WorldWideScience

Sample records for models offer 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. 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.

  3. 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).  

  4. 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).

  5. 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  

  6. 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.

  7. 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.

  8. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

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

  9. Offers

    CERN Multimedia

    Staff Association

    2015-01-01

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

  10. Offers

    CERN Document Server

    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 ...

  11. 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

  12. 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  

  13. 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

  14. 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)

  15. 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  

  16. Offers

    CERN Multimedia

    Staff Association

    2011-01-01

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

  17. 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.

  18. 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.  

  19. 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/

  20. Offers

    CERN Document Server

    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  

  1. Offers

    CERN Document Server

    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

    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).

  3. 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. ...

  4. 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/

  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. Offer

    CERN Multimedia

    Staff Association

    2011-01-01

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

  7. 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.

  8. 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...

  9. Offers

    CERN Document Server

    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...

  10. 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...

  11. Modeling for Insights

    Energy Technology Data Exchange (ETDEWEB)

    Jacob J. Jacobson; Gretchen Matthern

    2007-04-01

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

  12. 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.

  13. 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...

  14. Rhythmic displays of female gibbons offer insight into the origin of dance

    Science.gov (United States)

    Fan, Peng-Fei; Ma, Chang-Yong; Garber, Paul A.; Zhang, Wen; Fei, Han-Lan; Xiao, Wen

    2016-01-01

    Dance is a universal art form practiced by all human societies and has many functions including sexual attraction, social cohesion, and the therapeutic release of energy. Dance also has been reported in a small number of non-human primate species, in particular apes. However, its function has not been systematically evaluated. We observed 357 intentional, rhythmic, and nonverbal dance displays performed by four adult female cao vit gibbons (Nomascus nasutus) residing in four polygynous groups during 3000 h of observation in Bangliang, Guangxi, China. Females used dance to solicit copulations, as well as to promote a social bond with the group’s lone adult male. In addition, this display appears to represent a form of non-aggressive competition among adult females living in the same group. We found that a female who had a weaker social relationship with the breeding male increased her social and sexual access to the male by an increase in dancing frequency. Given that gibbons dance in various behavioral contexts, and appears to serve several important social and sexual functions, a greater understanding of this form of gestural communication offers an instructive model for examining the origin and evolution of dance in humans and other apes. PMID:27687686

  15. 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.

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

    Science.gov (United States)

    ... scientists will be better able to address the immune system’s role thanks to a new mouse model of scleroderma, which mirrors many aspects of the human disease. Shown here are immune cells (red) in skin from the sclerodermic mice. ...

  17. The genome of Austrofundulus limnaeus offers insights into extreme vertebrate stress tolerance and embryonic development.

    Science.gov (United States)

    Wagner, Josiah T; Singh, Param Priya; Romney, Amie L; Riggs, Claire L; Minx, Patrick; Woll, Steven C; Roush, Jake; Warren, Wesley C; Brunet, Anne; Podrabsky, Jason E

    2018-02-20

    The annual killifish Austrofundulus limnaeus inhabits ephemeral ponds in northern Venezuela, South America, and is an emerging extremophile model for vertebrate diapause, stress tolerance, and evolution. Embryos of A. limnaeus regularly experience extended periods of desiccation and anoxia as a part of their natural history and have unique metabolic and developmental adaptations. Currently, there are limited genomic resources available for gene expression and evolutionary studies that can take advantage of A. limnaeus as a unique model system. We describe the first draft genome sequence of A. limnaeus. The genome was assembled de novo using a merged assembly strategy and was annotated using the NCBI Eukaryotic Annotation Pipeline. We show that the assembled genome has a high degree of completeness in genic regions that is on par with several other teleost genomes. Using RNA-seq and phylogenetic-based approaches, we identify several candidate genes that may be important for embryonic stress tolerance and post-diapause development in A. limnaeus. Several of these genes include heat shock proteins that have unique expression patterns in A. limnaeus embryos and at least one of these may be under positive selection. The A. limnaeus genome is the first South American annual killifish genome made publicly available. This genome will be a valuable resource for comparative genomics to determine the genetic and evolutionary mechanisms that support the unique biology of annual killifishes. In a broader context, this genome will be a valuable tool for exploring genome-environment interactions and their impacts on vertebrate physiology and evolution.

  18. 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.

  19. 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...

  20. What Can Human Geography Offer Climate Change Modelling?

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2014-01-01

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

  1. 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.

  2. 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.

  3. 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.

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

    Science.gov (United States)

    Pittermann, Jarmila; Brodersen, Craig; Watkins, James E.

    2013-01-01

    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 focused on the physiological capacity and stress tolerance of both the sporophyte and the gametophyte generations. In this review, we examine these insights through the lens of plant water relations, 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 variously sized megaphylls are shared between ferns and more derived lineages, and offer an opportunity 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 gametophyte 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. PMID:23935601

  5. New insights in permafrost modelling

    Science.gov (United States)

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

    2017-04-01

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

  6. The evolution and loss of oil-offering flowers: new insights from dated phylogenies for angiosperms and bees

    OpenAIRE

    Renner, S. S.; Schaefer, H.

    2010-01-01

    The interactions between bees that depend on floral oil for their larvae and flowers that offer oil involve an intricate mix of obligate and facultative mutualisms. Using recent phylogenies, new data on oil-offering Cucurbitaceae, and molecular-dating, we ask when and how often oil-offering flowers and oil-foraging bees evolved, and how frequently these traits were lost in the cause of evolution. Local phylogenies and an angiosperm-wide tree show that oil flowers evolved at least 28 times and...

  7. The evolution and loss of oil-offering flowers: new insights from dated phylogenies for angiosperms and bees.

    Science.gov (United States)

    Renner, S S; Schaefer, H

    2010-02-12

    The interactions between bees that depend on floral oil for their larvae and flowers that offer oil involve an intricate mix of obligate and facultative mutualisms. Using recent phylogenies, new data on oil-offering Cucurbitaceae, and molecular-dating, we ask when and how often oil-offering flowers and oil-foraging bees evolved, and how frequently these traits were lost in the cause of evolution. Local phylogenies and an angiosperm-wide tree show that oil flowers evolved at least 28 times and that floral oil was lost at least 36-40 times. The oldest oil flower systems evolved shortly after the K/T boundary independently in American Malpighiaceae, tropical African Cucurbitaceae and Laurasian Lysimachia (Myrsinaceae); the ages of the South African oil flower/oil bee systems are less clear. Youngest oil flower clades include Calceolaria (Calceolariaceae), Iridaceae, Krameria (Krameriaceae) and numerous Orchidaceae, many just a few million years old. In bees, oil foraging evolved minimally seven times and dates back to at least 56 Ma (Ctenoplectra) and 53 Ma (Macropis). The co-occurrence of older and younger oil-offering clades in three of the four geographical regions (but not the Holarctic) implies that oil-foraging bees acquired additional oil hosts over evolutionary time. Such niche-broadening probably started with exploratory visits to flowers resembling oil hosts in scent or colour, as suggested by several cases of Muellerian or Batesian mimicry involving oil flowers.

  8. 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,…

  9. Value-exchange patterns in business models of intermediaries that offer negotiation services

    NARCIS (Netherlands)

    Zlatev, Z.V.; van Eck, Pascal; Wieringa, Roelf J.

    This document is a library of value-exchange patterns. A value-exchange pattern is a repeatedly occurring fragment in value-based business models. The collection is drawn out of business models of market intermediaries that offer negotiation services. The intermediaries are selected as a result of

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

    Directory of Open Access Journals (Sweden)

    Biswajit Sarkar

    2013-01-01

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

  11. 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.

  12. Modelling marine protected areas: insights and hurdles

    Science.gov (United States)

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

    2015-01-01

    Models provide useful insights into conservation and resource management issues and solutions. Their use to date has highlighted conditions under which no-take marine protected areas (MPAs) may help us to achieve the goals of ecosystem-based management by reducing pressures, and where they might fail to achieve desired goals. For example, static reserve designs are unlikely to achieve desired objectives when applied to mobile species or when compromised by climate-related ecosystem restructuring and range shifts. Modelling tools allow planners to explore a range of options, such as basing MPAs on the presence of dynamic oceanic features, and to evaluate the potential future impacts of alternative interventions compared with ‘no-action’ counterfactuals, under a range of environmental and development scenarios. The modelling environment allows the analyst to test if indicators and management strategies are robust to uncertainties in how the ecosystem (and the broader human–ecosystem combination) operates, including the direct and indirect ecological effects of protection. Moreover, modelling results can be presented at multiple spatial and temporal scales, and relative to ecological, economic and social objectives. This helps to reveal potential ‘surprises', such as regime shifts, trophic cascades and bottlenecks in human responses. Using illustrative examples, this paper briefly covers the history of the use of simulation models for evaluating MPA options, and discusses their utility and limitations for informing protected area management in the marine realm. PMID:26460131

  13. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    electricity in both the day-ahead and the balancing markets seeking to maximize its expected profit. Such model is mathematically rigorous, yet computationally efficient.The offering problem is cast as a two-stage stochastic mixed-integer linear programming model which maximizes the virtual power plant...... expected profit. The uncertain parameters, including the power output of the intermittent source and the market prices, are modeled via scenarios based upon historical data. The proposed model is applied to a realistic case study and conclusions are drawn. © 2013 Elsevier Ltd.......A virtual power plant aggregates various local production/consumption units that act in the market as a single entity. This paper considers a virtual power plant consisting of an intermittent source, a storage facility, and a dispatchable power plant. The virtual power plant sells and purchases...

  15. 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

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    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

  17. Special offers

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    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

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    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

  19. Offers INTERSOCCER

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      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!    

  20. 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.

  1. 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.

  2. Corvid caching : insights from a cognitive model

    NARCIS (Netherlands)

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

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

  3. Special Offers

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    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

  4. 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

  5. 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

  6. 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

  7. Modeling Insights into the Lunar Exosphere

    Science.gov (United States)

    Hurley, D.; Feldman, P. D.; Retherford, K. D.; Cook, J.; Stern, S. A.

    2012-12-01

    In addition to Apollo data from the 1970s and ground-based observations, recent data from the Lyman Alpha Mapping Project (LAMP) onboard the Lunar Reconnaissance Orbiter (LRO) are revealing the structure and variability of the lunar exosphere. LAMP has detected helium in the lunar exosphere having many sources of variability. We use a Monte Carlo model to interpret variability in the observations of helium in the lunar exosphere from LAMP. Some of the variability stems from a time-varying source rate. Because the helium in the lunar exosphere predominately derives from the solar wind, we investigate the timescale of transport from release on the dayside to the nightside where it is observed. The model computes transport times for various assumptions about the energy distribution during the initial release and the effects of subsequent surface interactions on the ballistic transport. Owing to the changing geometry of the LRO orbit, spatial gradients also factor into the variability of the observations. We study the expected column density of helium as a function of latitude and longitude using surface temperatures measured by Diviner. The spatial distribution resulting from model runs is strongly influenced by the surface temperature and the assumed thermalization parameter. These dependencies can be used to extract information about the surface interactions. We compare model latitude and longitude dependences to LAMP and Apollo data. Finally, using upstream solar wind measurements and the position of LRO, we calculate the model time-varying helium exosphere of the Moon for comparison with LAMP data obtained in January, June, and July of 2012, including three passages of the Moon through Earth's magnetotail.

  8. 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

    2013-06-01

    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. Recommendations are made for anatomy and physiology instructors who are involved in similar endeavors.

  9. 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.…

  10. Special offer

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    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  

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

  12. Insight

    Science.gov (United States)

    Ramesh, Priya; Wei, Annan; Welter, Elisabeth; Bamps, Yvan; Stoll, Shelley; Bukach, Ashley; Sajatovic, Martha; Sahoo, Satya S

    2015-11-01

    Insight is a Semantic Web technology-based platform to support large-scale secondary analysis of healthcare data for neurology clinical research. Insight features the novel use of: (1) provenance metadata, which describes the history or origin of patient data, in clinical research analysis, and (2) support for patient cohort queries across multiple institutions conducting research in epilepsy, which is the one of the most common neurological disorders affecting 50 million persons worldwide. Insight is being developed as a healthcare informatics infrastructure to support a national network of eight epilepsy research centers across the U.S. funded by the U.S. Centers for Disease Control and Prevention (CDC). This paper describes the use of the World Wide Web Consortium (W3C) PROV recommendation for provenance metadata that allows researchers to create patient cohorts based on the provenance of the research studies. In addition, the paper describes the use of descriptive logic-based OWL2 epilepsy ontology for cohort queries with "expansion of query expression" using ontology reasoning. Finally, the evaluation results for the data integration and query performance are described using data from three research studies with 180 epilepsy patients. The experiment results demonstrate that Insight is a scalable approach to use Semantic provenance metadata for context-based data analysis in healthcare informatics.

  13. Communicating Insights from Complex Simulation Models: A Gaming Approach.

    Science.gov (United States)

    Vennix, Jac A. M.; Geurts, Jac L. A.

    1987-01-01

    Describes design principles followed in developing an interactive microcomputer-based simulation to study financial and economic aspects of the Dutch social security system. The main goals are to improve participants' insights into the formal simulation model, and to improve policy development skills. Plans for future research are also discussed.…

  14. 3D Printing of Intracranial Aneurysms Using Fused Deposition Modeling Offers Highly Accurate Replications.

    Science.gov (United States)

    Frölich, A M J; Spallek, J; Brehmer, L; Buhk, J-H; Krause, D; Fiehler, J; Kemmling, A

    2016-01-01

    As part of a multicenter cooperation (Aneurysm-Like Synthetic bodies for Testing Endovascular devices in 3D Reality) with focus on implementation of additive manufacturing in neuroradiologic practice, we systematically assessed the technical feasibility and accuracy of several additive manufacturing techniques. We evaluated the method of fused deposition modeling for the production of aneurysm models replicating patient-specific anatomy. 3D rotational angiographic data from 10 aneurysms were processed to obtain volumetric models suitable for fused deposition modeling. A hollow aneurysm model with connectors for silicone tubes was fabricated by using acrylonitrile butadiene styrene. Support material was dissolved, and surfaces were finished by using NanoSeal. The resulting models were filled with iodinated contrast media. 3D rotational angiography of the models was acquired, and aneurysm geometry was compared with the original patient data. Reproduction of hollow aneurysm models was technically feasible in 8 of 10 cases, with aneurysm sizes ranging from 41 to 2928 mm(3) (aneurysm diameter, 3-19 mm). A high level of anatomic accuracy was observed, with a mean Dice index of 93.6% ± 2.4%. Obstructions were encountered in vessel segments of modeling is a promising technique, which allows rapid and precise replication of cerebral aneurysms. The porosity of the models can be overcome by surface finishing. Models produced with fused deposition modeling may serve as educational and research tools and could be used to individualize treatment planning. © 2016 by American Journal of Neuroradiology.

  15. 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.

  16. 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.

  17. 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...

  18. Serving Young Gifted Math Students: Educators Offer an Example of Implementing the Center for Talented Youth Model in Public Schools.

    Science.gov (United States)

    Corazza, Luciano; And Others

    1995-01-01

    This article describes the implementation in Brooklyn, New York, of the Diagnostic Testing and Prescriptive Instruction mathematics instruction model, which establishes the level of knowledge of each student and then offers instruction at the student's pace. Implementation involves teacher training, student selection, curriculum development, and…

  19. Technical assistance offered to community health programs through a resource model.

    Science.gov (United States)

    Merino, R; Fischer, E; Bosch, S J

    1985-01-01

    A multidisciplinary unit in the Department of Community Medicine, Mount Sinai School of Medicine, consists of a core group of specialists who plan, develop, and evaluate community health care programs. The primary tools used by the staff of the Services Coordination Unit, epidemiology and behavioral and management sciences, result in improved organization and coordination of health services and community resources. The small unit of specialists functions as a resource group, helping community groups address the complex problems of planning, organization, delivery, and financing of health services. By offering technical assistance rather than day-to-day health care services, the unit has established an education and training program in New York's East Harlem, which surrounds the medical school. Over the last 10 years, that approach has enhanced the administrative and financial viability of existing health programs in East Harlem. Since the unit's establishment, it has collaborated with a broad variety of community groups. More than 20 programs have resulted. The income generated by the unit completely covers the expenses and has done so since 1976; "seed money" was used for startup and the first 3 years of operation. The unit is paid for long-term services and for most consultations.

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

    Science.gov (United States)

    Wallace, Rodrick

    2014-10-01

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

  1. Optogenetic versus Electrical Stimulation of Human Cardiomyocytes: Modeling Insights

    Science.gov (United States)

    Williams, John C.; Entcheva, Emilia

    2015-01-01

    is not feasible due to electrochemical limitations. Our analysis offers insights for designing future new energy-efficient stimulation strategies in heart or brain. PMID:25902433

  2. 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…

  3. 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...

  4. Health Belief Model Offers Opportunities for Designing Weight Management Interventions for College Students.

    Science.gov (United States)

    McArthur, Laura H; Riggs, Alysse; Uribe, Franchesca; Spaulding, Trent J

    2017-10-30

    Identify weight-related beliefs of college students and test the predictive power of the Health Belief Model for body mass index (BMI). Cross-sectional online survey with beliefs measured on 5-point scales. University in North Carolina. Undergraduates (n = 516; 91.9%), females (n = 399; 71.3%), white non-Hispanic students (n = 507; 86.2%), and 20.3% of overweight or obese status. Perceived severity, susceptibility, barriers, benefits, and internal and external cues to action. One-way ANOVA and regression. Significance was P beliefs concerned benefits of healthy eating and physical activity (mean, 4.1 ± 0.7); weakest beliefs concerned barriers to adopting such behaviors (mean, 2.6 ± 0.9). The regression model was statistically significant (P beliefs were identified that could serve as the basis for weight-related interventions addressing specific concerns, needs, and goals of college students. Copyright © 2017 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  5. Ex vivo human pancreatic slice preparations offer a valuable model for studying pancreatic exocrine biology.

    Science.gov (United States)

    Liang, Tao; Dolai, Subhankar; Xie, Li; Winter, Erin; Orabi, Abrahim I; Karimian, Negar; Cosen-Binker, Laura I; Huang, Ya-Chi; Thorn, Peter; Cattral, Mark S; Gaisano, Herbert Y

    2017-04-07

    A genuine understanding of human exocrine pancreas biology and pathobiology has been hampered by a lack of suitable preparations and reliance on rodent models employing dispersed acini preparations. We have developed an organotypic slice preparation of the normal portions of human pancreas obtained from cancer resections. The preparation was assessed for physiologic and pathologic responses to the cholinergic agonist carbachol (Cch) and cholecystokinin (CCK-8), including 1) amylase secretion, 2) exocytosis, 3) intracellular Ca 2+ responses, 4) cytoplasmic autophagic vacuole formation, and 5) protease activation. Cch and CCK-8 both dose-dependently stimulated secretory responses from human pancreas slices similar to those previously observed in dispersed rodent acini. Confocal microscopy imaging showed that these responses were accounted for by efficient apical exocytosis at physiologic doses of both agonists and by apical blockade and redirection of exocytosis to the basolateral plasma membrane at supramaximal doses. The secretory responses and exocytotic events evoked by CCK-8 were mediated by CCK-A and not CCK-B receptors. Physiologic agonist doses evoked oscillatory Ca 2+ increases across the acini. Supraphysiologic doses induced formation of cytoplasmic autophagic vacuoles and activation of proteases (trypsin, chymotrypsin). Maximal atropine pretreatment that completely blocked all the Cch-evoked responses did not affect any of the CCK-8-evoked responses, indicating that rather than acting on the nerves within the pancreas slice, CCK cellular actions directly affected human acinar cells. Human pancreas slices represent excellent preparations to examine pancreatic cell biology and pathobiology and could help screen for potential treatments for human pancreatitis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

    Mariel, Petr; Meyerhoff, Jürgen

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Excellence in role modelling: insight and perspectives from the pros.

    Science.gov (United States)

    Wright, Scott M; Carrese, Joseph A

    2002-09-17

    Role modelling is an effective teaching method in medical education. We sought to better understand role modelling by examining the insights of respected physician role models. We conducted 30-minute in-depth interviews with 29 highly regarded role models at 2 large teaching hospitals. We coded the transcripts independently, and compared our coding for agreement. Content analysis identified several major categories of themes. The informants identified specific characteristics related to role modelling. Subcategories under the domain of personal qualities included interpersonal skills, a positive outlook, a commitment to excellence and growth, integrity and leadership. Under the domain of teaching, the subcategories were establishing rapport with learners, developing specific teaching philosophies and methods, and being committed to the growth of learners. Subjects thought there was some overlap between teaching and role modelling, but felt that the latter was more implicit and more encompassing. Being a strong clinician was regarded as necessary but not sufficient for being an exemplary physician role model. Perceived barriers to effective role modelling included being impatient and overly opinionated, being quiet, being overextended, and having difficulty remembering names and faces. Physician role models described role modeling consciousness, in that they specifically think about being role models when interacting with learners. Subjects believed that medical learners should emulate multiple role models. Highly regarded physician role models possess personal qualities, teaching abilities and exceptional clinical skills that outweigh their own barriers to serving as effective role models. Many of these positive attributes of role models represent behaviours that can be modified or skills that can be acquired.

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

    Science.gov (United States)

    Broecker, Wallace S.; Putnam, Aaron E.

    2013-10-01

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

  9. Modeling Defibrillation of the Heart: Approaches and Insights

    Science.gov (United States)

    Trayanova, Natalia; Constantino, Jason; Ashihara, Takashi; Plank, Gernot

    2012-01-01

    Cardiac defibrillation, as accomplished nowadays by automatic, implantable devices (ICDs), constitutes the most important means of combating sudden cardiac death. While ICD therapy has proved to be efficient and reliable, defibrillation is a traumatic experience. Thus, research on defibrillation mechanisms, particularly aimed at lowering defibrillation voltage, remains an important topic. Advancing our understanding towards a full appreciation of the mechanisms by which a shock interacts with the heart is the most promising approach to achieve this goal. The aim of this paper is to assess the current state-of-the-art in ventricular defibrillation modeling, focusing on both numerical modeling approaches and major insights that have been obtained using defibrillation models, primarily those of realistic ventricular geometry. The paper showcases the contributions that modeling and simulation have made to our understanding of the defibrillation process. The review thus provides an example of biophysically based computational modeling of the heart (i.e., cardiac defibrillation) that has advanced the understanding of cardiac electrophysiological interaction at the organ level and has the potential to contribute to the betterment of the clinical practice of defibrillation. PMID:22273793

  10. 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.

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Andrea Lisjak

    2014-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Isabel eHuang-Doran

    2016-06-01

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

  15. Characterizing poliovirus transmission and evolution: insights from modeling experiences with wild and vaccine-related polioviruses.

    Science.gov (United States)

    Duintjer Tebbens, Radboud J; Pallansch, Mark A; Kalkowska, Dominika A; Wassilak, Steven G F; Cochi, Stephen L; Thompson, Kimberly M

    2013-04-01

    With national and global health policymakers facing numerous complex decisions related to achieving and maintaining polio eradication, we expanded our previously developed dynamic poliovirus transmission model using information from an expert literature review process and including additional immunity states and the evolution of oral poliovirus vaccine (OPV). The model explicitly considers serotype differences and distinguishes fecal-oral and oropharyngeal transmission. We evaluated the model by simulating diverse historical experiences with polioviruses, including one country that eliminated wild poliovirus using both OPV and inactivated poliovirus vaccine (IPV) (USA), three importation outbreaks of wild poliovirus (Albania, the Netherlands, Tajikistan), one situation in which no circulating vaccine-derived polioviruses (cVDPVs) emerge despite annual OPV use and cessation (Cuba), three cVDPV outbreaks (Haiti, Madura Island in Indonesia, northern Nigeria), one area of current endemic circulation of all three serotypes (northern Nigeria), and one area with recent endemic circulation and subsequent elimination of multiple serotypes (northern India). We find that when sufficient information about the conditions exists, the model can reproduce the general behavior of poliovirus transmission and outbreaks while maintaining consistency in the generic model inputs. The assumption of spatially homogeneous mixing remains a significant limitation that affects the performance of the differential equation-based model when significant heterogeneities in immunity and mixing may exist. Further studies on OPV virus evolution and improved understanding of the mechanisms of mixing and transmission may help to better characterize poliovirus transmission in populations. Broad application of the model promises to offer insights in the context of global and national policy and economic models. © 2013 Society for Risk Analysis.

  16. 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

  17. 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

  18. 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.

  19. 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)

  20. 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

  1. 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.)

  2. 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

  3. Mathematical modeling of microtubule dynamics: insights into physiology and disease.

    Science.gov (United States)

    Buxton, Gavin A; Siedlak, Sandra L; Perry, George; Smith, Mark A

    2010-12-01

    Computer models of microtubule dynamics have provided the basis for many of the theories on the cellular mechanics of the microtubules, their polymerization kinetics, and the diffusion of tubulin and tau. In the three-dimensional model presented here, we include the effects of tau concentration and the hydrolysis of GTP-tubulin to GDP-tubulin and observe the emergence of microtubule dynamic instability. This integrated approach simulates the essential physics of microtubule dynamics in a cellular environment. The model captures the structure of the microtubules as they undergo steady state dynamic instabilities in this simplified geometry, and also yields the average number, length, and cap size of the microtubules. The model achieves realistic geometries and simulates cellular structures found in degenerating neurons in disease states such as Alzheimer disease. Further, this model can be used to simulate microtubule changes following the addition of antimitotic drugs which have recently attracted attention as chemotherapeutic agents. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. 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

  5. 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

  6. 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)

  7. Quantitative insight into models of Hedgehog signal transduction.

    Science.gov (United States)

    Farzan, Shohreh F; Ogden, Stacey K; Robbins, David J

    2010-01-01

    The Hedgehog (Hh) signaling pathway is an essential regulator of embryonic development and a key factor in carcinogenesis.(1,2) Hh, a secreted morphogen, activates intracellular signaling events via downstream effector proteins, which translate the signal to regulate target gene transcription.(3,4) In a recent publication, we quantitatively compared two commonly accepted models of Hh signal transduction.(5) Each model requires a different ratio of signaling components to be feasible. Thus, we hypothesized that knowing the steady-state ratio of core signaling components might allow us to distinguish between models. We reported vast differences in the molar concentrations of endogenous effectors of Hh signaling, with Smo present in limiting concentrations.(5) This extra view summarizes the implications of this endogenous ratio in relation to current models of Hh signaling and places our results in the context of recent work describing the involvement of guanine nucleotide binding protein Galphai and Cos2 motility.

  8. Uterine disorders and pregnancy complications: insights from mouse models

    OpenAIRE

    Lim, Hyunjung Jade; Wang, Haibin

    2010-01-01

    Much of our knowledge of human uterine physiology and pathology has been extrapolated from the study of diverse animal models, as there is no ideal system for studying human uterine biology in vitro. Although it remains debatable whether mouse models are the most suitable system for investigating human uterine function(s), gene-manipulated mice are considered by many the most useful tool for mechanistic analysis, and numerous studies have identified many similarities in female reproduction be...

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

    Science.gov (United States)

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

    2016-04-01

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

  10. Obsessive-compulsive disorder: Insights from animal models.

    Science.gov (United States)

    Szechtman, Henry; Ahmari, Susanne E; Beninger, Richard J; Eilam, David; Harvey, Brian H; Edemann-Callesen, Henriette; Winter, Christine

    2017-05-01

    Research with animal models of obsessive-compulsive disorder (OCD) shows the following: (1) Optogenetic studies in mice provide evidence for a plausible cause-effect relation between increased activity in cortico-basal ganglia-thalamo-cortical (CBGTC) circuits and OCD by demonstrating the induction of compulsive behavior with the experimental manipulation of the CBGTC circuit. (2) Parallel use of several animal models is a fruitful paradigm to examine the mechanisms of treatment effects of deep brain stimulation in distinct OCD endophenotypes. (3) Features of spontaneous behavior in deer mice constitute a rich platform to investigate the neurobiology of OCD, social ramifications of a compulsive phenotype, and test novel drugs. (4) Studies in animal models for psychiatric disorders comorbid with OCD suggest comorbidity may involve shared neural circuits controlling expression of compulsive behavior. (5) Analysis of compulsive behavior into its constitutive components provides evidence from an animal model for a motivational perspective on OCD. (6) Methods of behavioral analysis in an animal model translate to dissection of compulsive rituals in OCD patients, leading to diagnostic tests. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Quantitative modeling of chronic myeloid leukemia: insights from radiobiology

    Science.gov (United States)

    Radivoyevitch, Tomas; Hlatky, Lynn; Landaw, Julian

    2012-01-01

    Mathematical models of chronic myeloid leukemia (CML) cell population dynamics are being developed to improve CML understanding and treatment. We review such models in light of relevant findings from radiobiology, emphasizing 3 points. First, the CML models almost all assert that the latency time, from CML initiation to diagnosis, is at most ∼ 10 years. Meanwhile, current radiobiologic estimates, based on Japanese atomic bomb survivor data, indicate a substantially higher maximum, suggesting longer-term relapses and extra resistance mutations. Second, different CML models assume different numbers, between 400 and 106, of normal HSCs. Radiobiologic estimates favor values > 106 for the number of normal cells (often assumed to be the HSCs) that are at risk for a CML-initiating BCR-ABL translocation. Moreover, there is some evidence for an HSC dead-band hypothesis, consistent with HSC numbers being very different across different healthy adults. Third, radiobiologists have found that sporadic (background, age-driven) chromosome translocation incidence increases with age during adulthood. BCR-ABL translocation incidence increasing with age would provide a hitherto underanalyzed contribution to observed background adult-onset CML incidence acceleration with age, and would cast some doubt on stage-number inferences from multistage carcinogenesis models in general. PMID:22353999

  12. 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)

  13. 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.

  14. 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.

  15. [Gly14]-Humanin offers neuroprotection through glycogen synthase kinase-3β inhibition in a mouse model of intracerebral hemorrhage.

    Science.gov (United States)

    Wang, Tao; Huang, Ya; Zhang, Mingyang; Wang, Long; Wang, Yaoqi; Zhang, Lu; Dong, Wenwen; Chang, Pan; Wang, Zufeng; Chen, Xiping; Tao, Luyang

    2013-06-15

    Perihematomal brain edema formation and consequent cell death contribute to second brain injury resulting in severe neurological deficits and sometimes delayed fatality after intracerebral hemorrhage (ICH). [Gly14]-Humanin (HNG), a variant of Humanin (HN) in which the 14th amino acid serine is replaced with glycine, reduced Alzheimer's disease-relevant insults and improved neurological deficits in an ischemia stroke model. In the study, we aimed to evaluate whether HNG posttreatment attenuated early brain injury after ICH and whether the protective effect was associated with regulation of apoptosis via phosphatidylinositol 3-kinase (PI3K)-Akt/GSK-3β signaling. Male ICR mice were subjected to infusion of Type IV collagenase (to induce ICH) of saline (for shams) into the left striatum. ICH animals received vehicle, HNG (1 or 2.5 μg in 100 μl saline) administration intraperitoneally 1h post injury. Compared with vehicle, HNG-2.5 μg treatment improved neurological outcome and reduced brain edema at 24 and 72 h after surgery (P<0.05), but wortmannin (15 μg/kg, 90 min before HNG-2.5 μg, intravenously) obliterated the effect. HNG-2.5 μg also reduced cell insults and injury volume at 24 and 72 h after surgery (P<0.05, vs. vehicle). Furthermore, HNG-2.5 μg treatment increased p-Akt and Bcl-2 and decreased p-GSK-3β, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase expressions in the ipsilateral hemisphere (P<0.05, vs. vehicle), however, the effect was reversed by wortmannin. In conclusion, HNG treatment improved functional and morphological outcomes after experimental ICH in mice and the protective effect was associated with suppressing apoptosis through PI3K-Akt/GSK-3β signaling pathway. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. 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…

  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. 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.

  19. 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

  20. A logical model provides insights into T cell receptor signaling.

    Directory of Open Access Journals (Sweden)

    Julio Saez-Rodriguez

    2007-08-01

    Full Text Available Cellular decisions are determined by complex molecular interaction networks. Large-scale signaling networks are currently being reconstructed, but the kinetic parameters and quantitative data that would allow for dynamic modeling are still scarce. Therefore, computational studies based upon the structure of these networks are of great interest. Here, a methodology relying on a logical formalism is applied to the functional analysis of the complex signaling network governing the activation of T cells via the T cell receptor, the CD4/CD8 co-receptors, and the accessory signaling receptor CD28. Our large-scale Boolean model, which comprises 94 nodes and 123 interactions and is based upon well-established qualitative knowledge from primary T cells, reveals important structural features (e.g., feedback loops and network-wide dependencies and recapitulates the global behavior of this network for an array of published data on T cell activation in wild-type and knock-out conditions. More importantly, the model predicted unexpected signaling events after antibody-mediated perturbation of CD28 and after genetic knockout of the kinase Fyn that were subsequently experimentally validated. Finally, we show that the logical model reveals key elements and potential failure modes in network functioning and provides candidates for missing links. In summary, our large-scale logical model for T cell activation proved to be a promising in silico tool, and it inspires immunologists to ask new questions. We think that it holds valuable potential in foreseeing the effects of drugs and network modifications.

  1. Treacher Collins syndrome: New insights from animal models.

    Science.gov (United States)

    Tse, William Ka Fai

    2016-12-01

    Treacher Collins syndrome (TCS, OMIM: 154500), an autosomal-dominant craniofacial developmental syndrome that occurs in 1 out of every 50,000 live births, is characterized by craniofacial malformation. Mutations in TCOF1, POLR1C, or POLR1D have been identified in affected individuals. In addition to established mouse models, zebrafish models have recently emerged as an valuable method to study facial disease. In this report, we summarized the two updated articles working on the pathogenesis of the newly identified polr1c and polr1d TCS mutations (Lau et al., 2016; Noack Watt et al., 2016) and discussed the possibility of using the anti-oxidants to prevent or rescue the TCS facial phenotype (Sakai et al., 2016). Taken together, this article provides an update on the disease from basic information to pathogenesis, and further summarizes the suggested therapies from recent laboratory research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  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. 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. 

  4. 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.

  5. 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.

  6. Contemporary Phage Biology: From Classic Models to New Insights.

    Science.gov (United States)

    Ofir, Gal; Sorek, Rotem

    2018-03-08

    Bacteriophages, discovered about a century ago, have been pivotal as models for understanding the fundamental principles of molecular biology. While interest in phage biology declined after the phage "golden era," key recent developments, including advances in phage genomics, microscopy, and the discovery of the CRISPR-Cas anti-phage defense system, have sparked a renaissance in phage research in the past decade. This review highlights recently discovered unexpected complexities in phage biology, describes a new arsenal of phage genes that help them overcome bacterial defenses, and discusses advances toward documentation of the phage biodiversity on a global scale. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Subduction initiation and Obduction: insights from analog models

    Science.gov (United States)

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

    2013-12-01

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

  8. Genomic insights from the oleaginous model alga Nannochloropsis gaditana.

    Science.gov (United States)

    Jinkerson, Robert E; Radakovits, Randor; Posewitz, Matthew C

    2013-01-01

    Nannochloropsis species have emerged as leading phototrophic microorganisms for the production of biofuels. Several isolates produce large quantities of triacylglycerols, grow rapidly, and can be cultivated at industrial scales. Recently, the mitochondrial, plastid and nuclear genomes of Nannochloropsis gaditana were sequenced. Genomic interrogation revealed several key features that likely facilitate the oleaginous phenotype observed in Nannochloropsis, including an over-representation of genes involved in lipid biosynthesis. Here we present additional analyses on gene orientation, vitamin B12 requiring enzymes, the acetyl-CoA metabolic node, and codon usage in N. gaditana. Nuclear genome transformation methods are established with exogenous DNA integration occurring via either random incorporation or by homologous recombination, making Nannochloropsis amenable to both forward and reverse genetic engineering. Completion of a draft genomic sequence, establishment of transformation techniques, and robust outdoor growth properties have positioned Nannochloropsis as a new model alga with significant potential for further development into an integrated photons-to-fuel production platform.

  9. 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

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Belinda S Cowling

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

  12. 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.

  13. Mouse models of altered gonadotrophin action: insight into male reproductive disorders.

    Science.gov (United States)

    Jonas, Kim C; Oduwole, Olayiwola O; Peltoketo, Hellevi; Rulli, Susana B; Huhtaniemi, Ilpo T

    2014-10-01

    The advent of technologies to genetically manipulate the mouse genome has revolutionised research approaches, providing a unique platform to study the causality of reproductive disorders in vivo. With the relative ease of generating genetically modified (GM) mouse models, the last two decades have yielded multiple loss-of-function and gain-of-function mutation mouse models to explore the role of gonadotrophins and their receptors in reproductive pathologies. This work has provided key insights into the molecular mechanisms underlying reproductive disorders with altered gonadotrophin action, revealing the fundamental roles of these pituitary hormones and their receptors in the hypothalamic-pituitary-gonadal axis. This review will describe GM mouse models of gonadotrophins and their receptors with enhanced or diminished actions, specifically focusing on the male. We will discuss the mechanistic insights gained from these models into male reproductive disorders, and the relationship and understanding provided into male human reproductive disorders originating from altered gonadotrophin action. © 2014 Society for Reproduction and Fertility.

  14. 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.

  15. 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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  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. New insights into mammalian signaling pathways using microfluidic pulsatile inputs and mathematical modeling

    Science.gov (United States)

    Sumit, M.; Takayama, S.; Linderman, J. J.

    2016-01-01

    Temporally modulated input mimics physiology. This chemical communication strategy filters the biochemical noise through entrainment and phase-locking. Under laboratory conditions, it also expands the observability space for downstream responses. A combined approach involving microfluidic pulsatile stimulation and mathematical modeling has led to deciphering of hidden/unknown temporal motifs in several mammalian signaling pathways and has provided mechanistic insights, including how these motifs combine to form distinct band-pass filters and govern fate regulation under dynamic microenvironment. This approach can be utilized to understand signaling circuit architectures and to gain mechanistic insights for several other signaling systems. Potential applications include synthetic biology and biotechnology, in developing pharmaceutical interventions, and in developing lab-on-chip models. PMID:27868126

  20. New insights into mammalian signaling pathways using microfluidic pulsatile inputs and mathematical modeling.

    Science.gov (United States)

    Sumit, M; Takayama, S; Linderman, J J

    2017-01-23

    Temporally modulated input mimics physiology. This chemical communication strategy filters the biochemical noise through entrainment and phase-locking. Under laboratory conditions, it also expands the observability space for downstream responses. A combined approach involving microfluidic pulsatile stimulation and mathematical modeling has led to deciphering of hidden/unknown temporal motifs in several mammalian signaling pathways and has provided mechanistic insights, including how these motifs combine to form distinct band-pass filters and govern fate regulation under dynamic microenvironment. This approach can be utilized to understand signaling circuit architectures and to gain mechanistic insights for several other signaling systems. Potential applications include synthetic biology and biotechnology, in developing pharmaceutical interventions, and in developing lab-on-chip models.

  1. 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.

  2. Offers for our members

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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.

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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.

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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.

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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.

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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...

  7. Offers for our members

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    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.

  8. Offers for our members

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    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 &...

  9. 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.

  10. Fundamental studies of novel zwitterionic hybrid membranes: kinetic model and mechanism insights into strontium removal.

    Science.gov (United States)

    Zhu, Wen; Liu, Junsheng; Li, Meng

    2014-01-01

    A series of zwitterionic hybrid membranes were prepared via the ring opening of 1,3-propanesultone with the amine groups in the chains of TMSPEDA and a subsequent sol-gel process. Their kinetic models for strontium removal were investigated using three two-parameter kinetic equations (i.e., Lagergren pseudo-first order, pseudo-second order, and Elovich models). Adsorption mechanism was evaluated using intraparticle diffusion model, diffusion-chemisorption model, and Boyd equation. It was found that the adsorption of strontium ions on these zwitterionic hybrid membranes fitted well with the Lagergren pseudo-second order model. Mechanism insights suggested that diffusion-chemisorption was one of the main adsorption mechanisms. Boyd equation exhibited that film-diffusion mechanism might be the control process during the starting period. These findings are very useful in strontium removal from the stimulated radioactive wastewater.

  11. Fundamental Studies of Novel Zwitterionic Hybrid Membranes: Kinetic Model and Mechanism Insights into Strontium Removal

    Directory of Open Access Journals (Sweden)

    Wen Zhu

    2014-01-01

    Full Text Available A series of zwitterionic hybrid membranes were prepared via the ring opening of 1,3-propanesultone with the amine groups in the chains of TMSPEDA and a subsequent sol-gel process. Their kinetic models for strontium removal were investigated using three two-parameter kinetic equations (i.e., Lagergren pseudo-first order, pseudo-second order, and Elovich models. Adsorption mechanism was evaluated using intraparticle diffusion model, diffusion-chemisorption model, and Boyd equation. It was found that the adsorption of strontium ions on these zwitterionic hybrid membranes fitted well with the Lagergren pseudo-second order model. Mechanism insights suggested that diffusion-chemisorption was one of the main adsorption mechanisms. Boyd equation exhibited that film-diffusion mechanism might be the control process during the starting period. These findings are very useful in strontium removal from the stimulated radioactive wastewater.

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

    Science.gov (United States)

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

    2017-06-01

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

  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

    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

  14. Prediction, scenarios and insight: The uses of an end-to-end model

    Science.gov (United States)

    Steele, John H.

    2012-09-01

    A major function of ecosystem models is to provide extrapolations from observed data in terms of predictions or scenarios or insight. These models can be at various levels of taxonomic resolution such as total community production, abundance of functional groups, or species composition, depending on the data input as drivers. A 40-year dynamic simulation of end-to-end processes in the Georges Bank food web is used to illustrate the input/output relations and the insights gained at the three levels of food web aggregation. The focus is on the intermediate level and the longer term changes in three functional fish guilds - planktivores, benthivores and piscivores - in terms of three ecosystem-based metrics - nutrient input, relative productivity of plankton and benthos, and food intake by juvenile fish. These simulations can describe the long term constraints imposed on guild structure and productivity by energy fluxes over the 40 years but cannot explain concurrent switches in abundance of individual species within guilds. Comparing time series data for individual species with model output provides insights; but including the data in the model would confer only limited extra information. The advantages and limitations of the three levels of resolution of models in relation to ecosystem-based management are: The correlations between primary production and total yield of fish imply a “bottom-up” constraint on end-to-end energy flow through the food web that can provide predictions of such yields. Functionally defined metrics such as nutrient input, relative productivity of plankton and benthos and food intake by juvenile fish, represent bottom-up, mid-level and top-down forcing of the food web. Model scenarios using these metrics can demonstrate constraints on the productivity of these functionally defined guilds within the limits set by (1). Comparisons of guild simulations with time series of fish species provide insight into the switches in species dominance

  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. Effects of sub-clinical psychosis and cognitive insight on psychological well-being: a structural equation model.

    Science.gov (United States)

    Weintraub, Marc J; Weisman de Mamani, Amy

    2015-03-30

    Psychological well-being has been widely researched along the psychosis spectrum, and increased psychotic symptoms are generally associated with worse well-being. Additionally, the construct of insight has been extensively studied in schizophrenia. While having greater insight has many benefits for those with schizophrenia, a paradox exists in which greater insight is also associated with poorer psychological well-being. However, it is unclear whether the link between insight and poor well-being occurs only once serious psychopathology has been established, or whether this is a more universal process seen even at lower levels on the psychosis spectrum. We used a structural modeling approach in an ethnically diverse, non-clinical sample of 420 undergraduates to evaluate the association between sub-clinical psychosis, cognitive insight and psychological well-being. As hypothesized, results indicated that sub-clinical psychotic symptoms were negatively associated with psychological well-being. The insight paradox was also substantiated, as greater cognitive insight was associated with worse psychological well-being. However, cognitive insight did not moderate the association between symptoms and well-being. The link between sub-clinical psychotic symptoms and psychological well-being as well as the insight paradox appears to emerge even before reaching threshold for a psychotic disorder. Research and clinical implications are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. 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.

  18. Recent Insights in the Dynamical Structure of Cepheids' Atmosphere and Prospect Concerning Hydrodynamical Modelling

    Science.gov (United States)

    Nardetto, N.

    The link between the dynamical structure of Cepheid atmosphere and the distance scale calibration in the universe is now clearly established through a period-projection factor relation (Pp). However, to support future observations, we currently need fully consistent hydrodynamical models, including pulsating and evolutionary theories, convective energy transport, adaptive numerical meshes, and a refined calculation of the radiative transfer within the pulsating atmosphere and the expected circumstellar envelope (hereafter CSE). Confronting such models with observations (spectral line profiles, spatial- and spectral- visibility curves), will permit to resolve and/or strengthen subtle questions concerning (1) the limb-darkening, (2) the dynamical structure of Cepheids' atmosphere, (3) the expected interaction between the atmosphere and the CSE, and (4) it will bring new insights in determining the fundamental parameters of Cepheids. All these physical quantities are supposed furthermore to be linked to the pulsation period of Cepheids. From these studies, it will be possible to paint a glowing picture of all Cepheids within the instability strip, allowing an unprecedent calibration of the period-luminosity relation, leading to new insights in the fields of extragalactic distance scales and cosmology.

  19. Deep models for brain EM image segmentation: novel insights and improved performance.

    Science.gov (United States)

    Fakhry, Ahmed; Peng, Hanchuan; Ji, Shuiwang

    2016-08-01

    Accurate segmentation of brain electron microscopy (EM) images is a critical step in dense circuit reconstruction. Although deep neural networks (DNNs) have been widely used in a number of applications in computer vision, most of these models that proved to be effective on image classification tasks cannot be applied directly to EM image segmentation, due to the different objectives of these tasks. As a result, it is desirable to develop an optimized architecture that uses the full power of DNNs and tailored specifically for EM image segmentation. In this work, we proposed a novel design of DNNs for this task. We trained a pixel classifier that operates on raw pixel intensities with no preprocessing to generate probability values for each pixel being a membrane or not. Although the use of neural networks in image segmentation is not completely new, we developed novel insights and model architectures that allow us to achieve superior performance on EM image segmentation tasks. Our submission based on these insights to the 2D EM Image Segmentation Challenge achieved the best performance consistently across all the three evaluation metrics. This challenge is still ongoing and the results in this paper are as of June 5, 2015. https://github.com/ahmed-fakhry/dive : sji@eecs.wsu.edu. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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....

  5. 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...... and that space can be utilized as a lever when working to change the organization in favor of a more inclusive climate....

  6. 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

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

    DEFF Research Database (Denmark)

    Holck, Lotte

    Inclusion has long been associated with concerns of tearing down the ranked and filed “gendered and racialized” hierarchical spaces of traditional organizations, most infamously imbued in Taylorism and Scientific management with its Panopticon apparatus designed to sustain and stabilize the power......-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...

  8. Communication Theory Offers Insight into Mathematics Teachers' Talk

    Science.gov (United States)

    Forrest, Denise B.

    2008-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  10. 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...

  11. Is structural sensitivity a problem of oversimplified biological models? Insights from nested Dynamic Energy Budget models.

    Science.gov (United States)

    Aldebert, Clement; Kooi, Bob W; Nerini, David; Poggiale, Jean-Christophe

    2018-03-14

    Many current issues in ecology require predictions made by mathematical models, which are built on somewhat arbitrary choices. Their consequences are quantified by sensitivity analysis to quantify how changes in model parameters propagate into an uncertainty in model predictions. An extension called structural sensitivity analysis deals with changes in the mathematical description of complex processes like predation. Such processes are described at the population scale by a specific mathematical function taken among similar ones, a choice that can strongly drive model predictions. However, it has only been studied in simple theoretical models. Here, we ask whether structural sensitivity is a problem of oversimplified models. We found in predator-prey models describing chemostat experiments that these models are less structurally sensitive to the choice of a specific functional response if they include mass balance resource dynamics and individual maintenance. Neglecting these processes in an ecological model (for instance by using the well-known logistic growth equation) is not only an inappropriate description of the ecological system, but also a source of more uncertain predictions. Copyright © 2018. Published by Elsevier Ltd.

  12. Offers

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    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.

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

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

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

  16. OFFERS

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    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  

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

  18. Offers

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

  19. Offers

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    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

  20. Offer

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    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...

  1. Offers

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

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    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

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    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...

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Renata da Fontoura Budaszewski

    2016-10-01

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

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

    Science.gov (United States)

    Mahaffey, Barbara A.

    2010-01-01

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

  7. Insights into the relationships among capillary pressure, saturation, interfacial area and relative permeability using pore-network modeling

    NARCIS (Netherlands)

    Joekar-Niasar, V.; Hassanizadeh, S.M.; Leijnse, A.

    2008-01-01

    To gain insight in relationships among capillary pressure, interfacial area, saturation, and relative permeability in two-phase flow in porous media, we have developed two types of pore-network models. The first one, called tube model, has only one element type, namely pore throats. The second one

  8. Insights into the Relationships Among Capillary Pressure, Saturation, Interfacial Area and Relative Permeability Using Pore-Network Modeling

    NARCIS (Netherlands)

    Joekar-Niasar, V.; Hassanizadeh, S.M.; Leijnse, A.

    To gain insight in relationships among capillary pressure, interfacial area, saturation, and relative permeability in two-phase flow in porous media, we have developed two types of pore-network models. The first one, called tube model, has only one element type, namely pore throats. The second one

  9. Optimization of Catheter Ablation of Atrial Fibrillation: Insights Gained from Clinically-Derived Computer Models

    Directory of Open Access Journals (Sweden)

    Jichao Zhao

    2015-05-01

    Full Text Available Atrial fibrillation (AF is the most common heart rhythm disturbance, and its treatment is an increasing economic burden on the health care system. Despite recent intense clinical, experimental and basic research activity, the treatment of AF with current antiarrhythmic drugs and catheter/surgical therapies remains limited. Radiofrequency catheter ablation (RFCA is widely used to treat patients with AF. Current clinical ablation strategies are largely based on atrial anatomy and/or substrate detected using different approaches, and they vary from one clinical center to another. The nature of clinical ablation leads to ambiguity regarding the optimal patient personalization of the therapy partly due to the fact that each empirical configuration of ablation lines made in a patient is irreversible during one ablation procedure. To investigate optimized ablation lesion line sets, in silico experimentation is an ideal solution. 3D computer models give us a unique advantage to plan and assess the effectiveness of different ablation strategies before and during RFCA. Reliability of in silico assessment is ensured by inclusion of accurate 3D atrial geometry, realistic fiber orientation, accurate fibrosis distribution and cellular kinetics; however, most of this detailed information in the current computer models is extrapolated from animal models and not from the human heart. The predictive power of computer models will increase as they are validated with human experimental and clinical data. To make the most from a computer model, one needs to develop 3D computer models based on the same functionally and structurally mapped intact human atria with high spatial resolution. The purpose of this review paper is to summarize recent developments in clinically-derived computer models and the clinical insights they provide for catheter ablation.

  10. Analytical modeling provides new insight into complex mutual coupling between surface loops at ultrahigh fields.

    Science.gov (United States)

    Avdievich, N I; Pfrommer, A; Giapitzakis, I A; Henning, A

    2017-10-01

    Ultrahigh-field (UHF) (≥7 T) transmit (Tx) human head surface loop phased arrays improve both the Tx efficiency (B 1 + /√P) and homogeneity in comparison with single-channel quadrature Tx volume coils. For multi-channel arrays, decoupling becomes one of the major problems during the design process. Further insight into the coupling between array elements and its dependence on various factors can facilitate array development. The evaluation of the entire impedance matrix Z for an array loaded with a realistic voxel model or phantom is a time-consuming procedure when performed using electromagnetic (EM) solvers. This motivates the development of an analytical model, which could provide a quick assessment of the Z-matrix. In this work, an analytical model based on dyadic Green's functions was developed and validated using an EM solver and bench measurements. The model evaluates the complex coupling, including both the electric (mutual resistance) and magnetic (mutual inductance) coupling. Validation demonstrated that the model does well to describe the coupling at lower fields (≤3 T). At UHFs, the model also performs well for a practical case of low magnetic coupling. Based on the modeling, the geometry of a 400-MHz, two-loop transceiver array was optimized, such that, by simply overlapping the loops, both the mutual inductance and the mutual resistance were compensated at the same time. As a result, excellent decoupling (below -40 dB) was obtained without any additional decoupling circuits. An overlapped array prototype was compared (signal-to-noise ratio, Tx efficiency) favorably to a gapped array, a geometry which has been utilized previously in designs of UHF Tx arrays. Copyright © 2017 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

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

    2012-12-01

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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Sofie Van Holle

    2017-05-01

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

  20. Insights into the pathophysiology of ankylosing spondylitis: contributions from animal models.

    Science.gov (United States)

    Braem, Kirsten; Lories, Rik J

    2012-05-01

    The introduction of anti-tumor necrosis factor strategies has significantly changed the perspective and outcome of patients with ankylosing spondylitis and related spondyloarthritides. This breakthrough has also boosted further research efforts into the mechanisms of disease. As human tissue specimens of the spine and sacroiliac joints are very difficult to obtain and rarely allow mechanistic studies, most of the new concepts have emerged from different animal models of disease. In this review, we summarize insights into the role of HLA-B27 based on transgenic rat and mouse models, efforts into the identification of cell populations stimulating inflammation and molecular studies of pathological bone formation leading to ankylosis. Important progress has been made and novel hypotheses were put forward. These include the impact of HLA-B27 on endoplasmic reticulum stress and the unfolded protein response, the role of stromal cells in inflammation, the entheseal stress hypothesis and the identification of the bone morphogenetic protein and WNT signaling pathways as therapeutic targets for ankylosis. Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

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

    Science.gov (United States)

    Struben, Jeroen; Chan, Derek; Dubé, Laurette

    2014-12-01

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

  2. Insights from Modeling the Integrated Climate, Biogeochemical Cycles, Human Activities and Their Interactions in the ACME Earth System Model

    Science.gov (United States)

    Leung, L. R.; Thornton, P. E.; Riley, W. J.; Calvin, K. V.

    2017-12-01

    Towards the goal of understanding the contributions from natural and managed systems to current and future greenhouse gas fluxes and carbon-climate and carbon-CO2 feedbacks, efforts have been underway to improve representations of the terrestrial, river, and human components of the ACME earth system model. Broadly, our efforts include implementation and comparison of approaches to represent the nutrient cycles and nutrient limitations on ecosystem production, extending the river transport model to represent sediment and riverine biogeochemistry, and coupling of human systems such as irrigation, reservoir operations, and energy and land use with the ACME land and river components. Numerical experiments have been designed to understand how terrestrial carbon, nitrogen, and phosphorus cycles regulate climate system feedbacks and the sensitivity of the feedbacks to different model treatments, examine key processes governing sediment and biogeochemistry in the rivers and their role in the carbon cycle, and exploring the impacts of human systems in perturbing the hydrological and carbon cycles and their interactions. This presentation will briefly introduce the ACME modeling approaches and discuss preliminary results and insights from numerical experiments that lay the foundation for improving understanding of the integrated climate-biogeochemistry-human system.

  3. 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.

  4. 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.

  5. 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

  6. 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...

  7. 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 ...

  8. 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)

  9. 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.

  10. Structural insights into high density lipoprotein: Old models and new facts

    Directory of Open Access Journals (Sweden)

    Valentin eGogonea

    2016-01-01

    Full Text Available The physiological link between circulating high density lipoprotein (HDL levels and cardiovascular disease is well documented, albeit its intricacies are not well understood. An improved appreciation of HDL function and overall role in vascular health and disease requires at its foundation a better understanding of the lipoprotein's molecular structure, its formation, and its process of maturation through interactions with various plasma enzymes and cell receptors that intervene along the pathway of reverse cholesterol transport. This review focuses on summarizing recent developments in the field of lipid free apoA-I and HDL structure, with emphasis on new insights revealed by newly published nascent and spherical HDL models constructed by combining low resolution structures obtained from small angle neutron scattering (SANS with contrast variation and geometrical constraints derived from hydrogen-deuterium exchange (HDX, crosslinking mass spectrometry, electron microscopy, Förster resonance energy transfer, and electron spin resonance. Recently published low resolution structures of nascent and spherical HDL obtained from SANS with contrast variation and isotopic labeling of apolipoprotein A-I (apoA-I will be critically reviewed and discussed in terms of how they accommodate existing biophysical structural data from alternative approaches. The new low resolution structures revealed and also provided some answers to long standing questions concerning lipid organization and particle maturation of lipoproteins. The review will discuss the merits of newly proposed SANS based all atom models for nascent and spherical HDL, and compare them with accepted models. Finally, naturally occurring and bioengineered mutations in apoA-I, and their impact on HDL phenotype, are reviewed and discuss together with new therapeutics employed for restoring HDL function.

  11. Modeling Huntington disease in Drosophila: Insights into axonal transport defects and modifiers of toxicity.

    Science.gov (United States)

    Krench, Megan; Littleton, J Troy

    2013-01-01

    Huntington disease (HD) is an inherited neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in the huntingtin (Htt) gene. Despite years of research, there is no treatment that extends life for patients with the disorder. Similarly, little is known about which cellular pathways that are altered by pathogenic Huntingtin (Htt) protein expression are correlated with neuronal loss. As part of a longstanding effort to gain insights into HD pathology, we have been studying the protein in the context of the fruitfly Drosophila melanogaster. We generated transgenic HD models in Drosophila by engineering flies that carry a 12-exon fragment of the human Htt gene with or without the toxic trinucleotide repeat expansion. We also created variants with a monomeric red fluorescent protein (mRFP) tag fused to Htt that allows in vivo imaging of Htt protein localization and aggregation. While wild-type Htt remains diffuse throughout the cytoplasm of cells, pathogenic Htt forms insoluble aggregates that accumulate in neuronal soma and axons. Aggregates can physically block transport of numerous organelles along the axon. We have also observed that aggregates are formed quickly, within just a few hours of mutant Htt expression. To explore mechanisms of neurodegeneration in our HD model, we performed in vivo and in vitro screens to search for modifiers of viability and pathogenic Htt aggregation. Our results identified several novel candidates for HD therapeutics that can now be tested in mammalian models of HD. Furthermore, these experiments have highlighted the complex relationship between aggregates and toxicity that exists in HD.

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

    KAUST Repository

    Moreo, P.

    2009-11-14

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

  13. Inactive and active states and supramolecular organization of GPCRs: insights from computational modeling

    Science.gov (United States)

    Fanelli, Francesca; De Benedetti, Pier G.

    2006-08-01

    Herein we make an overview of the results of our computational experiments aimed at gaining insight into the molecular mechanisms of GPCR functioning either in their normal conditions or when hit by gain-of-function or loss-of-function mutations. Molecular simulations of a number of GPCRs in their wild type and mutated as well as free and ligand-bound forms were instrumental in inferring the structural features, which differentiate the mutation- and ligand-induced active from the inactive states. These features essentially reside in the interaction pattern of the E/DRY arginine and in the degree of solvent exposure of selected cytosolic domains. Indeed, the active states differ from the inactive ones in the weakening of the interactions made by the highly conserved arginine and in the increase in solvent accessibility of the cytosolic interface between helices 3 and 6. Where possible, the structural hallmarks of the active and inactive receptor states are translated into molecular descriptors useful for in silico functional screening of novel receptor mutants or ligands. Computational modeling of the supramolecular organization of GPCRs and their intracellular partners is the current challenge toward a deep understanding of their functioning mechanisms.

  14. 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

  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. 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

  17. Dilatant normal faulting in jointed cohesive rocks: insights from physical modeling

    Science.gov (United States)

    Kettermann, Michael; von Hagke, Christoph; Urai, Janos

    2016-04-01

    Dilatant faults often form in rocks containing pre-existing joints, but the effects of joints on fault segment linkage and fracture connectivity is not well understood. Studying evolution of dilatancy and influence of fractures on fault development provides insights on geometry of fault zones in brittle rocks and eventually allows for predicting their subsurface appearance. We assess the evolution of dilatant faults in fractured rocks using analogue models with cohesive powder. The upper layer contains pre-formed joint sets, and we vary the angle between joints and a rigid basement fault in our experiments. Analogue models were carried out in a manually driven deformation box (30x28x20 cm) with a 60° dipping pre-defined basement fault and 4.5 cm of displacement. To produce open joints prior to faulting, sheets of paper were mounted in the box to a depth of 5 cm at a spacing of 2.5 cm. Powder was then sieved into the box, embedding the paper almost entirely (column height of 19 cm), and the paper was removed. We tested the influence of different angles between the strike of the basement fault and the joint set (joint fault (JF) angles of 0°, 4°, 8°, 12°, 16°, 20°, and 25°). During deformation we captured structural information by time-lapse photography that allows particle imaging velocimetry analyses (PIV) to detect localized deformation at every increment of displacement. Post-mortem photogrammetry preserves the final 3-dimensional structure of the fault zone. Results show robust structural features in models: damage zone width increases by about 50 % and the number of secondary fractures within this zone by more than 100 % with increasing JF-angle. Interestingly, the map-view area fraction of open gaps increases by only 3%. Secondary joints and fault step-overs are oriented at a high angle to the primary joint orientation. Due to the length of the pre-existing open joints, areas far beyond the fractured regions are connected to the system. In contrast

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

    Science.gov (United States)

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

    2013-01-01

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

  19. (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)

  20. Marketing of initial public offering

    Directory of Open Access Journals (Sweden)

    Denčić-Mihajlov Ksenija

    2013-01-01

    Full Text Available The initial public offering offers the ability to obtain additional capital through the mechanism of the primary capital market and represents an important milestone in the life-cycle of privately-held corporations. The value and the number of realized IPO transactions at the global level are increasing. At the same time, due to IPO underpricing problem, the companies that are going public fail to collect requested amount of capital to fund future growth. Given the limited importance granted to marketing, and especially promotion, in the theory and practice in the process of evaluating and trading securities, the author addresses two subjects in this paper. Firstly, the author emphasizes the importance of defining and implementing appropriate marketing strategies in the initial public offering process, and secondly, discusses the impact of marketing expenditures in various instruments to reduce IPO underpricing and create value for shareholders of the company that is going public through the initial public offering.

  1. 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

  2. Personality structure among prisoners: how valid is the five-factor model, and can it offer support for Eysenck's theory of criminality?

    Science.gov (United States)

    Ireland, Jane L; Ireland, Carol A

    2011-02-01

    Research with offenders has tended to use a categorical system of diagnosis or a three-factor model. There is growing evidence among non-offending groups that a five-factor model (FFM), which is more holistic and emphasises strengths as well as limitations, may be more clinically useful. The purpose of this study was to test the validity of the FFM of personality in a sample of adult male prisoners. It was predicted that they would show higher scores for extraversion (E) and lower scores for emotional stability (ES) [the equivalent of higher neuroticism (N)], that E would be predicted by prison experience and age and that the FFM would be confirmed as a better fit to the data over Eysenck's three-factor [P(psychoticism)EN] model. Two independent samples of adult male prisoners were asked to complete the International Personality Item Pool while locked in their cells over the lunchtime period. Parallel and confirmatory factor analyses were used to test the hypotheses. There was a 65 and 75% response rate across the independent samples, resulting in samples of 259 and 183, respectively. Overall, more positive personality traits were evidenced across both samples. E was not predicted by prison experience or age, with increased ES related to increased age in only one sample. The best-fitting model comprised five factors, but represented a variant of the FFM. The value of applying broad conceptualisations of personality to special samples is discussed, with the importance of accounting for positive, as well as negative, traits acknowledged. The presence of increased positive traits in comparison to negative traits is not in keeping with Eysenck's original personality theory of criminal behaviour, with the study highlighting value in accounting more for environmental factors. Copyright © 2010 John Wiley & Sons, Ltd.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

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

    DEFF Research Database (Denmark)

    Kyriazakos, Sofoklis

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

  10. 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

  11. 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.

  12. 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.

  13. APCVD of ZnO: Al, insight and control by modeling

    NARCIS (Netherlands)

    Deelen, J. van; Illiberi, A.; Kniknie, B.J.; Steijvers, H.L.A.H.; Lankhorst, A.M.; Simons, P.J.P.M.

    2013-01-01

    Atmospheric pressure chemical vapor deposition (APCVD) of ZnO from diethyl zinc (DEZn) and t-butanol was performed using an industrial reactor design. Deposition profiles were recorded to gain insight in the position dependent variations in layer thickness in such a reactor. We observed that for a

  14. 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

  15. 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.

  16. Impact of great subduction earthquakes on the long-term forearc morphology, insight from mechanical modelling

    Science.gov (United States)

    Cubas, Nadaya

    2017-04-01

    The surge of great subduction earthquakes during the last fifteen years provided numerous observations requiring revisiting our understanding of large seismic events mechanics. For instance, we now have clear evidence that a significant part of the upper plate deformation is permanently acquired. The link between great earthquakes and long-term deformation offers a new perspective for the relief construction understanding. In addition, a better understanding of these relations could provide us with new constraints on earthquake mechanics. It is also of fundamental importance for seismic risk assessment. In this presentation, I will compile recent results obtained from mechanical modelling linking megathrust ruptures with upper-plate permanent deformation and discuss their impact. We will first show that, in good accordance with lab experiments, aseismic zones are characterized by frictions larger or equal to 0.1 whereas seismic asperities have dynamic frictions lower than 0.05. This difference will control the long-term upper-plate morphology. The larger values along aseismic zones allow the wedge to reach the critical state, and will lead to active thrust systems forming a relief. On the contrary, low dynamic friction along seismic asperities will place the taper in the sub-critical domain impeding any internal deformation. This will lead to the formation of forearc basins inducing negative gravity anomalies. Since aseismic zones have higher friction and larger taper, fully creeping segments will tend to develop peninsulas. On the contrary, fully locked segments with low dynamic friction and very low taper will favor subsiding coasts. The taper variation due to megathrust friction is also expressed through a correlation between coast-to-trench distance and forearc coupling (e.g., Mexican and South-American subduction zones). We will then discuss how variations of frictional properties along the megathrust can induce splay fault activation. For instance, we can

  17. 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.

  18. Improving the Functional Control of Aged Ferroelectrics Using Insights from Atomistic Modeling

    Science.gov (United States)

    Chapman, J. B. J.; Cohen, R. E.; Kimmel, A. V.; Duffy, D. M.

    2017-10-01

    We provide a fundamental insight into the microscopic mechanisms of the aging processes. Using large-scale molecular dynamics simulations of the prototypical ferroelectric material PbTiO3 , we demonstrate that the experimentally observed aging phenomena can be reproduced from intrinsic interactions of defect dipoles related to dopant-vacancy associates, even in the absence of extrinsic effects. We show that variation of the dopant concentration modifies the material's hysteretic response. We identify a universal method to reduce loss and tune the electromechanical properties of inexpensive ceramics for efficient technologies.

  19. 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

    .... To illustrate how such insights can be achieved a precise production system model that uses verbal working memory for performing a serial memory-span task through a strategic phonological loop...

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. An Insight to High Humidity-Caused Friction Modulation of Brake by Numerical Modeling of Dynamic Meniscus under Shearing

    Directory of Open Access Journals (Sweden)

    Liangbiao Chen

    2015-05-01

    Full Text Available To obtain an insight to high humidity-caused friction modulation in brake pad-rotor interface, the adhesion phenomenon due to a liquid bridge is simulated using an advanced particle method by varying the shearing speed of the interface. The method, called generalized interpolation material point for fluid-solid interactions (GIMP-FSI, was recently developed from the material point method (MPM for fluid-solid interactions at small scales where surface tension dominates, thus suitable for studying the partially wet brake friction due to high humidity at a scale of 10 m. Dynamic capillary effects due to surface tension and contact angles are simulated. Adhesion forces calculated by GIMP-FSI are consistent with those from the existing approximate meniscus models. Moreover, the numerical results show that capillary effects induce modulations of adhesion as slip speed changes. In particular, the adhesion modulation could be above 30% at low speed. This finding provides insights into how the high humidity-caused friction could cause modulations of brake, which are unable to be achieved by conventional models. Therefore, the numerical analysis helps to elucidate the complex friction mechanisms associated with brakes that are exposed to high humidity environments.

  5. Fundamental Studies of Novel Zwitterionic Hybrid Membranes: Kinetic Model and Mechanism Insights into Strontium Removal

    OpenAIRE

    Wen Zhu; Junsheng Liu; Meng Li

    2014-01-01

    A series of zwitterionic hybrid membranes were prepared via the ring opening of 1,3-propanesultone with the amine groups in the chains of TMSPEDA and a subsequent sol-gel process. Their kinetic models for strontium removal were investigated using three two-parameter kinetic equations (i.e., Lagergren pseudo-first order, pseudo-second order, and Elovich models). Adsorption mechanism was evaluated using intraparticle diffusion model, diffusion-chemisorption model, and Boyd equation. It was foun...

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

    NARCIS (Netherlands)

    Kavetski, D.; Fenicia, F.

    2011-01-01

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

  7. 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...

  8. Insights into Campylobacter jejuni colonization of the mammalian intestinal tract using a novel mouse model of infection.

    Science.gov (United States)

    Stahl, Martin; Vallance, Bruce A

    2015-01-01

    A lack of relevant disease models for Campylobacter jejuni has long been an obstacle to research into this common enteric pathogen. We recently published that mice deficient in Single IgG Interleukin-1 related receptor (SIGIRR), a repressor of MyD88-dependent innate immune signaling, were highly susceptible to enteric infection by murine bacterial pathogens. Subsequently, we successfully employed these mice as an animal model for the human pathogen C. jejuni and gained substantial new insights into infection by this pathogen. The infected mice developed significant intestinal inflammation, primarily via TLR4 stimulation. Furthermore, the resulting gastroenteritis was dependent on C. jejuni pathogenesis as bacterial strains suffering mutations in key virulence factors were attenuated in causing disease. The ability to infect SIGIRR-deficient mice with C. jejuni sheds new light onto how these bacteria colonize the mucus layer of the intestinal tract, invade epithelial cells, and raises new prospects for studying the virulence strategies and pathogenesis of C. jejuni.

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

    Science.gov (United States)

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

    2013-04-01

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

  10. Investigation of 3-D lateral variations on seismic waveform modeling, in preparation for the InSight mission to Mars

    Science.gov (United States)

    Drilleau, M.; Dubois, A.; Blanchette-Guertin, J. F.; Kawamura, T.; Lognonne, P. H.

    2015-12-01

    In 2016, the InSight mission will provide the very first seismic records from Mars after installing a seismometer on the surface of the Red Planet. Obtaining information on the deep 1-D seismic structure of Mars using a single geophysical station will be challenging. However, successful test inversions using body and surface waves have been presented in a preliminary study by Panning et al. (2015). Future investigations need now to focus on inversions making a complete use of the seismic waveform. An important challenge is to investigate the effects of 3-D lateral variations of seismic velocity structures on seismograms. The HOPT (Higher Order Perturbation Theory) code originally developed by P. Lognonné and E. Clévédé (Lognonné, 1991 ; Lognonné and Clévédé, 2002) and based on the perturbation theory allows for the computation of synthetic seismograms in a 3-D Earth. We adapted the code for Mars and computed surface wave synthetics in a 3-D planet, initially only considering the effects of the planet's ellipticity as well as the lateral variations in the depth of the Moho which are known through gravity measurements (e.g. Neumann et al., 2004). Additional constraints from lateral variations in topography will be the focus of future work. These synthetics can be compared to future seismic data in order to identify a suite of Martian internal structure models that best match the data. To do so, we first need to estimate the resolvable parameters concerning the Mars deep interior while considering the 3-D effects, which is the main goal of this study. Furthermore, in preparation for the InSight mission data return phase, the computation of these synthetic (but realistic) seismograms is primordial to test the softwares developed by the InSight Mars Quake and Mars Structure Services (in charge of locating the seismic events, and using them to assess the internal structure of Mars).

  11. 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

  12. 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...... as a generative tool and so far the empirical study includes only two co-creation-workshops, which is too few to make any solid conclusions. Still, the study indicates some interesting insights about the potentials and challenges the persona model has, when used as a generative tool....

  13. Transgenic mouse models in the study of reproduction: insights into GATA protein function.

    Science.gov (United States)

    Tevosian, Sergei G

    2014-07-01

    For the past 2 decades, transgenic technology in mice has allowed for an unprecedented insight into the transcriptional control of reproductive development and function. The key factor among the mouse genetic tools that made this rapid advance possible is a conditional transgenic approach, a particularly versatile method of creating gene deletions and substitutions in the mouse genome. A centerpiece of this strategy is an enzyme, Cre recombinase, which is expressed from defined DNA regulatory elements that are active in the tissue of choice. The regulatory DNA element (either genetically engineered or natural) assures Cre expression only in predetermined cell types, leading to the guided deletion of genetically modified (flanked by loxP or 'floxed' by loxP) gene loci. This review summarizes and compares the studies in which genes encoding GATA family transcription factors were targeted either globally or by Cre recombinases active in the somatic cells of ovaries and testes. The conditional gene loss experiments require detailed knowledge of the spatial and temporal expression of Cre activity, and the challenges in interpreting the outcomes are highlighted. These studies also expose the complexity of GATA-dependent regulation of gonadal gene expression and suggest that gene function is highly context dependent. © 2014 Society for Reproduction and Fertility.

  14. 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.,…

  15. 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.

  16. 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.

  17. 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.

  18. 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...

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

    Science.gov (United States)

    Widjaja, Wanty

    2010-01-01

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

  20. 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)…

  1. 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

  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

    2017-09-13

    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).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

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

    DEFF Research Database (Denmark)

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

    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...... been used to model normal visual attention, as well as identifying how the different parameters are affected by changes across the lifespan (McAvinue et al., 2012) and by attentional deficits such as neglect (Duncan et al., 1999). An auditory analogue would allow these same parameters to be measured...

  11. 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...

  12. 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...

  13. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-01

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

  15. 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.

  16. 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

  17. 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

  18. On the seasonal variability and eddies in the North Brazil Current: insights from model intercomparison experiments

    Science.gov (United States)

    Barnier, Bernard; Reynaud, Thierry; Beckmann, Aike; Böning, Claus; Molines, Jean-Marc; Barnard, Sally; Jia, Yanli

    The time dependent circulation of the North Brazil Current is studied with three numerical ocean circulation models, which differ by the vertical coordinate used to formulate the primitive equations. The models are driven with the same surface boundary conditions and their horizontal grid-resolution (isotropic, 1/3° at the equator) is in principle fine enough to permit the generation of mesoscale eddies. Our analysis of the mean seasonal currents concludes that the volume transport of the North Brazil Current (NBC) at the equator is principally determined by the strength of the meridional overturning, and suggests that the return path of the global thermohaline circulation is concentrated in the NBC. Models which simulate a realistic overturning at 24°N of the order of 16-18 Sv also simulate a realistic NBC transport of nearly 35 Sv comparable to estimates deduced from the most recent observations. In all models, the major part of this inflow of warm waters from the South Atlantic recirculates in the zonal equatorial current system, but the models also agree on the existence of a permanent coastal mean flow to the north-west, from the equator into the Carribean Sea, in the form of a continuous current or a succession of eddies. Important differences are found between models in their representation of the eddy field. The reasons invoked are the use of different subgrid-scale parameterisations, and differences in stability of the NBC retroflection loop because of differences in the representation of the effect of bottom friction according to the vertical coordinate that is used. Finally, even if differences noticed between models in the details of the seasonal mean circulation and water mass properties could be explained by differences in the eddy field, nonetheless the major characteristics (mean seasonal currents, volume and heat transports) appears to be at first order driven by the strength of the thermohaline circulation.

  19. 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.

  20. Insights into the rheological behaviors evolution of alginate dialdehyde crosslinked collagen solutions evaluated by numerical models.

    Science.gov (United States)

    Zhu, Shichen; Yu, Xiaoyue; Xiong, Shanbai; Liu, Ru; Gu, Zhipeng; You, Juan; Yin, Tao; Hu, Yang

    2017-09-01

    The elaboration of the rheological behaviors of alginate dialdehyde (ADA) crosslinked collagen solutions, along with the quantitative analysis via numerical models contribute to the controllable design of ADA crosslinked solution system's fluid mechanics performance during manufacturing process for collagen biomaterials. In the present work, steady shear flow, dynamical viscoelasticity, creep-recovery, thixotropy tests were performed to characterize the rheological behaviors of the collagen solutions incorporating of ADA from the different aspects and fitted with corresponding numerical models. It was found that pseudoplastic properties of all samples enhanced with increasing amounts of ADA, which was confirmed by the parameters calculated from the Ostwald-de Waele model, Carreau and Cross model, for instance, the non-Newtonian index (n) decreased from 0.786 to 0.201 and a great increase by 280 times in value of viscosity index (K) was obtained from Ostwald-de Waele model. The forth-mode Leonov model was selected to fit all dynamic modulus-frequency curves due to its higher fitting precision (R 2 >0.99). It could be found that the values of correlation shear viscosity (η k ) increased and the values of relaxation time (θ k ) decreased with increasing ADA at the fixed k value, suggesting that the incorporation of ADA accelerated the transformation of the collagen solutions from liquid-like to gel-like state due to more formation of CN linkages between aldehyde groups and lysine residues. Also, the curves of creep and recovery phase of the native and crosslinked collagen solutions were simulated well using Burger model and a semi-empirical model, respectively. The ability to resist to deformation and elasticity strengthened for the samples with higher amounts of ADA, accompanied with the important fact that compliance value (J 50 ) decreased from 56.317Pa -1 to 2.135Pa -1 and the recovery percentage (R creep ) increased from 2.651% to 28.217%. Finally, it was found

  1. 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.

  2. 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...

  3. 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...

  4. 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...

  5. 17 CFR 8.16 - Settlement offers.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Settlement offers. 8.16... offers. (a) The rules of an exchange may permit a respondent to submit a written offer of settlement to... committee may accept the offer of settlement, but may not alter its terms unless the respondent agrees. (b...

  6. 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

    that it was the difference in phytoplankton growth rates, and the associated change in photosynthetic oxygen production, that mainly contribute to creating differences in CBOD5 removal rates and the development of aerobic conditions. The model was also sensitive to atmospheric aeration rates at low temperature, providing...... environmental factors affecting treatment performance in arctic WSPs. A sensitivity analysis was used to provide a quantification of the relative uncertainties of parameters that exist within the described modeling framework. The model was able to qualitatively reproduce mesocosm experiment trends...... in phytoplankton growth, dissolved oxygen concentration, and the reduction of carbonaceous biochemical oxygen demand on Day 5 (CBOD5). These results demonstrated that CBOD5 reduction and oxygen state are very sensitive to organic loading regimes at low temperatures (5-15°C). The sensitivity analysis identified...

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

    Science.gov (United States)

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

    2011-10-01

    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.

  8. 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

  9. Insights into the pathogenesis of enteropathogenic E. coli using an improved intestinal enterocyte model.

    Directory of Open Access Journals (Sweden)

    Paul Dean

    Full Text Available Enteropathogenic E. coli (EPEC is a human pathogen that targets the small intestine, causing severe and often fatal diarrhoea in infants. A defining feature of EPEC disease is the loss (effacement of absorptive microvilli (MV from the surface of small intestinal enterocytes. Much of our understanding of EPEC pathogenesis is derived from studies using cell lines such as Caco-2 - the most extensively used small intestinal model. However, previous work has revealed fundamental differences between Caco-2 cells and in vivo differentiated enterocytes in relation to MV effacement. This, and the high heterogeneity and low transfection efficiency of the Caco-2 cell line prompted the isolation of several sub-clones (NCL-1-12 to identify a more tractable and improved in vivo-like cell model. Along with established Caco-2 clones (TC-7, BBE1, sub-clones were assessed for growth rate, apical surface morphology, epithelial barrier function and transfection efficiency. TC-7 cells provided the best all-round clone and exhibited highest levels of ectopic gene expression following cell polarisation. Novel alterations in EGFP-labelled mitochondria, that were not previously documented in non-polarised cell types, highlighted the potential of the TC-7 model for defining dynamic enterocyte-specific changes during infection. Crucially, the TC-7 cell line also mimicked ex vivo derived enterocytes with regard to MV effacement, enabling a better dissection of the process. Effacement activity caused by the EPEC protein Map in the Caco-2 but not ex vivo model, was linked to a defect in suppressing its Cdc42-dependent functionality. MV effacement activity of the EPEC protein EspF in the TC-7 model was dependent on its N-WASP binding motif, which is also shown to play an essential role in epithelial barrier dysfunction. Together, this study highlights the many advantages of using TC-7 cells as a small intestinal model to study host-pathogen interactions.

  10. 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.

  11. The Extended Perturbation Method: New Insights on the New Keynesian Model

    DEFF Research Database (Denmark)

    Andreasen, Martin Møller; Kronborg, Anders Farver

    This paper introduces the extended perturbation method, which improves upon standard perturbation by removing approximation errors under perfect foresight. For the New Keynesian model, we show that standard perturbation generates explosive sample paths because it does not account for the upper...... bound on inflation as implied by Calvo pricing. In contrast, extended perturbation generates stable dynamics as it enforces this bound. Extended perturbation also adds to existing evidence on downward nominal wage rigidities in the New Keynesian model, as we only find support for this friction when...... using standard perturbation but not when using the more accurate extended perturbation approximation....

  12. New Insights into Congenital Diaphragmatic Hernia – A Surgeon’s Introduction to CDH Animal Models

    Science.gov (United States)

    Chiu, Priscilla Pui Lam

    2014-01-01

    In recent decades, new research into the developmental defects and pathophysiological basis of congenital diaphragmatic hernia (CDH) has revealed opportunities for the development of innovative therapies. Importantly, the use of animal models to represent this anomaly in the laboratory has resulted in the discovery of many important genetic, epigenetic, and other molecular contributors to this condition. In this review, the most commonly used and newly devised animal models of CDH are presented to familiarize the reader with the latest innovations in the basic sciences. PMID:24809040

  13. New insights into congenital diaphragmatic hernia (CDH- a surgeon’s introduction to CDH animal models.

    Directory of Open Access Journals (Sweden)

    Priscilla Pui Lam Chiu

    2014-04-01

    Full Text Available In recent decades, new research into the developmental defects and pathophysiological basis of congenital diaphragmatic hernia has revealed opportunities for the development of innovative therapies. Importantly, the use of animal models to represent this anomaly in the laboratory has resulted in the discovery of many important genetic, epigenetic and other molecular contributors to this condition. In this review, the most commonly used and newly devised animal models of CDH are presented to familiarize the reader with the latest innovations in the basic sciences.

  14. New Insights into Congenital Diaphragmatic Hernia - A Surgeon's Introduction to CDH Animal Models.

    Science.gov (United States)

    Chiu, Priscilla Pui Lam

    2014-01-01

    In recent decades, new research into the developmental defects and pathophysiological basis of congenital diaphragmatic hernia (CDH) has revealed opportunities for the development of innovative therapies. Importantly, the use of animal models to represent this anomaly in the laboratory has resulted in the discovery of many important genetic, epigenetic, and other molecular contributors to this condition. In this review, the most commonly used and newly devised animal models of CDH are presented to familiarize the reader with the latest innovations in the basic sciences.

  15. 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…

  16. Improving Mechanical Insight into Ring Fault Initiation and Caldera Formation via Elastic Models of Magma Reservoir Inflation (Invited)

    Science.gov (United States)

    Grosfils, E. B.; McGovern, P. J.; Gregg, P. M.; Galgana, G. A.; Hurwitz, D. M.; Long, S.; Chestler, S.

    2013-12-01

    Elastic numerical models have become increasingly important for interpreting field data and gaining insight into the magmatic and volcanic processes spawned by shallow magma reservoirs on Earth and other planets. Using an approach introduced nearly a century ago, most researchers investigating magma reservoir inflation and rupture in response to the evolution of a subsurface magma reservoir have treated the reservoir as a cavity subjected only to over/underpressure in an otherwise unloaded elastic host. This approach is at times argued to be a more concise mathematical equivalent to solutions that retain a fully three-dimensional, gravitationally loaded stress tensor in the host rock. The two approaches are not equivalent, however, and detailed elucidation of this argument under diverse geological conditions (e.g., layering, edifice loading) has demonstrated the implications for several fundamental volcanic processes under an array of different conditions [cf. Grosfils, JVGR, 2007]. Given the importance of the link between subsurface magmatic processes and volcanic activity, gaining a better understanding of the basic assumptions underpinning these two endmember modeling approaches--and the attendant implications--is critical. In this presentation we intend to: (1) discuss what we see as the physical assumptions underpinning the two endmember model approaches, thereby framing a call for further field constraints upon the host rock conditions in the vicinity of a magma reservoir; (2) use models of ring fault formation and caldera initiation to illustrate the striking differences in outcome that can occur; (3) demonstrate that retaining the full gravitationally loaded host rock stress tensor reconciles comparable numerical and analogue model results, resolving persistent concerns regarding the ';mismatch' between outcomes obtained from these two complementary model styles; and, (4) briefly describe the importance--and limitations--of elastic model treatments when

  17. Insights on the energy-water nexus through modeling of the integrated water cycle

    Science.gov (United States)

    Leung, L. R.; Li, H. Y.; Zhang, X.; Wan, W.; Voisin, N.; Leng, G.

    2016-12-01

    For sustainable energy planning, understanding the impacts of climate change, land use change, and water management is essential as they all exert notable controls on streamflow and stream temperature that influence energy production. An integrated water model representing river processes, irrigation water use and water management has been developed and coupled to a land surface model to investigate the energy-water nexus. Simulations driven by two climate change projections with the RCP 4.5 and RCP 8.5 emissions scenarios, with and without water management, are analyzed to evaluate the individual and combined effects of climate change and water management on streamflow and stream temperature. The simulations revealed important impacts of climate change and water management on both floods and droughts. The simulations also revealed the dynamics of competition between changes in water demand and water availability in the climate mitigation (RCP 4.5) and business as usual (RCP 8.5) scenarios that influence streamflow and stream temperature, with important consequences to energy production. The integrated water model is being implemented to the Accelerated Climate Modeling for Energy (ACME) to enable investigation of the energy-water nexus in the fully coupled Earth system.

  18. Retrieving Backbone String Neighbors Provides Insights Into Structural Modeling of Membrane Proteins*

    Science.gov (United States)

    Sun, Jiang-Ming; Li, Tong-Hua; Cong, Pei-Sheng; Tang, Sheng-Nan; Xiong, Wen-Wei

    2012-01-01

    Identification of protein structural neighbors to a query is fundamental in structure and function prediction. Here we present BS-align, a systematic method to retrieve backbone string neighbors from primary sequences as templates for protein modeling. The backbone conformation of a protein is represented by the backbone string, as defined in Ramachandran space. The backbone string of a query can be accurately predicted by two innovative technologies: a knowledge-driven sequence alignment and encoding of a backbone string element profile. Then, the predicted backbone string is employed to align against a backbone string database and retrieve a set of backbone string neighbors. The backbone string neighbors were shown to be close to native structures of query proteins. BS-align was successfully employed to predict models of 10 membrane proteins with lengths ranging between 229 and 595 residues, and whose high-resolution structural determinations were difficult to elucidate both by experiment and prediction. The obtained TM-scores and root mean square deviations of the models confirmed that the models based on the backbone string neighbors retrieved by the BS-align were very close to the native membrane structures although the query and the neighbor shared a very low sequence identity. The backbone string system represents a new road for the prediction of protein structure from sequence, and suggests that the similarity of the backbone string would be more informative than describing a protein as belonging to a fold. PMID:22415040

  19. Retrieving backbone string neighbors provides insights into structural modeling of membrane proteins.

    Science.gov (United States)

    Sun, Jiang-Ming; Li, Tong-Hua; Cong, Pei-Sheng; Tang, Sheng-Nan; Xiong, Wen-Wei

    2012-07-01

    Identification of protein structural neighbors to a query is fundamental in structure and function prediction. Here we present BS-align, a systematic method to retrieve backbone string neighbors from primary sequences as templates for protein modeling. The backbone conformation of a protein is represented by the backbone string, as defined in Ramachandran space. The backbone string of a query can be accurately predicted by two innovative technologies: a knowledge-driven sequence alignment and encoding of a backbone string element profile. Then, the predicted backbone string is employed to align against a backbone string database and retrieve a set of backbone string neighbors. The backbone string neighbors were shown to be close to native structures of query proteins. BS-align was successfully employed to predict models of 10 membrane proteins with lengths ranging between 229 and 595 residues, and whose high-resolution structural determinations were difficult to elucidate both by experiment and prediction. The obtained TM-scores and root mean square deviations of the models confirmed that the models based on the backbone string neighbors retrieved by the BS-align were very close to the native membrane structures although the query and the neighbor shared a very low sequence identity. The backbone string system represents a new road for the prediction of protein structure from sequence, and suggests that the similarity of the backbone string would be more informative than describing a protein as belonging to a fold.

  20. 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.

  1. Modeling, Analysis, and Design Insights for Shuttle-based Compact Storage Systems

    NARCIS (Netherlands)

    E. Tappia (Elena); D. Roy (Debjit); M.B.M. de Koster (René); M. Melacini (Marco)

    2015-01-01

    textabstractShuttle-based compact systems are new automated multi-deep unit-load storage systems with lifts that promise both low operational cost and large volume flexibility. In this paper, we develop novel queuing network models to estimate the performance of both single-tier and multi-tier

  2. Modeling information flows in clinical decision support: key insights for enhancing system effectiveness

    NARCIS (Netherlands)

    Medlock, Stephanie; Wyatt, Jeremy C.; Patel, Vimla L.; Shortliffe, Edward H.; Abu-Hanna, Ameen

    2016-01-01

    A fundamental challenge in the field of clinical decision support is to determine what characteristics of systems make them effective in supporting particular types of clinical decisions. However, we lack such a theory of decision support itself and a model to describe clinical decisions and the

  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. 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

  5. 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

  6. Learning for mathematical insight: a longitudinal comparative study on modelling. (IF. 0,756)

    NARCIS (Netherlands)

    Keijzer, R.; Terwel, J.

    2003-01-01

    This paper reports on a longitudinal study of teaching and learning the subject of fractions in two matched groups of ten 9-10-year-old students. In the experimental group fractions are introduced using the bar and the number line as (mental) models, in the control group the subject is introduced by

  7. Future energy system challenges for Africa : Insights from Integrated Assessment Models

    NARCIS (Netherlands)

    Lucas, Paul L.; Nielsen, Jens; Calvin, Katherine; McCollum, David L.; Marangoni, Giacomo; Strefler, Jessica; van der Zwaan, Bob C C; van Vuuren, Detlef P.

    2015-01-01

    Although Africa's share in the global energy system is only small today, ongoing population growth and economic development imply that this can change significantly. Here, we discuss long-term energy-system developments in Africa using results of a recent model inter-comparison study on global

  8. Insights into the structural and functional aspects of rela by molecular modeling and docking calculations.

    Digital Repository Service at National Institute of Oceanography (India)

    Nath I.V.A.; LokaBharathi, P.A.; Deobagkar, D.D.

    in this direction are progressing. At present, no experimentally solved 3D structure is available for RelA. This was the motivation for us to conduct the present investigation. We built the hypothetical model of RelA in two Gram negative bacteria- P...

  9. The effects of hard water consumption on kidney function: Insights from mathematical modelling

    Science.gov (United States)

    Tambaru, David; Djahi, Bertha S.; Ndii, Meksianis Z.

    2018-03-01

    Most water sources in Nusa Tenggara Timur contain higher concentration of calcium and magnesium ions, which is known as hard water. Long-term consumption of hard water can cause kidney dysfunction, which may lead to the other diseases such as cerebrovascular disease, diabetes and others. Therefore, understanding the effects of hard water consumption on kidney function is of importance. This paper studies the transmission dynamics of kidney dysfunction due to the consumption of hard water using a mathematical model. We propose a new deterministic mathematical model comprising human and water compartments and conduct a global sensitivity analysis to determine the most influential parameters of the model. The Routh-Hurwitz criterion is used to examine the stability of the steady states. The results shows that the model has two steady states, which are locally stable. Moreover, we found that the most influential parameters are the maximum concentration of magnesium and calcium in the water, the increase rate of calcium and magnesium concentration in the water and the rate of effectiveness of water treatment. The results suggest that better water treatments are required to reduce the concentration of magnesium and calcium in the water. This aid in minimizing the probability of humans to attract kidney dysfunction. Furthermore, water-related data need to be collected for further investigation.

  10. Two-Branch Break-up Systems by a Single Mantle Plume: Insights from Numerical Modeling

    Science.gov (United States)

    Beniest, A.; Koptev, A.; Leroy, S.; Sassi, W.; Guichet, X.

    2017-10-01

    Thermomechanical modeling of plume-induced continental break-up reveals that the initial location of a mantle anomaly relative to a lithosphere inhomogeneity has a major impact on the geometry and timing of a rift-to-spreading system. Models with a warmer Moho temperature are more likely to result in "plume-centered" mode, where the rift and subsequent spreading axis grow directly above the plume. Models with weak far-field forcing are inclined to develop a "structural-inherited" mode, with lithosphere deformation localized at the lateral lithospheric boundary. Models of a third group cultivate two break-up branches (both "plume-centered" and "structural inherited") that form consecutively with a few million years delay. With our experimental setup, this break-up mode is sensitive to relatively small lateral variations of the initial anomaly position. We argue that one single mantle anomaly can be responsible for nonsimultaneous initiation and development of two rift-to-spreading systems in a lithosphere with a lateral strength contrast.

  11. 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.

  12. 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.

  13. Will subglacial rhyolite eruptions be explosive or intrusive? Some insights from analytical models

    Science.gov (United States)

    Tuffen, H.; McGarvie, D. W.; Gilbert, J. S.

    Simple analytical models of subglacial eruptions are presented, which simulate evolving subglacial cavities and volcanic edifices during rhyolitic eruptions beneath temperate glaciers. They show that the relative sizes of cavity and edifice may strongly influence the eruption mechanisms. Intrusive eruptions will occur if the edifice fills the cavity, with rising magma quenched within the edifice and slow melting of ice. Explosive magma-water interaction may occur if a water- or steam-filled gap develops above the edifice. Meltwater is assumed to drain away continuously, but any gap above the edifice will be filled by meltwater or steam. Ductile roof closure will occur if the glacier weight exceeds the cavity pressure and is modelled here using Nye's law. The results show that the effusion rate is an important control on the eruption style, with explosive eruptions favoured by large effusion rates. The models are used to explain contrasting eruption mechanisms during various Quaternary subglacial rhyolite eruptions at Torfajökull, Iceland. Although the models are simplistic, they are first attempts to unravel the complex feedbacks between subglacial eruption mechanisms and glacier response that can lead to a variety of eruptive scenarios and associated hazards.

  14. Fundulus as the Premier Teleost Model in Environmental Biology: Opportunities for New Insights Using Genomics

    Science.gov (United States)

    A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an ex...

  15. 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

  16. Fabric transpositions in granite plutons - an insight from non-scaled analogue modelling

    Czech Academy of Sciences Publication Activity Database

    Kratinová, Zuzana; Machek, Matěj; Kusbach, V.

    2010-01-01

    Roč. 75, č. 1 (2010), s. 267-277 ISSN 0016-7622 R&D Projects: GA AV ČR KJB300120702 Institutional research plan: CEZ:AV0Z30120515 Keywords : analogue modelling * magmatic fabrics * granite intrusions * rheology * AMS Subject RIV: DB - Geology ; Mineralogy Impact factor: 0.396, year: 2010

  17. Rangeland Livelihood Strategies under Varying Climate Regimes: Model Insights from Southern Kenya

    Directory of Open Access Journals (Sweden)

    Rebecca Kariuki

    2018-04-01

    Full Text Available Rangelands throughout sub-Saharan Africa are currently undergoing two major pressures: climate change (through altered rainfall and seasonality patterns and habitat fragmentation (brought by land use change driven by land demand for agriculture and conservation. Here we explore these dimensions, investigating the impact of land use change decisions, by pastoralists in southern Kenya rangelands, on human well-being and animal densities using an agent-based model. The constructed agent-based model uses input biomass data simulated by the Lund-Potsdam-Jena General Ecosystem Simulator (LPJ-GUESS dynamic vegetation model and parameterized with data from literature. Scenarios of land use change under different rainfall years, land tenure types and levels of wildlife conservation support were simulated. Reflecting reality, our results show livestock grazing as the predominant land use that changes with precipitation and land tenure leading to varying livelihood strategies. For example, agriculture is the most common livelihood in wet years and conservation levels increase with increasing support of wildlife conservation initiatives. Our model demonstrates the complex and multiple interactions between pastoralists, land management and the environment. We highlight the importance of understanding the conditions driving the sustainability of semi-arid rangelands and the communities they support, and the role of external actors, such as wildlife conservation investors, in East Africa.

  18. Integrating ecological insight derived from individual-based simulations and physiologically structured population models

    NARCIS (Netherlands)

    Nisbet, R.M.; Martin, B.T.; de Roos, A.M.

    2016-01-01

    Two contrasting approaches are widely used to derive population dynamics as an emergent property deriving from the physiology and behavior of individual organisms. "Individual-based models" (IBMs) are computer simulations where the "state" (e.g., age, size) of each individual in a population is fol-

  19. A novel insight into the cost–benefit model for the evolution of botanical carnivory

    Science.gov (United States)

    Pavlovič, Andrej; Saganová, Michaela

    2015-01-01

    Background 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. Scope 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. Conclusions 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. PMID:25948113

  20. 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

  1. Random-field Ising model: Insight from zero-temperature simulations

    Directory of Open Access Journals (Sweden)

    P.E. Theodorakis

    2014-12-01

    Full Text Available We enlighten some critical aspects of the three-dimensional (d=3 random-field Ising model (RFIM from simulations performed at zero temperature. We consider two different, in terms of the field distribution, versions of model, namely a Gaussian RFIM and an equal-weight trimodal RFIM. By implementing a computational approach that maps the ground-state of the system to the maximum-flow optimization problem of a network, we employ the most up-to-date version of the push-relabel algorithm and simulate large ensembles of disorder realizations of both models for a broad range of random-field values and systems sizes V=LxLxL, where L denotes linear lattice size and Lmax=156. Using as finite-size measures the sample-to-sample fluctuations of various quantities of physical and technical origin, and the primitive operations of the push-relabel algorithm, we propose, for both types of distributions, estimates of the critical field hmax and the critical exponent ν of the correlation length, the latter clearly suggesting that both models share the same universality class. Additional simulations of the Gaussian RFIM at the best-known value of the critical field provide the magnetic exponent ratio β/ν with high accuracy and clear out the controversial issue of the critical exponent α of the specific heat. Finally, we discuss the infinite-limit size extrapolation of energy- and order-parameter-based noise to signal ratios related to the self-averaging properties of the model, as well as the critical slowing down aspects of the algorithm.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. An analytical model for gas overpressure in slug-driven explosions: Insights into Strombolian volcanic eruptions

    Science.gov (United States)

    Del Bello, Elisabetta; Llewellin, Edward W.; Taddeucci, Jacopo; Scarlato, Piergiorgio; Lane, Steve J.

    2012-02-01

    Strombolian eruptions, common at basaltic volcanoes, are mildly explosive events that are driven by a large bubble of magmatic gas (a slug) rising up the conduit and bursting at the surface. Gas overpressure within the bursting slug governs explosion dynamics and vigor and is the main factor controlling associated acoustic and seismic signals. We present a theoretical investigation of slug overpressure based on magma-static and geometric considerations and develop a set of equations that can be used to calculate the overpressure in a slug when it bursts, slug length at burst, and the depth at which the burst process begins. We find that burst overpressure is controlled by two dimensionless parameters: V', which represents the amount of gas in the slug, and A', which represents the thickness of the film of magma that falls around the rising slug. Burst overpressure increases nonlinearly as V' and A' increase. We consider two eruptive scenarios: (1) the "standard model," in which magma remains confined to the vent during slug expansion, and (2) the "overflow model," in which slug expansion is associated with lava effusion, as occasionally observed in the field. We find that slug overpressure is higher for the overflow model by a factor of 1.2-2.4. Applying our model to typical Strombolian eruptions at Stromboli, we find that the transition from passive degassing to explosive bursting occurs for slugs with volume >24-230 m3, depending on magma viscosity and conduit diameter, and that at burst, a typical Strombolian slug (with a volume of 100-1000 m3) has an internal gas pressure of 1-5 bars and a length of 13-120 m. We compare model predictions with field data from Stromboli for low-energy "puffers," mildly explosive Strombolian eruptions, and the violently explosive 5 April 2003 paroxysm. We find that model predictions are consistent with field observations across this broad spectrum of eruptive styles, suggesting a common slug-driven mechanism; we propose that

  8. 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

  9. A model of radiation-induced cell killing: insights into mechanisms and applications for hadron therapy.

    Science.gov (United States)

    Ballarini, Francesca; Altieri, Saverio; Bortolussi, Silva; Giroletti, Elio; Protti, Nicoletta

    2013-09-01

    A mechanism-based, two-parameter biophysical model of cell killing was developed with the aim of elucidating the mechanisms underlying radiation-induced cell death and predicting cell killing by different radiation types, including protons and carbon ions at energies and doses of interest for cancer therapy. The model assumed that certain chromosome aberrations (dicentrics, rings and large deletions, called "lethal aberrations") lead to clonogenic inactivation, and that aberrations derive from μm-scale misrejoining of chromatin fragments, which in turn are produced by "dirty" double-strand breaks called "cluster lesions" (CLs). The average numbers of CLs per Gy per cell were left as a semi-free parameter and the threshold distance for chromatin-fragment rejoining was defined the second parameter. The model was "translated" into Monte Carlo code and provided simulated survival curves, which were compared with survival data on V79 cells exposed to protons, carbon ions and X rays. The agreement was good between simulations and survival data and supported the assumptions of the model at least for doses up to a few Gy. Dicentrics, rings and large deletions were found to be lethal not only for AG1522 cells exposed to X rays, as already reported by others, but also for V79 cells exposed to protons and carbon ions of different energies. Furthermore, the derived CL yields suggest that the critical DNA lesions leading to clonogenic inactivation are more complex than "clean" DSBs. After initial validation, the model was applied to characterize the particle and LET dependence of proton and carbon cell killing. Consistent with the proton data, the predicted fraction of inactivated cells after 2 Gy protons was 40-50% below 7.7 keV/μm, increased by a factor ∼1.6 between 7.7-30.5 keV/μm, and decreased by a factor ∼1.1 between 30.5-34.6 keV/μm. These LET values correspond to proton energies below a few MeV, which are always present in the distal region of hadron therapy

  10. 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

    that areas with a suitable LGM climate for the three temperate species (Apodemus flavicollis, Apodemus sylvaticus and Microtus arvalis) were largely restricted to the traditionally recognized southern refuge areas, i.e. mainly in the Mediterranean region, but also southernmost France and southern parts...... evidence. Our aim was to investigate the potential refuge locations using species distribution modelling to estimate the geographical distribution of suitable climatic conditions for selected rodent species during the LGM. Location Eurasia. Methods Presence/absence data for seven rodent species with range...... predictors of the species distributions across Siberia were projected onto LGM climate simulations to assess the distribution of climatically suitable areas. Results.The best distribution models provided good predictions of the present-day Siberian ranges of the study species. Their LGM projections showed...

  11. 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.

  12. Activation of dioxygen by copper metalloproteins and insights from model complexes.

    Science.gov (United States)

    Quist, David A; Diaz, Daniel E; Liu, Jeffrey J; Karlin, Kenneth D

    2017-04-01

    Nature uses dioxygen as a key oxidant in the transformation of biomolecules. Among the enzymes that are utilized for these reactions are copper-containing metalloenzymes, which are responsible for important biological functions such as the regulation of neurotransmitters, dioxygen transport, and cellular respiration. Enzymatic and model system studies work in tandem in order to gain an understanding of the fundamental reductive activation of dioxygen by copper complexes. This review covers the most recent advancements in the structures, spectroscopy, and reaction mechanisms for dioxygen-activating copper proteins and relevant synthetic models thereof. An emphasis has also been placed on cofactor biogenesis, a fundamentally important process whereby biomolecules are post-translationally modified by the pro-enzyme active site to generate cofactors which are essential for the catalytic enzymatic reaction. Significant questions remaining in copper-ion-mediated O 2 -activation in copper proteins are addressed.

  13. 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

  14. Inflammation Following Traumatic Brain Injury in Humans: Insights from Data-Driven and Mechanistic Models into Survival and Death

    Directory of Open Access Journals (Sweden)

    Andrew Abboud

    2016-09-01

    Full Text Available Inflammation induced by traumatic brain injury (TBI is a complex mediator of morbidity and mortality. We have previously demonstrated the utility of both data-driven and mechanistic models in settings of traumatic injury. We hypothesized that differential dynamic inflammation programs characterize TBI survivors vs. non-survivors, and sought to leverage computational modeling to derive novel insights into this life/death bifurcation. Thirteen inflammatory cytokines and chemokines were determined using Luminex™ in serial cerebrospinal fluid (CSF samples from 31 TBI patients over 5 days. In this cohort, 5 were non-survivors (Glasgow Outcome Scale [GOS] score = 1 and 26 were survivors (GOS > 1. A Pearson correlation analysis of initial injury (Glasgow Coma Scale [GCS] vs. GOS suggested that survivors and non-survivors had distinct clinical response trajectories to injury. Statistically significant differences in interleukin (IL-4, IL-5, IL-6, IL-8, IL-13, and tumor necrosis factor-α (TNF-α were observed between TBI survivors vs. non-survivors over 5 days. Principal Component Analysis and Dynamic Bayesian Network inference suggested differential roles of chemokines, TNF-α, IL-6, and IL-10, based upon which an ordinary differential equation model of TBI was generated. This model was calibrated separately to the time course data of TBI survivors vs. non-survivors as a function of initial GCS. Analysis of parameter values in ensembles of simulations from these models suggested differences in microglial and damage responses in TBI survivors vs. non-survivors. These studies suggest the utility of combined data-driven and mechanistic models in the context of human TBI.

  15. 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.

  16. OPEC, Saudi Arabia, and the Shale Revolution: Insights from Equilibrium Modelling and Oil Politics

    OpenAIRE

    Ansari, Dawud

    2017-01-01

    Why did OPEC not cut oil production in the wake of 2014’s price fall? This study aims at aiding the mostly qualitative discussion with quantitative evidence from computing quarterly partial market equilibria Q4 2011 – Q4 2015 under present short-term profit maximisation and different competition setups. Although the model performs reasonably well in explaining pre-2014 prices, all setups fail to capture low prices, which fall even beyond perfect competition outcomes. This result is robust wit...

  17. 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.

  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. 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

  20. 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

  1. Irreversibility of T-Cell Specification: Insights from Computational Modelling of a Minimal Network Architecture.

    Directory of Open Access Journals (Sweden)

    Erica Manesso

    Full Text Available A cascade of gene activations under the control of Notch signalling is required during T-cell specification, when T-cell precursors gradually lose the potential to undertake other fates and become fully committed to the T-cell lineage. We elucidate how the gene/protein dynamics for a core transcriptional module governs this important process by computational means.We first assembled existing knowledge about transcription factors known to be important for T-cell specification to form a minimal core module consisting of TCF-1, GATA-3, BCL11B, and PU.1 aiming at dynamical modeling. Model architecture was based on published experimental measurements of the effects on each factor when each of the others is perturbed. While several studies provided gene expression measurements at different stages of T-cell development, pure time series are not available, thus precluding a straightforward study of the dynamical interactions among these genes. We therefore translate stage dependent data into time series. A feed-forward motif with multiple positive feed-backs can account for the observed delay between BCL11B versus TCF-1 and GATA-3 activation by Notch signalling. With a novel computational approach, all 32 possible interactions among Notch signalling, TCF-1, and GATA-3 are explored by translating combinatorial logic expressions into differential equations for BCL11B production rate.Our analysis reveals that only 3 of 32 possible configurations, where GATA-3 works as a dimer, are able to explain not only the time delay, but very importantly, also give rise to irreversibility. The winning models explain the data within the 95% confidence region and are consistent with regard to decay rates.This first generation model for early T-cell specification has relatively few players. Yet it explains the gradual transition into a committed state with no return. Encoding logics in a rate equation setting allows determination of binding properties beyond what is

  2. 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.

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

    Science.gov (United States)

    Williams, Jonathan M.

    2017-01-01

    ABSTRACT Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. PMID:28151409

  4. Future energy system challenges for Africa: Insights from Integrated Assessment Models

    Energy Technology Data Exchange (ETDEWEB)

    Lucas, Paul; Nielsen, Jens; Calvin, Katherine V.; McCollum, David; Marangoni, Giacomo; Strefler, Jessica; van der Zwaan, Bob; Van Vuuren, Detlef

    2015-11-01

    Although Africa’s share in the global energy system is only small today, the ongoing population growth and economic development imply that this can change significantly. In this paper, we discuss long-term energy developments in Africa using the results of the LIMITS model inter-comparison study. The analysis focusses on the position of Africa in the wider global energy system and climate mitigation. The results show a considerable spread in model outcomes. Without specific climate policy, Africa’s share in global CO2 emissions is projected to increase from around 1-4% today to 3-23% by 2100. In all models, emissions only start to become really significant on a global scale after 2050. Furthermore, by 2030 still around 50% of total household energy use is supplied through traditional bio-energy, in contrast to existing ambitions from international organisations to provide access to modern energy for all. After 2050, the energy mix is projected to converge towards a global average energy mix with high shares of fossil fuels and electricity use. Finally, although the continent is now a large net exporter of oil and gas, towards 2050 it most likely needs most of its resources to meet its rapidly growing domestic demand. With respect to climate policy, the rapid expansion of the industrial and the power sector also create large mitigation potential and thereby the possibility to align the investment peak in the energy system with climate policy and potential revenues from international carbon trading.

  5. 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.

  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. 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)

  8. 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.

  9. Modeling the Lymphocytic Choriomeningitis Virus: Insights into understanding its epidemiology in the wild

    Science.gov (United States)

    Contreras, Christy; McKay, John; Blattman, Joseph; Holechek, Susan

    2015-03-01

    The lymphocytic choriomenigitis virus (LCMV) is a rodent-spread virus commonly recognized as causing neurological disease that exhibits asymptomatic pathology. The virus is a pathogen normally carried among rodents that can be transmitted to humans by direct or indirect contact with the virus in excretions and secretions from rodents and can cause aseptic meningitis and other conditions in humans. We consider an epidemiological system within rodent populations modeled by a system of ordinary differential equations that captures the dynamics of the diseases transmission and present our findings. The asymptotic nature of the pathogen plays a large role in its spread within a given population, which has motivated us to expand upon an existing SIRC model (Holechek et al in preparation) that accounts for susceptible-, infected-, recovered-, and carrier-mice on the basis of their gender. We are interested in observing and determining the conditions under which the carrier population will reach a disease free equilibrium, and we focus our investigation on the sensitivity of our model to gender, pregnancy related infection, and reproduction rate conditions.

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

    Directory of Open Access Journals (Sweden)

    A. D. Bottrill

    2012-11-01

    Full Text Available Dynamic models of subduction and continental collision are used to predict dynamic topography changes on the overriding plate. The modelling results show a distinct evolution of topography on the overriding plate, during subduction, continental collision and slab break-off. A prominent topographic feature is a temporary (few Myrs basin on the overriding plate after initial collision. This "collisional mantle dynamic basin" (CMDB is caused by slab steepening drawing, material away from the base of the overriding plate. Also, during this initial collision phase, surface uplift is predicted on the overriding plate between the suture zone and the CMDB, due to the subduction of buoyant continental material and its isostatic compensation. After slab detachment, redistribution of stresses and underplating of the overriding plate cause the uplift to spread further into the overriding plate. This topographic evolution fits the stratigraphy found on the overriding plate of the Arabia-Eurasia collision zone in Iran and south east Turkey. The sedimentary record from the overriding plate contains Upper Oligocene-Lower Miocene marine carbonates deposited between terrestrial clastic sedimentary rocks, in units such as the Qom Formation and its lateral equivalents. This stratigraphy shows that during the Late Oligocene–Early Miocene the surface of the overriding plate sank below sea level before rising back above sea level, without major compressional deformation recorded in the same area. Our modelled topography changes fit well with this observed uplift and subsidence.

  11. Modelling absorbing aerosol with ECHAM-HAM: Insights from regional studies

    Science.gov (United States)

    Tegen, Ina; Heinold, Bernd; Schepanski, Kerstin; Banks, Jamie; Kubin, Anne; Schacht, Jacob

    2017-04-01

    Quantifying distributions and properties of absorbing aerosol is a basis for investigations of interactions of aerosol particles with radiation and climate. While evaluations of aerosol models by field measurements can be particularly successful at the regional scale, such results need to be put into a global context for climate studies. We present an overview over studies performed at the Leibniz Institute for Tropospheric Research aiming at constraining the properties of mineral dust and soot aerosol in the global aerosol model ECHAM6-HAM2 based on different regional studies. An example is the impact of different sources for dust transported to central Asia, which is influenced, by far-range transport of dust from Arabia and the Sahara together with dust from local sources. Dust types from these different source regions were investigated in the context of the CADEX project and are expected to have different optical properties. For Saharan dust, satellite retrievals from MSG SEVIRI are used to constrain Saharan dust sources and optical properties. In the Arctic region, on one hand dust aerosol is simulated in the framework of the PalMod project. On the other hand aerosol measurements that will be taken during the DFG-funded (AC)3 field campaigns will be used to evaluate the simulated transport pathways of soot aerosol from European, North American and Asian sources, as well as the parameterization of soot ageing processes in ECHAM6-HAM2. Ultimately, results from these studies will improve the representation of aerosol absorption in the global model.

  12. Epidemiological Implications of Host Biodiversity and Vector Biology: Key Insights from Simple Models.

    Science.gov (United States)

    Dobson, Andrew D M; Auld, Stuart K J R

    2016-04-01

    Models used to investigate the relationship between biodiversity change and vector-borne disease risk often do not explicitly include the vector; they instead rely on a frequency-dependent transmission function to represent vector dynamics. However, differences between classes of vector (e.g., ticks and insects) can cause discrepancies in epidemiological responses to environmental change. Using a pair of disease models (mosquito- and tick-borne), we simulated substitutive and additive biodiversity change (where noncompetent hosts replaced or were added to competent hosts, respectively), while considering different relationships between vector and host densities. We found important differences between classes of vector, including an increased likelihood of amplified disease risk under additive biodiversity change in mosquito models, driven by higher vector biting rates. We also draw attention to more general phenomena, such as a negative relationship between initial infection prevalence in vectors and likelihood of dilution, and the potential for a rise in density of infected vectors to occur simultaneously with a decline in proportion of infected hosts. This has important implications; the density of infected vectors is the most valid metric for primarily zoonotic infections, while the proportion of infected hosts is more relevant for infections where humans are a primary host.

  13. A Structural Model for a Self-Assembled Nanotube Provides Insight into Its Exciton Dynamics

    Science.gov (United States)

    2016-01-01

    The design and synthesis of functional self-assembled nanostructures is frequently an empirical process fraught with critical knowledge gaps about atomic-level structure in these noncovalent systems. Here, we report a structural model for a semiconductor nanotube formed via the self-assembly of naphthalenediimide-lysine (NDI-Lys) building blocks determined using experimental 13C–13C and 13C–15N distance restraints from solid-state nuclear magnetic resonance supplemented by electron microscopy and X-ray powder diffraction data. The structural model reveals a two-dimensional-crystal-like architecture of stacked monolayer rings each containing ∼50 NDI-Lys molecules, with significant π-stacking interactions occurring both within the confines of the ring and along the long axis of the tube. Excited-state delocalization and energy transfer are simulated for the nanotube based on time-dependent density functional theory and an incoherent hopping model. Remarkably, these calculations reveal efficient energy migration from the excitonic bright state, which is in agreement with the rapid energy transfer within NDI-Lys nanotubes observed previously using fluorescence spectroscopy. PMID:26120375

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  17. Novel Insights into the Genetic Controls of Primitive and Definitive Hematopoiesis from Zebrafish Models

    Directory of Open Access Journals (Sweden)

    Raman Sood

    2012-01-01

    Full Text Available Hematopoiesis is a dynamic process where initiation and maintenance of hematopoietic stem cells, as well as their differentiation into erythroid, myeloid and lymphoid lineages, are tightly regulated by a network of transcription factors. Understanding the genetic controls of hematopoiesis is crucial as perturbations in hematopoiesis lead to diseases such as anemia, thrombocytopenia, or cancers, including leukemias and lymphomas. Animal models, particularly conventional and conditional knockout mice, have played major roles in our understanding of the genetic controls of hematopoiesis. However, knockout mice for most of the hematopoietic transcription factors are embryonic lethal, thus precluding the analysis of their roles during the transition from embryonic to adult hematopoiesis. Zebrafish are an ideal model organism to determine the function of a gene during embryonic-to-adult transition of hematopoiesis since bloodless zebrafish embryos can develop normally into early larval stage by obtaining oxygen through diffusion. In this review, we discuss the current status of the ontogeny and regulation of hematopoiesis in zebrafish. By providing specific examples of zebrafish morphants and mutants, we have highlighted the contributions of the zebrafish model to our overall understanding of the roles of transcription factors in regulation of primitive and definitive hematopoiesis.

  18. 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

  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. Mechanical Controls on Halokinesis in Layered Evaporite Sequences: Insights from 2D Geomechanical Forward Models

    Science.gov (United States)

    Goteti, Rajesh; Agar, Susan M.; Brown, John P.; Ball, Philip; Zuhlke, Rainer

    2017-04-01

    Mechanical stratification in LES (Layered Evaporate Sequences) can have a distinct impact on structural and depositional styles in rifted margin salt tectonics. The bulk mechanical response of an LES under geological loading is dependent, among other factors, on the relative proportions of salt and sediment, salt mobility and sedimentation rate. To assess the interactions among the aforementioned factors in a physically consistent manner, we present 2D, large-strain finite element models of an LES salt minibasin and diapirs. Loading from the deposition of alternating salt and sediment layers (i.e., LES), gravity and a prescribed geothermal gradient provide the driving force for halokinesis in the models. To accurately capture the mechanical impact of stratification within the modeled LES, salt is assigned a temperature-dependent visco-plastic rheology, whereas the sediments are assigned a non-associative cap-plasticity model that supports both compaction and shear localization. Perturbations in the initial salt-sediment interface are used to initiate the salt diapirs. Model results suggest that active diapirism in the basal halite layer initiates when the pressure at the base of the incipient salt diapir exceeds that beneath the minibasin. Vertical growth of the diapir is also accompanied by its lateral expansion at higher structural levels where it preferentially intrudes the adjacent pre- and syn-kinematic salt layers. This pressure pumping of deeper salt into shallow salt layers, can result in rapid thickness changes between successive sediment layers within the LES. Caution needs to be exercised as such thickness changes observed in seismic images may not be entirely due to the shifting of depocenters but also due to the lateral pumping of salt within the LES. The presence of salt layers at multiple structural levels decouples the deformation between successive clastic layers resulting in disharmomic folding with contrasting strain histories in the sedimentary

  1. 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

  2. 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.

  3. 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 (continental passive margins document the heterogeneous nature of the lithosphere characterized, among others, by lithological variations and structural inheritance. This contribution aims at investigating the mechanisms of extreme lithospheric thinning by exploring in particular the role of initial heterogeneities by coupling field observations from fossil passive margins and numerical models of lithospheric extension. Two field examples from the Alpine Tethys margins outcropping in the Eastern Alps (E Switzerland and 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

  4. Vaccine approaches to malaria control and elimination: Insights from mathematical models.

    Science.gov (United States)

    White, Michael T; Verity, Robert; Churcher, Thomas S; Ghani, Azra C

    2015-12-22

    A licensed malaria vaccine would provide a valuable new tool for malaria control and elimination efforts. Several candidate vaccines targeting different stages of the malaria parasite's lifecycle are currently under development, with one candidate, RTS,S/AS01 for the prevention of Plasmodium falciparum infection, having recently completed Phase III trials. Predicting the public health impact of a candidate malaria vaccine requires using clinical trial data to estimate the vaccine's efficacy profile--the initial efficacy following vaccination and the pattern of waning of efficacy over time. With an estimated vaccine efficacy profile, the effects of vaccination on malaria transmission can be simulated with the aid of mathematical models. Here, we provide an overview of methods for estimating the vaccine efficacy profiles of pre-erythrocytic vaccines and transmission-blocking vaccines from clinical trial data. In the case of RTS,S/AS01, model estimates from Phase II clinical trial data indicate a bi-phasic exponential profile of efficacy against infection, with efficacy waning rapidly in the first 6 months after vaccination followed by a slower rate of waning over the next 4 years. Transmission-blocking vaccines have yet to be tested in large-scale Phase II or Phase III clinical trials so we review ongoing work investigating how a clinical trial might be designed to ensure that vaccine efficacy can be estimated with sufficient statistical power. Finally, we demonstrate how parameters estimated from clinical trials can be used to predict the impact of vaccination campaigns on malaria using a mathematical model of malaria transmission. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Modeling Prolactin Actions in Breast Cancer in vivo: Insights from the NRL-PRL Mouse

    Science.gov (United States)

    O'Leary, Kathleen A.; Shea, Michael P.; Schuler, Linda A.

    2016-01-01

    Elevated exposure to prolactin is epidemiologically associated with an increased risk of aggressive ER+ breast cancer. To understand the underlying mechanisms and crosstalk with other oncogenic factors, we developed the NRL-PRL mouse. In this model, mammary expression of a rat prolactin transgene raises local exposure to prolactin without altering estrous cycling. Nulliparous females develop metastatic, histotypically diverse mammary carcinomas independent from ovarian steroids, and most are ER+. These characteristics resemble the human clinical disease, facilitating study of tumorigenesis, and identification of novel preventive and therapeutic approaches. PMID:25472540

  13. What controls biological production in coastal upwelling systems? Insights from a comparative modeling study

    Directory of Open Access Journals (Sweden)

    Z. Lachkar

    2011-10-01

    Full Text Available The magnitude of net primary production (NPP in Eastern Boundary Upwelling Systems (EBUS is traditionally viewed as directly reflecting the wind-driven upwelling intensity. Yet, different EBUS show different sensitivities of NPP to upwelling-favorable winds (Carr and Kearns, 2003. Here, using a comparative modeling study of the California Current System (California CS and Canary Current System (Canary CS, we show how physical and environmental factors, such as light, temperature and cross-shore circulation modulate the response of NPP to upwelling strength. To this end, we made a series of eddy-resolving simulations of the two upwelling systems using the Regional Oceanic Modeling System (ROMS, coupled to a nitrogen-based Nutrient-Phytoplankton-Zooplankton-Detritus (NPZD ecosystem model. Using identical ecological/biogeochemical parameters, our coupled model simulates a level of NPP in the California CS that is 50 % smaller than that in the Canary CS, in agreement with observationally based estimates. We find this much lower NPP in the California CS despite phytoplankton in this system having nearly 20 % higher nutrient concentrations available to fuel their growth. This conundrum can be explained by: (1 phytoplankton having a faster nutrient-replete growth in the Canary CS relative to the California CS; a consequence of more favorable light and temperature conditions in the Canary CS, and (2 the longer nearshore water residence times in the Canary CS, which permit a larger buildup of biomass in the upwelling zone, thereby enhancing NPP. The longer residence times in the Canary CS appear to be a result of the wider continental shelves and the lower mesoscale activity characterizing this upwelling system. This results in a weaker offshore export of nutrients and organic matter, thereby increasing local nutrient recycling and reducing the spatial decoupling between new and export production in the Canary CS. Our results suggest that climate change

  14. 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

  15. 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

  16. Insight into the novel inhibition mechanism of apigenin to Pneumolysin by molecular modeling

    Science.gov (United States)

    Niu, Xiaodi; Yang, Yanan; Song, Meng; Wang, Guizhen; Sun, Lin; Gao, Yawen; Wang, Hongsu

    2017-11-01

    In this study, the mechanism of apigenin inhibition was explored using molecular modelling, binding energy calculation, and mutagenesis assays. Energy decomposition analysis indicated that apigenin binds in the gap between domains 3 and 4 of PLY. Using principal component analysis, we found that binding of apigenin to PLY weakens the motion of domains 3 and 4. Consequently, these domains cannot complete the transition from monomer to oligomer, thereby blocking oligomerisation of PLY and counteracting its haemolytic activity. This inhibitory mechanism was confirmed by haemolysis assays, and these findings will promote the future development of an antimicrobial agent.

  17. Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

    Science.gov (United States)

    Sanz-Herrera, Jose A.; Reina-Romo, Esther

    2011-01-01

    Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields. PMID:22174660

  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

    2016-11-01

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. 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.

  20. 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.

  1. Evolution of Coronary Flow in an Experimental Slow Flow Model in Swines: Angiographic and Pathological Insights

    Directory of Open Access Journals (Sweden)

    Yupeng Bai

    2015-01-01

    Full Text Available Objective. Pathomechanism of coronary slow flow phenomenon remains largely unclear now. Present study observed the pathological and angiographic evolution in a pig model of coronary slow flow. Methods. Coronary slow flow was induced by repeat coronary injection of small doses of 40 µm microspheres in 18 male domestic pigs and angiographic and pathological changes were determined at 3 hours, 7 days, and 28 days after microspheres injection. Results. Compared to control group treated with coronary saline injection n=6 and baseline level, coronary flow was significantly reduced at 3 hours and 7 days but completely recovered at 28 days after coronary microsphere injection in slow flow group. Despite normal coronary flow at 28 days after microsphere injection, enhanced myocardial cytokine expression, left ventricular dysfunction, adverse remodelling, and ischemia/microembolism related pathological changes still persisted or even progressed from 3 hours to 28 days after coronary microsphere injection. Conclusions. Our results show that this large animal slow flow model could partly reflect the chronic angiographic, hemodynamic, and pathological changes of coronary slow flow and could be used to test new therapy strategies against the slow flow phenomenon.

  2. Modeling information flows in clinical decision support: key insights for enhancing system effectiveness.

    Science.gov (United States)

    Medlock, Stephanie; Wyatt, Jeremy C; Patel, Vimla L; Shortliffe, Edward H; Abu-Hanna, Ameen

    2016-09-01

    A fundamental challenge in the field of clinical decision support is to determine what characteristics of systems make them effective in supporting particular types of clinical decisions. However, we lack such a theory of decision support itself and a model to describe clinical decisions and the systems to support them. This article outlines such a framework. We present a two-stream model of information flow within clinical decision-support systems (CDSSs): reasoning about the patient (the clinical stream), and reasoning about the user (the cognitive-behavioral stream). We propose that CDSS "effectiveness" be measured not only in terms of a system's impact on clinical care, but also in terms of how (and by whom) the system is used, its effect on work processes, and whether it facilitates appropriate decisions by clinicians and patients. Future research into which factors improve the effectiveness of decision support should not regard CDSSs as a single entity, but should instead differentiate systems based on their attributes, users, and the decision being supported. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Finding the 'lost years' in green turtles: insights from ocean circulation models and genetic analysis.

    Science.gov (United States)

    Putman, Nathan F; Naro-Maciel, Eugenia

    2013-10-07

    Organismal movement is an essential component of ecological processes and connectivity among ecosystems. However, estimating connectivity and identifying corridors of movement are challenging in oceanic organisms such as young turtles that disperse into the open sea and remain largely unobserved during a period known as 'the lost years'. Using predictions of transport within an ocean circulation model and data from published genetic analysis, we present to our knowledge, the first basin-scale hypothesis of distribution and connectivity among major rookeries and foraging grounds (FGs) of green turtles (Chelonia mydas) during their 'lost years'. Simulations indicate that transatlantic dispersal is likely to be common and that recurrent connectivity between the southwestern Indian Ocean and the South Atlantic is possible. The predicted distribution of pelagic juvenile turtles suggests that many 'lost years hotspots' are presently unstudied and located outside protected areas. These models, therefore, provide new information on possible dispersal pathways that link nesting beaches with FGs. These pathways may be of exceptional conservation concern owing to their importance for sea turtles during a critical developmental period.

  4. 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.

  5. Smoldering multiple myeloma: pathophysiologic insights, novel diagnostics, clinical risk models, and treatment strategies.

    Science.gov (United States)

    Kazandjian, Dickran; Mailankody, Sham; Korde, Neha; Landgren, Ola

    2014-09-01

    Smoldering multiple myeloma (SMM) is a plasma cell disorder first described in 1980 when 6 patients were observed to meet the diagnostic criteria of multiple myeloma, defined as bone marrow plasmacytosis of 10% or greater or M protein level of 3 g/dL or greater, but did not have end-organ damage. Subsequent studies showed that the cumulative risk of SMM progression to symptomatic myeloma in 15 years was 73%. Since this time, advances have been made in understanding the biology of progression; namely, the contribution of branching evolution and microenvironment models to clonal heterogeneity. In parallel to this, clinical risk models using standard platforms of serum, bone marrow, and fluorescence in situ hybridization markers along with newer technologies of flow cytometry, gene expression profiling, and magnetic resonance imaging have been developed for prognostic stratification. Treatment has extended to the early myeloma category owing to more sensitive diagnostic approaches. The development of novel treatments will have to take into consideration our current knowledge of biological transformation. While it may be attractive to initiate early treatment in light of recent studies for high-risk SMM patients, clinical trial evidence of efficacy vs toxicity is still in its infancy. In our opinion, high-risk SMM patients should be strongly encouraged to enroll in treatment clinical trials, but treatment with unapproved agents or indications is not supported outside of trials.

  6. Treatment of amblyopia in the adult: insights from a new rodent model of visual perceptual learning

    Directory of Open Access Journals (Sweden)

    Joyce eBonaccorsi

    2014-07-01

    Full Text Available 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.

  7. 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.

  8. 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.

  9. New Force Field Model for Propylene Glycol: Insight to Local Structure and Dynamics.

    Science.gov (United States)

    Ferreira, Elisabete S C; Voroshylova, Iuliia V; Koverga, Volodymyr A; Pereira, Carlos M; Cordeiro, M Natália D S

    2017-12-07

    In this work we developed a new force field model (FFM) for propylene glycol (PG) based on the OPLS all-atom potential. The OPLS potential was refined using quantum chemical calculations, taking into account the densities and self-diffusion coefficients. The validation of this new FFM was carried out based on a wide range of physicochemical properties, such as density, enthalpy of vaporization, self-diffusion coefficients, isothermal compressibility, surface tension, and shear viscosity. The molecular dynamics (MD) simulations were performed over a large range of temperatures (293.15-373.15 K). The comparison with other force field models, such as OPLS, CHARMM27, and GAFF, revealed a large improvement of the results, allowing a better agreement with experimental data. Specific structural properties (radial distribution functions, hydrogen bonding and spatial distribution functions) were then analyzed in order to support the adequacy of the proposed FFM. Pure propylene glycol forms a continuous phase, displaying no microstructures. It is shown that the developed FFM gives rise to suitable results not only for pure propylene glycol but also for mixtures by testing its behavior for a 50 mol % aqueous propylene glycol solution. Furthermore, it is demonstrated that the addition of water to the PG phase produces a homogeneous solution and that the hydration interactions prevail over the propylene glycol self-association interactions.

  10. 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.

  11. 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.

  12. 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

  13. Near-atomic structural model for bacterial DNA replication initiation complex and its functional insights.

    Science.gov (United States)

    Shimizu, Masahiro; Noguchi, Yasunori; Sakiyama, Yukari; Kawakami, Hironori; Katayama, Tsutomu; Takada, Shoji

    2016-12-13

    Upon DNA replication initiation in Escherichia coli, the initiator protein DnaA forms higher-order complexes with the chromosomal origin oriC and a DNA-bending protein IHF. Although tertiary structures of DnaA and IHF have previously been elucidated, dynamic structures of oriC-DnaA-IHF complexes remain unknown. Here, combining computer simulations with biochemical assays, we obtained models at almost-atomic resolution for the central part of the oriC-DnaA-IHF complex. This complex can be divided into three subcomplexes; the left and right subcomplexes include pentameric DnaA bound in a head-to-tail manner and the middle subcomplex contains only a single DnaA. In the left and right subcomplexes, DnaA ATPases associated with various cellular activities (AAA+) domain III formed helices with specific structural differences in interdomain orientations, provoking a bend in the bound DNA. In the left subcomplex a continuous DnaA chain exists, including insertion of IHF into the DNA looping, consistent with the DNA unwinding function of the complex. The intervening spaces in those subcomplexes are crucial for DNA unwinding and loading of DnaB helicases. Taken together, this model provides a reasonable near-atomic level structural solution of the initiation complex, including the dynamic conformations and spatial arrangements of DnaA subcomplexes.

  14. 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.

  15. 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.

  16. Molecular mechanisms of liver ischemia reperfusion injury: Insights from transgenic knockout models

    Science.gov (United States)

    Datta, Gourab; Fuller, Barry J; Davidson, Brian R

    2013-01-01

    Ischemia reperfusion injury is a major obstacle in liver resection and liver transplantation surgery. Understanding the mechanisms of liver ischemia reperfusion injury (IRI) and developing strategies to counteract this injury will therefore reduce acute complications in hepatic resection and transplantation, as well as expanding the potential pool of usable donor grafts. The initial liver injury is initiated by reactive oxygen species which cause direct cellular injury and also activate a cascade of molecular mediators leading to microvascular changes, increased apoptosis and acute inflammatory changes with increased hepatocyte necrosis. Some adaptive pathways are activated during reperfusion that reduce the reperfusion injury. IRI involves a complex interplay between neutrophils, natural killer T-cells cells, CD4+ T cell subtypes, cytokines, nitric oxide synthases, haem oxygenase-1, survival kinases such as the signal transducer and activator of transcription, Phosphatidylinositol 3-kinases/Akt and nuclear factor κβ pathways. Transgenic animals, particularly genetic knockout models, have become a powerful tool at elucidating mechanisms of liver ischaemia reperfusion injury and are complementary to pharmacological studies. Targeted disruption of the protein at the genetic level is more specific and maintained than pharmacological inhibitors or stimulants of the same protein. This article reviews the evidence from knockout models of liver IRI about the cellular and molecular mechanisms underlying liver IRI. PMID:23555157

  17. 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.

  18. Decarbonation of subducting slabs: insight from thermomechanical-petrological numerical modelling

    Science.gov (United States)

    Gonzalez, Christopher M.; Gorczyk, Weronika; Gerya, Taras

    2015-04-01

    This work extends a numerical geodynamic modelling code (I2VIS) to simulate subduction of carbonated lithologies (altered basalts and carbonated sediments) into the mantle. Code modifications now consider devolatilisation of H2O-CO2 fluids, a CO2-melt solubility parameterisation for molten sediments, and allows for carbonation of mantle peridotites. The purpose is to better understand slab generated CO2 fluxes and consequent subduction of carbonates into the deep mantle via numerical simulation. Specifically, we vary two key model parameters: 1) slab convergence rate (1,2,3,4,5 cm y-1) and 2) converging oceanic slab age (20,40,60,80 Ma) based on a half-space cooling model. The aim is to elucidate the role subduction dynamics has (i.e., spontaneous sedimentary diapirism, slab roll-back, and shear heating) with respect to slab decarbonation trends not entirely captured in previous experimental and thermodynamic investigations. This is accomplished within a fully coupled petrological-thermomechanical modelling framework utilising a characteristics-based marker-in-cell technique capable of solving visco-plastic rheologies. The thermodynamic database is modified from its original state to reflect the addition of carbonate as CO2 added to the rock's overall bulk composition. Modifications to original lithological units and volatile bulk compositions are as follows: GLOSS average sediments (H2O: 7.29 wt% & CO2: 3.01 wt%), altered basalts (H2O: 2.63 wt% & CO2: 2.90 wt%), and metasomatised peridotite (H2O: 1.98 wt% & CO2: 1.5 wt%). We resolve stable mineralogy and extract rock properties via PerpleX at a resolution of 5K and 25 MPa. Devolatilisation/consumption and stability of H2O-CO2 fluid is determined by accessing the thermodynamic database. When fluid is released due to unstable conditions, it is tracked via markers that freely advect within the velocity field until consumed. 56 numerical models were completed and our results show excellent agreement in dynamics with

  19. Insights into the Sensitivity and Resilience of Riparian Ecosystems to Flow Regime Shifts Through a Coupled Ecogeomorpic Model

    Science.gov (United States)

    Diehl, R. M.; Wilcox, A. C.; Merritt, D. M.

    2017-12-01

    Management of river systems relies on an understanding of the relationship between flow and ecosystem properties. Flow response curves formalize this relationship by empirically linking the form and/or function of the biota or physical template of a river system to a change in flow properties. To gain insight into the coupled nature of riparian ecosystems, and make predictions about their response to a change in discharge, we built an ecogeomorphic model from a series of flow response curves based on data collected on the Yampa and Green Rivers, Colorado and Utah. These curves relate attributes of the flow regime to the 1) presence/absence of groupings of functionally similar plants (riparian response guilds), 2) plant cover density, and 3) plot-scale topographic response to a single flood event. Our model successfully identifies the spatial distribution of suitable plant guild habitat and has moderate success predicting the magnitude and direction of the geomorphic response to flood events. The shape of the resulting response curves are non-linear and exhibit clear thresholds. These features suggest that ecogeomorphic processes that shape riparian communities are at times highly sensitive, and at other times highly resilient, to the magnitude and direction of shifts in the flow regime. We explore this observation by comparing the trajectory of riparian ecosystem adjustment for three future flow scenarios in the Yampa River. The six plant guilds we model all show sensitivity to shifts in some part of the flow regime, and resilience to others. Erosional and depositional patterns respond in part to the shifts in guild distributions, but also in part in response to changes in flow hydraulics. Use of guilds in our model facilitates generalization across large environmental gradients and across systems. The linkages among environmental conditions, riparian plant community dynamics, and morphodynamics represented in our ecogeomorphic model makes this approach a powerful

  20. Impact of Mantle Wind on Subducting Plate Geometry and Interplate Pressure: Insights From Physical Modelling.

    Science.gov (United States)

    Boutelier, D.; Cruden, A. R.

    2005-12-01

    New physical models of subduction investigate the impact of large-scale mantle flow on the structure of the subducted slab and deformation of the downgoing and overriding plates. The experiments comprise two lithospheric plates made of highly filled silicone polymer resting on a model asthenosphere of low viscosity transparent silicone polymer. Subduction is driven by a piston that pushes the subducting plate at constant rate, a slab-pull force due to the relative density of the slab, and a basal drag force exerted by flow in the model asthenosphere. Large-scale mantle flow is imposed by a second piston moving at constant rate in a tunnel at the bottom of the experiment tank. Passive markers in the mantle track the evolution of flow during the experiment. Slab structure is recorded by side pictures of the experiment while horizontal deformation is studied via passive marker grids on top of both plates. The initial mantle flow direction beneath the overriding plate can be sub-horizontal or sub-vertical. In both cases, as the slab penetrates the mantle, the mantle flow pattern changes to accommodate the subducting high viscosity lithosphere. As the slab continues to descend, the imposed flow produces either over- or under-pressure on the lower surface of the slab depending on the initial mantle flow pattern (sub-horizontal or sub-vertical respectively). Over-pressure imposed on the slab lower surface promotes shallow dip subduction while under-pressure tends to steepen the slab. These effects resemble those observed in previous experiments when the overriding plate moves horizontally with respect to a static asthenosphere. Our experiments also demonstrate that a strong vertical drag force (due to relatively fast downward mantle flow) exerted on the slab results in a decrease in strain rate in both the downgoing and overriding plates, suggesting a decrease in interplate pressure. Furthermore, with an increase in drag force deformation in the downgoing plate can switch

  1. 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

  2. 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

    2016-09-28

    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(NH 2 ) 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(NH 2 ) 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(NH 2 ) 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

  3. 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

  4. 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

  5. Cardiac conduction system anomalies and sudden cardiac death: insights from murine models

    Directory of Open Access Journals (Sweden)

    Amelia Eva Aranega

    2012-06-01

    Full Text Available The cardiac conduction system (CCS is a series of specialized tissues in the heart responsible for the initiation and co-ordination of the heartbeat. Alterations in the CCS, especially the His-Purkinje system, have been identified as an important player in the generation of lethal arrhythmias. Unstable arrhythmias secondary to channelopathies highly increase the risk of sudden cardiac death (SCD. Sudden cardiac death is a major contributor to mortality in industrialized nations, and most cases of SCD in the young are related to inherited ion channel diseases. In this review we examine how murine transgenic models have contributed to understanding that a broad variety of cardiac arrhythmias involve the cardiac specialized conduction system and may lead to sudden cardiac death.

  6. 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

  7. 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.

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

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    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.

  9. 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.

  10. 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.

  11. 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.

  12. Insights into plant size-density relationships from models and agricultural crops.

    Science.gov (United States)

    Deng, Jianming; Zuo, Wenyun; Wang, Zhiqiang; Fan, Zhexuan; Ji, Mingfei; Wang, Genxuan; Ran, Jinzhi; Zhao, Changming; Liu, Jianquan; Niklas, Karl J; Hammond, Sean T; Brown, James H

    2012-05-29

    There is general agreement that competition for resources results in a tradeoff between plant mass, M, and density, but the mathematical form of the resulting thinning relationship and the mechanisms that generate it are debated. Here, we evaluate two complementary models, one based on the space-filling properties of canopy geometry and the other on the metabolic basis of resource use. For densely packed stands, both models predict that density scales as M(-3/4), energy use as M(0), and total biomass as M(1/4). Compilation and analysis of data from 183 populations of herbaceous crop species, 473 stands of managed tree plantations, and 13 populations of bamboo gave four major results: (i) At low initial planting densities, crops grew at similar rates, did not come into contact, and attained similar mature sizes; (ii) at higher initial densities, crops grew until neighboring plants came into contact, growth ceased as a result of competition for limited resources, and a tradeoff between density and size resulted in critical density scaling as M(-0.78), total resource use as M(-0.02), and total biomass as M(0.22); (iii) these scaling exponents are very close to the predicted values of M(-3/4), M(0), and M(1/4), respectively, and significantly different from the exponents suggested by some earlier studies; and (iv) our data extend previously documented scaling relationships for trees in natural forests to small herbaceous annual crops. These results provide a quantitative, predictive framework with important implications for the basic and applied plant sciences.

  13. Computational modeling of the hematopoietic erythroid-myeloid switch reveals insights into cooperativity, priming, and irreversibility.

    Directory of Open Access Journals (Sweden)

    Vijay Chickarmane

    2009-01-01

    Full Text Available Hematopoietic stem cell lineage choices are decided by genetic networks that are turned ON/OFF in a switch-like manner. However, prior to lineage commitment, genes are primed at low expression levels. Understanding the underlying molecular circuitry in terms of how it governs both a primed state and, at the other extreme, a committed state is of relevance not only to hematopoiesis but also to developmental systems in general. We develop a computational model for the hematopoietic erythroid-myeloid lineage decision, which is determined by a genetic switch involving the genes PU.1 and GATA-1. Dynamical models based upon known interactions between these master genes, such as mutual antagonism and autoregulation, fail to make the system bistable, a desired feature for robust lineage determination. We therefore suggest a new mechanism involving a cofactor that is regulated as well as recruited by one of the master genes to bind to the antagonistic partner that is necessary for bistability and hence switch-like behavior. An interesting fallout from this architecture is that suppression of the cofactor through external means can lead to a loss of cooperativity, and hence to a primed state for PU.1 and GATA-1. The PU.1-GATA-1 switch also interacts with another mutually antagonistic pair, C/EBPalpha-FOG-1. The latter pair inherits the state of its upstream master genes and further reinforces the decision due to several feedback loops, thereby leading to irreversible commitment. The genetic switch, which handles the erythroid-myeloid lineage decision, is an example of a network that implements both a primed and a committed state by regulating cooperativity through recruitment of cofactors. Perturbing the feedback between the master regulators and downstream targets suggests potential reprogramming strategies. The approach points to a framework for lineage commitment studies in general and could aid the search for lineage-determining genes.

  14. Auxin transport at cellular level: new insights supported by mathematical modelling

    Science.gov (United States)

    Hošek, Petr; Kubeš, Martin; Laňková, Martina; Dobrev, Petre I.; Klíma, Petr; Kohoutová, Milada; Petrášek, Jan; Hoyerová, Klára; Jiřina, Marcel; Zažímalová, Eva

    2012-01-01

    The molecular basis of cellular auxin transport is still not fully understood. Although a number of carriers have been identified and proved to be involved in auxin transport, their regulation and possible activity of as yet unknown transporters remain unclear. Nevertheless, using single-cell-based systems it is possible to track the course of auxin accumulation inside cells and to specify and quantify some auxin transport parameters. The synthetic auxins 2,4-dichlorophenoxyacetic acid (2,4-D) and naphthalene-1-acetic acid (NAA) are generally considered to be suitable tools for auxin transport studies because they are transported specifically via either auxin influx or efflux carriers, respectively. Our results indicate that NAA can be metabolized rapidly in tobacco BY-2 cells. The predominant metabolite has been identified as NAA glucosyl ester and it is shown that all NAA metabolites were retained inside the cells. This implies that the transport efficiency of auxin efflux transporters is higher than previously assumed. By contrast, the metabolism of 2,4-D remained fairly weak. Moreover, using data on the accumulation of 2,4-D measured in the presence of auxin transport inhibitors, it is shown that 2,4-D is also transported by efflux carriers. These results suggest that 2,4-D is a promising tool for determining both auxin influx and efflux activities. Based on the accumulation data, a mathematical model of 2,4-D transport at a single-cell level is proposed. Optimization of the model provides estimates of crucial transport parameters and, together with its validation by successfully predicting the course of 2,4-D accumulation, it confirms the consistency of the present concept of cellular auxin transport. PMID:22438304

  15. Crustal melting beneath orogenic plateaus: Insights from 3-D thermo-mechanical modeling

    Science.gov (United States)

    Chen, L.; Song, X.; Gerya, T.; Xu, T.; Chen, Y.

    2017-12-01

    Mid-crustal melting is widely documented within orogenic plateaus. However, the mechanism for its generation and its role in the evolution of orogenic plateaus remain poorly understood. Here we use 3-D thermo-mechanical models to investigate the physical controls for mid-crustal melting beneath orogenic plateaus and its consequences in plateau evolution. The results demonstrate that: 1) lateral lithospheric strength contrast between two colliding continents facilitates an episodic growth of orogenic plateau and mid-crustal melting; 2) slower convergence favors larger amount of melt; and 3) radioactive heating during crustal thickening plays the primary role in generating mid-crustal melting. Shear heating also plays a positive role in mid-crustal melting, but its role is secondary to radioactive heating. During collisional orogeny, it is the combination of crustal self-heating (radioactive/shear heating) and the contrast in radiogenic element concentration between the upper and lower crust that makes the base of the thickened upper crust favorable for in situ crustal melting at the mid-crust. We also demonstrate that the occurrence of the mid-crustal melting layer postdates the establishment of a broad orogenic plateau, and causes mechanical decoupling between the overlying upper crust and underlying lower crust by dramatically reducing mid-crustal strength. At the later stage, the melt-weakened layer flows outward in a localized channel and manifest its potential role in the marginal dominance of mid-crustal partial melting. Our models provide a self-consistent explanation for the low S-wave velocity zones widespread in the Tibetan middle crust, which are most prominent in the periphery of Tibet.

  16. Insights into tetracycline adsorption onto kaolinite and montmorillonite: experiments and modeling.

    Science.gov (United States)

    Zhao, Yanping; Gu, Xueyuan; Li, Shiyin; Han, Ruiming; Wang, Guoxiang

    2015-11-01

    Adsorption of tetracycline (TC) on kaolinite and montmorillonite was investigated using batch adsorption experiments with different pH, ionic strength, and surface coverage. As a result, pH and ionic strength-dependent adsorption of TC was observed for the two clay minerals. The adsorption of TC decreased with the increase of pH and ionic strength, and high initial TC concentration had high adsorption. In addition, a triple-layer model was used to predict the adsorption and surface speciation of TC on the two minerals. As a result, four complex species on kaolinite (≡X(-)∙H3TC(+), ≡X(-)∙H2TC(±), ≡SOH(0)∙H2TC(±), and ≡SOH(0)∙HTC(-)) and three species on montmorillonite (≡X(-)∙H3TC(+), ≡X(-)∙H2TC(±), and ≡SOH(0)∙HTC(-)) were structurally constrained by spectroscopy, and these species were also successfully fitted to the adsorption edges of TC. Three functional groups of TC were involved in these adsorption reactions, including the positively charged dimethylamino group, the C=O amide I group, and the C=O group at the C ring. Combining adsorption experiments and model in this study, the adsorption of TC on kaolinite and montmorillonite was mainly attributed to cation exchange on the surface sites (≡X(-)) compared to surface complexation on the edge sites (≡SOH) at natural soil pH condition. Moreover, the surface adsorption species, the corresponding adsorption modes, and the binding constants for the surface reactions were also estimated.

  17. What compensates the topography of southern Norway? Insights from thermo-isostatic modeling

    Science.gov (United States)

    Kolstrup, Marianne L.; Pascal, Christophe; Maupin, Valerie

    2012-10-01

    The origin of the high topography of the Norwegian Mountains is currently much debated. Several geophysical studies show that the uppermost mantle below southern Norway has anomalously low velocities as compared to other parts of the Baltic Shield. This study aims to shed lights on the structure of the lithospheric mantle below southern Norway by adapting and further refining a method based on isostatic and thermal equilibrium to compute temperature, temperature-related density and synthetic S-wave velocity in stable continental domains. The one-dimensional steady-state heat equation is used with topographic, Moho depth, crustal density and surface heat flow data. A condition of local isostasy is assumed and geoid undulations are used to constrain the range of possible lithosphere models. Results derived from this method suggest a thickening of the thermal lithosphere below southern Norway from west to east. The western part is found to have higher temperatures, lower densities and lower synthetic S-wave velocities than the eastern part, compatible with results from a recent P-wave travel time residual study. Comparison of the synthetic shear-velocity profiles beneath southwestern Norway with velocity profiles inverted from Rayleigh wave dispersion data suggests that the higher temperatures associated with a thinner lithosphere can explain parts of the seismic low-velocity anomaly. The inferred lithospheric structure is sensitive to uncertainties in the crustal input model, but the main features remain undisturbed by changes in the input data. The results show that the lithosphere of southwestern Norway can be in local isostatic equilibrium, if it is thinner and warmer than the lithosphere of eastern Norway. The present-day high topography may therefore be partially sustained by lower densities in the mantle lithosphere.

  18. Insights into plant size-density relationships from models and agricultural crops

    Science.gov (United States)

    Deng, Jianming; Zuo, Wenyun; Wang, Zhiqiang; Fan, Zhexuan; Ji, Mingfei; Wang, Genxuan; Ran, Jinzhi; Zhao, Changming; Liu, Jianquan; Niklas, Karl J.; Hammond, Sean T.; Brown, James H.

    2012-01-01

    There is general agreement that competition for resources results in a tradeoff between plant mass, M, and density, but the mathematical form of the resulting thinning relationship and the mechanisms that generate it are debated. Here, we evaluate two complementary models, one based on the space-filling properties of canopy geometry and the other on the metabolic basis of resource use. For densely packed stands, both models predict that density scales as M−3/4, energy use as M0, and total biomass as M1/4. Compilation and analysis of data from 183 populations of herbaceous crop species, 473 stands of managed tree plantations, and 13 populations of bamboo gave four major results: (i) At low initial planting densities, crops grew at similar rates, did not come into contact, and attained similar mature sizes; (ii) at higher initial densities, crops grew until neighboring plants came into contact, growth ceased as a result of competition for limited resources, and a tradeoff between density and size resulted in critical density scaling as M−0.78, total resource use as M−0.02, and total biomass as M0.22; (iii) these scaling exponents are very close to the predicted values of M−3/4, M0, and M1/4, respectively, and significantly different from the exponents suggested by some earlier studies; and (iv) our data extend previously documented scaling relationships for trees in natural forests to small herbaceous annual crops. These results provide a quantitative, predictive framework with important implications for the basic and applied plant sciences. PMID:22586097

  19. Auxin transport at cellular level: new insights supported by mathematical modelling.

    Science.gov (United States)

    Hosek, Petr; Kubes, Martin; Lanková, Martina; Dobrev, Petre I; Klíma, Petr; Kohoutová, Milada; Petrásek, Jan; Hoyerová, Klára; Jirina, Marcel; Zazímalová, Eva

    2012-06-01

    The molecular basis of cellular auxin transport is still not fully understood. Although a number of carriers have been identified and proved to be involved in auxin transport, their regulation and possible activity of as yet unknown transporters remain unclear. Nevertheless, using single-cell-based systems it is possible to track the course of auxin accumulation inside cells and to specify and quantify some auxin transport parameters. The synthetic auxins 2,4-dichlorophenoxyacetic acid (2,4-D) and naphthalene-1-acetic acid (NAA) are generally considered to be suitable tools for auxin transport studies because they are transported specifically via either auxin influx or efflux carriers, respectively. Our results indicate that NAA can be metabolized rapidly in tobacco BY-2 cells. The predominant metabolite has been identified as NAA glucosyl ester and it is shown that all NAA metabolites were retained inside the cells. This implies that the transport efficiency of auxin efflux transporters is higher than previously assumed. By contrast, the metabolism of 2,4-D remained fairly weak. Moreover, using data on the accumulation of 2,4-D measured in the presence of auxin transport inhibitors, it is shown that 2,4-D is also transported by efflux carriers. These results suggest that 2,4-D is a promising tool for determining both auxin influx and efflux activities. Based on the accumulation data, a mathematical model of 2,4-D transport at a single-cell level is proposed. Optimization of the model provides estimates of crucial transport parameters and, together with its validation by successfully predicting the course of 2,4-D accumulation, it confirms the consistency of the present concept of cellular auxin transport.

  20. 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

  1. 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

  2. Aerosol-Driven Surface Solar Dimming Over Asia: Insights from a Model-Observation Intercomparison

    Science.gov (United States)

    Persad, G.; Ming, Y.; Ramaswamy, V.

    2012-12-01

    Sun photometer and satellite data have indicated a reduction in surface solar radiation (SSR) over India and China during the second half of the 20th century that is at least partly due to anthropogenic aerosols. Recent integrated observational studies of aerosol properties also suggest that this SSR reduction may have a strong contribution from atmospheric absorption by carbonaceous aerosols over Asia. The reduction in SSR and associated redistribution of energy between the surface and atmosphere may have significant implications for regional hydrological systems like the summertime monsoon. Previous generations of general circulation models (GCMs), however, have been largely unsuccessful at recreating aerosol-driven trends in SSR, hindering theoretical investigation of causes and effects of these trends in regional climate. We analyze the behavior of SSR over Asia in the Geophysical Fluid Dynamics Laboratory's AM3 Atmospheric General Circulation Model—the updated aerosol treatment of which contains internal mixing of aerosols and interactive dry and wet deposition—in the context of new satellite and ground-based observational estimates of aerosol-driven SSR reduction. We find that AM3 is more successful than the previous generation of GCMs at recreating the observed SSR trend over South and East Asia and also suggests that as much as half of the clear-sky trend may be attributable to increases in atmospheric absorption in both regions. We will discuss the SSR and atmospheric absorption trends over China and India, as depicted in both observations and AM3, as well the particular aerosol processes responsible for the model's recreation of the trends and their implications for regional climate.

  3. 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.

  4. Earthquake Clustering on Normal Faults: Insight from Rate-and-State Friction Models

    Science.gov (United States)

    Biemiller, J.; Lavier, L. L.; Wallace, L.

    2016-12-01

    Temporal variations in slip rate on normal faults have been recognized in Hawaii and the Basin and Range. The recurrence intervals of these slip transients range from 2 years on the flanks of Kilauea, Hawaii to 10 kyr timescale earthquake clustering on the Wasatch Fault in the eastern Basin and Range. In addition to these longer recurrence transients in the Basin and Range, recent GPS results there also suggest elevated deformation rate events with recurrence intervals of 2-4 years. These observations suggest that some active normal fault systems are dominated by slip behaviors that fall between the end-members of steady aseismic creep and periodic, purely elastic, seismic-cycle deformation. Recent studies propose that 200 year to 50 kyr timescale supercycles may control the magnitude, timing, and frequency of seismic-cycle earthquakes in subduction zones, where aseismic slip transients are known to play an important role in total deformation. Seismic cycle deformation of normal faults may be similarly influenced by its timing within long-period supercycles. We present numerical models (based on rate-and-state friction) of normal faults such as the Wasatch Fault showing that realistic rate-and-state parameter distributions along an extensional fault zone can give rise to earthquake clusters separated by 500 yr - 5 kyr periods of aseismic slip transients on some portions of the fault. The recurrence intervals of events within each earthquake cluster range from 200 to 400 years. Our results support the importance of stress and strain history as controls on a normal fault's present and future slip behavior and on the characteristics of its current seismic cycle. These models suggest that long- to medium-term fault slip history may influence the temporal distribution, recurrence interval, and earthquake magnitudes for a given normal fault segment.

  5. Absence of warm-up during active avoidance learning in a rat model of anxiety vulnerability: Insights from computational modeling

    Directory of Open Access Journals (Sweden)

    Catherine E Myers

    2014-08-01

    Full Text Available Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of leverpress avoidance learning in Sprague-Dawley (SD rats, and in the inbred Wistar-Kyoto (WKY rat, which has been proposed as a model of anxiety vulnerability. We focus on warm-up, transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously-reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the standard inter-session interval is shortened from 48 to 24 hours, SD rats (but not WKY will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative, rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. Sonic hedgehog in normal and neoplastic proliferation: insight gained from human tumors and animal models.

    Science.gov (United States)

    Wetmore, Cynthia

    2003-02-01

    Cancer arises when a cell accumulates multiple genetic changes that allow it to elude the highly regulated balance between proliferation and apoptosis that an organism employs to suppress inappropriate growth. It has become evident that malignant transformation of a cell or group of cells often involves pathways that are active during normal development but are inappropriately regulated in neoplastic proliferation. Signaling via the Sonic hedgehog pathway is critical to vertebrate development and also appears to play an integral role in the initiation and propagation of some tumors of the muscle, skin and nervous system. Analyses of human tumors have revealed mutations in various components of the Sonic hedgehog signaling pathway that appear to result in the activation of this pathway, as inferred by the increased expression of the transcription factor, Gli1. Interestingly, a proportion of the human tumors and most of those arising in mouse models continue to express the normal Patched allele, suggesting the involvement of additional molecular events in the transformation of the haploinsufficient cells.

  13. 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.

  14. 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.

  15. 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)

  16. 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.

  17. Stem cell dynamics in muscle regeneration: Insights from live imaging in different animal models.

    Science.gov (United States)

    Ratnayake, Dhanushika; Currie, Peter D

    2017-06-01

    In recent years, live imaging has been adopted to study stem cells in their native environment at cellular resolution. In the skeletal muscle field, this has led to visualising the initial events of muscle repair in mouse, and the entire regenerative response in zebrafish. Here, we review recent discoveries in this field obtained from live imaging studies. Tracking of tissue resident stem cells, the satellite cells, following injury has captured the morphogenetic dynamics of stem/progenitor cells as they facilitate repair. Asymmetric satellite cell division generated a clonogenic progenitor pool, providing in vivo validation for this mechanism. Furthermore, there is an emerging role of stem/progenitor cell guidance at the injury site by cellular protrusions. This review concludes that live imaging is a critical tool for discovering the distinct processes that occur during regeneration, emphasising the importance of imaging in diverse animal models to capture the entire scope of stem cell functions. Also see the Video Abstract. Link to: https://youtube/tgUHSBD1N0g. © 2017 WILEY Periodicals, Inc.

  18. Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure.

    Science.gov (United States)

    Srinivasan, Prabhavathi; Bahnson, Brian J

    2010-03-08

    Plasma platelet-activating factor acetylhydrolase (PAF-AH), also called lipoprotein-associated phospholipase A₂ (Lp-PLA₂), is a group VIIA PLA₂ enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated, several studies have shown it to be an independent marker of cardiovascular diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller portion to HDL; the majority of the enzyme being associated with small dense LDL and VHDL-1 subclasses. Several studies suggest that the anti- or pro-atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL and HDL have been identified. However our understanding of the interaction of PAF-AH with LDL and HDL is still incomplete. In this review we present an overview of what is already known about the interaction of PAF-AH with lipoprotein particles, and we pose questions that are yet to be answered. The recently solved crystal structure of PAF-AH, along with functional work done by others is used as a guide to develop a model of interaction of PAF-AH with lipoprotein particles.

  19. Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure

    Directory of Open Access Journals (Sweden)

    Brian J. Bahnson

    2010-03-01

    Full Text Available Plasma platelet-activating factor acetylhydrolase (PAF-AH, also called lipoprotein-associated phospholipase A2 (Lp-PLA2, is a group VIIA PLA2 enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated, several studies have shown it to be an independent marker of cardiovascular diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller portion to HDL; the majority of the enzyme being associated with small dense LDL and VHDL-1 subclasses. Several studies suggest that the anti- or pro-atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL and HDL have been identified. However our understanding of the interaction of PAF-AH with LDL and HDL is still incomplete. In this review we present an overview of what is already known about the interaction of PAF-AH with lipoprotein particles, and we pose questions that are yet to be answered. The recently solved crystal structure of PAF-AH, along with functional work done by others is used as a guide to develop a model of interaction of PAF-AH with lipoprotein particles.

  20. 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.

  1. 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.

  2. Determinant Factors for Arterial Hemodynamics in Hypertension: Theoretical Insights From a Computational Model-Based Study.

    Science.gov (United States)

    Liang, Fuyou; Guan, Debao; Alastruey, Jordi

    2018-03-01

    Hypertension is a well-documented predictive factor for cardiovascular events. Clinical studies have extensively demonstrated the differential hemodynamic consequences of various antihypertensive drugs, but failed to clearly elucidate the underlying mechanisms due to the difficulty in performing a quantitative deterministic analysis based on clinical data that carry confounding information stemming from interpatient differences and the nonlinearity of cardiovascular hemodynamics. In the present study, a multiscale model of the cardiovascular system was developed to quantitatively investigate the relationships between hemodynamic variables and cardiovascular properties under hypertensive conditions, aiming to establish a theoretical basis for assisting in the interpretation of clinical observations or optimization of therapy. Results demonstrated that heart period, central arterial stiffness, and arteriolar radius were the major determinant factors for blood pressures and flow pulsatility indices both in large arteries and in the microcirculation. These factors differed in the degree and the way in which they affect hemodynamic variables due to their differential effects on wave reflections in the vascular system. In particular, it was found that the hemodynamic effects of varying arteriolar radius were considerably influenced by the state of central arterial stiffness, and vice versa, which implied the potential of optimizing antihypertensive treatment by selecting proper drugs based on patient-specific cardiovascular conditions. When analyzed in relation to clinical observations, the simulated results provided mechanistic explanations for the beneficial pressure-lowering effects of vasodilators as compared to β-blockers, and highlighted the significance of monitoring and normalizing arterial stiffness in the treatment of hypertension.

  3. New insight into oseophageal injury and protection in physiologically relevant animal models.

    Science.gov (United States)

    Zayachkivska, O; Pshyk-Titko, I; Hrycevych, N; Savytska, M

    2014-04-01

    Chronic diseases of lifestyle (CDL), the most common chronic group of non-infectious and non-transmissible diseases worldwide, which share the similar risk factors of unhealthy lifestyle, have become most recognized as a serious trigger in the genesis of oesophageal injury. Non-erosive oesophageal lesions (NEOL) are found more frequently than erosive or ulcer lesions in patients with reflux oesophagitis (RO) related to CDL. They also have restricted healing options, which often leads to carcinogenesis. Therefore, developing a physiologically relevant animal model of NEOL remains an urgent priority. One of triggers of CDL, postprandial hyperglycemia (PHG), which is characterized by hyperglycemic spikes, and overloading nitro-compounds leading to oxidative stress that may predispose to NEOL. The present study was designed to set up a model of RO related to CDL in rodents to understand mechanisms of oesophageal preulcerogenic injury under such conditions as food-associated long-term PHG, restrained water-immersion stress (WIS), and imbalance of entero-salivary nitrites recirculation (ESNR). Beneficial effects of L-tryptophan (L-Try) have already been described by many activities in kynurenine and melatonin (Mel) synthesis, redox reactions, which play a key role for cytoprotection and proliferation. Nevertheless, the effect of L-Try and Mel on NEOL under PHG is still unknown. An extract of Cucurbita maxim sweet seed (eCMS), which contains a high amount of antioxidants, also appear to play an important role in foregut cytoprotection. Thus, the second aim was to observe the effects of eCSE on oesophageal mucosa (OEM) in modification of ESNR (mESNR). Rats were used with without/with pre-treatment L-Try, Mel during WIS and PHG. In the second series of experiments rats were used with without/with CSE pre-treatment in mESNR; oral and OEM lesions were determined by histology; inflammation of OEM by lectin histochemistry; esophageal NO2(-), cNOS and iNOS via bioassays

  4. 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.

  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. New insight into motor adaptation to pain revealed by a combination of modelling and empirical approaches.

    Science.gov (United States)

    Hodges, P W; Coppieters, M W; MacDonald, D; Cholewicki, J

    2013-09-01

    Movement changes in pain. Unlike the somewhat stereotypical response of limb muscles to pain, trunk muscle responses are highly variable when challenged by pain in that region. This has led many to question the existence of a common underlying theory to explain the adaptation. Here, we tested the hypotheses that (1) adaptation in muscle activation in acute pain leads to enhanced spine stability, despite variation in the pattern of muscle activation changes; and (2) individuals would use a similar 'signature' pattern for tasks with different mechanical demands. In 17 healthy individuals, electromyography recordings were made from a broad array of anterior and posterior trunk muscles while participants moved slowly between trunk flexion and extension with and without experimentally induced back pain. Hypotheses were tested by estimating spine stability (Stability Index) with an electromyography-driven spine model and analysis of individual and overall (net) adaptations in muscle activation. The Stability Index (P individuals used the same pattern of adaptation in muscle activity. For most, the adaptation was similar between movement directions despite opposite movement demands. These data provide the first empirical confirmation that, in most individuals, acute back pain leads to increased spinal stability and that the pattern of muscle activity is not stereotypical, but instead involves an individual-specific response to pain. This adaptation is likely to provide short-term benefit to enhance spinal protection, but could have long-term consequences for spinal health. © 2013 European Federation of International Association for the Study of Pain Chapters.

  7. Convergent pharmacological mechanisms in impulsivity and addiction: insights from rodent models.

    Science.gov (United States)

    Jupp, B; Dalley, J W

    2014-10-01

    Research over the last two decades has widely demonstrated that impulsivity, in its various forms, is antecedent to the development of drug addiction and an important behavioural trait underlying the inability of addicts to refrain from continued drug use. Impulsivity describes a variety of rapidly and prematurely expressed behaviours that span several domains from impaired response inhibition to an intolerance of delayed rewards, and is a core symptom of attention deficit hyperactivity disorder (ADHD) and other brain disorders. Various theories have been advanced to explain how impulsivity interacts with addiction both causally and as a consequence of chronic drug abuse; these acknowledge the strong overlaps in neural circuitry and mechanisms between impulsivity and addiction and the seemingly paradoxical treatment of ADHD with stimulant drugs with high abuse potential. Recent years have witnessed unprecedented progress in the elucidation of pharmacological mechanisms underpinning impulsivity. Collectively, this work has significantly improved the prospect for new therapies in ADHD as well as our understanding of the neural mechanisms underlying the shift from recreational drug use to addiction. In this review, we consider the extent to which pharmacological interventions that target impulsive behaviour are also effective in animal models of addiction. We highlight several promising examples of convergence based on empirical findings in rodent-based studies. © 2014 The British Pharmacological Society.

  8. Mechanism for cyclization reaction by clavaminic acid synthase. Insights from modeling studies.

    Science.gov (United States)

    Borowski, Tomasz; de Marothy, Sven; Broclawik, Ewa; Schofield, Christopher J; Siegbahn, Per E M

    2007-03-27

    The mechanism of the oxidative cyclization reaction catalyzed by clavaminic acid synthase (CAS) was studied in silico. First, a classical molecular dynamics (MD) simulation was performed to obtain a realistic structure of the CAS-Fe(IV)=O-succinate-substrate complex; then potential of mean force (PMF) was calculated to assess the feasibility of the beta-lactam ring, more specifically its C4' corner, approaching the oxo atom. Based on the MD structure, a relatively large model of the active site region was selected and used in the B3LYP investigation of the reaction mechanism. The computational results suggest that once the oxoferryl species is formed, the oxidative cyclization catalyzed by CAS most likely involves either a mechanism involving C4'(S)-H bond cleavage of the monocyclic beta-lactam ring, or a biosynthetically unprecedented mechanism comprising (1) oxidation of the hydroxyl group of PCA to an O-radical, (2) retro-aldol-like decomposition of the O-radical to an aldehyde and a C-centered radical, which is stabilized by the captodative effect, (3) abstraction of a hydrogen atom from the C4'(S) position of the C-centered radical by the Fe(III)-OH species yielding an azomethine ylide, and (4) 1,3-dipolar cycloaddition to the ylide with aldehyde acting as a dipolarophile. Precedent for the new proposed mechanism comes from the reported synthesis of oxapenams via 1,3-dipolar cycloaddition reactions of aldehydes and ketones.

  9. Novel insights into SLC25A46-related pathologies in a genetic mouse model.

    Directory of Open Access Journals (Sweden)

    Maria Eirini Terzenidou

    2017-04-01

    Full Text Available The mitochondrial protein SLC25A46 has been recently identified as a novel pathogenic cause in a wide spectrum of neurological diseases, including inherited optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia and lethal congenital pontocerebellar hypoplasia. SLC25A46 is an outer membrane protein, member of the Solute Carrier 25 (SLC25 family of nuclear genes encoding mitochondrial carriers, with a role in mitochondrial dynamics and cristae maintenance. Here we identified a loss-of-function mutation in the Slc25a46 gene that causes lethal neuropathology in mice. Mutant mice manifest the main clinical features identified in patients, including ataxia, optic atrophy and cerebellar hypoplasia, which were completely rescued by expression of the human ortholog. Histopathological analysis revealed previously unseen lesions, most notably disrupted cytoarchitecture in the cerebellum and retina and prominent abnormalities in the neuromuscular junction. A distinct lymphoid phenotype was also evident. Our mutant mice provide a valid model for understanding the mechanistic basis of the complex SLC25A46-mediated pathologies, as well as for screening potential therapeutic interventions.

  10. 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.

  11. THE ACCOUNTANT INFORMATION. DEMAND AND OFFER

    OpenAIRE

    Irina CHIRITA; Ioana ZAHEU

    2008-01-01

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

  12. 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

  13. Insights into Mechanisms of Transmission and Pathogenesis from Transgenic Mouse Models of Prion Diseases.

    Science.gov (United States)

    Moreno, Julie A; Telling, Glenn C

    2017-01-01

    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 (TSEs), which frequently occur as epidemics. An increasing body of evidence indicates that the canonical mechanism of conformational corruption of cellular prion protein (PrP C ) by the pathogenic isoform (PrP Sc ) that is the basis of prion formation in TSEs 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 interspecies 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 occurred

  14. 3-D modelling of megaloolithid clutches: insights about nest construction and dinosaur behaviour.

    Directory of Open Access Journals (Sweden)

    Bernat Vila

    Full Text Available BACKGROUND: Megaloolithid eggs have long been associated with sauropod dinosaurs. Despite their extensive and worldwide fossil record, interpretations of egg size and shape, clutch morphology, and incubation strategy vary. The Pinyes locality in the Upper Cretaceous Tremp Formation in the southern Pyrenees, Catalonia provides new information for addressing these issues. Nine horizons containing Megaloolithus siruguei clutches are exposed near the village of Coll de Nargó. Tectonic deformation in the study area strongly influenced egg size and shape, which could potentially lead to misinterpretation of reproductive biology if 2D and 3D maps are not corrected for bed dip that results from tectonism. METHODOLOGY/FINDINGS: Detailed taphonomic study and three-dimensional modelling of fossil eggs show that intact M. siruguei clutches contained 20-28 eggs, which is substantially larger than commonly reported from Europe and India. Linear and grouped eggs occur in three superimposed levels and form an asymmetric, elongate, bowl-shaped profile in lateral view. Computed tomography data support previous interpretations that the eggs hatched within the substrate. Megaloolithid clutch sizes reported from other European and Indian localities are typically less than 15 eggs; however, these clutches often include linear or grouped eggs that resemble those of the larger Pinyes clutches and may reflect preservation of incomplete clutches. CONCLUSIONS/SIGNIFICANCE: We propose that 25 eggs represent a typical megaloolithid clutch size and smaller egg clusters that display linear or grouped egg arrangements reported at Pinyes and other localities may represent eroded remnants of larger clutches. The similarity of megaloolithid clutch morphology from localities worldwide strongly suggests common reproductive behaviour. The distinct clutch geometry at Pinyes and other localities likely resulted from the asymmetrical, inclined, and laterally compressed titanosaur pes

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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...

  20. 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...

  1. 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...

  2. 16 CFR 502.101 - Introductory offers.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Introductory offers. 502.101 Section 502.101... FAIR PACKAGING AND LABELING ACT Retail Sale Price Representations § 502.101 Introductory offers. (a) The term introductory offer means any printed matter consisting of the words “introductory offer” or...

  3. 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...

  4. 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...

  5. 16 CFR 238.2 - Initial offer.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Initial offer. 238.2 Section 238.2... § 238.2 Initial offer. (a) No statement or illustration should be used in any advertisement which..., or origin of the product offered, or which may otherwise misrepresent the product in such a manner...

  6. 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

  7. 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

  8. 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

  9. The origin of felsic microgranitoid enclaves: Insights from plagioclase crystal size distributions and thermodynamic models

    Science.gov (United States)

    Alves, Adriana; Pereira, Giovanna de Souza; Janasi, Valdecir de Assis; Higgins, Michael; Polo, Liza Angelica; Juriaans, Orlando Stanley; Ribeiro, Bruno Vieira

    2015-12-01

    Magma mixing is widely recognized in contemporary petrology as one of the primary igneous processes. Microgranitoid enclaves (MEs) are considered to be remnants of such mixing processes, and the term has a well-established genetic implication. However, microgranitoid enclaves span a wide range of compositions, and felsic varieties are also frequently reported. Nd-Sr isotope and textural data from felsic microgranitoid enclaves (FMEs), mafic microgranitoid enclaves (MMEs) and host granites from the Salto pluton, Itu Granitic Province, show that the cm-sized MMEs are dioritic, have medium-grained igneous textures and xenocrysts of alkali feldspar and quartz. The FMEs are cm- to meter-sized, have spheric shapes, show corrugated contacts with the host granites, and have resorbed feldspars and deformed quartz crystals interpreted as xenocrysts set in a fine-grained groundmass. Compared to the host granites, both MME and FME samples have increased FeO, MgO, TiO2, P2O5 and Zr contents, but their Sr and Nd isotope signatures are identical: FME 87Sr/86Sri = 0.7088-0.7063, εNdi = - 10.0 to - 10.2; MME 87Sr/86Sri = 0.7070, εNdi = - 10.5; host granite 87Sr/86Sri 0.7056-0.7060, εNdi = - 10.2 to - 10.3. These indicate that the enclaves derive from a similar source, although the melts from which they formed were probably hotter and chemically more primitive than their host granites. Crystal size distributions (CSDs) of plagioclase in samples drilled from rinds and cores of three FMEs show that the rind samples are systematically finer-grained than the samples from the cores, which indicates that the FMEs cooled inwards and contradict interpretations that the FMEs are autoliths. Thermal modeling suggests that a slightly more primitive, hotter magma would be thermally equilibrated with an evolved resident melt within weeks after mixing/mingling. Upon thermal equilibrium, the FMEs would have an increased crystal cargo, and the resulting touching framework would impart a solid

  10. New Insights About Large-Scale Delta Morphodynamics from a Coupled Model of Fluvial-Coastal Processes

    Science.gov (United States)

    Murray, A. B.; Ratliff, K. M.; Hutton, E.

    2017-12-01

    We use a newly developed delta model to explore the combined effects of sea-level rise (SLR) and variable wave influence on delta morphology, avulsion behavior, and autogenic sediment flux variability. Using the Community Surface Dynamics Modeling System framework and tools, we couple the River Avulsion and Floodplain Evolution Model (RAFEM) to the Coastline Evolution Model (CEM). RAFEM models the fluvial processes, including river profile evolution, floodplain deposition, and avulsions. CEM uses gradients in alongshore sediment transport to distribute the fluvial sediment along the coastline. A suite of recent experiments using the coupled model and the Dakota software toolkit lead to several new insights: 1) A preferential avulsion location (which scales with the backwater length) can arise for geometric reasons that are independent of the recently suggested importance of alternation between flood and inter-flood periods. 2) The angular distribution of waves, as well as the wave height, affect the avulsion timescale. Previous work suggested that the time between avulsions will increase with greater wave influence, and we find that this is true for an angular mix of waves that tends to smooth a fairly straight coastline (coastline diffusion), where river mouth progradation is slowed and avulsions are delayed. However, if the angular distribution of waves leads to locally smooth shorelines but large amplitude coastline features (anti-diffusive coastline evolution), then avulsion timescales are barely affected, even when wave influence is high. 3) Increasing SLR rates are expected to cause more frequent avulsions, and it does in laboratory deltas. Unexpectedly, we find that this is not the case for the river-dominated deltas in our coupled model, in which SLR-related transgression effectively decreases progradation, offsetting base-level-rise effects. This finding raises potentially important questions about the geometric differences between prototypical and

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.)

  16. Modeling long-range time-resolved charge-transfer within TDDFT: Insights from a 2-site lattice model

    Science.gov (United States)

    Fuks, Johanna; Maitra, Neepa

    2014-03-01

    It has been shown that approximate adiabatic TDDFT functionals dramatically fail to reproduce time-resolved long-range charge-transfer dynamics (LR-CTD). In order to decouple the impact of the adiabatic approximation and the choice of ground state (gs) functional it would be instructive to propagate using the adiabatically-exact (adia-ex) functional. Numerically this involves an iterative process at each time-step to find the gs potential for a given density, which converges badly for CTD due to regions of low density. To circumvent this, we use as model system an asymmetric 2-site Hubbard model with small hopping parameter, its small Hilbert space allows to perform a Levy-Lieb constrained search and find the exact gs Hartree-exchange-correlation (Hxc) functional. The later develops a sharp step feature in the long-range limit (limit of small hopping parameter). Both closed-shell to closed-shell and open-shell to open-shell LR-CT are investigated. By propagating the Kohn-Sham system in the presence of the exact gs Hxc functional under a resonant laser we are able to perform, for the first time, a fully self-consistent adia-ex propagation for CTD. We aknowledge financial support from the Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences ans Biosciences under Award DE-SC0008623 and NSF Grants CNS-0855217 and CNS-0958379.

  17. An in silico model of retinal cholesterol dynamics (RCD model): insights into the pathophysiology of dry AMD.

    Science.gov (United States)

    Zekavat, Seyedeh Maryam; Lu, James; Maugeais, Cyrille; Mazer, Norman A

    2017-07-01

    We developed an in silico mathematical model of retinal cholesterol (Ch) dynamics (RCD) to quantify the physiological rate of Ch turnover in the rod outer segment (ROS), the lipoprotein transport mechanisms by which Ch enters and leaves the outer retina, and the rates of drusen growth and macrophage-mediated clearance in dry age-related macular degeneration. Based on existing experimental data and mechanistic hypotheses, we estimated the Ch turnover rate in the ROS to be 1-6 pg/mm 2 /min, dependent on the rate of Ch recycling in the outer retina, and found comparable rates for LDL receptor-mediated endocytosis of Ch by the retinal pigment epithelium (RPE), ABCA1-mediated Ch transport from the RPE to the outer retina, ABCA1-mediated Ch efflux from the RPE to the choroid, and the secretion of 70 nm ApoB-Ch particles from the RPE. The drusen growth rate is predicted to increase from 0.7 to 4.2 μm/year in proportion to the flux of ApoB-Ch particles. The rapid regression of drusen may be explained by macrophage-mediated clearance if the macrophage density reaches ∼3,500 cells/mm 2 The RCD model quantifies retinal Ch dynamics and suggests that retinal Ch turnover and recycling, ApoB-Ch particle efflux, and macrophage-mediated clearance may explain the dynamics of drusen growth and regression. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  18. An in silico model of retinal cholesterol dynamics (RCD model): insights into the pathophysiology of dry AMD[S

    Science.gov (United States)

    Zekavat, Seyedeh Maryam; Lu, James; Maugeais, Cyrille; Mazer, Norman A.

    2017-01-01

    We developed an in silico mathematical model of retinal cholesterol (Ch) dynamics (RCD) to quantify the physiological rate of Ch turnover in the rod outer segment (ROS), the lipoprotein transport mechanisms by which Ch enters and leaves the outer retina, and the rates of drusen growth and macrophage-mediated clearance in dry age-related macular degeneration. Based on existing experimental data and mechanistic hypotheses, we estimated the Ch turnover rate in the ROS to be 1–6 pg/mm2/min, dependent on the rate of Ch recycling in the outer retina, and found comparable rates for LDL receptor-mediated endocytosis of Ch by the retinal pigment epithelium (RPE), ABCA1-mediated Ch transport from the RPE to the outer retina, ABCA1-mediated Ch efflux from the RPE to the choroid, and the secretion of 70 nm ApoB-Ch particles from the RPE. The drusen growth rate is predicted to increase from 0.7 to 4.2 μm/year in proportion to the flux of ApoB-Ch particles. The rapid regression of drusen may be explained by macrophage-mediated clearance if the macrophage density reaches ∼3,500 cells/mm2. The RCD model quantifies retinal Ch dynamics and suggests that retinal Ch turnover and recycling, ApoB-Ch particle efflux, and macrophage-mediated clearance may explain the dynamics of drusen growth and regression. PMID:28442497

  19. 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.

  20. 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

  1. 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

  2. The effects of gas-fluid-rock interactions on CO2 injection and storage: Insights from reactive transport modeling

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Y.; Xu, T.; Pruess, K.

    2008-10-15

    Possible means of reducing atmospheric CO{sub 2} emissions include injecting CO{sub 2} in petroleum reservoirs for Enhanced Oil Recovery or storing CO{sub 2} in deep saline aquifers. Large-scale injection of CO{sub 2} into subsurface reservoirs would induce a complex interplay of multiphase flow, capillary trapping, dissolution, diffusion, convection, and chemical reactions that may have significant impacts on both short-term injection performance and long-term fate of CO{sub 2} storage. Reactive Transport Modeling is a promising approach that can be used to predict the spatial and temporal evolution of injected CO{sub 2} and associated gas-fluid-rock interactions. This presentation will summarize recent advances in reactive transport modeling of CO{sub 2} storage and review key technical issues on (1) the short- and long-term behavior of injected CO{sub 2} in geological formations; (2) the role of reservoir mineral heterogeneity on injection performance and storage security; (3) the effect of gas mixtures (e.g., H{sub 2}S and SO{sub 2}) on CO{sub 2} storage; and (4) the physical and chemical processes during potential leakage of CO{sub 2} from the primary storage reservoir. Simulation results suggest that CO{sub 2} trapping capacity, rate, and impact on reservoir rocks depend on primary mineral composition and injecting gas mixtures. For example, models predict that the injection of CO{sub 2} alone or co-injection with H{sub 2}S in both sandstone and carbonate reservoirs lead to acidified zones and mineral dissolution adjacent to the injection well, and carbonate precipitation and mineral trapping away from the well. Co-injection of CO{sub 2} with H{sub 2}S and in particular with SO{sub 2} causes greater formation alteration and complex sulfur mineral (alunite, anhydrite, and pyrite) trapping, sometimes at a much faster rate than previously thought. The results from Reactive Transport Modeling provide valuable insights for analyzing and assessing the dynamic

  3. 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 ...

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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...

  9. 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...

  10. 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...

  11. Ultrasonic vocalizations in mouse models for speech and socio-cognitive disorders: insights into the evolution of vocal communication.

    Science.gov (United States)

    Fischer, J; Hammerschmidt, K

    2011-02-01

    Comparative analyses used to reconstruct the evolution of traits associated with the human language faculty, including its socio-cognitive underpinnings, highlight the importance of evolutionary constraints limiting vocal learning in non-human primates. After a brief overview of this field of research and the neural basis of primate vocalizations, we review studies that have addressed the genetic basis of usage and structure of ultrasonic communication in mice, with a focus on the gene FOXP2 involved in specific language impairments and neuroligin genes (NL-3 and NL-4) involved in autism spectrum disorders. Knockout of FoxP2 leads to reduced vocal behavior and eventually premature death. Introducing the human variant of FoxP2 protein into mice, in contrast, results in shifts in frequency and modulation of pup ultrasonic vocalizations. Knockout of NL-3 and NL-4 in mice diminishes social behavior and vocalizations. Although such studies may provide insights into the molecular and neural basis of social and communicative behavior, the structure of mouse vocalizations is largely innate, limiting the suitability of the mouse model to study human speech, a learned mode of production. Although knockout or replacement of single genes has perceptible effects on behavior, these genes are part of larger networks whose functions remain poorly understood. In humans, for instance, deficiencies in NL-4 can lead to a broad spectrum of disorders, suggesting that further factors (experiential and/or genetic) contribute to the variation in clinical symptoms. The precise nature as well as the interaction of these factors is yet to be determined. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  12. Myofibroblasts electrotonically coupled to cardiomyocytes alter conduction: insights at the cellular level from a detailed in silico tissue structure model

    Directory of Open Access Journals (Sweden)

    Florian Jousset

    2016-10-01

    Full Text Available Fibrotic myocardial remodeling is typically accompanied by the appearance of myofibroblasts (MFBs. In vitro, MFBs were shown to slow conduction and precipitate ectopic activity following gap junctional coupling to cardiomyocytes (CMCs. To gain further mechanistic insights into this arrhythmogenic MFB-CMC crosstalk, we performed numerical simulations in cell-based high-resolution two-dimensional tissue models that replicated experimental conditions. Cell dimensions were determined using confocal microscopy of single and co-cultured neonatal rat ventricular CMCs and MFBs. Conduction was investigated as a function of MFB density in three distinct cellular tissue architectures: CMC strands with endogenous MFBs, CMC strands with coating MFBs of two different sizes, and CMC strands with MFB inserts. Simulations were performed to identify individual contributions of heterocellular gap junctional coupling and of the specific electrical phenotype of MFBs. With increasing MFB density, both endogenous and coating MFBs slowed conduction. At MFB densities of 5-30%, conduction slowing was most pronounced in strands with endogenous MFBs due to the MFB-dependent increase in axial resistance. At MFB densities >40%, very slow conduction and spontaneous activity was primarily due to MFB-induced CMC depolarization. Coating MFBs caused non-uniformities of resting membrane potential, which were more prominent with large than with small MFBs. In simulations of MFB inserts connecting two CMC strands conduction delays increased with increasing insert lengths and block appeared for inserts >1.2 mm. Thus, electrophysiological properties of engineered CMC-MFB co-cultures depend on MFB density, MFB size and their specific positioning in respect to CMCs. These factors may influence conduction characteristics in the heterocellular myocardium.

  13. Mechanistic insights on ethanol dehydrogenation on Pd-Au model catalysts: a combined experimental and DFT study.

    Science.gov (United States)

    Evans, E J; Li, H; Yu, Wen-Yueh; Mullen, G M; Henkelman, G; Mullins, C Buddie

    2017-11-22

    In this study, we have combined ultra-high vacuum (UHV) experiments and density functional theory (DFT) calculations to investigate ethanol (EtOH) dehydrogenation on Pd-Au model catalysts. Using EtOH reactive molecular beam scattering (RMBS), EtOH temperature-programmed desorption (TPD), and DFT calculations, we show how different Pd ensemble sizes on Au(111) can affect the mechanism for EtOH dehydrogenation and H 2 production. The Au(111) surface with an initial coverage of 2 monolayers of Pd (2 ML Pd-Au) had the highest H 2 yield. However, the 1 ML Pd-Au catalyst showed the highest selectivity and stability, yielding appreciable amounts of only H 2 and acetaldehyde. Arrhenius plots of H 2 production confirm that the mechanisms for EtOH dehydrogenation differed between 1 and 2 ML Pd-Au, supporting the perceived difference in selectivity between the two surfaces. DFT calculations support this difference in mechanism, showing a dependence of the initial dehydrogenation selectivity of EtOH on the size of Pd ensemble. DFT binding energies and EtOH TPD confirm that EtOH has increasing surface affinity with increasing Pd ensemble size and Pd coverage, indicating that surfaces with more Pd are more likely to induce an EtOH reaction instead of desorb. Our theoretical results show that the synergistic influence of atomic ensemble and electronic effects on Pd/Au(111) can lead to different H 2 association energies and EtOH dehydrogenation capacities at different Pd ensembles. These results provide mechanistic insights into ethanol's dehydrogenation interactions with different sites on the Pd-Au surface and can potentially aid in bimetallic catalyst design for applications such as fuel cells.

  14. 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.

  15. Current Models of Investor State Dispute Settlement Are Bad for Health: The European Union Could Offer an Alternative; Comment on “The Trans-Pacific Partnership: Is It Everything We Feared for Health?”

    Directory of Open Access Journals (Sweden)

    Martin McKee

    2017-03-01

    Full Text Available 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, judgeled 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.

  16. Current Models of Investor State Dispute Settlement Are Bad for Health: The European Union Could Offer an Alternative; Comment on “The Trans-Pacific Partnership: Is It Everything We Feared for Health?”

    OpenAIRE

    Martin McKee; David Stuckler

    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.

  17. 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.

  18. A key role of practical training in higher education: what can traineeship offer to trainee translators?

    Directory of Open Access Journals (Sweden)

    Nataša Hirci

    2016-12-01

    Full Text Available This paper gives an outline of Traineeship at the Department of Translation, University of Ljubljana, designed as a practical, hands-on experience in translation work for students. In the re-design of the study programmes at the Department of Translation in line with the Bologna Reform, compulsory Traineeship was introduced as part of the MA course in Translation/Interpreting, offering students an insight into real-life translation situations while providing employers with an impression of their prospective employees. The main objective of Traineeship is to give an added-value to the MA course, provide job opportunities and offer students a practical experience while workingwith the state-of-the-art translation technologies. The trainees can apply their knowledge obtained at the faculty to real-life translation assignments while gaining new skills and experience which combined contribute to a more efficient integration into the translation market. The paper explores the specific approaches to the implementation of Traineeship at the Department of Translation developed over the last decade, offering a model of good practice to other traineeship organizers.

  19. Deformation of the Western Caribbean: Insights from Block and Geodynamic Models of Geodetic, Seismic and Geologic Data

    Science.gov (United States)

    La Femina, P. C.; Geirsson, H.; Kobayashi, D.

    2012-12-01

    Cocos - Caribbean convergence along the Middle America Trench, including subduction of the Cocos Ridge and seamount domain, and Nazca - Caribbean oblique convergence along the South Panama Deformed Belt have resulted in complex plate boundary zone deformation since Miocene - Pliocene time. Plate boundary evolution and upper plate deformation in the western Caribbean is well studied and indicates, 1) Quaternary migration of the volcanic arc toward the back-arc northwest of the Cocos Ridge; 2) Pleistocene to present northwestward motion of the Central American Fore Arc (CAFA); 3) Quaternary to present deformation within the Central Costa Rica Deformed Belt; 4) Miocene-Pliocene cessation of volcanism and uplift of the Cordillera de Talamanca inboard the ridge; 5) Quaternary to present shortening across the fore-arc Fila Costeña fold and thrust belt and back-arc North Panama Deformed Belt (NPDB); 6) Quaternary to present outer fore-arc uplift above the seamount domain (Nicoya Peninsula), and above (Osa Peninsula) and flanking (Burica Peninsula) the ridge; and 7) Quaternary to present faulting along the Sona-Azuero and Canal Discontinuity fault systems. We investigate the dynamic effects of Cocos and Nazca convergence along the entire Central American margin, and the implications on western Caribbean plate boundary evolution with a new GPS derived three-dimensional (horizontal and vertical) velocity field and kinematic block and geodynamic models. Specifically, we test the hypotheses that the Cocos Ridge is the main driver for upper plate deformation and that there is an independent Panama block. Our model results provide new Euler vectors for the CAFA and Panama block, rates of relative plate and block motions in the region, and constraints on interseismic coupling along the Middle America Trench and other major block bounding fault systems. These results are compared to existing geophysical and geologic data for the region and add insights into the rates of

  20. Long Non-Coding RNA Profiling in a Non-Alcoholic Fatty Liver Disease Rodent Model: New Insight into Pathogenesis

    Directory of Open Access Journals (Sweden)

    Yi Chen

    2017-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent chronic liver diseases worldwide with an unclear mechanism. Long non-coding RNAs (lncRNAs have recently emerged as important regulatory molecules. To better understand NAFLD pathogenesis, lncRNA and messenger RNA (mRNA microarrays were conducted in an NAFLD rodent model. Potential target genes of significantly changed lncRNA were predicted using cis/trans-regulatory algorithms. Gene Ontology (GO analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analysis were then performed to explore their function. In the current analysis, 89 upregulated and 177 downregulated mRNAs were identified, together with 291 deregulated lncRNAs. Bioinformatic analysis of these RNAs has categorized these RNAs into pathways including arachidonic acid metabolism, circadian rhythm, linoleic acid metabolism, peroxisome proliferator-activated receptor (PPAR signaling pathway, sphingolipid metabolism, steroid biosynthesis, tryptophan metabolism and tyrosine metabolism were compromised. Quantitative polymerase chain reaction (qPCR of representative nine mRNAs and eight lncRNAs (named fatty liver-related lncRNA, FLRL was conducted and this verified previous microarray results. Several lncRNAs, such as FLRL1, FLRL6 and FLRL2 demonstrated to be involved in circadian rhythm targeting period circadian clock 3 (Per3, Per2 and aryl hydrocarbon receptor nuclear translocator-like (Arntl, respectively. While FLRL8, FLRL3 and FLRL7 showed a potential role in PPAR signaling pathway through interaction with fatty acid binding protein 5 (Fabp5, lipoprotein lipase (Lpl and fatty acid desaturase 2 (Fads2. Functional experiments showed that interfering of lncRNA FLRL2 expression affected the expression of predicted target, circadian rhythm gene Arntl. Moreover, both FLRL2 and Arntl were downregulated in the NAFLD cellular model. The current study identified lncRNA and corresponding mRNA in NAFLD