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

    Deep brain stimulation (DBS) is a standard neurosurgical procedure used to treat motor symptoms in about 5% of patients with Parkinson's disease (PD). Despite the indisputable success of this procedure, the biological mechanisms underlying the clinical benefits of DBS have not yet been fully...... and exploring the physiological mechanisms which respond to this treatment strategy (i.e., DBS). Finally, we present new insights into the ways this computational model may help to elucidate the dynamic network effects produced in a cerebral structure when DBS is applied. (C) 2007 Elsevier Ltd. All rights...

  2. Improved understanding of protein complex offers insight into DNA

    Science.gov (United States)

    Summer Science Writing Internship Improved understanding of protein complex offers insight into DNA clearer understanding of the origin recognition complex (ORC) - a protein complex that directs DNA replication - through its crystal structure offers new insight into fundamental mechanisms of DNA replication

  3. Assuring Quality in Online Offerings: Insights from a University's Faculty

    Science.gov (United States)

    Budden, Connie B.; Budden, Heather L.; Hall, Michelle; Longman, Debbie G.

    2015-01-01

    As the growth of online education offered by universities accelerates and spreads, universities are increasingly grappling with concerns related to widespread availability and the maintenance of academic quality. The "Quality Matters at Southeastern" Program fosters quality through a peer review process and offers a certification process…

  4. 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).  

  5. 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.

  6. 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  

  7. 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).

  8. 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.

  9. 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.

  10. Offers

    CERN Document Server

    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 off...

  11. 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 ...

  12. 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

  13. 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  

  14. Offers

    CERN Multimedia

    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

  15. 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)

  16. 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  

  17. Offers

    CERN Document Server

    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.  

  18. 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.

  19. 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  

  20. 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/

  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

    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.  

  3. 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).

  4. 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. ...

  5. Offers

    CERN Multimedia

    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

  6. 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  

  7. Offers

    CERN Multimedia

    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...

  8. 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.

  9. 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/

  10. Offer

    CERN Document Server

    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.  

  11. 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, 20...

  12. 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...

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

    Science.gov (United States)

    ... Spotlight on Research Novel Insights Into Causes of Scleroderma Offer Potential New Treatment Strategies By Kirstie Saltsman, Ph.D. | December 15, 2013 In scleroderma, immune cells invade the skin, but the role ...

  14. Ethics in Publishing: Complexity Science and Human Factors Offer Insights to Develop a Just Culture.

    Science.gov (United States)

    Saurin, Tarcisio Abreu

    2016-12-01

    While ethics in publishing has been increasingly debated, there seems to be a lack of a theoretical framework for making sense of existing rules of behavior as well as for designing, managing and enforcing such rules. This letter argues that systems-oriented disciplines, such as complexity science and human factors, offer insights into new ways of dealing with ethics in publishing. Some examples of insights are presented. Also, a call is made for empirical studies that unveil the context and details of both retracted papers and the process of writing and publishing academic papers. This is expected to shed light on the complexity of the publication system as well as to support the development of a just culture, in which all participants are accountable.

  15. Patient narratives in Yelp reviews offer insight into opioid experiences and the challenges of pain management.

    Science.gov (United States)

    Graves, Rachel L; Goldshear, Jesse; Perrone, Jeanmarie; Ungar, Lyle; Klinger, Elissa; Meisel, Zachary F; Merchant, Raina M

    2018-03-01

    To characterize Yelp reviews about pain management and opioids. We manually coded and applied natural language processing to 836 Yelp reviews of US hospitals mentioning an opioid medication. Yelp reviews by patients and caregivers describing experiences with pain management and opioids had lower ratings compared with other reviews. Negative descriptions of pain management and opioid-related experiences were more commonly described than positive experiences, and the number of themes they reflected was more diverse. Yelp reviews offer insights into pain management and opioid use that are not assessed by traditional surveys. As a free, highly utilized source of unstructured narratives, Yelp may allow ongoing assessment of policies related to pain management and opioid use.

  16. Franchise Business Model: Theoretical Insights

    OpenAIRE

    Levickaitė, Rasa; Reimeris, Ramojus

    2010-01-01

    The article is based on literature review, theoretical insights, and deals with the topic of franchise business model. The objective of the paper is to analyse peculiarities of franchise business model and its developing conditions in Lithuania. The aim of the paper is to make an overview on franchise business model and its environment in Lithuanian business context. The overview is based on international and local theoretical insights. In terms of practical meaning, this article should be re...

  17. Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder.

    Science.gov (United States)

    Andrews, Shan V; Ellis, Shannon E; Bakulski, Kelly M; Sheppard, Brooke; Croen, Lisa A; Hertz-Picciotto, Irva; Newschaffer, Craig J; Feinberg, Andrew P; Arking, Dan E; Ladd-Acosta, Christine; Fallin, M Daniele

    2017-10-24

    Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly.

  18. Quality of tuberculosis care by Indian pharmacies: Mystery clients offer new insights

    Directory of Open Access Journals (Sweden)

    Rosalind Miller

    2018-01-01

    Full Text Available For many patients in India, pharmacies are their first point of contact, where most drugs, including antibiotics, can be purchased over-the-counter (OTC. Recent standardised (simulated patient studies, covering four Indian cities, provide new insights on how Indian pharmacies manage patients with suspected or known tuberculosis. Correct management of the simulated patients ranged from 13% to 62%, increasing with the certainty of the TB diagnosis. Antibiotics were frequently dispensed OTC to patients, with 16% to 37% receiving such drugs across the cases. On a positive note, these studies showed that no pharmacy dispensed first-line anti-TB drugs. Engagement of pharmacies is important to not only improve TB detection and care, but also limit the abuse of antibiotics.

  19. Recommendations from Friends Anytime and Anywhere: Toward a Model of Contextual Offer and Consumption Values

    Science.gov (United States)

    Shen, Xiao-Liang; Wang, Nan

    2013-01-01

    Abstract The ubiquity and portability of mobile devices provide additional opportunities for information retrieval. People can easily access mobile applications anytime and anywhere when they need to acquire specific context-aware recommendations (contextual offer) from their friends. This study, thus, represents an initial attempt to understand users' acceptance of a mobile-based social reviews platform, where recommendations from friends can be obtained with mobile devices. Based on the consumption value theory, a theoretical model is proposed and empirically examined using survey data from 218 mobile users. The findings demonstrate that contextual offers based on users' profiles, access time, and geographic positions significantly predict their value perceptions (utilitarian, hedonic, and social), which, in turn, affect their intention to use a mobile social reviews platform. This study is also believed to provide some useful insights to both research and practice. PMID:23530548

  20. Local and regional energy companies offering energy services: Key activities and implications for the business model

    International Nuclear Information System (INIS)

    Kindström, Daniel; Ottosson, Mikael

    2016-01-01

    Highlights: • Many companies providing energy services are experiencing difficulties. • This research identifies key activities for the provision of energy services. • Findings are aggregated to the business-model level providing managerial insights. • This research identifies two different business model innovation paths. • Energy companies may need to renew parts of, or the entire, business model. - Abstract: Energy services play a key role in increasing energy efficiency in the industry. The key actors in these services are the local and regional energy companies that are increasingly implementing energy services as part of their market offering and developing service portfolios. Although expectations for energy services have been high, progress has so far been limited, and many companies offering energy services, including energy companies, are experiencing difficulties in implementing energy services and providing them to the market. Overall, this research examines what is needed for local and regional energy companies to successfully implement energy services (and consequently provide them to the market). In doing this, a two-stage process is used: first, we identify key activities for the successful implementation of energy services, and second, we aggregate the findings to the business model level. This research demonstrates that to succeed in implementing energy services, an energy company may need to renew parts or all of its existing product-based business model, formulate a new business model, or develop coexisting multiple business models. By discussing two distinct business model innovation processes, this research demonstrates that there can be different paths to success.

  1. Determinants of Brand Equity: Offering a Model to Chocolate Industry

    OpenAIRE

    Emari Hossien

    2011-01-01

    This study examined the underlying dimensions of brand equity in the chocolate industry. For this purpose, researchers developed a model to identify which factors are influential in building brand equity. The second purpose was to assess brand loyalty and brand images mediating effect between brand attitude, brand personality, brand association with brand equity. The study employed structural equation modeling to investigate the causal relationships between the dimensions...

  2. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance.

    Science.gov (United States)

    Wei, Pengcheng; Song, Guangji; Shi, Mengyang; Zhou, Yafei; Liu, Yang; Lei, Jun; Chen, Peng; Yin, Lei

    2018-02-01

    Colistin is considered a last-resort antibiotic against most gram-negative bacteria. Recent discoveries of a plasmid-mediated, transferable mobilized colistin-resistance gene ( mcr-1) on all continents have heralded the imminent emergence of pan-drug-resistant superbacteria. The inner-membrane protein MCR-1 can catalyze the transfer of phosphoethanolamine (PEA) to lipid A, resulting in colistin resistance. However, little is known about the mechanism, and few drugs exist to address this issue. We present crystal structures revealing the MCR-1 catalytic domain (cMCR-1) as a monozinc metalloprotein with ethanolamine (ETA) and d-glucose, respectively, thus highlighting 2 possible substrate-binding pockets in the MCR-1-catalyzed PEA transfer reaction. Mutation of the residues involved in ETA and d-glucose binding impairs colistin resistance in recombinant Escherichia coli containing full-length MCR-1. Partial analogs of the substrate are used for cocrystallization with cMCR-1, providing valuable information about the family of PEA transferases. One of the analogs, ETA, causes clear inhibition of polymyxin B resistance, highlighting its potential for drug development. These data demonstrate the crucial role of the PEA- and lipid A-binding pockets and provide novel insights into the structure-based mechanisms, important drug-target hot spots, and a drug template for further drug development to combat the urgent, rising threat of MCR-1-mediated antibiotic resistance.-Wei, P., Song, G., Shi, M., Zhou, Y., Liu, Y., Lei, J., Chen, P., Yin, L. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance.

  3. What Can Human Geography Offer Climate Change Modelling?

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2014-01-01

    behaviour to economic rationality when construed in sophisticated climate models and sometimes in nongeographical representations. The need to comprehensively take into consideration methodological approaches concerning the interface of society-environment interactions seems highly relevant to contemporary...... regularities, rationalities, and pre-analytic assumptions. Lastly we discuss challenges of constructing nature(s) and how we better understand the (geo) politics of climate change modeling.......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...

  4. Next-generation sequencing and culture-based techniques offer complementary insights into fungi and prokaryotes in beach sands.

    Science.gov (United States)

    Romão, Daniela; Staley, Christopher; Ferreira, Filipa; Rodrigues, Raquel; Sabino, Raquel; Veríssimo, Cristina; Wang, Ping; Sadowsky, Michael; Brandão, João

    2017-06-15

    A next-generation sequencing (NGS) approach, in conjunction with culture-based methods, was used to examine fungal and prokaryotic communities for the presence of potential pathogens in beach sands throughout Portugal. Culture-based fungal enumeration revealed low and variable concentrations of the species targeted (yeasts and dermatophytes), which were underrepresented in the community characterized by NGS targeting the ITS1 region. Conversely, NGS indicated that the potentially pathogenic species Purpureocillium liliacinum comprised nearly the entire fungal community. Culturable fecal indicator bacterial concentrations were low throughout the study and unrelated to communities characterized by NGS. Notably, the prokaryotic communities characterized revealed a considerable abundance of archaea. Results highlight differences in communities between methods in beach sand monitoring but indicate the techniques offer complementary insights. Thus, there is a need to leverage culture-based methods with NGS methods, using a toolbox approach, to determine appropriate targets and metrics for beach sand monitoring to adequately protect public health. Copyright © 2017. Published by Elsevier Ltd.

  5. 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.

  6. 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,…

  7. Dash Cam videos on YouTube™ offer insights into factors related to moose-vehicle collisions.

    Science.gov (United States)

    Rea, Roy V; Johnson, Chris J; Aitken, Daniel A; Child, Kenneth N; Hesse, Gayle

    2018-03-26

    To gain a better understanding of the dynamics of moose-vehicle collisions, we analyzed 96 videos of moose-vehicle interactions recorded by vehicle dash-mounted cameras (Dash Cams) that had been posted to the video-sharing website YouTube™. Our objective was to determine the effects of road conditions, season and weather, moose behavior, and driver response to actual collisions compared to near misses when the collision was avoided. We identified 11 variables that were consistently observable in each video and that we hypothesized would help to explain a collision or near miss. The most parsimonious logistic regression model contained variables for number of moose, sight time, vehicle slows, and vehicle swerves (AIC c w = 0.529). This model had good predictive accuracy (AUC = 0.860, SE = 0.041). The only statistically significant variable from this model that explained the difference between moose-vehicle collisions and near misses was 'Vehicle slows'. Our results provide no evidence that road surface conditions (dry, wet, ice or snow), roadside habitat type (forested or cleared), the extent to which roadside vegetation was cleared, natural light conditions (overcast, clear, twilight, dark), season (winter, spring and summer, fall), the presence of oncoming traffic, or the direction from which the moose entered the roadway had any influence on whether a motorist collided with a moose. Dash Cam videos posted to YouTube™ provide a unique source of data for road safety planners trying to understand what happens in the moments just before a moose-vehicle collision and how those factors may differ from moose-vehicle encounters that do not result in a collision. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. 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.

  9. Business Process as a Service Model Based Business and IT Cloud Alignment as a Cloud Offering

    OpenAIRE

    Robert Woitsch; Wilfrid Utz

    2015-01-01

    Cloud computing proved to offer flexible IT solutions. Although large enterprises may benefit from this technology, SMEs are falling behind in cloud usage due to missing ITcompetence and hence lose the ability to efficiently adapt their IT to their business needs. This paper introduces the project idea of the H2020 project CloudSocket, by elaborating the idea of Business Processes as a Service (BPaaS), where concept models and semantics are applied to align business processes with Cloud deplo...

  10. Model Based Business and IT Cloud Alignment as a Cloud Offering

    OpenAIRE

    Robert Woitsch; Wilfrid Utz

    2015-01-01

    Cloud computing proved to offer flexible IT solutions. Although large enterprises may benefit from this technology by educating their IT departments, SMEs are dramatically falling behind in cloud usage and hence lose the ability to efficiently adapt their IT to their business needs. This paper introduces the project idea of the H2020 project CloudSocket, by elaborating the idea of Business Processes as a Service, where concept models and semantics are applied to align business pro...

  11. New Insights from Rodent Models of Fatty Liver Disease

    Science.gov (United States)

    2011-01-01

    Abstract Rodent models of fatty liver disease are essential research tools that provide a window into disease pathogenesis and a testing ground for prevention and treatment. Models come in many varieties involving dietary and genetic manipulations, and sometimes both. High-energy diets that induce obesity do not uniformly cause fatty liver disease; this has prompted close scrutiny of specific macronutrients and nutrient combinations to determine which have the greatest potential for hepatotoxicity. At the same time, diets that do not cause obesity or the metabolic syndrome but do cause severe steatohepatitis have been exploited to study factors important to progressive liver injury, including cell death, oxidative stress, and immune activation. Rodents with a genetic predisposition to overeating offer yet another model in which to explore the evolution of fatty liver disease. In some animals that overeat, steatohepatitis can develop even without resorting to a high-energy diet. Importantly, these models and others have been used to document that aerobic exercise can prevent or reduce fatty liver disease. This review focuses primarily on lessons learned about steatohepatitis from manipulations of diet and eating behavior. Numerous additional insights about hepatic lipid metabolism, which have been gained from genetically engineered mice, are also mentioned. Antioxid. Redox Signal. 15, 535–550. PMID:21126212

  12. [Offered income, salary expectations, and the economic activity of married women: an analytic model].

    Science.gov (United States)

    Lollivier, S

    1984-06-01

    This study uses data from tax declarations for 40,000 French households for 1975 to propose a model that permits quantification of the effects of certain significant factors on the economic activity of married women. The PROBIT model of analysis of variance was used to determine the specific effect of several variables, including age of the woman, number of children under 25 years of age in the household, the age of the youngest child, husband's income and socioprofessional status, wife's level and type of education, size of community of residence and region of residence. The principal factors influencing activity rates were found to be educational level, age, and to those of childless women, but activity rates dropped by about 30% for mothers of 2 and even more for mothers of 3 or more children. Influence of the place of residence and the husband's income were associated with lesser disparities. The reasons for variations in female labor force participation can be viewed as analogous to a balance. Underlying factors can increase or decrease the income the woman hopes to earn (offered income) as well as the minimum income for which she will work (required salary). A TOBIT model was constructed in which income was a function of age, education, geographic location, and number of children, and salary required was a function of the variables related to the husband including income and socioprofessional status. For most of the effects considered, the observed variation in activity rates resulted from variations in offered income. The husband's income influences only the desired salary. The offered income decreases and the required salary increases when the number of children is 2 or more, reducing the rate of activity. More educated women have slightly greater salary expectations, but command much higher salaries, resulting in an increased rate of professional activity.

  13. Special Offers

    CERN Multimedia

    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

  14. 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

  15. 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

  16. Offers INTERSOCCER

    CERN Multimedia

    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!    

  17. Offer acceptance practices and geographic variability in allocation model for end-stage liver disease at transplant.

    Science.gov (United States)

    Wey, Andrew; Pyke, Joshua; Schladt, David P; Gentry, Sommer E; Weaver, Tim; Salkowski, Nicholas; Kasiske, Bertram L; Israni, Ajay K; Snyder, Jon J

    2018-04-01

    Offer acceptance practices may cause geographic variability in allocation Model for End-Stage Liver Disease (aMELD) score at transplant and could magnify the effect of donor supply and demand on aMELD variability. To evaluate these issues, offer acceptance practices of liver transplant programs and donation service areas (DSAs) were estimated using offers of livers from donors recovered between January 1, 2016, and December 31, 2016. Offer acceptance practices were compared with liver yield, local placement of transplanted livers, donor supply and demand, and aMELD at transplant. Offer acceptance was associated with liver yield (odds ratio, 1.32; P offer acceptance (r = 0.09; P = 0.50). Additionally, the association between DSA-level donor-to-candidate ratios and aMELD at transplant did not change after adjustment for offer acceptance. The average squared difference in median aMELD at transplant across DSAs was 24.6; removing the effect of donor-to-candidate ratios reduced the average squared differences more than removing the effect of program-level offer acceptance (33% and 15% reduction, respectively). Offer acceptance practices and donor-to-candidate ratios independently contributed to geographic variability in aMELD at transplant. Thus, neither offer acceptance nor donor-to-candidate ratios can explain all of the geographic variability in aMELD at transplant. Liver Transplantation 24 478-487 2018 AASLD. © 2018 by the American Association for the Study of Liver Diseases.

  18. Osteoarthritis: new insights in animal models.

    Science.gov (United States)

    Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human 'idiopathic' OA, with late onset and slow progression, it is perhaps wise not to be overly enthusiastic about animal models that show severe chondrodysplasia and very early OA. Advantage by using genetically engineered mouse models, in comparison with other surgically induced models, is that molecular etiology is known. Find potential molecular markers for the onset of the disease and pay attention to the role of gender and environmental factors should be very helpful in the study of mice that acquire premature OA. Surgically induced destabilization of joint is the most widely used induction method. These models allow the temporal control of disease induction and follow predictable progression of the disease. In animals, ACL transection and meniscectomy show a speed of onset and severity of disease higher than in humans after same injury.

  19. Increasing reach by offering choices: Results from an innovative model for statewide services for smoking cessation.

    Science.gov (United States)

    Keller, Paula A; Schillo, Barbara A; Kerr, Amy N; Lien, Rebecca K; Saul, Jessie; Dreher, Marietta; Lachter, Randi B

    2016-10-01

    Although state quitlines provide free telephone counseling and often include nicotine replacement therapy (NRT), reach remains limited (1-2% in most states). More needs to be done to engage all smokers in the quitting process. A possible strategy is to offer choices of cessation services through quitlines and to reduce registration barriers. In March 2014, ClearWay Minnesota SM implemented a new model for QUITPLAN® Services, the state's population-wide cessation services. Tobacco users could choose the QUITPLAN® Helpline or one or more Individual QUITPLAN® Services (NRT starter kit, text messaging, email program, or quit guide). The program website was redesigned, online enrollment was added, and a new advertising campaign was created and launched. In 2014-2015, we evaluated whether these changes increased reach. We also assessed quit attempts, quit outcomes, predictors of 30-day abstinence, and average cost per quit via a seven-month follow-up survey. Between March 2014-February 2015, 15,861 unique tobacco users registered, which was a 169% increase over calendar year 2013. The majority of participants made a quit attempt (83.7%). Thirty-day point prevalence abstinence rates (responder rates) were 26.1% for QUITPLAN Services overall, 29.6% for the QUITPLAN Helpline, and 25.5% for Individual QUITPLAN Services. Several variables predicted quit outcomes, including receiving only one call from the Helpline and using both the Helpline and the NRT starter kit. Providing greater choice of cessation services and reducing registration barriers have the potential to engage more tobacco users, foster more quit attempts, and ultimately lead to long-term cessation and reductions in prevalence. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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

  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 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

  2. 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

  3. Melatonin receptors: latest insights from mouse models

    Science.gov (United States)

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

    2014-01-01

    Summary Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications towards 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. PMID:24903552

  4. Osteoarthritis: New Insights in Animal Models

    OpenAIRE

    Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human ‘idiopathic’ OA, with late onset and slow progression, it is perha...

  5. Esophageal Cancer: Insights from Mouse Models

    Directory of Open Access Journals (Sweden)

    Marie-Pier Tétreault

    2015-01-01

    Full Text Available Esophageal cancer is the eighth leading cause of cancer and the sixth most common cause of cancer-related death worldwide. Despite recent advances in the development of surgical techniques in combination with the use of radiotherapy and chemotherapy, the prognosis for esophageal cancer remains poor. The cellular and molecular mechanisms that drive the pathogenesis of esophageal cancer are still poorly understood. Hence, understanding these mechanisms is crucial to improving outcomes for patients with esophageal cancer. Mouse models constitute valuable tools for modeling human cancers and for the preclinical testing of therapeutic strategies in a manner not possible in human subjects. Mice are excellent models for studying human cancers because they are similar to humans at the physiological and molecular levels and because they have a shorter gestation time and life cycle. Moreover, a wide range of well-developed technologies for introducing genetic modifications into mice are currently available. In this review, we describe how different mouse models are used to study esophageal cancer.

  6. 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

  7. 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

  8. 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  

  9. Special offer

    CERN Multimedia

    Staff Association

    2011-01-01

    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. 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.…

  11. Optimization of calculation models of maintenance offers for new civil engines

    OpenAIRE

    Pechoutre, Jean-Baptiste

    2011-01-01

    The sales support department performs calculations concerning maintenance offerings for civil engines based on the use of complex tools. This report describes the missions conducted during my Master's thesis: firstly, the establishment of a monitoring and security tool in the process of calculating maintenance costs. The second achievement is the creation of a tool for decision support in order to estimate and compare some of the maintenance costs associated with the use of the new commercial...

  12. Hybrid discrete choice models: Gained insights versus increasing effort

    International Nuclear Information System (INIS)

    Mariel, Petr; Meyerhoff, Jürgen

    2016-01-01

    Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

  13. Hybrid discrete choice models: Gained insights versus increasing effort

    Energy Technology Data Exchange (ETDEWEB)

    Mariel, Petr, E-mail: petr.mariel@ehu.es [UPV/EHU, Economía Aplicada III, Avda. Lehendakari Aguire, 83, 48015 Bilbao (Spain); Meyerhoff, Jürgen [Institute for Landscape Architecture and Environmental Planning, Technical University of Berlin, D-10623 Berlin, Germany and The Kiel Institute for the World Economy, Duesternbrooker Weg 120, 24105 Kiel (Germany)

    2016-10-15

    Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

  14. The Turbulent Interstellar Medium: Insights and Questions from Numerical Models

    OpenAIRE

    Mac Low, Mordecai-Mark; de Avillez, Miguel A.; Korpi, Maarit J.

    2003-01-01

    "The purpose of numerical models is not numbers but insight." (Hamming) In the spirit of this adage, and of Don Cox's approach to scientific speaking, we discuss the questions that the latest generation of numerical models of the interstellar medium raise, at least for us. The energy source for the interstellar turbulence is still under discussion. We review the argument for supernovae dominating in star forming regions. Magnetorotational instability has been suggested as a way of coupling di...

  15. Michigan's Physician Group Incentive Program offers a regional model for incremental 'fee for value' payment reform.

    Science.gov (United States)

    Share, David A; Mason, Margaret H

    2012-09-01

    Blue Cross Blue Shield of Michigan partnered with providers across the state to create an innovative, "fee for value" physician incentive program that would deliver high-quality, efficient care. The Physician Group Incentive Program rewards physician organizations-formal groups of physicians and practices that can accept incentive payments on behalf of their members-based on the number of quality and utilization measures they adopt, such as generic drug dispensing rates, and on their performance on these measures across their patient populations. Physicians also receive payments for implementing a range of patient-centered medical home capabilities, such as patient registries, and they receive higher fees for office visits for incorporating these capabilities into routine practice while also improving performance. Taken together, the incentive dollars, fee increases, and care management payments amount to a potential increase in reimbursement of 40 percent or more from Blue Cross Blue Shield of Michigan for practices designated as high-performing patient-centered medical homes. At the same time, we estimate that implementing the patient-centered medical home capabilities was associated with $155 million in lower medical costs in program year 2011 for Blue Cross Blue Shield of Michigan members. We intend to devote a higher percentage of reimbursement over time to communities of caregivers that offer high-value, system-based care, and a lower percentage of reimbursement to individual physicians on a service-specific basis.

  16. 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…

  17. Integrated Payment And Delivery Models Offer Opportunities And Challenges For Residential Care Facilities.

    Science.gov (United States)

    Grabowski, David C; Caudry, Daryl J; Dean, Katie M; Stevenson, David G

    2015-10-01

    Under health care reform, new financing and delivery models are being piloted to integrate health and long-term care services for older adults. Programs using these models generally have not included residential care facilities. Instead, most of them have focused on long-term care recipients in the community or the nursing home. Our analyses indicate that individuals living in residential care facilities have similarly high rates of chronic illness and Medicare utilization when compared with matched individuals in the community and nursing home, and rates of functional dependency that fall between those of their counterparts in the other two settings. These results suggest that the residential care facility population could benefit greatly from models that coordinated health and long-term care services. However, few providers have invested in the infrastructure needed to support integrated delivery models. Challenges to greater care integration include the private-pay basis for residential care facility services, which precludes shared savings from reduced Medicare costs, and residents' preference for living in a home-like, noninstitutional environment. Project HOPE—The People-to-People Health Foundation, Inc.

  18. Focal species and landscape "naturalness" corridor models offer complementary approaches for connectivity conservation planning

    Science.gov (United States)

    Meade Krosby; Ian Breckheimer; D. John Pierce; Peter H. Singleton; Sonia A. Hall; Karl C. Halupka; William L. Gaines; Robert A. Long; Brad H. McRae; Brian L. Cosentino; Joanne P. Schuett-Hames

    2015-01-01

    Context   The dual threats of habitat fragmentation and climate change have led to a proliferation of approaches for connectivity conservation planning. Corridor analyses have traditionally taken a focal species approach, but the landscape ‘‘naturalness’’ approach of modeling connectivity among areas of low human modification has gained popularity...

  19. Integrated Payment and Delivery Models Offer Opportunities and Challenges for Residential Care Facilities

    OpenAIRE

    Grabowski, David C.; Caudry, Daryl J.; Dean, Katie M.; Stevenson, David G.

    2015-01-01

    Under health care reform, a series of new financing and delivery models are being piloted to integrate health and long-term care services for older adults. To date, these programs have not encompassed residential care facilities, with most programs focusing on long-term care recipients in the community or the nursing home. Our analyses indicate that individuals living in residential care facilities have similarly high rates of chronic illness and Medicare utilization when compared with simila...

  20. Pokémon-Go: Why Augmented Reality Games Offer Insights for Enhancing Public Health Interventions on Obesity-Related Diseases.

    Science.gov (United States)

    Wong, Ming Chao; Turner, Paul; MacIntyre, Kate; Yee, Kwang Chien

    2017-01-01

    Stimulating widespread interests of the population to participate in behavioural changes through information and technology has been an aim of much health informatics research. The recent widespread participation of the augmented reality game Pokémon Go which encourages exercises, provides significant insights into the potential of information technology to improve healthcare intervention on obesity-related disease. Does Pokémon Go point to another way of achieving health benefits using mobile devices? This paper analyses the features of Pokémon Go in relation to potential health benefits. This paper suggests from the perspective of a user on changes to the game that potentially could help with obesity, mental health cardiovascular health and vitamin D deficiencies. While the impact of augmented reality games on improving exercises might be substantial, the question of sustainability and likely long-term health outcomes remain debatable. The rapid uptake of Pokémon Go by the population around the world, however, should serve as a useful lesson for information and technological design to improve outcomes obesity-related diseases in the future.

  1. Cement Augmentation in Sacroiliac Screw Fixation Offers Modest Biomechanical Advantages in a Cadaver Model.

    Science.gov (United States)

    Osterhoff, Georg; Dodd, Andrew E; Unno, Florence; Wong, Angus; Amiri, Shahram; Lefaivre, Kelly A; Guy, Pierre

    2016-11-01

    Sacroiliac screw fixation in elderly patients with pelvic fractures is prone to failure owing to impaired bone quality. Cement augmentation has been proposed as a possible solution, because in other anatomic areas this has been shown to reduce screw loosening. However, to our knowledge, this has not been evaluated for sacroiliac screws. We investigated the potential biomechanical benefit of cement augmentation of sacroiliac screw fixation in a cadaver model of osteoporotic bone, specifically with respect to screw loosening, construct survival, and fracture-site motion. Standardized complete sacral ala fractures with intact posterior ligaments in combination with ipsilateral upper and lower pubic rami fractures were created in osteoporotic cadaver pelves and stabilized by three fixation techniques: sacroiliac (n = 5) with sacroiliac screws in S1 and S2, cemented (n = 5) with addition of cement augmentation, and transsacral (n = 5) with a single transsacral screw in S1. A cyclic loading protocol was applied with torque (1.5 Nm) and increasing axial force (250-750 N). Screw loosening, construct survival, and sacral fracture-site motion were measured by optoelectric motion tracking. A sample-size calculation revealed five samples per group to be required to achieve a power of 0.80 to detect 50% reduction in screw loosening. Screw motion in relation to the sacrum during loading with 250 N/1.5 Nm was not different among the three groups (sacroiliac: 1.2 mm, range, 0.6-1.9; cemented: 0.7 mm, range, 0.5-1.3; transsacral: 1.1 mm, range, 0.6-2.3) (p = 0.940). Screw subsidence was less in the cemented group (3.0 mm, range, 1.2-3.7) compared with the sacroiliac (5.7 mm, range, 4.7-10.4) or transsacral group (5.6 mm, range, 3.8-10.5) (p = 0.031). There was no difference with the numbers available in the median number of cycles needed until failure; this was 2921 cycles (range, 2586-5450) in the cemented group, 2570 cycles (range, 2500-5107) for the sacroiliac specimens, and

  2. 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.

  3. 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.

  4. A Representation for Gaining Insight into Clinical Decision Models

    Science.gov (United States)

    Jimison, Holly B.

    1988-01-01

    For many medical domains uncertainty and patient preferences are important components of decision making. Decision theory is useful as a representation for such medical models in computer decision aids, but the methodology has typically had poor performance in the areas of explanation and user interface. The additional representation of probabilities and utilities as random variables serves to provide a framework for graphical and text insight into complicated decision models. The approach allows for efficient customization of a generic model that describes the general patient population of interest to a patient- specific model. Monte Carlo simulation is used to calculate the expected value of information and sensitivity for each model variable, thus providing a metric for deciding what to emphasize in the graphics and text summary. The computer-generated explanation includes variables that are sensitive with respect to the decision or that deviate significantly from what is typically observed. These techniques serve to keep the assessment and explanation of the patient's decision model concise, allowing the user to focus on the most important aspects for that patient.

  5. 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.

  6. Hydraulic root water uptake models: old concerns and new insights

    Science.gov (United States)

    Couvreur, V.; Carminati, A.; Rothfuss, Y.; Meunier, F.; Vanderborght, J.; Javaux, M.

    2014-12-01

    Root water uptake (RWU) affects underground water dynamics, with consequences on plant water availability and groundwater recharge. Even though hydrological and climate models are sensitive to RWU parameters, no consensus exists on the modelling of this process. Back in the 1940ies, Van Den Honert's catenary approach was the first to investigate the use of connected hydraulic resistances to describe water flow in whole plants. However concerns such as the necessary computing when architectures get complex made this approach premature. Now that computing power increased dramatically, hydraulic RWU models are gaining popularity, notably because they naturally produce observed processes like compensatory RWU and hydraulic redistribution. Yet major concerns remain. Some are more fundamental: according to hydraulic principles, plant water potential should equilibrate with soil water potential when the plant does not transpire, which is not a general observation when using current definitions of bulk or average soil water potential. Other concerns regard the validation process: water uptake distribution is not directly measurable, which makes it hard to demonstrate whether or not hydraulic models are more accurate than other models. Eventually parameterization concerns exist: root hydraulic properties are not easily measurable, and would even fluctuate on an hourly basis due to processes like aquaporin gating. While offering opportunities to validate hydraulic RWU models, newly developed observation techniques also make us realize the increasing complexity of processes involved in soil-plant hydrodynamics, such as the change of rhizosphere hydraulic properties with soil drying. Surprisingly, once implemented into hydraulic models, these processes do not necessarily translate into more complex emerging behavior at plant scale, and might justify the use of simplified representations of the soil-plant hydraulic system.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. New insight into unstable hillslopes hydrology from hydrogeochemical modelling.

    Science.gov (United States)

    Bertrand, C.; Marc, V.; Malet, J.-P.

    2010-05-01

    and mineralogical analyses or from the literature (kinetics constants). The simulations showed that pH, sulphate and calcium concentrations in groundwater could be reproduced from reasonable assumptions. However, the observed high concentrations in magnesium and sodium were not correctly simulated by the model. Furthermore, a particular anomaly in the Na+ concentration was observed in the most active part of the landslide. Lastly, isotopic investigation showed that groundwater 3H content in this sector was significantly lower than groundwater content in the other parts of the landslide and lower than the mean rainwater content. This result showed that the mean groundwater age in the active part was probably higher than elsewhere in the landslide. All these arguments led us to conclude that groundwater was locally recharged with saline waters from areas outside the watershed, coming up through the bedrock using major discontinuities. This assumption is in agreement with the geological context. de Montety, V., V. Marc, C. Emblanch, J.-P. Malet, C. Bertrand, O. Maquaire, and T. A. Bogaard, 2007, Identifying the origin of groundwater and flow processes in complex landslides affecting black marls: insights from a hydrochemical survey.: Earth Surface Processes and Landforms, v. 32, p. 32-48. Malet, J.-P. and Maquaire, O., 2003. Black marl earthflows mobility and long-term seasonal dynamic in southeastern France. In: Picarelli, L. (Ed). Proceedings of the International Conference on Fast Slope Movements: Prediction and Prevention for Risk Mitigation. Patron Editore, Bologna: 333-340. Maquaire, O., Malet, J.-P., Remaître, A., Locat, J., Klotz, S. and Guillon, J., 2003. Instability conditions of marly hillslopes: towards landsliding or gullying? The case of the Barcelonnette Bassin, South East France. Engineering Geology, 70(1-2): 109-130. Parkhurst, D.L. and Appelo, C.A.J., 1999, User's guide to PHREEQC (version 2)--A computer program for speciation, batch-reaction, one

  13. Current Models of Investor State Dispute Settlement Are Bad for Health: The European Union Could Offer an Alternative

    Science.gov (United States)

    McKee, Martin; Stuckler, David

    2017-01-01

    In this commentary, we endorse concerns about the health impact of the trans-pacific partnership (TPP), paying particular attention to its mechanisms for investor state dispute settlement. We then describe the different, judge-led approach being advocated by the European Commission team negotiating the Trans-Atlantic Trade and Investment Partnership, arguing that, while not perfect, it offers significant advantages. PMID:28812799

  14. 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

  15. Modeling Insight into Battery Electrolyte Electrochemical Stability and Interfacial Structure.

    Science.gov (United States)

    Borodin, Oleg; Ren, Xiaoming; Vatamanu, Jenel; von Wald Cresce, Arthur; Knap, Jaroslaw; Xu, Kang

    2017-12-19

    Electroactive interfaces distinguish electrochemistry from chemistry and enable electrochemical energy devices like batteries, fuel cells, and electric double layer capacitors. In batteries, electrolytes should be either thermodynamically stable at the electrode interfaces or kinetically stable by forming an electronically insulating but ionically conducting interphase. In addition to a traditional optimization of electrolytes by adding cosolvents and sacrificial additives to preferentially reduce or oxidize at the electrode surfaces, knowledge of the local electrolyte composition and structure within the double layer as a function of voltage constitutes the basis of manipulating an interphase and expanding the operating windows of electrochemical devices. In this work, we focus on how the molecular-scale insight into the solvent and ion partitioning in the electrolyte double layer as a function of applied potential could predict changes in electrolyte stability and its initial oxidation and reduction reactions. In molecular dynamics (MD) simulations, highly concentrated lithium aqueous and nonaqueous electrolytes were found to exclude the solvent molecules from directly interacting with the positive electrode surface, which provides an additional mechanism for extending the electrolyte oxidation stability in addition to the well-established simple elimination of "free" solvent at high salt concentrations. We demonstrate that depending on their chemical structures, the anions could be designed to preferentially adsorb or desorb from the positive electrode with increasing electrode potential. This provides additional leverage to dictate the order of anion oxidation and to effectively select a sacrificial anion for decomposition. The opposite electrosorption behaviors of bis(trifluoromethane)sulfonimide (TFSI) and trifluoromethanesulfonate (OTF) as predicted by MD simulation in highly concentrated aqueous electrolytes were confirmed by surface enhanced infrared

  16. Physically-insightful equivalent circuit models for electromagnetic periodic structures

    Science.gov (United States)

    Mesa, F.; Rodríguez-Berral, R.; Medina, F.

    2018-02-01

    In this presentation it will be discussed how to obtain analytical or quasi-analytical equivalent circuits to deal with periodic structures such as frequency selective surfaces and/or metasurfaces. Both the topology and the values of the involved elements of these circuits are obtained from a basic rationale to solve the corresponding integral equation. This procedure, besides providing a very efficient analysis/design tool, allows for a good physical insight into the operating mechanisms of the structure in contrast with the almost blind numerical scheme of commercial simulators.

  17. 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)

  18. When to stop drying fruit: Insights from hygrothermal modelling

    International Nuclear Information System (INIS)

    Defraeye, Thijs

    2017-01-01

    Highlights: • Partial dehydration reduces energy consumption and processing time and improves product quality. • This study gives a quantitative insight in when fruit drying should be stopped. • Decrease in dryer residence time of 2%, 24% and 70% are found for different stopping criteria. - Abstract: Stopping the drying process prior to complete dehydration reduces energy consumption and processing time but can also improve product quality. Using hygrothermal simulations, different stopping criteria are evaluated, which are based on the final water activity and residual moisture content in the fruit. Their impact on drying time and moisture redistribution kinetics inside fruit is quantified. One of the variants leads to a significant reduction in residence time in the dryer (24%), compared to full dehydration. For this variant, drying is stopped when the average moisture content in the sample reaches the value corresponding to an equilibrium water activity of 60% in the sample, as determined from the sorption isotherm. At the same time, this variant does not induce problems with fruit spoilage, as a sufficiently low water activity is reached after moisture redistribution during relaxation in the ambient environment. In addition, the relation of the drying time to the drying air temperature was quantified for all stopping criteria, as well as the impact of the humidity of the ambient environment in which the dried fruits are placed afterwards. This study gives a better quantitative insight in when fruit drying should be stopped, given specific drying conditions, without having to compromise food safety.

  19. Design and validation of a model to offer environmental consulting services to minimize oil pollution at gas stations: case study: a gas station in Costa Rica

    International Nuclear Information System (INIS)

    Calderon Hernandez, Teresita

    2016-01-01

    An environmental consulting service was designed and validated to minimize hydrocarbon contamination at gas stations, to be used by Migliore S.A. in order to strengthen and increase the number of services offered in the market niche of these companies. A matrix was synthesized with tools such as SWOT, deployment of the Quality Function Deployment (QFD) and international analysis. With the standardized protocols it will be possible to increase in a fluid way, the offer of consulting services. The final validation of the model allowed to verify the functionality of the same, through the generation of solid evaluation criteria that allowed a good knowledge of the gas station, case study, to offer a timely solution to your particular case, in a simple way and harmonious. The company providing environmental consulting services Migliore S.A. can count on a better commercial development, using the designed model [es

  20. 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.

  1. 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

    2018-04-01

    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

  2. Innovative gas offers

    International Nuclear Information System (INIS)

    Sala, O.; Mela, P.; Chatelain, F.

    2007-01-01

    New energy offers are progressively made available as the opening of gas market to competition becomes broader. How are organized the combined offers: gas, electricity, renewable energies and energy services? What are the marketing strategies implemented? Three participants at this round table present their offer and answer these questions. (J.S.)

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

    KAUST Repository

    Moreo, P.; Gaffney, E. A.; Garcí a-Aznar, J. M.; Doblaré , M.

    2009-01-01

    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

  4. Insight into model mechanisms through automatic parameter fitting: a new methodological framework for model development.

    Science.gov (United States)

    Tøndel, Kristin; Niederer, Steven A; Land, Sander; Smith, Nicolas P

    2014-05-20

    Striking a balance between the degree of model complexity and parameter identifiability, while still producing biologically feasible simulations using modelling is a major challenge in computational biology. While these two elements of model development are closely coupled, parameter fitting from measured data and analysis of model mechanisms have traditionally been performed separately and sequentially. This process produces potential mismatches between model and data complexities that can compromise the ability of computational frameworks to reveal mechanistic insights or predict new behaviour. In this study we address this issue by presenting a generic framework for combined model parameterisation, comparison of model alternatives and analysis of model mechanisms. The presented methodology is based on a combination of multivariate metamodelling (statistical approximation of the input-output relationships of deterministic models) and a systematic zooming into biologically feasible regions of the parameter space by iterative generation of new experimental designs and look-up of simulations in the proximity of the measured data. The parameter fitting pipeline includes an implicit sensitivity analysis and analysis of parameter identifiability, making it suitable for testing hypotheses for model reduction. Using this approach, under-constrained model parameters, as well as the coupling between parameters within the model are identified. The methodology is demonstrated by refitting the parameters of a published model of cardiac cellular mechanics using a combination of measured data and synthetic data from an alternative model of the same system. Using this approach, reduced models with simplified expressions for the tropomyosin/crossbridge kinetics were found by identification of model components that can be omitted without affecting the fit to the parameterising data. Our analysis revealed that model parameters could be constrained to a standard deviation of on

  5. Osteoarthritis and metabolic dysregulation: insights from a preclinical model

    NARCIS (Netherlands)

    Visser, H.M. de

    2018-01-01

    This thesis aims to identify the effect of metabolic factors, inflammatory processes and obesity in the pathophysiology of osteoarthritis (OA), using a high-fat diet and/or traumatic injury in a small animal model. The first part of this thesis describes, the rat Groove model of OA, using a one-time

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

    NARCIS (Netherlands)

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

    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

  7. 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

  8. Water security, risk, and economic growth: Insights from a dynamical systems model

    Science.gov (United States)

    Dadson, Simon; Hall, Jim W.; Garrick, Dustin; Sadoff, Claudia; Grey, David; Whittington, Dale

    2017-08-01

    Investments in the physical infrastructure, human capital, and institutions needed for water resources management have been noteworthy in the development of most civilizations. These investments affect the economy in two distinct ways: (i) by improving the factor productivity of water in multiple economic sectors, especially those that are water intensive such as agriculture and energy and (ii) by reducing acute and chronic harmful effects of water-related hazards like floods, droughts, and water-related diseases. The need for capital investment to mitigate risks and promote economic growth is widely acknowledged, but prior conceptual work on the relationship between water-related investments and economic growth has focused on the productive and harmful roles of water in the economy independently. Here the two influences are combined using a simple, dynamical systems model of water-related investment, risk, and growth. In cases where initial water security is low, initial investment in water-related assets enables growth. Without such investment, losses due to water-related hazards exert a drag on economic growth and may create a poverty trap. The presence and location of the poverty trap is context-specific and depends on the exposure of productive water-related assets to water-related risk. Exogenous changes in water-related risk can potentially push an economy away from a growth path toward a poverty trap. Our investigation shows that an inverted-U-shaped investment relation between the level of investment in water security and the current level of water security leads to faster rates of growth than the alternatives that we consider here, and that this relation is responsible for the "S"-curve that is posited in the literature. These results illustrate the importance of accounting for environmental and health risks in economic models and offer insights for the design of robust policies for investment in water-related productive assets to manage risk, in the face

  9. Business models for telehealth in the US: analyses and insights

    Directory of Open Access Journals (Sweden)

    Pereira F

    2017-02-01

    Full Text Available Francis Pereira Data Sciences and Operations, Marshall School of Business, University of Southern, Los Angeles, CA, USAAbstract: A growing shortage of medical doctors and nurses, globally, coupled with increasing life expectancy, is generating greater cost pressures on health care, in the US and globally. In this respect, telehealth can help alleviate these pressures, as well as extend medical services to underserved or unserved areas. However, its relatively slow adoption in the US, as well as in other markets, suggests the presence of barriers and challenges. The use of a business model framework helps identify the value proposition of telehealth as well as these challenges, which include identifying the right revenue model, organizational structure, and, perhaps more importantly, the stakeholders in the telehealth ecosystem. Successful and cost-effective deployment of telehealth require a redefinition of the ecosystem and a comprehensive review of all benefits and beneficiaries of such a system; hence a reassessment of all the stakeholders that could benefit from such a system, beyond the traditional patient–health provider–insurer model, and thus “who should pay” for such a system, and the driving efforts of a “keystone” player in developing this initiative would help. Keywords: telehealth, business model framework, stakeholders, ecosystem, VISOR business Model

  10. Insights Into the Bifunctional Aphidicolan-16-ß-ol Synthase Through Rapid Biomolecular Modeling Approaches.

    Science.gov (United States)

    Hirte, Max; Meese, Nicolas; Mertz, Michael; Fuchs, Monika; Brück, Thomas B

    2018-01-01

    Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modeling techniques offer an alternative route to study the enzyme's reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modeling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modeling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789, and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modeling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially restricted location of

  11. Insights Into the Bifunctional Aphidicolan-16-ß-ol Synthase Through Rapid Biomolecular Modeling Approaches

    Directory of Open Access Journals (Sweden)

    Max Hirte

    2018-04-01

    Full Text Available Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modeling techniques offer an alternative route to study the enzyme's reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modeling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modeling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789, and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modeling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially

  12. Insights into the bifunctional Aphidicolan-16-ß-ol synthase through rapid biomolecular modelling approaches

    Science.gov (United States)

    Hirte, Max; Meese, Nicolas; Mertz, Michael; Fuchs, Monika; Brück, Thomas B.

    2018-04-01

    Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modelling techniques offer an alternative route to study the enzyme’s reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modelling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modelling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789 and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modelling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially restricted location

  13. Reactor pressure vessel embrittlement: Insights from neural network modelling

    Science.gov (United States)

    Mathew, J.; Parfitt, D.; Wilford, K.; Riddle, N.; Alamaniotis, M.; Chroneos, A.; Fitzpatrick, M. E.

    2018-04-01

    Irradiation embrittlement of steel pressure vessels is an important consideration for the operation of current and future light water nuclear reactors. In this study we employ an ensemble of artificial neural networks in order to provide predictions of the embrittlement using two literature datasets, one based on US surveillance data and the second from the IVAR experiment. We use these networks to examine trends with input variables and to assess various literature models including compositional effects and the role of flux and temperature. Overall, the networks agree with the existing literature models and we comment on their more general use in predicting irradiation embrittlement.

  14. The spin-charge-family theory offers understanding of the triangle anomalies cancellation in the standard model

    Energy Technology Data Exchange (ETDEWEB)

    Mankoc Borstnik, N.S. [University of Ljubljana (Slovenia); Nielsen, H.B.F. [Niels Bohr Institute, Copenhagen (Denmark)

    2017-12-15

    The standard model has for massless quarks and leptons ''miraculously'' no triangle anomalies due to the fact that the sum of all possible traces T r[τ{sup Ai}τ{sup Bj}τ{sup Ck}] - where τ{sup Ai}, τ{sup Bi} and τ{sup Ck} are the generators of one, of two or of three of the groups SU(3), SU(2) and U(1) - over the representations of one family of the left handed fermions and anti-fermions (and separately of the right handed fermions and anti-fermions), contributing to the triangle currents, is equal to zero.{sup [1-4]} It is demonstrated in this paper that this cancellation of the standard model triangle anomaly follows straightforwardly if the SO(3, 1), SU(2), U(1) and SU(3) are the subgroups of the orthogonal group SO(13, 1), as it is in the spin-charge-family theory.{sup [5-22]} We comment on the SO(10) anomaly cancellation, which works if handedness and charges are related ''by hand''. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  15. Insights into channel dysfunction from modelling and molecular dynamics simulations.

    Science.gov (United States)

    Musgaard, Maria; Paramo, Teresa; Domicevica, Laura; Andersen, Ole Juul; Biggin, Philip C

    2018-04-01

    Developments in structural biology mean that the number of different ion channel structures has increased significantly in recent years. Structures of ion channels enable us to rationalize how mutations may lead to channelopathies. However, determining the structures of ion channels is still not trivial, especially as they necessarily exist in many distinct functional states. Therefore, the use of computational modelling can provide complementary information that can refine working hypotheses of both wild type and mutant ion channels. The simplest but still powerful tool is homology modelling. Many structures are available now that can provide suitable templates for many different types of ion channels, allowing a full three-dimensional interpretation of mutational effects. These structural models, and indeed the structures themselves obtained by X-ray crystallography, and more recently cryo-electron microscopy, can be subjected to molecular dynamics simulations, either as a tool to help explore the conformational dynamics in detail or simply as a means to refine the models further. Here we review how these approaches have been used to improve our understanding of how diseases might be linked to specific mutations in ion channel proteins. This article is part of the Special Issue entitled 'Channelopathies.' Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. 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

  17. 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.

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

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Stein, J.

    2017-01-01

    The discovery, development and use of genetic rodent models of absence epilepsy have led to a new theory about the origin of absence seizures, which has gained impact within the international epilepsy community. A focal zone has been identified in the perioral region of the somatosensory cortex in

  19. 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…

  20. Application of hydropedological insights in hydrological modelling of ...

    African Journals Online (AJOL)

    In this paper the output of a digital soil mapping exercise was used as the soil input into a distributed hydrological model (ACRU) for a test site within the Stevenson-Hamilton Research Supersite, Kruger National Park (South ... The outputs evaluated included both streamflow and soil water content at selected soil profiles.

  1. 3D pancreatic carcinoma spheroids induce a matrix-rich, chemoresistant phenotype offering a better model for drug testing

    International Nuclear Information System (INIS)

    Longati, Paola; Heuchel, Rainer L; Jia, Xiaohui; Eimer, Johannes; Wagman, Annika; Witt, Michael-Robin; Rehnmark, Stefan; Verbeke, Caroline; Toftgård, Rune; Löhr, Matthias

    2013-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer related death. It is lethal in nearly all patients, due to an almost complete chemoresistance. Most if not all drugs that pass preclinical tests successfully, fail miserably in the patient. This raises the question whether traditional 2D cell culture is the correct tool for drug screening. The objective of this study is to develop a simple, high-throughput 3D model of human PDAC cell lines, and to explore mechanisms underlying the transition from 2D to 3D that might be responsible for chemoresistance. Several established human PDAC and a KPC mouse cell lines were tested, whereby Panc-1 was studied in more detail. 3D spheroid formation was facilitated with methylcellulose. Spheroids were studied morphologically, electron microscopically and by qRT-PCR for selected matrix genes, related factors and miRNA. Metabolic studies were performed, and a panel of novel drugs was tested against gemcitabine. Comparing 3D to 2D cell culture, matrix proteins were significantly increased as were lumican, SNED1, DARP32, and miR-146a. Cell metabolism in 3D was shifted towards glycolysis. All drugs tested were less effective in 3D, except for allicin, MT100 and AX, which demonstrated effect. We developed a high-throughput 3D cell culture drug screening system for pancreatic cancer, which displays a strongly increased chemoresistance. Features associated to the 3D cell model are increased expression of matrix proteins and miRNA as well as stromal markers such as PPP1R1B and SNED1. This is supporting the concept of cell adhesion mediated drug resistance

  2. Applications of the SWAT Model Special Section: Overview and Insights.

    Science.gov (United States)

    Gassman, Philip W; Sadeghi, Ali M; Srinivasan, Raghavan

    2014-01-01

    The Soil and Water Assessment Tool (SWAT) model has emerged as one of the most widely used water quality watershed- and river basin-scale models worldwide, applied extensively for a broad range of hydrologic and/or environmental problems. The international use of SWAT can be attributed to its flexibility in addressing water resource problems, extensive networking via dozens of training workshops and the several international conferences that have been held during the past decade, comprehensive online documentation and supporting software, and an open source code that can be adapted by model users for specific application needs. The catalyst for this special collection of papers was the 2011 International SWAT Conference & Workshops held in Toledo, Spain, which featured over 160 scientific presentations representing SWAT applications in 37 countries. This special collection presents 22 specific SWAT-related studies, most of which were presented at the 2011 SWAT Conference; it represents SWAT applications on five different continents, with the majority of studies being conducted in Europe and North America. The papers cover a variety of topics, including hydrologic testing at a wide range of watershed scales, transport of pollutants in northern European lowland watersheds, data input and routing method effects on sediment transport, development and testing of potential new model algorithms, and description and testing of supporting software. In this introduction to the special section, we provide a synthesis of these studies within four main categories: (i) hydrologic foundations, (ii) sediment transport and routing analyses, (iii) nutrient and pesticide transport, and (iv) scenario analyses. We conclude with a brief summary of key SWAT research and development needs. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  3. Insights from quantum cognitive models for organizational decision making

    OpenAIRE

    White, L.C.; Pothos, E. M.; Busemeyer, J. R.

    2015-01-01

    Organizational decision making is often explored with theories from the heuristics and biases research program, which have demonstrated great value as descriptions of how people in organizations make decisions. Nevertheless, rational analysis and classical probability theory are still seen by many as the best accounts of how decisions should be made and classical probability theory is the preferred framework for cognitive modelling for many researchers. The focus of this work is quantum proba...

  4. 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. 

  5. 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.

  6. Empirical study of long-range connections in a road network offers new ingredient for navigation optimization models

    International Nuclear Information System (INIS)

    Wang, Pu; Liu, Like; Li, Xiamiao; Li, Guanliang; González, Marta C

    2014-01-01

    Navigation problem in lattices with long-range connections has been widely studied to understand the design principles for optimal transport networks; however, the travel cost of long-range connections was not considered in previous models. We define long-range connection in a road network as the shortest path between a pair of nodes through highways and empirically analyze the travel cost properties of long-range connections. Based on the maximum speed allowed in each road segment, we observe that the time needed to travel through a long-range connection has a characteristic time T h  ∼ 29 min, while the time required when using the alternative arterial road path has two different characteristic times T a  ∼ 13 and 41 min and follows a power law for times larger than 50 min. Using daily commuting origin–destination matrix data, we additionally find that the use of long-range connections helps people to save about half of the travel time in their daily commute. Based on the empirical results, we assign a more realistic travel cost to long-range connections in two-dimensional square lattices, observing dramatically different minimum average shortest path 〈l〉 but similar optimal navigation conditions. (paper)

  7. Empirical study of long-range connections in a road network offers new ingredient for navigation optimization models

    Science.gov (United States)

    Wang, Pu; Liu, Like; Li, Xiamiao; Li, Guanliang; González, Marta C.

    2014-01-01

    Navigation problem in lattices with long-range connections has been widely studied to understand the design principles for optimal transport networks; however, the travel cost of long-range connections was not considered in previous models. We define long-range connection in a road network as the shortest path between a pair of nodes through highways and empirically analyze the travel cost properties of long-range connections. Based on the maximum speed allowed in each road segment, we observe that the time needed to travel through a long-range connection has a characteristic time Th ˜ 29 min, while the time required when using the alternative arterial road path has two different characteristic times Ta ˜ 13 and 41 min and follows a power law for times larger than 50 min. Using daily commuting origin-destination matrix data, we additionally find that the use of long-range connections helps people to save about half of the travel time in their daily commute. Based on the empirical results, we assign a more realistic travel cost to long-range connections in two-dimensional square lattices, observing dramatically different minimum average shortest path but similar optimal navigation conditions.

  8. 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.

  9. 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 the glial cell activation: (1) via IP3 production and Ca2+ release from the endoplasmic reticulum and (2) via increase of the extracellular potassium concentration, glia depolarization, and opening of voltage-dependent Ca2+ channels. We suggest that the second pathway is the more significant...

  10. Elastase-induced pulmonary emphysema: insights from experimental models

    Directory of Open Access Journals (Sweden)

    Mariana A. Antunes

    2011-12-01

    Full Text Available Several distinct stimuli can be used to reproduce histological and functional features of human emphysema, a leading cause of disability and death. Since cigarette smoke is the main cause of emphysema in humans, experimental researches have attempted to reproduce this situation. However, this is an expensive and cumbersome method of emphysema induction, and simpler, more efficacious alternatives have been sought. Among these approaches, elastolytic enzymes have been widely used to reproduce some characteristics of human cigarette smoke-induced disease, such as: augmentation of airspaces, inflammatory cell influx into the lungs, and systemic inflammation. Nevertheless, the use of elastase-induced emphysema models is still controversial, since the disease pathways involved in elastase induction may differ from those occurring in smoke-induced emphysema. This indicates that the choice of an emphysema model may impact the results of new therapies or drugs being tested. The aim of this review is to compare the mechanisms of disease induction in smoke and elastase emphysema models, to describe the differences among various elastase models, and to establish the advantages and disadvantages of elastase-induced emphysema models. More studies are required to shed light on the mechanisms of elastase-induced emphysema.Diversos estímulos podem ser utilizados para reproduzir características histológicas e funcionais do enfisema humano, uma das principais causas de incapacidade e morte. Uma vez que a fumaça de cigarro é a principal causa de enfisema em humanos, estudos experimentais têm tentado reproduzir esta situação. No entanto, esse é um método dispendioso e complicado para a indução do enfisema e, alternativas mais simples e eficazes, têm sido pesquisadas. Entre essas abordagens, enzimas elastolíticas vêm sendo amplamente utilizadas para reproduzir algumas das características do enfisema humano, tais como: aumento dos espaços a

  11. Tectonic drivers of the Wrangell block: Insights on fore-arc sliver processes from 3-D geodynamic models of Alaska

    Science.gov (United States)

    Haynie, K. L.; Jadamec, M. A.

    2017-07-01

    Intracontinental shear zones can play a key role in understanding how plate convergence is manifested in the upper plate in regions of oblique subduction. However, the relative role of the driving forces from the subducting plate and the resisting force from within intracontinental shear zones is not well understood. Results from high-resolution, geographically referenced, instantaneous 3-D geodynamic models of flat slab subduction at the oblique convergent margin of Alaska are presented. These models investigate how viscosity and length of the Denali fault intracontinental shear zone as well as coupling along the plate boundary interface modulate motion of the Wrangell block fore-arc sliver and slip across the Denali fault. Models with a weak Denali fault (1017 Pa s) and strong plate coupling (1021 Pa s) were found to produce the fastest motions of the Wrangell block (˜10 mm/yr). The 3-D models predict along-strike variation in motion along the Denali fault, changing from dextral strike-slip motion in the eastern segment to oblique convergence toward the fault apex. Models further show that the flat slab drives oblique motion of the Wrangell block and contributes to 20% (models with a short fault) and 28% (models with a long fault) of the observed Quaternary slip rates along the Denali fault. The 3-D models provide insight into the general processes of fore-arc sliver mechanics and also offer a 3-D framework for interpreting hazards in regions of flat slab subduction.

  12. Strabismus and the Oculomotor System: Insights from Macaque Models

    Science.gov (United States)

    Das, Vallabh E.

    2017-01-01

    Disrupting binocular vision in infancy leads to strabismus and oftentimes to a variety of associated visual sensory deficits and oculomotor abnormalities. Investigation of this disorder has been aided by the development of various animal models, each of which has advantages and disadvantages. In comparison to studies of binocular visual responses in cortical structures, investigations of neural oculomotor structures that mediate the misalignment and abnormalities of eye movements have been more recent, and these studies have shown that different brain areas are intimately involved in driving several aspects of the strabismic condition, including horizontal misalignment, dissociated deviations, A and V patterns of strabismus, disconjugate eye movements, nystagmus, and fixation switch. The responses of cells in visual and oculomotor areas that potentially drive the sensory deficits and also eye alignment and eye movement abnormalities follow a general theme of disrupted calibration, lower sensitivity, and poorer specificity compared with the normally developed visual oculomotor system. PMID:28532347

  13. Cellulose synthases: new insights from crystallography and modeling.

    Science.gov (United States)

    Slabaugh, Erin; Davis, Jonathan K; Haigler, Candace H; Yingling, Yaroslava G; Zimmer, Jochen

    2014-02-01

    Detailed information about the structure and biochemical mechanisms of cellulose synthase (CelS) proteins remained elusive until a complex containing the catalytic subunit (BcsA) of CelS from Rhodobacter sphaeroides was crystalized. Additionally, a 3D structure of most of the cytosolic domain of a plant CelS (GhCESA1 from cotton, Gossypium hirsutum) was produced by computational modeling. This predicted structure contributes to our understanding of how plant CelS proteins may be similar and different as compared with BcsA. In this review, we highlight how these structures impact our understanding of the synthesis of cellulose and other extracellular polysaccharides. We show how the structures can be used to generate hypotheses for experiments testing mechanisms of glucan synthesis and translocation in plant CelS. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. 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.

  15. IR sensor design insight from missile-plume prediction models

    Science.gov (United States)

    Rapanotti, John L.; Gilbert, Bruno; Richer, Guy; Stowe, Robert

    2002-08-01

    Modern anti-tank missiles and the requirement of rapid deployment have significantly reduced the use of passive armour in protecting land vehicles. Vehicle survivability is becoming more dependent on sensors, computers and countermeasures to detect and avoid threats. An analysis of missile propellants suggests that missile detection based on plume characteristics alone may be more difficult than anticipated. Currently, the passive detection of missiles depends on signatures with a significant ultraviolet component. This approach is effective in detecting anti-aircraft missiles that rely on powerful motors to pursue high-speed aircraft. The high temperature exhaust from these missiles contains significant levels of carbon dioxide, water and, often, metal oxides such as alumina. The plumes emits strongest in the infrared, 1 to 5micrometers , regions with a significant component of the signature extending into the ultraviolet domain. Many anti-tank missiles do not need the same level of propulsion and radiate significantly less. These low velocity missiles, relying on the destructive force of shaped-charge warhead, are more difficult to detect. There is virtually no ultraviolet component and detection based on UV sensors is impractical. The transition in missile detection from UV to IR is reasonable, based on trends in imaging technology, but from the analysis presented in this paper even IR imagers may have difficulty in detecting missile plumes. This suggests that the emphasis should be placed in the detection of the missile hard body in the longer wavelengths of 8 to 12micrometers . The analysis described in this paper is based on solution of the governing equations of plume physics and chemistry. These models will be used to develop better sensors and threat detection algorithms.

  16. Seismic variability of subduction thrust faults: Insights from laboratory models

    Science.gov (United States)

    Corbi, F.; Funiciello, F.; Faccenna, C.; Ranalli, G.; Heuret, A.

    2011-06-01

    Laboratory models are realized to investigate the role of interface roughness, driving rate, and pressure on friction dynamics. The setup consists of a gelatin block driven at constant velocity over sand paper. The interface roughness is quantified in terms of amplitude and wavelength of protrusions, jointly expressed by a reference roughness parameter obtained by their product. Frictional behavior shows a systematic dependence on system parameters. Both stick slip and stable sliding occur, depending on driving rate and interface roughness. Stress drop and frequency of slip episodes vary directly and inversely, respectively, with the reference roughness parameter, reflecting the fundamental role for the amplitude of protrusions. An increase in pressure tends to favor stick slip. Static friction is a steeply decreasing function of the reference roughness parameter. The velocity strengthening/weakening parameter in the state- and rate-dependent dynamic friction law becomes negative for specific values of the reference roughness parameter which are intermediate with respect to the explored range. Despite the simplifications of the adopted setup, which does not address the problem of off-fault fracturing, a comparison of the experimental results with the depth distribution of seismic energy release along subduction thrust faults leads to the hypothesis that their behavior is primarily controlled by the depth- and time-dependent distribution of protrusions. A rough subduction fault at shallow depths, unable to produce significant seismicity because of low lithostatic pressure, evolves into a moderately rough, velocity-weakening fault at intermediate depths. The magnitude of events in this range is calibrated by the interplay between surface roughness and subduction rate. At larger depths, the roughness further decreases and stable sliding becomes gradually more predominant. Thus, although interplate seismicity is ultimately controlled by tectonic parameters (velocity of

  17. An optimisation approach for capacity planning: modelling insights and empirical findings from a tactical perspective

    Directory of Open Access Journals (Sweden)

    Andréa Nunes Carvalho

    2017-09-01

    Full Text Available Abstract The academic literature presents a research-practice gap on the application of decision support tools to address tactical planning problems in real-world organisations. This paper addresses this gap and extends a previous action research relative to an optimisation model applied for tactical capacity planning in an engineer-to-order industrial setting. The issues discussed herein raise new insights to better understand the practical results that can be achieved through the proposed model. The topics presented include the modelling of objectives, the representation of the production process and the costing approach, as well as findings regarding managerial decisions and the scope of action considered. These insights may inspire ideas to academics and practitioners when developing tools for capacity planning problems in similar contexts.

  18. 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

  19. Offers for our members

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    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.

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    Summer is coming, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 25 € instead of 31 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your Staff Association 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.  

  1. 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.

  2. Offers for our members

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    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.

  3. Modeling Double Subjectivity for Gaining Programmable Insights: Framing the Case of Uber

    Directory of Open Access Journals (Sweden)

    Loretta Henderson Cheeks

    2017-09-01

    Full Text Available The Internet is the premier platform that enable the emergence of new technologies. Online news is unstructured narrative text that embeds facts, frames, and amplification that can influence society attitudes about technology adoption. Online news sources are carriers of voluminous amounts of news for reaching significantly large audience and have no geographical or time boundaries. The interplay of complex and dynamical forces among authors and readers allow for progressive emergent and latent properties to exhibit. Our concept of “Double subjectivity” provides a new paradigm for exploring complementary programmable insights of deeply buried meanings in a system. The ability to understand internal embeddedness in a large collection of related articles are beyond the reach of existing computational tools, and are hence left to human readers with unscalable results. This paper uncovers the potential to utilize advanced machine learning in a new way to automate the understanding of implicit structures and their associated latent meanings to give an early human-level insight into emergent technologies, with a concrete example of “Uber”. This paper establishes the new concept of double subjectivity as an instrument for large-scale machining of unstructured text and introduces a social influence model for the discovery of distinct pathways into emerging technology, and hence an insight. The programmable insight reveals early spatial and temporal opinion shift monitoring in complex networks in a structured way for computational treatment and visualization.

  4. Offers for our members

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    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.

  5. Offers for our members

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    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.

  6. Offers for our members

    CERN Multimedia

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    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.

  7. Offers for our members

    CERN Multimedia

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    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.

  8. Success of mainstream partial nitritation/anammox demands integration of engineering, microbiome and modeling insights.

    Science.gov (United States)

    Agrawal, Shelesh; Seuntjens, Dries; Cocker, Pieter De; Lackner, Susanne; Vlaeminck, Siegfried E

    2018-04-01

    Twenty years ago, mainstream partial nitritation/anammox (PN/A) was conceptually proposed as pivotal for a more sustainable treatment of municipal wastewater. Its economic potential spurred research, yet practice awaits a comprehensive recipe for microbial resource management. Implementing mainstream PN/A requires transferable and operable ways to steer microbial competition as to meet discharge requirements on a year-round basis at satisfactory conversion rates. In essence, the competition for nitrogen, organic carbon and oxygen is grouped into 'ON/OFF' (suppression/promotion) and 'IN/OUT' (wash-out/retention and seeding) strategies, selecting for desirable conversions and microbes. Some insights need mechanistic understanding, while empirical observations suffice elsewhere. The provided methodological R&D framework integrates insights in engineering, microbiome and modeling. Such synergism should catalyze the implementation of energy-positive sewage treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Offer for our members

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    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. For those of you already insured with the company, contact your current advisor. Others may contact a counsel...

  10. 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 &...

  11. Offers for our members

    CERN Multimedia

    Staff Association

    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.

  12. Tackling the workforce crisis in district nursing: can the Dutch Buurtzorg model offer a solution and a better patient experience? A mixed methods case study.

    Science.gov (United States)

    Drennan, Vari M; Calestani, Melania; Ross, Fiona; Saunders, Mary; West, Peter

    2018-06-06

    Despite policy intentions for more healthcare out of hospital, district nursing services face multiple funding and staffing challenges, which compromise the care delivered and policy objectives. What is the impact of the adapted Buurtzorg model on feasibility, acceptability and effective outcomes in an English district nursing service? Mixed methods case study. Primary care. Neighbourhood nursing team (Buurtzorg model), patients and carers, general practitioners (GPs), other health professionals, managers and conventional district nurses. The adapted Buurtzorg model of community nursing demonstrated feasibility and acceptability to patients, carers, GPs and other health professionals. For many patients, it was preferable to previous experiences of district nursing in terms of continuity in care, improved support of multiple long-term conditions (encompassing physical, mental and social factors) and proactive care. For the neighbourhood nurses, the ability to make operational and clinical decisions at team level meant adopting practices that made the service more responsive, accessible and efficient and offered a more attractive working environment. Challenges were reported by nurses and managers in relation to the recognition and support of the concept of self-managing teams within a large bureaucratic healthcare organisation. While there were some reports of clinical effectiveness and efficiency, this was not possible to quantify, cost or compare with the standard district nursing service. The adapted Buurtzorg model of neighbourhood nursing holds potential for addressing issues of concern to patients, carers and staff in the community. The two interacting innovations, that is, a renewed focus on patient and carer-centred care and the self-managing team, were implemented in ways that patients, carers, other health professionals and nurses could identify difference for both the nursing care and also the nurses' working lives. It now requires longer term

  13. 1300 nm and 890 nm OCT images of oral cancer tissue engineered models and biopsy samples offer complimentary performance (Conference Presentation)

    Science.gov (United States)

    Boadi, Joseph; Byers, Robert A.; Fernandes, Jon; Mittar, Shweta; Hearnden, Vanessa; Lu, Zenghai; MacNeil, Sheila; Thornhill, Martin; Murdoch, Craig; Hunter, Keith D.; McKechnie, Alasdair; Matcher, Stephen J.

    2016-02-01

    OCT has demonstrated great potential to non-invasively detect oral epithelial cancers, potentially guiding biopsy and surgical resection. On non-ophthalmic tissues the preferred illumination wavelength is 1300 nm. Previous studies on skin have shown that useful image data can also be obtained at shorter wavelengths, with systems at 1060 nm and 820 nm offering reduced depth penetration but higher contrast. Here we apply a similar comparison to tissue engineered models of oral cancer and also to human biopsy samples, generally finding a similar trend. 1300 nm multi-beam OCT (Michelson Diagnostics EX1301) visualises stromal structures and surface keratin more clearly, providing useful image contrast down to around 1 mm. This system was compared with an ultra-high resolution home-built system operating at 890 nm (2.5 micron resolution vs 7.5 micron axial resolution for the EX1301). The UHR system reveals epithelial features more clearly, especially in the DOK pre-invasive cell line model and the biopsy samples. The relative effects of center wavelength vs axial resolution in generating the differential, wavelength-dependent contrast are assessed and the OCT biopsy images are compared with contemporary histology.

  14. Prevalence, level and distribution of Salmonella in shipments of imported capsicum and sesame seed spice offered for entry to the United States: observations and modeling results.

    Science.gov (United States)

    Van Doren, Jane M; Blodgett, Robert J; Pouillot, Régis; Westerman, Ann; Kleinmeier, Daria; Ziobro, George C; Ma, Yinqing; Hammack, Thomas S; Gill, Vikas; Muckenfuss, Martin F; Fabbri, Linda

    2013-12-01

    In response to increased concerns about spice safety, the United States Food and Drug Administration (FDA) initiated research to characterize the prevalence and levels of Salmonella in imported spices. 299 imported dried capsicum shipments and 233 imported sesame seed shipments offered for entry to the United States were sampled. Observed Salmonella shipment prevalence was 3.3% (1500 g examined; 95% CI 1.6-6.1%) for capsicum and 9.9% (1500 g; 95% Confidence Interval (CI) 6.3-14%) for sesame seed. Within shipment contamination was not inconsistent with a Poisson distribution. Shipment mean Salmonella level estimates among contaminated shipments ranged from 6 × 10(-4) to 0.09 (capsicum) or 6 × 10(-4) to 0.04 (sesame seed) MPN/g. A gamma-Poisson model provided the best fit to observed data for both imported shipments of capsicum and imported shipments of sesame seed sampled in this study among the six parametric models considered. Shipment mean levels of Salmonella vary widely between shipments; many contaminated shipments contain low levels of contamination. Examination of sampling plan efficacy for identifying contaminated spice shipments from these distributions indicates that sample size of spice examined is critical. Sampling protocols examining 25 g samples are predicted to be able to identify a small fraction of contaminated shipments of imported capsicum or sesame seeds. Published by Elsevier Ltd.

  15. Hydroclimate variability in Scandinavia over the last millennium - insights from a climate model-proxy data comparison

    Science.gov (United States)

    Seftigen, Kristina; Goosse, Hugues; Klein, Francois; Chen, Deliang

    2017-12-01

    The integration of climate proxy information with general circulation model (GCM) results offers considerable potential for deriving greater understanding of the mechanisms underlying climate variability, as well as unique opportunities for out-of-sample evaluations of model performance. In this study, we combine insights from a new tree-ring hydroclimate reconstruction from Scandinavia with projections from a suite of forced transient simulations of the last millennium and historical intervals from the CMIP5 and PMIP3 archives. Model simulations and proxy reconstruction data are found to broadly agree on the modes of atmospheric variability that produce droughts-pluvials in the region. Despite these dynamical similarities, large differences between simulated and reconstructed hydroclimate time series remain. We find that the GCM-simulated multi-decadal and/or longer hydroclimate variability is systematically smaller than the proxy-based estimates, whereas the dominance of GCM-simulated high-frequency components of variability is not reflected in the proxy record. Furthermore, the paleoclimate evidence indicates in-phase coherencies between regional hydroclimate and temperature on decadal timescales, i.e., sustained wet periods have often been concurrent with warm periods and vice versa. The CMIP5-PMIP3 archive suggests, however, out-of-phase coherencies between the two variables in the last millennium. The lack of adequate understanding of mechanisms linking temperature and moisture supply on longer timescales has serious implications for attribution and prediction of regional hydroclimate changes. Our findings stress the need for further paleoclimate data-model intercomparison efforts to expand our understanding of the dynamics of hydroclimate variability and change, to enhance our ability to evaluate climate models, and to provide a more comprehensive view of future drought and pluvial risks.

  16. Model for the techno-economic analysis of common work of wind power and CCGT power plant to offer constant level of power in the electricity market

    Science.gov (United States)

    Tomsic, Z.; Rajsl, I.; Filipovic, M.

    2017-11-01

    Wind power varies over time, mainly under the influence of meteorological fluctuations. The variations occur on all time scales. Understanding these variations and their predictability is of key importance for the integration and optimal utilization of wind in the power system. There are two major attributes of variable generation that notably impact the participation on power exchanges: Variability (the output of variable generation changes and resulting in fluctuations in the plant output on all time scales) and Uncertainty (the magnitude and timing of variable generation output is less predictable, wind power output has low levels of predictability). Because of these variability and uncertainty wind plants cannot participate to electricity market, especially to power exchanges. For this purpose, the paper presents techno-economic analysis of work of wind plants together with combined cycle gas turbine (CCGT) plant as support for offering continues power to electricity market. A model of wind farms and CCGT plant was developed in program PLEXOS based on real hourly input data and all characteristics of CCGT with especial analysis of techno-economic characteristics of different types of starts and stops of the plant. The Model analyzes the followings: costs of different start-stop characteristics (hot, warm, cold start-ups and shutdowns) and part load performance of CCGT. Besides the costs, the technical restrictions were considered such as start-up time depending on outage duration, minimum operation time, and minimum load or peaking capability. For calculation purposes, the following parameters are necessary to know in order to be able to economically evaluate changes in the start-up process: ramp up and down rate, time of start time reduction, fuel mass flow during start, electricity production during start, variable cost of start-up process, cost and charges for life time consumption for each start and start type, remuneration during start up time regarding

  17. First insight into the viral community of the cnidarian model metaorganism Aiptasia using RNA-Seq data

    KAUST Repository

    Brü wer, Jan D.; Voolstra, Christian R.

    2018-01-01

    of the globally threatened coral reef ecosystems. To gain first insight into viruses associated with the coral model system Aiptasia (sensu Exaiptasia pallida), we analyzed an existing RNA-Seq dataset of aposymbiotic, partially populated, and fully symbiotic

  18. Computational models of the pulmonary circulation: Insights and the move towards clinically directed studies

    Science.gov (United States)

    Tawhai, Merryn H.; Clark, Alys R.; Burrowes, Kelly S.

    2011-01-01

    Biophysically-based computational models provide a tool for integrating and explaining experimental data, observations, and hypotheses. Computational models of the pulmonary circulation have evolved from minimal and efficient constructs that have been used to study individual mechanisms that contribute to lung perfusion, to sophisticated multi-scale and -physics structure-based models that predict integrated structure-function relationships within a heterogeneous organ. This review considers the utility of computational models in providing new insights into the function of the pulmonary circulation, and their application in clinically motivated studies. We review mathematical and computational models of the pulmonary circulation based on their application; we begin with models that seek to answer questions in basic science and physiology and progress to models that aim to have clinical application. In looking forward, we discuss the relative merits and clinical relevance of computational models: what important features are still lacking; and how these models may ultimately be applied to further increasing our understanding of the mechanisms occurring in disease of the pulmonary circulation. PMID:22034608

  19. 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.

  20. A numerical insight into elastomer normally closed micro valve actuation with cohesive interfacial cracking modelling

    Science.gov (United States)

    Wang, Dongyang; Ba, Dechun; Hao, Ming; Duan, Qihui; Liu, Kun; Mei, Qi

    2018-05-01

    Pneumatic NC (normally closed) valves are widely used in high density microfluidics systems. To improve actuation reliability, the actuation pressure needs to be reduced. In this work, we utilize 3D FEM (finite element method) modelling to get an insight into the valve actuation process numerically. Specifically, the progressive debonding process at the elastomer interface is simulated with CZM (cohesive zone model) method. To minimize the actuation pressure, the V-shape design has been investigated and compared with a normal straight design. The geometrical effects of valve shape has been elaborated, in terms of valve actuation pressure. Based on our simulated results, we formulate the main concerns for micro valve design and fabrication, which is significant for minimizing actuation pressures and ensuring reliable operation.

  1. Water versus DNA: new insights into proton track-structure modelling in radiobiology and radiotherapy.

    Science.gov (United States)

    Champion, C; Quinto, M A; Monti, J M; Galassi, M E; Weck, P F; Fojón, O A; Hanssen, J; Rivarola, R D

    2015-10-21

    Water is a common surrogate of DNA for modelling the charged particle-induced ionizing processes in living tissue exposed to radiations. The present study aims at scrutinizing the validity of this approximation and then revealing new insights into proton-induced energy transfers by a comparative analysis between water and realistic biological medium. In this context, a self-consistent quantum mechanical modelling of the ionization and electron capture processes is reported within the continuum distorted wave-eikonal initial state framework for both isolated water molecules and DNA components impacted by proton beams. Their respective probability of occurrence-expressed in terms of total cross sections-as well as their energetic signature (potential and kinetic) are assessed in order to clearly emphasize the differences existing between realistic building blocks of living matter and the controverted water-medium surrogate. Consequences in radiobiology and radiotherapy will be discussed in particular in view of treatment planning refinement aiming at better radiotherapy strategies.

  2. Offerings from an urchin.

    Science.gov (United States)

    Ernst, Susan G

    2011-10-15

    There is a natural curiosity about how organisms give rise to offspring like themselves through a series of reproducible developmental events and how, once mature, these offspring mate and continue the process giving rise the next generation. In the mid-1800s investigators started using gametes and embryos to explore this process. Although the observations and experimental approaches changed over time, embryologists and developmental biologists after them, sought understanding of development and inheritance through the study of gametes and embryos. It is argued here that in their quests to understand these processes embryologists made major conceptual advances that were seminal to the origins of genetics and to the origins of molecular biology. Furthermore these advances derived from the distinct perspective of those investigators with focused interest on the development of the organism. In this essay fundamental discoveries that originated with the sea urchin embryo as an experimental system are used to illustrate this position. The sea urchin has a long and uninterrupted history as a model organism that helped prepare the ground for the emergence of genetics and contributed important aspects to understanding of the central dogma of molecular biology. As molecular biology came of age new concepts and technology of the discipline were transformative for developmental biology and to this day the reciprocal inductive interactions between molecular biology and developmental biology continue to revitalize each other. Copyright © 2011 Elsevier Inc. All rights reserved.

  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...... rates that previously were obtained only from extrapolations of results from in vitro kinetic experiments performed over short timescales. For example, recent next-generation sequencing of ancient DNA reveals purine bases as one of the main targets of postmortem hydrolytic damage, through base...... elimination and strand breakage. It also shows substantially increased rates of DNA base-loss at guanosine. In this review, we argue that the latter results from an electron resonance structure unique to guanosine rather than adenosine having an extra resonance structure over guanosine as previously suggested....

  4. 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

  5. Unusual antigen presentation offers new insight into HIV vaccine design.

    Science.gov (United States)

    McMichael, Andrew J; Picker, Louis J

    2017-06-01

    Recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong CD8+ T cell responses that are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E restricted, have been identified. MHC-E therefore can present a wide range of epitope peptides to CD8+ T cells, alongside its well defined role in presenting a conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural killer cells. Here we explore the antigen processing pathways involved in these atypical T cell responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Study Offers Keen Insights into Professional Development Research

    Science.gov (United States)

    Killion, Joellen

    2017-01-01

    Joellen Killion is senior advisor to Learning Forward. In each issue of "The Learning Professional", Killion explores a recent research study to help practitioners understand the impact of particular professional learning practices on student outcomes. In this Issue Mary Kennedy conducts a review and analysis of the research on…

  7. 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.

  8. 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.

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

    DEFF Research Database (Denmark)

    Holck, Lotte

    : In fact it can be enacted as an obstacle to inclusion, in that it induces an opaque power structure difficult to navigate for non-traditional members. My research demonstrates how analyzing the organizational space an external ‘effect’, as embodiment and as the product of membership actions, can render......-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...

  10. Modelling the Course of an HIV Infection: Insights from Ecology and Evolution

    Directory of Open Access Journals (Sweden)

    Carsten Magnus

    2012-10-01

    Full Text Available The Human Immunodeficiency Virus (HIV is one of the most threatening viral agents. This virus infects approximately 33 million people, many of whom are unaware of their status because, except for flu-like symptoms right at the beginning of the infection during the acute phase, the disease progresses more or less symptom-free for 5 to 10 years. During this asymptomatic phase, the virus slowly destroys the immune system until the onset of AIDS when opportunistic infections like pneumonia or Kaposi’s sarcoma can overcome immune defenses. Mathematical models have played a decisive role in estimating important parameters (e.g., virion clearance rate or life-span of infected cells. However, most models only account for the acute and asymptomatic latency phase and cannot explain the progression to AIDS. Models that account for the whole course of the infection rely on different hypotheses to explain the progression to AIDS. The aim of this study is to review these models, present their technical approaches and discuss the robustness of their biological hypotheses. Among the few models capturing all three phases of an HIV infection, we can distinguish between those that mainly rely on population dynamics and those that involve virus evolution. Overall, the modeling quest to capture the dynamics of an HIV infection has improved our understanding of the progression to AIDS but, more generally, it has also led to the insight that population dynamics and evolutionary processes can be necessary to explain the course of an infection.

  11. Organization, maturation and plasticity of multisensory integration: Insights from computational modelling studies

    Directory of Open Access Journals (Sweden)

    Cristiano eCuppini

    2011-05-01

    Full Text Available In this paper, we present two neural network models - devoted to two specific and widely investigated aspects of multisensory integration - in order to evidence the potentialities of computational models to gain insight into the neural mechanisms underlying organization, development and plasticity of multisensory integration in the brain. The first model considers visual-auditory interaction in a midbrain structure named Superior Colliculus (SC. The model is able to reproduce and explain the main physiological features of multisensory integration in SC neurons and to describe how SC integrative capability – not present at birth - develops gradually during postnatal life depending on sensory experience with cross-modal stimuli. The second model tackles the problem of how tactile stimuli on a body part and visual (or auditory stimuli close to the same body part are integrated in multimodal parietal neurons to form the perception of peripersonal (i.e., near space. The model investigates how the extension of peripersonal space - where multimodal integration occurs - may be modified by experience such as use of a tool to interact with the far space. The utility of the modelling approach relies on several aspects: i The two models, although devoted to different problems and simulating different brain regions, share some common mechanisms (lateral inhibition and excitation, non-linear neuron characteristics, recurrent connections, competition, Hebbian rules of potentiation and depression that may govern more generally the fusion of senses in the brain, and the learning and plasticity of multisensory integration. ii The models may help interpretation of behavioural and psychophysical responses in terms of neural activity and synaptic connections. iii The models can make testable predictions that can help guiding future experiments in order to validate, reject, or modify the main assumptions.

  12. Plant metabolic modeling: achieving new insight into metabolism and metabolic engineering.

    Science.gov (United States)

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

    2014-10-01

    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. © 2014 American Society of Plant Biologists. All rights reserved.

  13. 48 CFR 570.303-3 - Late offers, modifications of offers, and withdrawals of offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Late offers, modifications of offers, and withdrawals of offers. 570.303-3 Section 570.303-3 Federal Acquisition Regulations... PROPERTY Contracting Procedures for Leasehold Interests in Real Property 570.303-3 Late offers...

  14. 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...

  15. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

      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...

  16. 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  

  17. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

    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.

  18. Offers

    CERN Multimedia

    Staff association

    2014-01-01

        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...

  19. 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.

  20. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    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...

  1. 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

  2. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    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...

  3. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    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 !

  4. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    John J. Pilch

    1995-12-01

    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.

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

    Science.gov (United States)

    da Fontoura Budaszewski, Renata; von Messling, Veronika

    2016-10-11

    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.

  7. Natural and molecular history of prolactinoma: insights from a Prlr-/- mouse model.

    Science.gov (United States)

    Bernard, Valérie; Villa, Chiara; Auguste, Aurélie; Lamothe, Sophie; Guillou, Anne; Martin, Agnès; Caburet, Sandrine; Young, Jacques; Veitia, Reiner A; Binart, Nadine

    2018-01-19

    Lactotroph adenoma, also called prolactinoma, is the most common pituitary tumor but little is known about its pathogenesis. Mouse models of prolactinoma can be useful to better understand molecular mechanisms involved in abnormal lactotroph cell proliferation and secretion. We have previously developed a prolactin receptor deficient ( Prlr -/- ) mouse, which develops prolactinoma. The present study aims to explore the natural history of prolactinoma formation in Prlr -/- mice, using hormonal, radiological, histological and molecular analyses to uncover mechanisms involved in lactotroph adenoma development. Prlr -/- females develop large secreting prolactinomas from 12 months of age, with a penetrance of 100%, mimicking human aggressive densely granulated macroprolactinoma, which is a highly secreting subtype. Mean blood PRL measurements reach 14 902 ng/mL at 24 months in Prlr -/- females while PRL levels were below 15 ng/mL in control mice ( p model in ACI rats, we pinpointed 218 concordantly differentially expressed (DE) genes involved in cell cycle, mitosis, cell adhesion molecules, dopaminergic synapse and estrogen signaling. Pathway/gene-set enrichment analyses suggest that the transcriptomic dysregulation in both models of prolactinoma might be mediated by a limited set of transcription factors (i.e., STAT5, STAT3, AhR, ESR1, BRD4, CEBPD, YAP, FOXO1) and kinases (i.e., JAK2, AKT1, BRAF, BMPR1A, CDK8, HUNK, ALK, FGFR1, ILK). Our experimental results and their bioinformatic analysis provide insights into early genomic changes in murine models of the most frequent human pituitary tumor.

  8. Effects of prenatal alcohol exposure (PAE): insights into FASD using mouse models of PAE.

    Science.gov (United States)

    Petrelli, Berardino; Weinberg, Joanne; Hicks, Geoffrey G

    2018-04-01

    The potential impact of prenatal alcohol exposure (PAE) varies considerably among exposed individuals, with some displaying serious alcohol-related effects and many others showing few or no overt signs of fetal alcohol spectrum disorder (FASD). In animal models, variables such as nutrition, genetic background, health, other drugs, and stress, as well as dosage, duration, and gestational timing of exposure to alcohol can all be controlled in a way that is not possible in a clinical situation. In this review we examine mouse models of PAE and focus on those with demonstrated craniofacial malformations, abnormal brain development, or behavioral phenotypes that may be considered FASD-like outcomes. Analysis of these data should provide a valuable tool for researchers wishing to choose the PAE model best suited to their research questions or to investigate established PAE models for FASD comorbidities. It should also allow recognition of patterns linking gestational timing, dosage, and duration of PAE, such as recognizing that binge alcohol exposure(s) during early gestation can lead to severe FASD outcomes. Identified patterns could be particularly insightful and lead to a better understanding of the molecular mechanisms underlying FASD.

  9. 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. PMID:27335513

  10. Insights from a history of seasonal inflow forecasting with a conceptual hydrologic model

    Science.gov (United States)

    Druce, Donald J.

    2001-08-01

    BC Hydro has used a conceptual hydrologic model for forecasting the seasonal inflows to its Mica project, on the Columbia River, for more than 20 years. The model estimates the snowpack on the forecast date using recently observed weather data and then calculates the runoff response to approximately 30 historical weather sequences over the remainder of the year. The ensemble of equally likely seasonal inflows makes up the forecast. Forecasts are issued as of the first of each month from January to August. The same model and modeller have made all of such forecasts for the Mica project. While some may see this as a failure to progress, others may see it as an unique opportunity to learn how well an older hydrologic model has performed, in practice, over the long term. Comments on both perspectives are offered, after the analyses of the forecasts have been presented. The forecasts have been analysed, as of each of the monthly forecast dates, to determine the accuracy of the mean and to establish any differences between ex post and ex ante measures of uncertainty. Results are then compared with those from a regression model that has also been used for forecasting the seasonal inflows to the Mica project over the same period of record.

  11. Hydrologic characteristics of freshwater mussel habitat: novel insights from modeled flows

    Science.gov (United States)

    Drew, C. Ashton; Eddy, Michele; Kwak, Thomas J.; Cope, W. Gregory; Augspurger, Tom

    2018-01-01

    The ability to model freshwater stream habitat and species distributions is limited by the spatially sparse flow data available from long-term gauging stations. Flow data beyond the immediate vicinity of gauging stations would enhance our ability to explore and characterize hydrologic habitat suitability. The southeastern USA supports high aquatic biodiversity, but threats, such as landuse alteration, climate change, conflicting water-resource demands, and pollution, have led to the imperilment and legal protection of many species. The ability to distinguish suitable from unsuitable habitat conditions, including hydrologic suitability, is a key criterion for successful conservation and restoration of aquatic species. We used the example of the critically endangered Tar River Spinymussel (Parvaspina steinstansana) and associated species to demonstrate the value of modeled flow data (WaterFALL™) to generate novel insights into population structure and testable hypotheses regarding hydrologic suitability. With ordination models, we: 1) identified all catchments with potentially suitable hydrology, 2) identified 2 distinct hydrologic environments occupied by the Tar River Spinymussel, and 3) estimated greater hydrological habitat niche breadth of assumed surrogate species associates at the catchment scale. Our findings provide the first demonstrated application of complete, continuous, regional modeled hydrologic data to freshwater mussel distribution and management. This research highlights the utility of modeling and data-mining methods to facilitate further exploration and application of such modeled environmental conditions to inform aquatic species management. We conclude that such an approach can support landscape-scale management decisions that require spatial information at fine resolution (e.g., enhanced National Hydrology Dataset catchments) and broad extent (e.g., multiple river basins).

  12. Modeling fMRI signals can provide insights into neural processing in the cerebral cortex.

    Science.gov (United States)

    Vanni, Simo; Sharifian, Fariba; Heikkinen, Hanna; Vigário, Ricardo

    2015-08-01

    Every stimulus or task activates multiple areas in the mammalian cortex. These distributed activations can be measured with functional magnetic resonance imaging (fMRI), which has the best spatial resolution among the noninvasive brain imaging methods. Unfortunately, the relationship between the fMRI activations and distributed cortical processing has remained unclear, both because the coupling between neural and fMRI activations has remained poorly understood and because fMRI voxels are too large to directly sense the local neural events. To get an idea of the local processing given the macroscopic data, we need models to simulate the neural activity and to provide output that can be compared with fMRI data. Such models can describe neural mechanisms as mathematical functions between input and output in a specific system, with little correspondence to physiological mechanisms. Alternatively, models can be biomimetic, including biological details with straightforward correspondence to experimental data. After careful balancing between complexity, computational efficiency, and realism, a biomimetic simulation should be able to provide insight into how biological structures or functions contribute to actual data processing as well as to promote theory-driven neuroscience experiments. This review analyzes the requirements for validating system-level computational models with fMRI. In particular, we study mesoscopic biomimetic models, which include a limited set of details from real-life networks and enable system-level simulations of neural mass action. In addition, we discuss how recent developments in neurophysiology and biophysics may significantly advance the modelling of fMRI signals. Copyright © 2015 the American Physiological Society.

  13. A mathematical model for carbon dioxide elimination: an insight for tuning mechanical ventilation.

    Science.gov (United States)

    Pomprapa, Anake; Schwaiberger, David; Lachmann, Burkhard; Leonhardt, Steffen

    2014-01-01

    The aim is to provide better understanding of carbon dioxide (CO2) elimination during ventilation for both the healthy and atelectatic condition, derived in a pressure-controlled mode. Therefore, we present a theoretical analysis of CO2 elimination of healthy and diseased lungs. Based on a single-compartment model, CO2 elimination is mathematically modeled and its contours were plotted as a function of temporal settings and driving pressure. The model was validated within some level of tolerance on an average of 4.9% using porcine dynamics. CO2 elimination is affected by various factors, including driving pressure, temporal variables from mechanical ventilator settings, lung mechanics and metabolic rate. During respiratory care, CO2 elimination is a key parameter for bedside monitoring, especially for patients with pulmonary disease. This parameter provides valuable insight into the status of an atelectatic lung and of cardiopulmonary pathophysiology. Therefore, control of CO2 elimination should be based on the fine tuning of the driving pressure and temporal ventilator settings. However, for critical condition of hypercapnia, airway resistance during inspiration and expiration should be additionally measured to determine the optimal percent inspiratory time (%TI) to maximize CO2 elimination for treating patients with hypercapnia.

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

    International Nuclear Information System (INIS)

    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. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    Science.gov (United States)

    Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand

    2015-01-01

    Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases. PMID:25650393

  16. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    Directory of Open Access Journals (Sweden)

    Shobi Veleri

    2015-02-01

    Full Text Available Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases.

  17. The physiology of blood loss and shock: New insights from a human laboratory model of hemorrhage.

    Science.gov (United States)

    Schiller, Alicia M; Howard, Jeffrey T; Convertino, Victor A

    2017-04-01

    The ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of the various physiological mechanisms that are active during volume loss and that have the ability to stave off hemodynamic collapse. This review provides new insights about the physiology that underlies blood loss and shock in humans through the development of a simulated model of hemorrhage using lower body negative pressure. In this review, we present controlled experimental results through utilization of the lower body negative pressure human hemorrhage model that provide novel insights on the integration of physiological mechanisms critical to the compensation for volume loss. We provide data obtained from more than 250 human experiments to classify human subjects into two distinct groups: those who have a high tolerance and can compensate well for reduced central blood volume (e.g. hemorrhage) and those with low tolerance with poor capacity to compensate.We include the conceptual introduction of arterial pressure and cerebral blood flow oscillations, reflex-mediated autonomic and neuroendocrine responses, and respiration that function to protect adequate tissue oxygenation through adjustments in cardiac output and peripheral vascular resistance. Finally, unique time course data are presented that describe mechanistic events associated with the rapid onset of hemodynamic failure (i.e. decompensatory shock). Impact Statement Hemorrhage is the leading cause of death in both civilian and military trauma. The work submitted in this review is important because it advances the understanding of mechanisms that contribute to the total integrated physiological compensations for inadequate tissue oxygenation (i.e. shock) that arise from hemorrhage. Unlike an animal model, we introduce the utilization of lower body negative pressure as a noninvasive model that allows for the study of progressive

  18. Using Small Models for Big Issues : Exploratory System Dynamics Modelling and Analysis for Insightful Crisis Management

    NARCIS (Netherlands)

    Pruyt, E.

    2010-01-01

    The main goal of this paper is to explain and illustrate different exploratory uses of small System Dynamics models for analysis and decision support in case of dynamically complex issues that are deeply uncertain. The applied focuss of the paper is the field of inter/national safety and security.

  19. 16 CFR 238.2 - Initial offer.

    Science.gov (United States)

    2010-01-01

    ... § 238.2 Initial offer. (a) No statement or illustration should be used in any advertisement which creates a false impression of the grade, quality, make, value, currency of model, size, color, usability...

  20. Cell adhesion and spreading at a charged interface: Insight into the mechanism using surface techniques and mathematical modelling

    International Nuclear Information System (INIS)

    DeNardis, Nadica Ivošević; Ilić, Jadranka Pečar; Ružić, Ivica; Pletikapić, Galja

    2015-01-01

    intermolecular interactions and reorganization of molecules in the film. Our findings offer an insight into the mechanism of algal cell adhesion and spreading at charged interfaces, relevant for electroporation based studies

  1. Epigenome remodelling in breast cancer: insights from an early in vitro model of carcinogenesis.

    Science.gov (United States)

    Locke, Warwick J; Clark, Susan J

    2012-11-15

    Epigenetic gene regulation has influence over a diverse range of cellular functions, including the maintenance of pluripotency, differentiation, and cellular identity, and is deregulated in many diseases, including cancer. Whereas the involvement of epigenetic dysregulation in cancer is well documented, much of the mechanistic detail involved in triggering these changes remains unclear. In the current age of genomics, the development of new sequencing technologies has seen an influx of genomic and epigenomic data and drastic improvements in both resolution and coverage. Studies in cancer cell lines and clinical samples using next-generation sequencing are rapidly delivering spectacular insights into the nature of the cancer genome and epigenome. Despite these improvements in technology, the timing and relationship between genetic and epigenetic changes that occur during the process of carcinogenesis are still unclear. In particular, what changes to the epigenome are playing a driving role during carcinogenesis and what influence the temporal nature of these changes has on cancer progression are not known. Understanding the early epigenetic changes driving breast cancer has the exciting potential to provide a novel set of therapeutic targets or early-disease biomarkers or both. Therefore, it is important to find novel systems that permit the study of initial epigenetic events that potentially occur during the first stages of breast cancer. Non-malignant human mammary epithelial cells (HMECs) provide an exciting in vitro model of very early breast carcinogenesis. When grown in culture, HMECs are able to temporarily escape senescence and acquire a pre-malignant breast cancer-like phenotype (variant HMECs, or vHMECs). Cultured HMECs are composed mainly of cells from the basal breast epithelial layer. Therefore, vHMECs are considered to represent the basal-like subtype of breast cancer. The transition from HMECs to vHMECs in culture recapitulates the epigenomic

  2. New Insight into Combined Model and Revised Model for RTD Curves in a Multi-strand Tundish

    Science.gov (United States)

    Lei, Hong

    2015-12-01

    The analysis for the residence time distribution (RTD) curve is one of the important experimental technologies to optimize the tundish design. But there are some issues about RTD analysis model. Firstly, the combined (or mixed) model and the revised model give different analysis results for the same RTD curve. Secondly, different upper limits of integral in the numerator for the mean residence time give different results for the same RTD curve. Thirdly, the negative dead volume fraction sometimes appears at the outer strand of the multi-strand tundish. In order to solve the above problems, it is necessary to have a deep insight into the RTD curve and to propose a reasonable method to analyze the RTD curve. The results show that (1) the revised model is not appropriate to treat with the RTD curve; (2) the conception of the visual single-strand tundish and the combined model with the dimensionless time at the cut-off point are applied to estimate the flow characteristics in the multi-strand tundish; and that (3) the mean residence time at each exit is the key parameter to estimate the similarity of fluid flow among strands.

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

    Energy Technology Data Exchange (ETDEWEB)

    Eugène, Sarah, E-mail: Sarah.Eugene@inria.fr; Doumic, Marie, E-mail: Philippe.Robert@inria.fr, E-mail: Marie.Doumic@inria.fr [INRIA de Paris, 2 Rue Simone Iff, CS 42112, 75589 Paris Cedex 12 (France); Sorbonne Universités, UPMC Université Pierre et Marie Curie, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005 Paris (France); Xue, Wei-Feng, E-mail: W.F.Xue@kent.ac.uk [School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ (United Kingdom); Robert, Philippe, E-mail: Philippe.Robert@inria.fr [INRIA de Paris, 2 Rue Simone Iff, CS 42112, 75589 Paris Cedex 12 (France)

    2016-05-07

    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.

  4. 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.

  5. Top Mysteries of the Mind: Insights From the Default Space Model of Consciousness

    Directory of Open Access Journals (Sweden)

    Ravinder Jerath

    2018-04-01

    Full Text Available Aside from the nature of consciousness itself, there are still many unsolved problems in the neurosciences. Despite the vast and quickly growing body of work in this field, we still find ourselves perplexed at seemingly simple qualities of our mental being such as why we need to sleep. The neurosciences are at least beginning to take a hold on these mysteries and are working toward solving them. We hold a perspective that metastable consciousness models, specifically the Default Space Model (DSM, provide insights into these mysteries. In this perspective article, we explore some of these curious questions in order to elucidate the interesting points they bring up. The DSM is a dynamic, global theory of consciousness that involves the maintenance of an internal, 3D simulation of the external, physical world which is the foundation and structure of consciousness. This space is created and filled by multiple frequencies of membrane potential oscillations throughout the brain and body which are organized, synchronized and harmonized by the thalamus. The veracity of the DSM is highlighted here in its ability to further understanding of some of the most puzzling problems in neuroscience.

  6. Insights into coronary collateral formation from a novel porcine semiacute infarction model.

    Science.gov (United States)

    Krackhardt, Florian; Harnoss, Jonathan M; Waliszewski, Matthias W; Ritter, Zully; Granzow, Susanne; Felsenberg, Dieter; Neumann, Konrad; Lerman, Lilian O; Hillmeister, Philipp; Gebker, Rolf; Paetsch, Ingo; Riediger, Fabian; Bramlage, Peter; Buschmann, Ivo R

    2018-03-01

    For patients with severe ischemic heart disease, complete revascularization by a percutaneous coronary intervention or coronary artery bypass grafting is often not achieved and may still cause residual angina. In case of progressive coronary artery occlusions, therapeutic arteriogenesis constitutes a promising strategy for increasing blood supply to the ischemic myocardium. Whether the formation of collaterals in the hypofused myocardium is angiogenetic in nature or based on preformed coronary artery anastomoses remains debatable. The objectives of this research were (i) the development of an appropriate research methodology to study a humanoid animal semiacute infarction model with low mortality and (ii) to answer the question of whether collateral revascularization follows a pre-existing 'blueprint'. A porcine model was chosen in which a step-wise vessel occlusion was performed by implantation of a copper stent into the distal left anterior descending artery. Vessel occlusion and collateral development were confirmed in vivo every 14 days up to day 56 by repeated coronary angiography and myocardial perfusion measurement using cardiac MRI. After the completion of the in-vivo imaging studies, animals were euthanized and collateral growth was evaluated using microcomputer tomography. Our porcine model of semiacute noninvasive coronary artery occlusion confirmed the existence of preformed coronary anastomoses and the proliferation of functional vessels in hypoperfused myocardium. Repetitive intra-animal MRIs showed the functional impact of these growing collaterals. The confirmation of preformed coronary anastomoses during the process of collateralization (natural bypasses) offers a preclinical avenue to carry out arteriogenetic pharmaceutical research in patients with ischemic heart disease.

  7. Insights into Working Memory from The Perspective of The EPIC Architecture for Modeling Skilled Perceptual-Motor and Cognitive Human Performance

    National Research Council Canada - National Science Library

    Kieras, David

    1998-01-01

    Computational modeling of human perceptual-motor and cognitive performance based on a comprehensive detailed information- processing architecture leads to new insights about the components of working memory...

  8. 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.

  9. Security of supply and retail competition in the European gas market. Some model-based insights

    International Nuclear Information System (INIS)

    Abada, Ibrahim; Massol, Olivier

    2011-04-01

    In this paper, we analyze the impact of uncertain disruptions in gas supply upon gas retailer contracting behavior and consequent price and welfare implications in a gas market characterized by long-term gas contracts using a static Cournot model. In order to most realistically describe the economical situation, our representation divides the market into two stages: the upstream market that links, by means of long-term contracts, producers in exporting countries (Russia, Algeria, etc.) to local retailers who bring gas to the consuming countries to satisfy local demands in the downstream market. Disruption costs are modeled using short-run demand functions. First we mathematically develop a general model and write the associated KKT conditions, then we propose some case studies, under iso-elasticity assumptions, for the long-short-run inverse-demand curves in order to predict qualitatively and quantitatively the impacts of supply disruptions on Western European gas trade. In the second part, we study in detail the German gas market of the 1980's to explain the supply choices of the German retailer, and we derive interesting conclusions and insights concerning the amounts and prices of natural gas brought to the market. The last part of the paper is dedicated to a study of the Bulgarian gas market, which is greatly dependent on the Russian gas supplies and hence very sensitive to interruption risks. Some interesting conclusions are derived concerning the necessity to economically regulate the market, by means of gas amounts control, if the disruption probability is high enough. (authors)

  10. Seismic attenuation in fractured porous media: insights from a hybrid numerical and analytical model

    International Nuclear Information System (INIS)

    Ekanem, A M; Li, X Y; Chapman, M; Main, I G

    2015-01-01

    Seismic attenuation in fluid-saturated porous rocks can occur by geometric spreading, wave scattering or the internal dissipation of energy, most likely due to the squirt-flow mechanism. In principle, the pattern of seismic attenuation recorded on an array of sensors contains information about the medium, in terms of material heterogeneity and anisotropy, as well as material properties such as porosity, crack density, and pore-fluid composition and mobility. In practice, this inverse problem is challenging. Here we provide some insights into the effects of internal dissipation by analysing synthetic data produced by a hybrid numerical and analytical model for seismic wave propagation in a fractured medium embedded within a layered geological structure. The model is made up of one anisotropic and three isotropic horizontal layers. The anisotropic layer consists of a porous, fluid-saturated material containing vertically aligned inclusions representing a set of fractures. This combination allows squirt-flow to occur between the pores in the matrix and the model fractures. Our results show that the fluid mobility and the associated relaxation time of the fluid-pressure gradient control the frequency range over which attenuation occurs. This induced attenuation increases with incidence angle and azimuth away from the fracture strike-direction. Azimuthal variations in the induced attenuation are elliptical allowing the fracture orientations to be obtained from the axes of the ellipse. These observations hold out the potential of using seismic attenuation as an additional diagnostic in the characterisation of rock formations for a variety of applications including hydrocarbon exploration and production, subsurface storage of CO 2 , and geothermal energy extraction. (paper)

  11. 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.

  12. 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

  13. Model for the techno-economic analysis of common work of wind power and CCGT power plant to offer constant level of power in the electricity market

    Directory of Open Access Journals (Sweden)

    Tomsic Z.

    2017-01-01

    For calculation purposes, the following parameters are necessary to know in order to be able to economically evaluate changes in the start-up process: ramp up and down rate, time of start time reduction, fuel mass flow during start, electricity production during start, variable cost of start-up process, cost and charges for life time consumption for each start and start type, remuneration during start up time regarding expected or unexpected starts, the cost and revenues for balancing energy (important when participating in electricity market, and the cost or revenues for CO2-certificates. Main motivation for this analysis is to investigate possibilities to participate on power exchanges by offering continues guarantied power from wind plants by backing-up them with CCGT power plant.

  14. Climate change induced transformations of agricultural systems: insights from a global model

    Science.gov (United States)

    Leclère, D.; Havlík, P.; Fuss, S.; Schmid, E.; Mosnier, A.; Walsh, B.; Valin, H.; Herrero, M.; Khabarov, N.; Obersteiner, M.

    2014-12-01

    Climate change might impact crop yields considerably and anticipated transformations of agricultural systems are needed in the coming decades to sustain affordable food provision. However, decision-making on transformational shifts in agricultural systems is plagued by uncertainties concerning the nature and geography of climate change, its impacts, and adequate responses. Locking agricultural systems into inadequate transformations costly to adjust is a significant risk and this acts as an incentive to delay action. It is crucial to gain insight into how much transformation is required from agricultural systems, how robust such strategies are, and how we can defuse the associated challenge for decision-making. While implementing a definition related to large changes in resource use into a global impact assessment modelling framework, we find transformational adaptations to be required of agricultural systems in most regions by 2050s in order to cope with climate change. However, these transformations widely differ across climate change scenarios: uncertainties in large-scale development of irrigation span in all continents from 2030s on, and affect two-thirds of regions by 2050s. Meanwhile, significant but uncertain reduction of major agricultural areas affects the Northern Hemisphere’s temperate latitudes, while increases to non-agricultural zones could be large but uncertain in one-third of regions. To help reducing the associated challenge for decision-making, we propose a methodology exploring which, when, where and why transformations could be required and uncertain, by means of scenario analysis.

  15. Climate change induced transformations of agricultural systems: insights from a global model

    International Nuclear Information System (INIS)

    Leclère, D; Havlík, P; Mosnier, A; Walsh, B; Valin, H; Khabarov, N; Obersteiner, M; Fuss, S; Schmid, E; Herrero, M

    2014-01-01

    Climate change might impact crop yields considerably and anticipated transformations of agricultural systems are needed in the coming decades to sustain affordable food provision. However, decision-making on transformational shifts in agricultural systems is plagued by uncertainties concerning the nature and geography of climate change, its impacts, and adequate responses. Locking agricultural systems into inadequate transformations costly to adjust is a significant risk and this acts as an incentive to delay action. It is crucial to gain insight into how much transformation is required from agricultural systems, how robust such strategies are, and how we can defuse the associated challenge for decision-making. While implementing a definition related to large changes in resource use into a global impact assessment modelling framework, we find transformational adaptations to be required of agricultural systems in most regions by 2050s in order to cope with climate change. However, these transformations widely differ across climate change scenarios: uncertainties in large-scale development of irrigation span in all continents from 2030s on, and affect two-thirds of regions by 2050s. Meanwhile, significant but uncertain reduction of major agricultural areas affects the Northern Hemisphere’s temperate latitudes, while increases to non-agricultural zones could be large but uncertain in one-third of regions. To help reducing the associated challenge for decision-making, we propose a methodology exploring which, when, where and why transformations could be required and uncertain, by means of scenario analysis. (letter)

  16. Cognitive Enhancers for Facilitating Drug Cue Extinction: Insights from Animal Models

    Science.gov (United States)

    Nic Dhonnchadha, Bríd Áine; Kantak, Kathleen M.

    2011-01-01

    Given the success of cue exposure (extinction) therapy combined with a cognitive enhancer for reducing anxiety, it is anticipated that this approach will prove more efficacious than exposure therapy alone in preventing relapse in individuals with substance use disorders. Several factors may undermine the efficacy of exposure therapy for substance use disorders, but we suspect that neurocognitive impairments associated with chronic drug use are an important contributing factor. Numerous insights on these issues are gained from research using animal models of addiction. In this review, the relationship between brain sites whose learning, memory and executive functions are impaired by chronic drug use and brain sites that are important for effective drug cue extinction learning is explored first. This is followed by an overview of animal research showing improved treatment outcome for drug addiction (e.g. alcohol, amphetamine, cocaine, heroin) when explicit extinction training is conducted in combination with acute dosing of a cognitive-enhancing drug. The mechanism by which cognitive enhancers are thought to exert their benefits is by facilitating consolidation of drug cue extinction memory after activation of glutamatergic receptors. Based on the encouraging work in animals, factors that may be important for the treatment of drug addiction are considered. PMID:21295059

  17. 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.

  18. Offering Incentives from the Outside

    DEFF Research Database (Denmark)

    Emmanuel, Nikolas G.

    2017-01-01

    Incentives offer a good deal of underexplored opportunities to help manage conflict by encouraging political bargaining. This study has two primary objectives. First, it furthers the discussion of how external third parties can help manage conflicts. Second, it offers a typology of the available ...

  19. Neuroprotective effects of estrogen in CNS injuries: insights from animal models

    Directory of Open Access Journals (Sweden)

    Raghava N

    2017-07-01

    Full Text Available Narayan Raghava,1 Bhaskar C Das,2 Swapan K Ray1 1Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA; 2Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA Abstract: Among the estrogens that are biosynthesized in the human body, 17β-estradiol (estradiol or E2 is the most common and the best estrogen for neuroprotection in animal models of the central nervous system (CNS injuries such as spinal cord injury (SCI, traumatic brain injury (TBI, and ischemic brain injury (IBI. These CNS injuries are not only serious health problems, but also enormous economic burden on the patients, their families, and the society at large. Studies from animal models of these CNS injuries provide insights into the multiple neuroprotective mechanisms of E2 and also suggest the possibility of translating the therapeutic efficacy of E2 in the treatment SCI, TBI, and IBI in humans in the near future. The pathophysiology of these injuries includes loss of motor function in the limbs, arms and their extremities, cognitive deficit, and many other serious consequences including life-threatening paralysis, infection, and even death. The potential application of E2 therapy to treat the CNS injuries may become a trend as the results are showing significant therapeutic benefits of E2 for neuroprotection when administered into the animal models of SCI, TBI, and IBI. This article describes the plausible mechanisms how E2 works with or without the involvement of estrogen receptors and provides an overview of the known neuroprotective effects of E2 in these three CNS injuries in different animal models. Because activation of estrogen receptors has profound implications in maintaining and also affecting normal physiology, there are notable impediments in translating E2 therapy to the clinics for neuroprotection in CNS injuries in humans. While E2 may not yet be the sole molecule for

  20. Learning from a paradox: recent insights into Fanconi anaemia through studying mouse models

    Directory of Open Access Journals (Sweden)

    Sietske T. Bakker

    2013-01-01

    Full Text Available Fanconi anaemia (FA is a rare autosomal recessive or X-linked inherited disease characterised by an increased incidence of bone marrow failure (BMF, haematological malignancies and solid tumours. Cells from individuals with FA show a pronounced sensitivity to DNA interstrand crosslink (ICL-inducing agents, which manifests as G2-M arrest, chromosomal aberrations and reduced cellular survival. To date, mutations in at least 15 different genes have been identified that cause FA; the products of all of these genes are thought to function together in the FA pathway, which is essential for ICL repair. Rapidly following the discovery of FA genes, mutant mice were generated to study the disease and the affected pathway. These mutant mice all show the characteristic cellular ICL-inducing agent sensitivity, but only partially recapitulate the developmental abnormalities, anaemia and cancer predisposition seen in individuals with FA. Therefore, the usefulness of modelling FA in mice has been questioned. In this Review, we argue that such scepticism is unjustified. We outline that haematopoietic defects and cancer predisposition are manifestations of FA gene defects in mice, albeit only in certain genetic backgrounds and under certain conditions. Most importantly, recent work has shown that developmental defects in FA mice also arise with concomitant inactivation of acetaldehyde metabolism, giving a strong clue about the nature of the endogenous lesion that must be repaired by the functional FA pathway. This body of work provides an excellent example of a paradox in FA research: that the dissimilarity, rather than the similarity, between mice and humans can provide insight into human disease. We expect that further study of mouse models of FA will help to uncover the mechanistic background of FA, ultimately leading to better treatment options for the disease.

  1. 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.

  2. 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

  3. Estimation of daily reference evapotranspiration (ETo) using artificial intelligence methods: Offering a new approach for lagged ETo data-based modeling

    Science.gov (United States)

    Mehdizadeh, Saeid

    2018-04-01

    Evapotranspiration (ET) is considered as a key factor in hydrological and climatological studies, agricultural water management, irrigation scheduling, etc. It can be directly measured using lysimeters. Moreover, other methods such as empirical equations and artificial intelligence methods can be used to model ET. In the recent years, artificial intelligence methods have been widely utilized to estimate reference evapotranspiration (ETo). In the present study, local and external performances of multivariate adaptive regression splines (MARS) and gene expression programming (GEP) were assessed for estimating daily ETo. For this aim, daily weather data of six stations with different climates in Iran, namely Urmia and Tabriz (semi-arid), Isfahan and Shiraz (arid), Yazd and Zahedan (hyper-arid) were employed during 2000-2014. Two types of input patterns consisting of weather data-based and lagged ETo data-based scenarios were considered to develop the models. Four statistical indicators including root mean square error (RMSE), mean absolute error (MAE), coefficient of determination (R2), and mean absolute percentage error (MAPE) were used to check the accuracy of models. The local performance of models revealed that the MARS and GEP approaches have the capability to estimate daily ETo using the meteorological parameters and the lagged ETo data as inputs. Nevertheless, the MARS had the best performance in the weather data-based scenarios. On the other hand, considerable differences were not observed in the models' accuracy for the lagged ETo data-based scenarios. In the innovation of this study, novel hybrid models were proposed in the lagged ETo data-based scenarios through combination of MARS and GEP models with autoregressive conditional heteroscedasticity (ARCH) time series model. It was concluded that the proposed novel models named MARS-ARCH and GEP-ARCH improved the performance of ETo modeling compared to the single MARS and GEP. In addition, the external

  4. (How) does sectoral detail affect the robustness of policy insights from energy system models? The refining sector's example

    International Nuclear Information System (INIS)

    Nicolas, Claire; Saint-Antonin, Valerie; Tchung-Ming, Stephane

    2014-01-01

    In this research, we rekindle an old debate by questioning the impact on mitigating policy evaluation of detailing a sub-sector in a global energy-transportation model. We chose the refining sector because it is a relevant case of a sector for which representation widely differs across models and because it offers a unique set of complex joint production in the energy sector. To investigate whether the level of detail in the description of the refinery impacts optimal mitigation options, we take the example of a long-term, national, linear programming based, energy-transport system model (TIMES based). We found that the refinery description used in the energy system model matters when trying to evaluate energy or climate policy applied to the transportation sector. It impacts the policy costs but also the technology trajectories chosen at the optimum. Essentially, the balance between energy efficiency and carbon intensity of transport may be affected by the accuracy of the description of the pivotal refining sector. Consequently, increasing this sector accuracy level should not only be motivated by the wish to gain wider quantitative insights on potential evolution of the energy system but also by the wish to improve the robustness of the model outcomes. (authors)

  5. 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

  6. 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

  7. 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

  8. Insight into the relationship between impulsivity and substance abuse from studies using animal models.

    Science.gov (United States)

    Winstanley, Catharine A; Olausson, Peter; Taylor, Jane R; Jentsch, J David

    2010-08-01

    Drug use disorders are often accompanied by deficits in the capacity to efficiently process reward-related information and to monitor, suppress, or override reward-controlled behavior when goals are in conflict with aversive or immediate outcomes. This emerging deficit in behavioral flexibility and impulse control may be a central component of the progression to addiction, as behavior becomes increasingly driven by drugs and drug-associated cues at the expense of more advantageous activities. Understanding how neural mechanisms implicated in impulse control are affected by addictive drugs may therefore prove a useful strategy in the search for new treatment options. Animal models of impulsivity and addiction could make a significant contribution to this endeavor. Here, some of the more common behavioral paradigms used to measure different aspects of impulsivity across species are outlined, and the importance of the response to reward-paired cues in such paradigms is discussed. Naturally occurring differences in forms of impulsivity have been found to be predictive of future drug self-administration, but drug exposure can also increase impulsive responding. Such data are in keeping with the suggestion that impulsivity may contribute to multiple stages within the spiral of addiction. From a neurobiological perspective, converging evidence from rat, monkey, and human studies suggest that compromised functioning within the orbitofrontal cortex may critically contribute to the cognitive sequelae of drug abuse. Changes in gene transcription and protein expression within this region may provide insight into the mechanism underlying drug-induced cortical hypofunction, reflecting new molecular targets for the treatment of uncontrolled drug-seeking and drug-taking behavior.

  9. 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

  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. Implementing a physical soil water flow model with minimal soil characteristics and added value offered by surface soil moisture measurements assimilation.

    Science.gov (United States)

    Chanzy, André

    2010-05-01

    Soil moisture is a key variable for many soil physical and biogeochemical processes. Its dynamic results from water fluxes in soil and at its boundaries, as well as soil water storage properties. If the water flows are dominated by diffusive processes, modelling approaches based on the Richard's equation or the Philip and de Vries coupled heat and water flow equations lead to a satisfactory representation of the soil moisture dynamic. However, It requires the characterization of soil hydraulic functions, the initialisation and the boundary conditions, which are expensive to obtain. The major problem to assess soil moisture for decision making or for representing its spatiotemporal evolution over complex landscape is therefore the lack of information to run the models. The aim of the presentation is to analyse how a soil moisture model can be implemented when only climatic data and basic soil information are available (soil texture, organic matter) and what would be the added of making a few soil moisture measurements. We considered the field scale, which is the key scale for decision making application (the field being the management unit for farming system) and landscape modelling (field size being comparable to the computation unit of distributed hydrological models). The presentation is limited to the bare soil case in order to limit the complexity of the system and the TEC model based on Philip and De Vries equations is used in this study. The following points are addressed: o the within field spatial variability. This spatial variability can be induced by the soil hydraulic properties and/or by the amount of infiltrated water induced by water rooting towards infiltration areas. We analyse how an effective parameterization of soil properties and boundary conditions can be used to simulate the field average moisture. o The model implementation with limited information. We propose strategies that can be implemented when information are limited to soil texture and

  12. Hypogonadotropic hypogonadism and metabolic syndrome: insights from the high-fat diet experimental rabbit animal model.

    Science.gov (United States)

    Morelli, Annamaria; Vignozzi, Linda; Maggi, Mario

    2016-06-01

    The etiology of metabolic syndrome (MetS) is complex and involves the interplay between environmental, lifestyle and genetic determinants. MetS in men can be associated with a biochemical pattern of partial hypogonadotropic hypogonadism (HH). A similar pattern has been noted in both men and women with a variety of acute illnesses and chronic diseases, and there is ongoing debate regarding whether this phenomenon might adaptive (e.g. diverting resources from reproduction into survival), or maladaptive (e.g. anemia, sarcopenia, osteopenia and fatigue of androgen-deficiency amplify and widen the adverse consequences of the original disease-trigger). In women with hypothalamic amenorrhea (HA-HH secondary to chronic bioenergetic deficit from dietary restriction and/or intensive exercise), a genetic link to congenital HH (CHH) was recently established; women carrying monoallelic CHH gene mutations will typically not develop CHH, but are significantly more susceptible to HA. However, the male reproductive axis seems to be more resistant to similar environmental insults. In contrast, MetS-associated HH (mHH) is specifically a male phenomenon; the reproductive phenotype of females with MetS tending instead towards hyperandrogenism, rather than hypogonadism. The underlying pathogenic mechanisms responsible for mHH have not been clearly identified and, as yet, there has been no investigation of a potential role for CHH mutation carriage in its etiology. Over the decades, the use of either genetic- or diet-induced obesity and/or MetS animal models has greatly helped to illuminate the complex etiology of metabolic dysregulation, but the strong relationship between obesity/MetS and mHH in males has been largely neglected, with little or no information about the regulation of reproductive function by metabolic factors under conditions of bioenergetic excess. However, the pathogenic link between MetS and HH in males has been recently investigated in an animal model of high fat

  13. 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

  14. New offer for our members

    CERN Document Server

    Staff Association

    2018-01-01

    Evolution 2, your specialist for Outdoor Adventures Be it for a ski lesson, a parachute jump or for a mountain bike descent, come live an unforgettable experience with our outdoor specialists. Benefit from a 10 % discount on all activities: Offer is open to SA members and their family members living in the same household, upon presentation of the membership card. Offer available for all bookings made between 1 June 2018 and 30 May 2019. Offer available on all the Evoltion2 sites. A wide range of summer and winter activities. More information on http://evolution2.com/ Contact and reservation : +33 (0)4.50.02.63.35 management@evolution2.com

  15. 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 attracts...... billion dollar investments every year. The technology and Internet evolution have contributed significantly to the creation of eHealth within the Healthcare sector that aims to improve citizens’ health and wellbeing. Nevertheless, the barriers to entry in this highly regulated business sector are huge...... and therefore integrated eHealth solutions fail to reach high levels of penetration. Considering this as big challenge, the paper presents a hybrid business models that is able to efficiently address the Healthcare sector stakeholders and create prosperous opportunities for eHealth solutions for startup...

  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. 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. 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.

  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. The offerings from the Hyperboreans.

    Science.gov (United States)

    Ruck, C A

    1983-08-01

    The ancient Greeks believed that the fruits of agriculture could be harvested only if one first appeased the spirit of the primitive avatars from which the edible crop had been evolved over the centuries through hybridization and cultivation. On occasion, this appeasement was secured through the sacrifice of a human victim, a person who for various reasons could be considered to represent a similar primitivism. By the classical age, this extreme form of sacrificial appeasement appears to have been reserved for times of unusual crisis, such as pestilence or natural disaster, for at such times, the resurgent forces of primitivism seemed to threaten the entire civilization with regression back to its wilder origins. Other forms of appeasement were ordinarily substituted for the actual offering of a human victim. Amongst these was the enactment of puberty rites, for the natural growth and maturation of an individual could be thought to symbolize this same evolutionary process. Each infant is born as a wild creature who must develop into a socialized adult through the metaphoric death of its former self as it assumes the responsibilities of civilized life in crossing the threshold to sexual maturity. A similar symbolic victim was customarily represented by the offering of first fruits. A portion of the cultivated crop was prematurely cut and consecrated to redeem and release the ripening harvest from the dangerous contamination with the spirits of its pre-agricultural precedents. On the island of Delos, a special version of this consecration was performed. Each year, the various Greek cities would send a sheaf of unripened grain to the sanctuary of the god Apollo and his twin sister Artemis. Amongst these annual offerings, there was one that was supposed to have originated from the Hyperboreans, a mythical people who were thought to live in the original homeland of the two gods. This special Hyperborean offering differed from the others, for it was said to contain a

  1. Decarbonation and carbonation processes in the slab and mantle wedge - insights from thermomechanical modeling

    Science.gov (United States)

    Gonzalez, C. M.; Gorczyk, W.; Connolly, J. A.; Gerya, T.; Hobbs, B. E.; Ord, A.

    2013-12-01

    Subduction zones offer one of the most geologically active and complex systems to investigate. They initiate a process in which crustal sediments are recycled, mantle heterogeneities arise, and mantle wedge refertilization occurs via slab derived volatiles and magma generation. Slab derived volatiles, consisting primarily of H2O - CO2 fluids, are especially critical in subduction evolution as they rheologically weaken the mantle wedge, decrease solidus temperatures, and rock-fluid interactions result in metasomatism. While the effects of H2O in these processes have been well studied in the past decades, CO2's role remains open for much scientific study. This is partly attributed to the sensitivity of decarbonation to the thermal gradient of the subduction zone, bulk compositions (sediments, basalts, peridotites) and redox state of the mantle. Here we show benchmarking results of a subduction scenario that implements carbonation-decarbonation reactions into a fully coupled petrological-thermomechanical numerical modeling code. We resolve stable mineralogy and extract rock properties via Perple_X at a resolution of 5°C and 25 MPa. The numerical technique employed is a characteristics-based marker-in-cell technique with conservative finite-differences that includes visco-elastic-plastic rheologies (I2ELVIS). The devolatilized fluids are tracked via markers that are either generated or consumed based on P-T conditions. The fluids are also allowed to freely advect within the velocity field. The hosts for CO2 in this system are computed via GLOSS average sediments (H2O: 7.29 wt% & CO2: 3.01 wt%), metabasalts ( H2O: 2.63 & CO2: 2.90 wt%), and ophicarbonates (H2O: 1.98 wt% & CO2: 5.00 wt%). Our results demonstrate the feasibility of applying this decarbonation-carbonation numerical method to a range of geodynamic scenarios that simulate the removal of CO2 from the subducting slab. Such applicable scenarios include sediment diapirism into the convecting wedge and better

  2. New Paradigms for the Study of Ocular Alphaherpesvirus Infections: Insights into the Use of Non-Traditional Host Model Systems

    Directory of Open Access Journals (Sweden)

    Matthew R. Pennington

    2017-11-01

    Full Text Available Ocular herpesviruses, most notably human alphaherpesvirus 1 (HSV-1, canid alphaherpesvirus 1 (CHV-1 and felid alphaherpesvirus 1 (FHV-1, infect and cause severe disease that may lead to blindness. CHV-1 and FHV-1 have a pathogenesis and induce clinical disease in their hosts that is similar to HSV-1 ocular infections in humans, suggesting that infection of dogs and cats with CHV-1 and FHV-1, respectively, can be used as a comparative natural host model of herpesvirus-induced ocular disease. In this review, we discuss both strengths and limitations of the various available model systems to study ocular herpesvirus infection, with a focus on the use of these non-traditional virus-natural host models. Recent work has demonstrated the robustness and reproducibility of experimental ocular herpesvirus infections in dogs and cats, and, therefore, these non-traditional models can provide additional insights into the pathogenesis of ocular herpesvirus infections.

  3. Insights to Engineered Geothermal System Performance Using Gringarten-Witherspoon-Ohnishi Analytical Solutions and Fracture Network Models

    Science.gov (United States)

    Doe, T.; McLaren, R.; Finilla, A.

    2017-12-01

    An enduring legacy of Paul Witherspoon and his students and colleagues has been both the development of geothermal energy and the bases of modern fractured-rock hydrogeology. One of the seminal contributions to the geothermal field was Gringarten, Witherspoon, and Ohnishi's analytical models for enhanced geothermal systems. Although discrete fracture network (DFN) modeling developed somewhat independently in the late 1970s, Paul Witherspoon's foresight in promoting underground in situ testing at the Stripa Mine in Sweden was a major driver in Lawrence Berkeley Laboratory's contributions to its development.This presentation looks extensions of Gringarten's analytical model into discrete fracture network modeling as a basis for providing further insights into the challenges and opportunities of engineered geothermal systems. The analytical solution itself has many insightful applications beyond those presented in the original paper. The definition of dimensionless time by itself shows that thermal breakthrough has a second power dependence on surface area and on flow rate. The fracture intensity also plays a strong role, as it both increases the surface area and decrease his flow rate per fracture. The improvement of EGS performance with fracture intensity reaches a limit where thermal depletion of the rock lags only slightly behind the thermal breakthrough of cold water in the fracture network.Simple network models, which couple a DFN generator (FracMan) with a hydrothermally coupled flow solver (HydroGeoSphere) expand on Gringarten's concepts to show that realistic heterogeneity of spacing and transmissivity significantly degrades EGS performance. EGS production in networks of stimulated fractures initially follows Gringarten's type curves, with a later deviation is the smaller rock blocks thermally deplete and the entire stimulated volume acts as a single sink. Three-dimensional models of EGS performance show the critical importance of the relative magnitudes of

  4. Chemical Insights from Carbon 1s Photoelectron Spectroscopy and Theoretical Modeling

    International Nuclear Information System (INIS)

    Oltedal, Velaug M

    2007-05-01

    Inner-shell ionization energies provide local probes of the charge distribution in molecules and of the ability of a molecule to accept charge at specific sites. As such, core-ionization energies are related to and may provide insight into other chemical properties that depend on the same ability. X-ray photoelectron spectroscopy (XPS) is the preferred tool for exploring core-ionization energies. In the present work, synchrotron radiation was used to acquire photoelectron spectra of several carbon-containing molecules in the gas phase. Carbon 1s ionization energies are of special interest because of the vital role of organic molecules in life processes. A prerequisite for obtaining accurate ionization energies is access to reliable methods for calibration of the energies. This work has been concerned with establishing procedures for very accurate calibration of C1s ionization energies

  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. Policy offers protection from harassment

    Science.gov (United States)

    McNutt, Marcia

    We face a number of legal and ethical issues in our work as scientists and as AGU members. To uphold the highest ethical standards in our professional activities, the Council has adopted policies on free access to published material, ethics in publishing, and misconduct in science. But what about guidelines to govern the personal behavior that constitutes harassment, sexual or otherwise?For years the AGU headquarters staff has had a policy that offers protection from harassment and rules for dealing with it, but the membership went without one until 1994. That year the Council adopted a policy that extends to the membership as well as to the staff and the vendors they encounter at meetings. The law only requires a policy to prevent harassment in the workplace, but the Council felt that a harassment policy was particularly important for members because the subtle behavior that can constitute harassment is most likely to occur at events that combine work and social interaction, such as the meetings, conferences, and training seminars that AGU members attend.

  8. Operational Limitations of Arctic Waste Stabilization Ponds: Insights from Modeling Oxygen Dynamics and Carbon Removal

    DEFF Research Database (Denmark)

    Ragush, Colin M.; Gentleman, Wendy C.; Hansen, Lisbeth Truelstrup

    2018-01-01

    Presented here is a mechanistic model of the biological dynamics of the photic zone of a single-cell arctic waste stabilization pond (WSP) for the prediction of oxygen concentration and the removal of oxygen-demanding substances. The model is an exploratory model to assess the limiting environmen...

  9. Empirical validation of landscape resistance models: insights from the Greater Sage-Grouse (Centrocercus urophasianus)

    Science.gov (United States)

    Andrew J. Shirk; Michael A. Schroeder; Leslie A. Robb; Samuel A. Cushman

    2015-01-01

    The ability of landscapes to impede species’ movement or gene flow may be quantified by resistance models. Few studies have assessed the performance of resistance models parameterized by expert opinion. In addition, resistance models differ in terms of spatial and thematic resolution as well as their focus on the ecology of a particular species or more generally on the...

  10. Organization of left–right coordination of neuronal activity in the mammalian spinal cord: Insights from computational modelling

    Science.gov (United States)

    Shevtsova, Natalia A; Talpalar, Adolfo E; Markin, Sergey N; Harris-Warrick, Ronald M; Kiehn, Ole; Rybak, Ilya A

    2015-01-01

    Different locomotor gaits in mammals, such as walking or galloping, are produced by coordinated activity in neuronal circuits in the spinal cord. Coordination of neuronal activity between left and right sides of the cord is provided by commissural interneurons (CINs), whose axons cross the midline. In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified inhibitory (V0D) and excitatory (V0V) subtypes of V0 CINs and excitatory V3 CINs. The model also includes the ipsilaterally projecting excitatory V2a interneurons mediating excitatory drive to the V0V CINs. The proposed network architectures and CIN connectivity allow the models to closely reproduce and suggest mechanistic explanations for several experimental observations. These phenomena include: different speed-dependent contributions of V0D and V0V CINs and V2a interneurons to left–right alternation of neural activity, switching gaits between the left–right alternating walking-like activity and the left–right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN pathways and suggest explanations for how these pathways maintain alternating and synchronous gaits at different locomotor speeds. The models propose testable predictions about the neural organization and operation of mammalian locomotor circuits. Key points Coordination of neuronal activity between left and right sides of the mammalian spinal cord is provided by several sets of commissural interneurons (CINs) whose axons cross the midline. Genetically identified inhibitory V

  11. Model representations of kerogen structures: An insight from density functional theory calculations and spectroscopic measurements.

    Science.gov (United States)

    Weck, Philippe F; Kim, Eunja; Wang, Yifeng; Kruichak, Jessica N; Mills, Melissa M; Matteo, Edward N; Pellenq, Roland J-M

    2017-08-01

    Molecular structures of kerogen control hydrocarbon production in unconventional reservoirs. Significant progress has been made in developing model representations of various kerogen structures. These models have been widely used for the prediction of gas adsorption and migration in shale matrix. However, using density functional perturbation theory (DFPT) calculations and vibrational spectroscopic measurements, we here show that a large gap may still remain between the existing model representations and actual kerogen structures, therefore calling for new model development. Using DFPT, we calculated Fourier transform infrared (FTIR) spectra for six most widely used kerogen structure models. The computed spectra were then systematically compared to the FTIR absorption spectra collected for kerogen samples isolated from Mancos, Woodford and Marcellus formations representing a wide range of kerogen origin and maturation conditions. Limited agreement between the model predictions and the measurements highlights that the existing kerogen models may still miss some key features in structural representation. A combination of DFPT calculations with spectroscopic measurements may provide a useful diagnostic tool for assessing the adequacy of a proposed structural model as well as for future model development. This approach may eventually help develop comprehensive infrared (IR)-fingerprints for tracing kerogen evolution.

  12. Insights on the impact of systematic model errors on data assimilation performance in changing catchments

    Science.gov (United States)

    Pathiraja, S.; Anghileri, D.; Burlando, P.; Sharma, A.; Marshall, L.; Moradkhani, H.

    2018-03-01

    The global prevalence of rapid and extensive land use change necessitates hydrologic modelling methodologies capable of handling non-stationarity. This is particularly true in the context of Hydrologic Forecasting using Data Assimilation. Data Assimilation has been shown to dramatically improve forecast skill in hydrologic and meteorological applications, although such improvements are conditional on using bias-free observations and model simulations. A hydrologic model calibrated to a particular set of land cover conditions has the potential to produce biased simulations when the catchment is disturbed. This paper sheds new light on the impacts of bias or systematic errors in hydrologic data assimilation, in the context of forecasting in catchments with changing land surface conditions and a model calibrated to pre-change conditions. We posit that in such cases, the impact of systematic model errors on assimilation or forecast quality is dependent on the inherent prediction uncertainty that persists even in pre-change conditions. Through experiments on a range of catchments, we develop a conceptual relationship between total prediction uncertainty and the impacts of land cover changes on the hydrologic regime to demonstrate how forecast quality is affected when using state estimation Data Assimilation with no modifications to account for land cover changes. This work shows that systematic model errors as a result of changing or changed catchment conditions do not always necessitate adjustments to the modelling or assimilation methodology, for instance through re-calibration of the hydrologic model, time varying model parameters or revised offline/online bias estimation.

  13. 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.

  14. World energy insight 2011

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-11-15

    The World Energy Insight 2011 is the official publication of the World Energy Council. It includes interviews, articles and case studies from a distinguished panel of World Energy Council Officers, CEOs, government ministers, academics and opinion formers from all areas of the energy sector and provides perspectives from around the globe. Government, industry and NGO's offer both policy and technology perspectives. The insights within this publication add to the work that WEC is doing to provide the forum for energy leaders, along with the on-going WEC studies and programmes on Energy Policies, 2050 Energy Scenarios, Energy Resources & Technologies, Energy for Urban Innovation, Rules Of Energy Trade and Global Energy Access.

  15. 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)…

  16. 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...

  17. 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

  18. Spatial competition for biogas production using insights from retail location models

    DEFF Research Database (Denmark)

    Bojesen, Mikkel; Birkin, M.; Clarke, G.

    2014-01-01

    production sector. Through a two-step approach by combining a location-allocation model with a production constrained spatial interaction model, this paper addresses the dual problem of determining optimal location and production capacity. What-if scenarios, in combination with the strategic economic...

  19. Single- versus dual-process models of lexical decision performance: insights from response time distributional analysis.

    Science.gov (United States)

    Yap, Melvin J; Balota, David A; Cortese, Michael J; Watson, Jason M

    2006-12-01

    This article evaluates 2 competing models that address the decision-making processes mediating word recognition and lexical decision performance: a hybrid 2-stage model of lexical decision performance and a random-walk model. In 2 experiments, nonword type and word frequency were manipulated across 2 contrasts (pseudohomophone-legal nonword and legal-illegal nonword). When nonwords became more wordlike (i.e., BRNTA vs. BRANT vs. BRANE), response latencies to nonwords were slowed and the word frequency effect increased. More important, distributional analyses revealed that the Nonword Type = Word Frequency interaction was modulated by different components of the response time distribution, depending on the specific nonword contrast. A single-process random-walk model was able to account for this particular set of findings more successfully than the hybrid 2-stage model. (c) 2006 APA, all rights reserved.

  20. 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

  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. 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.

    2017-08-01

    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'.

  3. 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.

  4. 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.

  5. Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies.

    Science.gov (United States)

    Lee, Jin Hee; Lee, Yoonji; Ryu, HyungChul; Kang, Dong Wook; Lee, Jeewoo; Lazar, Jozsef; Pearce, Larry V; Pavlyukovets, Vladimir A; Blumberg, Peter M; Choi, Sun

    2011-04-01

    The transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel composed of four monomers with six transmembrane helices (TM1-TM6). TRPV1 is found in the central and peripheral nervous system, and it is an important therapeutic target for pain relief. We describe here the construction of a tetrameric homology model of rat TRPV1 (rTRPV1). We experimentally evaluated by mutational analysis the contribution of residues of rTRPV1 contributing to ligand binding by the prototypical TRPV1 agonists, capsaicin and resiniferatoxin (RTX). We then performed docking analysis using our homology model. The docking results with capsaicin and RTX showed that our homology model was reliable, affording good agreement with our mutation data. Additionally, the binding mode of a simplified RTX (sRTX) ligand as predicted by the modeling agreed well with those of capsaicin and RTX, accounting for the high binding affinity of the sRTX ligand for TRPV1. Through the homology modeling, docking and mutational studies, we obtained important insights into the ligand-receptor interactions at the molecular level which should prove of value in the design of novel TRPV1 ligands.

  6. 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 (O 2sat ) 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 O 2sat 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 O 2sat 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).

  7. 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.

  8. 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

  9. An Analytical Model That Provides Insights into Various C2 Issues

    National Research Council Canada - National Science Library

    Taylor, James G; Neta, Beny; Shugart, Peter A

    2004-01-01

    .... A Lanchester-type model of force-on-force combat that reflects C2 architecture at the platform level is developed through a detailed analysis of the target-engagement cycle for a single typical firer...

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

    DEFF Research Database (Denmark)

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

    modelled using a log-logistic function than an exponential function. A more challenging difference is that in the partial report task, there is more target-distractor confusion for auditory than visual stimuli. This failure of object-formation (prior to attentional object-selection) is not yet effectively......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......, 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...

  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. Insights into Parkinson's disease models and neurotoxicity using non-invasive imaging

    International Nuclear Information System (INIS)

    Sanchez-Pernaute, Rosario; Brownell, Anna-Liisa; Jenkins, Bruce G.; Isacson, Ole

    2005-01-01

    Loss of dopamine in the nigrostriatal system causes a severe impairment in motor function in patients with Parkinson's disease and in experimental neurotoxic models of the disease. We have used non-invasive imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (MRI) to investigate in vivo the changes in the dopamine system in neurotoxic models of Parkinson's disease. In addition to classic neurotransmitter studies, in these models, it is also possible to characterize associated and perhaps pathogenic factors, such as the contribution of microglia activation and inflammatory responses to neuronal damage. Functional imaging techniques are instrumental to our understanding and modeling of disease mechanisms, which should in turn lead to development of new therapies for Parkinson's disease and other neurodegenerative disorders

  13. Desert locust populations, rainfall and climate change: insights from phenomenological models using gridded monthly data

    OpenAIRE

    Tratalos, Jamie A.; Cheke, Robert A.; Healey, Richard G.; Stenseth, Nils Chr.

    2010-01-01

    Using autocorrelation analysis and autoregressive integrated moving average (ARIMA)modelling, we analysed a time series of the monthly number of 1° grid squares infested with desert locust Schistocerca gregaria swarms throughout the geographical range of the species from 1930–1987. Statistically significant first- and higher-order autocorrelations were found in the series. Although endogenous components captured much of the variance, adding rainfall data improved endogenous ARIMA models and r...

  14. Insight into collision zone dynamics from topography: numerical modelling results and observations

    OpenAIRE

    A. D. Bottrill; J. van Hunen; M. B. Allen

    2012-01-01

    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) 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...

  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. 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...

  17. Animal Models of Post-Traumatic Stress Disorder and Recent Neurobiological Insights

    Science.gov (United States)

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

    2014-01-01

    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 develop 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- 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 co-morbid conditions such as alcohol use disorder (AUD). Future studies will continue to refine preclinical PTSD models in hopes of capitalizing on their potential to deliver new and more efficacious treatments for PTSD and associated psychiatric disorders. PMID:25083568

  18. Recovery as a model of care? Insights from an Australian case study.

    Science.gov (United States)

    Hungerford, Catherine

    2014-03-01

    The terms "model of health care," "service model." and "nursing model of practice" are often used interchangeably in practice, policy, and research, despite differences in definitions. This article considers these terms in the context of consumer-centred recovery and its implementation into a publicly-funded health service organization in Australia. Findings of a case study analysis are used to inform the discussion, which considers the diverse models of health care employed by health professionals; together with the implications for organizations worldwide that are responsible for operationalizing recovery approaches to health care. As part of the discussion, it is suggested that the advent of recovery-oriented services, rather than recovery models of health care, presents challenges for the evaluation of the outcomes of these services. At the same time, this situation provides opportunities for mental health nurses to lead the way, by developing rigorous models of practice that support consumers who have acute, chronic, or severe mental illness on their recovery journey; and generate positive, measureable outcomes.

  19. Long-range transport and global fractionation of POPs: insights from multimedia modeling studies

    International Nuclear Information System (INIS)

    Scheringer, M.; Salzmann, M.; Stroebe, M.; Wegmann, F.; Fenner, K.; Hungerbuehler, K.

    2004-01-01

    The long-range transport of persistent organic pollutants (POPs) is investigated with two multimedia box models of the global system. ChemRange is a purely evaluative, one-dimensional steady-state (level III) model; CliMoChem is a two-dimensional model with different temperatures, land/water ratios and vegetation types in different latitudinal zones. Model results are presented for three case studies: (i) the effect of atmospheric aerosol particles on the long-range transport of POPs, (ii) the effect of oceanic deposition on the long-range transport of different PCB congeners, (iii) the global fractionation of different PCB congeners. The model results for these case studies show: (i) the low atmospheric half-lives estimated for several organochlorine pesticides are likely to be inconsistent with the observed long-range transport of these compounds; (ii) export to the deep sea reduces the potential for long-range transport of highly hydrophobic compounds (but does not remove these chemicals from the biosphere); (iii) there are different meanings of the term global fractionation that refer to different aspects of the fractionation process and need to be distinguished. The case-study results further indicate that the influences of varying environmental conditions on the physicochemical properties and the degradation rate constants of POPs need to be determined. - Multimedia box models are applied to case studies of the behavior of POPs

  20. 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.

  1. TLRs to cytokines: mechanistic insights from the imiquimod mouse model of psoriasis.

    Science.gov (United States)

    Flutter, Barry; Nestle, Frank O

    2013-12-01

    Psoriasis is an inflammatory disease of the skin affecting 2-3% of the population, characterized by a thickening of the epidermis and immune infiltrates throughout the dermis and epidermis, causing skin lesions that can seriously affect quality of life. The study of psoriasis has historically been hampered by the lack of good animal models. Various genetically induced models exist, which have provided some information about possible mechanisms of disease, but these models rely mostly on intrinsic imbalances of homeostasis. However, a mouse model of psoriasiform dermatitis caused by the repeated topical application of Aldara™ containing 5% imiquimod was described in 2009. The mechanisms of action of Aldara™ are complex. Imiquimod is an effective ligand for TLR7 (and TLR8 in humans) and also interferes with adenosine receptor signaling. In addition, isostearic acid present in the Aldara™ vehicle has been shown to be biologically active and of importance for activating the inflammasome. Interestingly, the repetitive application of Aldara™ reveals a complex aetiology involving multiple cell types, cytokines, and inflammatory pathways. In this review, we will dissect the findings of the imiquimod model to date and ask how this model can inform us about the immunological aspects of human disease. © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

    Science.gov (United States)

    Wilczynski, Bartek; Furlong, Eileen E M

    2010-04-15

    Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  3. New insights into soil temperature time series modeling: linear or nonlinear?

    Science.gov (United States)

    Bonakdari, Hossein; Moeeni, Hamid; Ebtehaj, Isa; Zeynoddin, Mohammad; Mahoammadian, Abdolmajid; Gharabaghi, Bahram

    2018-03-01

    Soil temperature (ST) is an important dynamic parameter, whose prediction is a major research topic in various fields including agriculture because ST has a critical role in hydrological processes at the soil surface. In this study, a new linear methodology is proposed based on stochastic methods for modeling daily soil temperature (DST). With this approach, the ST series components are determined to carry out modeling and spectral analysis. The results of this process are compared with two linear methods based on seasonal standardization and seasonal differencing in terms of four DST series. The series used in this study were measured at two stations, Champaign and Springfield, at depths of 10 and 20 cm. The results indicate that in all ST series reviewed, the periodic term is the most robust among all components. According to a comparison of the three methods applied to analyze the various series components, it appears that spectral analysis combined with stochastic methods outperformed the seasonal standardization and seasonal differencing methods. In addition to comparing the proposed methodology with linear methods, the ST modeling results were compared with the two nonlinear methods in two forms: considering hydrological variables (HV) as input variables and DST modeling as a time series. In a previous study at the mentioned sites, Kim and Singh Theor Appl Climatol 118:465-479, (2014) applied the popular Multilayer Perceptron (MLP) neural network and Adaptive Neuro-Fuzzy Inference System (ANFIS) nonlinear methods and considered HV as input variables. The comparison results signify that the relative error projected in estimating DST by the proposed methodology was about 6%, while this value with MLP and ANFIS was over 15%. Moreover, MLP and ANFIS models were employed for DST time series modeling. Due to these models' relatively inferior performance to the proposed methodology, two hybrid models were implemented: the weights and membership function of MLP and

  4. A kidney offer acceptance decision tool to inform the decision to accept an offer or wait for a better kidney.

    Science.gov (United States)

    Wey, Andrew; Salkowski, Nicholas; Kremers, Walter K; Schaffhausen, Cory R; Kasiske, Bertram L; Israni, Ajay K; Snyder, Jon J

    2018-04-01

    We developed a kidney offer acceptance decision tool to predict the probability of graft survival and patient survival for first-time kidney-alone candidates after an offer is accepted or declined, and we characterized the effect of restricting the donor pool with a maximum acceptable kidney donor profile index (KDPI). For accepted offers, Cox proportional hazards models estimated these probabilities using transplanted kidneys. For declined offers, these probabilities were estimated by considering the experience of similar candidates who declined offers and the probability that declining would lead to these outcomes. We randomly selected 5000 declined offers and estimated these probabilities 3 years post-offer had the offers been accepted or declined. Predicted outcomes for declined offers were well calibrated (offers been accepted, the probabilities of graft survival and patient survival were typically higher. However, these advantages attenuated or disappeared with higher KDPI, candidate priority, and local donor supply. Donor pool restrictions were associated with worse 3-year outcomes, especially for candidates with high allocation priority. The kidney offer acceptance decision tool could inform offer acceptance by characterizing the potential risk-benefit trade-off associated with accepting or declining an offer. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. 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.

  6. Uranium sorption to natural substrates-insights provided by isotope exchange, selective extraction and surface complexation modelling approaches

    International Nuclear Information System (INIS)

    Waite, T.D.; Payne T.E.; Davis, J.A.

    1993-01-01

    An extensive experimental program has been conducted over the last three years into the interaction of U(VI) with both single oxides and clays and complex natural substrates from the weathered zone in the vicinity of a uranium ore body in northern Australia. While iron oxides have frequently been considered to account for much of the uptake on such natural substrates, the results of laboratory open-quotes pH edgeclose quotes studies and of isotope exchange and selective extraction studies suggest that other phases must also play a significant role in controlling the partitioning of U(VI) between solid and solution phases. Supporting studies on kaolinite, the dominant clay in this system, provide insight into the most appropriate method of modelling the interaction of U(VI) with these natural substrates. The problems still remaining in adequately describing sorption of radionuclides and trace elements to complex natural substrates are discussed

  7. Rat models of 17β-estradiol-induced mammary cancer reveal novel insights into breast cancer etiology and prevention.

    Science.gov (United States)

    Shull, James D; Dennison, Kirsten L; Chack, Aaron C; Trentham-Dietz, Amy

    2018-03-01

    Numerous laboratory and epidemiologic studies strongly implicate endogenous and exogenous estrogens in the etiology of breast cancer. Data summarized herein suggest that the ACI rat model of 17β-estradiol (E2)-induced mammary cancer is unique among rodent models in the extent to which it faithfully reflects the etiology and biology of luminal types of breast cancer, which together constitute ~70% of all breast cancers. E2 drives cancer development in this model through mechanisms that are largely dependent upon estrogen receptors and require progesterone and its receptors. Moreover, mammary cancer development appears to be associated with generation of oxidative stress and can be modified by multiple dietary factors, several of which may attenuate the actions of reactive oxygen species. Studies of susceptible ACI rats and resistant COP or BN rats provide novel insights into the genetic bases of susceptibility and the biological processes regulated by genetic determinants of susceptibility. This review summarizes research progress resulting from use of these physiologically relevant rat models to advance understanding of breast cancer etiology and prevention.

  8. Effects of calcium (Ca(2+)) extrusion mechanisms on electrophysiological properties in a hypoglossal motoneuron: insight from a mathematical model.

    Science.gov (United States)

    Horn, Kyle G; Solomon, Irene C

    2014-01-01

    Spike-frequency dynamics and spike shape can provide insight into the types of ion channels present in any given neuron and give a sense for the precise response any neuron may have to a given input stimulus. Motoneuron firing frequency over time is especially important due to its direct effect on motor output. Of particular interest is intracellular Ca(2+), which exerts a powerful influence on both firing properties over time and spike shape. In order to better understand the cellular mechanisms for the regulation of intracellular Ca(2+) and their effect on spiking behavior, we have modified a computational model of an HM to include a variety of Ca(2+) handling processes. For the current study, a series of HM models that include Ca(2+) pumps, Na(+)/Ca(2+) exchangers, and a generic exponential decay of excess Ca(2+) were generated. Simulations from these models indicate that although each extrusion mechanism exerts a similar effect on voltage, the firing properties change distinctly with the inclusion of additional Ca(2+)-related mechanisms: BK channels, Ca(2+) buffering, and diffusion of [Ca(2+)]i modeled via a linear diffusion partial differential equation. While an exponential decay of Ca(2+) seems to adequately capture short-term changes in firing frequency seen in biological data, internal diffusion of Ca(2+) appears to be necessary for capturing longer term frequency changes. © 2014 Elsevier B.V. All rights reserved.

  9. Kinematic evolution of fold and thrust belts. Insights from experimental modeling

    International Nuclear Information System (INIS)

    Ueta, Keiichi

    2011-01-01

    Physical experiments were performed to gain a better understanding on the kinematic evolution of fold and thrust belts. The present study focuses on deformation of sedimentary cover caused by thrust and reverse movements along the basement fault. Our physical models comprise dry quartz sand representing brittle sedimentary rock and viscous silicone polymer representing overpressured mudstone. Computerized X-ray tomography was applied to the experiments to analyze the kinematic evolution of fold and thrust belts. In the sand models, the width of deformation zone above thrust was wider than that above reverse fault, because back thrust developed on the hanging wall of reverse fault. Within the physical models composed of dry sand and silicone polymer, minor folds and thrusts with minor displacement developed on the footwall of the major monoclinal flexure. These results compare well with the geometry and kinematic evolution of the fold and thrust belts in Japan. (author)

  10. Morphology and stratal geometry of the Antarctic continental shelf: Insights from models

    Science.gov (United States)

    Cooper, Alan K.; Barker, Peter F.; Brancolini, Giuliano

    1997-01-01

    Reconstruction of past ice-sheet fluctuations from the stratigraphy of glaciated continental shelves requires understanding of the relationships among the stratal geometry, glacial and marine sedimentary processes, and ice dynamics. We investigate the formation of the morphology and the broad stratal geometry of topsets on the Antarctic continental shelf with numerical models. Our models assume that the stratal geometry and morphology are principally the results of time-integrated effects of glacial erosion and sedimentation related to the location of the seaward edge of the grounded ice. The location of the grounding line varies with time almost randomly across the shelf. With these simple assumptions, the models can successfully mimic salient features of the morphology and the stratal geometry. The models suggest that the current shelf has gradually evolved to its present geometry by many glacial advances and retreats of the grounding line to different locations across the shelf. The locations of the grounding line do not appear to be linearly correlated with either fluctuations in the 5 l s O record (which presumably represents changes in the global ice volume) or with the global sea-level curve, suggesting that either a more complex relationship exists or local effects dominate. The models suggest that erosion of preglacial sediments is confined to the inner shelf, and erosion decreases and deposition increases toward the shelf edge. Some of the deposited glacial sediments must be derived from continental erosion. The sediments probably undergo extensive transport and reworking obliterating much of the evidence for their original depositional environment. The flexural rigidity and the tectonic subsidence of the underlying lithosphere modify the bathymetry of the shelf, but probably have little effect on the stratal geometry. Our models provide several guidelines for the interpretation of unconformities, the nature of preserved topset deposits, and the

  11. Modelling the rebound effect with network theory: An insight into the European freight transport sector

    International Nuclear Information System (INIS)

    Ruzzenenti, Franco; Basosi, Riccardo

    2017-01-01

    This paper presents a two pronged approach to the study of the rebound effect, with the aim of assessing the magnitude of the effect in the European freight transport sector and proposing a new modelling framework based on network theory. The (direct) rebound effect is assessed with: 1) an econometric regression; 2) a model based on network theory and statistical mechanics. According to the econometric model the European road freight transport sector undergone a negative rebound between of −74% between 1998 and 2007 and −146% between 1998 and 2011. The network analysis delivers an estimation of network rebound ranging between −29.37% and −7.25. Overall, these results indicate that energy efficiency in Europe, between 1998 and 2011, succeed in reducing the energy consumptions amid an increasing demand for transports. Results on rebound estimation depend on the decision of using GDP as an exogenous variable, an assumption that leaves questions open about the causality chain between growth and transports. Furthermore, the network analysis highlights a structural change –a migration of production factors offshore, that might partially explain this negative effect. In this view, rebound effect analysis on a local or regional scale is becoming more and more uncertain in a globally interconnected economic context. - Highlights: • An evaluation of direct rebound effect in the freight transports with an econometric model is performed. • A new concept of rebound effect based on network theory is presented and implemented. • A comparative analysis of the two different approaches is developed. • Both models indicate that the there was a negative rebound effect in European freight transports. • Network theory proved to be a promising approach to energy systems and rebound effect modelling.

  12. First insight into the viral community of the cnidarian model metaorganism Aiptasia using RNA-Seq data

    KAUST Repository

    Brüwer, Jan D.

    2018-03-01

    Current research posits that all multicellular organisms live in symbioses with associated microorganisms and form so-called metaorganisms or holobionts. Cnidarian metaorganisms are of specific interest given that stony corals provide the foundation of the globally threatened coral reef ecosystems. To gain first insight into viruses associated with the coral model system Aiptasia (sensu Exaiptasia pallida), we analyzed an existing RNA-Seq dataset of aposymbiotic, partially populated, and fully symbiotic Aiptasia CC7 anemones with Symbiodinium. Our approach included the selective removal of anemone host and algal endosymbiont sequences and subsequent microbial sequence annotation. Of a total of 297 million raw sequence reads, 8.6 million (∼3%) remained after host and endosymbiont sequence removal. Of these, 3,293 sequences could be assigned as of viral origin. Taxonomic annotation of these sequences suggests that Aiptasia is associated with a diverse viral community, comprising 116 viral taxa covering 40 families. The viral assemblage was dominated by viruses from the families Herpesviridae (12.00%), Partitiviridae (9.93%), and Picornaviridae (9.87%). Despite an overall stable viral assemblage, we found that some viral taxa exhibited significant changes in their relative abundance when Aiptasia engaged in a symbiotic relationship with Symbiodinium. Elucidation of viral taxa consistently present across all conditions revealed a core virome of 15 viral taxa from 11 viral families, encompassing many viruses previously reported as members of coral viromes. Despite the non-random selection of viral genetic material due to the nature of the sequencing data analyzed, our study provides a first insight into the viral community associated with Aiptasia. Similarities of the Aiptasia viral community with those of corals corroborate the application of Aiptasia as a model system to study coral holobionts. Further, the change in abundance of certain viral taxa across different

  13. 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

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

    International Nuclear Information System (INIS)

    El Naqa, I.

    2015-01-01

    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. 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

    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...... lemmus and Microtus oeconomus), suitable climate was predicted from the Atlantic coast eastward across central Europe and into Russia. Main conclusions. Our results support the idea of more northerly refuge areas in Europe, indicating that boreal species would have found suitable living conditions over...

  16. 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.

  17. Crustal deformation mechanism in southeastern Tibetan Plateau: Insights from numerical modeling

    Science.gov (United States)

    Li, Y.; Liu, S.; Chen, L.

    2017-12-01

    The Indo-Asian collision developed the complicated crustal deformation around the southeastern Tibetan plateau. Numerous models have proposed to explain the crustal deformation, but the mechanism remains controversial, especially the increasing multi-geophysics data, which demonstrate the existence of lower velocity, lower resistivity and high conductivity, implying that lower crustal flow is responsible for the crustal deformation, arguing for the lower crust flow model. To address the relations between the crust flow and the surface deformation, we employ a three-dimensional viscoelastic finite model to investigate the possible influence on the surface deformation, and discuss the stress field distribution under the model. Our preliminary results suggest that lower crustal flow plays an important role in crustal deformation in southeastern Tibetan plateau. The best fitting is achieved when the flow velocity of the lower crust is approximately 10-11 mm/a faster than that of the upper crust. Crustal rheological properties affect regional crustal deformation, when the viscosity of the middle and lower crust in the South China block reaches 1022 and 1023 Pa.s, respectively; the predicted match observations well, especially for the magnitude within the South China block. The maximum principal stress field exhibits clear zoning, gradually shifting from an approximately east-west orientation in the northern Bayan Har block to southeast in the South China block, southwest in the western Yunnan block, and a radially divergent distribution in the Middle Yunnan and Southern Yunnan blocks.

  18. Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection.

    Science.gov (United States)

    Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

    2017-01-01

    Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung.

  19. Sustainable energy development in Austria until 2020: Insights from applying the integrated model 'e3.at'

    International Nuclear Information System (INIS)

    Stocker, Andrea; Grossmann, Anett; Madlener, Reinhard; Wolter, Marc Ingo

    2011-01-01

    This paper reports on the Austrian research project 'Renewable energy in Austria: Modeling possible development trends until 2020'. The project investigated possible economic and ecological effects of a substantially increased use of renewable energy sources in Austria. Together with stakeholders and experts, three different scenarios were defined, specifying possible development trends for renewable energy in Austria. The scenarios were simulated for the period 2006-2020, using the integrated environment-energy-economy model 'e3.at'. The modeling results indicate that increasing the share of renewable energy sources in total energy use is an important but insufficient step towards achieving a sustainable energy system in Austria. A substantial increase in energy efficiency and a reduction of residential energy consumption also form important cornerstones of a sustainable energy policy. - Highlights: → Together with stakeholders three renewable energy scenarios for Austria were defined. → The scenarios were simulated using an integrated environment-energy-economy model. → Increasing the share of renewables in total energy use is important but insufficient. → Efficiency and a cut of energy use are also essential for a sustainable energy system.

  20. Strain localization at the margins of strong lithospheric domains: insights from analogue models

    NARCIS (Netherlands)

    Calignano, Elisa; Sokoutis, Dimitrios; Willingshofer, Ernst; Gueydan, Frederic; Cloetingh, Sierd

    The lateral variation of the mechanical properties of continental lithosphere is an important factor controlling the localization of deformation and thus the deformation history and geometry of intra-plate mountain belts. A series of three-layer lithospheric-scale analog models, with a strong domain

  1. Insights into mortality patterns and causes of death through a process point of view model.

    Science.gov (United States)

    Anderson, James J; Li, Ting; Sharrow, David J

    2017-02-01

    Process point of view (POV) models of mortality, such as the Strehler-Mildvan and stochastic vitality models, represent death in terms of the loss of survival capacity through challenges and dissipation. Drawing on hallmarks of aging, we link these concepts to candidate biological mechanisms through a framework that defines death as challenges to vitality where distal factors defined the age-evolution of vitality and proximal factors define the probability distribution of challenges. To illustrate the process POV, we hypothesize that the immune system is a mortality nexus, characterized by two vitality streams: increasing vitality representing immune system development and immunosenescence representing vitality dissipation. Proximal challenges define three mortality partitions: juvenile and adult extrinsic mortalities and intrinsic adult mortality. Model parameters, generated from Swedish mortality data (1751-2010), exhibit biologically meaningful correspondences to economic, health and cause-of-death patterns. The model characterizes the twentieth century epidemiological transition mainly as a reduction in extrinsic mortality resulting from a shift from high magnitude disease challenges on individuals at all vitality levels to low magnitude stress challenges on low vitality individuals. Of secondary importance, intrinsic mortality was described by a gradual reduction in the rate of loss of vitality presumably resulting from reduction in the rate of immunosenescence. Extensions and limitations of a distal/proximal framework for characterizing more explicit causes of death, e.g. the young adult mortality hump or cancer in old age are discussed.

  2. Role of Stat in Skin Carcinogenesis: Insights Gained from Relevant Mouse Models

    International Nuclear Information System (INIS)

    Macias, E.; Rao, D.; DiGiovanni, J.; DiGiovanni, J.; DiGiovanni, J.

    2013-01-01

    Signal transducer and activator of transcription 3 (Stat) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat-deficient mice have revealed that Stat plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat-deficient mouse models has demonstrated that Stat is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat in skin tumor progression. Studies using similar Stat-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat is an attractive target for skin cancer prevention and treatment.

  3. 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.…

  4. Conformity, Anticonformity and Polarization of Opinions: Insights from a Mathematical Model of Opinion Dynamics

    Directory of Open Access Journals (Sweden)

    Tyll Krueger

    2017-07-01

    Full Text Available 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 or to control polarized debates and predict their outcomes. In this paper, we present a version of the q-voter model of opinion dynamics with two types of responses to social influence: conformity (like in the original q-voter model and anticonformity. We put the model on a social network with the double-clique topology in order to check how the interplay between those responses impacts the opinion dynamics in a population divided into two antagonistic segments. The model is analyzed analytically, numerically and by means of Monte Carlo simulations. Our results show that the system undergoes two bifurcations as the number of cross-links between cliques changes. Below the first critical point, consensus in the entire system is possible. Thus, two antagonistic cliques may share the same opinion only if they are loosely connected. Above that point, the system ends up in a polarized state.

  5. 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

  6. Deeper Insight into the Diels-Alder Reaction through the Activation Strain Model

    NARCIS (Netherlands)

    Fernandez, Israel; Bickelhaupt, F. Matthias

    2016-01-01

    In this Focus Review, we present the application of the so-called Activation Strain Model of chemical reactivity to the Diels–Alder cycloaddition reaction. To this end, representative recent examples have been selected to illustrate the power of this new computational approach to gain a deeper

  7. Deeper Insight into the Diels-Alder Reaction through the Activation Strain Model

    NARCIS (Netherlands)

    Fernandez, I.; Bickelhaupt, F.M.

    2016-01-01

    The Diels–Alder (DA) cycloaddition reaction has the ability to significantly increase molecular complexity regioselectively and stereospecifically in a single synthetic step. In this review it is discussed how the activation strain model of chemical reactivity reveals the physical factors that

  8. Biogenic silica dissolution in diatom aggregates: insights from reactive transport modelling

    KAUST Repository

    Moriceau, B; Laruelle, GG; Passow, U; Van Cappellen, P; Ragueneau, O

    2014-01-01

    , 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

  9. Phase Behavior of Semiflexible-Flexible Diblock Copolymer Melt: Insight from Mesoscale Modeling.

    Czech Academy of Sciences Publication Activity Database

    Beránek, P.; Posel, Zbyšek

    2016-01-01

    Roč. 16, č. 8 (2016), s. 7832-7835 ISSN 1533-4880 R&D Projects: GA MŠk(CZ) LH12020 Institutional support: RVO:67985858 Keywords : conformational asymmetry * dissipative particle dynamics * mesoscale modeling Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.483, year: 2016

  10. Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity.

    Science.gov (United States)

    Ellegood, J; Anagnostou, E; Babineau, B A; Crawley, J N; Lin, L; Genestine, M; DiCicco-Bloom, E; Lai, J K Y; Foster, J A; Peñagarikano, O; Geschwind, D H; Pacey, L K; Hampson, D R; Laliberté, C L; Mills, A A; Tam, E; Osborne, L R; Kouser, M; Espinosa-Becerra, F; Xuan, Z; Powell, C M; Raznahan, A; Robins, D M; Nakai, N; Nakatani, J; Takumi, T; van Eede, M C; Kerr, T M; Muller, C; Blakely, R D; Veenstra-VanderWeele, J; Henkelman, R M; Lerch, J P

    2015-02-01

    Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.

  11. Stress, overeating, and obesity: Insights from human studies and preclinical models.

    Science.gov (United States)

    Razzoli, Maria; Pearson, Carolyn; Crow, Scott; Bartolomucci, Alessandro

    2017-05-01

    Eating disorders and obesity have become predominant in human society. Their association to modern lifestyle, encompassing calorie-rich diets, psychological stress, and comorbidity with major diseases are well documented. Unfortunately the biological basis remains elusive and the pharmacological treatment inadequate, in part due to the limited availability of valid animal models. Human research on binge eating disorder (BED) proves a strong link between stress exposure and bingeing: state-levels of stress and negative affect are linked to binge eating in individuals with BED both in laboratory settings and the natural environment. Similarly, classical animal models of BED reveal an association between acute exposure to stressors and binging but they are often associated with unchanged or decreased body weight, thus reflecting a negative energy balance, which is uncommon in humans where most commonly BED is associated with excessive or unstable body weight gain. Recent mouse models of subordination stress induce spontaneous binging and hyperphagia, altogether more closely mimicking the behavioral and metabolic features of human BED. Therefore the translational relevance of subordination stress models could facilitate the identification of the neurobiological basis of BED and obesity-associated disease and inform on the development of innovative therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Automated analyses of model-driven artifacts : obtaining insights into industrial application of MDE

    NARCIS (Netherlands)

    Mengerink, J.G.M.; Serebrenik, A.; Schiffelers, R.R.H.; van den Brand, M.G.J.

    2017-01-01

    Over the past years, there has been an increase in the application of model driven engineering in industry. Similar to traditional software engineering, understanding how technologies are actually used in practice is essential for developing good tooling, and decision making processes.

  13. New fundamental insights into capacitance modeling of laterally nonuniform MOS devices

    NARCIS (Netherlands)

    Aarts, A.C.T.; Hout, van der R.; Paasschens, J.C.J.; Scholten, A.J.; Willemsen, M.B.; Klaassen, D.B.M.

    2006-01-01

    In compact transistor modeling for circuit simulation, the capacitances of conventional MOS devices are commonly determined as the derivatives of terminal charges, which in their turn are obtained from the so-called Ward-Dutton charge partitioning scheme. For devices with a laterally nonuniform

  14. Polycrystalline magma behaviour in dykes: Insights from high-resolution numerical models

    Science.gov (United States)

    Yamato, Philippe; Duretz, Thibault; Tartèse, Romain; May, Dave

    2013-04-01

    The presence of a crystalline load in magmas modifies their effective rheology and thus their flow behaviour. In dykes, for instance, the presence of crystals denser than the melt reduces the ascent velocity and modifies the shape of the velocity profile from a Newtonian Poiseuille flow to a Bingham type flow. Nevertheless, several unresolved issues still remain poorly understood and need to be quantified: (1) What are the mechanisms controlling crystals segregation during magma ascent in dykes? (2) How does crystals transportation within a melt depend on their concentration, geometry, size and density? (3) Do crystals evolve in isolation to each other or as a cluster? (4) What is the influence of considering inertia of the melt within the system? In this study, we present numerical models following the setup previously used in Yamato et al. (2012). Our model setup simulates an effective pressure gradient between the base and the top of a channel (representing a dyke), by pushing a rigid piston into a magmatic mush that comprised crystals and melt and perforated by a hole. The initial resolution of the models (401x1551 nodes) has been doubled in order to ensure that the smallest crystalline fractions are sufficiently well resolved. Results show that the melt phase can be squeezed out from a crystal-rich magma when subjected to a given pressure gradient range and that clustering of crystals might be an important parameter controlling their behaviour. This demonstrates that crystal-melt segregation in dykes during magma ascent constitutes a viable mechanism for magmatic differentiation of residual melts. These results also explain how isolated crystal clusters and melt pockets, with different chemistry, can be formed. In addition, we discuss the impact of taking into account inertia in our models. Reference: Yamato, P., Tartèse, R., Duretz, T., May, D.A., 2012. Numerical modelling of magma transport in dykes. Tectonophysics 526-529, 97-109.

  15. Insight into the hydraulics and resilience of Ponderosa pine seedlings using a mechanistic ecohydrologic model

    Science.gov (United States)

    Maneta, M. P.; Simeone, C.; Dobrowski, S.; Holden, Z.; Sapes, G.; Sala, A.; Begueria, S.

    2017-12-01

    In semiarid regions, drought-induced seedling mortality is considered to be caused by failure in the tree hydraulic column. Understanding the mechanisms that cause hydraulic failure and death in seedlings is important, among other things, to diagnose where some tree species may fail to regenerate, triggering demographic imbalances in the forest that could result in climate-driven shifts of tree species. Ponderosa pine is a common lower tree line species in the western US. Seedlings of ponderosa pine are often subject to low soil water potentials, which require lower water potentials in the xylem and leaves to maintain the negative pressure gradient that drives water upward. The resilience of the hydraulic column to hydraulic tension is species dependent, but from greenhouse experiments, we have identified general tension thresholds beyond which loss of xylem conductivity becomes critical, and mortality in Ponderosa pine seedlings start to occur. We describe this hydraulic behavior of plants using a mechanistic soil-vegetation-atmosphere transfer model. Before we use this models to understand water-stress induced seedling mortality at the landscape scale, we perform a modeling analysis of the dynamics of soil moisture, transpiration, leaf water potential and loss of plant water conductivity using detailed data from our green house experiments. The analysis is done using a spatially distributed model that simulates water fluxes, energy exchanges and water potentials in the soil-vegetation-atmosphere continuum. Plant hydraulic and physiological parameters of this model were calibrated using Monte Carlo methods against information on soil moisture, soil hydraulic potential, transpiration, leaf water potential and percent loss of conductivity in the xylem. This analysis permits us to construct a full portrait of the parameter space for Ponderosa pine seedling and generate posterior predictive distributions of tree response to understand the sensitivity of transpiration

  16. Competition or cooperation in transboundary fish stocks management: Insight from a dynamical model.

    Science.gov (United States)

    Nguyen, Trong Hieu; Brochier, Timothée; Auger, Pierre; Trinh, Viet Duoc; Brehmer, Patrice

    2018-06-14

    An idealized system of a shared fish stock associated with different exclusive economic zones (EEZ) is modelled. Parameters were estimated for the case of the small pelagic fisheries shared between Southern Morocco, Mauritania and the Senegambia. Two models of fishing effort distribution were explored. The first one considers independent national fisheries in each EEZ, with a cost per unit of fishing effort that depends on local fishery policy. The second one considers the case of a fully cooperative fishery performed by an international fleet freely moving across the borders. Both models are based on a set of six ordinary differential equations describing the time evolution of the fish biomass and the fishing effort. We take advantage of the two time scales to obtain a reduced model governing the total fish biomass of the system and fishing efforts in each zone. At the fast equilibrium, the fish distribution follows the ideal free distribution according to the carrying capacity in each area. Different equilibria can be reached according to management choices. When fishing fleets are independent and national fishery policies are not harmonized, in the general case, competition leads after a few decades to a scenario where only one fishery remains sustainable. In the case of sub-regional agreement acting on the adjustment of cost per unit of fishing effort in each EEZ, we found that a large number of equilibria exists. In this last case the initial distribution of fishing effort strongly impact the optimal equilibrium that can be reached. Lastly, the country with the highest carrying capacity density may get less landings when collaborating with other countries than if it minimises its fishing costs. The second fully cooperative model shows that a single international fishing fleet moving freely in the fishing areas leads to a sustainable equilibrium. Such findings should foster regional fisheries organizations to get potential new ways for neighbouring fish stock

  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 NO 2 yields and the corresponding energy efficiency for NO x formation for different N 2 /O 2 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 NO x . The results indicate that vibrational excitation of N 2 in the gliding arc contributes significantly to activating the N 2 molecules, and leads to an energy efficient way of NO x production, compared to the thermal process. Based on the underlying chemistry, the model allows us to propose solutions on how to further improve the NO x 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. 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.

  19. Sludge reduction by ozone: Insights and modeling of the dose-response effects.

    Science.gov (United States)

    Fall, C; Silva-Hernández, B C; Hooijmans, C M; Lopez-Vazquez, C M; Esparza-Soto, M; Lucero-Chávez, M; van Loosdrecht, M C M

    2018-01-15

    Applying ozone to the return flow in an activated sludge (AS) process is a way for reducing the residual solids production. To be able to extend the activated sludge models to the ozone-AS process, adequate prediction of the tri-atoms effects on the particulate COD fractions is needed. In this study, the biomass inactivation, COD mineralization, and solids dissolution were quantified in batch tests and dose-response models were developed as a function of the reacted ozone doses (ROD). Three kinds of model-sludge were used. S1 was a lab-cultivated synthetic sludge with two components (heterotrophs X H and X P ). S2 was a digestate of S1 almost made by the endogenous residues, X P . S3 was from a municipal activated sludge plant. The specific ozone uptake rate (SO 3 UR, mgO 3 /gCOD.h) was determined as a tool for characterizing the reactivity of the sludges. SO 3 UR increased with the X H fraction and decreased with more X P . Biomass inactivation was exponential (e -β.ROD ) as a function of the ROD doses. The percentage of solids reduction was predictable through a linear model (C Miner  + Y sol ROD), with a fixed part due to mineralization (C Miner ) and a variable part from the solubilization process. The parameters of the models, i.e. the inactivation and the dissolution yields (β, 0.008-0.029 (mgO 3 /mgCOD ini ) -1 vs Y sol , 0.5-2.8 mg COD sol /mgO 3 ) varied in magnitude, depending on the intensity of the scavenging reactions and potentially the compactness of the flocs for each sludge. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. 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.

  1. 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.

  2. Students' Visualisation of Chemical Reactions--Insights into the Particle Model and the Atomic Model

    Science.gov (United States)

    Cheng, Maurice M. W.

    2018-01-01

    This paper reports on an interview study of 18 Grade 10-12 students' model-based reasoning of a chemical reaction: the reaction of magnesium and oxygen at the submicro level. It has been proposed that chemical reactions can be conceptualised using two models: (i) the "particle model," in which a reaction is regarded as the simple…

  3. 48 CFR 25.503 - Group offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Group offers. 25.503... PROGRAMS FOREIGN ACQUISITION Evaluating Foreign Offers-Supply Contracts 25.503 Group offers. (a) If the solicitation or an offer specifies that award can be made only on a group of line items or on all line items...

  4. 48 CFR 570.306 - Evaluating offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Evaluating offers. 570.306... Real Property 570.306 Evaluating offers. (a) You must evaluate offers solely in accordance with the... solicitation. The file must include the basis for evaluation, an analysis of each offer, and a summary of...

  5. 48 CFR 225.503 - Group offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Group offers. 225.503... OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Evaluating Foreign Offers-Supply Contracts 225.503 Group offers. Evaluate group offers in accordance with FAR 25.503, but apply the evaluation...

  6. Unlocking the coral calcification process: Insights from boron isotope measurements and a skeletal growth model

    Science.gov (United States)

    Mollica, N. R.; Guo, W.; Cohen, A. L.; Huang, K. F.; Foster, G. L.; Donald, H.; Solow, A.

    2017-12-01

    Carbonate skeletons of scleractinian corals are important archives of ocean climate and environmental change. However, corals don't accrete their skeletons directly from ambient seawater, but from a calcifying fluid whose composition is strongly regulated. There is mounting evidence that the carbonate chemistry of this calcifying fluid significantly impacts the amount of carbonate the coral can precipitate, which in turn affects the geochemical composition of the skeleton produced. However the mechanistic link between calcifying fluid (cf) chemistry, particularly the up-regulation of pHcf and thereby aragonite saturation state (Ωcf), and coral calcification is not well understood. We explored this link by combining boron isotope measurements with in situ measurements of seawater temperature, salinity, and DIC to estimate Ωcf of nine Porites corals from four Pacific reefs. Associated calcification rates were quantified for each core via CT scanning. We do not observe a relationship between calcification rates and Ωcf or Ωsw. Instead, when we deconvolve calcification into linear extension and skeletal density, a significant correlation is observed between density and Ωcf, and also Ωsw while extension does not correlate with either. These observations are consistent with the two-step model of coral calcification, in which skeleton is secreted in two distinct phases: vertical extension creating new skeletal elements, followed by lateral thickening of existing elements that are covered by living tissue. We developed a numerical model of Porites skeletal growth that builds on this two-step model and links skeletal density with the external seawater environment via its influence on the chemistry of coral calcifying fluid. We validated the model using existing coral skeletal datasets from six Porites species collected across five reef sites, and quantified the effects of each seawater parameter (e.g. temperature, pH, DIC) on skeletal density. Our findings illustrate

  7. Reverse fault growth and fault interaction with frictional interfaces: insights from analogue models

    Science.gov (United States)

    Bonanno, Emanuele; Bonini, Lorenzo; Basili, Roberto; Toscani, Giovanni; Seno, Silvio

    2017-04-01

    The association of faulting and folding is a common feature in mountain chains, fold-and-thrust belts, and accretionary wedges. Kinematic models are developed and widely used to explain a range of relationships between faulting and folding. However, these models may result not to be completely appropriate to explain shortening in mechanically heterogeneous rock bodies. Weak layers, bedding surfaces, or pre-existing faults placed ahead of a propagating fault tip may influence the fault propagation rate itself and the associated fold shape. In this work, we employed clay analogue models to investigate how mechanical discontinuities affect the propagation rate and the associated fold shape during the growth of reverse master faults. The simulated master faults dip at 30° and 45°, recalling the range of the most frequent dip angles for active reverse faults that occurs in nature. The mechanical discontinuities are simulated by pre-cutting the clay pack. For both experimental setups (30° and 45° dipping faults) we analyzed three different configurations: 1) isotropic, i.e. without precuts; 2) with one precut in the middle of the clay pack; and 3) with two evenly-spaced precuts. To test the repeatability of the processes and to have a statistically valid dataset we replicate each configuration three times. The experiments were monitored by collecting successive snapshots with a high-resolution camera pointing at the side of the model. The pictures were then processed using the Digital Image Correlation method (D.I.C.), in order to extract the displacement and shear-rate fields. These two quantities effectively show both the on-fault and off-fault deformation, indicating the activity along the newly-formed faults and whether and at what stage the discontinuities (precuts) are reactivated. To study the fault propagation and fold shape variability we marked the position of the fault tips and the fold profiles for every successive step of deformation. Then we compared

  8. Multisensory-Based Rehabilitation Approach: Translational Insights from Animal Models to Early Intervention

    Directory of Open Access Journals (Sweden)

    Giulia Purpura

    2017-07-01

    Full Text Available Multisensory processes permit combinations of several inputs, coming from different sensory systems, allowing for a coherent representation of biological events and facilitating adaptation to environment. For these reasons, their application in neurological and neuropsychological rehabilitation has been enhanced in the last decades. Recent studies on animals and human models have indicated that, on one hand multisensory integration matures gradually during post-natal life and development is closely linked to environment and experience and, on the other hand, that modality-specific information seems to do not benefit by redundancy across multiple sense modalities and is more readily perceived in unimodal than in multimodal stimulation. In this review, multisensory process development is analyzed, highlighting clinical effects in animal and human models of its manipulation for rehabilitation of sensory disorders. In addition, new methods of early intervention based on multisensory-based rehabilitation approach and their applications on different infant populations at risk of neurodevelopmental disabilities are discussed.

  9. A novel insight into the cost-benefit model for the evolution of botanical carnivory.

    Science.gov (United States)

    Pavlovič, Andrej; Saganová, Michaela

    2015-06-01

    The cost-benefit model for the evolution of botanical carnivory provides a conceptual framework for interpreting a wide range of comparative and experimental studies on carnivorous plants. This model assumes that the modified leaves called traps represent a significant cost for the plant, and this cost is outweighed by the benefits from increased nutrient uptake from prey, in terms of enhancing the rate of photosynthesis per unit leaf mass or area (AN) in the microsites inhabited by carnivorous plants. This review summarizes results from the classical interpretation of the cost-benefit model for evolution of botanical carnivory and highlights the costs and benefits of active trapping mechanisms, including water pumping, electrical signalling and accumulation of jasmonates. Novel alternative sequestration strategies (utilization of leaf litter and faeces) in carnivorous plants are also discussed in the context of the cost-benefit model. Traps of carnivorous plants have lower AN than leaves, and the leaves have higher AN after feeding. Prey digestion, water pumping and electrical signalling represent a significant carbon cost (as an increased rate of respiration, RD) for carnivorous plants. On the other hand, jasmonate accumulation during the digestive period and reprogramming of gene expression from growth and photosynthesis to prey digestion optimizes enzyme production in comparison with constitutive secretion. This inducibility may have evolved as a cost-saving strategy beneficial for carnivorous plants. The similarities between plant defence mechanisms and botanical carnivory are highlighted. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. 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.

  11. Eddy dynamics over continental slopes under retrograde winds: Insights from a model inter-comparison

    Science.gov (United States)

    Wang, Yan; Stewart, Andrew L.

    2018-01-01

    Mesoscale eddies are ubiquitous in the ocean and play a key role in exchanges across continental slopes. In this study the properties of wind-driven baroclinic turbulence are investigated using eddy-resolving process simulations, focusing on the case of retrograde winds that arises around the margins of the subtropical gyres. In contrast to a flat-bottomed ocean, over steep slopes eddies develop from baroclinic instabilities are confined to the top few hundred meters. Deeper in the water column baroclinic instability and vertical momentum transfer are suppressed, so wind-input momentum is exported toward the open ocean by eddies before traversing down to the ocean bed. Close to the sloping topography, eddy energy sourced from the upper ocean is converted to potential energy, steepening isopycnals and driving bottom-trapped prograde flows. This process is associated with upgradient lateral buoyancy fluxes and downgradient isopycnal potential vorticity fluxes, and cannot be reproduced via linear stability calculations. These properties of wind-driven shelf/slope turbulence are contrasted against simulations with flat bathymetry. The key differences described above hinge on the flow close to the steep topographic slope, which may be sensitive to the model's vertical coordinate system. The simulations are therefore replicated using models that employ geopotential coordinates, terrain-following coordinates, and isopycnal coordinates. Quantitative inter-model discrepancies in the momentum and energy budgets are much more pronounced in the presence of a steep bottom slope. However, the key findings of this study are consistent across the models, suggesting that they are robust and warrant incorporation into parameterizations of eddy transfer across continental slopes.

  12. Insight into vibrational circular dichroism of proteins by density functional modeling

    Czech Academy of Sciences Publication Activity Database

    Kessler, Jiří; Andrushchenko, Valery; Kapitán, J.; Bouř, Petr

    2018-01-01

    Roč. 20, č. 7 (2018), s. 4926-4935 ISSN 1463-9076 R&D Projects: GA MŠk(CZ) LTC17012; GA ČR(CZ) GA16-05935S; GA ČR(CZ) GA16-04902S Institutional support: RVO:61388963 Keywords : Raman optical activity * molecular property tensors * coupled oscillator model Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 4.123, year: 2016

  13. Mechanisms Of Saucer-Shaped Sill Emplacement: Insight From Experimental Modeling

    Science.gov (United States)

    Galland, O.; Planke, S.; Malthe-Sørenssen, A.; Polteau, S.; Svensen, H.; Podladchikov, Y. Y.

    2006-12-01

    It has been recently demonstrated that magma intrusions in sedimentary basins had a strong impact on petroleum systems. Most of these intrusions are sills, and especially saucer-shaped sills. These features can be observed in many sedimentary basins (i.e. the Karoo basin, South Africa; the Norwegian and North Sea; the Tunguska basin, Siberia; the Neuquén basin in Argentina). The occurrence of such features in so various settings suggests that their emplacement results from fundamental processes. However, the mechanisms that govern their formation remain poorly constrained. Experiments were conducted to simulate the emplacement of saucer-shaped magma intrusions in sedimentary basins. The model rock and magma were fine-grained silica flour and molten vegetable oil, respectively. This modeling technique allows simultaneous simulation of magma emplacement and brittle deformation at a basin scale. For our purpose, we performed our experiments without external deformation. During the experiments, the oil was injected horizontally at constant flow rate within the silica flour. Then the oil initially emplaced in a sill, whereas the surface of the model inflated into a smooth dome. Subsequently, the oil propagated upwards along inclined sheets, finally reaching the surface at the edge of the dome. The resulting geometries of the intrusions were saucer-shaped sills. Then the oil solidified, and the model was cut in serial cross-sections through which the structures of the intrusive body and of the overburden can be observed. In order to constraint the processes governing the emplacement of such features, we performed a parametric study based on a set of experiments in which we systematically varied parameters such as the depth of emplacement and the injection flow rate of the oil. Our results showed that saucer diameters are larger at deeper level of emplacement. Opposite trend was obtained with varying injection flow rates. Based on our results, we conducted a detailed

  14. Dome Structures Above Sills and Saucer-Shaped Sills: Insights From Experimental Modeling

    Science.gov (United States)

    Planke, S.; Galland, O.; Malthe-Sørenssen, A.

    2007-12-01

    Saucer-shaped magma and sand intrusions are common features in sedimentary basins. They result from fundamental processes for the emplacement of fluids in shallow sedimentary basins. Seismic data show that the overburden above saucer-shaped intrusions is usually deformed and exhibits a dome-like structure. The formation of such structures, and the associated deformation, are of primary importance in the evolution of petroleum systems. In this presentation, we report on experimental investigation of the deformation processes associated with the intrusion of saucer-shaped intrusions into sedimentary basins. The experimental setup consists of molten low-viscosity oil injected into fine-grained silica flour (see Galland et al., this session). It properly simulates the emplacement of saucer-shaped intrusions and the deformation of the country rock. During experiments, the surface of the model is digitalized through a structured light technique based on moiré projection principle. Such a tool provides topographic maps of the model and allows a periodic (every 1.5 s) monitoring of the model surface. When the model magma starts intruding, a symetrical dome rises above the inlet. As injection proceeds, the dome inflates and widens. Subsequently, the dome evolves to a plateau-like feature, with nearly flat surface and steep edges. The plateau keeps lifting up, but nearly stoppes widening. At the end of the experiments, the intruding liquid erupts at the edge of the plateau. The intrusion formed in the experiment is a typical saucer-shaped sill. The evolution of the deforming surface reflects the evolution of the intrusion. We infer that the first doming phase corresponds to the emplacement of a horizontal basal sill by open fracturing. The dome-to-plateau transition corresponds to a transition of the liquid emplacement mechanism from basal sill to inclined sheet. We suggest that the emplacement of the inclined sheets results from shear fracturing at the dome edge.

  15. Hydrodynamics of isohydric and anisohydric trees: insights from models and measurements

    Science.gov (United States)

    Novick, K. A.; Oishi, A. C.; Roman, D. T.; Benson, M. C.; Miniat, C.

    2016-12-01

    In an effort to understand and predict the mechanisms that govern tree response to hydrologic stress, plant hydraulic theory, which classifies trees along a continuum of isohydric to anisohydric water use strategies, is increasingly being used. Isohydry maintains relatively constant leaf water potential during periods of water stress, promoting wide hydraulic safety margins that reduce the risk of xylem cavitation. In contrast, anisohydry allows leaf water potential to fall as soil water potential falls, but in doing so trees incur a greater risk of hydraulic failure. As a result, unique patterns of stomatal functioning between isohydric and anisohydric species are both predicted and observed in leaf-, tree-, and stand-level water use. We use a novel model formulation to examine the dynamics of three mechanisms that are potentially limiting to leaf-level gas exchange in trees during drought: (1) a `demand limitation' driven by an assumption of stomatal optimization of water loss and carbon uptake; (2) `hydraulic limitation' of water movement from the roots to the leaves; and (3) `non-stomatal' limitations imposed by declining leaf water status within the leaf. Model results suggest that species-specific `economics' of stomatal behavior may play an important role in differentiating species along the continuum of isohydric to anisohydric behavior; specifically, we show that non-stomatal and demand limitations may reduce stomatal conductance and increase leaf water potential, promoting wide safety margins characteristic of isohydric species. Direct comparisons of modeled and measured stomatal conductance further indicated that non-stomatal and demand limitations reproduced observed patterns of tree water use well for an isohydric species but that a hydraulic limitation likely applies in the case of an anisohydric species. This modeling framework used in concert with climate data may help land managers and scientists predict when and what forest species and communities

  16. Balancing reserves within a decarbonized European electricity system in 2050. From market developments to model insights

    International Nuclear Information System (INIS)

    Lorenz, Casimir

    2017-01-01

    This paper expands the discussion about future balancing reserve provision to the long-term perspective of 2050. Most pathways for a transformation towards a decarbonized electricity sector rely on very high shares of fluctuating renewables. This can be a challenge for the provision of balancing reserves, although their influence on the balancing cost is unclear. Apart from the transformation of the generation portfolio, various technical and regulatory developments within the balancing framework might further influence balancing costs: i) dynamic dimensioning of balancing reserves, ii) provision by fluctuating renewables or new (battery) storage technologies, and iii) exchange of balancing reserves between balancing zones. The first part of this paper discusses and transforms these developments into quantitative scenario definitions. The second part applies these scenarios to dynELMOD (dynamic Electricity Model), an investment model of the European electricity system that is extended to include balancing reserve provision. In contrast to other models applied in most papers on balancing reserves, this model is capable of evaluating the interdependencies between developments in balancing reserve provision and high shares of fluctuating renewables jointly. The results show that balancing reserve cost can be kept at current levels for a renewable electricity system until 2050, when using a dynamic reserve sizing horizon. Apart from the sizing horizon, storage capacity withholding duration and additional balancing demand from RES are the main driver of balancing costs. Renewables participation in balancing provision is mainly important for negative reserves, while storages play an important role for the provision of positive reserves. However, only on very few occasions, additional storage investments are required for balancing reserve provision, as most of the time sufficient storage capacities are available in the electricity system.

  17. Balancing reserves within a decarbonized European electricity system in 2050. From market developments to model insights

    Energy Technology Data Exchange (ETDEWEB)

    Lorenz, Casimir [German Institute for Economic Research (DIW Berlin), Berlin (Germany). Dept. of Energy, Transportation, Environment; Univ. of Technology, Berlin (Germany). Workgroup for Infrastructure Policy (WIP)

    2017-03-30

    This paper expands the discussion about future balancing reserve provision to the long-term perspective of 2050. Most pathways for a transformation towards a decarbonized electricity sector rely on very high shares of fluctuating renewables. This can be a challenge for the provision of balancing reserves, although their influence on the balancing cost is unclear. Apart from the transformation of the generation portfolio, various technical and regulatory developments within the balancing framework might further influence balancing costs: i) dynamic dimensioning of balancing reserves, ii) provision by fluctuating renewables or new (battery) storage technologies, and iii) exchange of balancing reserves between balancing zones. The first part of this paper discusses and transforms these developments into quantitative scenario definitions. The second part applies these scenarios to dynELMOD (dynamic Electricity Model), an investment model of the European electricity system that is extended to include balancing reserve provision. In contrast to other models applied in most papers on balancing reserves, this model is capable of evaluating the interdependencies between developments in balancing reserve provision and high shares of fluctuating renewables jointly. The results show that balancing reserve cost can be kept at current levels for a renewable electricity system until 2050, when using a dynamic reserve sizing horizon. Apart from the sizing horizon, storage capacity withholding duration and additional balancing demand from RES are the main driver of balancing costs. Renewables participation in balancing provision is mainly important for negative reserves, while storages play an important role for the provision of positive reserves. However, only on very few occasions, additional storage investments are required for balancing reserve provision, as most of the time sufficient storage capacities are available in the electricity system.

  18. Impact of the lithosphere on dynamic topography: Insights from analogue modeling

    OpenAIRE

    Sembroni, Andrea; Kiraly, Agnes; Faccenna, Claudio; Funiciello, Francesca; Becker, Thorsten W.; Goblig, Jan; Fernandez, Manel

    2017-01-01

    Density anomalies beneath the lithosphere are expected to generate dynamic topography at the Earth's surface due to the induced mantle flow stresses which scale linearly with density anomalies, while the viscosity of the upper mantle is expected to control uplift rates. However, limited attention has been given to the role of the lithosphere. Here we present results from analogue modeling of the interactions between a density anomaly rising in the mantle and the lithosphere in a Newtonian sys...

  19. Carnivore translocations and conservation: insights from population models and field data for fishers (Martes pennanti.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Lewis

    Full Text Available Translocations are frequently used to restore extirpated carnivore populations. Understanding the factors that influence translocation success is important because carnivore translocations can be time consuming, expensive, and controversial. Using population viability software, we modeled reintroductions of the fisher, a candidate for endangered or threatened status in the Pacific states of the US. Our model predicts that the most important factor influencing successful re-establishment of a fisher population is the number of adult females reintroduced (provided some males are also released. Data from 38 translocations of fishers in North America, including 30 reintroductions, 5 augmentations and 3 introductions, show that the number of females released was, indeed, a good predictor of success but that the number of males released, geographic region and proximity of the source population to the release site were also important predictors. The contradiction between model and data regarding males may relate to the assumption in the model that all males are equally good breeders. We hypothesize that many males may need to be released to insure a sufficient number of good breeders are included, probably large males. Seventy-seven percent of reintroductions with known outcomes (success or failure succeeded; all 5 augmentations succeeded; but none of the 3 introductions succeeded. Reintroductions were instrumental in reestablishing fisher populations within their historical range and expanding the range from its most-contracted state (43% of the historical range to its current state (68% of the historical range. To increase the likelihood of translocation success, we recommend that managers: 1 release as many fishers as possible, 2 release more females than males (55-60% females when possible, 3 release as many adults as possible, especially large males, 4 release fishers from a nearby source population, 5 conduct a formal feasibility assessment, and

  20. A model system to give an insight into the behaviour of gold nanoparticles under ion irradiation

    International Nuclear Information System (INIS)

    Ramjauny, Y.

    2010-01-01

    Nano-composites fabricated with ion-based techniques have a number of attractive characteristics. However, the main and most crucial difficulty in obtaining commercial NPs-based devices is the inability to produce a suitable narrow size and spatial NP distributions. The objective of this thesis is twofold: i) to go further in the description of the behavior of the ion-driven NPs and ii) to overcome the limitations related to the ion-beam techniques providing a guideline methodology to rationalize the synthesis of NPs when ion-beams are used. Thus, a model system is fabricated. It consists of chemically synthesized metallic nanoparticles sandwiched between two silica layers. We show how the ion irradiation and the temperature can be used to tune the size distribution of the embedded NPs. Moreover, we show that when an initially large NPs size distribution is considered, the study of the growth kinetic of the NPs under irradiation can be problematic. Our model system is than used to investigate in detail the behavior of the NPs under irradiation. We show that the evolution of the precipitate phase under irradiation is successfully described by an Ostwald ripening mechanism in an open system limited by the diffusion. Moreover, the concentration threshold for nucleation as well as the surface tension and the gold diffusivity in silica under irradiation is estimated. Finally, direct and inverse Ostwald ripening processes under irradiation are systematically investigated and the existing theoretical models experimentally checked. (author)

  1. Structural insights into a high affinity nanobody:antigen complex by homology modelling.

    Science.gov (United States)

    Skottrup, Peter Durand

    2017-09-01

    Porphyromonas gingivalis is a major periodontitis-causing pathogens. P. gingivalis secrete a cysteine protease termed RgpB, which is specific for Arg-Xaa bonds in substrates. Recently, a nanobody-based assay was used to demonstrate that RgpB could represent a novel diagnostic target, thereby simplifying. P. gingivalis detection. The nanobody, VHH7, had a high binding affinity and was specific for RgpB, when tested towards the highly identical RgpA. In this study a homology model of VHH7 was build. The complementarity determining regions (CDR) comprising the paratope residues responsible for RgpB 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. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Investigating the Effects of Underplating at Raukumara Peninsula, New Zealand: Insights from DEM Modeling

    Science.gov (United States)

    Farrell, W. C.; Morgan, J.

    2017-12-01

    It is thought that subcretion and underplating are important processes at subduction zones worldwide. Despite its proposed common occurrence, the physical mechanisms controlling if underplating occurs and the rate of its associated uplift are poorly understood. Basic questions about the tectonic and geomechanical parameters governing subduction channel stability, subcretion, and the rate and shape of associated uplift have proven difficult to answer. In this study we employ the Discrete Element Method (DEM) to address these questions, using the Raukumara Peninsula of New Zealand as the real-world basis of many of our model inputs. Multiple geophysical datasets suggest that the Raukumara Peninsula is underlain by underplated sediments at Moho depths, and these may be responsible for anomalously high rates of uplift in the area. The combined geologic, geophysical, and geodetic data from the region serve to constrain model geometries and boundary conditions, allowing us to test the mechanisms for underplating and upper crustal response. The effects of surface processes and potential for shallow trenchward sliding are also investigated in the modeling effort.

  3. New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling.

    Science.gov (United States)

    Erickson, Keesha E; Rukhlenko, Oleksii S; Posner, Richard G; Hlavacek, William S; Kholodenko, Boris N

    2018-03-05

    RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisition of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Insights using the molecular model of Lipoxygenase from Finger millet (Eleusine coracana (L.)).

    Science.gov (United States)

    Tiwari, Apoorv; Avashthi, Himanshu; Jha, Richa; Srivastava, Ambuj; Kumar Garg, Vijay; Wasudev Ramteke, Pramod; Kumar, Anil

    2016-01-01

    Lipoxygenase-1 (LOX-1) protein provides defense against pests and pathogens and its presence have been positively correlated with plant resistance against pathogens. Linoleate is a known substrate of lipoxygenase and it induces necrosis leading to the accumulation of isoflavonoid phytoalexins in plant leaves. Therefore, it is of interest to study the structural features of LOX-1 from Finger millet. However, the structure ofLOX-1 from Finger millet is not yet known. A homology model of LOX-1 from Finger millet is described. Domain architecture study suggested the presence of two domains namely PLAT (Phospho Lipid Acyl Transferase) and lipoxygenase. Molecular docking models of linoleate with lipoxygenase from finger millet, rice and sorghum are reported. The features of docked models showed that finger millet have higher pathogen resistance in comparison to other cereal crops. This data is useful for the molecular cloning of fulllength LOX-1 gene for validating its role in improving plant defense against pathogen infection and for various other biological processes.

  5. Towards a product independent ERP training model: An Insight from a literature review

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Motahar

    2018-03-01

    Full Text Available ERP can be called as one of the most significant contributions of computer science and particularly information systems for the business environment which can support all complicated business process of an organisation including sale, purchase, warehouse and manufacturing into a single database. For such complex system like ERP, implementation involves much collaboration which raises the concern of the success of the project. Among most significant success and failure factors of ERP implementation cited in the literature are training and consultation. For many years the majority of ERP vendors promote their product specific training models as long-term and expensive allowing the organisation to gain knowledge of the ERP system and the way it handles the business process. However, recent studies showed that ERP training can be conducted in the short term and with minimum investment and yet to be effective. Findings triggered a signal and opened a new door for research to investigate vendor-independent training models that require limited investment in training and consultancy. This paper aims to provide an overview of the literature; highlighting the research methods and theories used by authors towards building ERP training models and methods.

  6. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    Directory of Open Access Journals (Sweden)

    Michael D. Burkitt

    2017-02-01

    Full Text Available 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.

  7. 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

  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. Insights into persistence mechanisms of a zoonotic virus in bat colonies using a multispecies metapopulation model.

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    Margarita Pons-Salort

    Full Text Available Rabies is a worldwide zoonosis resulting from Lyssavirus infection. In Europe, Eptesicus serotinus is the most frequently reported bat species infected with Lyssavirus, and thus considered to be the reservoir of European bat Lyssavirus type 1 (EBLV-1. To date, the role of other bat species in EBLV-1 epidemiology and persistence remains unknown. Here, we built an EBLV-1-transmission model based on local observations of a three-cave and four-bat species (Myotis capaccinii, Myotis myotis, Miniopterus schreibersii, Rhinolophus ferrumequinum system in the Balearic Islands, for which a 1995-2011 serological dataset indicated the continuous presence of EBLV-1. Eptesicus serotinus was never observed in the system during the 16-year follow-up and therefore was not included in the model. We used the model to explore virus persistence mechanisms and to assess the importance of each bat species in the transmission dynamics. We found that EBLV-1 could not be sustained if transmission between M. schreibersii and other bat species was eliminated, suggesting that this species serves as a regional reservoir. Global sensitivity analysis using Sobol's method revealed that following the rate of autumn-winter infectious contacts, M. schreibersii's incubation- and immune-period durations, but not the infectious period length, were the most relevant factors driving virus persistence.

  10. Insights into Persistence Mechanisms of a Zoonotic Virus in Bat Colonies Using a Multispecies Metapopulation Model

    Science.gov (United States)

    Pons-Salort, Margarita; Serra-Cobo, Jordi; Jay, Flora; López-Roig, Marc; Lavenir, Rachel; Guillemot, Didier; Letort, Véronique; Bourhy, Hervé; Opatowski, Lulla

    2014-01-01

    Rabies is a worldwide zoonosis resulting from Lyssavirus infection. In Europe, Eptesicus serotinus is the most frequently reported bat species infected with Lyssavirus, and thus considered to be the reservoir of European bat Lyssavirus type 1 (EBLV-1). To date, the role of other bat species in EBLV-1 epidemiology and persistence remains unknown. Here, we built an EBLV-1−transmission model based on local observations of a three-cave and four-bat species (Myotis capaccinii, Myotis myotis, Miniopterus schreibersii, Rhinolophus ferrumequinum) system in the Balearic Islands, for which a 1995–2011 serological dataset indicated the continuous presence of EBLV-1. Eptesicus serotinus was never observed in the system during the 16-year follow-up and therefore was not included in the model. We used the model to explore virus persistence mechanisms and to assess the importance of each bat species in the transmission dynamics. We found that EBLV-1 could not be sustained if transmission between M. schreibersii and other bat species was eliminated, suggesting that this species serves as a regional reservoir. Global sensitivity analysis using Sobol's method revealed that following the rate of autumn−winter infectious contacts, M. schreibersii's incubation- and immune-period durations, but not the infectious period length, were the most relevant factors driving virus persistence. PMID:24755619

  11. Elucidating cytochrome C release from mitochondria: insights from an in silico three-dimensional model.

    Science.gov (United States)

    Tam, Zhi Yang; Cai, Yi Hui; Gunawan, Rudiyanto

    2010-11-17

    Mitochondrial regulation of apoptosis depends on the programmed release of proapoptotic proteins such as cytochrome c (Cyt c) through the outer mitochondrial membrane (OMM). Although a few key processes involved in this release have been identified, including the liberation of inner membrane-bound Cyt c and formation of diffusible pores on the OMM, other details like the transport of Cyt c within complex mitochondrial compartments, e.g., the cristae and crista junctions, are not yet fully understood (to our knowledge). In particular, a remodeling of the inner mitochondrial membrane accompanying apoptosis seen in a few studies, in which crista junctions widen, has been hypothesized to be a necessary step in the Cyt c release. Using a three-dimensional spatial modeling of mitochondrial crista and the crista junction, model simulations and analysis illustrated how the interplay among solubilization of Cyt c, fast diffusion of Cyt c, and OMM permeabilization gives rise to the observed experimental release profile. Importantly, the widening of the crista junction was found to have a negligible effect on the transport of free Cyt c from cristae. Finally, model simulations showed that increasing the fraction of free/loosely-bound Cyt c can sensitize the cell to apoptotic stimuli in a threshold manner, which may explain increased sensitivity to cell death associated with aging. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  12. Insight into collision zone dynamics from topography: numerical modelling results and observations

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    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.

  13. The role of alpha-rhythm states in perceptual learning: insights from experiments and computational models

    Directory of Open Access Journals (Sweden)

    Rodrigo eSigala

    2014-04-01

    Full Text Available 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.

  14. 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.

  15. Insights from computational modeling in inflammation and acute rejection in limb transplantation.

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    Dolores Wolfram

    Full Text Available Acute skin rejection in vascularized composite allotransplantation (VCA is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection.

  16. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

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    Melissa Lo Monaco

    2018-01-01

    Full Text Available Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs or induced pluripotent stem cells (iPSCs have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  17. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.

    Science.gov (United States)

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  18. Use of profile hidden Markov models in viral discovery: current insights

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    Reyes A

    2017-07-01

    Full Text Available Alejandro Reyes,1–3 João Marcelo P Alves,4 Alan Mitchell Durham,5 Arthur Gruber4 1Department of Biological Sciences, Universidad de los Andes, Bogotá, Colombia; 2Department of Pathology and Immunology, Center for Genome Sciences and Systems Biology, Washington University in Saint Louis, St Louis, MO, USA; 3Max Planck Tandem Group in Computational Biology, Universidad de los Andes, Bogotá, Colombia; 4Department of Parasitology, Institute of Biomedical Sciences, 5Department of Computer Science, Institute of Mathematics and Statistics, Universidade de São Paulo, São Paulo, Brazil Abstract: Sequence similarity searches are the bioinformatic cornerstone of molecular sequence analysis for all domains of life. However, large amounts of divergence between organisms, such as those seen among viruses, can significantly hamper analyses. Profile hidden Markov models (profile HMMs are among the most successful approaches for dealing with this problem, which represent an invaluable tool for viral identification efforts. Profile HMMs are statistical models that convert information from a multiple sequence alignment into a set of probability values that reflect position-specific variation levels in all members of evolutionarily related sequences. Since profile HMMs represent a wide spectrum of variation, these models show higher sensitivity than conventional similarity methods such as BLAST for the detection of remote homologs. In recent years, there has been an effort to compile viral sequences from different viral taxonomic groups into integrated databases, such as Prokaryotic Virus Orthlogous Groups (pVOGs and database of profile HMMs (vFam database, which provide functional annotation, multiple sequence alignments, and profile HMMs. Since these databases rely on viral sequences collected from GenBank and RefSeq, they suffer in variable extent from uneven taxonomic sampling, with low sequence representation of many viral groups, which affects the

  19. Export of earthquake-triggered landslides in active mountain ranges: insights from 2D morphodynamic modelling.

    Science.gov (United States)

    Croissant, Thomas; Lague, Dimitri; Davy, Philippe; Steer, Philippe

    2016-04-01

    In active mountain ranges, large earthquakes (Mw > 5-6) trigger numerous landslides that impact river dynamics. These landslides bring local and sudden sediment piles that will be eroded and transported along the river network causing downstream changes in river geometry, transport capacity and erosion efficiency. The progressive removal of landslide materials has implications for downstream hazards management and also for understanding landscape dynamics at the timescale of the seismic cycle. The export time of landslide-derived sediments after large-magnitude earthquakes has been studied from suspended load measurements but a full understanding of the total process, including the coupling between sediment transfer and channel geometry change, still remains an issue. Note that the transport of small sediment pulses has been studied in the context of river restoration, but the magnitude of sediment pulses generated by landslides may make the problem different. Here, we study the export of large volumes (>106 m3) of sediments with the 2D hydro-morphodynamic model, Eros. This model uses a new hydrodynamic module that resolves a reduced form of the Saint-Venant equations with a particle method. It is coupled with a sediment transport and lateral and vertical erosion model. Eros accounts for the complex retroactions between sediment transport and fluvial geometry, with a stochastic description of the floods experienced by the river. Moreover, it is able to reproduce several features deemed necessary to study the evacuation of large sediment pulses, such as river regime modification (single-thread to multi-thread), river avulsion and aggradation, floods and bank erosion. Using a synthetic and simple topography we first present how granulometry, landslide volume and geometry, channel slope and flood frequency influence 1) the dominance of pulse advection vs. diffusion during its evacuation, 2) the pulse export time and 3) the remaining volume of sediment in the catchment

  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. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms

    Science.gov (United States)

    Widdows, Kate L.; Panitchob, Nuttanont; Crocker, Ian P.; Please, Colin P.; Hanson, Mark A.; Sibley, Colin P.; Johnstone, Edward D.; Sengers, Bram G.; Lewis, Rohan M.; Glazier, Jocelyn D.

    2015-01-01

    Uptake of system L amino acid substrates into isolated placental plasma membrane vesicles in the absence of opposing side amino acid (zero-trans uptake) is incompatible with the concept of obligatory exchange, where influx of amino acid is coupled to efflux. We therefore hypothesized that system L amino acid exchange transporters are not fully obligatory and/or that amino acids are initially present inside the vesicles. To address this, we combined computational modeling with vesicle transport assays and transporter localization studies to investigate the mechanisms mediating [14C]l-serine (a system L substrate) transport into human placental microvillous plasma membrane (MVM) vesicles. The carrier model provided a quantitative framework to test the 2 hypotheses that l-serine transport occurs by either obligate exchange or nonobligate exchange coupled with facilitated transport (mixed transport model). The computational model could only account for experimental [14C]l-serine uptake data when the transporter was not exclusively in exchange mode, best described by the mixed transport model. MVM vesicle isolates contained endogenous amino acids allowing for potential contribution to zero-trans uptake. Both L-type amino acid transporter (LAT)1 and LAT2 subtypes of system L were distributed to MVM, with l-serine transport attributed to LAT2. These findings suggest that exchange transporters do not function exclusively as obligate exchangers.—Widdows, K. L., Panitchob, N., Crocker, I. P., Please, C. P., Hanson, M. A., Sibley, C. P., Johnstone, E. D., Sengers, B. G., Lewis, R. M., Glazier, J. D. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms. PMID:25761365

  2. A β-solenoid model of the Pmel17 repeat domain: insights to the formation of functional amyloid fibrils

    Science.gov (United States)

    Louros, Nikolaos N.; Baltoumas, Fotis A.; Hamodrakas, Stavros J.; Iconomidou, Vassiliki A.

    2016-02-01

    Pmel17 is a multidomain protein involved in biosynthesis of melanin. This process is facilitated by the formation of Pmel17 amyloid fibrils that serve as a scaffold, important for pigment deposition in melanosomes. A specific luminal domain of human Pmel17, containing 10 tandem imperfect repeats, designated as repeat domain (RPT), forms amyloid fibrils in a pH-controlled mechanism in vitro and has been proposed to be essential for the formation of the fibrillar matrix. Currently, no three-dimensional structure has been resolved for the RPT domain of Pmel17. Here, we examine the structure of the RPT domain by performing sequence threading. The resulting model was subjected to energy minimization and validated through extensive molecular dynamics simulations. Structural analysis indicated that the RPT model exhibits several distinct properties of β-solenoid structures, which have been proposed to be polymerizing components of amyloid fibrils. The derived model is stabilized by an extensive network of hydrogen bonds generated by stacking of highly conserved polar residues of the RPT domain. Furthermore, the key role of invariant glutamate residues is proposed, supporting a pH-dependent mechanism for RPT domain assembly. Conclusively, our work attempts to provide structural insights into the RPT domain structure and to elucidate its contribution to Pmel17 amyloid fibril formation.

  3. 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.

  4. Insights in Fault Flow Behaviour from Onshore Nigeria Petroleum System Modelling

    Directory of Open Access Journals (Sweden)

    Woillez Marie-Noëlle

    2017-09-01

    Full Text Available Faults are complex geological features acting either as permeability barrier, baffle or drain to fluid flow in sedimentary basins. Their role can be crucial for over-pressure building and hydrocarbon migration, therefore they have to be properly integrated in basin modelling. The ArcTem basin simulator included in the TemisFlow software has been specifically designed to improve the modelling of faulted geological settings and to get a numerical representation of fault zones closer to the geological description. Here we present new developments in the simulator to compute fault properties through time as a function of available geological parameters, for single-phase 2D simulations. We have used this new prototype to model pressure evolution on a siliciclastic 2D section located onshore in the Niger Delta. The section is crossed by several normal growth faults which subdivide the basin into several sedimentary units and appear to be lateral limits of strong over-pressured zones. Faults are also thought to play a crucial role in hydrocarbons migration from the deep source rocks to shallow reservoirs. We automatically compute the Shale Gouge Ratio (SGR along the fault planes through time, as well as the fault displacement velocity. The fault core permeability is then computed as a function of the SGR, including threshold values to account for shale smear formation. Longitudinal fault fluid flow is enhanced during periods of high fault slip velocity. The method allows us to simulate both along-fault drainages during the basin history as well as overpressure building at present-day. The simulated pressures are at first order within the range of observed pressures we had at our disposal.

  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. Water retention of repellent and subcritical repellent soils: New insights from model and experimental investigations

    Science.gov (United States)

    Czachor, H.; Doerr, S. H.; Lichner, L.

    2010-01-01

    SummarySoil organic matter can modify the surface properties of the soil mineral phase by changing the surface tension of the mineral surfaces. This modifies the soil's solid-water contact angle, which in turn would be expected to affect its water retention curve (SWRC). Here we model the impact of differences in the soil pore-water contact angle on capillarity in non-cylindrical pores by accounting for their complex pore geometry. Key outcomes from the model include that (i) available methods for measuring the Young's wetting angle on soil samples are insufficient in representing the wetting angle in the soil pore space, (ii) the wetting branch of water retention curves is strongly affected by the soil pore-water contact angle, as manifest in the wetting behavior of water repellent soils, (iii) effects for the drying branch are minimal, indicating that both wettable and water repellent soils should behave similarly, and (vi) water retention is a feature not of only wettable soils, but also soils that are in a water repellent state. These results are tested experimentally by determining drying and wetting branches for (a) 'model soil' (quartz sands with four hydrophobization levels) and (b) five field soil samples with contrasting wettability, which were used with and without the removal of the soil organic matter. The experimental results support the theoretical predictions and indicate that small changes in wetting angle can cause switches between wettable and water repellent soil behavior. This may explain the common observation that relatively small changes in soil water content can cause substantial changes in soil wettability.

  7. 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.

  8. 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

  9. 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.

  10. Molecular modeling of human neutral sphingomyelinase provides insight into its molecular interactions.

    Science.gov (United States)

    Dinesh; Goswami, Angshumala; Suresh, Panneer Selvam; Thirunavukkarasu, Chinnasamy; Weiergräber, Oliver H; Kumar, Muthuvel Suresh

    2011-01-01

    The neutral sphingomyelinase (N-SMase) is considered a major candidate for mediating the stress-induced production of ceramide, and it plays an important role in cell-cycle arrest, apoptosis, inflammation, and eukaryotic stress responses. Recent studies have identified a small region at the very N-terminus of the 55 kDa tumour necrosis factor receptor (TNF-R55), designated the neutral sphingomyelinase activating domain (NSD) that is responsible for the TNF-induced activation of N-SMase. There is no direct association between TNF-R55 NSD and N-SMase; instead, a protein named factor associated with N-SMase activation (FAN) has been reported to couple the TNF-R55 NSD to N-SMase. Since the three-dimensional fold of N-SMase is still unknown, we have modeled the structure using the protein fold recognition and threading method. Moreover, we propose models for the TNF-R55 NSD as well as the FAN protein in order to study the structural basis of N-SMase activation and regulation. Protein-protein interaction studies suggest that FAN is crucially involved in mediating TNF-induced activation of the N-SMase pathway, which in turn regulates mitogenic and proinflammatory responses. Inhibition of N-SMase may lead to reduction of ceramide levels and hence may provide a novel therapeutic strategy for inflammation and autoimmune diseases. Molecular dynamics (MD) simulations were performed to check the stability of the predicted model and protein-protein complex; indeed, stable RMS deviations were obtained throughout the simulation. Furthermore, in silico docking of low molecular mass ligands into the active site of N-SMase suggests that His135, Glu48, Asp177, and Asn179 residues play crucial roles in this interaction. Based on our results, these ligands are proposed to be potent and selective N-SMase inhibitors, which may ultimately prove useful as lead compounds for drug development.

  11. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Terrestrial N Cycling And C Storage: Some Insights From A Process-based Land Surface Model

    Science.gov (United States)

    Zaehle, S.; Friend, A. D.; Friedlingstein, P.

    2008-12-01

    We present results of a new land surface model, O-CN, which includes a process-based coupling between the terrestrial cycling of energy, water, carbon, and nitrogen. The model represents the controls of the terrestrial nitrogen (N) cycling on carbon (C) pools and fluxes through photosynthesis, respiration, changes in allocation, and soil organic matter decomposition, and explicitly accounts for N leaching and gaseous losses. O-CN has been shown to give realistic results in comparison to observations at a wide range of scales, including in situ flux measurements, productivity databases, and atmospheric CO2 concentration data. O-CN is run for three free air carbon dioxide enrichment (FACE) sites (Duke, Oak Ridge, Aspen), and reproduces observed magnitudes of changes in net primary productivity, foliage area and foliage N content. Several alternative hypotheses concerning the control of N on vegetation growth and decomposition, including effects of diluting foliage N concentrations, down-regulation of photosynthesis and respiration, acclimation of C allocation patterns and biological N fixation, are tested with respect to their effect on long- term C sequestration estimate. Differences in initial N availability, small transient changes in N inputs and the assumed plasticity of C:N stoichiometry can lead to substantial differences in the simulated long-term changes in productivity and C sequestration. We discuss the capacity of observations obtained at FACE sites to evaluate these alternative hypotheses, and investigate implications of a transient versus instantaneous increase in atmospheric carbon dioxide for the magnitude of the simulated limiting effect of N on C cycling. Finally, we re-examine earlier model-based assessments of the terrestrial C sequestration potential using a global transient O-CN simulation driven by increases in atmospheric CO2, N deposition and climatic changes over the 21st century.

  13. The seismic cycle at subduction thrusts: 1. Insights from laboratory models

    KAUST Repository

    Corbi, F.; Funiciello, F.; Moroni, M.; van Dinther, Y.; Mai, Paul Martin; Dalguer, L. A.; Faccenna, C.

    2013-01-01

    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.

  14. How do salt withdrawal minibasins form? Insights from forward modelling, and implications for hydrocarbon migration

    Science.gov (United States)

    Peel, Frank J.

    2014-09-01

    Existing models for the initiation of salt withdrawal minibasins focus on the role of triggers that exist within the minibasin, either stratigraphic (e.g. differential deposition) or tectonic (extension, translation or contraction). Existing studies tend to focus on complex settings, such as continental margins, which contain many different potential triggering mechanisms. It can be difficult in these settings to identify which process is responsible for minibasin initiation, or the influence of individual factors on their subsequent development. Salt withdrawal minibasins also exist in simpler settings, without any obvious intrinsic trigger; the region of the North German Basin used by Trusheim (1960) in the classic definition of salt withdrawal geometries was of this nature. There is no overall basal or surface slope, no major lateral movement, and there is no depositional heterogeneity. Previously recognized trigger processes for minibasin initiation do not apply in this benign setting, suggesting that other, potentially more fundamental, influences may be at work. A simple forward-modelling approach shows how, in the absence of any other mechanism, a new minibasin can develop as the consequence of salt movement driven by its neighbour, and families of withdrawal minibasins can propagate across a region from a single seed point. This new mechanism may explain how some minibasins appear to initiate before the sediment density has exceeded that of the underlying salt. The forward modelling also indicates that some minibasins begin to invert to form turtle anticlines before the underlying salt has been evacuated, so that the timing of turtle formation may not be diagnostic of weld formation. This mechanism may also give rise to salt-cored turtles that have a lens of salt trapped beneath their cores. These new findings have implications for hydrocarbon migration and trapping.

  15. 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.

  16. Insights into the diurnal cycle of global Earth outgoing radiation using a numerical weather prediction model

    Science.gov (United States)

    Gristey, Jake J.; Chiu, J. Christine; Gurney, Robert J.; Morcrette, Cyril J.; Hill, Peter G.; Russell, Jacqueline E.; Brindley, Helen E.

    2018-04-01

    A globally complete, high temporal resolution and multiple-variable approach is employed to analyse the diurnal cycle of Earth's outgoing energy flows. This is made possible via the use of Met Office model output for September 2010 that is assessed alongside regional satellite observations throughout. Principal component analysis applied to the long-wave component of modelled outgoing radiation reveals dominant diurnal patterns related to land surface heating and convective cloud development, respectively explaining 68.5 and 16.0 % of the variance at the global scale. The total variance explained by these first two patterns is markedly less than previous regional estimates from observations, and this analysis suggests that around half of the difference relates to the lack of global coverage in the observations. The first pattern is strongly and simultaneously coupled to the land surface temperature diurnal variations. The second pattern is strongly coupled to the cloud water content and height diurnal variations, but lags the cloud variations by several hours. We suggest that the mechanism controlling the delay is a moistening of the upper troposphere due to the evaporation of anvil cloud. The short-wave component of modelled outgoing radiation, analysed in terms of albedo, exhibits a very dominant pattern explaining 88.4 % of the variance that is related to the angle of incoming solar radiation, and a second pattern explaining 6.7 % of the variance that is related to compensating effects from convective cloud development and marine stratocumulus cloud dissipation. Similar patterns are found in regional satellite observations, but with slightly different timings due to known model biases. The first pattern is controlled by changes in surface and cloud albedo, and Rayleigh and aerosol scattering. The second pattern is strongly coupled to the diurnal variations in both cloud water content and height in convective regions but only cloud water content in marine

  17. Late Quaternary Variability of Arctic Sea Ice: Insights From Biomarker Proxy Records and Model Simulations

    Science.gov (United States)

    Stein, R. H.; Fahl, K.; Gierz, P.; Niessen, F.; Lohmann, G.

    2017-12-01

    Over the last about four decades, coinciding with global warming and atmospheric CO2increase, the extent and thickness of Arctic sea ice has decreased dramatically, a decrease much more rapid than predicted by climate models. The driving forces of this change are still not fully understood. In this context, detailed paleoclimatic records going back beyond the timescale of direct observations, i.e., high-resolution Holocene records but also records representing more distant warm periods, may help to to distinguish and quantify more precisely the natural and anthropogenic greenhouse gas forcing of global climate change and related sea ice decrease. Here, we concentrate on sea ice biomarker records representing the penultimate glacial/last interglacial (MIS 6/MIS 5e) and the Holocene time intervals. Our proxy records are compared with climate model simulations using a coupled atmosphere-ocean general circulation model (AOGCM). Based on our data, polynya-type sea ice conditions probably occurred off the major ice sheets along the northern Barents and East Siberian continental margins during late MIS 6. Furthermore, we demonstrate that even during MIS 5e, i.e., a time interval when the high latitudes have been significantly warmer than today, sea ice existed in the central Arctic Ocean during summer, whereas sea ice was significantly reduced along the Barents Sea continental margin influenced by Atlantic Water inflow. Assuming a closed Bering Strait (no Pacific Water inflow) during early MIS 5, model simulations point to a significantly reduced sea ice cover in the central Arctic Ocean, a scenario that is however not supported by the proxy record and thus seems to be less realistic. Our Holocene biomarker proxy records from the Chukchi Sea indicate that main factors controlling the millennial Holocene variability in sea ice are probably changes in surface water and heat flow from the Pacific into the Arctic Ocean as well as the long-term decrease in summer insolation

  18. Deeper Insight into the Diels-Alder Reaction through the Activation Strain Model.

    Science.gov (United States)

    Fernández, Israel; Bickelhaupt, F Matthias

    2016-12-06

    In this Focus Review, we present the application of the so-called Activation Strain Model of chemical reactivity to the Diels-Alder cycloaddition reaction. To this end, representative recent examples have been selected to illustrate the power of this new computational approach to gain a deeper quantitative understanding of this fundamental process in chemistry. We cover a wide range of issues, such as, the "endo-rule", reactivity trends emerging from systematic variation in the reactants' strain, and cycloaddition reactions involving relevant species in material science, that is, fullerenes, polycyclic aromatic hydrocarbons and nanotubes. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Influence of Roughness-Induced Slip on Colloid Transport: Experimental and Modelling Insights

    Science.gov (United States)

    Rasmuson, J. A.; Johnson, W. P.

    2017-12-01

    A limitation of classic colloid filtration theory is that it applies only to smooth surfaces, yet most natural surfaces present some degree of nano- to micro-scale roughness. A large volume of research has been dedicated to understanding the effects of roughness on particle attachment at the nano-scale since these interactions dictate field scale transport behavior. It has been previously demonstrated that roughness imposes a finite slip vector at the surface that causes particles to experience higher near-surface velocities than would be expected over a smooth surface. Slip near a rough surface can affect two primary mechanisms of particle attenuation: 1) interception of the surface (finding a landing spot) and 2) arrest on the surface (sticking the landing). However, a clear designation on how slip affects particle transport near rough surfaces is missing. The goal of this study was to provide a guide for the height of the slip layer and contact surface in reference to the mean-plane for rough surfaces. Direct observation was used to measure near-surface velocities of particles translating near surfaces of varying roughness spanning three orders of magnitude. The influence of roughness on particle transport was investigated using computational fluid dynamics (CFD) modeling with rough surfaces measured with atomic force microscopy (AFM). The CFD and experimental results were used to calibrate a Lagrangian particle transport model that utilizes simple modifications to the flow field for a smooth surface using statistically based roughness parameters. Advantages of the Lagrangian model are significantly decreased computation times and applicability to a wide range of natural surfaces without explicitly simulating individual asperities. The results suggest that the no-slip boundary should be placed at the bottom of the maximum asperity valleys, and that the contact surface should be placed at the root mean square (RMS) roughness above the mean plane. Collector

  20. Structural insights into a high affinity nanobody:antigen complex by homology modelling

    DEFF Research Database (Denmark)

    Skottrup, Peter Durand

    2017-01-01

    Porphyromonas gingivalis is a major periodontitis-causing pathogens. P. gingivalis secrete a cysteine protease termed RgpB, which is specific for Arg-Xaa bonds in substrates. Recently, a nanobody-based assay was used to demonstrate that RgpB could represent a novel diagnostic target, thereby...... simplifying. P. gingivalis detection. The nanobody, VHH7, had a high binding affinity and was specific for RgpB, when tested towards the highly identical RgpA. In this study a homology model of VHH7 was build. The complementarity determining regions (CDR) comprising the paratope residues responsible for Rgp...

  1. Closing the phosphorus cycle in a food system: insights from a modelling exercise.

    Science.gov (United States)

    van Kernebeek, H R J; Oosting, S J; van Ittersum, M K; Ripoll-Bosch, R; de Boer, I J M

    2018-05-21

    Mineral phosphorus (P) used to fertilise crops is derived from phosphate rock, which is a finite resource. Preventing and recycling mineral P waste in the food system, therefore, are essential to sustain future food security and long-term availability of mineral P. The aim of our modelling exercise was to assess the potential of preventing and recycling P waste in a food system, in order to reduce the dependency on phosphate rock. To this end, we modelled a hypothetical food system designed to produce sufficient food for a fixed population with a minimum input requirement of mineral P. This model included representative crop and animal production systems, and was parameterised using data from the Netherlands. We assumed no import or export of feed and food. We furthermore assumed small P soil losses and no net P accumulation in soils, which is typical for northwest European conditions. We first assessed the minimum P requirement in a baseline situation, that is 42% of crop waste is recycled, and humans derived 60% of their dietary protein from animals (PA). Results showed that about 60% of the P waste in this food system resulted from wasting P in human excreta. We subsequently evaluated P input for alternative situations to assess the (combined) effect of: (1) preventing waste of crop and animal products, (2) fully recycling waste of crop products, (3) fully recycling waste of animal products and (4) fully recycling human excreta and industrial processing water. Recycling of human excreta showed most potential to reduce P waste from the food system, followed by prevention and finally recycling of agricultural waste. Fully recycling P could reduce mineral P input by 90%. Finally, for each situation, we studied the impact of consumption of PA in the human diet from 0% to 80%. The optimal amount of animal protein in the diet depended on whether P waste from animal products was prevented or fully recycled: if it was, then a small amount of animal protein in the human

  2. Ordering Dynamics in Neuron Activity Pattern Model: An Insight to Brain Functionality.

    Directory of Open Access Journals (Sweden)

    Jasleen Gundh

    Full Text Available 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.

  3. 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.

  4. 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.

  5. The economics of greenhouse gas mitigation: Insights from illustrative global abatement scenarios modelling

    International Nuclear Information System (INIS)

    Gurney, Andrew; Ahammad, Helal; Ford, Melanie

    2009-01-01

    In this paper the Global Trade and Environment Model (GTEM) and MAGICC are used to simulate a number of global emission mitigation scenarios devised by the EMF 22 Transition Scenarios group in which radiative forcing goals and the architecture of developing economies' participation in hypothetical mitigation actions are varied. This paper presents a reference case of the world economy to 2100 and analyses some key regional and global results for the various global mitigation scenarios, including emission prices, emission levels, primary energy consumption and economic growth. Modelling results suggest that a transition to a low-carbon world would require a significant decarbonisation of electricity generation without necessarily cutting the electricity output in the long run. With the uptake of hybrids and non-fossil-fuel technologies, the transport sector could make an important contribution to global abatement of greenhouse gases. Furthermore, with substantial international mitigation efforts and uptake of low- and/or zero-emission technologies, the achievement of 3.7 W/m 2 and 4.5 W/m 2 radiative forcing targets by the end of the century could occur at emission prices of up to $550/t CO 2 -e. However, achieving the 2.6 W/m 2 (overshoot) radiative forcing target would require considerably higher emission prices and an immediate global mitigation action.

  6. Streaming potential modeling in fractured rock: Insights into the identification of hydraulically active fractures

    Science.gov (United States)

    Roubinet, D.; Linde, N.; Jougnot, D.; Irving, J.

    2016-05-01

    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 interactions. This implies that fractures associated with strong SP amplitudes are likely to be hydraulically conductive, attracting fluid flow from the surrounding matrix.

  7. fiReproxies: A computational model providing insight into heat-affected archaeological lithic assemblages.

    Science.gov (United States)

    Sorensen, Andrew C; Scherjon, Fulco

    2018-01-01

    Evidence for fire use becomes increasingly sparse the further back in time one looks. This is especially true for Palaeolithic assemblages. Primary evidence of fire use in the form of hearth features tends to give way to clusters or sparse scatters of more durable heated stone fragments. In the absence of intact fireplaces, these thermally altered lithic remains have been used as a proxy for discerning relative degrees of fire use between archaeological layers and deposits. While previous experimental studies have demonstrated the physical effects of heat on stony artefacts, the mechanisms influencing the proportion of fire proxy evidence within archaeological layers remain understudied. This fundamental study is the first to apply a computer-based model (fiReproxies) in an attempt to simulate and quantify the complex interplay of factors that ultimately determine when and in what proportions lithic artefacts are heated by (anthropogenic) fires. As an illustrative example, we apply our model to two hypothetical archaeological layers that reflect glacial and interglacial conditions during the late Middle Palaeolithic within a generic simulated cave site to demonstrate how different environmental, behavioural and depositional factors like site surface area, sedimentation rate, occupation frequency, and fire size and intensity can, independently or together, significantly influence the visibility of archaeological fire signals.

  8. Thinning of heterogeneous lithosphere: insights from field observations and numerical modelling

    Science.gov (United States)

    Petri, B.; Duretz, T.; Mohn, G.; Schmalholz, S. M.

    2017-12-01

    The nature and mechanisms of formation of extremely thinned continental crust (N Italy) and in the Southern Alps (N Italy) were selected for their exceptional level of preservation of rift-related structures. This situation enables us to characterize (1) the pre-rift architecture of the continental lithosphere, (2) the localization of rift-related deformation in distinct portion of the lithosphere and (3) the interaction between initial heterogeneities of the lithosphere and rift-related structures. In a second stage, these observations are integrated in high-resolution, two-dimensional thermo-mechanical models taking into account various patterns of initial mechanical heterogeneities. Our results show the importance of initial pre-rift architecture of the continental lithosphere during rifting. Key roles are given to high-angle and low-angle normal faults, anastomosing shear-zones and decoupling horizons. We propose that during the first stages of thinning, deformation is strongly controlled by the complex pre-rift architecture of the lithosphere, localized along major structures responsible for the lateral extrusion of mid to lower crustal levels. This extrusion juxtaposes mechanically stronger levels in the hyper-thinned continental crust, being exhumed by subsequent low-angle normal faults. Altogether, these results highlight the critical role of the extraction of mechanically strong layers of the lithosphere during the extreme thinning of the continental lithosphere and allows to propose a new model for the formation of continental passive margins.

  9. 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.

  10. 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.

  11. 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.

  12. Novel insights into obesity and diabetes through genome-scale metabolic modeling

    Directory of Open Access Journals (Sweden)

    Leif eVäremo

    2013-04-01

    Full Text Available The growing prevalence of metabolic diseases, such as obesity and diabetes, are putting a high strain on global healthcare systems as well as increasing the demand for efficient treatment strategies. More than 360 million people worldwide are suffering from type 2 diabetes and, with the current trends, the projection is that 10% of the global adult population will be affected by 2030. In light of the systemic properties of metabolic diseases as well as the interconnected nature of metabolism, it is necessary to begin taking a holistic approach to study these diseases. Human genome-scale metabolic models (GEMs are topological and mathematical representations of cell metabolism and have proven to be valuable tools in the area of systems biology. Successful applications of GEMs include the process of gaining further biological and mechanistic understanding of diseases, finding potential biomarkers and identifying new drug targets. This review will focus on the modeling of human metabolism in the field of obesity and diabetes, showing its vast range of applications of clinical importance as well as point out future challenges.

  13. INSIGHTS INTO THE MECHANICS OF CYTOKINETIC RING ASSEMBLY USING 3D MODELING.

    Science.gov (United States)

    Bidone, Tamara Carla; Tang, Haosu; Vavylonis, Dimitrios

    During fission yeast cytokinesis, actin filaments nucleated by cortical formin Cdc12 are captured by myosin motors bound to a band of cortical nodes. The myosin motors exert forces that pull nodes together into a contractile ring. Cross-linking interactions help align actin filaments and nodes into a single bundle. Mutations in the myosin motor domain and changes in the concentration of cross-linkers alpha-actinin and fimbrin alter the morphology of the condensing network, leading to clumps, rings or extended meshworks. How the contractile tension developing during ring formation depends on the interplay between network morphology, myosin motor activity, cross-linking and actin filament turnover remains to be elucidated. We addressed this question using a 3D computational model in which semiflexible actin filaments (represented as beads connected by springs) grow from formins, can be captured by myosin in neighboring nodes, and get cross-linked with one another through an attractive interaction. We identify regimes of tension generation between connected nodes under a wide set of conditions regarding myosin dynamics and strength of cross-linking between actin filaments. We find conditions that maximize circumferential tension, correlate them with network morphology and propose experiments to test these predictions. This work addresses "Morphogenesis of soft and living matter" using computational modeling to simulate cytokinetic ring assembly from the key molecular mechanisms of viscoelastic cross-linked actin networks that include active molecular motors.

  14. 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.

  15. 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.

  16. Thrust initiation and its control on tectonic wedge geometry: An insight from physical and numerical models

    Science.gov (United States)

    Bose, Santanu; Mandal, Nibir; Saha, Puspendu; Sarkar, Shamik; Lithgow-Bertelloni, Carolina

    2014-10-01

    We performed a series of sandbox experiments to investigate the initiation of thrust ramping in tectonic wedges on a mechanically continuous basal decollement. The experiments show that the decollement slope (β) is the key factor in controlling the location of thrust initiation with respect to the backstop (i.e. tectonic suture line). For β = 0, the ramping begins right at the backstop, followed by sequential thrusting in the frontal direction, leading to a typical mono-vergent wedge. In contrast, the ramp initiates away from the backstop as β > 0. Under this boundary condition an event of sequential back thrusting takes place prior to the onset of frontal thrust progression. These two-coupled processes eventually give rise to a bi-vergent geometry of the thrust wedge. Using the Drucker-Prager failure criterion in finite element (FE) models, we show the location of stress intensification to render a mechanical basis for the thrust initiation away from the backstop if β > 0. Our physical and FE model results explain why the Main Central Thrust (MCT) is located far away from the Indo-Tibetan plate contact (ITSZ) in the Himalayan fold-and-thrust belts.

  17. Linearization effect in multifractal analysis: Insights from the Random Energy Model

    Science.gov (United States)

    Angeletti, Florian; Mézard, Marc; Bertin, Eric; Abry, Patrice

    2011-08-01

    The analysis of the linearization effect in multifractal analysis, and hence of the estimation of moments for multifractal processes, is revisited borrowing concepts from the statistical physics of disordered systems, notably from the analysis of the so-called Random Energy Model. Considering a standard multifractal process (compound Poisson motion), chosen as a simple representative example, we show the following: (i) the existence of a critical order q∗ beyond which moments, though finite, cannot be estimated through empirical averages, irrespective of the sample size of the observation; (ii) multifractal exponents necessarily behave linearly in q, for q>q∗. Tailoring the analysis conducted for the Random Energy Model to that of Compound Poisson motion, we provide explicative and quantitative predictions for the values of q∗ and for the slope controlling the linear behavior of the multifractal exponents. These quantities are shown to be related only to the definition of the multifractal process and not to depend on the sample size of the observation. Monte Carlo simulations, conducted over a large number of large sample size realizations of compound Poisson motion, comfort and extend these analyses.

  18. Adolescence as a period of vulnerability and intervention in schizophrenia: Insights from the MAM Model

    Science.gov (United States)

    Gomes, Felipe V.; Rincón-Cortés, Millie; Grace, Anthony A.

    2016-01-01

    Adolescence is a time of extensive neuroanatomical, functional and chemical reorganization of the brain, which parallels substantial maturational changes in behavior and cognition. Environmental factors that impinge on the timing of these developmental factors, including stress and drug exposure, increase the risk for psychiatric disorders. Indeed, antecedents to affective and psychotic disorders, which have clinical and pathophysiological overlap, are commonly associated with risk factors during adolescence that predispose to these disorders. In the context of schizophrenia, psychosis typically begins in late adolescence/early adulthood, which has been replicated by animal models. Rats exposed during gestational day (GD) 17 to the mitotoxin methylazoxymethanol acetate (MAM) exhibit behavioral, pharmacological, and anatomical characteristics consistent with an animal model of schizophrenia. Here we provide an overview of adolescent changes within the dopamine system and the PFC and review recent findings regarding the effects of stress and cannabis exposure during the peripubertal period as risk factors for the emergence of schizophrenia-like deficits. Finally, we discuss peripubertal interventions appearing to circumvent the emergence of adult schizophrenia-like deficits. PMID:27235082

  19. 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.

  20. 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

  1. Witnessing traumatic events and post-traumatic stress disorder: Insights from an animal model.

    Science.gov (United States)

    Patki, Gaurav; Salvi, Ankita; Liu, Hesong; Salim, Samina

    2015-07-23

    It is becoming increasingly recognized that post-traumatic stress disorder (PTSD) can be acquired vicariously from witnessing traumatic events. Recently, we published an animal model called the "Trauma witness model" (TWM) which mimics PTSD-like symptoms in rats from witnessing daily traumatic events (social defeat of cage mate) [14]. Our TWM does not result in any physical injury. This is a major procedural advantage over the typical intruder paradigm in which it is difficult to delineate the inflammatory response of tissue injury and the response elicited from emotional distress. Using TWM paradigm, we examined behavioral and cognitive effects in rats [14] however, the long-term persistence of PTSD-like symptoms or a time-course of these events (anxiety and depression-like behaviors and cognitive deficits) and the contribution of olfactory and auditory stress vs visual reinforcement were not examined. This study demonstrates that some of the features of PTSD-like symptoms in rats are reversible after a significant time lapse of the witnessing of traumatic events. We also have established that witnessing is critical to the PTSD-like phenotype and cannot be acquired solely due to auditory or olfactory stresses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. Revisiting the Euganean Geothermal System (NE Italy) - insights from large scale hydrothermal modelling

    Science.gov (United States)

    Pola, Marco; Cacace, Mauro; Fabbri, Paolo; Piccinini, Leonardo; Zampieri, Dario; Dalla Libera, Nico

    2017-04-01

    As one of the largest and most extensive utilized geothermal system in northern Italy, the Euganean Geothermal System (EGS, Veneto region, NE Italy) has long been the subject of still ongoing studies. Hydrothermal waters feeding the system are of meteoric origin and infiltrate in the Veneto Prealps, to the north of the main geothermal area. The waters circulate for approximately 100 km in the subsurface of the central Veneto, outflowing with temperatures from 65°C to 86°C to the southwest near the cities of Abano Terme and Montegrotto Terme. The naturally emerging waters are mainly used for balneotherapeutic purposes, forming the famous Euganean spa district. This preferential outflow is thought to have a relevant structural component producing a high secondary permeability localized within an area of limited extent (approx. 25 km2). This peculiar structure is associated with a local network of fractures resulting from transtentional tectonics of the regional Schio-Vicenza fault system (SVFS) bounding the Euganean Geothermal Field (EGF). In the present study, a revised conceptual hydrothermal model for the EGS based on the regional hydrogeology and structural geology is proposed. Particularly, this work aims to quantify: (1) the role of the regional SVFS, and (2) the impact of the high density local fractures mesh beneath the EGF on the regional-to-local groundwater flow circulation at depths and its thermal configuration. 3D coupled flow and heat transport numerical simulations inspired by the newly developed conceptual model are carried out to properly quantify the results from these interactions. Consistently with the observations, the obtained results provide indication for temperatures in the EGF reservoir being higher than in the surrounding areas, despite a uniform basal regional crustal heat inflow. In addition, they point to the presence of a structural causative process for the localized outflow, in which deep-seated groundwater is preferentially

  7. Employer health insurance offerings and employee enrollment decisions.

    Science.gov (United States)

    Polsky, Daniel; Stein, Rebecca; Nicholson, Sean; Bundorf, M Kate

    2005-10-01

    To determine how the characteristics of the health benefits offered by employers affect worker insurance coverage decisions. The 1996-1997 and the 1998-1999 rounds of the nationally representative Community Tracking Study Household Survey. We use multinomial logistic regression to analyze the choice between own-employer coverage, alternative source coverage, and no coverage among employees offered health insurance by their employer. The key explanatory variables are the types of health plans offered and the net premium offered. The models include controls for personal, health plan, and job characteristics. When an employer offers only a health maintenance organization married employees are more likely to decline coverage from their employer and take-up another offer (odds ratio (OR)=1.27, phealth plan coverage an employer offers affects whether its employees take-up insurance, but has a smaller effect on overall coverage rates for workers and their families because of the availability of alternative sources of coverage. Relative to offering only a non-HMO plan, employers offering only an HMO may reduce take-up among those with alternative sources of coverage, but increase take-up among those who would otherwise go uninsured. By modeling the possibility of take-up through the health insurance offers from the employer of the spouse, the decline in coverage rates from higher net premiums is less than previous estimates.

  8. New insights in the standard model of quantum physics in Clifford algebra

    CERN Document Server

    Daviau, Claude

    2013-01-01

    Why Clifford algebra is the true mathematical frame of the standard model of quantum physics. Why the time is everywhere oriented and why the left side shall never become the right side. Why positrons have also a positive proper energy. Why there is a Planck constant. Why a mass is not a charge. Why a system of particles implies the existence of the inverse of the individual wave function. Why a fourth neutrino should be a good candidate for black matter. Why concepts as “parity” and “reverse” are essential. Why the electron of a H atom is in only one bound state. Plus 2 very remarkable identities, and the invariant wave equations that they imply. Plus 3 generations and 4 neutrinos. Plus 5 dimensions in the space and 6 dimensions in space-time…

  9. Transition from static to kinetic friction: insights from a 2D model.

    Science.gov (United States)

    Trømborg, J; Scheibert, J; Amundsen, D S; Thøgersen, K; Malthe-Sørenssen, A

    2011-08-12

    We describe a 2D spring-block model for the transition from static to kinetic friction at an elastic-slider-rigid-substrate interface obeying a minimalistic friction law (Amontons-Coulomb). By using realistic boundary conditions, a number of previously unexplained experimental results on precursory microslip fronts are successfully reproduced. From the analysis of the interfacial stresses, we derive a prediction for the evolution of the precursor length as a function of the applied loads, as well as an approximate relationship between microscopic and macroscopic friction coefficients. We show that the stress buildup due to both elastic loading and microslip-related relaxations depends only weakly on the underlying shear crack propagation dynamics. Conversely, crack speed depends strongly on both the instantaneous stresses and the friction coefficients, through a nontrivial scaling parameter.

  10. 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

  11. Topological model of composite fermions in the cyclotron band generator picture: New insights

    Science.gov (United States)

    Staśkiewicz, Beata

    2018-03-01

    A combinatorial group theory in the braid groups is correlated with the unusual "anyon" statistic of particles in 2D Hall system in the fractional quantum regime well. On this background has been derived cyclotron band generator as a modification and generalization band generator, first established to solve the word and conjugacy problems in the braid group terms. Topological commensurability condition has been embraced by canonical factors - like, based on the concept of parallel descending cycles. Owing to this we can mathematically capture the general hierarchy of correlated states in the lowest Landau level, describing the fractional quantum Hall effect hierarchy, in terms of cyclotron band generators, especially for those being beyond conventional composite fermions model. It has been also shown that cyclotron braid subgroups, developed for interpretation of Laughlin correlations, are a special case of the right-angled Artin groups.

  12. Intestinal Stem Cell Niche Insights Gathered from Both In Vivo and Novel In Vitro Models

    Directory of Open Access Journals (Sweden)

    Nikolce Gjorevski

    2017-01-01

    Full Text Available Intestinal stem cells are located at the base of the crypts and are surrounded by a complex structure called niche. This environment is composed mainly of epithelial cells and stroma which provides signals that govern cell maintenance, proliferation, and differentiation. Understanding how the niche regulates stem cell fate by controlling developmental signaling pathways will help us to define how stem cells choose between self-renewal and differentiation and how they maintain their undifferentiated state. Tractable in vitro assay systems, which reflect the complexity of the in vivo situation but provide higher level of control, would likely be crucial in identifying new players and mechanisms controlling stem cell function. Knowledge of the intestinal stem cell niche gathered from both in vivo and novel in vitro models may help us improve therapies for tumorigenesis and intestinal damage and make autologous intestinal transplants a feasible clinical practice.

  13. Cardiovascular Benefits of Moderate Exercise Training in Marfan Syndrome: Insights From an Animal Model.

    Science.gov (United States)

    Mas-Stachurska, Aleksandra; Siegert, Anna-Maria; Batlle, Monsterrat; Gorbenko Del Blanco, Darya; Meirelles, Thayna; Rubies, Cira; Bonorino, Fabio; Serra-Peinado, Carla; Bijnens, Bart; Baudin, Julio; Sitges, Marta; Mont, Lluís; Guasch, Eduard; Egea, Gustavo

    2017-09-25

    Marfan syndrome (MF) leads to aortic root dilatation and a predisposition to aortic dissection, mitral valve prolapse, and primary and secondary cardiomyopathy. Overall, regular physical exercise is recommended for a healthy lifestyle, but dynamic sports are strongly discouraged in MF patients. Nonetheless, evidence supporting this recommendation is lacking. Therefore, we studied the role of long-term dynamic exercise of moderate intensity on the MF cardiovascular phenotype. In a transgenic mouse model of MF ( Fbn1 C1039G/+ ), 4-month-old wild-type and MF mice were subjected to training on a treadmill for 5 months; sedentary littermates served as controls for each group. Aortic and cardiac remodeling was assessed by echocardiography and histology. The 4-month-old MF mice showed aortic root dilatation, elastic lamina rupture, and tunica media fibrosis, as well as cardiac hypertrophy, left ventricular fibrosis, and intramyocardial vessel remodeling. Over the 5-month experimental period, aortic root dilation rate was significantly greater in the sedentary MF group, compared with the wild-type group (∆mm, 0.27±0.07 versus 0.13±0.02, respectively). Exercise significantly blunted the aortic root dilation rate in MF mice compared with sedentary MF littermates (∆mm, 0.10±0.04 versus 0.27±0.07, respectively). However, these 2 groups were indistinguishable by aortic root stiffness, tunica media fibrosis, and elastic lamina ruptures. In MF mice, exercise also produced cardiac hypertrophy regression without changes in left ventricular fibrosis. Our results in a transgenic mouse model of MF indicate that moderate dynamic exercise mitigates the progression of the MF cardiovascular phenotype. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  14. Insights on TTL Dehydration Mechanisms from Microphysical Modelling of Aircraft Observations

    Science.gov (United States)

    Ueyama, R.; Pfister, L.; Jensen, E.

    2014-01-01

    The Tropical Tropopause Layer (TTL), a transition layer between the upper troposphere and lower stratosphere in the tropics, serves as the entryway of various trace gases into the stratosphere. Of particular interest is the transport of water vapor through the TTL, as WV is an important greenhouse gas and also plays a significant role in stratospheric chemistry by affecting polar stratospheric cloud formation and the ozone budget. While the dominant control of stratospheric water vapor by tropical cold point temperatures via the "freeze-drying" process is generally well understood, the details of the TTL dehydration mechanisms, including the relative roles of deep convection, atmospheric waves and cloud microphysical processes, remain an active area of research. The dynamical and microphysical processes that influence TTL water vapor concentrations are investigated in simulations of cloud formation and dehydration along air parcel trajectories. We first confirm the validity of our Lagrangian models in a case study involving measurements from the Airborne Tropical TRopopause EXperiment (ATTREX) flights over the central and eastern tropical Pacific in Oct-Nov 2011 and Jan-Feb 2013. ERA-Interim winds and seasonal mean heating rates from Yang et al. (2010) are used to advance parcels back in time from the flight tracks, and time-varying vertical profiles of water vapor along the diabatic trajectories are calculated in a one-dimensional cloud model as in Jensen and Pfister (2004) but with more reliable temperature field, wave and convection schemes. The simulated water vapor profiles demonstrate a significant improvement over estimates based on the Lagrangian Dry Point, agreeing well with aircraft observations when the effects of cloud microphysics, subgrid-scale gravity waves and convection are included. Following this approach, we examine the dynamical and microphysical control of TTL water vapor in the 30ºS-30ºN latitudinal belt and elucidate the dominant processes

  15. Decarbonation in an intracratonic setting: Insight from petrological-thermomechanical modeling

    Science.gov (United States)

    Gonzalez, Christopher M.; Gorczyk, Weronika

    2017-08-01

    Cratons form the stable core roots of the continental crust. Despite long-term stability, cratons have failed in the past. Cratonic destruction (e.g., North Atlantic Craton) due to chemical rejuvenation at the base of the lithosphere remains poorly constrained numerically. We use 2-D petrological-thermomechanical models to assess cratonic rifting characteristics and mantle CO2 degassing in the presence of a carbonated subcontinental lithospheric mantle (SCLM). We test two tectonothermal SCLM compositions: Archon (depleted) and Tecton (fertilized) using 2 CO2 wt % in the bulk composition to represent a metasomatized SCLM. We parameterize cratonic breakup via extensional duration (7-12 Ma; full breakup), tectonothermal age, TMoho (300-600°C), and crustal rheology. The two compositions with metasomatized SCLMs share similar rifting features and decarbonation trends during initial extension. However, we show long-term (>67 Ma) stability differences due to lithospheric density contrasts between SCLM compositions. The Tecton model shows convective removal and thinning of the metasomatized SCLM during failed rifting. The Archon composition remained stable, highlighting the primary role for SCLM density even when metasomatized at its base. In the short-term, three failed rifting characteristics emerge: failed rifting without decarbonation, failed rifting with decarbonation, and semifailed rifting with dry asthenospheric melting and decarbonation. Decarbonation trends were greatest in the failed rifts, reaching peak fluxes of 94 × 104 kg m-3. Increased TMoho did not alter the effects of rifting or decarbonation. Lastly, we show mantle regions where decarbonation, mantle melting in the presence of carbonate, and preservation of carbonated mantle occur during rifting.

  16. Biofuels, tax policies and oil prices in France: Insights from a dynamic CGE model

    International Nuclear Information System (INIS)

    Doumax, Virginie; Philip, Jean-Marc; Sarasa, Cristina

    2014-01-01

    The 2009 Renewable Energies Directive (RED) has set up ambitious targets concerning biofuel consumption in the European Union by 2020. Nevertheless, budgetary constraints and growing concerns about the environmental integrity of first-generation biofuels have imposed a phasing out of the fiscal instruments to promote them. Focusing on France, this paper combines an exogenous increase in oil prices and tax policies on fossil fuels. The objective is to determine the efficiency of an alternative incentive scheme for biodiesel consumption based on a higher price of the fossil fuel substitute. Policy simulations are implemented through a dynamic computable general equilibrium (CGE) model calibrated on 2009 French data. The results show that the 10% biodiesel mandate set by the RED would not be achieved even if the fixed taxes on diesel reach the same level as those on gasoline. Although integrating the rise in oil prices into the fiscal framework improves the biodiesel penetration rate, it remains below the target. Moreover, we find that the effects of biofuel consumption are limited to the biofuel chain sectors. In other agricultural sectors, the substitution effect of biodiesel with diesel is partially offset by the pricing effect induced by higher energy production costs. - Highlights: • We represent the French biodiesel production chain through a dynamic CGE model. • We examine the efficiency of alternative support schemes to biodiesel in France. • Ambitious targets require substantial additional taxes on diesel and rising oil prices. • Spillover effects are limited to the biodiesel chain sectors. • Energy-intensive sectors suffer from higher production costs

  17. Homology modeling and protein engineering of alkane monooxygenase in Burkholderia thailandensis MSMB121: in silico insights.

    Science.gov (United States)

    Jain, Chakresh Kumar; Gupta, Money; Prasad, Yamuna; Wadhwa, Gulshan; Sharma, Sanjeev Kumar

    2014-07-01

    The degradation of hydrocarbons plays an important role in the eco-balancing of petroleum products, pesticides and other toxic products in the environment. The degradation of hydrocarbons by microbes such as Geobacillus thermodenitrificans, Burkhulderia, Gordonia sp. and Acinetobacter sp. has been studied intensively in the literature. The present study focused on the in silico protein engineering of alkane monooxygenase (ladA)-a protein involved in the alkane degradation pathway. We demonstrated the improvement in substrate binding energy with engineered ladA in Burkholderia thailandensis MSMB121. We identified an ortholog of ladA monooxygenase found in B. thailandensis MSMB121, and showed it to be an enzyme involved in an alkane degradation pathway studied extensively in Geobacillus thermodenitrificans. Homology modeling of the three-dimensional structure of ladA was performed with a crystal structure (protein databank ID: 3B9N) as a template in MODELLER 9v11, and further validated using PROCHECK, VERIFY-3D and WHATIF tools. Specific amino acids were substituted in the region corresponding to amino acids 305-370 of ladA protein, resulting in an enhancement of binding energy in different alkane chain molecules as compared to wild protein structures in the docking experiments. The substrate binding energy with the protein was calculated using Vina (Implemented in VEGAZZ). Molecular dynamics simulations were performed to study the dynamics of different alkane chain molecules inside the binding pockets of wild and mutated ladA. Here, we hypothesize an improvement in binding energies and accessibility of substrates towards engineered ladA enzyme, which could be further facilitated for wet laboratory-based experiments for validation of the alkane degradation pathway in this organism.

  18. Cardio-respiratory development in bird embryos: new insights from a venerable animal model

    Directory of Open Access Journals (Sweden)

    Warren W. Burggren

    Full Text Available ABSTRACT The avian embryo is a time-honored animal model for understanding vertebrate development. A key area of extensive study using bird embryos centers on developmental phenotypic plasticity of the cardio-respiratory system and how its normal development can be affected by abiotic factors such as temperature and oxygen availability. Through the investigation of the plasticity of development, we gain a better understanding of both the regulation of the developmental process and the embryo's capacity for self-repair. Additionally, experiments with abiotic and biotic stressors during development have helped delineate not just critical windows for avian cardio-respiratory development, but the general characteristics (e.g., timing and dose-dependence of critical windows in all developing vertebrates. Avian embryos are useful in exploring fetal programming, in which early developmental experiences have implications (usually negative later in life. The ability to experimentally manipulate the avian embryo without the interference of maternal behavior or physiology makes it particularly useful in future studies of fetal programming. The bird embryo is also a key participant in studies of transgenerational epigenetics, whether by egg provisioning or effects on the germline that are transmitted to the F1 generation (or beyond. Finally, the avian embryo is heavily exploited in toxicology, in which both toxicological testing of potential consumer products as well as the consequences of exposure to anthropogenic pollutants are routinely carried out in the avian embryo. The avian embryo thus proves useful on numerous experimental fronts as an animal model that is concurrently both of adequate complexity and sufficient simplicity for probing vertebrate cardio-respiratory development.

  19. Looking back to move forward on model validation: insights from a global model of agricultural land use

    International Nuclear Information System (INIS)

    Baldos, Uris Lantz C; Hertel, Thomas W

    2013-01-01

    Global agricultural models are becoming indispensable in the debate over climate change impacts and mitigation policies. Therefore, it is becoming increasingly important to validate these models and identify critical areas for improvement. In this letter, we illustrate both the opportunities and the challenges in undertaking such model validation, using the SIMPLE model of global agriculture. We look back at the long run historical period 1961–2006 and, using a few key historical drivers—population, incomes and total factor productivity—we find that SIMPLE is able to accurately reproduce historical changes in cropland use, crop price, crop production and average crop yields at the global scale. Equally important is our investigation into how the specific assumptions embedded in many agricultural models will likely influence these results. We find that those global models which are largely biophysical—thereby ignoring the price responsiveness of demand and supply—are likely to understate changes in crop production, while failing to capture the changes in cropland use and crop price. Likewise, global models which incorporate economic responses, but do so based on limited time series estimates of these responses, are likely to understate land use change and overstate price changes. (letter)

  20. The Nucleation and Propagation of Thrust Ramps: Insights from Quantitative Analysis of Frictional Analog (Sandbox) Models

    Science.gov (United States)

    Sen, P.; Haq, S. S.; Marshak, S.

    2012-12-01

    Particle Imaging Velocimetry (PIV) provides a unique opportunity to analyze deformation in sandbox analog models at a scale that allows documentation of movement within and around individual shear structures. We employed PIV analysis to quantify deformation in sandbox experiments designed to simulate the initiation of thrust ramps developed during crustal shortening (i.e., contractional deformation). Our intent was to answer a long-standing question: Do ramps initiate at the tip of a detachment, or do they initiate in the interior of a deforming layer and propagate up-dip and down-dip until they link to the detachment at a location to the hinterland of the detachment's tip line? Most geometric studies of ramp-flat geometries in fold-thrust belts assume that ramps propagate up-dip from the tip of the detachment, and grow only in one direction. Field studies, in contrast, reveal that layer-parallel shortening structures develop to the foreland of the last ramp to form, suggesting that ramps initiate in a thrust sheet that has already undergone displacement above a detachment. Published sandbox models, using color-sand marker layers, support this idea. To test this idea further, we set up a model using a 3 m-long by 0.31-m wide glass-walled sandbox with a rigid backstop. The sand layer was sifted onto a sheet of mylar that could be pulled beneath the rigid backstop. Sand used in our experiments consisted of <250 μm-diameter grains. We carried out multiple runs using 4 cm, 5 cm and 6 cm-thick layers. Images were acquired over 1 mm displacement intervals using an 18 mega-pixel camera. By moving the camera at specific steps during the experiment, we sampled the development of several thrust ramps. The images taken during experimental runs were analyzed with a MATLAB-based program called 'PIV LAB' that utilizes an image cross-correlation subroutine to determine displacement fields of the sand particles. Our results demonstrate that: (1) thrust ramps initiate within the

  1. From regional pulse vaccination to global disease eradication: insights from a mathematical model of poliomyelitis.

    Science.gov (United States)

    Browne, Cameron J; Smith, Robert J; Bourouiba, Lydia

    2015-07-01

    Mass-vaccination campaigns are an important strategy in the global fight against poliomyelitis and measles. The large-scale logistics required for these mass immunisation campaigns magnifies the need for research into the effectiveness and optimal deployment of pulse vaccination. In order to better understand this control strategy, we propose a mathematical model accounting for the disease dynamics in connected regions, incorporating seasonality, environmental reservoirs and independent periodic pulse vaccination schedules in each region. The effective reproduction number, Re, is defined and proved to be a global threshold for persistence of the disease. Analytical and numerical calculations show the importance of synchronising the pulse vaccinations in connected regions and the timing of the pulses with respect to the pathogen circulation seasonality. Our results indicate that it may be crucial for mass-vaccination programs, such as national immunisation days, to be synchronised across different regions. In addition, simulations show that a migration imbalance can increase Re and alter how pulse vaccination should be optimally distributed among the patches, similar to results found with constant-rate vaccination. Furthermore, contrary to the case of constant-rate vaccination, the fraction of environmental transmission affects the value of Re when pulse vaccination is present.

  2. Pharmacologic approaches to cerebral aging and neuroplasticity: insights from the stroke model.

    Science.gov (United States)

    Chollet, François

    2013-03-01

    Brain plasticity is an intrinsic characteristic of the nervous system that allows continuous remodeling of brain functions in pathophysiological conditions. Although normal aging is associated with morphological modifications and decline of cerebral functions, brain plasticity is at least partially preserved in elderly individuals. A growing body of evidence supports the notion that cognitive enrichment and aerobic training induce a dynamic reorganization of higher cerebral functions, thereby helping to maintain operational skills in the elderly and reducing the incidence of dementia. The stroke model clearly shows that spontaneous brain plasticity exists after a lesion, even in old patients, and that it can be modulated through external factors like rehabilitation and drugs. Whether drugs can be used with the aim of modulating the effects of physical training or cognitive stimulation in healthy aged people has not been addressed until now. The risk:benefit ratio will be the key question with regard to the ethical aspect of this challenge. We review in this article the main aspects of human brain plasticity as shown in patients with stroke, the drug modulation of brain plasticity and its consequences on recovery, and finally we address the question of the influence of aging on brain plasticity.

  3. Assessing the potential for fish predation to impact zebra mussels (Dreissena polymorpha): Insight from bioenergetics models

    Science.gov (United States)

    Eggleton, M.A.; Miranda, L.E.; Kirk, J.P.

    2004-01-01

    Rates of annual food consumption and biomass were modeled for several fish species across representative rivers and lakes in eastern North America. Results were combined to assess the relative potential of fish predation to impact zebra mussels (Dreissena polymorpha). Predicted annual food consumption by fishes in southern waters was over 100% greater than that in northern systems because of warmer annual water temperatures and presumed increases in metabolic demand. Although generally increasing with latitude, biomasses of several key zebra mussel fish predators did not change significantly across latitudes. Biomasses of some less abundant fish predators did increase significantly with latitude, but increases were not of the magnitude to offset predicted decreases in food consumption. Our results generally support the premise that fishes in rivers and lakes of the southern United States (U.S.) have inherently greater potential to impact zebra mussels by predation. Our simulations may provide a partial explanation of why zebra mussel invasions have not been as rapid and widespread in southern U.S. waters compared to the Great Lakes region. ?? Blackwell Munksgaard, 2004.

  4. Neural mechanisms regulating different forms of risk-related decision-making: Insights from animal models.

    Science.gov (United States)

    Orsini, Caitlin A; Moorman, David E; Young, Jared W; Setlow, Barry; Floresco, Stan B

    2015-11-01

    Over the past 20 years there has been a growing interest in the neural underpinnings of cost/benefit decision-making. Recent studies with animal models have made considerable advances in our understanding of how different prefrontal, striatal, limbic and monoaminergic circuits interact to promote efficient risk/reward decision-making, and how dysfunction in these circuits underlies aberrant decision-making observed in numerous psychiatric disorders. This review will highlight recent findings from studies exploring these questions using a variety of behavioral assays, as well as molecular, pharmacological, neurophysiological, and translational approaches. We begin with a discussion of how neural systems related to decision subcomponents may interact to generate more complex decisions involving risk and uncertainty. This is followed by an overview of interactions between prefrontal-amygdala-dopamine and habenular circuits in regulating choice between certain and uncertain rewards and how different modes of dopamine transmission may contribute to these processes. These data will be compared with results from other studies investigating the contribution of some of these systems to guiding decision-making related to rewards vs. punishment. Lastly, we provide a brief summary of impairments in risk-related decision-making associated with psychiatric disorders, highlighting recent translational studies in laboratory animals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. A possible role for the immune system in adult neurogenesis: new insights from an invertebrate model.

    Science.gov (United States)

    Harzsch, Steffen; von Bohlen Und Halbach, Oliver

    2016-04-01

    Persistent neurogenesis in the adult brain of both vertebrates and invertebrates was previously considered to be driven by self-renewing neuronal stem cells of ectodermal origin. Recent findings in an invertebrate model challenge this view and instead provide evidence for a recruitment of neuronal precursors from a non-neuronal source. In the brain of adult crayfish, a neurogenic niche was identified that contributes progeny to the adult central olfactory pathway. The niche may function in attracting cells from the hemolymph and transforming them into cells with a neuronal fate. This finding implies that the first-generation neuronal precursors located in the crayfish neurogenic niche are not self-renewing. Evidence is summarized in support of a critical re-evaluation of long-term self-renewal of mammalian neuronal stem cells. Latest findings suggest that a tight link between the immune system and the system driving adult neurogenesis may not only exist in the crayfish but also in mammals. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. A three-compartment model for micropollutants sorption in sludge: methodological approach and insights.

    Science.gov (United States)

    Barret, Maialen; Patureau, Dominique; Latrille, Eric; Carrère, Hélène

    2010-01-01

    In sludge resulting from wastewater treatment, organic micropollutants sorb to particles and to dissolved/colloidal matter (DCM). Both interactions may influence their physical and biological fate throughout the wastewater treatment processes. To our knowledge, sludge has never been considered as a three-compartment matrix, in which micropollutants coexist in three states: freely dissolved, sorbed-to-particles and sorbed-to-DCM. A methodology is proposed to concomitantly determine equilibrium constants of sorption to particles (K(part)) and to DCM (K(DCM)). Polycyclic Aromatic Hydrocarbons (PAHs) were chosen as model compounds for the experiments. The logarithm of estimated equilibrium constants ranged from 3.1 to 4.3 and their usual correlation to PAH hydrophobicity was verified. Moreover, PAH affinities for particles and for DCM could be compared. Affinity for particles was found to be stronger, probably due to their physical and chemical characteristics. This work provided a useful tool to assess the freely dissolved, sorbed-to-particles and sorbed-to-DCM concentrations of contaminants, which are necessary to accurately predict their fate. Besides, guidelines to investigate the link between sorption and the fundamental concept of bioavailability were proposed. (c) 2009 Elsevier Ltd. All rights reserved.

  7. Crude oil market efficiency and modeling. Insights from the multiscaling autocorrelation pattern

    International Nuclear Information System (INIS)

    Alvarez-Ramirez, Jose; Alvarez, Jesus; Solis, Ricardo

    2010-01-01

    Empirical research on market inefficiencies focuses on the detection of autocorrelations in price time series. In the case of crude oil markets, statistical support is claimed for weak efficiency over a wide range of time-scales. However, the results are still controversial since theoretical arguments point to deviations from efficiency as prices tend to revert towards an equilibrium path. This paper studies the efficiency of crude oil markets by using lagged detrended fluctuation analysis (DFA) to detect delay effects in price autocorrelations quantified in terms of a multiscaling Hurst exponent (i.e., autocorrelations are dependent of the time scale). Results based on spot price data for the period 1986-2009 indicate important deviations from efficiency associated to lagged autocorrelations, so imposing the random walk for crude oil prices has pronounced costs for forecasting. Evidences in favor of price reversion to a continuously evolving mean underscores the importance of adequately incorporating delay effects and multiscaling behavior in the modeling of crude oil price dynamics. (author)

  8. Crude oil market efficiency and modeling. Insights from the multiscaling autocorrelation pattern

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez-Ramirez, Jose [Departamento de Ingenieria de Procesos e Hidraulica, Universidad Autonoma Metropolitana-Iztapalapa, Apartado Postal 55-534, Mexico D.F., 09340 (Mexico); Departamento de Economia, Universidad Autonoma Metropolitana-Iztapalapa, Apartado Postal 55-534, Mexico D.F., 09340 (Mexico); Alvarez, Jesus [Departamento de Ingenieria de Procesos e Hidraulica, Universidad Autonoma Metropolitana-Iztapalapa, Apartado Postal 55-534, Mexico D.F., 09340 (Mexico); Solis, Ricardo [Departamento de Economia, Universidad Autonoma Metropolitana-Iztapalapa, Apartado Postal 55-534, Mexico D.F., 09340 (Mexico)

    2010-09-15

    Empirical research on market inefficiencies focuses on the detection of autocorrelations in price time series. In the case of crude oil markets, statistical support is claimed for weak efficiency over a wide range of time-scales. However, the results are still controversial since theoretical arguments point to deviations from efficiency as prices tend to revert towards an equilibrium path. This paper studies the efficiency of crude oil markets by using lagged detrended fluctuation analysis (DFA) to detect delay effects in price autocorrelations quantified in terms of a multiscaling Hurst exponent (i.e., autocorrelations are dependent of the time scale). Results based on spot price data for the period 1986-2009 indicate important deviations from efficiency associated to lagged autocorrelations, so imposing the random walk for crude oil prices has pronounced costs for forecasting. Evidences in favor of price reversion to a continuously evolving mean underscores the importance of adequately incorporating delay effects and multiscaling behavior in the modeling of crude oil price dynamics. (author)

  9. Nile Red Staining for Oil Determination in Microalgal Cells: A New Insight through Statistical Modelling

    Directory of Open Access Journals (Sweden)

    Ronald Halim

    2015-01-01

    Full Text Available In the wake of global warming and rapid fossil fuel depletion, microalgae emerge as promising feedstocks for sustainable biofuel production. Nile red staining acts as a rapid diagnostic tool to measure the amount of biodiesel-convertible lipid that the cells accumulate. There is a need for the development of a more uniform staining procedure. In its first phase, this study examined the dependence of microalgal Nile red fluorescence (Tetraselmis suecica in terms of its most pertinent staining variables. A quadratic surface model that successfully described the Nile red fluorescence intensity as a composite function of its variables was generated (r2=0.86. Cell concentration was shown to have a significant effect on the fluorescence intensity. Up to a certain threshold, fluorescence intensity was shown to increase with Nile red dye concentration. In its second phase, the study reviewed findings from previous Nile red studies to elucidate some of the fundamental mechanism underlying the diffusion of Nile red dye molecules into the microalgal cells and their subsequent interaction with intracellular lipids. Through the review process, we were able to develop a simple framework that provided a set of guidelines for the standardization of the Nile red staining procedure across different microalgal species.

  10. Helium behavior in oxide dispersion strengthened (ODS) steel: Insights from ab initio modeling

    Science.gov (United States)

    Sun, Dan; Li, Ruihuan; Ding, Jianhua; Huang, Shaosong; Zhang, Pengbo; Lu, Zheng; Zhao, Jijun

    2018-02-01

    Using first-principles calculations, we systemically investigate the energetics and stability behavior of helium (He) atoms and small Hen (n = 2-4) clusters inside oxide dispersion strengthened (ODS) steel, as well as the incorporation of large amount of He atoms inside Y2O3 crystal. From the energetic point of view, He atom inside Y2O3 cluster is most stable, followed by the interstitial sites at the α-Fe/Y2O3 interface, and the tetrahedral interstitial sites inside α-Fe region. We further consider Hen (n = 2-4) clusters at the tetrahedral interstitial site surrounded by four Y atoms, which is the most stable site in the ODS steel model. The incorporation energies of all these Hen clusters are lower than that of single He atom in α-Fe, while the binding energy between two He atoms is relatively small. With insertion of 15 He atoms into 80-atom unit cell of Y2O3 crystal, the incorporation energy of He atoms is still lower than that of He4 cluster in α-Fe crystal. These theoretical results suggest that He atoms tend to aggregate inside Y2O3 clusters or at the α-Fe/Y2O3 interface, which is beneficial to prevent the He embrittlement in ODS steels.

  11. Welfare Effects of Water Variability in Agriculture. Insights from a Multimarket Model

    Directory of Open Access Journals (Sweden)

    Roberto Ponce

    2015-06-01

    Full Text Available The purpose of this research is to assess the welfare effects of climate change on the Chilean agricultural sector, with special focus on changes in water availability. The productive impacts of climate change on the agricultural sector are well analyzed at both a global and national level. There is, however, a lack of evidence about the aggregated impacts, considering both demand and supply. This study tries to fill this gap by using a multimarket model, specifically designed for the Chilean agricultural sector. According to our results, changes in water availability will have modest welfare impacts, with an average decrease of total surplus of 4.3%, minor price changes (around −1%, and no significant impacts on total agricultural land. Despite the small aggregated effects, it is expected that climate change will have uneven consequences across regions and activities. For instance, even though the southern zone (zone 3 shows the smallest income changes −14% (average, the impacts within the zone range from 1% to 52% decrease in agricultural net income. This situation suggests large distributional consequences of climate change for the Chilean agricultural sector.

  12. Where does subduction initiate and die? Insights from global convection models with continental drift

    Science.gov (United States)

    Ulvrova, Martina; Williams, Simon; Coltice, Nicolas; Tackley, Paul

    2017-04-01

    Plate tectonics is a prominent feature on Earth. Together with the underlying convecting mantle, plates form a self-organized system. In order to understand the dynamics of the coupled system, subduction of the lithospheric plates plays the key role since it links the exterior with the interior of the planet. In this work we study subduction initiation and death with respect to the position of the continental rafts. Using thermo-mechanical numerical calculations we investigate global convection models featuring self-consistent plate tectonics and continental drifting employing a pseudo-plastic rheology and testing the effect of a free surface. We consider uncompressible mantle convection in Boussinesq approximation that is basaly and internaly heated. Our calculations indicate that the presence of the continents alterns stress distribution within a certain distance from the margins. Intra-oceanic subudction initiation is favorable during super-continent cycles while the initiation at passive continental margin prevails when continents are dispersed. The location of subduction initiation is additionally controlled by the lithospheric strength. Very weak lithosphere results in domination of intra-oceanic subduction initiation. The subduction zones die more easily in the vicinity of the continent due to the strong rheological contrast between the oceanic and continental lithosphere. In order to compare our findings with subduction positions through time recorded on Earth, we analyse subduction birth in global plate reconstruction back to 410 My.

  13. The retinal phenotype of Usher syndrome: pathophysiological insights from animal models.

    Science.gov (United States)

    El-Amraoui, Aziz; Petit, Christine

    2014-03-01

    The Usher syndrome (USH) is the most prevalent cause of inherited deaf-blindness. Three clinical subtypes, USH1-3, have been defined, and ten USH genes identified. The hearing impairment due to USH gene defects has been shown to result from improper organisation of the hair bundle, the sound receptive structure of sensory hair cells. In contrast, the cellular basis of the visual defect is less well understood as this phenotype is absent in almost all the USH mouse models that faithfully mimic the human hearing impairment. Structural and molecular interspecies discrepancies regarding photoreceptor calyceal processes and the association with the distribution of USH1 proteins have recently been unravelled, and have led to the conclusion that a defect in the USH1 protein complex-mediated connection between the photoreceptor outer segment and the surrounding calyceal processes (in both rods and cones), and the inner segment (in rods only), probably causes the USH1 retinal dystrophy in humans. Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  14. Naringenin improves learning and memory in an Alzheimer's disease rat model: Insights into the underlying mechanisms.

    Science.gov (United States)

    Ghofrani, Saeed; Joghataei, Mohammad-Taghi; Mohseni, Simin; Baluchnejadmojarad, Tourandokht; Bagheri, Maryam; Khamse, Safoura; Roghani, Mehrdad

    2015-10-05

    Alzheimer's disease (AD) is one of the prevalent neurological disorders of the central nervous system hallmarked by increased beta-amyloid (Aβ) deposition and ensuing learning and memory deficit. In the present study, the beneficial effect of naringenin on improvement of learning and memory was evaluated in an Alzheimer's disease rat model. The Aβ-injected rats showed a lower alternation score in Y-maze task, impairment of retention and recall capability in passive avoidance test, and lower correct choices and higher errors in radial arm maze (RAM) task as compared to sham group in addition to enhanced oxidative stress and apoptosis. Naringenin, but not a combination of naringenin and fulvestrant (an estrogenic receptor antagonist) significantly improved the performance of Aβ-injected rats in passive avoidance and RAM tasks. Naringenin pretreatment of Aβ-injected rats also lowered hippocampal malondialdehyde (MDA) with no significant effect on nitrite and superoxide dismutase (SOD) activity in addition to lowering apoptosis. These results suggest naringenin pretreatment attenuates Aβ-induced impairment of learning and memory through mitigation of lipid peroxidation and apoptosis and its beneficial effect is somewhat mediated via estrogenic pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody Transport

    Directory of Open Access Journals (Sweden)

    Yanqun Xu

    2017-01-01

    Full Text Available Pregnant women are at high risk for infection by pathogens. Vertical transmission of infectious agents, such as Zika, hepatitis B, and cytomegalovirus during pregnancy, remains a public health problem, associated with dire outcomes for the neonate. Thus, a safe prophylactic and therapeutic approach for protecting the mother and the neonate from infections remains a high priority. Our work is focused on better understanding the safety and efficacy determinants of IgG antibody preparations when used during pregnancy to benefit the mother and her baby. Using pregnant guinea pigs, we demonstrated that biodistribution of administered IgG to the fetus increases with gestation and results in lower maternal and higher fetal antibody concentrations as pregnancy progresses. Data suggests that partition of antibody immunotherapy to the fetal compartment may contribute to a lower maternal exposure (as measured by the AUC and a shorter mean residence time of the IgG therapeutic at the end of pregnancy compared to nonpregnant age-matched controls, irrespective of the administered dose. Our studies provide insights on the importance of selecting an efficacious dose in pregnancy that takes into account IgG biodistribution to the fetus. The use of appropriate animal models of placental transfer and infectious disease during pregnancy would facilitate pharmacokinetic modeling to derive a starting dose in clinical trials.

  16. Impact of a Cosmic Body into Earth's Ocean and the Generation of Large Tsunami Waves: Insight from Numerical Modeling

    Science.gov (United States)

    Wünnemann, K.; Collins, G. S.; Weiss, R.

    2010-12-01

    The strike of a cosmic body into a marine environment differs in several respects from impact on land. Oceans cover approximately 70% of the Earth's surface, implying not only that oceanic impact is a very likely scenario for future impacts but also that most impacts in Earth's history must have happened in marine environments. Therefore, the study of oceanic impact is imperative in two respects: (1) to quantify the hazard posed by future oceanic impacts, including the potential threat of large impact-generated tsunami-like waves, and (2) to reconstruct Earth's impact record by accounting for the large number of potentially undiscovered crater structures in the ocean crust. Reconstruction of the impact record is of crucial importance both for assessing the frequency of collision events in the past and for better predicting the probability of future impact. We summarize the advances in the study of oceanic impact over the last decades and focus in particular on how numerical models have improved our understanding of cratering in the oceanic environment and the generation of waves by impact. We focus on insight gleaned from numerical modeling studies into the deceleration of the projectile by the water, cratering of the ocean floor, the late stage modification of the crater due to gravitational collapse, and water resurge. Furthermore, we discuss the generation and propagation of large tsunami-like waves as a result of a strike of a cosmic body in marine environments.

  17. Insight into the Am-O Phase Equilibria: A Thermodynamic Study Coupling High-Temperature XRD and CALPHAD Modeling.

    Science.gov (United States)

    Epifano, Enrica; Guéneau, Christine; Belin, Renaud C; Vauchy, Romain; Lebreton, Florent; Richaud, Jean-Christophe; Joly, Alexis; Valot, Christophe; Martin, Philippe M

    2017-07-03

    In the frame of minor actinide transmutation, americium can be diluted in UO 2 and (U, Pu)O 2 fuels burned in fast neutron reactors. The first mandatory step to foresee the influence of Am on the in-reactor behavior of transmutation targets or fuel is to have fundamental knowledge of the Am-O binary system and, in particular, of the AmO 2-x phase. In this study, we coupled HT-XRD (high-temperature X-ray diffraction) experiments with CALPHAD thermodynamic modeling to provide new insights into the structural properties and phase equilibria in the AmO 2-x -AmO 1.61+x -Am 2 O 3 domain. Because of this approach, we were able for the first time to assess the relationships between temperature, lattice parameter, and hypostoichiometry for fcc AmO 2-x . We showed the presence of a hyperstoichiometric existence domain for the bcc AmO 1.61+x phase and the absence of a miscibility gap in the fcc AmO 2-x phase, contrary to previous representations of the phase diagram. Finally, with the new experimental data, a new CALPHAD thermodynamic model of the Am-O system was developed, and an improved version of the phase diagram is presented.

  18. Full-length model of the human galectin-4 and insights into dynamics of inter-domain communication

    Science.gov (United States)

    Rustiguel, Joane K.; Soares, Ricardo O. S.; Meisburger, Steve P.; Davis, Katherine M.; Malzbender, Kristina L.; Ando, Nozomi; Dias-Baruffi, Marcelo; Nonato, Maria Cristina

    2016-09-01

    Galectins are proteins involved in diverse cellular contexts due to their capacity to decipher and respond to the information encoded by β-galactoside sugars. In particular, human galectin-4, normally expressed in the healthy gastrointestinal tract, displays differential expression in cancerous tissues and is considered a potential drug target for liver and lung cancer. Galectin-4 is a tandem-repeat galectin characterized by two carbohydrate recognition domains connected by a linker-peptide. Despite their relevance to cell function and pathogenesis, structural characterization of full-length tandem-repeat galectins has remained elusive. Here, we investigate galectin-4 using X-ray crystallography, small- and wide-angle X-ray scattering, molecular modelling, molecular dynamics simulations, and differential scanning fluorimetry assays and describe for the first time a structural model for human galectin-4. Our results provide insight into the structural role of the linker-peptide and shed light on the dynamic characteristics of the mechanism of carbohydrate recognition among tandem-repeat galectins.

  19. Assessing surface water flood risk and management strategies under future climate change: Insights from an Agent-Based Model.

    Science.gov (United States)

    Jenkins, K; Surminski, S; Hall, J; Crick, F

    2017-10-01

    Climate change and increasing urbanization are projected to result in an increase in surface water flooding and consequential damages in the future. In this paper, we present insights from a novel Agent Based Model (ABM), applied to a London case study of surface water flood risk, designed to assess the interplay between different adaptation options; how risk reduction could be achieved by homeowners and government; and the role of flood insurance and the new flood insurance pool, Flood Re, in the context of climate change. The analysis highlights that while combined investment in property-level flood protection and sustainable urban drainage systems reduce surface water flood risk, the benefits can be outweighed by continued development in high risk areas and the effects of climate change. In our simulations, Flood Re is beneficial in its function to provide affordable insurance, even under climate change. However, the scheme does face increasing financial pressure due to rising surface water flood damages. If the intended transition to risk-based pricing is to take place then a determined and coordinated strategy will be needed to manage flood risk, which utilises insurance incentives, limits new development, and supports resilience measures. Our modelling approach and findings are highly relevant for the ongoing regulatory and political approval process for Flood Re as well as for wider discussions on the potential of insurance schemes to incentivise flood risk management and climate adaptation in the UK and internationally. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The Morphological Characteristics and Mechanical Formation of Giant Radial Dike Swarms on Venus: An Overview Emphasizing Recent Numerical Modeling Insights

    Science.gov (United States)

    McGovern, P. J., Jr.; Grosfils, E. B.; Le Corvec, N.; Ernst, R. E.; Galgana, G. A.

    2017-12-01

    Over 200 giant radial dike swarms have been identified on Venus using Magellan data, yielding insight into morphological characteristics long since erased by erosion and other processes on Earth. Since such radial dike systems are typically associated with magma reservoirs, large volcanoes and/or larger-scale plume activity—and because dike geometry reflects stress conditions at the time of intrusion—assessing giant radial dike formation in the context of swarm morphology can place important constraints upon this fundamental volcanotectonic process. Recent numerical models reveal that, contrary to what is reported in much of the published literature, it is not easy, mechanically, to produce either large or small radial dike systems. After extensive numerical examination of reservoir inflation, however, under conditions ranging from a simple halfspace to complex flexural loading, we have thus far identified four scenarios that produce radial dike systems. Two of these scenarios yield dike systems akin to those often associated with shield and stratocone volcanoes on Earth, while the other two, our focus here, are more consistent with the giant radial dike system geometries catalogued on Venus. In this presentation we will (a) review key morphological characteristics of the giant radial systems identified on Venus, (b) briefly illustrate why it is not easy, mechanically, to produce a radial dike system, (c) present the two volcanological circumstances we have identified that do allow a giant radial dike system to form, and (d) discuss current model limitations and potentially fruitful directions for future research.

  1. New insights into the 2012 Emilia (Italy) seismic sequence through advanced numerical modeling of ground deformation InSAR measurements

    Science.gov (United States)

    Tizzani, P.; Castaldo, R.; Solaro, G.; Pepe, S.; Bonano, M.; Casu, F.; Manunta, M.; Manzo, M.; Pepe, A.; Samsonov, S.; Lanari, R.; Sansosti, E.

    2013-05-01

    We provide new insights into the two main seismic events that occurred in 2012 in the Emilia region, Italy. We extend the results from previous studies based on analytical inversion modeling of GPS and RADARSAT-1 InSAR measurements by exploiting RADARSAT-2 data. Moreover, we benefit from the available large amount of geological and geophysical information through finite element method (FEM) modeling implemented in a structural-mechanical context to investigate the impact of known buried structures on the modulation of the ground deformation field. We find that the displacement pattern associated with the 20 May event is consistent with the activation of a single fault segment of the inner Ferrara thrust, in good agreement with the analytical solution. In contrast, the interpretation of the 29 May episode requires the activation of three different fault segments and a block roto-translation of the Mirandola anticline. The proposed FEM-based methodology is applicable to other seismic areas where the complexity of buried structures is known and plays a fundamental role in the modulation of the associated surface deformation pattern.

  2. Simulations of CYP51A from Aspergillus fumigatus in a model bilayer provide insights into triazole drug resistance.

    Science.gov (United States)

    Nash, Anthony; Rhodes, Johanna

    2018-04-01

    Azole antifungal drugs target CYP51A in Aspergillus fumigatus by binding with the active site of the protein, blocking ergosterol biosynthesis. Resistance to azole antifungal drugs is now common, with a leucine to histidine amino acid substitution at position 98 the most frequent, predominantly conferring resistance to itraconazole, although cross-resistance has been reported in conjunction with other mutations. In this study, we create a homology model of CYP51A using a recently published crystal structure of the paralog protein CYP51B. The derived structures, wild type, and L98H mutant are positioned within a lipid membrane bilayer and subjected to molecular dynamics simulations in order improve the accuracy of both models. The structural analysis from our simulations suggests a decrease in active site surface from the formation of hydrogen bonds between the histidine substitution and neighboring polar side chains, potentially preventing the binding of azole drugs. This study yields a biologically relevant structure and set of dynamics of the A. fumigatus Lanosterol 14 alpha-demethylase enzyme and provides further insight into azole antifungal drug resistance.

  3. Distribution modelling of pre-Columbian California grasslands with soil phytoliths: New insights for prehistoric grassland ecology and restoration.

    Science.gov (United States)

    Fick, Stephen E; Evett, Rand R

    2018-01-01

    Historical reconstructions of plant community distributions are useful for biogeographic studies and restoration planning, but the quality of insights gained depends on the depth and reliability of historical information available. For the Central Valley of California, one of the most altered terrestrial ecosystems on the planet, this task is particularly difficult given poor historical documentation and sparse relict assemblages of pre-invasion plant species. Coastal and interior prairies were long assumed to have been dominated by perennial bunchgrasses, but this hypothesis has recently been challenged. We evaluated this hypothesis by creating species distribution models (SDMs) using a novel approach based on the abundance of soil phytoliths (microscopic particles of biogenic silica used as a proxy for long-term grass presence) extracted from soil samples at locations statewide. Modeled historical grass abundance was consistently high along the coast and to a lesser extent in higher elevation foothills surrounding the Central Valley. SDMs found strong associations with mean temperature, temperature variability, and precipitation variability, with higher predicted abundance in regions with cooler, equable temperatures and moderated rainfall, mirroring the pattern for modern perennial grass distribution across the state. The results of this study strongly suggest that the pre-Columbian Central Valley of California was not dominated by grasses. Using soil phytolith data as input for SDMs is a promising new method for predicting the extent of prehistoric grass distributions where alternative historical datasets are lacking.

  4. Ovarian tumor attachment, invasion and vascularization reflect unique microenvironments in the peritoneum:Insights from xenograft and mathematical models

    Directory of Open Access Journals (Sweden)

    Mara P. Steinkamp

    2013-05-01

    Full Text Available Ovarian cancer relapse is often characterized by metastatic spread throughout the peritoneal cavity with tumors attached to multiple organs. In this study, interaction of ovarian tumor cells with the peritoneal tumor microenvironment was evaluated in a xenograft model based on intraperitoneal injection of fluorescent SKOV3.ip1 ovarian cancer cells. Intra-vital microscopy of mixed GFP-RFP cell populations injected into the peritoneum demonstrated that tumor cells aggregate and attach as mixed spheroids, emphasizing the importance of homotypic adhesion in tumor formation. Electron microscopy provided high resolution structural information about local attachment sites. Experimental measurements from the mouse model were used to build a three-dimensional cellular Potts ovarian tumor model (OvTM that examines ovarian tumor cell attachment, chemotaxis, growth and vascularization. OvTM simulations provide insight into the relative influence of tumor cell-cell adhesion, oxygen availability, and local architecture on tumor growth and morphology. Notably, tumors on the mesentery, omentum or spleen readily invade the open architecture, while tumors attached to the gut encounter barriers that restrict invasion and instead rapidly expand into the peritoneal space. Simulations suggest that rapid neovascularization of SKOV3.ip1 tumors is triggered by constitutive release of angiogenic factors in the absence of hypoxia. This research highlights the importance of cellular adhesion and tumor microenvironment in the seeding of secondary ovarian tumors on diverse organs within the peritoneal cavity. Results of the OvTM simulations indicate that invasion is strongly influenced by features underlying the mesothelial lining at different sites, but is also affected by local production of chemotactic factors. The integrated in vivo mouse model and computer simulations provide a unique platform for evaluating targeted therapies for ovarian cancer relapse.

  5. Understanding the unique biogeochemistry of the Mediterranean Sea: Insights from a coupled phosphorus and nitrogen model

    Science.gov (United States)

    Powley, Helen R.; Krom, Michael D.; Van Cappellen, Philippe

    2017-06-01

    The Mediterranean Sea (MS) is an oligotrophic basin whose offshore water column exhibits low dissolved inorganic phosphorus (P) and nitrogen (N) concentrations, unusually high nitrate (NO3) to phosphate (PO4) ratios, and distinct biogeochemical differences between the Western Mediterranean Sea (WMS) and Eastern Mediterranean Sea (EMS). A new mass balance model of P and N cycling in the WMS is coupled to a pre-existing EMS model to understand these biogeochemical features. Estimated land-derived inputs of reactive P and N to the WMS and EMS are similar per unit surface area, but marine inputs are 4 to 5 times greater for the WMS, which helps explain the approximately 3 times higher primary productivity of the WMS. The lateral inputs of marine sourced inorganic and organic P support significant fractions of new production in the WMS and EMS, similar to subtropical gyres. The mass balance calculations imply that the MS is net heterotrophic: dissolved organic P and N entering the WMS and EMS, primarily via the Straits of Gibraltar and Sicily, are mineralized to PO4 and NO3 and subsequently exported out of the basin by the prevailing anti-estuarine circulation. The high deepwater (DW) molar NO3:PO4 ratios reflect the high reactive N:P ratio of inputs to the WMS and EMS, combined with low denitrification rates. The lower DW NO3:PO4 ratio of the WMS (21) compared to the EMS (28) reflects lower reactive N:P ratios of inputs to the WMS, including the relatively low N:P ratio of Atlantic surface water flowing into the WMS.Plain Language SummaryThe Mediterranean Sea (MS) is a marine desert: it exhibits extremely low biological productivity despite being almost entirely surrounded by land with high nutrient loadings from a large coastal population. To explain this paradox, we analyze the sources and fate of the two main nutrient elements that support the production of marine biomass, phosphorus (P), and nitrogen (N). We find that the main source of P and N to the MS is inflow

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

    Science.gov (United States)

    Guo, Shaodong

    2014-01-01

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

  7. Insights into mechanisms of transmission and pathogenesis from transgenic mouse models of prion diseases

    Science.gov (United States)

    Moreno, Julie A.; Telling, Glenn C.

    2018-01-01

    Prions represent a new paradigm of protein-mediated information transfer. In the case of mammals, prions are the cause of fatal, transmissible neurodegenerative diseases, sometimes referred to as transmissible spongiform encephalopathies (TSE’s), which frequently occur as epidemics. An increasing body of evidence indicates that the canonical mechanism of conformational corruption of cellular prion protein (PrPC) by the pathogenic isoform (PrPSc) that is the basis of prion formation in TSE’s, is common to a spectrum of proteins associated with various additional human neurodegenerative disorders, including the more common Alzheimer’s and Parkinson’s diseases. The peerless infectious properties of TSE prions, and the unparalleled tools for their study, therefore enable elucidation of mechanisms of template-mediated conformational propagation that are generally applicable to these related disease states. Many unresolved issues remain including the exact molecular nature of the prion, the detailed cellular and molecular mechanisms of prion propagation, and the means by which prion diseases can be both genetic and infectious. In addition, we know little about the mechanism by which neurons degenerate during prion diseases. Tied to this, the physiological role of the normal form of the prion protein remains unclear and it is uncertain whether or not loss of this function contributes to prion pathogenesis. The factors governing the transmission of prions between species remain unclear, in particular the means by which prion strains and PrP primary structure interact to affect inter-species prion transmission. Despite all these unknowns, advances in our understanding of prions have occurred because of their transmissibility to experimental animals and the development of transgenic (Tg) mouse models has done much to further our understanding about various aspects of prion biology. In this review we will focus on advances in our understanding of prion biology that

  8. The seismic cycle at subduction thrusts: Insights from seismo-thermo-mechanical models

    KAUST Repository

    van Dinther, Y.

    2013-12-01

    The underestimation of the size of recent megathrust earthquakes illustrates our limited understanding of their spatiotemporal occurrence and governing physics. To unravel their relation to associated subduction dynamics and long-term deformation, we developed a 2-D continuum viscoelastoplastic model that uses an Eulerian-Lagrangian finite difference framework with similar on- and off-fault physics. We extend the validation of this numerical tool to a realistic subduction zone setting that resembles Southern Chile. The resulting quasi-periodic pattern of quasi-characteristic M8–M9 megathrust events compares quantitatively with observed recurrence and earthquake source parameters, albeit at very slow coseismic speeds. Without any data fitting, surface displacements agree with GPS data recorded before and during the 2010 M8.8 Maule earthquake, including the presence of a second-order flexural bulge. These surface displacements show cycle-to-cycle variations of slip deficits, which overall accommodate ∼5% of permanent internal shortening. We find that thermally (and stress) driven creep governs a spontaneous conditionally stable downdip transition zone between temperatures of ∼350°C and ∼450°C. Ruptures initiate above it (and below the forearc Moho), propagate within it, interspersed by small intermittent events, and arrest below it as ductile shearing relaxes stresses. Ruptures typically propagate upward along lithological boundaries and widen as pressures drop. The main thrust is constrained to be weak due to fluid-induced weakening required to sustain regular subduction and to generate events with natural characteristics (fluid pressures of ∼75–99% of solid pressures). The agreement with a range of seismological, geodetic, and geological observations demonstrates the validity and strength of this physically consistent seismo-thermo-mechanical approach.

  9. Precise control of polymer coated nanopores by nanoparticle additives: Insights from computational modeling

    Energy Technology Data Exchange (ETDEWEB)

    Eskandari Nasrabad, Afshin; Coalson, Rob D. [Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260 (United States); Jasnow, David [Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, Pennsylvania 15260 (United States); Zilman, Anton [Department of Physics, University of Toronto, Toronto, Ontario M5S 1A7 (Canada)

    2016-08-14

    Polymer-nanoparticle composites are a promising new class of materials for creation of controllable nano-patterned surfaces and nanopores. We use coarse-grained molecular dynamics simulations augmented with analytical theory to study the structural transitions of surface grafted polymer layers (brushes) induced by infiltration of nanoparticles that are attracted to the polymers in the layer. We systematically compare two different polymer brush geometries: one where the polymer chains are grafted to a planar surface and the other where the chains are grafted to the inside of a cylindrical nanochannel. We perform a comprehensive study of the effects of the material parameters such as the polymer chain length, chain grafting density, nanoparticle size, strength of attraction between nanoparticles and polymer monomers, and, in the case of the cylindrically grafted brush, the radius of the cylinder. We find a very general behavioral motif for all geometries and parameter values: the height of the polymer brush is non-monotonic in the nanoparticle concentration in solution. As the nanoparticle concentration increases, the brush height first decreases and after passing through a minimum value begins to increase, resulting in the swelling of the nanoparticle infused brush. These morphological features may be useful for devising tunable “smart” nano-devices whose effective dimensions can be reversibly and precisely adjusted by changing the nanoparticle concentration in solution. The results of approximate Self-Consistent Field Theory (SCFT) calculations, applicable in the regime of strong brush stretching, are compared to the simulation results. The SCFT calculations are found to be qualitatively, even semi-quantitatively, accurate when applied within their intended regime of validity, and provide a useful and efficient tool for modeling such materials.

  10. New insights into the properties of pubescent surfaces: peach fruit as a model.

    Science.gov (United States)

    Fernández, Victoria; Khayet, Mohamed; Montero-Prado, Pablo; Heredia-Guerrero, José Alejandro; Liakopoulos, Georgios; Karabourniotis, George; Del Río, Víctor; Domínguez, Eva; Tacchini, Ignacio; Nerín, Cristina; Val, Jesús; Heredia, Antonio

    2011-08-01

    The surface of peach (Prunus persica 'Calrico') is covered by a dense indumentum, which may serve various protective purposes. With the aim of relating structure to function, the chemical composition, morphology, and hydrophobicity of the peach skin was assessed as a model for a pubescent plant surface. Distinct physicochemical features were observed for trichomes versus isolated cuticles. Peach cuticles were composed of 53% cutan, 27% waxes, 23% cutin, and 1% hydroxycinnamic acid derivatives (mainly ferulic and p-coumaric acids). Trichomes were covered by a thin cuticular layer containing 15% waxes and 19% cutin and were filled by polysaccharide material (63%) containing hydroxycinnamic acid derivatives and flavonoids. The surface free energy, polarity, and work of adhesion of intact and shaved peach surfaces were calculated from contact angle measurements of water, glycerol, and diiodomethane. The removal of the trichomes from the surface increased polarity from 3.8% (intact surface) to 23.6% and decreased the total surface free energy chiefly due to a decrease on its nonpolar component. The extraction of waxes and the removal of trichomes led to higher fruit dehydration rates. However, trichomes were found to have a higher water sorption capacity as compared with isolated cuticles. The results show that the peach surface is composed of two different materials that establish a polarity gradient: the trichome network, which has a higher surface free energy and a higher dispersive component, and the cuticle underneath, which has a lower surface free energy and higher surface polarity. The significance of the data concerning water-plant surface interactions is discussed within a physiological context.

  11. Controls on the global distribution of contourite drifts: Insights from an eddy-resolving ocean model

    Science.gov (United States)

    Thran, Amanda C.; Dutkiewicz, Adriana; Spence, Paul; Müller, R. Dietmar

    2018-05-01

    Contourite drifts are anomalously high sediment accumulations that form due to reworking by bottom currents. Due to the lack of a comprehensive contourite database, the link between vigorous bottom water activity and drift occurrence has yet to be demonstrated on a global scale. Using an eddy-resolving ocean model and a new georeferenced database of 267 contourites, we show that the global distribution of modern contourite drifts strongly depends on the configuration of the world's most powerful bottom currents, many of which are associated with global meridional overturning circulation. Bathymetric obstacles frequently modify flow direction and intensity, imposing additional finer-scale control on drift occurrence. Mean bottom current speed over contourite-covered areas is only slightly higher (2.2 cm/s) than the rest of the global ocean (1.1 cm/s), falling below proposed thresholds deemed necessary to re-suspend and redistribute sediments (10-15 cm/s). However, currents fluctuate more frequently and intensely over areas with drifts, highlighting the role of intermittent, high-energy bottom current events in sediment erosion, transport, and subsequent drift accumulation. We identify eddies as a major driver of these bottom current fluctuations, and we find that simulated bottom eddy kinetic energy is over three times higher in contourite-covered areas in comparison to the rest of the ocean. Our work supports previous hypotheses which suggest that contourite deposition predominantly occurs due to repeated acute events as opposed to continuous reworking under average-intensity background flow conditions. This suggests that the contourite record should be interpreted in terms of a bottom current's susceptibility to experiencing periodic, high-speed current events. Our results also highlight the potential role of upper ocean dynamics in contourite sedimentation through its direct influence on deep eddy circulation.

  12. Eruption cycles in a basaltic andesite system: insights from numerical modeling

    Science.gov (United States)

    Smekens, J. F.; Clarke, A. B.; De'Michieli Vitturi, M.

    2015-12-01

    Persistently active explosive volcanoes are characterized by short explosive bursts, which often occur at periodic intervals numerous times per day, spanning years to decades. Many of these systems present relatively evolved compositions (andesite to rhyolite), and their cyclic activity has been the subject of extensive work (e.g., Soufriere Hills Volcano, Montserrat). However, the same periodic behavior can also be observed at open systems of more mafic compositions, such as Semeru in Indonesia or Karymsky in Kamchatka for example. In this work, we use DOMEFLOW, a 1D transient numerical model of magma ascent, to identify the conditions that lead to and control periodic eruptions in basaltic andesite systems, where the viscosity of the liquid phase can be drastically lower. Periodic behavior occurs for a very narrow range of conditions, for which the mass balance between magma flux and open-system gas escape repeatedly generates a viscous plug, pressurizes the magma beneath the plug, and then explosively disrupts it. The characteristic timescale and magnitude of the eruptive cycles are controlled by the overall viscosity of the magmatic mixture, with higher viscosities leading to longer cycles and lower flow rates at the top of the conduit. Cyclic eruptions in basaltic andesite systems are observed for higher crystal contents, smaller conduit radii, and over a wider range of chamber pressures than the andesitic system, all of which are the direct consequence of a decrease in viscosity of the melt phase, and in turn in the intensity of the viscous forces generated by the system. Results suggest that periodicity can exist in more mafic systems with relatively lower chamber pressures than andesite and rhyolite systems, and may explain why more mafic magmas sometimes remain active for decades.

  13. Altered retrieval of melodic information in congenital amusia: insights from dynamic causal modeling of MEG data.

    Science.gov (United States)

    Albouy, Philippe; Mattout, Jérémie; Sanchez, Gaëtan; Tillmann, Barbara; Caclin, Anne

    2015-01-01

    Congenital amusia is a neuro-developmental disorder that primarily manifests as a difficulty in the perception and memory of pitch-based materials, including music. Recent findings have shown that the amusic brain exhibits altered functioning of a fronto-temporal network during pitch perception and short-term memory. Within this network, during the encoding of melodies, a decreased right backward frontal-to-temporal connectivity was reported in amusia, along with an abnormal connectivity within and between auditory cortices. The present study investigated whether connectivity patterns between these regions were affected during the short-term memory retrieval of melodies. Amusics and controls had to indicate whether sequences of six tones that were presented in pairs were the same or different. When melodies were different only one tone changed in the second melody. Brain responses to the changed tone in "Different" trials and to its equivalent (original) tone in "Same" trials were compared between groups using Dynamic Causal Modeling (DCM). DCM results confirmed that congenital amusia is characterized by an altered effective connectivity within and between the two auditory cortices during sound processing. Furthermore, right temporal-to-frontal message passing was altered in comparison to controls, with notably an increase in "Same" trials. An additional analysis in control participants emphasized that the detection of an unexpected event in the typically functioning brain is supported by right fronto-temporal connections. The results can be interpreted in a predictive coding framework as reflecting an abnormal prediction error sent by temporal auditory regions towards frontal areas in the amusic brain.

  14. Altered retrieval of melodic information in congenital amusia: Insights from Dynamic Causal Modeling of MEG data

    Directory of Open Access Journals (Sweden)

    Philippe eAlbouy

    2015-02-01

    Full Text Available Congenital amusia is a neuro-developmental disorder that primarily manifests as a difficulty in the perception and memory of pitch-based materials, including music. Recent findings have shown that the amusic brain exhibits altered functioning of a fronto-temporal network during pitch perception and memory. Within this network, during the encoding of melodies, a decreased right backward frontal-to-temporal connectivity was reported in amusia, along with an abnormal connectivity within and between auditory cortices. The present study investigated whether connectivity patterns between these regions were affected during the retrieval of melodies. Amusics and controls had to indicate whether sequences of six tones that were presented in pairs were the same or different. When melodies were different only one tone changed in the second melody. Brain responses to the changed tone in Different trials and to its equivalent (original tone in Same trials were compared between groups using Dynamic Causal Modeling (DCM. DCM results confirmed that congenital amusia is characterized by an altered effective connectivity within and between the two auditory cortices during sound processing. Furthermore, right temporal-to-frontal message passing was altered in comparison to controls, with an increase in Same trials and a decrease in Different trials. An additional analysis in control participants emphasized that the detection of an unexpected event in the typically functioning brain is supported by right fronto-temporal connections. The results can be interpreted in a predictive coding framework as reflecting an abnormal prediction error sent by temporal auditory regions towards frontal areas in the amusic brain.

  15. Insights into an Optimization of Plasmodium vivax Sal-1 In Vitro Culture: The Aotus Primate Model

    Science.gov (United States)

    Obaldía, Nicanor; Nuñez, Marlon; Dutary, Sahir; Lim, Caeul; Barnes, Samantha; Kocken, Clemens H. M.; Duraisingh, Manoj T.; Adams, John H.; Pasini, Erica M.

    2016-01-01

    Malaria is one of the most significant tropical diseases, and of the Plasmodium species that cause human malaria, P. vivax is the most geographically widespread. However, P. vivax remains a relatively neglected human parasite since research is typically limited to laboratories with direct access to parasite isolates from endemic field settings or from non-human primate models. This restricted research capacity is in large part due to the lack of a continuous P. vivax in vitro culture system, which has hampered the ability for experimental research needed to gain biological knowledge and develop new therapies. Consequently, efforts to establish a long-term P. vivax culture system are confounded by our poor knowledge of the preferred host cell and essential nutrients needed for in vitro propagation. Reliance on very heterogeneous P. vivax field isolates makes it difficult to benchmark parasite characteristics and further complicates development of a robust and reliable culture method. In an effort to eliminate parasite variability as a complication, we used a well-defined Aotus-adapted P. vivax Sal-1 strain to empirically evaluate different short-term in vitro culture conditions and compare them with previous reported attempts at P. vivax in vitro culture Most importantly, we suggest that reticulocyte enrichment methods affect invasion efficiency and we identify stabilized forms of nutrients that appear beneficial for parasite growth, indicating that P. vivax may be extremely sensitive to waste products. Leuko-depletion methods did not significantly affect parasite development. Formatting changes such as shaking and static cultures did not seem to have a major impact while; in contrast, the starting haematocrit affected both parasite invasion and growth. These results support the continued use of Aotus-adapted Sal-1 for development of P. vivax laboratory methods; however, further experiments are needed to optimize culture conditions to support long-term parasite

  16. The seismic cycle at subduction thrusts: Insights from seismo-thermo-mechanical models

    KAUST Repository

    van Dinther, Y.; Gerya, T. V.; Dalguer, L. A.; Mai, Paul Martin; Morra, G.; Giardini, D.

    2013-01-01

    The underestimation of the size of recent megathrust earthquakes illustrates our limited understanding of their spatiotemporal occurrence and governing physics. To unravel their relation to associated subduction dynamics and long-term deformation, we developed a 2-D continuum viscoelastoplastic model that uses an Eulerian-Lagrangian finite difference framework with similar on- and off-fault physics. We extend the validation of this numerical tool to a realistic subduction zone setting that resembles Southern Chile. The resulting quasi-periodic pattern of quasi-characteristic M8–M9 megathrust events compares quantitatively with observed recurrence and earthquake source parameters, albeit at very slow coseismic speeds. Without any data fitting, surface displacements agree with GPS data recorded before and during the 2010 M8.8 Maule earthquake, including the presence of a second-order flexural bulge. These surface displacements show cycle-to-cycle variations of slip deficits, which overall accommodate ∼5% of permanent internal shortening. We find that thermally (and stress) driven creep governs a spontaneous conditionally stable downdip transition zone between temperatures of ∼350°C and ∼450°C. Ruptures initiate above it (and below the forearc Moho), propagate within it, interspersed by small intermittent events, and arrest below it as ductile shearing relaxes stresses. Ruptures typically propagate upward along lithological boundaries and widen as pressures drop. The main thrust is constrained to be weak due to fluid-induced weakening required to sustain regular subduction and to generate events with natural characteristics (fluid pressures of ∼75–99% of solid pressures). The agreement with a range of seismological, geodetic, and geological observations demonstrates the validity and strength of this physically consistent seismo-thermo-mechanical approach.

  17. Failure Mechanical Behavior of Australian Strathbogie Granite at High Temperatures: Insights from Particle Flow Modeling

    Directory of Open Access Journals (Sweden)

    Sheng-Qi Yang

    2017-05-01

    Full Text Available Thermally induced damage has an important influence on rock mechanics and engineering, especially for high-level radioactive waste repositories, geological carbon storage, underground coal gasification, and hydrothermal systems. Additionally, the wide application of geothermal heat requires knowledge of the geothermal conditions of reservoir rocks at elevated temperature. However, few methods to date have been reported for investigating the micro-mechanics of specimens at elevated temperatures. Therefore, this paper uses a cluster model in particle flow code in two dimensions (PFC2D to simulate the uniaxial compressive testing of Australian Strathbogie granite at various elevated temperatures. The peak strength and ultimate failure mode of the granite specimens at different elevated temperatures obtained by the numerical methods are consistent with those obtained by experimentation. Since the tensile force is always concentrated around the boundary of the crystal, cracks easily occur at the intergranular contacts, especially between the b-b and b-k boundaries where less intragranular contact is observed. The intergranular and intragranular cracking of the specimens is almost constant with increasing temperature at low temperature, and then it rapidly and linearly increases. However, the inflection point of intergranular micro-cracking is less than that of intragranular cracking. Intergranular cracking is more easily induced by a high temperature than intragranular cracking. At an elevated temperature, the cumulative micro-crack counts curve propagates in a stable way during the active period, and it has no unstable crack propagation stage. The micro-cracks and parallel bond forces in the specimens with elevated temperature evolution and axial strain have different characteristics than those at lower temperature. More branch fractures and isolated wider micro-cracks are generated with increasing temperature when the temperature is over 400

  18. Thermal history of the Acoculco geothermal system, eastern Mexico: Insights from numerical modeling and radiocarbon dating

    Science.gov (United States)

    Canet, Carles; Trillaud, Frederic; Prol-Ledesma, Rosa María; González-Hernández, Galia; Peláez, Berenice; Hernández-Cruz, Berenice; Sánchez-Córdova, María M.

    2015-10-01

    Acoculco is a geothermal prospective area hosted by a volcanic caldera complex in the eastern Trans-Mexican Volcanic Belt. Surface manifestations are scarce and consist of gas discharges (CO2-rich) and acid-sulfate springs of low temperature, whereas hydrothermal explosive activity is profusely manifested by meter-scale craters and mounds of hydrothermal debris and breccias. Silicic alteration extends for several square kilometers around the zone with gas manifestations and explosive features, affecting surficial volcanic rocks, primarily tuffs and breccias. In the subsurface, an argillic alteration zone (ammonium illite) extends down to a depth of ∼ 600 m, and underneath it a propylitic zone (epidote-calcite-chlorite) occurs down to ∼ 1000 m. Thermal logs from an exploratory borehole (EAC-1, drilled in 1995 down to 1810 m) showed a conductive heat transfer regime under high geothermal gradient (∼ 140 °C/1000 m). In contrast, the thermal profile established from temperatures of homogenization of fluid inclusions-measured on core samples from the same drill hole-suggests that convection occurred in the past through the upper ~ 1400 m of the geothermal system. A drop in permeability due to the precipitation of alteration minerals would have triggered the cessation of the convective heat transfer regime to give place to a conductive one. With the purpose of determining when the transition of heat transfer regime occurred, we developed a 1D model that simulates the time-depth distribution of temperature. According to our numerical simulations, this transition happened ca. 7000 years ago; this date is very recent compared to the lifespan of the geothermal system. In addition, radiocarbon chronology indicates that the hydrothermal explosive activity postdates the end of the convective heat transfer regime, having dated at least three explosive events, at 4867-5295, 1049-1417 and 543-709 y cal. BP. Therefore, hydrothermal explosions arise from the self-sealing of

  19. Seismometers on Europa: Insights from Modeling and Antarctic Ice Shelf Analogs (Invited)

    Science.gov (United States)

    Schmerr, N. C.; Brunt, K. M.; Cammarano, F.; Hurford, T. A.; Lekic, V.; Panning, M. P.; Rhoden, A.; Sauber, J. M.

    2013-12-01

    The outer satellites of the Solar System are a diverse suite of objects that span a large spectrum of sizes, compositions, and evolutionary histories; constraining their internal structures is key for understanding their formation, evolution, and dynamics. In particular, Jupiter's icy satellite Europa has compelling evidence for the existence of a global subsurface ocean beneath a surface layer of water ice. This ocean decouples the ice shell from the solid silicate mantle, and amplifies tidally driven large-scale surface deformation. The complex fissures and cracks seen by orbital flybys suggest brittle failure is an ongoing and active process in the ice crust, therefore indicating a high level of associated seismic activity. Seismic probing of the ice, oceanic, and rocky layers would provide altogether new information on the structure, evolution, and even habitability of Europa. Any future missions (penetrators, landers, and rovers) planning to take advantage of seismometers to image the Europan interior would need to be built around predictions for the expected background noise levels, seismicity, wavefields, and elastic properties of the interior. A preliminary suite of seismic velocity profiles for Europa has been calculated using moment of inertia constraints, planetary mass and density, estimates of moon composition, thermal structure, and experimentally determined relationships of elastic properties for relevant materials at pressure, temperature and depth. While the uncertainties in these models are high, they allow us to calculate a first-order seismic response using 1-D and 3-D high frequency wave propagation codes for global and regional scale structures. Here, we show how future seismic instruments could provide detailed elastic information and reduced uncertainties on the internal structure of Europa. For example, receiver functions and surface wave orbits calculated for a single seismic instrument would provide information on crustal thickness and

  20. Pathways to nephron loss starting from glomerular diseases-insights from animal models.

    Science.gov (United States)

    Kriz, Wilhelm; LeHir, Michel

    2005-02-01

    Studies of glomerular diseases in animal models show that progression toward nephron loss starts with extracapillary lesions, whereby podocytes play the central role. If injuries remain bound within the endocapillary compartment, they will undergo recovery or be repaired by scaring. Degenerative, inflammatory and dysregulative mechanisms leading to nephron loss are distinguished. In addition to several other unique features, the dysregulative mechanisms leading to collapsing glomerulopathy are particular in that glomeruli and tubules are affected in parallel. In contrast, in degenerative and inflammatory diseases, tubular injury is secondary to glomerular lesions. In both of the latter groups of diseases, the progression starts in the glomerulus with the loss of the separation between the tuft and Bowman's capsule by forming cell bridges (parietal cells and/or podocytes) between the glomerular and the parietal basement membranes. Cell bridges develop into tuft adhesions to Bowman's capsule, which initiate the formation of crescents, either by misdirected filtration (proteinaceous crescents) or by epithelial cell proliferation (cellular crescents). Crescents may spread over the entire circumference of the glomerulus and, via the glomerulotubular junction, may extend onto the tubule. Two mechanisms concerning the transfer of a glomerular injury onto the tubulointerstitium are discussed: (1) direct encroachment of extracapillary lesions and (2) protein leakage into tubular urine, resulting in injury to the tubule and the interstitium. There is evidence that direct encroachment is the crucial mechanism. Progression of chronic renal disease is underlain by a vicious cycle which passes on the damage from lost and/or damaged nephrons to so far healthy nephrons. Presently, two mechanisms are discussed: (1) the loss of nephrons leads to compensatory mechanisms in the remaining nephrons (glomerular hypertension, hyperfiltration, hypertrophy) which increase their

  1. Strain localisation in mechanically layered rocks beneath detachment zones: insights from numerical modelling

    Directory of Open Access Journals (Sweden)

    L. Le Pourhiet

    2013-04-01

    Full Text Available We have designed a series of fully dynamic numerical simulations aimed at assessing how the orientation of mechanical layering in rocks controls the orientation of shear bands and the depth of penetration of strain in the footwall of detachment zones. Two parametric studies are presented. In the first one, the influence of stratification orientation on the occurrence and mode of strain localisation is tested by varying initial dip of inherited layering in the footwall with regard to the orientation of simple shear applied at the rigid boundary simulating a rigid hanging wall, all scaling and rheological parameter kept constant. It appears that when Mohr–Coulomb plasticity is being used, shear bands are found to localise only when the layering is being stretched. This corresponds to early deformational stages for inital layering dipping in the same direction as the shear is applied, and to later stages for intial layering dipping towards the opposite direction of shear. In all the cases, localisation of the strain after only γ=1 requires plastic yielding to be activated in the strong layer. The second parametric study shows that results are length-scale independent and that orientation of shear bands is not sensitive to the viscosity contrast or the strain rate. However, decreasing or increasing strain rate is shown to reduce the capacity of the shear zone to localise strain. In the later case, the strain pattern resembles a mylonitic band but the rheology is shown to be effectively linear. Based on the results, a conceptual model for strain localisation under detachment faults is presented. In the early stages, strain localisation occurs at slow rates by viscous shear instabilities but as the layered media is exhumed, the temperature drops and the strong layers start yielding plastically, forming shear bands and localising strain at the top of the shear zone. Once strain localisation has occured, the deformation in the shear band becomes

  2. The IRP/IRE system in vivo: insights from mouse models

    Directory of Open Access Journals (Sweden)

    Nicole eWilkinson

    2014-07-01

    Full Text Available Iron regulatory proteins 1 and 2 (IRP1 and IRP2 post-transcriptionally control the expression of several mRNAs encoding proteins of iron, oxygen and energy metabolism. The mechanism involves their binding to iron responsive elements (IREs in the untranslated regions of target mRNAs, thereby controlling mRNA translation or stability. Whereas IRP2 functions solely as an RNA-binding protein, IRP1 operates as either an RNA-binding protein or a cytosolic aconitase. Early experiments in cultured cells established a crucial role of IRPs in regulation of cellular iron metabolism. More recently, studies in mouse models with global or localized Irp1 and/or Irp2 deficiencies uncovered new physiological functions of IRPs in the context of systemic iron homeostasis. Thus, IRP1 emerged as a key regulator of erythropoiesis and iron absorption by controlling hypoxia inducible factor 2α (HIF2α mRNA translation, while IRP2 appears to dominate the control of iron uptake and heme biosynthesis in erythroid progenitor cells by regulating the expression of transferrin receptor 1 (TfR1 and 5-aminolevulinic acid synthase 2 (ALAS2 mRNAs, respectively. Targeted disruption of either Irp1 or Irp2 in mice is associated with distinct phenotypic abnormalities. Thus, Irp1-/- mice develop polycythemia and pulmonary hypertension, while Irp2-/- mice present with microcytic anemia, iron overload in the intestine and the liver, and neurologic defects. Combined disruption of both Irp1 and Irp2 is incombatible with life and leads to early embryonic lethality. Mice with intestinal- or liver-specific disruption of both Irps are viable at birth but die later on due to malabsorption or liver failure, respectively. Adult mice lacking both Irps in the intestine exhibit a profound defect in dietary iron absorption due to a mucosal block that is caused by the de-repression of ferritin mRNA translation. Herein, we discuss the physiological function of the IRE/IRP regulatory system.

  3. Muscle Signaling in Exercise Intolerance: Insights from the McArdle Mouse Model.

    Science.gov (United States)

    Fiuza-Luces, Carmen; Nogales-Gadea, Gisela; García-Consuegra, Inés; Pareja-Galeano, Helios; Rufián-Vázquez, Laura; Pérez, Laura M; Andreu, Antoni L; Arenas, Joaquín; Martín, Miguel Angel; Pinós, Tomàs; Lucia, Alejandro; Morán, María

    2016-08-01

    We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of the McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of "exercise intolerance," is to compare the skeletal muscle tissue of McArdle, heterozygous, and healthy (wild-type [wt]) mice. We analyzed in quadriceps muscle of p.R50X/p.R50X (n = 4), p.R50X/wt (n = 6), and wt/wt mice (n = 5) (all male, 8 wk old) molecular markers of energy-sensing pathways, oxidative phosphorylation and autophagy/proteasome systems, oxidative damage, and sarcoplasmic reticulum Ca handling. We found a significant group effect for total adenosine monophosphate-(AMP)-activated protein kinase (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P = 0.012 and 0.033), with higher mean values in p.R50X/p.R50X mice versus the other two groups. The absence of a massive accumulation of ubiquitinated proteins, autophagosomes, or lysosomes in p.R50X/p.R50X mice suggested no major alterations in autophagy/proteasome systems. Citrate synthase activity was lower in p.R50X/p.R50X mice versus the other two groups (P = 0.036), but no statistical effect existed for respiratory chain complexes. We found higher levels of 4-hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared with the wt/wt group (P = 0.011). Sarco(endo)plasmic reticulum ATPase 1 levels detected at 110 kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice compared with wt/wt animals (P = 0.076), but their enzyme activity was normal. We also found an accumulation of phosphorylated sarco(endo)plasmic reticulum ATPase 1 in p.R50X/p.R50X animals. Myophosphorylase deficiency causes alterations in sensory energetic pathways together with some evidence of oxidative damage and alterations in Ca handling but with no major alterations in oxidative phosphorylation capacity or autophagy/ubiquitination pathways, which suggests that

  4. 17 CFR 230.253 - Offering circular.

    Science.gov (United States)

    2010-04-01

    .... Repetition of information should be avoided; cross-referencing of information within the document is... COMPLETENESS OF ANY OFFERING CIRCULAR OR OTHER SELLING LITERATURE. THESE SECURITIES ARE OFFERED PURSUANT TO AN...

  5. Recommended survey designs for occupancy modelling using motion-activated cameras: insights from empirical wildlife data

    Directory of Open Access Journals (Sweden)

    Graeme Shannon

    2014-08-01

    Full Text Available Motion-activated cameras are a versatile tool that wildlife biologists can use for sampling wild animal populations to estimate species occurrence. Occupancy modelling provides a flexible framework for the analysis of these data; explicitly recognizing that given a species occupies an area the probability of detecting it is often less than one. Despite the number of studies using camera data in an occupancy framework, there is only limited guidance from the scientific literature about survey design trade-offs when using motion-activated cameras. A fuller understanding of these trade-offs will allow researchers to maximise available resources and determine whether the objectives of a monitoring program or research study are achievable. We use an empirical dataset collected from 40 cameras deployed across 160 km2 of the Western Slope of Colorado, USA to explore how survey effort (number of cameras deployed and the length of sampling period affects the accuracy and precision (i.e., error of the occupancy estimate for ten mammal and three virtual species. We do this using a simulation approach where species occupancy and detection parameters were informed by empirical data from motion-activated cameras. A total of 54 survey designs were considered by varying combinations of sites (10–120 cameras and occasions (20–120 survey days. Our findings demonstrate that increasing total sampling effort generally decreases error associated with the occupancy estimate, but changing the number of sites or sampling duration can have very different results, depending on whether a species is spatially common or rare (occupancy = ψ and easy or hard to detect when available (detection probability = p. For rare species with a low probability of detection (i.e., raccoon and spotted skunk the required survey effort includes maximizing the number of sites and the number of survey days, often to a level that may be logistically unrealistic for many studies. For common

  6. On the formation, growth, and shapes of solution pipes - insights from numerical modeling

    Science.gov (United States)

    Szymczak, Piotr; Tredak, Hanna; Upadhyay, Virat; Kondratiuk, Paweł; Ladd, Anthony J. C.

    2015-04-01

    Cylindrical, vertical structures called solution pipes are a characteristic feature of epikarst, encountered in different parts of the world, both in relatively cold areas such as England and Poland (where their formation is linked to glacial processes) [1] and in coastal areas in tropical or subtropical climate (Bermuda, Australia, South Africa, Caribbean, Mediterranean) [2,3]. They are invariably associated with weakly cemented, porous limestones and relatively high groundwater fluxes. Many of them develop under the colluvial sandy cover and contain the fill of clayey silt. Although it is widely accepted that they are solutional in origin, the exact mechanism by which the flow becomes focused is still under debate. The hypotheses include the concentration of acidified water around stems and roots of plants, or the presence of pre-existing fractures or steeply dipping bedding planes, which would determine the points of entry for the focused groundwater flows. However, there are field sites where neither of this mechanisms was apparently at play and yet the pipes are formed in large quantities [1]. In this communication we show that the systems of solution pipes can develop spontaneously in nearly uniform matrix due to the reactive-infiltration instability: a homogeneous porous matrix is unstable with respect to small variations in local permeability; regions of high permeability dissolve faster because of enhanced transport of reactants, which leads to increased rippling of the front. This leads to the formation of a system of solution pipes which then advance into the matrix. We study this process numerically, by a combination of 2d- and 3d-simulations, solving the coupled flow and transport equations at the Darcy scale. The relative simplicity of this system (pipes developing in a uniform porous matrix, without any pre-existing structure) makes it very attractive from the modeling standpoint. We quantify the factors which control the pipe diameters and the

  7. 43 CFR 12.715 - Evaluating offers.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Evaluating offers. 12.715 Section 12.715... Act-Supplies § 12.715 Evaluating offers. (a) Unless the head of the grantee organization or a designee at a level no lower than the grantee's designated awarding official determines otherwise, the offered...

  8. 5 CFR 536.104 - Reasonable offer.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Reasonable offer. 536.104 Section 536.104... Provisions § 536.104 Reasonable offer. (a) For the purpose of determining whether grade retention eligibility or entitlement must be terminated under § 536.207 or 536.208, the offer of a position is a reasonable...

  9. 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) The Agency will offer a borrower, who submits a prepayment request meeting the conditions of § 3560...

  10. 48 CFR 12.205 - Offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Offers. 12.205 Section 12... ACQUISITION OF COMMERCIAL ITEMS Special Requirements for the Acquisition of Commercial Items 12.205 Offers. (a) Where technical information is necessary for evaluation of offers, agencies should, as part of market...

  11. 32 CFR 536.64 - Final offers.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Final offers. 536.64 Section 536.64 National... UNITED STATES Investigation and Processing of Claims § 536.64 Final offers. (a) When claims personnel... less than the amount claimed, a settlement authority will make a written final offer within his or her...

  12. 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 ‘...

  13. Innovative gas offers; Les offres gazieres innovantes

    Energy Technology Data Exchange (ETDEWEB)

    Sala, O.; Mela, P. [Gaz de France (GDF), 75 - Paris (France); Chatelain, F. [Primagaz, 75 - Paris (France)

    2007-07-01

    New energy offers are progressively made available as the opening of gas market to competition becomes broader. How are organized the combined offers: gas, electricity, renewable energies and energy services? What are the marketing strategies implemented? Three participants at this round table present their offer and answer these questions. (J.S.)

  14. Exploring the persona model as a tool to generate user insight through co-creation with users in the early phase of a design project

    DEFF Research Database (Denmark)

    Hansen, Jane Holm; Haase, Louise Møller

    2017-01-01

    The persona model is a widely know tool for synthesizing user research. A persona is a hypothetical archetype based on actual users, which is typically created to create a shared understanding of the user in the design team. Previous research has focused on the personal model as a consensus......-making tool. However, in this paper the aim is to explore, whether the persona model can also be useful and valuable for collecting user insights. More specifically, the paper investigates the potentials and challenges of using the persona model as a generative tool to achieve user insight, when co......-creating with the user in the early phase of a design project. A modified persona template with fixed parameters has been introduced to users in two co-creation workshops. The users were asked to fill in the persona template based on their own experiences. This study is a first endeavor into exploring the persona model...

  15. Computational Modelling of Dapsone Interaction With Dihydropteroate Synthase in Mycobacterium leprae; Insights Into Molecular Basis of Dapsone Resistance in Leprosy.

    Science.gov (United States)

    Chaitanya V, Sundeep; Das, Madhusmita; Bhat, Pritesh; Ebenezer, Mannam

    2015-10-01

    The molecular basis for determination of resistance to anti-leprosy drugs is the presence of point mutations within the genes of Mycobacterium leprae (M. leprae) that encode active drug targets. The downstream structural and functional implications of these point mutations on drug targets were scarcely studied. In this study, we utilized computational tools to develop native and mutant protein models for 5 point mutations at codon positions 53 and 55 in 6-hydroxymethyl-7, 8-dihydropteroate synthase (DHPS) of M. leprae, an active target for dapsone encoded by folp1 gene, that confer resistance to dapsone. Molecular docking was performed to identify variations in dapsone interaction with mutant DHPS in terms of hydrogen bonding, hydrophobic interactions, and energy changes. Schrodinger Suite 2014-3 was used to build homology models and in performing molecular docking. An increase in volume of the binding cavities of mutant structures was noted when compared to native form indicating a weakening in interaction (60.7 Å(3) in native vs. 233.6 Å(3) in Thr53Ala, 659.9 Å(3) in Thr53Ile, 400 Å(3) for Thr53Val, 385 Å(3) for Pro55Arg, and 210 Å(3) for Pro55Leu). This was also reflected by changes in hydrogen bonds and decrease in hydrophobic interactions in the mutant models. The total binding energy (ΔG) decreased significantly in mutant forms when compared to the native form (-51.92 Kcal/mol for native vs. -35.64, -35.24, -46.47, -47.69, and -41.36 Kcal/mol for mutations Thr53Ala, Thr53Ile, Thr53Val, Pro55Arg, and Pro55Leu, respectively. In brief, this analysis provided structural and mechanistic insights to the degree of dapsone resistance contributed by each of these DHPS mutants in leprosy. © 2015 Wiley Periodicals, Inc.

  16. Modelling detrital coral grain-size and age: Insights from sediment abrasion process of Yongle Atoll of South China Sea

    Science.gov (United States)

    Li, Y.; Zou, X.; Ge, C.; Tan, M.; Wang, C.

    2017-12-01

    Reef islands situated on the rims of atolls are composed almost exclusively of bioclastic materials locally supplied from adjacent coral reefs. Major skeletal component of these islands include coral, coralline algae, mollusks and foraminifera, produced in adjacent reefs. As the island builder, the bioclastic material is the sedimentary products, which also is the point of penetration to decipher the process. The bioclast of coral islands decrease in size with the transportation process. The grain-size provides a proxy record for the abrasion history of the unconsolidated sediment. The 230Th age of coral record the abrasion time. We hereby present a model to calculate the abrasion rate based on the data of 230Th age and grain-size of Yongle Atoll of Xisha Island, South China Sea. The grain size pattern in Yongle Atoll environment have confirm that the coral article diminution behave exponentially. The sediment composition of Yongle Atoll is identified, coral is dominant sediment constituent and the Th230 age is shown to exert an age distribution characteristics of coral detritus. We illustrate this approach by calculate the coral debris age of Xude Atoll, which located near the Yongle Atoll and then by comparing actual measured age and calculated age and to explore the dependence of the model. Observed 230 Th ages are well matched by predicted ages for medium age sediment. A poorer match for young and old sediment may result from some combination of large analytical uncertainties in the detrital ages and inhomogeneous erosion rates within the atoll. Such mismatches emphasize the need for more accurate kinematic models and for sampling strategies that are adapted to atoll-specific geologic and geomorphic conditions. Results presented constitute important new insights into regional sediment abrasion processed and on the evolution of coral atoll islands.

  17. Polynomial meta-models with canonical low-rank approximations: Numerical insights and comparison to sparse polynomial chaos expansions

    Energy Technology Data Exchange (ETDEWEB)

    Konakli, Katerina, E-mail: konakli@ibk.baug.ethz.ch; Sudret, Bruno

    2016-09-15

    The growing need for uncertainty analysis of complex computational models has led to an expanding use of meta-models across engineering and sciences. The efficiency of meta-modeling techniques relies on their ability to provide statistically-equivalent analytical representations based on relatively few evaluations of the original model. Polynomial chaos expansions (PCE) have proven a powerful tool for developing meta-models in a wide range of applications; the key idea thereof is to expand the model response onto a basis made of multivariate polynomials obtained as tensor products of appropriate univariate polynomials. The classical PCE approach nevertheless faces the “curse of dimensionality”, namely the exponential increase of the basis size with increasing input dimension. To address this limitation, the sparse PCE technique has been proposed, in which the expansion is carried out on only a few relevant basis terms that are automatically selected by a suitable algorithm. An alternative for developing meta-models with polynomial functions in high-dimensional problems is offered by the newly emerged low-rank approximations (LRA) approach. By exploiting the tensor–product structure of the multivariate basis, LRA can provide polynomial representations in highly compressed formats. Through extensive numerical investigations, we herein first shed light on issues relating to the construction of canonical LRA with a particular greedy algorithm involving a sequential updating of the polynomial coefficients along separate dimensions. Specifically, we examine the selection of optimal rank, stopping criteria in the updating of the polynomial coefficients and error estimation. In the sequel, we confront canonical LRA to sparse PCE in structural-mechanics and heat-conduction applications based on finite-element solutions. Canonical LRA exhibit smaller errors than sparse PCE in cases when the number of available model evaluations is small with respect to the input

  18. Polynomial meta-models with canonical low-rank approximations: Numerical insights and comparison to sparse polynomial chaos expansions

    International Nuclear Information System (INIS)

    Konakli, Katerina; Sudret, Bruno

    2016-01-01

    The growing need for uncertainty analysis of complex computational models has led to an expanding use of meta-models across engineering and sciences. The efficiency of meta-modeling techniques relies on their ability to provide statistically-equivalent analytical representations based on relatively few evaluations of the original model. Polynomial chaos expansions (PCE) have proven a powerful tool for developing meta-models in a wide range of applications; the key idea thereof is to expand the model response onto a basis made of multivariate polynomials obtained as tensor products of appropriate univariate polynomials. The classical PCE approach nevertheless faces the “curse of dimensionality”, namely the exponential increase of the basis size with increasing input dimension. To address this limitation, the sparse PCE technique has been proposed, in which the expansion is carried out on only a few relevant basis terms that are automatically selected by a suitable algorithm. An alternative for developing meta-models with polynomial functions in high-dimensional problems is offered by the newly emerged low-rank approximations (LRA) approach. By exploiting the tensor–product structure of the multivariate basis, LRA can provide polynomial representations in highly compressed formats. Through extensive numerical investigations, we herein first shed light on issues relating to the construction of canonical LRA with a particular greedy algorithm involving a sequential updating of the polynomial coefficients along separate dimensions. Specifically, we examine the selection of optimal rank, stopping criteria in the updating of the polynomial coefficients and error estimation. In the sequel, we confront canonical LRA to sparse PCE in structural-mechanics and heat-conduction applications based on finite-element solutions. Canonical LRA exhibit smaller errors than sparse PCE in cases when the number of available model evaluations is small with respect to the input

  19. Dynamic morphology of gas hydrate on a methane bubble in water: Observations and new insights for hydrate film models

    Science.gov (United States)

    Warzinski, Robert P.; Lynn, Ronald; Haljasmaa, Igor; Leifer, Ira; Shaffer, Frank; Anderson, Brian J.; Levine, Jonathan S.

    2014-10-01

    Predicting the fate of subsea hydrocarbon gases escaping into seawater is complicated by potential formation of hydrate on rising bubbles that can enhance their survival in the water column, allowing gas to reach shallower depths and the atmosphere. The precise nature and influence of hydrate coatings on bubble hydrodynamics and dissolution is largely unknown. Here we present high-definition, experimental observations of complex surficial mechanisms governing methane bubble hydrate formation and dissociation during transit of a simulated oceanic water column that reveal a temporal progression of deep-sea controlling mechanisms. Synergistic feedbacks between bubble hydrodynamics, hydrate morphology, and coverage characteristics were discovered. Morphological changes on the bubble surface appear analogous to macroscale, sea ice processes, presenting new mechanistic insights. An inverse linear relationship between hydrate coverage and bubble dissolution rate is indicated. Understanding and incorporating these phenomena into bubble and bubble plume models will be necessary to accurately predict global greenhouse gas budgets for warming ocean scenarios and hydrocarbon transport from anthropogenic or natural deep-sea eruptions.

  20. State of the art in the insight into experimentally observed mesons and baryons predicted by current fundamental models of particle physics

    International Nuclear Information System (INIS)

    Bednar, M.; Hron, J.

    2001-01-01

    Current insight into mesons and baryons is highlighted, their classification is given, and their arrangement into multiplets is described. A brief chronological overview of discoveries of the most important mesons and baryons is presented, followed by a description of the attempts to find fundamental particles between mesons and baryons, which could be composed of other mesons and baryons (Fermi-Yang model, Sakata model, Ikea-Ohnuki-Ogawa model). The attempts ultimately led to the formulation of the quark model. The quark structure of some mesons and baryons is presented. The quark model foresees the existence of mesons and baryons that have not yet been discovered. (Z.J.)

  1. Using Satellite Remote Sensing and Modelling for Insights into N02 Air Pollution and NO2 Emissions

    Science.gov (United States)

    Lamsal, L. N.; Martin, R. V.; Krotkov, N. A.; Bucsela, E. J.; Celarier, E. A.; vanDonkelaar, A.; Parrish, D.

    2012-01-01

    Nitrogen oxides (NO(x)) are key actors in air quality and climate change. Satellite remote sensing of tropospheric NO2 has developed rapidly with enhanced spatial and temporal resolution since initial observations in 1995. We have developed an improved algorithm and retrieved tropospheric NO2 columns from Ozone Monitoring Instrument. Column observations of tropospheric NO2 from the nadir-viewing satellite sensors contain large contributions from the boundary layer due to strong enhancement of NO2 in the boundary layer. We infer ground-level NO2 concentrations from the OMI satellite instrument which demonstrate significant agreement with in-situ surface measurements. We examine how NO2 columns measured by satellite, ground-level NO2 derived from satellite, and NO(x) emissions obtained from bottom-up inventories relate to world's urban population. We perform inverse modeling analysis of NO2 measurements from OMI to estimate "top-down" surface NO(x) emissions, which are used to evaluate and improve "bottom-up" emission inventories. We use NO2 column observations from OMI and the relationship between NO2 columns and NO(x) emissions from a GEOS-Chem model simulation to estimate the annual change in bottom-up NO(x) emissions. The emission updates offer an improved estimate of NO(x) that are critical to our understanding of air quality, acid deposition, and climate change.

  2. An insight into the formation of severe ozone episodes: modeling the 21/03/01 event in the ESCOMPTE region

    Science.gov (United States)

    Lasry, Fanny; Coll, Isabelle; Buisson, Emmanuel

    2005-03-01

    High ozone concentrations are observed more and more frequently in the lower troposphere. The development of such polluted episodes is linked to a complex set of chemical, physical and dynamical parameters that interact with each other. To improve air quality, it is necessary to understand and quantify the role of all these processes on the intensity of ozone formation. The ESCOMPTE program, especially dedicated to the numerical simulation of photochemical episodes, offers an ideal frame to investigate details of the roles of many of these processes through 3D modeling. This paper presents the analysis, with a 3D eulerian model, of a severe and local episode of ozone pollution that occurred on the 21st of March 2001 in the ESCOMPTE region. This episode is particularly interesting due to the intensity of the observed ozone peaks (450 μg/m 3 during 15 mn) but also because it did not occur in summer but at the beginning of spring. As part of the premodeling work of the ESCOMPTE program, this study focuses on the sensitivity of the simulated ozone peaks to various chemical and physical phenomena (long-range transport, industrial emissions, local dynamic phenomena…) to determine their influence on the rise of high local photooxidant concentrations and to better picture the photochemistry of the ESCOMPTE region. Through sensitivity tests to dynamical calculation resolution and emissions, this paper shows how the combination of sea and pond breezes with emissions of reactive VOCs can generate local intense ozone peaks.

  3. Supplementary Material for: Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

    KAUST Repository

    Phelan, Jody

    2016-01-01

    Abstract Background Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. Methods To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. Results The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. Conclusions Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel

  4. Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

    KAUST Repository

    Phelan, Jody

    2016-03-23

    Background Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. Methods To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. Results The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. Conclusions Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance

  5. Africa Insight

    African Journals Online (AJOL)

    Africa Insight is a quarterly, peer-reviewed journal of the Africa Institute of South Africa. It is accredited by the South African National Department of Higher Education and Training (DHET) and is indexed in the International Bibliography of Social Science (IBSS). It is a multi-disciplinary journal primarily focusing on African ...

  6. Caregiver Insightfulness and Young Children’s Violence Exposure: Testing a Relational Model of Risk and Resilience

    Science.gov (United States)

    Gray, Sarah A. O.; Forbes, Danielle; Briggs-Gowan, Margaret; Carter, Alice S.

    2016-01-01

    This study employed a relational post-traumatic stress frame to explore the co-contribution of young children’s exposure to violence and caregiver insightfulness on child behavioral outcomes in a high-risk, non-referred sample of caregivers and preschoolers (n = 64; mean age 3.83 years, SD = .77). Caregiver insightfulness did not have a main effect on child outcomes but did moderate the relation between violence exposure and child behavior across all observed outcomes. Violence-exposed children with non-insightful caregivers demonstrated higher caregiver-rated internalizing and externalizing behaviors and observer-rated negative affect than all other groups. Among children not exposed to violence, insightfulness was not related to children’s behavior problems or negative affect, suggesting violence-specific processes. Though cross-sectional, results suggest that the effects of violence and caregiver insightfulness on child outcomes are contingent on one another and that caregiver insightfulness may play a protective role in contexts of violence. PMID:26503175

  7. World energy insight 2011

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-11-15

    The World Energy Insight 2011 is the official publication of the World Energy Council. It includes interviews, articles and case studies from a distinguished panel of World Energy Council Officers, CEOs, government ministers, academics and opinion formers from all areas of the energy sector and provides perspectives from around the globe. Government, industry and NGO's offer both policy and technology perspectives. The insights within this publication add to the work that WEC is doing to provide the forum for energy leaders, along with the on-going WEC studies and programmes on Energy Policies, 2050 Energy Scenarios, Energy Resources & Technologies, Energy for Urban Innovation, Rules Of Energy Trade and Global Energy Access.

  8. 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...

  9. Complexities in barrier island response to sea level rise: Insights from numerical model experiments, North Carolina Outer Banks

    Science.gov (United States)

    Moore, Laura J.; List, Jeffrey H.; Williams, S. Jeffress; Stolper, David

    2010-09-01

    .g., previous slopes, sediment budgets, etc.) in determining migration trajectories and therefore how a barrier island will respond to sea level rise. Although simple analytical calculations may predict barrier response in simplified coastal environments (e.g., constant slope, constant sea level rise rate, etc.), our model experiments demonstrate that morphological-behavior modeling is necessary to provide critical insights regarding changes that may occur in environments having complex geometries, especially when multiple parameters change simultaneously.

  10. Warburg effect's manifestation in aggressive pheochromocytomas and paragangliomas: insights from a mouse cell model applied to human tumor tissue.

    Directory of Open Access Journals (Sweden)

    Stephanie M J Fliedner

    Full Text Available A glycolytic profile unifies a group of pheochromocytomas and paragangliomas (PHEOs/PGLs with distinct underlying gene defects, including von Hippel-Lindau (VHL and succinate dehydrogenase B (SDHB mutations. Nevertheless, their tumor aggressiveness is distinct: PHEOs/PGLs metastasize rarely in VHL-, but frequently in SDHB-patients. To date, the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown. Recently, however, an excellent model to study aggressive PHEOs (mouse tumor tissue (MTT cells has been developed from mouse PHEO cells (MPC. We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness, which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs. The increase of glucose transporter 1 in VHL, and of hexokinase 2 in VHL and SDHB, confirmed their glycolytic profile. In agreement with the cell model and in support of decoupling of glycolysis, the Krebs cycle and oxidative phosphorylation (OXPHOS, SDHB tumors showed increased lactate dehydrogenase levels. In SDHB-PGLs OXPHOS complex activity was increased at complex III and, as expected, decreased at complex II. Moreover, protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors. Although there was no direct evidence for increased reactive oxygen species production, elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs. For the first time, we show that despite dysfunction in complex II and evidence for a glycolytic phenotype, the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS. In addition, we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs, proteins that have been proposed as promising therapeutic targets in other cancers. This study provides new insight into pathogenic mechanisms in

  11. Complexities in barrier island response to sea level rise: Insights from numerical model experiments, North Carolina Outer Banks

    Science.gov (United States)

    Moore, Laura J.; List, Jeffrey H.; Williams, S. Jeffress; Stolper, David

    2010-01-01

    .g., previous slopes, sediment budgets, etc.) in determining migration trajectories and therefore how a barrier island will respond to sea level rise. Although simple analytical calculations may predict barrier response in simplified coastal environments (e.g., constant slope, constant sea level rise rate, etc.), our model experiments demonstrate that morphological-behavior modeling is necessary to provide critical insights regarding changes that may occur in environments having complex geometries, especially when multiple parameters change simultaneously.

  12. How can accelerated development of bioenergy contribute to the future UK energy mix? Insights from a MARKAL modelling exercise

    Directory of Open Access Journals (Sweden)

    Anandarajah Gabrial

    2009-07-01

    Full Text Available Abstract Background This work explores the potential contribution of bioenergy technologies to 60% and 80% carbon reductions in the UK energy system by 2050, by outlining the potential for accelerated technological development of bioenergy chains. The investigation was based on insights from MARKAL modelling, detailed literature reviews and expert consultations. Due to the number and complexity of bioenergy pathways and technologies in the model, three chains and two underpinning technologies were selected for detailed investigation: (1 lignocellulosic hydrolysis for the production of bioethanol, (2 gasification technologies for heat and power, (3 fast pyrolysis of biomass for bio-oil production, (4 biotechnological advances for second generation bioenergy crops, and (5 the development of agro-machinery for growing and harvesting bioenergy crops. Detailed literature searches and expert consultations (looking inter alia at research and development needs and economic projections led to the development of an 'accelerated' dataset of modelling parameters for each of the selected bioenergy pathways, which were included in five different scenario runs with UK-MARKAL (MED. The results of the 'accelerated runs' were compared with a low-carbon (LC-Core scenario, which assesses the cheapest way to decarbonise the energy sector. Results Bioenergy was deployed in larger quantities in the bioenergy accelerated technological development scenario compared with the LC-Core scenario. In the electricity sector, solid biomass was highly utilised for energy crop gasification, displacing some deployment of wind power, and nuclear and marine to a lesser extent. Solid biomass was also deployed for heat in the residential sector from 2040 in much higher quantities in the bioenergy accelerated technological development scenario compared with LC-Core. Although lignocellulosic ethanol increased, overall ethanol decreased in the transport sector in the bioenergy

  13. 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.

  14. Centromeric DNA characterization in the model grass Brachypodium distachyon provides insights on the evolution of the genus.

    Science.gov (United States)

    Li, Yinjia; Zuo, Sheng; Zhang, Zhiliang; Li, Zhanjie; Han, Jinlei; Chu, Zhaoqing; Hasterok, Robert; Wang, Kai

    2018-03-01

    Brachypodium distachyon is a well-established model monocot plant, and its small and compact genome has been used as an accurate reference for the much larger and often polyploid genomes of cereals such as Avena sativa (oats), Hordeum vulgare (barley) and Triticum aestivum (wheat). Centromeres are indispensable functional units of chromosomes and they play a core role in genome polyploidization events during evolution. As the Brachypodium genus contains about 20 species that differ significantly in terms of their basic chromosome numbers, genome size, ploidy levels and life strategies, studying their centromeres may provide important insight into the structure and evolution of the genome in this interesting and important genus. In this study, we isolated the centromeric DNA of the B. distachyon reference line Bd21 and characterized its composition via the chromatin immunoprecipitation of the nucleosomes that contain the centromere-specific histone CENH3. We revealed that the centromeres of Bd21 have the features of typical multicellular eukaryotic centromeres. Strikingly, these centromeres contain relatively few centromeric satellite DNAs; in particular, the centromere of chromosome 5 (Bd5) consists of only ~40 kb. Moreover, the centromeric retrotransposons in B. distachyon (CRBds) are evolutionarily young. These transposable elements are located both within and adjacent to the CENH3 binding domains, and have similar compositions. Moreover, based on the presence of CRBds in the centromeres, the species in this study can be grouped into two distinct lineages. This may provide new evidence regarding the phylogenetic relationships within the Brachypodium genus. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

  15. Rayleigh Wave Ellipticity Modeling and Inversion for Shallow Structure at the Proposed InSight Landing Site in Elysium Planitia, Mars

    Science.gov (United States)

    Knapmeyer-Endrun, Brigitte; Golombek, Matthew P.; Ohrnberger, Matthias

    2017-10-01

    The SEIS (Seismic Experiment for Interior Structure) instrument onboard the InSight mission will be the first seismometer directly deployed on the surface of Mars. From studies on the Earth and the Moon, it is well known that site amplification in low-velocity sediments on top of more competent rocks has a strong influence on seismic signals, but can also be used to constrain the subsurface structure. Here we simulate ambient vibration wavefields in a model of the shallow sub-surface at the InSight landing site in Elysium Planitia and demonstrate how the high-frequency Rayleigh wave ellipticity can be extracted from these data and inverted for shallow structure. We find that, depending on model parameters, higher mode ellipticity information can be extracted from single-station data, which significantly reduces uncertainties in inversion. Though the data are most sensitive to properties of the upper-most layer and show a strong trade-off between layer depth and velocity, it is possible to estimate the velocity and thickness of the sub-regolith layer by using reasonable constraints on regolith properties. Model parameters are best constrained if either higher mode data can be used or additional constraints on regolith properties from seismic analysis of the hammer strokes of InSight's heat flow probe HP3 are available. In addition, the Rayleigh wave ellipticity can distinguish between models with a constant regolith velocity and models with a velocity increase in the regolith, information which is difficult to obtain otherwise.

  16. 12 CFR 335.501 - Tender offers.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Tender offers. 335.501 Section 335.501 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY SECURITIES OF NONMEMBER INSURED BANKS § 335.501 Tender offers. The provisions of the applicable and currently...

  17. 43 CFR 12.815 - Evaluating offers.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Evaluating offers. 12.815 Section 12.815 Public Lands: Interior Office of the Secretary of the Interior ADMINISTRATIVE AND AUDIT REQUIREMENTS AND... Act-Construction Materials § 12.815 Evaluating offers. (a) The restrictions of the Buy American Act do...

  18. 48 CFR 2825.203 - Evaluating offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Evaluating offers. 2825.203 Section 2825.203 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE Socioeconomic Programs FOREIGN ACQUISITION Buy American Act-Construction Materials 2825.203 Evaluating offers. The HCA, or...

  19. Proteus, New Insights for a New Age

    National Research Council Canada - National Science Library

    Waddell, William; Kim, Joanne; Smith, Jack

    2004-01-01

    .... The Proteus concept offers a range of new insights that, when used in the planning process, will assist military, intelligence, and industry leaders in their efforts to prepare for future success...

  20. 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.