fluxes estimated by multiple watershed-scale models with distinct mathematical frameworks reflecting different system dynamics. We simulated total mercury (HgT, the sum of filtered and particulate forms) concentrations and fluxes from a Coastal Plain watershed (McTier Creek) using three watershed Hg models and an empirical load model. Model output was compared with observed in-stream HgT. We found that shallow subsurface flow is a potentially important transport mechanism of particulate HgT during periods when connectivity between the uplands and surface waters is maximized. Other processes (e.g., stream bank erosion, sediment re-suspension) may increase particulate HgT in the water column. Simulations and data suggest that variable source area (VSA) flow and lack of rainfall interactions with surface soil horizons result in increased dissolved HgT concentrations unrelated to DOC mobilization following precipitation events. Although flushing of DOC-HgT complexes from surface soils can also occur during this period, DOC-complexed HgT becomes more important during base flow conditions. TOPLOAD simulations highlight saturated subsurface flow as a primary driver of daily HgT loadings, but shallow subsurface flow is important for HgT loads during high-flow events. Results suggest limited seasonal trends in HgT dynamics.

  17. Nitrogen Fixation by Gliding Arc Plasma: Better Insight by Chemical Kinetics Modelling.

    Science.gov (United States)

    Wang, Weizong; Patil, Bhaskar; Heijkers, Stjin; Hessel, Volker; Bogaerts, Annemie

    2017-05-22

    The conversion of atmospheric nitrogen into valuable compounds, that is, so-called nitrogen fixation, is gaining increased interest, owing to the essential role in the nitrogen cycle of the biosphere. Plasma technology, and more specifically gliding arc plasma, has great potential in this area, but little is known about the underlying mechanisms. Therefore, we developed a detailed chemical kinetics model for a pulsed-power gliding-arc reactor operating at atmospheric pressure for nitrogen oxide synthesis. Experiments are performed to validate the model and reasonable agreement is reached between the calculated and measured NO and NO2 yields and the corresponding energy efficiency for NOx formation for different N2 /O2 ratios, indicating that the model can provide a realistic picture of the plasma chemistry. Therefore, we can use the model to investigate the reaction pathways for the formation and loss of NOx . The results indicate that vibrational excitation of N2 in the gliding arc contributes significantly to activating the N2 molecules, and leads to an energy efficient way of NOx production, compared to the thermal process. Based on the underlying chemistry, the model allows us to propose solutions on how to further improve the NOx formation by gliding arc technology. Although the energy efficiency of the gliding-arc-based nitrogen fixation process at the present stage is not comparable to the world-scale Haber-Bosch process, we believe our study helps us to come up with more realistic scenarios of entering a cutting-edge innovation in new business cases for the decentralised production of fertilisers for agriculture, in which low-temperature plasma technology might play an important role. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Insights on the role of accurate state estimation in coupled model parameter estimation by a conceptual climate model study

    Science.gov (United States)

    Yu, Xiaolin; Zhang, Shaoqing; Lin, Xiaopei; Li, Mingkui

    2017-03-01

    The uncertainties in values of coupled model parameters are an important source of model bias that causes model climate drift. The values can be calibrated by a parameter estimation procedure that projects observational information onto model parameters. The signal-to-noise ratio of error covariance between the model state and the parameter being estimated directly determines whether the parameter estimation succeeds or not. With a conceptual climate model that couples the stochastic atmosphere and slow-varying ocean, this study examines the sensitivity of state-parameter covariance on the accuracy of estimated model states in different model components of a coupled system. Due to the interaction of multiple timescales, the fast-varying atmosphere with a chaotic nature is the major source of the inaccuracy of estimated state-parameter covariance. Thus, enhancing the estimation accuracy of atmospheric states is very important for the success of coupled model parameter estimation, especially for the parameters in the air-sea interaction processes. The impact of chaotic-to-periodic ratio in state variability on parameter estimation is also discussed. This simple model study provides a guideline when real observations are used to optimize model parameters in a coupled general circulation model for improving climate analysis and predictions.

  19. Inflammation Following Traumatic Brain Injury in Humans: Insights from Data-Driven and Mechanistic Models into Survival and Death

    Directory of Open Access Journals (Sweden)

    Andrew Abboud

    2016-09-01

    Full Text Available Inflammation induced by traumatic brain injury (TBI is a complex mediator of morbidity and mortality. We have previously demonstrated the utility of both data-driven and mechanistic models in settings of traumatic injury. We hypothesized that differential dynamic inflammation programs characterize TBI survivors vs. non-survivors, and sought to leverage computational modeling to derive novel insights into this life/death bifurcation. Thirteen inflammatory cytokines and chemokines were determined using Luminex™ in serial cerebrospinal fluid (CSF samples from 31 TBI patients over 5 days. In this cohort, 5 were non-survivors (Glasgow Outcome Scale [GOS] score = 1 and 26 were survivors (GOS > 1. A Pearson correlation analysis of initial injury (Glasgow Coma Scale [GCS] vs. GOS suggested that survivors and non-survivors had distinct clinical response trajectories to injury. Statistically significant differences in interleukin (IL-4, IL-5, IL-6, IL-8, IL-13, and tumor necrosis factor-α (TNF-α were observed between TBI survivors vs. non-survivors over 5 days. Principal Component Analysis and Dynamic Bayesian Network inference suggested differential roles of chemokines, TNF-α, IL-6, and IL-10, based upon which an ordinary differential equation model of TBI was generated. This model was calibrated separately to the time course data of TBI survivors vs. non-survivors as a function of initial GCS. Analysis of parameter values in ensembles of simulations from these models suggested differences in microglial and damage responses in TBI survivors vs. non-survivors. These studies suggest the utility of combined data-driven and mechanistic models in the context of human TBI.

  20. Inflammation Following Traumatic Brain Injury in Humans: Insights from Data-Driven and Mechanistic Models into Survival and Death

    Science.gov (United States)

    Abboud, Andrew; Mi, Qi; Puccio, Ava; Okonkwo, David; Buliga, Marius; Constantine, Gregory; Vodovotz, Yoram

    2016-01-01

    Inflammation induced by traumatic brain injury (TBI) is a complex mediator of morbidity and mortality. We have previously demonstrated the utility of both data-driven and mechanistic models in settings of traumatic injury. We hypothesized that differential dynamic inflammation programs characterize TBI survivors vs. non-survivors, and sought to leverage computational modeling to derive novel insights into this life/death bifurcation. Thirteen inflammatory cytokines and chemokines were determined using Luminex™ in serial cerebrospinal fluid (CSF) samples from 31 TBI patients over 5 days. In this cohort, 5 were non-survivors (Glasgow Outcome Scale [GOS] score = 1) and 26 were survivors (GOS > 1). A Pearson correlation analysis of initial injury (Glasgow Coma Scale [GCS]) vs. GOS suggested that survivors and non-survivors had distinct clinical response trajectories to injury. Statistically significant differences in interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, and tumor necrosis factor-α (TNF-α) were observed between TBI survivors vs. non-survivors over 5 days. Principal Component Analysis and Dynamic Bayesian Network inference suggested differential roles of chemokines, TNF-α, IL-6, and IL-10, based upon which an ordinary differential equation model of TBI was generated. This model was calibrated separately to the time course data of TBI survivors vs. non-survivors as a function of initial GCS. Analysis of parameter values in ensembles of simulations from these models suggested differences in microglial and damage responses in TBI survivors vs. non-survivors. These studies suggest the utility of combined data-driven and mechanistic models in the context of human TBI. PMID:27729864

  1. Commentary on the Liquid Metallic Hydrogen Model of the Sun: Insight Relative to Coronal Holes, Sunspots, and Solar Activity

    Directory of Open Access Journals (Sweden)

    Robitaille P.-M.

    2013-04-01

    Full Text Available While mankind will always remain unable to sample the interior of the Sun, the presence of sunspots and coronal holes can provide clues as to its subsurface structure. Insight relative to the solar body can also be gained by recognizing that the Sun must exist in the condensed state and support a discrete lattice structure, as required for the production of its continuous spectrum. In this regard, the layered liquid metallic hydrogen lattice advanced as a condensed model of the Sun (Robitaille P.M. Liquid Metallic Hydrogen: A Building Block for the Liquid Sun. Progr. Phys ., 2011, v. 3, 60–74; Robitaille P.M. Liquid Metallic Hydrogen II: A Critical Assessment of Current and Primordial Helium Levels in Sun. Progr. Phys ., 2013, v. 2, 35–47; Robitaille J.C. and Robitaille P.M. Liquid Metallic Hydrogen III. Intercalation and Lattice Exclusion Versus Gravitational Settling and Their Consequences Relative to Internal Structure, Surface Activity, and Solar Winds in the Sun. Progr. Phys ., 2013, v. 2, in press provides the ability to add structure to the solar interior. This constitutes a significant advantage over the gaseous solar models. In fact, a layered liquid metallic hydrogen lattice and the associated intercalation of non-hydrogen elements can help to account for the position of sunspots and coronal holes. At the same time, this model provides a greater understanding of the mechanisms which drive solar winds and activity.

  2. Pore-scale network modeling of microbially induced calcium carbonate precipitation: Insight into scale dependence of biogeochemical reaction rates

    Science.gov (United States)

    Qin, Chao-Zhong; Hassanizadeh, S. Majid; Ebigbo, Anozie

    2016-11-01

    The engineering of microbially induced calcium carbonate precipitation (MICP) has attracted much attention in a number of applications, such as sealing of CO2 leakage pathways, soil stabilization, and subsurface remediation of radionuclides and toxic metals. The goal of this work is to gain insight into pore-scale processes of MICP and scale dependence of biogeochemical reaction rates. This will help us develop efficient field-scale MICP models. In this work, we have developed a comprehensive pore-network model for MICP, with geochemical speciation calculated by the open-source PHREEQC module. A numerical pseudo-3-D micromodel as the computational domain was generated by a novel pore-network generation method. We modeled a three-stage process in the engineering of MICP including the growth of biofilm, the injection of calcium-rich medium, and the precipitation of calcium carbonate. A number of test cases were conducted to illustrate how calcite precipitation was influenced by different operating conditions. In addition, we studied the possibility of reducing the computational effort by simplifying geochemical calculations. Finally, the effect of mass transfer limitation of possible carbonate ions in a pore element on calcite precipitation was explored.

  3. Streaming potential modeling in fractured rock: Insights into the identification of hydraulically active fractures

    CERN Document Server

    Roubinet, D; Jougnot, D; Irving, J

    2016-01-01

    Numerous field experiments suggest that the self-potential (SP) geophysical method may allow for the detection of hydraulically active fractures and provide information about fracture properties. However, a lack of suitable numerical tools for modeling streaming potentials in fractured media prevents quantitative interpretation and limits our understanding of how the SP method can be used in this regard. To address this issue, we present a highly efficient two-dimensional discrete-dual-porosity approach for solving the fluid flow and associated self-potential problems in fractured rock. Our approach is specifically designed for complex fracture networks that cannot be investigated using standard numerical methods. We then simulate SP signals associated with pumping conditions for a number of examples to show that (i) accounting for matrix fluid flow is essential for accurate SP modeling and (ii) the sensitivity of SP to hydraulically active fractures is intimately linked with fracture-matrix fluid interaction...

  4. Large-scale modeling provides insights into Arabidopsis's acclimation to changing light and temperature conditions.

    Science.gov (United States)

    Töpfer, Nadine; Niokoloski, Zoran

    2013-09-01

    Classical flux balance analysis predicts steady-state flux distributions that maximize a given objective function. A recent study, Schuetz et al., (1) demonstrated that competing objectives constrain the metabolic fluxes in E. coli. For plants, with multiple cell types, fulfilling different functions, the objectives remain elusive and, therefore, hinder the prediction of actual fluxes, particularly for changing environments. In our study, we presented a novel approach to predict flux capacities for a large collection of metabolic pathways under eight different temperature and light conditions. (2) By integrating time-series transcriptomics data to constrain the flux boundaries of the metabolic model, we captured the time- and condition-specific state of the network. Although based on a single time-series experiment, the comparison of these capacities to a novel null model for transcript distribution allowed us to define a measure for differential behavior that accounts for the underlying network structure and the complex interplay of metabolic pathways.

  5. How do subduction processes contribute to forearc Andean uplift? Insights from numerical models

    Science.gov (United States)

    Martinod, J.; Regard, V.; Letourmy, Y.; Henry, H.; Hassani, R.; Baratchart, S.; Carretier, S.

    2016-05-01

    We present numerical models to study how changes in the process of subduction may explain the observed Quaternary uplift of the Andean forearc region. Indeed, most segments of the South American Pacific coasts between 16 and 32° S have been uplifting since the Lower Pleistocene, following a period of stability of the forearc region. Models confirm that local uplift is expected to occur above ridges, this phenomenon being predominant in central Peru where the Nazca Ridge is subducting. We investigate the effects of slab pull, interplate friction and convergence velocity on the vertical displacements of the overriding plate. We propose that the global tendency to coastal uplift is accompanying the deceleration of the Nazca-South America convergence that occurred in the Pleistocene. In contrast, forearc subsidence may accompany increasing convergence velocities, as suggested by the subsidence history of the South America active margin.

  6. Poly (lactic-co-glycolic acid) controlled release systems: experimental and modeling insights

    Science.gov (United States)

    Hines, Daniel J.; Kaplan, David L.

    2013-01-01

    Poly-lactic-co-glycolic acid (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in drug release device formulation. Mathematical modeling is a useful tool for identifying, characterizing, and predicting the mechanisms of controlled release. The advantages and limitations of poly (lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled release technology that utilize PLGA. Mathematical modeling applied towards controlled release rates from PLGA-based devices will also be discussed to provide a complete picture of state of the art understanding of the control achievable with this polymeric system, as well as the limitations. PMID:23614648

  7. Poly(lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights.

    Science.gov (United States)

    Hines, Daniel J; Kaplan, David L

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) has been the most successful polymeric biomaterial used in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in the formulation of drug release devices. Mathematical modeling is a useful tool for identifying, characterizing, and predicting mechanisms of controlled release. The advantages and limitations of poly(lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled-release technology that utilize PLGA. Mathematical modeling applied toward controlled-release rates from PLGA-based devices also will be discussed to provide a complete picture of a state-of-the-art understanding of the control that can be achieved with this polymeric system, as well as the limitations.

  8. Structural insights into a high affinity nanobody:antigen complex by homology modelling

    DEFF Research Database (Denmark)

    Skottrup, Peter Durand

    2017-01-01

    B binding were identified and used as input to the docking. Furthermore, residues likely involved in the RgpB epitope was identified based upon RgpB:RgpA alignment and analysis of residue surface accessibility. CDR residues and putitative RgpB epitope residues were used as input to an information-driven...... flexible docking approach using the HADDOCK server. Analysis of the VHH7:RgpB model demonstrated that the epitope was found in the immunoglobulin-like domain and residue pairs located at the molecular paratope:epitope interface important for complex stability was identified. Collectively, the VHH7 homology...... model and VHH7:RgpB docking supplies knowledge of the residues involved in the high affinity interaction. This information could prove valuable in the design of an antibody-drug conjugate for specific RgpB targeting....

  9. A model of radiation-induced cell killing: insights into mechanisms and applications for hadron therapy.

    Science.gov (United States)

    Ballarini, Francesca; Altieri, Saverio; Bortolussi, Silva; Giroletti, Elio; Protti, Nicoletta

    2013-09-01

    A mechanism-based, two-parameter biophysical model of cell killing was developed with the aim of elucidating the mechanisms underlying radiation-induced cell death and predicting cell killing by different radiation types, including protons and carbon ions at energies and doses of interest for cancer therapy. The model assumed that certain chromosome aberrations (dicentrics, rings and large deletions, called "lethal aberrations") lead to clonogenic inactivation, and that aberrations derive from μm-scale misrejoining of chromatin fragments, which in turn are produced by "dirty" double-strand breaks called "cluster lesions" (CLs). The average numbers of CLs per Gy per cell were left as a semi-free parameter and the threshold distance for chromatin-fragment rejoining was defined the second parameter. The model was "translated" into Monte Carlo code and provided simulated survival curves, which were compared with survival data on V79 cells exposed to protons, carbon ions and X rays. The agreement was good between simulations and survival data and supported the assumptions of the model at least for doses up to a few Gy. Dicentrics, rings and large deletions were found to be lethal not only for AG1522 cells exposed to X rays, as already reported by others, but also for V79 cells exposed to protons and carbon ions of different energies. Furthermore, the derived CL yields suggest that the critical DNA lesions leading to clonogenic inactivation are more complex than "clean" DSBs. After initial validation, the model was applied to characterize the particle and LET dependence of proton and carbon cell killing. Consistent with the proton data, the predicted fraction of inactivated cells after 2 Gy protons was 40-50% below 7.7 keV/μm, increased by a factor ∼1.6 between 7.7-30.5 keV/μm, and decreased by a factor ∼1.1 between 30.5-34.6 keV/μm. These LET values correspond to proton energies below a few MeV, which are always present in the distal region of hadron therapy

  10. The Fate of the Red Cells: Insights from Two Models of Severe Malarial Anemia

    Science.gov (United States)

    2011-03-07

    Couper KN. Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease. Parasitology 2010;137:755-772...of uninfected erythrocytes. Parasitology 1999;119 ( Pt 2):127-133. 23. Price RN, Simpson JA, Nosten F et al. Factors contributing to anemia after...Br.Med.Bull. 1972;28:22-27. 62. Sabchareon A, Burnouf T, Ouattara D et al. Parasitologic and clinical human response to immunoglobulin

  11. Novel insight into glucagon receptor action: lessons from knockout and transgenic mouse models

    OpenAIRE

    Vuguin, P. M.; Charron, M. J.

    2011-01-01

    Using knockout and transgenic technology, genetically modified animal models allowed us to understand the role of glucagon signalling in metabolism. Mice with a global deletion of the glucagon receptor gene (Gcgr) were designed using gene targeting. The phenotype of Gcgr−/− mouse provided important clues about the role of Gcgr in foetal growth, pancreatic development and glucose and lipid homeostasis. The lack of Gcgr activation was associated with: (i) hypoglycaemic pregnancies, poor foetal ...

  12. Modeling hydrodynamics of large lagoons: Insights from the Albemarle-Pamlico Estuarine System

    Science.gov (United States)

    Clunies, Gregory J.; Mulligan, Ryan P.; Mallinson, David J.; Walsh, J. P.

    2017-04-01

    Large estuaries are influenced by winds over adjacent coastal ocean and land areas causing significant spatial variations in water levels, currents and surface waves. In this study we apply a numerical model to simulate hydrodynamics and waves in the Albemarle-Pamlico Estuarine System, a large and shallow back-barrier basin in eastern North Carolina, over a one-month study period (September 2008) with observations from several storm wind events of differing time scales and directions. Model performance is evaluated for a spatially varying wind field from the North American Regional Reanalysis (NARR) dataset in comparison to spatially uniform forcing from wind observations at offshore, coastal and land-based sites across the region. A spatially uniform wind field from offshore winds observations results in statistically better hydrodynamic simulations of water levels (R = 0.88) in the estuaries than NARR (R = 0.48) after comparison with measurements and indicates the importance of strong marine winds over most of the estuary surface area. The influence of a prominent bathymetric feature on hydrodynamics in Pamlico Sound is also investigated by numerically removing a 30 km long and 2-3 m deep shoal from the model grid and replacing it with an idealized depth of 6 m. The removal of the shoal increases water level setup by 14% at the estuarine shoreline, decreases current magnitudes by up to 40% in the shoal region and increases significant wave heights locally by up to 25% in the sound, indicating the importance of this relict geomorphic feature as a major control on the hydrodynamic response of the system during wind events. The results suggest that increasing the water depth over the shoal can lead to higher storm surges and wave heights with the possibility of increased inundation and erosion of the back-barrier and mainland coastal regions. The complex bathymetry and marine wind influence are critical input conditions for modeling large and shallow lagoonal

  13. Effect of aseismic ridge subduction on slab geometry and overriding plate deformation: Insights from analogue modeling

    OpenAIRE

    Martinod, Joseph; Guillaume, Benjamin; Espurt, Nicolas; Faccenna, Claudio; Funiciello, Francesca; Regard, Vincent

    2013-01-01

    International audience; We present analogue models simulating the subduction of a buoyant ridge beneath an advancing overriding plate whose velocity is imposed by lateral boundary conditions. We analyze the 3D geometry of the slab, the deformation and topography of the overriding plate. Ridge subduction diminishes the dip of the slab, eventually leading to the appearance of a horizontal slab segment. This result contrasts with that obtained in free subduction experiments, in which ridge subdu...

  14. DRAVET SYNDROME Insights into pathophysiology and therapy from a mouse model of Dravet syndrome

    OpenAIRE

    Oakley, John C; Kalume, Franck; Catterall, William A.

    2011-01-01

    Mutations in voltage-gated sodium channels are associated with epilepsy syndromes with a wide range of severity. Complete loss of function in the Nav1.1 channel encoded by the SCN1A gene is associated with severe myoclonic epilepsy in infancy (SMEI), a devastating infantile-onset epilepsy with ataxia, cognitive dysfunction, and febrile and afebrile seizures resistant to current medications. Genetic mouse models of SMEI have been created that strikingly recapitulate the SMEI phenotype includin...

  15. Combinatorial pharmacophore modeling of organic cation transporter 2 (OCT2) inhibitors: insights into multiple inhibitory mechanisms.

    Science.gov (United States)

    Xu, Yuan; Liu, Xian; Li, Shanshan; Zhou, Nannan; Gong, Likun; Luo, Cheng; Luo, Xiaomin; Zheng, Mingyue; Jiang, Hualiang; Chen, Kaixian

    2013-12-02

    Organic cation transporter 2 (OCT2) is responsible for the entry step of many drugs in renal elimination, of which the changing activity may cause unwanted drug-drug interactions (DDIs). To develop drugs with favorable safety profile and provide instruction for rational clinical drug administration, it is of great interest to investigate the multiple mechanisms of OCT2 inhibition. In this study, we designed a combinatorial scheme to screen the optimum combination of pharmacophores from a pool of hypotheses established based on 162 OCT2 inhibitors. Among them, one single pharmacophore hypothesis represents a potential binding mode that may account for one unique inhibitory mechanism, and the obtained pharmacophore combination describes the multimechanisms of OCT2 inhibition. The final model consists of four individual pharmacophores, i.e., DHPR18, APR2, PRR5 and HHR4. Given a query ligand, it is considered as an inhibitor if it matches at least one of the hypotheses, or a noninhibitor if it fails to match any of four hypotheses. Our combinatorial pharmacophore model performs reasonably well to discriminate inhibitors and noninhibitors, yielding an overall accuracy around 0.70 for a test set containing 81 OCT2 inhibitors and 218 noninhibitors. Intriguingly, we found that the number of matched hypotheses was positively correlated with inhibition rate, which coincides with the pharmacophore modeling result of P-gp substrate binding. Further analysis suggested that the hypothesis PRR5 was responsible for competitive inhibition of OCT2, and other hypotheses were important for interaction between the inhibitor and OCT2. In light of the results, a hypothetical model for inhibiting transporting mediated by OCT2 was proposed.

  16. Understanding Chinese American Adolescents’ Developmental Outcomes: Insights From the Family Stress Model

    OpenAIRE

    Benner, Aprile D.; Kim, Su Yeong

    2010-01-01

    In this brief report, we investigated whether the Family Stress Model could be replicated with a sample of Chinese American families. Path analyses with 444 adolescents and their parents provided support for the model’s generalizability. Specifically, mothers’ and fathers’ reports of economic status (i.e., income, financial and job instability) were associated with parents’ economic stress. Economic stress and economic status were related to parental depressive symptoms, which, in turn, were ...

  17. Reducing Ambulance Diversion at Hospital and Regional Levels: Systemic Review of Insights from Simulation Models

    Directory of Open Access Journals (Sweden)

    M Kit Delgado

    2013-09-01

    Full Text Available Introduction: Optimal solutions for reducing diversion without worsening emergency department (ED crowding are unclear. We performed a systematic review of published simulation studies to identify: 1 the tradeoff between ambulance diversion and ED wait times; 2 the predicted impact of patient flow interventions on reducing diversion; and 3 the optimal regional strategy for reducing diversion.Methods: Data Sources: Systematic review of articles using MEDLINE, Inspec, Scopus. Additional studies identified through bibliography review, Google Scholar, and scientific conference proceedings. Study Selection: Only simulations modeling ambulance diversion as a result of ED crowding or inpatient capacity problems were included. Data extraction: Independent extraction by two authors using predefined data fields.Results: We identified 5,116 potentially relevant records; 10 studies met inclusion criteria. In models that quantified the relationship between ED throughput times and diversion, diversion was found to only minimally improve ED waiting room times. Adding holding units for inpatient boarders and ED-based fast tracks, improving lab turnaround times, and smoothing elective surgery caseloads were found to reduce diversion considerably. While two models found a cooperative agreement between hospitals is necessary to prevent defensive diversion behavior by a hospital when a nearby hospital goes on diversion, one model found there may be more optimal solutions for reducing region wide wait times than a regional ban on diversion.Conclusion: Smoothing elective surgery caseloads, adding ED fast tracks as well as holding units for inpatient boarders, improving ED lab turnaround times, and implementing regional cooperative agreements among hospitals. [West J Emerg Med. 2013;14(5:489-498.

  18. Insights into the formation and dynamics of coignimbrite plumes from one-dimensional models

    Science.gov (United States)

    Engwell, S. L.; de'Michieli Vitturi, M.; Esposti Ongaro, T.; Neri, A.

    2016-06-01

    Coignimbrite plumes provide a common and effective mechanism by which large volumes of fine-grained ash are injected into the atmosphere. Nevertheless, controls on formation of these plumes as a function of eruptive conditions are still poorly constrained. Herein, two 1-D axysymmetric steady state models were coupled, the first describing the parent pyroclastic density current and the second describing plume rise. Global sensitivity analysis is applied to investigate controls on coignimbrite plume formation and describe coignimbrite source and the maximum plume height attained. For a range of initial mass flow rates between 108 and 1010 kg/s, modeled liftoff distance (the distance at which neutral buoyancy is attained), assuming radial supercritical flow, is controlled by the initial flow radius, gas mass fraction, flow thickness, and temperature. The predicted decrease in median grain size between flow initiation and plume liftoff is negligible. Calculated initial plume vertical velocities, assuming uniform liftoff velocity over the pyroclastic density current invasion area, are much greater (several tens of m/s) than those previously used in modeling coignimbrite plumes (1 m/s). Such velocities are inconsistent with the fine grain size of particles lofted into coignimbrite plumes, highlighting an unavailability of large clasts, possibly due to particle segregation within the flow, prior to plume formation. Source radius and initial vertical velocity have the largest effect on maximum plume height, closely followed by initial temperature. Modeled plume heights are between 25 and 47 km, comparable with Plinian eruption columns, highlighting the potential of such events for distributing fine-grained ash over significant areas.

  19. Dense Root Removal by Asymmetric Delamination in Sierra Nevada, California: Insights from Numerical Modeling

    Science.gov (United States)

    Valera, J.; Negredo, A. M.; Billen, M.

    2008-12-01

    Recent studies provide compelling evidence for an event of removal of lithospheric mantle in southern -and possibly central- Sierra Nevada (SN) mountains, California (Zandt et al., Nature, 431, 2004). A sequential history of foundering of the ultramafic root of the Sierra Nevada batholith, with a pronounced asymmetric flow, is proposed to explain a number of geophysical and geological observations, including a fast seismic velocity in the mantle located to the west of the SN crest, a gap in the Moho, recent subsidence and tilting of the Sierra Nevada, and a change in mineralogy of the xenolith population recorded at the surface. In the present study we focus on the quantitative evaluation of this conceptual model. We apply new thermo- mechanical algorithms, developed in MATLAB code, suitable to study the temporal evolution of laterally migrating lithospheric delamination. The motion equation, formulated in terms of the stream function, and the coupled thermal equation are solved applying finite difference techniques. Our physical modeling is shown to properly reproduce the first order features of the conceptual model for lithospheric delamination in the Sierra Nevada. We investigate the evolution of a dense ultramafic root, which brings about a Rayleigh-Taylor gravitational instability. Following our preliminary results, the presence of a fluid-weakened lithosphere, located just east of Sierra Nevada, is required to reproduce the asymmetric development of this instability, as previously proposed by Zandt et al. (2004). This weak rheology zone, which is modeled by means of a reduced viscosity, is shown to enable the ascent of asthenospheric material and westward propagation of delamination. Our predictions are also consistent with the previous inference of the V-shaped cone of crust being dragged down into the downwelling mantle (i.e., the Moho gap). Present results highlight that viscous drag is also likely responsible for present-day surface subsidence.

  20. 16 CFR 502.101 - Introductory offers.

    Science.gov (United States)

    2010-01-01

    ... FAIR PACKAGING AND LABELING ACT Retail Sale Price Representations § 502.101 Introductory offers. (a... retail sale at a price lower than the anticipated ordinary and customary retail sale price. (b) The... duration in excess of 6 months. (4) At the time of making the introductory offer promotion, the...

  1. 16 CFR 238.2 - Initial offer.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Initial offer. 238.2 Section 238.2 Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES AGAINST BAIT ADVERTISING § 238.2 Initial offer. (a) No statement or illustration should be used in any advertisement...

  2. 7 CFR 3560.656 - Incentives offers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Incentives offers. 3560.656 Section 3560.656... AGRICULTURE DIRECT MULTI-FAMILY HOUSING LOANS AND GRANTS Housing Preservation § 3560.656 Incentives offers. (a....653(d), incentives to agree to the restrictive-use period in § 3560.662 if the following conditions...

  3. An offer you can’t refuse

    OpenAIRE

    Fletcher, Roland

    2001-01-01

    The general requirements of a valid contract must contain an offer, acceptance, consideration, intention, capacity and if necessary the correct formation, eg, does the contract have to be in writing. The focus of this article will be on offer, acceptance, consideration and an invitation to treat when dealing with contracts concluded during an auction.

  4. 17 CFR 230.252 - Offering statement.

    Science.gov (United States)

    2010-04-01

    ..., language and pagination. The requirements for offering statements are the same as those specified in § 230... Officer, a majority of the members of its board of directors or other governing body, and each selling... that contains the following language: This offering statement shall become qualified on the...

  5. Home-care companies' offerings take off.

    Science.gov (United States)

    Lutz, S

    1991-06-03

    Some home infusion therapy companies have been the beneficiaries of cash infusions thanks to the bullish reception of public offerings this year. The lucrative industry, reimbursed primarily by private payers and one of the fastest growing in healthcare, has long been a favorite on Wall Street. The companies plan to use proceeds from the successful offerings to pay off debt and finance expansion.

  6. Exhumation and shortening distribution in the Taiwan orogen: insights from thermomechanical modeling

    Science.gov (United States)

    Mouthereau, F.; Yamato, P.; Burov, E.

    2007-12-01

    The Taiwan orogen has long been regarded as a case example for studying exhumation and erosion processes in association with mountain building. In the recent years, the increasing number of thermochronometric data (mainly ZFT and AFT ages) has allowed to better understanding the deep-seated tectonic processes. For instance, using thermomechanical wedge modelling, up to 50% of underplating has been proposed to explain the observed distribution of FT ages. So it would appear that a large amount of materials added to the orogen originated in more deeper and ductile parts of the crust. The nature of this additional flux (velocity, mechanism of deformation) is however poorly constrained in the current thermomechanical model. Our concern is to use a fully- coupled visco-elasto-plastic themomechanical numerical model to reproduce the observed FT ages and long- term distribution of shortening. To this aim we use the numerical code PARA(O)VOZ based on F.L.A.C. (Fast Lagrangian Analysis of Continua) algorithm. Our results show that the particular distribution of shortening across the Taiwan belt as well as the rapid exhumation and thermal conditions in the hinterland are well accounted for by two superimposed flows of upper and lower crustal rocks decoupled from the subducting Eurasian mantle.

  7. The slow demise of Easter Island: insights from a modelling investigation

    Directory of Open Access Journals (Sweden)

    Gunnar eBrandt

    2015-02-01

    Full Text Available The history of Easter Island and its supposed social-ecological collapse is often taken as a grim warning for the modern world. However, while the loss of a once lush palm forest is largely uncontested, causes and timing of the collapse remain controversial, because many paleoeological and archaeological data are afflicted with considerable uncertainties. According to a scenario named ecocide, the overharvesting of palm trees triggered a dramatic population decline, whereas a contrasting view termed genocide deems diseases and enslavement introduced by Europeans as the main reasons for the collapse. We propose here a third possibility, a slow demise, in which aspects of both ecocide and genocide concur to produce a long and slow decline of the society. We use a dynamic model to illustrate the consequences of the three alternatives with respect to the fate of the paleoecological system of the island.While none of the three model scenarios can be safely ruled out given the uncertainties of the available data, the slow demise appears to be the most plausible model scenario, in particular when considering the temporal pattern of deforestation as inferred from radiocarbon dates of charcoal remains.

  8. Spatial Impairment and Memory in Genetic Disorders: Insights from Mouse Models

    Directory of Open Access Journals (Sweden)

    Sang Ah Lee

    2017-02-01

    Full Text Available Research across the cognitive and brain sciences has begun to elucidate some of the processes that guide navigation and spatial memory. Boundary geometry and featural landmarks are two distinct classes of environmental cues that have dissociable neural correlates in spatial representation and follow different patterns of learning. Consequently, spatial navigation depends both on the type of cue available and on the type of learning provided. We investigated this interaction between spatial representation and memory by administering two different tasks (working memory, reference memory using two different environmental cues (rectangular geometry, striped landmark in mouse models of human genetic disorders: Prader-Willi syndrome (PWScrm+/p− mice, n = 12 and Beta-catenin mutation (Thr653Lys-substituted mice, n = 12. This exploratory study provides suggestive evidence that these models exhibit different abilities and impairments in navigating by boundary geometry and featural landmarks, depending on the type of memory task administered. We discuss these data in light of the specific deficits in cognitive and brain function in these human syndromes and their animal model counterparts.

  9. Spatial Impairment and Memory in Genetic Disorders: Insights from Mouse Models

    Science.gov (United States)

    Lee, Sang Ah; Tucci, Valter; Vallortigara, Giorgio

    2017-01-01

    Research across the cognitive and brain sciences has begun to elucidate some of the processes that guide navigation and spatial memory. Boundary geometry and featural landmarks are two distinct classes of environmental cues that have dissociable neural correlates in spatial representation and follow different patterns of learning. Consequently, spatial navigation depends both on the type of cue available and on the type of learning provided. We investigated this interaction between spatial representation and memory by administering two different tasks (working memory, reference memory) using two different environmental cues (rectangular geometry, striped landmark) in mouse models of human genetic disorders: Prader-Willi syndrome (PWScrm+/p− mice, n = 12) and Beta-catenin mutation (Thr653Lys-substituted mice, n = 12). This exploratory study provides suggestive evidence that these models exhibit different abilities and impairments in navigating by boundary geometry and featural landmarks, depending on the type of memory task administered. We discuss these data in light of the specific deficits in cognitive and brain function in these human syndromes and their animal model counterparts. PMID:28208764

  10. The role of alpha-rhythm states in perceptual learning: insights from experiments and computational models

    Science.gov (United States)

    Sigala, Rodrigo; Haufe, Sebastian; Roy, Dipanjan; Dinse, Hubert R.; Ritter, Petra

    2014-01-01

    During the past two decades growing evidence indicates that brain oscillations in the alpha band (~10 Hz) not only reflect an “idle” state of cortical activity, but also take a more active role in the generation of complex cognitive functions. A recent study shows that more than 60% of the observed inter-subject variability in perceptual learning can be ascribed to ongoing alpha activity. This evidence indicates a significant role of alpha oscillations for perceptual learning and hence motivates to explore the potential underlying mechanisms. Hence, it is the purpose of this review to highlight existent evidence that ascribes intrinsic alpha oscillations a role in shaping our ability to learn. In the review, we disentangle the alpha rhythm into different neural signatures that control information processing within individual functional building blocks of perceptual learning. We further highlight computational studies that shed light on potential mechanisms regarding how alpha oscillations may modulate information transfer and connectivity changes relevant for learning. To enable testing of those model based hypotheses, we emphasize the need for multidisciplinary approaches combining assessment of behavior and multi-scale neuronal activity, active modulation of ongoing brain states and computational modeling to reveal the mathematical principles of the complex neuronal interactions. In particular we highlight the relevance of multi-scale modeling frameworks such as the one currently being developed by “The Virtual Brain” project. PMID:24772077

  11. Insight into collision zone dynamics from topography: numerical modelling results and observations

    Directory of Open Access Journals (Sweden)

    A. D. Bottrill

    2012-11-01

    Full Text Available Dynamic models of subduction and continental collision are used to predict dynamic topography changes on the overriding plate. The modelling results show a distinct evolution of topography on the overriding plate, during subduction, continental collision and slab break-off. A prominent topographic feature is a temporary (few Myrs basin on the overriding plate after initial collision. This "collisional mantle dynamic basin" (CMDB is caused by slab steepening drawing, material away from the base of the overriding plate. Also, during this initial collision phase, surface uplift is predicted on the overriding plate between the suture zone and the CMDB, due to the subduction of buoyant continental material and its isostatic compensation. After slab detachment, redistribution of stresses and underplating of the overriding plate cause the uplift to spread further into the overriding plate. This topographic evolution fits the stratigraphy found on the overriding plate of the Arabia-Eurasia collision zone in Iran and south east Turkey. The sedimentary record from the overriding plate contains Upper Oligocene-Lower Miocene marine carbonates deposited between terrestrial clastic sedimentary rocks, in units such as the Qom Formation and its lateral equivalents. This stratigraphy shows that during the Late Oligocene–Early Miocene the surface of the overriding plate sank below sea level before rising back above sea level, without major compressional deformation recorded in the same area. Our modelled topography changes fit well with this observed uplift and subsidence.

  12. Insight into collision zone dynamics from topography: numerical modelling results and observations

    Science.gov (United States)

    Bottrill, A. D.; van Hunen, J.; Allen, M. B.

    2012-11-01

    Dynamic models of subduction and continental collision are used to predict dynamic topography changes on the overriding plate. The modelling results show a distinct evolution of topography on the overriding plate, during subduction, continental collision and slab break-off. A prominent topographic feature is a temporary (few Myrs) basin on the overriding plate after initial collision. This "collisional mantle dynamic basin" (CMDB) is caused by slab steepening drawing, material away from the base of the overriding plate. Also, during this initial collision phase, surface uplift is predicted on the overriding plate between the suture zone and the CMDB, due to the subduction of buoyant continental material and its isostatic compensation. After slab detachment, redistribution of stresses and underplating of the overriding plate cause the uplift to spread further into the overriding plate. This topographic evolution fits the stratigraphy found on the overriding plate of the Arabia-Eurasia collision zone in Iran and south east Turkey. The sedimentary record from the overriding plate contains Upper Oligocene-Lower Miocene marine carbonates deposited between terrestrial clastic sedimentary rocks, in units such as the Qom Formation and its lateral equivalents. This stratigraphy shows that during the Late Oligocene-Early Miocene the surface of the overriding plate sank below sea level before rising back above sea level, without major compressional deformation recorded in the same area. Our modelled topography changes fit well with this observed uplift and subsidence.

  13. Insight into collision zone dynamics from topography: numerical modelling results and observations

    Directory of Open Access Journals (Sweden)

    A. D. Bottrill

    2012-07-01

    Full Text Available Dynamic models of subduction and continental collision are used to predict dynamic topography changes on the overriding plate. The modelling results show a distinct evolution of topography on the overriding plate, during subduction, continental collision and slab break-off. A prominent topographic feature is a temporary (few Myrs deepening in the area of the back arc-basin after initial collision. This collisional mantle dynamic basin (CMDB is caused by slab steepening drawing material away from the base of the overriding plate. Also during this initial collision phase, surface uplift is predicted on the overriding plate between the suture zone and the CMDB, due to the subduction of buoyant continental material and its isostatic compensation. After slab detachment, redistribution of stresses and underplating of the overriding plate causes the uplift to spread further into the overriding plate. This topographic evolution fits the stratigraphy found on the overriding plate of the Arabia-Eurasia collision zone in Iran and south east Turkey. The sedimentary record from the overriding plate contains Upper Oligocene-Lower Miocene marine carbonates deposited between terrestrial clastic sedimentary rocks, in units such as the Qom Formation and its lateral equivalents. This stratigraphy shows that during the Late Oligocene-Early Miocene the surface of the overriding plate sank below sea level before rising back above sea level, without major compressional deformation recorded in the same area. This uplift and subsidence pattern correlates well with our modelled topography changes.

  14. Epidemiological Implications of Host Biodiversity and Vector Biology: Key Insights from Simple Models.

    Science.gov (United States)

    Dobson, Andrew D M; Auld, Stuart K J R

    2016-04-01

    Models used to investigate the relationship between biodiversity change and vector-borne disease risk often do not explicitly include the vector; they instead rely on a frequency-dependent transmission function to represent vector dynamics. However, differences between classes of vector (e.g., ticks and insects) can cause discrepancies in epidemiological responses to environmental change. Using a pair of disease models (mosquito- and tick-borne), we simulated substitutive and additive biodiversity change (where noncompetent hosts replaced or were added to competent hosts, respectively), while considering different relationships between vector and host densities. We found important differences between classes of vector, including an increased likelihood of amplified disease risk under additive biodiversity change in mosquito models, driven by higher vector biting rates. We also draw attention to more general phenomena, such as a negative relationship between initial infection prevalence in vectors and likelihood of dilution, and the potential for a rise in density of infected vectors to occur simultaneously with a decline in proportion of infected hosts. This has important implications; the density of infected vectors is the most valid metric for primarily zoonotic infections, while the proportion of infected hosts is more relevant for infections where humans are a primary host.

  15. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    Science.gov (United States)

    Williams, Jonathan M.

    2017-01-01

    ABSTRACT Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. PMID:28151409

  16. A Review of Source Models of the 2015 Illapel, Chile Earthquake and Insights from Tsunami Data

    Science.gov (United States)

    Satake, Kenji; Heidarzadeh, Mohammad

    2017-01-01

    The 16 September 2015 Illapel, Chile, earthquake and associated tsunami have been studied by many researchers from various aspects. This paper reviews studies on the source model of the earthquake and examines tsunami data. The Illapel earthquake occurred in the source region of previous earthquakes in 1943 and 1880. The earthquake source was studied using various geophysical data, such as near-field seismograms, teleseismic waveform and backprojection, GPS and InSAR data, and tsunami waveforms. Most seismological analyses show a duration of 100 s with a peak at 50 s. The spatial distribution has some variety, but they all have the largest slip varying from 5 to 16 m located at 31°S, 72°W, which is 70 km NW of the epicenter. The shallow slip seems to be extended to the trench axis. A deeper slip patch was proposed from high-frequency seismic data. A tsunami earthquake model with a total duration of 250 s and a third asperity south of the epicenter is also proposed, but we show that the tsunami data do not support this model.

  17. Novel Insights into the Genetic Controls of Primitive and Definitive Hematopoiesis from Zebrafish Models

    Directory of Open Access Journals (Sweden)

    Raman Sood

    2012-01-01

    Full Text Available Hematopoiesis is a dynamic process where initiation and maintenance of hematopoietic stem cells, as well as their differentiation into erythroid, myeloid and lymphoid lineages, are tightly regulated by a network of transcription factors. Understanding the genetic controls of hematopoiesis is crucial as perturbations in hematopoiesis lead to diseases such as anemia, thrombocytopenia, or cancers, including leukemias and lymphomas. Animal models, particularly conventional and conditional knockout mice, have played major roles in our understanding of the genetic controls of hematopoiesis. However, knockout mice for most of the hematopoietic transcription factors are embryonic lethal, thus precluding the analysis of their roles during the transition from embryonic to adult hematopoiesis. Zebrafish are an ideal model organism to determine the function of a gene during embryonic-to-adult transition of hematopoiesis since bloodless zebrafish embryos can develop normally into early larval stage by obtaining oxygen through diffusion. In this review, we discuss the current status of the ontogeny and regulation of hematopoiesis in zebrafish. By providing specific examples of zebrafish morphants and mutants, we have highlighted the contributions of the zebrafish model to our overall understanding of the roles of transcription factors in regulation of primitive and definitive hematopoiesis.

  18. Understanding Ground Motion in Las Vegas: Insights from Data Analysis and Two-Dimensional Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Rodgers, A; Tkalcic, H; McCallen, D

    2004-02-05

    Seismic ground motions are amplified in low velocity sedimentary basins relative to adjacent sites on high velocity hard rock. We used historical recordings of NTS nuclear explosions and earthquake recordings in Las Vegas Valley to quantify frequency-dependent basin amplification using Standard Spectral Ratios. We show that amplifications, referred to as site response, can reach a factor of 10 in the frequency band 0.4-2.0 Hz. Band-averaged site response between 0.4-2.0 Hz is strongly correlated with basin depth. However, it is also well known that site response is related to shallow shear-wave velocity structure. We simulated low frequency (f<1Hz) ground motion and site response with two-dimensional elastic finite difference simulations. We demonstrate that physically plausible models of the shallow subsurface, including low velocity sedimentary structure, can predict relative amplification as well as some of the complexity in the observed waveforms. This study demonstrates that site response can be modeled without invoking complex and computationally expensive three-dimensional structural models.

  19. Oblique Convergence Tectonics in Northern Taiwan-Ryukyu Area:Insights from Sandbox Modeling

    Science.gov (United States)

    Li, Z.; Lu, C. Y.

    2015-12-01

    Taiwan located on the boundary between Eurasian Plate and Philippine Sea Plate and as a results of convergence of these two plates. The specific process of Taiwan orogeny is a hot issue for many years. Sandbox modeling is a way to simulate the mountain building process. The previous studies of 3D sandbox modeling in Taiwan are more concentrated on the effect of basement high and arc-continent collision but few noted the effect of opening of Okinawa Trough. This 3D experiment aims at the structure of northern Taiwan, adds a sandpaper machine which could move in experiment that simulate the opening of Okinawa Trough, and tries to explain the tectonic evolution in northern Taiwan. Result of experimental modeling proves that: (1) the Ryukyu Arc is pulled apart and moving southward as the opening of Okinawa Trough, (2) direction of Ryukyu Arc changed between southern part and middle-northern part due to the opening of Okinawa Trough, (3) Ilan Plain subsidence caused by the opening of Okinawa Trough.

  20. The role of nitrogen fixation in neotropical dry forests: insights from ecosystem modeling and field data

    Science.gov (United States)

    Trierweiler, A.; Xu, X.; Gei, M. G.; Powers, J. S.; Medvigy, D.

    2016-12-01

    Tropical dry forests (TDFs) have immense functional diversity and face multiple resource constraints (both water and nutrients). Legumes are abundant and exhibit a wide diversity of N2-fixing strategies in TDFs. The abundance and diversity of legumes and their interaction with N2-fixing bacteria may strongly control the coupled carbon-nitrogen cycle in the biome and influence whether TDFs will be particularly vulnerable or uniquely adapted to projected global change. However, the importance of N2-fixation in TDFs and the carbon cost of acquiring N through symbiotic relationships are not fully understood. Here, we use models along with field measurements to examine the role of legumes, nitrogen fixation, and plant-symbiont nutrient exchanges in TDFs. We use a new version of the Ecosystem Demography (ED2) model that has been recently parameterized for TDFs. The new version incorporates plant-mycorrhizae interactions and multiple resource constraints (carbon, nitrogen, phosphorus, and water). We represent legumes and other functional groups found in TDFs with a range of resource acquisition strategies. In the model, plants then can dynamically adjust their carbon allocation and nutrient acquisition strategies (e.g. N2-fixing bacteria and mycorrhizal fungi) according to the nutrient limitation status. We test (i) the model's performance against a nutrient gradient of field sites in Costa Rica and (ii) the model's sensitivity to the carbon cost to acquire N through fixation and mycorrhizal relationships. We also report on simulated tree community responses to ongoing field nutrient fertilization experiments. We found that the inclusion of the N2-fixation legume plant functional traits were critical to reproducing community dynamics of Costa Rican field TDF sites and have a large impact on forest biomass. Simulated ecosystem fixation rates matched the magnitude and temporal patterns of field measured fixation. Our results show that symbiotic nitrogen fixation plays an

  1. The Formation of Widespread Volcanically Filled Crater Floors on Mars: Insights from Modeling and Observations

    Science.gov (United States)

    Edwards, C. S.; Asimow, P. D.; Stewart, S. T.; Ehlmann, B. L.

    2014-12-01

    The identification and mapping of compositionally (olivine-/pyroxene-enriched), thermophysically (rocky), and morphologically (flat floors with lobate margins, no visible ejecta/central peak) distinct infilled craters over the majority of the martian cratered southern highlands coupled with the ancient formation age of floor materials (~3.5-4Ga) recently resulted in the interpretation that volcanic infilling was the likely responsible process. However, the source of this material is enigmatic, as no vents are observed and these deposits do not occur in association with any specific volcanic or geographic provinces, leading to the proposal that impact excavation-induced decompression melting of a mantle source may be responsible for the intra-crater materials. The conditions under which impact-induced decompression melting occurs, if at all, are not well constrained. In this work, we present the quantitative modeling of this process by coupling the pMELTS thermodynamic model for silicate magmas to a CTH shock physics impact model with realistic rock rheology. Initial conditions are established for early to modern Mars with mantle potential temperatures (1250-1550˚C), surface heat fluxes (20-80 mW/m2) and radiogenic crustal heat production (1x10-10-1.0x10-12 W/kg) with a crustal composition of Adirondack class basalts and mantle composition following Dreibus and Wanke. Early results (~80km lithosphere, 1350˚C mantle potential temperature) show ~5-7% excess melt generated at the lithosphere-asthenosphere boundary for large craters (e.g. 180 km). These impact events also create zones of high shear strain/fracture systems that propagate through the entire brittle lithosphere. In general the thinner lithosphere and higher mantle potential temperature conditions on early planetary bodies should produce more melt at a given crater size and allow for the translation of this process to smaller crater sizes like those observed on Mars. If pre-existing melt is trapped below

  2. Oxygen isotope trajectories of crystallizing melts: Insights from modeling and the plutonic record

    Science.gov (United States)

    Bucholz, Claire E.; Jagoutz, Oliver; VanTongeren, Jill A.; Setera, Jacob; Wang, Zhengrong

    2017-06-01

    Elevated oxygen isotope values in igneous rocks are often used to fingerprint supracrustal alteration or assimilation of material that once resided near the surface of the earth. The δ18O value of a melt, however, can also increase through closed-system fractional crystallization. In order to quantify the change in melt δ18O due to crystallization, we develop a detailed closed-system fractional crystallization mass balance model and apply it to six experimentally- and naturally-determined liquid lines of descent (LLDs), which cover nearly complete crystallization intervals (melt fractions of 1 to content, will control the specific δ18O path of a crystallizing melt. Hydrous melts, typical of subduction zones, undergo larger increases in δ18O during early stages of crystallization due to their lower magmatic temperatures, greater initial increases in SiO2 content, and high temperature stability of low δ18O phases, such as oxides, amphibole, and anorthitic plagioclase (versus albite). Conversely, relatively dry, tholeiitic melts only experience significant increases in δ18O at degrees of crystallization greater than 80%. Total calculated increases in melt δ18O of 1.0-1.5‰ can be attributed to crystallization from ∼50 to 70 wt.% SiO2 for modeled closed-system crystallizing melt compositions. As an example application, we compare our closed system model results to oxygen isotope mineral data from two natural plutonic sequences, a relatively dry, tholeiitic sequence from the Upper and Upper Main Zones (UUMZ) of the Bushveld Complex (South Africa) and a high-K, hydrous sequence from the arc-related Dariv Igneous Complex (Mongolia). These two sequences were chosen as their major and trace element compositions appear to have been predominantly controlled by closed-system fractional crystallization and their LLDs have been modeled in detail. We calculated equilibrium melt δ18O values using the measured mineral δ18O values and calculated mineral

  3. Perceived value creation process: focus on the company offer

    Directory of Open Access Journals (Sweden)

    Irena Pandža Bajs

    2012-12-01

    Full Text Available In the competitive business environment, as the number of rational consumers faced with many choices increases, companies can achieve their dominance best by applying the business concepts oriented to consumers in order to deliver a value which is different and better than that of their competitors. Among the various products on the market, an educated consumer chooses the offer that provides the greatest value for him/her. Therefore, it is essential for each company to determine how consumers perceive the value of its offer, and which factors determine the high level of perceived value for current and potential consumers. An analysis of these factors provides guidance on how to improve the existing offer and what the offer to be delivered in the future should be like. That could increase the perceived value of the company offer and result in a positive impact on consumer satisfaction and on establishing a stronger, longterm relationship with consumers. The process of defining the perceived value of a particular market offer is affected by the factors of the respective company’s offer as well as by competition factors, consumer factors and buying process factors. The aim of this paper is to analyze the relevant knowledge about the process of creating the perceived value of the company’s market offer and the factors that influence this process. The paper presents a conceptual model of the perceived value creation process in consumers’ mind.

  4. Crustal and Fault Strengths from Critical Taper Measurements: Insights into the behavior of Accretionary Wedges using Distinct-Element Models

    Science.gov (United States)

    Strayer, L.; Suppe, J.

    2012-12-01

    It is increasingly clear that many major faults are weak relative to quasistatic friction because of dynamical effects involving the microprocesses of high-velocity friction and the energetics of large-scale fault rupture. Even at the toes of accretionary wedges where velocity strengthening is expected, large displacements can occur dynamically. We seek to better understand the relationship between the large-scale strength of such faults and of the crust containing them over a timescale much greater than seismic cycles. Critical-taper theory provides straightforward quantitative relationships between accretionary wedge geometry and absolute basal fault and wedge strengths with minimal assumptions. Wedge tapers constrain the far-field stresses under which detachments slip and wedges grow during wedge-growing events, whether they are dynamical or quasistatic. To date most applications of wedge mechanics to accretionary wedges involve analog and numerical modeling with largely conceptual insight, for example illuminating the role of geological heterogeneity. Here we demonstrate that recent theoretical advances that are successful in extracting absolute wedge and detachment strengths from the geometry of active wedges can also be applied to extract large-scale strengths in distinct element numerical models in both mechanically homogeneous and heterogeneous wedges. The distinct element method (DEM) is an ideal tool for the study and modeling of critical taper wedges: model wedges can be initially cohesive (bonded) or cohesionless. Faults and folds form naturally as the result of progressive bond breakage during shortening and wedge growth. Heterogeneity can be introduced by creating layered groups of particles of differing mechanical properties. The DEM suffers to some extent in that macro material properties cannot be directly prescribed but rather must be defined by a modest number of micro-properties and the process in necessarily iterative and developing a wide

  5. Augmenting Predictive Modeling Tools with Clinical Insights for Care Coordination Program Design and Implementation.

    Science.gov (United States)

    Johnson, Tracy L; Brewer, Daniel; Estacio, Raymond; Vlasimsky, Tara; Durfee, Michael J; Thompson, Kathy R; Everhart, Rachel M; Rinehart, Deborath J; Batal, Holly

    2015-01-01

    The Center for Medicare and Medicaid Innovation (CMMI) awarded Denver Health's (DH) integrated, safety net health care system $19.8 million to implement a "population health" approach into the delivery of primary care. This major practice transformation builds on the Patient Centered Medical Home (PCMH) and Wagner's Chronic Care Model (CCM) to achieve the "Triple Aim": improved health for populations, care to individuals, and lower per capita costs. This paper presents a case study of how DH integrated published predictive models and front-line clinical judgment to implement a clinically actionable, risk stratification of patients. This population segmentation approach was used to deploy enhanced care team staff resources and to tailor care-management services to patient need, especially for patients at high risk of avoidable hospitalization. Developing, implementing, and gaining clinical acceptance of the Health Information Technology (HIT) solution for patient risk stratification was a major grant objective. In addition to describing the Information Technology (IT) solution itself, we focus on the leadership and organizational processes that facilitated its multidisciplinary development and ongoing iterative refinement, including the following: team composition, target population definition, algorithm rule development, performance assessment, and clinical-workflow optimization. We provide examples of how dynamic business intelligence tools facilitated clinical accessibility for program design decisions by enabling real-time data views from a population perspective down to patient-specific variables. We conclude that population segmentation approaches that integrate clinical perspectives with predictive modeling results can better identify high opportunity patients amenable to medical home-based, enhanced care team interventions.

  6. What controls biological productivity in coastal upwelling systems? Insights from a comparative modeling study

    Science.gov (United States)

    Lachkar, Z.; Gruber, N.

    2011-06-01

    The magnitude of the biological productivity in Eastern Boundary Upwelling Systems (EBUS) is traditionally viewed as directly reflecting the upwelling intensity. Yet, different EBUS show different sensitivities of productivity to upwelling-favorable winds (Carr and Kearns, 2003). Here, using a comparative modeling study of the California Current System (California CS) and Canary Current System (Canary CS), we show how physical and environmental factors, such as light, temperature and cross-shore circulation modulate the response of biological productivity to upwelling strength. To this end, we made a series of eddy-resolving simulations of the California CS and Canary CS using the Regional Ocean Modeling System (ROMS), coupled to a nitrogen based Nutrient-Phytoplankton-Zooplankton-Detritus (NPZD) ecosystem model. We find the nutrient content of the euphotic zone to be 20 % smaller in the Canary CS relative to the California CS. Yet, the biological productivity is 50 % smaller in the latter. This is due to: (1) a faster nutrient-replete growth in the Canary CS relative to the California CS, related to a more favorable light and temperature conditions in the Canary CS, and (2) the longer nearshore water residence times in the Canary CS which lead to larger buildup of biomass in the upwelling zone, thereby enhancing the productivity. The longer residence times in the Canary CS appear to be associated with the wider continental shelves and the lower eddy activity characterizing this upwelling system. This results in a weaker offshore export of nutrients and organic matter, thereby increasing local nutrient recycling and enhancing the coupling between new and export production in the Northwest African system. Our results suggest that climate change induced perturbations such as upwelling favorable wind intensification might lead to contrasting biological responses in the California CS and the Canary CS, with major implications for the biogeochemical cycles and fisheries

  7. What controls biological productivity in coastal upwelling systems? Insights from a comparative modeling study

    Directory of Open Access Journals (Sweden)

    Z. Lachkar

    2011-06-01

    Full Text Available The magnitude of the biological productivity in Eastern Boundary Upwelling Systems (EBUS is traditionally viewed as directly reflecting the upwelling intensity. Yet, different EBUS show different sensitivities of productivity to upwelling-favorable winds (Carr and Kearns, 2003. Here, using a comparative modeling study of the California Current System (California CS and Canary Current System (Canary CS, we show how physical and environmental factors, such as light, temperature and cross-shore circulation modulate the response of biological productivity to upwelling strength. To this end, we made a series of eddy-resolving simulations of the California CS and Canary CS using the Regional Ocean Modeling System (ROMS, coupled to a nitrogen based Nutrient-Phytoplankton-Zooplankton-Detritus (NPZD ecosystem model. We find the nutrient content of the euphotic zone to be 20 % smaller in the Canary CS relative to the California CS. Yet, the biological productivity is 50 % smaller in the latter. This is due to: (1 a faster nutrient-replete growth in the Canary CS relative to the California CS, related to a more favorable light and temperature conditions in the Canary CS, and (2 the longer nearshore water residence times in the Canary CS which lead to larger buildup of biomass in the upwelling zone, thereby enhancing the productivity. The longer residence times in the Canary CS appear to be associated with the wider continental shelves and the lower eddy activity characterizing this upwelling system. This results in a weaker offshore export of nutrients and organic matter, thereby increasing local nutrient recycling and enhancing the coupling between new and export production in the Northwest African system. Our results suggest that climate change induced perturbations such as upwelling favorable wind intensification might lead to contrasting biological responses in the California CS and the Canary CS, with major implications for the biogeochemical cycles

  8. The shape of the Aegean MCC's, Insights from 3D numerical modelling

    Science.gov (United States)

    Le Pourhiet, L.; Denèle, Y.; Huet, B.; Jolivet, L.

    2010-12-01

    The Aegean sea is a back arc basin in which the continental lithosphere has been stretched through the tertiary leaving several diachronous belts of Metamorphic Core Complexes (MCCs). The Aegean MCCs present two classes of shapes. Some are elongated in the direction of the lineation (A-type e.g. Naxos, Paros..) while the others are elongated in a direction normal to the lineation (B-type e.g. Tinos, Evvia ...). While it is well established from 1 and 2D modeling that MCC's forms when the lower crust is weak, the reason for the diversity of shape remains an open question. The A-type domes are not only elongated in shape; their P-T-t paths indicate a clear phase of warming during the exhumation and they also present migmatites (which are not observed in the other islands). Several hypothesis may be drawn. The elongated domes could result from 1) the competition of boudinage versus normal constriction folding, 2) lateral variation of the thickness or the temperature of the crust resulting in local buoyant instability (R-T instability) or 3) lateral gradient of deformation. This contribution presents the preliminary results obtained with thermo-mechanical models in which we test the influence of a local plutonic intrusions, along strike variation of extensional rate, and lateral boundary condition (normal shortening or extension) on the shape of the domes. As this problem is inherently three dimensional, the models were computed on our computer cluster using Gale/Underworld an ALE method with visco-plastic temperature dependent rheologies.

  9. Preformed template fluctuations promote fibril formation: insights from lattice and all-atom models.

    Science.gov (United States)

    Kouza, Maksim; Co, Nguyen Truong; Nguyen, Phuong H; Kolinski, Andrzej; Li, Mai Suan

    2015-04-14

    Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite the fact that the fibril formation process is very slow and thus poses a significant challenge for theoretical and experimental studies, a number of alternative pictures of molecular mechanisms of amyloid fibril formation have been recently proposed. What seems to be common for the majority of the proposed models is that fibril elongation involves the formation of pre-nucleus seeds prior to the creation of a critical nucleus. Once the size of the pre-nucleus seed reaches the critical nucleus size, its thermal fluctuations are expected to be small and the resulting nucleus provides a template for sequential (one-by-one) accommodation of added monomers. The effect of template fluctuations on fibril formation rates has not been explored either experimentally or theoretically so far. In this paper, we make the first attempt at solving this problem by two sets of simulations. To mimic small template fluctuations, in one set, monomers of the preformed template are kept fixed, while in the other set they are allowed to fluctuate. The kinetics of addition of a new peptide onto the template is explored using all-atom simulations with explicit water and the GROMOS96 43a1 force field and simple lattice models. Our result demonstrates that preformed template fluctuations can modulate protein aggregation rates and pathways. The association of a nascent monomer with the template obeys the kinetics partitioning mechanism where the intermediate state occurs in a fraction of routes to the protofibril. It was shown that template immobility greatly increases the time of incorporating a new peptide into the preformed template compared to the fluctuating template case. This observation has also been confirmed by simulation using lattice models and may be invoked to understand the role of template fluctuations in

  10. Pesticide nonextractable residue formation in soil: insights from inverse modeling of degradation time series.

    Science.gov (United States)

    Loos, Martin; Krauss, Martin; Fenner, Kathrin

    2012-09-18

    Formation of soil nonextractable residues (NER) is central to the fate and persistence of pesticides. To investigate pools and extent of NER formation, an established inverse modeling approach for pesticide soil degradation time series was evaluated with a Monte Carlo Markov Chain (MCMC) sampling procedure. It was found that only half of 73 pesticide degradation time series from a homogeneous soil source allowed for well-behaved identification of kinetic parameters with a four-pool model containing a parent compound, a metabolite, a volatile, and a NER pool. A subsequent simulation indeed confirmed distinct parameter combinations of low identifiability. Taking the resulting uncertainties into account, several conclusions regarding NER formation and its impact on persistence assessment could nonetheless be drawn. First, rate constants for transformation of parent compounds to metabolites were correlated to those for transformation of parent compounds to NER, leading to degradation half-lives (DegT50) typically not being larger than disappearance half-lives (DT50) by more than a factor of 2. Second, estimated rate constants were used to evaluate NER formation over time. This showed that NER formation, particularly through the metabolite pool, may be grossly underestimated when using standard incubation periods. It further showed that amounts and uncertainties in (i) total NER, (ii) NER formed from the parent pool, and (iii) NER formed from the metabolite pool vary considerably among data sets at t→∞, with no clear dominance between (ii) and (iii). However, compounds containing aromatic amine moieties were found to form significantly more total NER when extrapolating to t→∞ than the other compounds studied. Overall, our study stresses the general need for assessing uncertainties, identifiability issues, and resulting biases when using inverse modeling of degradation time series for evaluating persistence and NER formation.

  11. Petrological and two-phase flow modelling of deep arc crust: insights on continental crust formation

    Science.gov (United States)

    Riel, Nicolas; Bouilhol, Pierre; van Hunen, Jeroen; Cornet, Julien

    2017-04-01

    The genesis of felsic crust is generally attributed to two main processes: the differentiation of primary magmas by crystallization within the crust or uppermost mantle and the partial melting of older crustal rocks. The Mixing/Assimilation/Hybridization of these magmas in the deep crust (MASH zone) and their subsequent segregation constitutes the principal process by which continents have become differentiated into a more mafic, residual lower crust and a more felsic and hydrated upper crust. Although this model describes qualitatively how continental crust forms, little is known on the physical and chemical mechanisms occurring at the root of volcanic arcs. To assess the dynamics of partial melting, melt injection and hybridization in the deep crust, a new 2-D two-phase flow code using finite volume method has been developed. The formulation takes into account: (i) melt flow through porosity waves/channels, (ii) heat transfer, assuming local thermal equilibrium between solid and liquid, (iii) thermodynamic modelling of stable phases and (iv) injection of mantle-derived melt at the Moho. Our parametric study shows that pressure, heat influx and melt:rock ratio are the main parameters controlling the volume and composition of differentiated magma. Overall the composition of segregated products scatters in two groups: felsic (80-68% SiO2) and intermediate (60-52% SiO2), with an average andesitic composition. The bimodal distribution is controlled by amphibole which buffer the composition of segregated products to high SiO2-content when stable. As the amphibole-out melting reaction is crossed segregated products become intermediate. When compared to available geological evidence, the liquid line of descent of mantle-derived magma do not fit the Mg# versus silica trends of exposed volcanic arcs. Instead our modelling results show that reactive flow of those same magma through a mafic crust is able to reproduce such trends.

  12. T-tubule disruption promotes calcium alternans in failing ventricular myocytes: mechanistic insights from computational modeling.

    Science.gov (United States)

    Nivala, Michael; Song, Zhen; Weiss, James N; Qu, Zhilin

    2015-02-01

    In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the effects of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in "orphaned" RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF.

  13. Mantle flow and dynamic topography associated with slab window opening: Insights from laboratory models

    Science.gov (United States)

    Guillaume, Benjamin; Moroni, Monica; Funiciello, Francesca; Martinod, Joseph; Faccenna, Claudio

    2010-12-01

    We present dynamically self-consistent mantle-scale laboratory models that have been conducted to improve our understanding of the influence of slab window opening on subduction dynamics, mantle flow and associated dynamic topography over geological time scales. The adopted setup consists of a two-layer linearly viscous system simulating the subduction of a fixed plate of silicone (lithosphere) under negative buoyancy in a viscous layer of glucose syrup (mantle). Our experimental setting is also characterized by a constant-width rectangular window located at the center of a laterally confined slab, modeling the case of the interaction of a trench-parallel spreading ridge with a wide subduction zone. We found that the opening of a slab window does not produce consistent changes of the geometry and the kinematics of the slab. On the contrary, slab-induced mantle circulation, quantified both in the vertical and horizontal sections using the Feature Tracking image analysis technique, is strongly modified. In particular, rollback subduction and the opening of the slab window generate a complex mantle circulation pattern characterized by the presence of poloidal and toroidal components, with the importance of each evolving according to kinematic stages. Mantle coming from the oceanic domain floods through the slab window, indenting the supra-slab mantle zone and producing its deformation without any mixing between mantle portions. The opening of the slab window and the upwelling of sub-slab mantle produce a regional-scale non-isostatic topographic uplift of the overriding plate that would correspond to values ranging between ca. 1 and 5 km in nature. Assuming that our modeling results can be representative of the natural behavior of subduction zones, we compared them to the tectonics and volcanism of the Patagonian subduction zone. We found that the anomalous backarc volcanism that has been developing since the middle Miocene could result from the lateral flow of sub

  14. Structural insights into Saccharomyces cerevisiae Msh4-Msh5 complex function using homology modeling.

    Directory of Open Access Journals (Sweden)

    Ramaswamy Rakshambikai

    Full Text Available The Msh4-Msh5 protein complex in eukaryotes is involved in stabilizing Holliday junctions and its progenitors to facilitate crossing over during Meiosis I. These functions of the Msh4-Msh5 complex are essential for proper chromosomal segregation during the first meiotic division. The Msh4/5 proteins are homologous to the bacterial mismatch repair protein MutS and other MutS homologs (Msh2, Msh3, Msh6. Saccharomyces cerevisiae msh4/5 point mutants were identified recently that show two fold reduction in crossing over, compared to wild-type without affecting chromosome segregation. Three distinct classes of msh4/5 point mutations could be sorted based on their meiotic phenotypes. These include msh4/5 mutations that have a crossover and viability defects similar to msh4/5 null mutants; b intermediate defects in crossing over and viability and c defects only in crossing over. The absence of a crystal structure for the Msh4-Msh5 complex has hindered an understanding of the structural aspects of Msh4-Msh5 function as well as molecular explanation for the meiotic defects observed in msh4/5 mutations. To address this problem, we generated a structural model of the S. cerevisiae Msh4-Msh5 complex using homology modeling. Further, structural analysis tailored with evolutionary information is used to predict sites with potentially critical roles in Msh4-Msh5 complex formation, DNA binding and to explain asymmetry within the Msh4-Msh5 complex. We also provide a structural rationale for the meiotic defects observed in the msh4/5 point mutations. The mutations are likely to affect stability of the Msh4/5 proteins and/or interactions with DNA. The Msh4-Msh5 model will facilitate the design and interpretation of new mutational data as well as structural studies of this important complex involved in meiotic chromosome segregation.

  15. Preformed template fluctuations promote fibril formation: Insights from lattice and all-atom models

    Energy Technology Data Exchange (ETDEWEB)

    Kouza, Maksim, E-mail: mkouza@chem.uw.edu.pl; Kolinski, Andrzej [Faculty of Chemistry, University of Warsaw, ul. Pasteura 1, 02-093 Warszaw (Poland); Co, Nguyen Truong [Department of Physics, Institute of Technology, National University of HCM City, 268 Ly Thuong Kiet Street, District 10, Ho Chi Minh City (Viet Nam); Institute for Computational Science and Technology, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City (Viet Nam); Nguyen, Phuong H. [Laboratoire de Biochimie Theorique, UPR 9080 CNRS, IBPC, Universite Paris 7, 13 rue Pierre et Marie Curie, 75005 Paris (France); Li, Mai Suan, E-mail: masli@ifpan.edu.pl [Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw (Poland)

    2015-04-14

    Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Despite the fact that the fibril formation process is very slow and thus poses a significant challenge for theoretical and experimental studies, a number of alternative pictures of molecular mechanisms of amyloid fibril formation have been recently proposed. What seems to be common for the majority of the proposed models is that fibril elongation involves the formation of pre-nucleus seeds prior to the creation of a critical nucleus. Once the size of the pre-nucleus seed reaches the critical nucleus size, its thermal fluctuations are expected to be small and the resulting nucleus provides a template for sequential (one-by-one) accommodation of added monomers. The effect of template fluctuations on fibril formation rates has not been explored either experimentally or theoretically so far. In this paper, we make the first attempt at solving this problem by two sets of simulations. To mimic small template fluctuations, in one set, monomers of the preformed template are kept fixed, while in the other set they are allowed to fluctuate. The kinetics of addition of a new peptide onto the template is explored using all-atom simulations with explicit water and the GROMOS96 43a1 force field and simple lattice models. Our result demonstrates that preformed template fluctuations can modulate protein aggregation rates and pathways. The association of a nascent monomer with the template obeys the kinetics partitioning mechanism where the intermediate state occurs in a fraction of routes to the protofibril. It was shown that template immobility greatly increases the time of incorporating a new peptide into the preformed template compared to the fluctuating template case. This observation has also been confirmed by simulation using lattice models and may be invoked to understand the role of template fluctuations in

  16. Neotropical Siluriformes as a Model for Insights on Determining Biodiversity of Animal Groups.

    Directory of Open Access Journals (Sweden)

    Renata Rúbia Ota

    Full Text Available We performed an analysis of the descriptions of new species of Neotropical Siluriformes (catfishes to estimate the number of new species that remain to be described for a complete knowledge on biodiversity of this order, to verify the effectiveness of taxonomic support, and to identify trends and present relevant information for future policies. We conducted a literature review of species descriptions between January 1990 and August 2014. The following metadata were recorded from each article: year of publication, number of species, journal and impact factor, family(s of the described species, number of authors, age of the authors and coauthors, country of the first author's institution and ecoregion of the type-locality. From accumulation of descriptions, we built an estimate model for number of species remaining to be described. We found 595 described species in 402 articles. The data demonstrated that there has been an increased understanding of the diversity of Siluriformes over the last 25 years in the Neotropical region, although 35% of the species still remain to be described. The model estimated that with the current trends and incentives, the biodiversity will be known in almost seven decades. We have reinforced the idea that greater joint efforts should be made by society and the scientific community to obtain this knowledge in a shorter period of time through enhanced programs for promoting science, training and the advancement of professionals before undiscovered species become extinct. The model built in this study can be used for similar estimates of other groups of animals.

  17. Potential Bias in Projecting Future Regional Megadrought Risk: Insights From A Global Data-Model Framework

    Science.gov (United States)

    Overpeck, J. T.; Ault, T.; Cole, J. E.; Fasullo, J.; Loope, G. R.; Parsons, L. A.; Stevenson, S.

    2015-12-01

    Megadrought is one of the most significant and costly climate extremes, and one that stakeholders (e.g., water and other resource managers) the world over wish to understand better; in particular, they need estimates of the risk of severe droughts as a function of drought frequency, severity, duration, and atmospheric greenhouse gas concentration. In many dry-climate regions of the globe, megadrought is synonymous with multi-decadal drought. However, in other regions, megadrought can be defined as extended drought, mostly not seen in the period of instrumental observations, and that would have large impacts if it were to occur in the future. New and published paleoclimatic observations allow us to understand the spectrum of drought in many regions of the globe; droughts exceeding 50 years have occurred in recent Earth history in southwestern North America, sub-Saharan Africa, the Mediterranean and Australia, whereas shorter megadroughts have occurred in Monsoon Asia, Amazonia and elsewhere. Data-model comparisons for regions with sufficiently long (e.g., 1000-2000 years) records of observed hydroclimatic variability suggest that state-of-the-art models can provide realistic estimates of interannual to decadal drought risk, but underestimate the risk of megadrought. Likely reasons for this shortcoming are the lack of sufficient multi-decadal variability in simulations of the past and future, plus an underappreciated understanding about how temperature variability and land-surface feedbacks interact with hydrological and ecological drought, as well as the roles played by unusually wet hydroclimatic extremes (e.g., ENSO related) in ending droughts of long duration. Paleoclimatic records also provide the opportunity to estimate how much models underestimate megadrought risk as a function of locale, frequency, severity, duration, and atmospheric greenhouse gas concentration; they also aid in providing stakeholders with bias-corrected estimates of megadrought risk.

  18. The seismic cycle at subduction thrusts: 1. Insights from laboratory models

    KAUST Repository

    Corbi, F.

    2013-04-01

    Subduction megathrust earthquakes occur at the interface between the subducting and overriding plates. These hazardous phenomena are only partially understood because of the absence of direct observations, the restriction of the instrumental seismic record to the past century, and the limited resolution/completeness of historical to geological archives. To overcome these restrictions, modeling has become a key-tool to study megathrust earthquakes. We present a novel model to investigate the seismic cycle at subduction thrusts using complementary analog (paper 1) and numerical (paper 2) approaches. Here we introduce a simple scaled gelatin-on-sandpaper setup including realistic tectonic loading, spontaneous rupture nucleation, and viscoelastic response of the lithosphere. Particle image velocimetry allows to derive model deformation and earthquake source parameters. Analog earthquakes are characterized by “quasi-periodic” recurrence. Consistent with elastic theory, the interseismic stage shows rearward motion, subsidence in the outer wedge and uplift of the “coastal area” as a response of locked plate interface at shallow depth. The coseismic stage exhibits order of magnitude higher velocities and reversal of the interseismic deformation pattern in the seaward direction, subsidence of the coastal area, and uplift in the outer wedge. Like natural earthquakes, analog earthquakes generally nucleate in the deeper portion of the rupture area and preferentially propagate upward in a crack-like fashion. Scaled rupture width-slip proportionality and seismic moment-duration scaling verifies dynamic similarities with earthquakes. Experimental repeatability is statistically verified. Comparing analog results with natural observations, we conclude that this technique is suitable for investigating the parameter space influencing the subduction interplate seismic cycle.

  19. Reconstruction of the Morasko meteoroid impact—Insight from numerical modeling

    Science.gov (United States)

    Bronikowska, M.; Artemieva, N. A.; Wünnemann, K.

    2017-08-01

    The Morasko strewn field located near Poznań, Poland comprises seven impact craters with diameters ranging from 20 to 90 m, all of which were formed in glacial sediments around 5000 yr ago. Numerous iron meteorites have been recovered in the area and their distribution suggests a projectile with the trajectory from NE to SW. Similar impact events producing crater strewn fields on average happen every 500 yr and pose a serious risk for modern civilization, which is why it is of utmost importance to study terrestrial strewn fields in detail. In this work, we investigate the Morasko meteoroid passage through the atmosphere, the distribution of its fragments on the ground, and the process of forming individual craters by means of numerical modeling. By combining atmospheric entry modeling, Pi-group scaling of transient crater size and hydrocode simulations of impact processes, we constructed a comprehensive model of the Morasko strewn field formation. We determined the preatmospheric parameters of the Morasko meteoroid. The entry mass is between 600 and 1100 tons, the velocity range is between 16 and 18 km s-1, and the trajectory angle is 30-40°. Such entry velocities and trajectory angles do not deviate from typical values for near-Earth asteroids, although the initial mass we determined can be considered as small. Our studies on velocities and masses of crater-forming fragments showed that the biggest Morasko crater was formed by a projectile about 1.5 m in diameter with the impact velocity 10 km s-1. Environmental consequences of the Morasko impact event are very localized.

  20. Subduction Initiation from a Stagnant Lid: New Insights from Numerical Models with a Free Surface

    Science.gov (United States)

    Crameri, Fabio; Tackley, Paul

    2016-04-01

    Subduction initiation is key in understanding the dynamic evolution of the Earth and its fundamental difference to all other rocky planetary bodies in our solar system. Despite recent progress, the question about how a stiff, mostly stagnant planetary lid can break and become part in the global overturn of the mantle is still unresolved. Here, we present results on subduction initiation obtained by dynamically self-consistent, time-dependent numerical modelling of mantle convection and single-sided subduction (Crameri et al., 2012b) using the finite-difference, multigrid code StagYY (Tackley 2008). We show that the stress distribution and resulting deformation of the lithosphere is strongly controlled by the top boundary formulation: A free surface enables surface topography and plate bending, increases gravitational sliding of the plates and leads to more realistic, lithosphere-scale shear zones. As a consequence, subduction initiation induced by regional mantle flow is significantly favoured by a free surface compared to the commonly-applied, vertically-fixed (i.e., free-slip) surface. In addition, we present global, three-dimensional mantle convection experiments (see e.g. Crameri and Tackley, 2014) that employ basal heating that leads to narrow mantle plumes. Narrow mantle plumes impinging on the base of the plate cause locally weak plate segments and a large topography at the lithosphere-asthenosphere boundary. Both are shown to be key to induce subduction initiation. Finally, our model self-consistently reproduces an episodic lid with a fast global overturn due to the hotter mantle developed below a former stagnant lid. We conclude that once in a stagnant-lid mode, a planet (like Venus) thus preferentially evolves by temporally discrete, global overturn events rather than by a continuous recycling of lid. REFERENCES Crameri, F, Tackley, P.J, Meilick, I, Gerya, T.V, Kaus, B.J.P (2012) A free plate surface and weak oceanic crust produce single-sided subduction

  1. What controls biological production in coastal upwelling systems? Insights from a comparative modeling study

    Directory of Open Access Journals (Sweden)

    Z. Lachkar

    2011-10-01

    Full Text Available The magnitude of net primary production (NPP in Eastern Boundary Upwelling Systems (EBUS is traditionally viewed as directly reflecting the wind-driven upwelling intensity. Yet, different EBUS show different sensitivities of NPP to upwelling-favorable winds (Carr and Kearns, 2003. Here, using a comparative modeling study of the California Current System (California CS and Canary Current System (Canary CS, we show how physical and environmental factors, such as light, temperature and cross-shore circulation modulate the response of NPP to upwelling strength. To this end, we made a series of eddy-resolving simulations of the two upwelling systems using the Regional Oceanic Modeling System (ROMS, coupled to a nitrogen-based Nutrient-Phytoplankton-Zooplankton-Detritus (NPZD ecosystem model. Using identical ecological/biogeochemical parameters, our coupled model simulates a level of NPP in the California CS that is 50 % smaller than that in the Canary CS, in agreement with observationally based estimates. We find this much lower NPP in the California CS despite phytoplankton in this system having nearly 20 % higher nutrient concentrations available to fuel their growth. This conundrum can be explained by: (1 phytoplankton having a faster nutrient-replete growth in the Canary CS relative to the California CS; a consequence of more favorable light and temperature conditions in the Canary CS, and (2 the longer nearshore water residence times in the Canary CS, which permit a larger buildup of biomass in the upwelling zone, thereby enhancing NPP. The longer residence times in the Canary CS appear to be a result of the wider continental shelves and the lower mesoscale activity characterizing this upwelling system. This results in a weaker offshore export of nutrients and organic matter, thereby increasing local nutrient recycling and reducing the spatial decoupling between new and export production in the Canary CS. Our results suggest that climate change

  2. From quantifying historical LULCC impacts to optimizing land management for climate mitigation: Insights from climate modelling

    Science.gov (United States)

    Davin, E.; Lejeune, Q.; Seneviratne, S. I.

    2015-12-01

    Human activities have profoundly transformed the land surface through land use/land cover change (LULCC). The consequence of this transformation is twofold: First, the conversion from natural to anthropogenic systems exert a direct forcing on climate (through both biogeochemical and biogeophysical processes); Second the transformed ecosystems may modify land-atmosphere feedback mechanisms thus modulating the response to climate change or to specific weather events. The first point will be illustrated by reviewing recent modelling results, including LUCID and CMIP5 model intercomparisons, to shed some light on the relative importance of LULCC versus other climate forcings. Given the importance of LULCC impacts at the regional scale, some recent efforts to improve the representation of land processes in regional climate models [1] as well as a regional assessment of the impact of amazonian deforestation [2] will be presented. The second point will be discussed through two examples. First, the fact that LULCC may modulate certain modes of variability will be illustrated based on model experiments highlighting the regional interplay between ENSO variability and amazonian deforestation. Second, we will show that peak temperatures during heat waves can be strongly influenced locally by the type of land cover or land management practices. In particular no-till farming, by increasing surface albedo, can lead to a substantial attenuation of hot temperatures during heat waves, in part due to a more efficient radiative cooling effect during cloud-free conditions [3]. References:[1] Davin, E.L. and S.I. Seneviratne (2012), Role of land surface processes and diffuse/direct radiation partitioning in simulating the European climate, Biogeosciences, 9, 1695-1707, doi:10.5194/bg-9-1695-2012.[2] Lejeune, Q., E.L. Davin, B. Guillod and S.I. Seneviratne (2015), Influence of Amazonian deforestation on the future evolution of regional surface fluxes, circulation, surface temperature and

  3. Modeling prolactin actions in breast cancer in vivo: insights from the NRL-PRL mouse.

    Science.gov (United States)

    O'Leary, Kathleen A; Shea, Michael P; Schuler, Linda A

    2015-01-01

    Elevated exposure to prolactin (PRL) is epidemiologically associated with an increased risk of aggressive ER+ breast cancer. To understand the underlying mechanisms and crosstalk with other oncogenic factors, we developed the NRL-PRL mouse. In this model, mammary expression of a rat prolactin transgene raises local exposure to PRL without altering estrous cycling. Nulliparous females develop metastatic, histotypically diverse mammary carcinomas independent from ovarian steroids, and most are ER+. These characteristics resemble the human clinical disease, facilitating study of tumorigenesis, and identification of novel preventive and therapeutic approaches.

  4. Mechanisms of atrial fibrillation termination by rapidly unbinding Na+ channel blockers: insights from mathematical models and experimental correlates.

    Science.gov (United States)

    Comtois, Philippe; Sakabe, Masao; Vigmond, Edward J; Munoz, Mauricio; Texier, Anne; Shiroshita-Takeshita, Akiko; Nattel, Stanley

    2008-10-01

    Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is a problem of growing proportions. Recent studies have increased interest in fast-unbinding Na(+) channel blockers like vernakalant (RSD1235) and ranolazine for AF therapy, but the mechanism of efficacy is poorly understood. To study how fast-unbinding I(Na) blockers affect AF, we developed realistic mathematical models of state-dependent Na(+) channel block, using a lidocaine model as a prototype, and studied the effects on simulated cholinergic AF in two- and three-dimensional atrial substrates. We then compared the results with in vivo effects of lidocaine on vagotonic AF in dogs. Lidocaine action was modeled with the Hondeghem-Katzung modulated-receptor theory and maximum affinity for activated Na(+) channels. Lidocaine produced frequency-dependent Na(+) channel blocking and conduction slowing effects and terminated AF in both two- and three-dimensional models with concentration-dependent efficacy (maximum approximately 89% at 60 microM). AF termination was not related to increases in wavelength, which tended to decrease with the drug, but rather to decreased source Na(+) current in the face of large ACh-sensitive K(+) current-related sinks, leading to the destabilization of primary generator rotors and a great reduction in wavebreak, which caused primary rotor annihilations in the absence of secondary rotors to resume generator activity. Lidocaine also reduced the variability and maximum values of the dominant frequency distribution during AF. Qualitatively similar results were obtained in vivo for lidocaine effects on vagal AF in dogs, with an efficacy of 86% at 2 mg/kg iv, as well as with simulations using the guarded-receptor model of lidocaine action. These results provide new insights into the mechanisms by which rapidly unbinding class I antiarrhythmic agents, a class including several novel compounds of considerable promise, terminate AF.

  5. Organic aerosol concentration and composition over Europe: insights from comparison of regional model predictions with aerosol mass spectrometer factor analysis

    Directory of Open Access Journals (Sweden)

    C. Fountoukis

    2014-03-01

    Full Text Available A detailed three-dimensional regional chemical transport model (PMCAMx was applied over Europe focusing on the formation and chemical transformation of organic matter. Three periods representative of different seasons were simulated, corresponding to intensive field campaigns. An extensive set of AMS measurements was used to evaluate the model and, using factor analysis results, gain more insight into the sources and transformations of organic aerosol (OA. Overall, the agreement between predictions and measurements for OA concentration is encouraging with the model reproducing two thirds of the data (daily average mass concentrations within a factor of two. Oxygenated OA (OOA is predicted to contribute 93% to total OA during May, 87% during winter and 96% during autumn with the rest consisting of fresh primary OA (POA. Predicted OOA concentrations compare well with the observed OOA values for all periods with an average fractional error of 0.53 and a bias equal to −0.07 (mean error = 0.9 μg m−3, mean bias = −0.2 μg m−3. The model systematically underpredicts fresh POA in most sites during late spring and autumn (mean bias up to −0.8 μg m−3. Based on results from a source apportionment algorithm running in parallel with PMCAMx, most of the POA originates from biomass burning (fires and residential wood combustion and therefore biomass burning OA is most likely underestimated in the emission inventory. The model performs well at all sites when the PMF-estimated low volatility OOA is compared against the OA with C* ≤ 0.1 μg m−3 and semivolatile OOA against the OA with C* > 0.1 μg m−3 respectively.

  6. Economic Dispatch of Demand Response Balancing through Asymmetric Block Offers

    DEFF Research Database (Denmark)

    O'Connell, Niamh; Pinson, Pierre; Madsen, Henrik

    2015-01-01

    load to provide a response to the power system and the subsequent need to recover. The conventional system dispatch algorithm is altered to facilitate the dispatch of demand response units alongside generating units using the proposed offer structure. The value of demand response is assessed through...... case studies that dispatch flexible supermarket refrigeration loads for the provision of regulating power. The demand resource is described by a set of asymmetric blocks, and a set of four blocks offers is shown to offer cost savings for the procurement of regulating power in excess of 20......%. For comparative purposes, the cost savings achievable with a fully observable and controllable demand response resource are evaluated, using a time series model of the refrigeration loads. The fully modeled resource offers greater savings; however the difference is small and potentially insufficient to justify...

  7. The Influence of Dissolution on Bedrock Channel Evolution: Insights from Modelling and Field Observations

    Science.gov (United States)

    Thaler, E.; Myre, J. M.; Covington, M. D.

    2015-12-01

    Despite the large global distribution of soluble bedrock, fluvial geomorphological studies typically regard dissolution as a negligible erosion mechanism in bedrock channels when compared to rates of mechanical erosion. Limited prior field observations have suggested that at the transition from insoluble to soluble substrate bedrock channels become wider, less steep, or both. By extending the Fastscape landscape evolution model to include dissolution as an erosion mechanism, we repeatedly produce landscapes with trunk streams consistent with field observations. However, in small tributaries, channel steepening occurs at the contact of the insoluble and soluble lithologies. Furthermore, as the main channel in a basin encounters the soluble layer, the increased erosion due to dissolution acts produces a local increase in the rate of base level lowering, resulting in steepening of channels upstream of the lithologic contact. The increased erosion at the lithological contact in the main stem also causes hillsope steepening in the soluble reaches. Independent field observations in the Buffalo National River Basin agree with the model results. Knickpoints and slot canyons are common at the lithologic contact in small tributaries, and channel widening occurs in soluble reaches in the main stem.

  8. Paying attention to attention in recognition memory: insights from models and electrophysiology.

    Science.gov (United States)

    Dubé, Chad; Payne, Lisa; Sekuler, Robert; Rotello, Caren M

    2013-12-01

    Reliance on remembered facts or events requires memory for their sources, that is, the contexts in which those facts or events were embedded. Understanding of source retrieval has been stymied by the fact that uncontrolled fluctuations of attention during encoding can cloud results of key importance to theoretical development. To address this issue, we combined electrophysiology (high-density electroencephalogram, EEG, recordings) with computational modeling of behavioral results. We manipulated subjects' attention to an auditory attribute, whether the source of individual study words was a male or female speaker. Posterior alpha-band (8-14 Hz) power in subjects' EEG increased after a cue to ignore the voice of the person who was about to speak. Receiver-operating-characteristic analysis validated our interpretation of oscillatory dynamics as a marker of attention to source information. With attention under experimental control, computational modeling showed unequivocally that memory for source (male or female speaker) reflected a continuous signal detection process rather than a threshold recollection process.

  9. Evolution of Coronary Flow in an Experimental Slow Flow Model in Swines: Angiographic and Pathological Insights

    Directory of Open Access Journals (Sweden)

    Yupeng Bai

    2015-01-01

    Full Text Available Objective. Pathomechanism of coronary slow flow phenomenon remains largely unclear now. Present study observed the pathological and angiographic evolution in a pig model of coronary slow flow. Methods. Coronary slow flow was induced by repeat coronary injection of small doses of 40 µm microspheres in 18 male domestic pigs and angiographic and pathological changes were determined at 3 hours, 7 days, and 28 days after microspheres injection. Results. Compared to control group treated with coronary saline injection n=6 and baseline level, coronary flow was significantly reduced at 3 hours and 7 days but completely recovered at 28 days after coronary microsphere injection in slow flow group. Despite normal coronary flow at 28 days after microsphere injection, enhanced myocardial cytokine expression, left ventricular dysfunction, adverse remodelling, and ischemia/microembolism related pathological changes still persisted or even progressed from 3 hours to 28 days after coronary microsphere injection. Conclusions. Our results show that this large animal slow flow model could partly reflect the chronic angiographic, hemodynamic, and pathological changes of coronary slow flow and could be used to test new therapy strategies against the slow flow phenomenon.

  10. Molecular interaction of PCB153 to human serum albumin: Insights from spectroscopic and molecular modeling studies

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chao; Fang, Senbiao; Cao, Huiming; Lu, Yan; Ma, Yaqiong [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Wei, Dongfeng [Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700 (China); Xie, Xiaoyun [College of Earth and Environmental Science, Lanzhou University, Lanzhou 730000 (China); Liu, Xiaohua [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Li, Xin [College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471003 (China); Fei, Dongqing [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Zhao, Chunyan, E-mail: zhaochy07@lzu.edu.cn [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China)

    2013-03-15

    Highlights: ► We identify the binding mode of PCB153 to human serum albumin (HSA). ► Spectroscopic and molecular modeling results reveal that PCB153 binds at the site II. ► The interaction is mainly governed by hydrophobic and hydrogen bond forces. ► The work helps to probe transporting, distribution and toxicity effect of PCBs. -- Abstract: Polychlorinated biphenyls (PCBs) possessed much potential hazard to environment because of its chemical stability and biological toxicity. Here, we identified the binding mode of a representative compound, PCB153, to human serum albumin (HSA) using fluorescence and molecular dynamics simulation methods. The fluorescence study showed that the intrinsic fluorescence of HSA was quenched by addition of PCB153 through a static quenching mechanism. The thermodynamic analysis proved the binding behavior was mainly governed by hydrophobic force. Furthermore, as evidenced by site marker displacement experiments using two probe compounds, it revealed that PCB153 acted exactly on subdomain IIIA (site II) of HSA. On the other hand, the molecular dynamics studies as well as free energy calculations made another important contribution to understand the conformational changes of HSA and the stability of HSA-PCB153 system. Molecular docking revealed PCB153 can bind in a large hydrophobic activity of subdomain IIIA by the hydrophobic interaction and hydrogen bond interactions between chlorine atoms and residue ASN391. The present work provided reasonable models helping us further understand the transporting, distribution and toxicity effect of PCBs when it spread into human blood serum.

  11. Dynamics of ubiquitin-mediated signalling: insights from mathematical modelling and experimental studies.

    Science.gov (United States)

    Nguyen, Lan K

    2016-05-01

    Post-translational modification of cellular proteins by ubiquitin is a pivotal regulatory event that controls not only protein degradation, but also a variety of non-proteolytic functions. Ubiquitination is involved in a broad array of physiological processes, and its dysregulation has been associated with many human diseases, including neuronal disorders and cancers. Ubiquitin-mediated signalling has thus come to the forefront of biomedical research. It is increasingly apparent that ubiquitination is a highly complex and dynamic process, evidenced by a myriad of ways of ubiquitin chain formation, tightly regulatory mechanisms involving E3 ligases and deubiquitinating enzymes and extensive crosstalk with other post-translational modifications. To unravel the complexity of ubiquitination and understand the dynamic properties of ubiquitin-mediated signalling are challenging, but critical topics in ubiquitin research, which will undoubtedly benefit our effort in developing strategies that could target ubiquitin signalling for therapeutics. Computational modelling and model-based approaches are emerging as promising tools that help tackle the complexity and provide useful frameworks for quantitative and dynamical analysis of ubiquitin signalling. In this article, I will discuss recent advances in our understanding of the dynamic behaviour of ubiquitination from both theoretical and experimental studies, and aspects of ubiquitin signalling that may have major dynamical consequences. It is expected the discussed issues will be of relevant interest to both the ubiquitin and systems biology fields.

  12. Effects of Mechanical Properties on Tumor Invasion: Insights from a Cellular Model

    KAUST Repository

    Li, YZ

    2014-08-01

    Understanding the regulating mechanism of tumor invasion is of crucial importance for both fundamental cancer research and clinical applications. Previous in vivo experiments have shown that invasive cancer cells dissociate from the primary tumor and invade into the stroma, forming an irregular invasive morphology. Although cell movements involved in tumor invasion are ultimately driven by mechanical forces of cell-cell interactions and tumor-host interactions, how these mechanical properties affect tumor invasion is still poorly understood. In this study, we use a recently developed two-dimensional cellular model to study the effects of mechanical properties on tumor invasion. We study the effects of cell-cell adhesions as well as the degree of degradation and stiffness of extracellular matrix (ECM). Our simulation results show that cell-cell adhesion relationship must be satisfied for tumor invasion. Increased adhesion to ECM and decreased adhesion among tumor cells result in invasive tumor behaviors. When this invasive behavior occurs, ECM plays an important role for both tumor morphology and the shape of invasive cancer cells. Increased stiffness and stronger degree of degradation of ECM promote tumor invasion, generating more aggressive tumor invasive morphologies. It can also generate irregular shape of invasive cancer cells, protruding towards ECM. The capability of our model suggests it a useful tool to study tumor invasion and might be used to propose optimal treatment in clinical applications.

  13. Treatment of amblyopia in the adult: insights from a new rodent model of visual perceptual learning

    Science.gov (United States)

    Bonaccorsi, Joyce; Berardi, Nicoletta; Sale, Alessandro

    2014-01-01

    Amblyopia is the most common form of impairment of visual function affecting one eye, with a prevalence of about 1–5% of the total world population. Amblyopia usually derives from conditions of early functional imbalance between the two eyes, owing to anisometropia, strabismus, or congenital cataract, and results in a pronounced reduction of visual acuity and severe deficits in contrast sensitivity and stereopsis. It is widely accepted that, due to a lack of sufficient plasticity in the adult brain, amblyopia becomes untreatable after the closure of the critical period in the primary visual cortex. However, recent results obtained both in animal models and in clinical trials have challenged this view, unmasking a previously unsuspected potential for promoting recovery even in adulthood. In this context, non invasive procedures based on visual perceptual learning, i.e., the improvement in visual performance on a variety of simple visual tasks following practice, emerge as particularly promising to rescue discrimination abilities in adult amblyopic subjects. This review will survey recent work regarding the impact of visual perceptual learning on amblyopia, with a special focus on a new experimental model of perceptual learning in the amblyopic rat. PMID:25076874

  14. Dynamical effects of subducting ridges: Insights from 3-D laboratory models

    CERN Document Server

    Martinod, Joseph; Faccenna, Claudio; Labanieh, Shasa; Regard, Vincent; 10.1111/j.1365-246X.2005.02797.x

    2010-01-01

    We model the subduction of buoyant ridges and plateaus to study their effect on slab dynamics. Oceanic ridges parallel to the trench have a stronger effect on the process of subduction because they simultaneously affect a longer trench segment. Large buoyant slab segments sink more slowly into the asthenosphere, and their subduction result in a diminution of the velocity of subduction of the plate. We observe a steeping of the slab below those buoyant anomalies, resulting in smaller radius of curvature of the slab, that augments the energy dissipated in folding the plate and further diminishes the velocity of subduction. When the 3D geometry of a buoyant plateau is modelled, the dip of the slab above the plateau decreases, as a result of the larger velocity of subduction of the dense "normal" oceanic plate on both sides of the plateau. Such a perturbation of the dip of the slab maintains long time after the plateau has been entirely incorporated into the subduction zone. We compare experiments with the presen...

  15. The mitochondrial theory of aging: insight from transgenic and knockout mouse models.

    Science.gov (United States)

    Jang, Youngmok C; Van Remmen, Holly

    2009-04-01

    A substantial body of evidence has accumulated over the past 35 years in support of a role for oxidative damage to the mitochondrial respiratory chain and mitochondrial DNA in the determination of mammalian lifespan. The goal of this review is to provide a concise summary of recent studies using transgenic and knockout mouse models with altered expression of mitochondrial antioxidant enzymes (MnSOD (Sod2Tg and Sod2(+/-)), thioredoxin 2 (Trx2(+/-)), mitochondrial targeted catalase (mCAT) and mutant mice models that have been genetically manipulated to increase mitochondrial deletions or mutations (Polgamma(D257A/D257A) mutant mice) to examine the role of mitochondrial oxidative stress in aging. The majority of studies using these strategies do not support a clear role for mitochondrial oxidative stress or a vicious cycle of oxidative damage in the determination of lifespan in mice and furthermore do not support the free radical theory of aging. However, several key questions remain to be addressed and clearly more studies are required to fully understand the role of mitochondria in age-related disease and aging.

  16. Thrust-wrench fault interference in a brittle medium: new insights from analogue modelling experiments

    Science.gov (United States)

    Rosas, Filipe; Duarte, Joao; Schellart, Wouter; Tomas, Ricardo; Grigorova, Vili; Terrinha, Pedro

    2015-04-01

    We present analogue modelling experimental results concerning thrust-wrench fault interference in a brittle medium, to try to evaluate the influence exerted by different prescribed interference angles in the formation of morpho-structural interference fault patterns. All the experiments were conceived to simulate simultaneous reactivation of confining strike-slip and thrust faults defining a (corner) zone of interference, contrasting with previously reported discrete (time and space) superposition of alternating thrust and strike-slip events. Different interference angles of 60°, 90° and 120° were experimentally investigated by comparing the specific structural configurations obtained in each case. Results show that a deltoid-shaped morpho-structural pattern is consistently formed in the fault interference (corner) zone, exhibiting a specific geometry that is fundamentally determined by the different prescribed fault interference angle. Such angle determines the orientation of the displacement vector shear component along the main frontal thrust direction, determining different fault confinement conditions in each case, and imposing a complying geometry and kinematics of the interference deltoid structure. Model comparison with natural examples worldwide shows good geometric and kinematic similarity, pointing to the existence of matching underlying dynamic process. Acknowledgments This work was sponsored by the Fundação para a Ciência e a Tecnologia (FCT) through project MODELINK EXPL/GEO-GEO/0714/2013.

  17. Is HIV short-sighted? Insights from a multistrain nested model.

    Science.gov (United States)

    Lythgoe, Katrina A; Pellis, Lorenzo; Fraser, Christophe

    2013-10-01

    An important component of pathogen evolution at the population level is evolution within hosts. Unless evolution within hosts is very slow compared to the duration of infection, the composition of pathogen genotypes within a host is likely to change during the course of an infection, thus altering the composition of genotypes available for transmission as infection progresses. We develop a nested modeling approach that allows us to follow the evolution of pathogens at the epidemiological level by explicitly considering within-host evolutionary dynamics of multiple competing strains and the timing of transmission. We use the framework to investigate the impact of short-sighted within-host evolution on the evolution of virulence of human immunodeficiency virus (HIV), and find that the topology of the within-host adaptive landscape determines how virulence evolves at the epidemiological level. If viral reproduction rates increase significantly during the course of infection, the viral population will evolve a high level of virulence even though this will reduce the transmission potential of the virus. However, if reproduction rates increase more modestly, as data suggest, our model predicts that HIV virulence will be only marginally higher than the level that maximizes the transmission potential of the virus.

  18. Finding the 'lost years' in green turtles: insights from ocean circulation models and genetic analysis.

    Science.gov (United States)

    Putman, Nathan F; Naro-Maciel, Eugenia

    2013-10-07

    Organismal movement is an essential component of ecological processes and connectivity among ecosystems. However, estimating connectivity and identifying corridors of movement are challenging in oceanic organisms such as young turtles that disperse into the open sea and remain largely unobserved during a period known as 'the lost years'. Using predictions of transport within an ocean circulation model and data from published genetic analysis, we present to our knowledge, the first basin-scale hypothesis of distribution and connectivity among major rookeries and foraging grounds (FGs) of green turtles (Chelonia mydas) during their 'lost years'. Simulations indicate that transatlantic dispersal is likely to be common and that recurrent connectivity between the southwestern Indian Ocean and the South Atlantic is possible. The predicted distribution of pelagic juvenile turtles suggests that many 'lost years hotspots' are presently unstudied and located outside protected areas. These models, therefore, provide new information on possible dispersal pathways that link nesting beaches with FGs. These pathways may be of exceptional conservation concern owing to their importance for sea turtles during a critical developmental period.

  19. Langevin power curve analysis for numerical WEC models with new insights on high frequency power performance

    CERN Document Server

    Mücke, Tanja A; Milan, Patrick; Peinke, Joachim

    2015-01-01

    Based on the Langevin equation it has been proposed to obtain power curves for wind turbines from high frequency data of wind speed measurements u(t) and power output P (t). The two parts of the Langevin approach, power curve and drift field, give a comprehensive description of the conversion dynamic over the whole operating range of the wind turbine. The method deals with high frequent data instead of 10 min means. It is therefore possible to gain a reliable power curve already from a small amount of data per wind speed. Furthermore, the method is able to visualize multiple fixed points, which is e.g. characteristic for the transition from partial to full load or in case the conversion process deviates from the standard procedures. In order to gain a deeper knowledge it is essential that the method works not only for measured data but also for numerical wind turbine models and synthetic wind fields. Here, we characterize the dynamics of a detailed numerical wind turbine model and calculate the Langevin power...

  20. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models

    Directory of Open Access Journals (Sweden)

    Fabio Demontis

    2013-11-01

    Full Text Available A characteristic feature of aged humans and other mammals is the debilitating, progressive loss of skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies.

  1. From an animal model of an attentional deficit towards new insights into the pathophysiology of schizophrenia.

    Science.gov (United States)

    Feldon, J; Weiner, I

    1992-10-01

    The paper presents an animal model of schizophrenic-like attentional deficit, consisting of an inability to ignore irrelevant stimuli. It is based on the paradigm of latent inhibition (LI), in which animals learn to ignore repeatedly presented stimuli not followed by meaningful consequences. In a series of experiments it was demonstrated that the capacity to ignore irrelevant stimuli is lost in rats treated with systemic or intra-accumbens injections of amphetamine, in normal volunteers given amphetamine, in high "psychosis-prone" persons, in acute schizophrenic patients and in untreated male adult rats that were raised until weaning under conditions of extremely restricted stimulation. In addition, LI is lost following the disruption of the hippocampal input to the nucleus accumbens. In all of the above conditions tested for antagonism by anti-psychotic drugs a loss of LI is reversed. On the basis of these results we propose an animal model which accommodates a neurodevelopmental dysfunction, hippocampal pathology, mesolimbic DA overactivity, vulnerability to stress, and gender differences, all of which have been postulated as factors in the pathophysiology of schizophrenia.

  2. An adaptive process model of motor learning: insights for the teaching of motor skills.

    Science.gov (United States)

    Tani, Go; Corrêa, Umberto Cesar; Basso, Luciano; Benda, Rodolfo Novellino; Ugrinowitsch, Herbert; Choshi, Koji

    2014-01-01

    This article presents an outline of a non-equilibrium model, in which motor learning is explained as a continuous process of stabilization and adaptation. The article also shows how propositions derived from this model have been tested, and discusses possible practical implications of some supporting evidence to the teaching of motor skills. The stabilization refers to a process of functional stabilization that is achieved through negative feedback mechanisms. Initially, inconsistent and incorrect responses are gradually reduced, leading to a spatial-temporal patterning of the action. The adaptation is one in which new skills are formed from the reorganization of those already acquired through the flexibility of the system, reorganization of the skill structure, or self-organization. In order to provide learners with competency for adaptation, teachers should (a) guide students to learn motor skills taking into account that the stabilization of performance is just a transitory state that must be dismantled to achieve higher levels of complexity; (b) be clear which parts (micro) compose the skills and how they interact in order to form the whole (macro); (c) manipulate the skills in terms of their temporal, spatial, and/or spatiotemporal dimensions; (d) organize practice initially in a constant way, and then in a varied regimen (random) when the motor skills involve requirements of time and force; and, inversely for motor skills with spatial demands; and (e), provide a moderate frequency of feedback.

  3. Nuclear magnetic shielding constants of liquid water: Insights from hybrid quantum mechanics/molecular mechanics models

    Science.gov (United States)

    Kongsted, Jacob; Nielsen, Christian B.; Mikkelsen, Kurt V.; Christiansen, Ove; Ruud, Kenneth

    2007-01-01

    We present a gauge-origin independent method for the calculation of nuclear magnetic shielding tensors of molecules in a structured and polarizable environment. The method is based on a combination of density functional theory (DFT) or Hartree-Fock wave functions with molecular mechanics. The method is unique in the sense that it includes three important properties that need to be fulfilled in accurate calculations of nuclear magnetic shielding constants: (i) the model includes electron correlation effects, (ii) the model uses gauge-including atomic orbitals to give gauge-origin independent results, and (iii) the effect of the environment is treated self-consistently using a discrete reaction-field methodology. The authors present sample calculations of the isotropic nuclear magnetic shielding constants of liquid water based on a large number of solute-solvent configurations derived from molecular dynamics simulations employing potentials which treat solvent polarization either explicitly or implicitly. For both the O17 and H1 isotropic shielding constants the best predicted results compare fairly well with the experimental data, i.e., they reproduce the experimental solvent shifts to within 4ppm for the O17 shielding and 1ppm for the H1 shielding.

  4. Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

    Directory of Open Access Journals (Sweden)

    Esther Reina-Romo

    2011-11-01

    Full Text Available Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields.

  5. Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

    Science.gov (United States)

    Sanz-Herrera, Jose A.; Reina-Romo, Esther

    2011-01-01

    Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields. PMID:22174660

  6. Assessing pneumococcal meningitis association with viral respiratory infections and antibiotics: insights from statistical and mathematical models.

    Science.gov (United States)

    Opatowski, Lulla; Varon, Emmanuelle; Dupont, Claire; Temime, Laura; van der Werf, Sylvie; Gutmann, Laurent; Boëlle, Pierre-Yves; Watier, Laurence; Guillemot, Didier

    2013-08-01

    Pneumococcus is an important human pathogen, highly antibiotic resistant and a major cause of bacterial meningitis worldwide. Better prevention requires understanding the drivers of pneumococcal infection incidence and antibiotic susceptibility. Although respiratory viruses (including influenza) have been suggested to influence pneumococcal infections, the underlying mechanisms are still unknown, and viruses are rarely considered when studying pneumococcus epidemiology. Here, we propose a novel mathematical model to examine hypothetical relationships between Streptococcus pneumoniae meningitis incidence (SPMI), acute viral respiratory infections (AVRIs) and antibiotic exposure. French time series of SPMI, AVRI and penicillin consumption over 2001-2004 are analysed and used to assess four distinct virus-bacteria interaction submodels, ascribing the interaction on pneumococcus transmissibility and/or pathogenicity. The statistical analysis reveals strong associations between time series: SPMI increases shortly after AVRI incidence and decreases overall as the antibiotic-prescription rate rises. Model simulations require a combined impact of AVRI on both pneumococcal transmissibility (up to 1.3-fold increase at the population level) and pathogenicity (up to threefold increase) to reproduce the data accurately, along with diminished epidemic fitness of resistant pneumococcal strains causing meningitis (0.97 (0.96-0.97)). Overall, our findings suggest that AVRI and antibiotics strongly influence SPMI trends. Consequently, vaccination protecting against respiratory virus could have unexpected benefits to limit invasive pneumococcal infections.

  7. Nuclear magnetic shielding constants of liquid water: insights from hybrid quantum mechanics/molecular mechanics models.

    Science.gov (United States)

    Kongsted, Jacob; Nielsen, Christian B; Mikkelsen, Kurt V; Christiansen, Ove; Ruud, Kenneth

    2007-01-21

    We present a gauge-origin independent method for the calculation of nuclear magnetic shielding tensors of molecules in a structured and polarizable environment. The method is based on a combination of density functional theory (DFT) or Hartree-Fock wave functions with molecular mechanics. The method is unique in the sense that it includes three important properties that need to be fulfilled in accurate calculations of nuclear magnetic shielding constants: (i) the model includes electron correlation effects, (ii) the model uses gauge-including atomic orbitals to give gauge-origin independent results, and (iii) the effect of the environment is treated self-consistently using a discrete reaction-field methodology. The authors present sample calculations of the isotropic nuclear magnetic shielding constants of liquid water based on a large number of solute-solvent configurations derived from molecular dynamics simulations employing potentials which treat solvent polarization either explicitly or implicitly. For both the (17)O and (1)H isotropic shielding constants the best predicted results compare fairly well with the experimental data, i.e., they reproduce the experimental solvent shifts to within 4 ppm for the (17)O shielding and 1 ppm for the (1)H shielding.

  8. Near-atomic structural model for bacterial DNA replication initiation complex and its functional insights.

    Science.gov (United States)

    Shimizu, Masahiro; Noguchi, Yasunori; Sakiyama, Yukari; Kawakami, Hironori; Katayama, Tsutomu; Takada, Shoji

    2016-12-13

    Upon DNA replication initiation in Escherichia coli, the initiator protein DnaA forms higher-order complexes with the chromosomal origin oriC and a DNA-bending protein IHF. Although tertiary structures of DnaA and IHF have previously been elucidated, dynamic structures of oriC-DnaA-IHF complexes remain unknown. Here, combining computer simulations with biochemical assays, we obtained models at almost-atomic resolution for the central part of the oriC-DnaA-IHF complex. This complex can be divided into three subcomplexes; the left and right subcomplexes include pentameric DnaA bound in a head-to-tail manner and the middle subcomplex contains only a single DnaA. In the left and right subcomplexes, DnaA ATPases associated with various cellular activities (AAA+) domain III formed helices with specific structural differences in interdomain orientations, provoking a bend in the bound DNA. In the left subcomplex a continuous DnaA chain exists, including insertion of IHF into the DNA looping, consistent with the DNA unwinding function of the complex. The intervening spaces in those subcomplexes are crucial for DNA unwinding and loading of DnaB helicases. Taken together, this model provides a reasonable near-atomic level structural solution of the initiation complex, including the dynamic conformations and spatial arrangements of DnaA subcomplexes.

  9. Modeling Physical Processes at the Nanoscale—Insight into Self-Organization of Small Systems (abstract)

    Science.gov (United States)

    Proykova, Ana

    2009-04-01

    Essential contributions have been made in the field of finite-size systems of ingredients interacting with potentials of various ranges. Theoretical simulations have revealed peculiar size effects on stability, ground state structure, phases, and phase transformation of systems confined in space and time. Models developed in the field of pure physics (atomic and molecular clusters) have been extended and successfully transferred to finite-size systems that seem very different—small-scale financial markets, autoimmune reactions, and social group reactions to advertisements. The models show that small-scale markets diverge unexpectedly fast as a result of small fluctuations; autoimmune reactions are sequences of two discontinuous phase transitions; and social groups possess critical behavior (social percolation) under the influence of an external field (advertisement). Some predicted size-dependent properties have been experimentally observed. These findings lead to the hypothesis that restrictions on an object's size determine the object's total internal (configuration) and external (environmental) interactions. Since phases are emergent phenomena produced by self-organization of a large number of particles, the occurrence of a phase in a system containing a small number of ingredients is remarkable.

  10. Ordering Dynamics in Neuron Activity Pattern Model: An Insight to Brain Functionality.

    Science.gov (United States)

    Gundh, Jasleen; Singh, Awaneesh; Singh, R K Brojen

    2015-01-01

    We study the domain ordering kinetics in d = 2 ferromagnets which corresponds to populated neuron activities with both long-ranged interactions, V(r) ∼ r-n and short-ranged interactions. We present the results from comprehensive Monte Carlo (MC) simulations for the nonconserved Ising model with n ≥ 2, interaction range considering near and far neighbors. Our model results could represent the long-ranged neuron kinetics (n ≤ 4) in consistent with the same dynamical behaviour of short-ranged case (n ≥ 4) at far below and near criticality. We found that emergence of fast and slow kinetics of long and short ranged case could imitate the formation of connections among near and distant neurons. The calculated characteristic length scale in long-ranged interaction is found to be n independent (L(t) ∼ t1/(n-2)), whereas short-ranged interaction follows L(t) ∼ t1/2 law and approximately preserve universality in domain kinetics. Further, we did the comparative study of phase ordering near the critical temperature which follows different behaviours of domain ordering near and far critical temperature but follows universal scaling law.

  11. Binding of carbendazim to bovine serum albumin: Insights from experimental and molecular modeling studies

    Science.gov (United States)

    Li, Jinhua; Zhang, Yulei; Hu, Lin; Kong, Yaling; Jin, Changqing; Xi, Zengzhe

    2017-07-01

    Carbendazim (CBZ) is a widely used benzimidazole fungicide in agriculture to control a wide range of fruit and vegetable pathogens, which may lead to potential health hazards. To evaluate the potential toxicity of CBZ, the binding mechanism of bovine serum albumin (BSA) with CBZ was investigated by the fluorescence quenching technology, UV absorbance spectra, circular dichroism (CD), and molecular modeling. The fluorescence titration and UV absorbance spectra revealed that the fluorescence quenching mechanism of BSA by CBZ was a combined quenching process. In addition, the studies of CD spectra suggested that the binding of CBZ to BSA changed the secondary structure of protein. Furthermore, the thermodynamic functions of enthalpy change (ΔH0) and entropy change (ΔS0) for the reaction were calculated to be 24.87 kJ mol-1 and 162.95 J mol-1 K-1 according to Van't Hoff equation. These data suggested that hydrophobic interaction play a major role in the binding of CBZ to BSA, which was in good agreement with the result of molecular modeling study.

  12. Homology modeling of Homo sapiens lipoic acid synthase: Substrate docking and insights on its binding mode.

    Science.gov (United States)

    Krishnamoorthy, Ezhilarasi; Hassan, Sameer; Hanna, Luke Elizabeth; Padmalayam, Indira; Rajaram, Rama; Viswanathan, Vijay

    2017-05-07

    Lipoic acid synthase (LIAS) is an iron-sulfur cluster mitochondrial enzyme which catalyzes the final step in the de novo pathway for the biosynthesis of lipoic acid, a potent antioxidant. Recently there has been significant interest in its role in metabolic diseases and its deficiency in LIAS expression has been linked to conditions such as diabetes, atherosclerosis and neonatal-onset epilepsy, suggesting a strong inverse correlation between LIAS reduction and disease status. In this study we use a bioinformatics approach to predict its structure, which would be helpful to understanding its role. A homology model for LIAS protein was generated using X-ray crystallographic structure of Thermosynechococcus elongatus BP-1 (PDB ID: 4U0P). The predicted structure has 93% of the residues in the most favour region of Ramachandran plot. The active site of LIAS protein was mapped and docked with S-Adenosyl Methionine (SAM) using GOLD software. The LIAS-SAM complex was further refined using molecular dynamics simulation within the subsite 1 and subsite 3 of the active site. To the best of our knowledge, this is the first study to report a reliable homology model of LIAS protein. This study will facilitate a better understanding mode of action of the enzyme-substrate complex for future studies in designing drugs that can target LIAS protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology

    Science.gov (United States)

    Dey, Aditi; Castleton, Anna Z.; Schwab, Claire; Samuel, Edward; Sivakumaran, Janani; Beaton, Brendan; Zareian, Nahid; Zhang, Christie Yu; Rai, Lena; Enver, Tariq; Moorman, Anthony V.; Fielding, Adele K.

    2014-01-01

    The distinct nature of acute lymphoblastic leukemia (ALL) in adults, evidenced by inferior treatment outcome and different genetic landscape, mandates specific studies of disease-initiating mechanisms. In this study, we used NOD/LtSz-scid IL2Rγ nullc (NSG) mouse xenotransplantation approaches to elucidate leukemia-initiating cell (LIC) biology in primary adult precursor B (pre-B) ALL to optimize disease modeling. In contrast with xenografting studies of pediatric ALL, we found that modification of the NSG host environment using preconditioning total body irradiation (TBI) was indispensable for efficient engraftment of adult non-t(4;11) pre-B ALL, whereas t(4;11) pre-B ALL was successfully reconstituted without this adaptation. Furthermore, TBI-based xenotransplantation of non-t(4;11) pre-B ALL enabled detection of a high frequency of LICs (<1:6900) and permitted frank leukemic engraftment from a remission sample containing drug-resistant minimal residual disease. Investigation of TBI-sensitive stromal-derived factor-1/chemokine receptor type 4 signaling revealed greater functional dependence of non-t(4;11) pre-B ALL on this niche-based interaction, providing a possible basis for the differential engraftment behavior. Thus, our studies establish the optimal conditions for experimental modeling of human adult pre-B ALL and demonstrate the critical protumorogenic role of microenvironment-derived SDF-1 in regulating adult pre-B LIC activity that may present a therapeutic opportunity. PMID:24825861

  14. Atomic level insights into realistic molecular models of dendrimer-drug complexes through MD simulations

    Science.gov (United States)

    Jain, Vaibhav; Maiti, Prabal K.; Bharatam, Prasad V.

    2016-09-01

    Computational studies performed on dendrimer-drug complexes usually consider 1:1 stoichiometry, which is far from reality, since in experiments more number of drug molecules get encapsulated inside a dendrimer. In the present study, molecular dynamic (MD) simulations were implemented to characterize the more realistic molecular models of dendrimer-drug complexes (1:n stoichiometry) in order to understand the effect of high drug loading on the structural properties and also to unveil the atomistic level details. For this purpose, possible inclusion complexes of model drug Nateglinide (Ntg) (antidiabetic, belongs to Biopharmaceutics Classification System class II) with amine- and acetyl-terminated G4 poly(amidoamine) (G4 PAMAM(NH2) and G4 PAMAM(Ac)) dendrimers at neutral and low pH conditions are explored in this work. MD simulation analysis on dendrimer-drug complexes revealed that the drug encapsulation efficiency of G4 PAMAM(NH2) and G4 PAMAM(Ac) dendrimers at neutral pH was 6 and 5, respectively, while at low pH it was 12 and 13, respectively. Center-of-mass distance analysis showed that most of the drug molecules are located in the interior hydrophobic pockets of G4 PAMAM(NH2) at both the pH; while in the case of G4 PAMAM(Ac), most of them are distributed near to the surface at neutral pH and in the interior hydrophobic pockets at low pH. Structural properties such as radius of gyration, shape, radial density distribution, and solvent accessible surface area of dendrimer-drug complexes were also assessed and compared with that of the drug unloaded dendrimers. Further, binding energy calculations using molecular mechanics Poisson-Boltzmann surface area approach revealed that the location of drug molecules in the dendrimer is not the decisive factor for the higher and lower binding affinity of the complex, but the charged state of dendrimer and drug, intermolecular interactions, pH-induced conformational changes, and surface groups of dendrimer do play an

  15. Sediment mobility and bed armoring in the St Clair River: insights from hydrodynamic modeling

    Science.gov (United States)

    Liu, Xiaofeng; Parker, Gary; Czuba, Jonathan A.; Oberg, Kevin; Mier, Jose M.; Best, James L.; Parsons, Daniel R.; Ashmore, Peter; Krishnappan, Bommanna G.; Garcia, Marcelo H.

    2012-01-01

    The lake levels in Lake Michigan-Huron have recently fallen to near historical lows, as has the elevation difference between Lake Michigan-Huron compared to Lake Erie. This decline in lake levels has the potential to cause detrimental impacts on the lake ecosystems, together with social and economic impacts on communities in the entire Great Lakes region. Results from past work suggest that morphological changes in the St Clair River, which is the only natural outlet for Lake Michigan-Huron, could be an appreciable factor in the recent trends of lake level decline. A key research question is whether bed erosion within the river has caused an increase in water conveyance, therefore, contributed to the falling lake level. In this paper, a numerical modeling approach with field data is used to investigate the possibility of sediment movement in the St Clair River and assess the likelihood of morphological change under the current flow regime. A two-dimensional numerical model was used to study flow structure, bed shear stress, and sediment mobility/armoring over a range of flow discharges. Boundary conditions for the numerical model were provided by detailed field measurements that included high-resolution bathymetry and three-dimensional flow velocities. The results indicate that, without considering other effects, under the current range of flow conditions, the shear stresses produced by the river flow are too low to transport most of the coarse bed sediment within the reach and are too low to cause substantial bed erosion or bed scour. However, the detailed maps of the bed show mobile bedforms in the upper St Clair River that are indicative of sediment transport. Relatively high shear stresses near a constriction at the upstream end of the river and at channel bends could cause local scour and deposition. Ship-induced propeller wake erosion also is a likely cause of sediment movement in the entire reach. Other factors that may promote sediment movement, such as ice

  16. INVESTIGATION OF LITHOSPHERIC STRUCTURE IN MONGOLIA: INSIGHTS FROM INSAR OBSERVATIONS AND MODELLING

    Directory of Open Access Journals (Sweden)

    Z. Jing

    2017-09-01

    Full Text Available The western Mongolia is a seismically active intracontinental region, with ongoing tectonic deformation and widespread seismicity related to the far-field effects of India-Eurasia collision. During the 20th century, four earthquakes with the magnitude larger than 8 occurred in the western Mongolia and its surrounding regions, providing a unique opportunity to study the geodynamics of intracontinental tectonic deformations. The 1957 magnitude 8.3 Gobi-Altai earthquake is one of the largest seismic events. The deformation pattern of rupture zone associated with this earthquake is complex, involving left-lateral strike-slip and reverse dip-slip faulting on several distinct geological structures in a 264 × 40 km wide zone. To understand the relationship between the observed postseismic surface deformation and the rheological structure of the upper lithosphere, Interferometric Synthetic Aperture Radar (InSAR data are used to study the 1957 earthquake. Then we developed a postseismic model in a spherical, radially layered elastic-viscoelastic Earth based on InSAR results, and further analysed the dominant contribution to the surface deformation. This work is important for understanding not only the regional tectonics, but also the structure and dynamics of the lithosphere. SAR data were acquired from the ERS1/2 and Envisat from 1996 to 2010. Using the Repeat Orbit Interferometry Package (ROI_PAC, 124 postseismic interferograms are produced on four adjacent tracks. By stacking these interferograms, the maximum InSAR line-of-sight deformation rate along the Gobi-Altai fault zone is obtained. The main results are as follows: (1 The maximum InSAR line-of-sight deformation velocity along this large fault zone is about 6 mm/yr; (2 The modelled surface deformation suggests that the viscoelastic relaxation is the most reasonable mechanism to explain the observed surface motion; (3 The optimal model cover the Gobi-Altai seismogenic thickness is 10

  17. Investigation of Lithospheric Structure in Mongolia: Insights from Insar Observations and Modelling

    Science.gov (United States)

    Jing, Z.; Bihong, F.; Pilong, S.; Qiang, G.

    2017-09-01

    The western Mongolia is a seismically active intracontinental region, with ongoing tectonic deformation and widespread seismicity related to the far-field effects of India-Eurasia collision. During the 20th century, four earthquakes with the magnitude larger than 8 occurred in the western Mongolia and its surrounding regions, providing a unique opportunity to study the geodynamics of intracontinental tectonic deformations. The 1957 magnitude 8.3 Gobi-Altai earthquake is one of the largest seismic events. The deformation pattern of rupture zone associated with this earthquake is complex, involving left-lateral strike-slip and reverse dip-slip faulting on several distinct geological structures in a 264 × 40 km wide zone. To understand the relationship between the observed postseismic surface deformation and the rheological structure of the upper lithosphere, Interferometric Synthetic Aperture Radar (InSAR) data are used to study the 1957 earthquake. Then we developed a postseismic model in a spherical, radially layered elastic-viscoelastic Earth based on InSAR results, and further analysed the dominant contribution to the surface deformation. This work is important for understanding not only the regional tectonics, but also the structure and dynamics of the lithosphere. SAR data were acquired from the ERS1/2 and Envisat from 1996 to 2010. Using the Repeat Orbit Interferometry Package (ROI_PAC), 124 postseismic interferograms are produced on four adjacent tracks. By stacking these interferograms, the maximum InSAR line-of-sight deformation rate along the Gobi-Altai fault zone is obtained. The main results are as follows: (1) The maximum InSAR line-of-sight deformation velocity along this large fault zone is about 6 mm/yr; (2) The modelled surface deformation suggests that the viscoelastic relaxation is the most reasonable mechanism to explain the observed surface motion; (3) The optimal model cover the Gobi-Altai seismogenic thickness is 10 km; (4) The

  18. A way to synchronize models with seismic faults for earthquake forecasting: Insights from a simple stochastic model

    CERN Document Server

    González, A; Gómez, J B; Pacheco, A F; Gonzalez, Alvaro; Vazquez-Prada, Miguel; Gomez, Javier B.; Pacheco, Amalio F.

    2005-01-01

    Numerical models of seismic faults are starting to be used for determining the future behaviour of seismic faults and fault networks. Their final goal would be to forecast future large earthquakes. In order to use them for this task, it is necessary to synchronize each model with the current status of the actual fault or fault network it simulates (just as, for example, meteorologists synchronize their models with the atmosphere by incorporating current atmospheric data in them). However, lithospheric dynamics is largely unobservable: important parameters cannot (or can rarely) be measured in Nature. Earthquakes, though, provide indirect but measurable clues of the stress and strain status in the lithosphere, which should be helpful for the accurate synchronization of the models. The rupture area is one of the measurable parameters of actual earthquakes. Here we explore how this can be used to at least synchronize fault models between themselves and forecast synthetic earthquakes. Our purpose here is to forec...

  19. Genome sequence analysis of the model grass Brachypodium distachyon: insights into grass genome evolution

    Energy Technology Data Exchange (ETDEWEB)

    Schulman, Al

    2009-08-09

    Three subfamilies of grasses, the Erhardtoideae (rice), the Panicoideae (maize, sorghum, sugar cane and millet), and the Pooideae (wheat, barley and cool season forage grasses) provide the basis of human nutrition and are poised to become major sources of renewable energy. Here we describe the complete genome sequence of the wild grass Brachypodium distachyon (Brachypodium), the first member of the Pooideae subfamily to be completely sequenced. Comparison of the Brachypodium, rice and sorghum genomes reveals a precise sequence- based history of genome evolution across a broad diversity of the grass family and identifies nested insertions of whole chromosomes into centromeric regions as a predominant mechanism driving chromosome evolution in the grasses. The relatively compact genome of Brachypodium is maintained by a balance of retroelement replication and loss. The complete genome sequence of Brachypodium, coupled to its exceptional promise as a model system for grass research, will support the development of new energy and food crops

  20. Sites of action of sleep and wake drugs: insights from model organisms.

    Science.gov (United States)

    Rihel, Jason; Schier, Alexander F

    2013-10-01

    Small molecules have been used since antiquity to regulate our sleep. Despite the explosion of diverse drugs to treat problems of too much or too little sleep, the detailed mechanisms of action and especially the neuronal targets by which these compounds alter human behavioural states are not well understood. Research efforts in model systems such as mouse, zebrafish and fruit fly are combining conditional genetics and optogenetics with pharmacology to map the effects of sleep-promoting drugs onto neural circuits. Recent studies raise the possibility that many small molecules alter sleep and wake via specific sets of critical neurons rather than through the global modulation of multiple brain targets. These findings also uncover novel brain areas as sleep/wake regulators and indicate that the development of circuit-selective drugs might alleviate sleep disorders with fewer side effects. Published by Elsevier Ltd.