WorldWideScience

Sample records for concerted kinase interplay

  1. A concerted kinase interplay identifies PPARgamma as a molecular target of ghrelin signaling in macrophages.

    Directory of Open Access Journals (Sweden)

    Annie Demers

    2009-11-01

    Full Text Available The peroxisome proliferator-activator receptor PPARgamma plays an essential role in vascular biology, modulating macrophage function and atherosclerosis progression. Recently, we have described the beneficial effect of combined activation of the ghrelin/GHS-R1a receptor and the scavenger receptor CD36 to induce macrophage cholesterol release through transcriptional activation of PPARgamma. Although the interplay between CD36 and PPARgamma in atherogenesis is well recognized, the contribution of the ghrelin receptor to regulate PPARgamma remains unknown. Here, we demonstrate that ghrelin triggers PPARgamma activation through a concerted signaling cascade involving Erk1/2 and Akt kinases, resulting in enhanced expression of downstream effectors LXRalpha and ABC sterol transporters in human macrophages. These effects were associated with enhanced PPARgamma phosphorylation independently of the inhibitory conserved serine-84. Src tyrosine kinase Fyn was identified as being recruited to GHS-R1a in response to ghrelin, but failure of activated Fyn to enhance PPARgamma Ser-84 specific phosphorylation relied on the concomitant recruitment of docking protein Dok-1, which prevented optimal activation of the Erk1/2 pathway. Also, substitution of Ser-84 preserved the ghrelin-induced PPARgamma activity and responsiveness to Src inhibition, supporting a mechanism independent of Ser-84 in PPARgamma response to ghrelin. Consistent with this, we found that ghrelin promoted the PI3-K/Akt pathway in a Galphaq-dependent manner, resulting in Akt recruitment to PPARgamma, enhanced PPARgamma phosphorylation and activation independently of Ser-84, and increased expression of LXRalpha and ABCA1/G1. Collectively, these results illustrate a complex interplay involving Fyn/Dok-1/Erk and Galphaq/PI3-K/Akt pathways to transduce in a concerted manner responsiveness of PPARgamma to ghrelin in macrophages.

  2. Concert

    CERN Multimedia

    Swing de fou

    2011-01-01

    Swing de Fou, JAZZ New Orleans,  en concert Jeudi 24 Novembre - Versoix 20h00 - Les Caves de Bon-Séjour - Sextet 25 Novembre - Chêne-Bourg 20h30 - Salle Point Favre – Octet Concerts exceptionnels, Avec invitée spéciale : Rosana Mancarella, cantatrice Lyrique Mezzo Soprano des théâtres Arena di Verona et La Scala Di Milano Arrangements de Daniele Verdesca, professeur compositeur aux conservatoires de Nyon et Yverdon, & Gérôme Gautschi professeur compositeur de trombone à Genève Info : http://swingdefou.ch/concerts.php

  3. Concert

    CERN Multimedia

    Staff Association

    2017-01-01

    Small Capella Friday 2 June at 18.00 CERN Meyrin, Main Auditorium Free admission Moscow chamber choir Small Capella arose within the walls of Children‘s musical school No. 10, and evolved over the years into a mixed choir of people of various age and occupation, open to anyone fond of choral music. The repertoire includes Russian and foreign classical music, sacred music, folk songs, contemporary choral compositions. The concert will include solo vocal and piano pieces.

  4. Interplay between TGF-β signaling and receptor tyrosine kinases in tumor development.

    Science.gov (United States)

    Shi, Qiaoni; Chen, Ye-Guang

    2017-10-01

    Transforming growth factor-β (TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in various diseases including tumor formation. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), also play key roles in the development and progression of many types of tumors. It has been realized that TGF-β signaling and RTK pathways interact with each other and their interplay is important for cancer development. They are mutually regulated and cooperatively modulate cell survival and migration, epithelial-mesenchymal transition, and tumor microenvironment to accelerate tumorigenesis and tumor metastasis. RTKs can modulate Smad-dependent transcription or cooperate with TGF-β to potentiate its oncogenic activity, while TGF-β signaling can in turn control RTK signaling by regulating their activities or expression. This review summarizes current understandings of the interplay between TGF-β signaling and RTKs and its influence on tumor development.

  5. Concert Club

    CERN Document Server

    Concert Club

    2010-01-01

    CERN MEYRIN (terminus bus 56-CERN) Entrée B - Bâtiment 500 - Amphithéâtre Mardi 26 janvier à 20 h 30 Le quintette Liliane JAQUES, flûte traversière Jade AZKOUL, guitare Gaëlle POIRIER, accordéon Mirella VEDEVA, contrebasse Gueorgui POPOV, piano Au programme Portraits d’Astor PIAZZOLLA Entrée libre Nos concerts sur notre site : www.concerts-cern.com et sur les sites : www.whys.org et www.agendadegeneve.ch

  6. CONCERT CLUB

    CERN Document Server

    Concert club

    2010-01-01

    CERN MEYRIN (terminus bus 56-CERN) entrée B - bâtiment 500 - amphithéâtre Mardi 19 janvier 2010 à 20 h 30 Klaus MAURER violon Joanna BRZEZINSKA piano Au programme : Chopin, Rodrigo * * * * * Mardi 26 janvier 2010 à 20 h 30 Le quintette Liliane JAQUES flûte traversière Jade AZKOUL guitare Gaëlle POIRIER accordéon Mirella VEDEVA contrebasse Gueorgui POPOV piano Au programme : Portraits d’Astor Piazzlla   entrée libre Nos concerts sur notre site : www.concerts-cern.com et sur les sites : www.whys.org et www.agendadegeneve.ch

  7. Concerts & Opera

    Index Scriptorium Estoniae

    2008-01-01

    Kristjan Järvi dirigeerimas Vienna Tonkünstler Orchestra't 16. veebr. Leedsis Town Hallis (esitusel ka Arvo Pärdi Symphony No. 3), 20. veebr. Bristolis ja 23. veebr. Basingstoke'is. Neeme Järvi dirigeerimas Royal Scottish National Orcestra't 23. veebr. Glasgowis Royal Concert Hallis ja 24. veebr. Edinburghis Queens Hallis

  8. Concert Club

    CERN Document Server

    Concert Club

    CERN MEYRIN (terminus bus 56-CERN) Entrée B - bâtiment 500 - Amphithéâtre Mardi 1er Décembre 2009 à 20 h 30 Patrick VO VANG PHUC piano Au programme : Scarlatti, Mozart, Schubert, Debussy * * * * * Mardi 8 Décembre 2009 à 20 h 30 « CRESCENDO » duo de guitares avec Danielle VILLARD et Luciano ROSSETTI Au programme : Johnson, J.S Bach, Vivaldi, Scheidler, Pujol, Albeniz, Granados, Rizzuti, Satie, Rivoal * * * * * Dimanche 13 décembre 2009 à 17 h 00 piano à 4 mains avec Christel BARBERI et Jean-Pierre VARONE Au programme : Brahms, Schubert, Rachmaninov Entrée libre Nos concerts sur notre site : www.concerts-cern.com et sur les sites : www.whys.org et www.agendadegeneve.ch  

  9. Interplay between intergrin-linked kinase and ribonuclease inhibitor affects growth and metastasis of bladder cancer through signaling ILK pathways.

    Science.gov (United States)

    Zhuang, Xiang; Lv, Mengxin; Zhong, Zhenyu; Zhang, Luyu; Jiang, Rong; Chen, Junxia

    2016-08-30

    Integrin-linked kinase (ILK) is a multifunctional adaptor protein which is involved with protein signalling within cells to modulate malignant (cancer) cell movement, cell cycle, metastasis and epithelial-mesenchymal transition (EMT). Our previous experiment demonstrated that ILK siRNA inhibited the growth and induced apoptosis of bladder cancer cells as well as increased the expression of Ribonuclease inhibitor (RI), an important cytoplasmic protein with many functions. We also reported that RI overexpression inhibited ILK and phosphorylation of AKT and GSK3β. ILK and RI gene both locate on chromosome 11p15 and the two genes are always at the adjacent position of same chromosome during evolution, which suggest that ILK and RI could have some relationship. However, underlying interacting mechanisms remain unclear between them. Here, we postulate that RI might regulate ILK signaling pathway via interacting with ILK. Co-immunoprecipitation, GST pull-down and co-localization under laser confocal microscope assay were used to determine the interaction between ILK and RI exogenously and endogenously. Furthermore, we further verified that there is a direct binding between the two proteins by fluorescence resonance energy transfer (FRET) in cells. Next, The effects of interplay between ILK and RI on the key target protein expressions of PI3K/AKT/mTOR signaling pathway were determined by western blot, immunohistochemistry and immunofluorescence assay in vivo and in vitro. Finally, the interaction was assessed using nude mice xenograft model. We first found that ILK could combine with RI both in vivo and in vitro by GST pull-down, co-immunoprecipitation (Co-IP) and FRET. The protein levels of ILK and RI revealed a significant inverse correlation in vivo and in vitro. Subsequently, The results showed that up-regulating ILK could increase cell proliferation, change cell morphology and regulate cell cycle. We also demonstrated that the overexpression of ILK remarkably

  10. Modulation of fatty acid synthase degradation by concerted action of p38 MAP kinase, E3 ligase COP1, and SH2-tyrosine phosphatase Shp2.

    Science.gov (United States)

    Yu, Jianxiu; Deng, Rong; Zhu, Helen H; Zhang, Sharon S; Zhu, Changhong; Montminy, Marc; Davis, Roger; Feng, Gen-Sheng

    2013-02-08

    The Src-homology 2 (SH2) domain-containing tyrosine phosphatase Shp2 has been known to regulate various signaling pathways triggered by receptor and cytoplasmic tyrosine kinases. Here we describe a novel function of Shp2 in control of lipid metabolism by mediating degradation of fatty acid synthase (FASN). p38-phosphorylated COP1 accumulates in the cytoplasm and subsequently binds FASN through Shp2 here as an adapter, leading to FASN-Shp2-COP1 complex formation and FASN degradation mediated by ubiquitination pathway. By fasting p38 is activated and stimulates FASN protein degradation in mice. Consistently, the FASN protein levels are dramatically elevated in mouse liver and pancreas in which Shp2/Ptpn11 is selectively deleted. Thus, this study identifies a new activity for Shp2 in lipid metabolism.

  11. Musical Students’ Concert Practice

    Directory of Open Access Journals (Sweden)

    Aleksandr S. Plokhotnyuk

    2012-12-01

    Full Text Available . The article presents detailed analysis of performance training of future teachers of music at higher educational establishments and offers ways to overcome the problem of musical students’ concert practice organization.

  12. Cyclization in concert

    NARCIS (Netherlands)

    Fraaije, Marco W.; Mattevi, Andrea

    2008-01-01

    The berberine bridge enzyme catalyzes the crucial step in the biosynthesis of an important class of alkaloids through a reaction that cannot be carried out using conventional organic chemistry tools. Characterization of the enzyme demonstrates a concerted mechanism that couples two distinct chemical

  13. Concerts-club

    CERN Multimedia

    Concerts-club

    2012-01-01

      Avis à tous les musiciens et mélomanes Le Concerts-Club du CERN reprend du service ! Après une longue pause due, entre autres, aux travaux de rénovation de l’Amphithéâtre, une nouvelle équipe s’est lancée dans la reprise de l’organisation du Concerts-Club, à raison d’un concert par mois. 1er concert : mardi 20 mars à 20h30 Lieu : CERN-Meyrin : Entrée B – Bâtiment 500 – Amphithéâtre Prochaines dates : Mardi 24 avril 2012 Mardi 15 mai  2012 Mardi 19 juin  2012 Pour donner au Club l’élan nécessaire au redémarrage, les changements suivants ont été mis en place : – Possibilité d’être membre du Club : carte à Fr 25.00 par an. – Entr&e...

  14. Teaching bioinformatics in concert.

    Directory of Open Access Journals (Sweden)

    Anya L Goodman

    2014-11-01

    Full Text Available Can biology students without programming skills solve problems that require computational solutions? They can if they learn to cooperate effectively with computer science students. The goal of the in-concert teaching approach is to introduce biology students to computational thinking by engaging them in collaborative projects structured around the software development process. Our approach emphasizes development of interdisciplinary communication and collaboration skills for both life science and computer science students.

  15. Film in concert

    OpenAIRE

    2017-01-01

    From the very beginning of cinema, music always played an important role in the history of filmmaking. Nonetheless, film music is judged by critics as a kind of low-grade art form. However, the majority of film score composers enjoyed a classical education and composed as well for the silver screen as for the concert hall. Film music also has its roots in the musical era of romanticism. Therefore, symphonic film scores can be regarded as program music in a broader sense. These scores were inf...

  16. Concert: Harvestehuder Kammersymphonie

    CERN Multimedia

    Staff Association

    2017-01-01

    Harvestehuder Kammersymphonie (Hamburg) Tuesday 23 May at 18.00 Main Auditorium (CERN Meyrin)   Tradition et modernité constituent le lien entre tous les musiciens de l’orchestre. La littérature orchestrale de la période classique à l’époque moderne figure régulièrement à leurs programmes. Composé de près d’une centaine d’instrumentistes de toutes professions, l'enthousiasme et la qualité musicale constituent la priorité absolue de leur activité. Après des voyages gagnant en Brésil et Angleterre, une délégation de cet ensemble est de passage dans la région. Ils sont très heureux de pouvoir donner un concert au CERN.

  17. Standing Concertation Committee

    CERN Multimedia

    HR Department

    2009-01-01

    Ordinary Meeting on 11 May 2009 The meeting of the Standing Concertation Committee held on 11 May 2009 was entirely dedicated to the preparation of the TREF meeting on 19 & 20 May 2009. The Committee took note, discussed and agreed on some clarifications on a number of documents and presentations that the Management planned to submit and/or present to TREF on the following subjects: • Personnel statistics 2008: J. Purvis presented the Personnel Statistics for 2008 prepared by HR Department. In line with the previous year, key messages were firstly, a general reduction in staff (2544 to 2400, - 6%), secondly, a reduction in administrative services personnel (from 422 to 387, - 8%) and thirdly, a marked increase in the number of Users and Unpaid Associates (from 8369 to 9140, + 9%) • Five-Yearly Review 2010: A series of draft documents were submitted for discussion, comprising an introductory document explaining the statutory basis for the following four document...

  18. Standing Concertation Committee

    CERN Multimedia

    HR Department

    2009-01-01

    The main items discussed at the meetings of the Standing Concertation Committee in the first quarter of 2009 included: Merit Appraisal and Recognition Scheme (MARS) 2009 exercise The committee took note of 2009 MARS ceiling guidelines giving the advancement budget by career path and amounting to approx 1.80% of the basic salary bill. To this will be added 250 steps CERN-wide, financed by savings from implementation of the international indemnity for 2007, 2008 and the first half of 2009. The specific Senior Staff Guidelines, including the proposed number of promotions from Career Path E to F, were also noted. The guidelines with respect to step distribution were also noted: the minima and maxima remain the same as in previous years. Compliance with the guidelines will continue to be monitored closely (more details, including a frequently asked questions section). It was also noted that Financial Awards (awards for extraordinary service and responsibility allowances) may b...

  19. Standing Concertation Committee

    CERN Document Server

    HR Department

    2010-01-01

    Main issues examined at the meeting of 2 October 2009 The October 2009 meeting of the Standing Concertation Committee was entirely devoted to preparation of TREF’s meeting on 21-22 October. The Committee took note of, discussed and agreed on clarifications needed to some of the documents and presentations that the Management intended to submit and/or present to TREF on the following subjects: Equal opportunities The Committee took note of a preliminary report on equal opportunities at CERN drawn up by D. Chromek-Burckhart, the Equal Opportunities Officer, and T. Smith, Chairman of the Equal Opportunities Advisory Panel, containing in particular a proposal for a new process for resolving harassment conflicts. Technical analysis of the CERN Health Insurance Scheme - Actuary’s Report The Committee took note of a presentation by P. Charpentier, Chairman of the CERN Health Insurance Supervisory Board (CHIS Board), on the 2009 actuarial report on the CERN Health Insurance Scheme (CHIS). Th...

  20. Standing Concertation Commmittee

    CERN Document Server

    HR Department

    2007-01-01

    Ordinary meeting on 2 november 2007 Extraordinary meeting on 12 November 2007 The main items discussed at the meetings of the Standing Concertation Committee on 2 November 2007 and 12 November included: Restaurants Supervisory Committee Report The committee took note of the report by the chairman of the Restaurants Supervisory Committee (RSC), T. Lagrange. In particular, it was recorded that, in Restaurant No. 1, the new kitchen and free flow arrangements had been inaugurated and all works had been commissioned on schedule in October 2007.The contractor, Novae, had taken over maintenance of the new kitchen. Some price increases were to be expected in the coming months due mainly to strong increases in the cost of basic ingredients. A problem with bad smells in the area of Restaurant No. 1 was being taken care of by tuning the ventilation system. The RSC wished to thank the management and staff of Restaurant No. 2 for their cooperation while Restaurant No 1 was ...

  1. STANDING CONCERTATION COMMMITTEE

    CERN Multimedia

    HR Department

    2008-01-01

    ORDINARY MEETING ON 27 FEBRUARY 2008 The main items discussed at the meetings of the Standing Concertation Committee on 27 February 2008 included: Short-term Saved Leave Scheme The committee noted that, by the end of February 2008, some 600 staff had subscribed to the short-term saved leave scheme: approx 58% had subscribed 1 slice, 14% two slices, 5% three slices and 23% four slices. Administrative Circular No. 4 (Rev. 4) - Unemployment Insurance Scheme The committee agreed to recommend Administrative Circular No. 4 (Rev. 4) - Unemployment Insurance Scheme to the Director-General for approval. Administrative Circular No. 30 (Rev. 2) - Financial benefits upon taking up appointment and termination of contract The committee agreed to recommend Administrative Circular No. 30 (Rev. 2) - Financial Benefits upon taking up appointment and termination of contract to the Director-General for approval. Progressive Retirement Programme The Progressive Retirement Programme (PRP) was extended for a further year to 3...

  2. Standing Concertation Committee

    CERN Document Server

    HR Department

    2008-01-01

    ORDINARY MEETING ON 27 FEBRUARY 2008 The main items discussed at the meetings of the Standing Concertation Committee on 27 February 2008 included: Short-term Saved Leave Scheme The Committee noted that, by the end of February 2008, some 600 staff had enrolled in the short-term saved leave scheme: approx. 58% had signed up for 1 slice, 14% for two slices, 5% for three slices and 23% for four slices. Administrative Circular No. 4 (Rev. 4) - Unemployment Insurance Scheme The Committee agreed to recommend the Director-General to approve Administrative Circular No. 4 (Rev. 4) - Unemployment Insurance Scheme. Administrative Circular No. 30 (Rev. 2) - Financial benefits upon taking up appointment and termination of contract The Committee agreed to recommend the Director-General to approve Administrative Circular No. 30 (Rev. 2) - Financial Benefits upon taking up appointment and termination of contract. Progressive Retirement Programme The Progressive Retirement Programme (PR...

  3. Concert Viewing Headphones

    Directory of Open Access Journals (Sweden)

    Kazuya Atsuta

    2011-01-01

    Full Text Available An audiovisual interface equipped with a projector, an inclina-tion sensor, and a distance sensor for zoom control has been developed that enables a user to selectively view and listen to specific performers in a video-taped group performance. Dubbed Concert Viewing Headphones, it has both image and sound processing functions. The image processing extracts the portion of the image indicated by the user and projects it free of distortion on the front and side walls. The sound processing creates imaginary microphones for those performers without one so that the user can hear the sound from any performer. Testing using images and sounds captured using a fisheye-lens camera and 37 lavalier microphones showed that sound locali-zation was fastest when an inverse square function was used for the sound mixing and that the zoom function was useful for locating the desired sound performance.

  4. Choeur du CERN : Concert

    CERN Multimedia

    CERN Choir

    2017-01-01

    Une œuvre à découvrir! La grande Missa pro defunctis de François-Joseph Gossec (1734-1829) est le chef-d’œuvre tôt venu (à vingt-cinq ans) d’un compositeur qui vivra encore 70 ans après sa création. Elle a connu la gloire, puis s’est fait un peu oublier. Pas du tout le monde cependant : des musicologues ont montré ce que le Requiem de Mozart lui devait ; et il suffit de l’avoir entendue pour comprendre pourquoi Berlioz (qui avait vingt-six ans à la mort de Gossec) en a été impressionné : les nombreux cuivres et bois répartis dans des endroits plus ou moins cachés de la salle de concert pour exprimer les frayeurs du Jugement dernier annoncent son Requiem – et celui de Verdi. Mais « plus encore que par...

  5. Standing Concertation Committee

    CERN Multimedia

    2007-01-01

    Ordinary meeting on 30 January 2007 The main items discussed at the meeting of the Standing Concertation Committee on 30 January 2007 included: Administrative Circular No. 26: with the introduction of the merit recognition system in the framework of the 5-yearly review of CERN employment conditions, Administrative Circular No. 26 has been revised. The committee took note of the revised document which is being finalized for submission to the Director-General for approval in the near future. Technical analysis of CERN Health Insurance Scheme: the Committee was informed that a group has been set up by the Director-General to analyse the financial situation of the CERN Health Insurance Scheme in the short and long term, and to propose measures to ensure that the Scheme remains in financial balance, with adequate cover, over the medium term. The group's terms of reference and membership were communicated. Voluntary programmes It was announced that the programmes: 'part-time work as a pre-retirement measure...

  6. Standing Concertation Committee

    CERN Multimedia

    2007-01-01

    ORDINARY MEETING ON 30 JANUARY 2007 The main items discussed at the meeting of the Standing Concertation Committee on 30 January 2007 included: Administrative Circular No. 26: with the introduction of the merit recognition system in the framework of the 5-yearly review of CERN employment conditions, Administrative Circular No. 26 has been revised. The Committee took note of the revised document which is being finalized for submission to the Director-General for approval in the near future. Technical analysis of CERN Health Insurance Scheme: the Committee was informed that a group has been set up by the Director-General to analyse the financial situation of the CERN Health Insurance Scheme in the short and long term, and to propose measures to ensure that the Scheme remains in financial balance, with adequate cover, over the medium term. The group's terms of reference and membership were communicated. Voluntary programmes It was announced that the programmes: 'part-time work as a pre-retirement mea...

  7. Standing Concertation Commmittee

    CERN Multimedia

    HR Department

    2007-01-01

    Ordinary meeting on 27 February 2007 The main items discussed at the meeting of the Standing Concertation Committee on 27 February 2007 included: Saved Leave Scheme (SLS): It was announced that a Management/Staff Association working group had been set up to discuss the Saved Leave Scheme (SLS): Members: M. Büttner, E. Chiaveri (chair), Ph. Defert, D. Klem, M. Vitasse, J.-M. Saint-Viteux. It was noted that the Staff Association was launching a questionnaire on SLS and distributed to all members of the personnel. Merit Recognition Guidelines : in the context of the new Merit Appraisal and Recognition Scheme (MARS), the committee took note of the CERN-wide 2007 Merit Recognition Guidelines, including the Frequently Asked Questions on HR Department's dedicated website. Information on CERN's medium and long-term plans (MTP-LTP)/Contract renewals/ External mobility The Committee took note of the information provided on CERN's MTP-LTP and of documentation distributed at the meeting by the Staff Associatio...

  8. Standing Concertation Committee

    CERN Document Server

    HR Department

    2007-01-01

    ORDINARY MEETING ON 27 FEBRUARY 2007 The main items discussed at the meeting of the Standing Concertation Committee on 27 February 2007 included: Saved Leave Scheme (SLS): It was announced that a Management/Staff Association working group had been set up to discuss the Saved Leave Scheme (SLS): Members : M. Büttner, E. Chiaveri (chair), Ph. Defert, D. Klem, M. Vitasse, J.-M. Saint-Viteux. It was noted that the Staff Association was launching a questionnaire on SLS and distributed to all members of the personnel. Merit Recognition Guidelines: In the context of the new Merit Appraisal and Recognition Scheme (MARS), the committee took note of the CERN-wide 2007 Merit Recognition Guidelines, including the Frequently Asked Questions on HR Department's dedicated website. Information on CERN's medium and long-term plans (MTP-LTP)/Contract renewals/ External mobility The Committee took note of the information provided on CERN's MTP-LTP and of documentation distributed at the meeting by the Staff ...

  9. STANDING CONCERTATION COMMITTEE

    CERN Multimedia

    2003-01-01

    ORDINARY MEETING ON 29 SEPTEMBER 2003 Original: English This meeting was devoted to the main topics summarised below. 1 Follow-up from the meetings of TREF and the Finance Committee in September 2003 The last meeting of TREF had been devoted to presentations and clarifications on the 5-Yearly Review process. The content and planning of the 2005 Review are matters for the next Management, which will be presented to TREF next year. Underlining that due account has to be taken of the limited resources available to conduct such an exercise, the Staff Association stated that it looks forward to the concertation process at the SCC in preparing the next 5-Yearly Review to define an optimum set of topics in order to ensure that CERN can attract, retain and motivate the personnel that it needs to remain a centre of excellence. The Chairman of the SCC recalled that an information document on the Cost-Variation Index for 2004 had been transmitted to the Finance Committee last September and that complete information o...

  10. Standing concertation commmittee

    CERN Multimedia

    HR Department

    2009-01-01

    MEETINGS ON 2 AND 9 DECEMBER 2008 The main items discussed at the meetings of the Standing Concertation Committee on 2 and 9 December 2008 included: Medical Service Report 2007 The Committee took note of the report by Dr. E. Reymond (see http://sc-me.web.cern.ch/sc-me/fr/indexFR.htm) and of a number of points raised during the discussion. It was noted that the number of professional accidents declined in 2007 (361 accidents) in comparison with 2006 (483), as well as their gravity and frequency. The CERN Medical Service carried out a study on cancer prevalence (number of cases) and incidence (new cases per year per 100000 people), between 1993 and 2007, which identified some prostate, breast and colorectal cancers, though less than in the two Host States. Specific preventive actions will be promoted by the CERN CHISboard and the Medical Service in this context as well as in other areas. The committee expressed its thanks to all members of the Medical Service for their work i...

  11. A Concert with Striking Force

    DEFF Research Database (Denmark)

    Steijn, Arthur

    2014-01-01

    An hour before the percussion concert, members of the audience are already filling the foyer of the Copenhagen Opera House. Something special is to happen before the doors to the concert hall open. Percussion instruments—bass drums, bongos, and even a marimba—are exhibited, and people are encoura...

  12. E-Infrastructure Concertation Meeting

    CERN Multimedia

    Katarina Anthony

    2010-01-01

    The 8th e-Infrastructure Concertation Meeting was held in the Globe from 4 to 5 November to discuss the development of Europe’s distributed computing and storage resources.   Project leaders attend the E-Concertation Meeting at the Globe on 5 November 2010. © Corentin Chevalier E-Infrastructures have become an indispensable tool for scientific research, linking researchers to virtually unlimited e-resources like the grid. The recent e-Infrastructure Concertation Meeting brought together e-Science project leaders to discuss the development of this tool in the European context. The meeting was part of an ongoing initiative to develop a world-class e-infrastructure resource that would establish European leadership in e-Science. The e-Infrastructure Concertation Meeting was organised by the Commission Services (EC) with the support of e-ScienceTalk. “The Concertation meeting at CERN has been a great opportunity for e-ScienceTalk to meet many of the 38 new proje...

  13. Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation

    Science.gov (United States)

    Sferruzzi-Perri, Amanda N.; López-Tello, Jorge; Fowden, Abigail L.; Constancia, Miguel

    2016-01-01

    Pregnancy success and life-long health depend on a cooperative interaction between the mother and the fetus in the allocation of resources. As the site of materno-fetal nutrient transfer, the placenta is central to this interplay; however, the relative importance of the maternal versus fetal genotypes in modifying the allocation of resources to the fetus is unknown. Using genetic inactivation of the growth and metabolism regulator, Pik3ca (encoding PIK3CA also known as p110α, α/+), we examined the interplay between the maternal genome and the fetal genome on placental phenotype in litters of mixed genotype generated through reciprocal crosses of WT and α/+ mice. We demonstrate that placental growth and structure were impaired and associated with reduced growth of α/+ fetuses. Despite its defective development, the α/+ placenta adapted functionally to increase the supply of maternal glucose and amino acid to the fetus. The specific nature of these changes, however, depended on whether the mother was α/+ or WT and related to alterations in endocrine and metabolic profile induced by maternal p110α deficiency. Our findings thus show that the maternal genotype and environment programs placental growth and function and identify the placenta as critical in integrating both intrinsic and extrinsic signals governing materno-fetal resource allocation. PMID:27621448

  14. Living Room vs. Concert Hall: Patterns of Music Consumption in Flanders

    Science.gov (United States)

    Roose, Henk; Stichele, Alexander Vander

    2010-01-01

    In this article we probe the interplay between public and private music consumption using a large-scale survey of the Flemish population in Belgium. We analyze whether public and private music consumption have different correlates and to what extent there is convergence between the genres that people listen to at home and at concerts. Results show…

  15. Interplay between calcineurin and the Slt2 MAP-kinase in mediating cell wall integrity, conidiation and virulence in the insect fungal pathogen Beauveria bassiana.

    Science.gov (United States)

    Huang, Shuaishuai; He, Zhangjiang; Zhang, Shiwei; Keyhani, Nemat O; Song, Yulin; Yang, Zhi; Jiang, Yahui; Zhang, Wenli; Pei, Yan; Zhang, Yongjun

    2015-10-01

    The entomopathogenic fungus, Beauveria bassiana, is of environmental and economic importance as an insect pathogen, currently used for the biological control of a number of pests. Cell wall integrity and conidiation are critical parameters for the ability of the fungus to infect insects and for production of the infectious propagules. The contribution of calcineurin and the Slt2 MAP kinase to cell wall integrity and development in B. bassiana was investigated. Gene knockouts of either the calcineurin CNA1 subunit or the Slt2 MAP kinase resulted in decreased tolerance to calcofluor white and high temperature. In contrast, the Δcna1 strain was more tolerant to Congo red but more sensitive to osmotic stress (NaCl, sorbitol) than the wild type, whereas the Δslt2 strain had the opposite phenotype. Changes in cell wall structure and composition were seen in the Δslt2 and Δcna1 strains during growth under cell wall stress as compared to the wild type. Both Δslt2 and Δcna1 strains showed significant alterations in growth, conidiation, and viability. Elevation of intracellular ROS levels, and decreased conidial hydrophobicity and adhesion to hydrophobic surfaces, were also seen for both mutants, as well as decreased virulence. Under cell wall stress conditions, inactivation of Slt2 significantly repressed CN-mediated phosphatase activity suggesting some level of cross talk between the two pathways. Comparative transcriptome profiling of the Δslt2 and Δcna1 strains revealed alterations in the expression of distinct gene sets, with overlap in transcripts involved in cell wall integrity, stress response, conidiation and virulence. These data illustrate convergent and divergent phenotypes and targets of the calcineurin and Slt2 pathways in B. bassiana. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. INTERPLAY OF SORBITOL PATHWAY OF GLUCOSE METABOLISM, 12/15-LIPOXYGENASE, AND MITOGEN-ACTIVATED PROTEIN KINASES IN THE PATHOGENESIS OF DIABETIC PERIPHERAL NEUROPATHY

    Science.gov (United States)

    Stavniichuk, Roman; Shevalye, Hanna; Hirooka, Hiroko; Nadler, Jerry L.; Obrosova, Irina G.

    2012-01-01

    The interactions among multiple pathogenetic mechanisms of diabetic peripheral neuropathy largely remain unexplored. Increased activity of aldose reductase, the first enzyme of the sorbitol pathway, leads to accumulation of cytosolic Ca++, essentially required for 12/15-lipoxygenase activation. The latter, in turn, causes oxidative-nitrosative stress, an important trigger of MAPK phosphorylation. This study therefore evaluated the interplay of aldose reductase, 12/15-lipoxygenase, and MAPKs in diabetic peripheral neuropathy. In experiment 1, male control and streptozotocin-diabetic mice were maintained with or without the aldose reductase inhibitor fidarestat, 16 mg kg−1 d−1, for 12 weeks. In experiment 2, male control and streptozotocin-diabetic wild-type (C57Bl6/J) and 12/15-lipoxygenase-deficient mice were used. Fidarestat treatment did not affect diabetes-induced increase in glucose concentrations, but normalized sorbitol and fructose concentrations (enzymatic spectrofluorometric assays) as well as 12(S) hydroxyeicosatetraenoic concentration (ELISA), a measure of 12/15-lipoxygenase activity, in the sciatic nerve and spinal cord. 12/15-lipoxygenase expression in these two tissues (Western blot analysis) as well as dorsal root ganglia (immunohistochemistry) was similarly elevated in untreated and fidarestat-treated diabetic mice. 12/15-lipoxygenase gene deficiency prevented diabetesassociated p38 MAPK and ERK, but not SAPK/JNK, activation in the sciatic nerve (Western blot analysis) and all three MAPK activation in the dorsal root ganglia (immunohistochemistry). In contrast, spinal cord p38 MAPK, ERK, and SAPK/JNK were similarly activated in diabetic wild-type and 12/15-lipoxygenase−/− mice. These findings identify the nature and tissue specificity of interactions among three major mechanisms of diabetic peripheral neuropathy, and suggest that combination treatments, rather than monotherapies, can sometimes be an optimal choice for its management. PMID

  17. The functional interplay between protein kinase CK2 and CCA1 transcriptional activity is essential for clock temperature compensation in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Sergi Portolés

    2010-11-01

    Full Text Available Circadian rhythms are daily biological oscillations driven by an endogenous mechanism known as circadian clock. The protein kinase CK2 is one of the few clock components that is evolutionary conserved among different taxonomic groups. CK2 regulates the stability and nuclear localization of essential clock proteins in mammals, fungi, and insects. Two CK2 regulatory subunits, CKB3 and CKB4, have been also linked with the Arabidopsis thaliana circadian system. However, the biological relevance and the precise mechanisms of CK2 function within the plant clockwork are not known. By using ChIP and Double-ChIP experiments together with in vivo luminescence assays at different temperatures, we were able to identify a temperature-dependent function for CK2 modulating circadian period length. Our study uncovers a previously unpredicted mechanism for CK2 antagonizing the key clock regulator CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1. CK2 activity does not alter protein accumulation or subcellular localization but interferes with CCA1 binding affinity to the promoters of the oscillator genes. High temperatures enhance the CCA1 binding activity, which is precisely counterbalanced by the CK2 opposing function. Altering this balance by over-expression, mutation, or pharmacological inhibition affects the temperature compensation profile, providing a mechanism by which plants regulate circadian period at changing temperatures. Therefore, our study establishes a new model demonstrating that two opposing and temperature-dependent activities (CCA1-CK2 are essential for clock temperature compensation in Arabidopsis.

  18. Not your grandfather's concert hall

    Science.gov (United States)

    Cooper, Russell; Malenka, Richard; Griffith, Charles; Friedlander, Steven

    2004-05-01

    The opening of Judy and Arthur Zankel Hall on 12 September 2003, restores Andrew Carnegie's original 1891 concept of having three outstanding auditoriums of different sizes under one roof, and creates a 21st-century venue for music performance and education. With concerts ranging from early music to avant-garde multimedia productions, from jazz to world music, and from solo recitals to chamber music, Zankel Hall expands the breadth and depth of Carnegie Hall's offerings. It allows for the integration of programming across three halls with minifestivals tailored both to the size and strengths of each hall and to the artists and music to be performed. The new flexible space also provides Carnegie Hall with an education center equipped with advanced communications technology. This paper discusses the unique program planned for this facility and how the architects, theatre consultants, and acousticians developed a design that fulfilled the client's expectations and coordinated the construction of the facility under the floor of the main Isaac Stern Auditorium without having to cancel a single performance.

  19. Chinese Islam: A Complete Concert

    Directory of Open Access Journals (Sweden)

    Zvi Ben-Dor Benite

    2017-06-01

    Full Text Available Matthew S. Erie, China and Islam: The Prophet, the Party, and Law. Cambridge University Press, 2016. 472 pp. $140 (cloth/e-book. Jonathan Lipman, ed., Islamic Thought in China: Sino-Muslim Intellectual Evolution from the 17th to the 20th Century. Edinburgh University Press, 2016. 288 pp. £70 (cloth; e-book. Roberta Tontini, Muslim Sanzijing: Shifts and Continuities in the Definition of Islam in China. Brill, 2016. 238 pp. $125 (cloth. Why study a Chinese “minority” and its history? The task of scholars of Chinese Islam since the 1990s has been twofold: on the one hand, we have wanted to study Islam in China in its Chinese social and cultural context, as opposed to imagining it as a single separate entity, and to show that its history is relevant and meaningful for Chinese history in general. One could almost say that this goal was achieved a while ago. The next task has been to make the study of Chinese Islam and its history meaningful and useful for the greater community of scholars of Islam in general. It seems to me that with the books reviewed here, and with others in the making, we are getting close to reaching this target. In 1910, Marshall Broomhall’s Islam in China declared that Chinese Islam was a “neglected problem.” These books show that it is no longer neglected, and no longer a “problem”; rather, it is an exciting topic. Indeed, a complete, even if not harmonious, concert.

  20. Concertation or Consultation. That is the question.

    CERN Multimedia

    Staff Association

    2018-01-01

    In April 2017 (as reported in Echo No. 268), the Staff Association, when invited to an Enlarged Directorate meeting, stressed that “concertation requires a positive attitude and mutual trust. […] The Staff Association is firmly committed in this respect but does not consider that the concertation process is as effective as we should like”. The continued lack, for the Staff Association, of an effective concertation process led to a revisiting of the situation in June 2017 (Echo No. 271), in an article that stressed the importance of the concertation process at CERN since it was introduced in 1983, the year in which the Standing Concertation Committee (SCC) replaced the Standing Consultation Committee. The importance of concertation was also highlighted by Mr Bernard Dormy, Chair of TREF, in an interview he gave to the Staff Association at the end of January 2018 (Echo No. 284), when he retired from his position as the Chair of the Forum. “To sum it up, I would certainl...

  1. Concertation rather than Consultation or Negotiation!

    CERN Multimedia

    Staff Association

    2017-01-01

    At CERN, the Concertation between the Management and the Personnel has been in effect since 1983, the year in which the Standing Concertation Committee (SCC) came to replace the Standing Consultation Committee. Since then, the concertation process has been enshrined in the Staff Rules and Regulations, which define its scope of application: “Any proposed measures of a general nature regarding the conditions of employment or association of members of the personnel shall be the subject of discussion within the SCC” (S VII 1.08). More generally, all questions relating to the employment and working conditions of the members of personnel are discussed in the SCC, including in particular issues of remuneration, social protection (CHIS and Pension Fund), career evolution... In Article S VII 1.07 of the Staff Rules and Regulations it is also stated that: “Discussion shall mean a procedure whereby the Director-General and the Staff Association concert together to try to reach a common po...

  2. CONCERT MANAGEMENT IN CROATIA: OBSTACLES AND CHALLENGES

    Directory of Open Access Journals (Sweden)

    Irina Basara

    2016-12-01

    Full Text Available The concept of concert management in the Republic of Croatia encounters numerous obstacles in any attempt to institutionalize it. Unlike other countries in the European Union, there is no register of the concert stages, venues as well as facilities for the provision of hearing / consumption of music in the form of performances. Process management organization is incomplete, and institutions that are closely associated with such events do not carry out the classification, categorization and analysis of events that are within the concerts' domain. Commercial music, economically far most cost-effective, is completely ignored and within the framework of cultural events not even the slightest attention is given to it. On the contrary, it is considered the music of poor quality and completely irrelevant. This paper tries to frame the mentioned genre, which includes various musical directions that economically bring significant benefits and help the survival of these related activities indirectly, and ultimately have a positive impact on the economy. Comparing global trends it speaks about the position of the Croatian music industry and lists the main obstacles for setting up a solid foundation for the construction of an adequate system of indexation of concert businesses that, as part of the creative industries records a meteoric economic growth.

  3. Room acoustic properties of concert halls

    DEFF Research Database (Denmark)

    Gade, Anders Christian

    1996-01-01

    A large database of values of various room acoustic parameters has provided the basis for statistical analyses of how and how much the acoustic properties of concert halls are influenced by their size, shape, and absorption area (as deduced from measured reverberation time). The data have been...

  4. Distinct mechanisms act in concert to mediate cell cycle arrest.

    Science.gov (United States)

    Toettcher, Jared E; Loewer, Alexander; Ostheimer, Gerard J; Yaffe, Michael B; Tidor, Bruce; Lahav, Galit

    2009-01-20

    In response to DNA damage, cells arrest at specific stages in the cell cycle. This arrest must fulfill at least 3 requirements: it must be activated promptly; it must be sustained as long as damage is present to prevent loss of genomic information; and after the arrest, cells must re-enter into the appropriate cell cycle phase to ensure proper ploidy. Multiple molecular mechanisms capable of arresting the cell cycle have been identified in mammalian cells; however, it is unknown whether each mechanism meets all 3 requirements or whether they act together to confer specific functions to the arrest. To address this question, we integrated mathematical models describing the cell cycle and the DNA damage signaling networks and tested the contributions of each mechanism to cell cycle arrest and re-entry. Predictions from this model were then tested with quantitative experiments to identify the combined action of arrest mechanisms in irradiated cells. We find that different arrest mechanisms serve indispensable roles in the proper cellular response to DNA damage over time: p53-independent cyclin inactivation confers immediate arrest, whereas p53-dependent cyclin downregulation allows this arrest to be sustained. Additionally, p21-mediated inhibition of cyclin-dependent kinase activity is indispensable for preventing improper cell cycle re-entry and endoreduplication. This work shows that in a complex signaling network, seemingly redundant mechanisms, acting in a concerted fashion, can achieve a specific cellular outcome.

  5. ANALYSIS MUSIC CONCERTS ADOPTING THE MATHEMATICAL MODEL OF HIT PHENOMENA

    OpenAIRE

    Kawahata Yasuko; Genda Etsuo; Ishii Akira

    2013-01-01

    A mathematical model for the hit phenomenon in entertainment within a society is presented as a stochastic process of interactions of human dynamics. In this paper, we analyzed music to the concert.Knowing the cost of advertising the concert is difficult. But exposure to the media of the artist can be seen. We tried to analysis of music concert itself by performing a prediction of reputation of artists during the concert tour from this exposure.In this paper, The world most pop...

  6. Synergistic Synthetic Biology: Units in Concert

    International Nuclear Information System (INIS)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

  7. Synergistic Synthetic Biology: Units in Concert

    Science.gov (United States)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

  8. The Flux Database Concerted Action (invited paper)

    International Nuclear Information System (INIS)

    Mitchell, N.G.; Donnelly, C.E.

    2000-01-01

    The background to the IUR action on the development of a flux database for radionuclide transfer in soil-plant systems is summarised. The action is discussed in terms of the objectives, the deliverables and the progress achieved by the flux database working group. The paper describes the background to the current initiative, outlines specific features of the database and supporting documentation, and presents findings from the working group's activities. The aim of the IUR flux database working group is to bring together researchers to collate data from current experimental studies investigating aspects of radionuclide transfer in soil-plant systems. The database will incorporate parameters describing the time-dependent transfer of radionuclides between soil, plant and animal compartments. Work under the EC Concerted Action considers soil-plant interactions. This initiative has become known as the radionuclide flux database. It is emphasised that the word flux is used in this case simply to indicate the flow of radionuclides between compartments in time. (author)

  9. State-of-the-art research: Reflections on a concerted Nordic-Baltic nuclear energy effort

    Energy Technology Data Exchange (ETDEWEB)

    Husdal, Lars; Tveit, Jesper; Vaagen, Jan S; Ridikas, Danas

    2009-09-15

    Quite a few hold the view that nuclear energy will have its renaissance in the not too distant future. Technology is, however, a necessary, but not sufficient condition. The needed prerequisites represent a complex issue. With increasing energy demand and depletion of non-renewable energy resources, nuclear will have to prove its role in an increasing energy mix, globally, regionally and often also nationally. Based on its history, experience with coordinated interplay in electricity production from a variety of energy sources, and science engagements, we argue for a future Nordic/Baltic SHOWCASE: A nuclear weapons free and proliferation safe nuclear energy supplier in the region, with a concerted role in competence building and in international ventures, and with focus on operation, safety, economy and societal aspects. (Author)

  10. State-of-the-art research: Reflections on a concerted Nordic-Baltic nuclear energy effort

    International Nuclear Information System (INIS)

    Husdal, Lars; Tveit, Jesper; Vaagen, Jan S.; Ridikas, Danas

    2009-09-01

    Quite a few hold the view that nuclear energy will have its renaissance in the not too distant future. Technology is, however, a necessary, but not sufficient condition. The needed prerequisites represent a complex issue. With increasing energy demand and depletion of non-renewable energy resources, nuclear will have to prove its role in an increasing energy mix, globally, regionally and often also nationally. Based on its history, experience with coordinated interplay in electricity production from a variety of energy sources, and science engagements, we argue for a future Nordic/Baltic SHOWCASE: A nuclear weapons free and proliferation safe nuclear energy supplier in the region, with a concerted role in competence building and in international ventures, and with focus on operation, safety, economy and societal aspects. (Author)

  11. Acoustic investigations of concert halls for rock music

    DEFF Research Database (Denmark)

    Adelman-Larsen, Niels Werner; Thompson, Eric Robert; Gade, Anders Christian

    2007-01-01

    Objective measurement data and subjective evaluations have been collected from 20 small-/medium-sized halls in Denmark used for amplified rhythmic music concerts (pop, rock, jazz). The purpose of the study was to obtain knowledge about optimum acoustic conditions for this type of hall. The study...... is motivated by the fact that most concert tickets sold in Denmark relate to concerts within these genres in this kind of venue. The subjective evaluations were carried out by professional musicians and sound engineers who responded on the basis of their experiences working in these (and other) halls. From...

  12. Cosmos in Concert: Combining astronomy and classical music

    Science.gov (United States)

    Kremer, Kyle

    2018-01-01

    Cosmos in Concert is an outreach initiative designed to combine astronomy education with classical music. Over the past several years, this program has presented large-scale multimedia shows for symphony orchestras, educational programs at K-12 schools, and research-oriented university collaborations designed to develop techniques for the sonification of data. Cosmos in Concert has collaborated with institutions including Fermi National Lab, the Adler Planetarium, the Bienen School of Music, and the Colburn School of Music. In this talk, I will give a brief overview of some of the main Cosmos in Concert initiatives and discuss ways these initiatives may be implemented at other institutions.

  13. Concert | United Nations Orchestra at CERN | 19 September

    CERN Multimedia

    2014-01-01

    The United Nations Orchestra will give a concert on the occasion of CERN’s 60th anniversary.   Under the baton of conductor and artistic director Antoine Marguier, the Orchestra will have the pleasure to accompany the soloist Maestro Matteo Fedeli, who, under the patronage of the Permanent Mission of Italy to the United Nations, will perform on a Stradivarius violin. The programme for the concert comprises: Jacques Offenbach, Orpheus in the Underworld Overture Franz von Suppé, Poet and Peasant Overture Camille Saint-Saëns, Introduction & Rondo Capriccioso for solo violin and orchestra Georges Bizet, Carmen Suite No. 1 Franz Lehár, Gold and Silver Waltz Gioachino Rossini, William Tell Overture   Doors open at 6 p.m. The concert will take place in a marquee behind the Globe of Science and Innovation, CERN Book your ticket here.

  14. Native Frames: Disentangling Sequential from Concerted Three-Body Fragmentation

    Science.gov (United States)

    Rajput, Jyoti; Severt, T.; Berry, Ben; Jochim, Bethany; Feizollah, Peyman; Kaderiya, Balram; Zohrabi, M.; Ablikim, U.; Ziaee, Farzaneh; Raju P., Kanaka; Rolles, D.; Rudenko, A.; Carnes, K. D.; Esry, B. D.; Ben-Itzhak, I.

    2018-03-01

    A key question concerning the three-body fragmentation of polyatomic molecules is the distinction of sequential and concerted mechanisms, i.e., the stepwise or simultaneous cleavage of bonds. Using laser-driven fragmentation of OCS into O++C++S+ and employing coincidence momentum imaging, we demonstrate a novel method that enables the clear separation of sequential and concerted breakup. The separation is accomplished by analyzing the three-body fragmentation in the native frame associated with each step and taking advantage of the rotation of the intermediate molecular fragment, CO2 + or CS2 + , before its unimolecular dissociation. This native-frame method works for any projectile (electrons, ions, or photons), provides details on each step of the sequential breakup, and enables the retrieval of the relevant spectra for sequential and concerted breakup separately. Specifically, this allows the determination of the branching ratio of all these processes in OCS3 + breakup. Moreover, we find that the first step of sequential breakup is tightly aligned along the laser polarization and identify the likely electronic states of the intermediate dication that undergo unimolecular dissociation in the second step. Finally, the separated concerted breakup spectra show clearly that the central carbon atom is preferentially ejected perpendicular to the laser field.

  15. Gala Concert for the 50th Anniversary of CERN

    CERN Multimedia

    2004-01-01

    The CERN 50th Anniversary celebrations will wrap up with music on 18 December with a Gala Concert by the Philharmonic Orchestra of London in Victoria Hall, Geneva. The orchestra will be directed by Tommaso Placidi, a young talented conductor, and will also enjoy the presence of Maxim Vengerov as first violin. This evening is organised by Mrs Suzanne Hurter, with the support of private companies as well as of the city and the canton of Geneva. The concert will begin with the Overture of Wagner's Flying Dutchman. Maxim Vengerov will then interpret Beethoven's Concert for violin and orchestra. The second part of the concert will be devoted to Tschaikovsky's Fourth Symphony. Tickets cost between 35CHF and 140 CHF according to the seat. People working at CERN will have a 10% discount. You may buy your tickets at the Kiosque FK inside the building Pfister Meubles in Meyrin (ch de Rianbosson 5-9) and get your discount by showing your CERN card. Find out more about the seats available, go to the Resaplus Ticket Book...

  16. Concerted Cultivation and Music Learning: Global Issues and Local Variations

    Science.gov (United States)

    Ilari, Beatriz

    2013-01-01

    "Concerted cultivation" has been described as a common, urban middle-class practice concerning the enrollment of children in a variety of age-specific activities that may promote the learning of valuable life skills as well as the development of individual abilities (Lareau, 2003). Music is one such activity. This study investigated the…

  17. Family Music Concerts: Bringing Families, Music Students, and Music Together

    Science.gov (United States)

    Kenney, Susan Hobson

    2014-01-01

    This article describes how conductors of the top performing groups and music education faculty at one university collaborated to create a Family Concert Series for parents and children of all ages, including infants in arms. Recognizing the conflict between "The first three years of life are the most important for educating a young child in…

  18. Parenting Priorities and Pressures: Furthering Understanding of "Concerted Cultivation"

    Science.gov (United States)

    Vincent, Carol; Maxwell, Claire

    2016-01-01

    This paper re-examines the purposes of a planned and intentional parenting style--"concerted cultivation"--for different middle-class groups, highlighting that social class fraction, ethnicity, and also individual family disposition, guides understandings of the purposes of enrolling children in particular enrichment activities. We…

  19. Electronic Performance Monitoring: An Organizational Justice and Concertive Control Perspective.

    Science.gov (United States)

    Alder, G. Stoney; Tompkins, Phillip K.

    1997-01-01

    Applies theories of organizational justice/concertive control to account for contradictions inherent in electronic monitoring of workers by organizations. Argues that results are usually positive when workers are involved in the design and implementation of monitoring systems, and monitoring is restricted to performance-related activities with…

  20. THE ORIGIN OF CONCERT MUSIC IN NIGERIA, 1850 - 1920 ...

    African Journals Online (AJOL)

    Mitch

    Studies on the origins of concert music in Nigeria often dwell on aspects of the ... chronicle its development from its earliest beginnings to the present. ... their children, trying to live as much as possible like Victoria gentlemen.' (Ajayi .... entertainment began in 1822 the movement for a public hall that bore fruit in the building.

  1. Prehospital severity scoring at major rock concert events.

    Science.gov (United States)

    Erickson, T B; Koenigsberg, M; Bunney, E B; Schurgin, B; Levy, P; Willens, J; Tanner, L

    1997-01-01

    Rock and contemporary music concerts are popular, recurrent events requiring on-site medical staffing. To describe a novel severity score used to stratify the level of acuity of patients presenting to first-aid stations at these events. Retrospective review of charts generated at the first-aid stations of five major rock concerts within a 60,000 spectator capacity, outdoor, professional sports stadium. Participants included all concert patrons presenting to the stadium's first-aid stations as patients. Data were collected on patient demographics, history of drug or ethanol usage while at the concert event, first-aid station time, treatment rendered, diagnosis, and disposition. All patients evaluated were retrospectively assigned a "DRUG-ROCK" Injury Severity Score (DRISS) to stratify their level of acuity. Individual concert events and patient dispositions were compared statistically using chi-square, Fisher's exact, and the ANOVA Mean tests. Approximately 250,000 spectators attended the five concert events. First-aid stations evaluated 308 patients (utilization rate of 1.2 per 1,000 patrons). The most common diagnosis was minor trauma (130; 42%), followed in frequency by ethanol/illicit drug intoxication (98; 32%). The average time in the first-aid station was 23.5 +/- 22.5 minutes (+/- standard deviation; range: 5-150 minutes). Disposition of patients included 100 (32.5%) who were treated and released; 98 (32%) were transported by paramedics to emergency departments (EDs); and 110 (35.5%) signed-out against medical advise (AMA), refusing transport. The mean DRISS was 4.1 (+/- 2.65). Two-thirds (67%) of the study population were ranked as mild by DRISS criteria (score = 1-4), with 27% rated as moderate (score = 5-9), and 6% severe (score > 10). The average of severity scores was highest (6.5) for patients transported to hospitals, and statistically different from the scores of the average of the treated and released and AMA groups (p rock concerts.

  2. Audience noise in concert halls during musical performances

    DEFF Research Database (Denmark)

    Jeong, Cheol-Ho; Marie, Pierre; Brunskog, Jonas

    2012-01-01

    functions of the sound pressure levels were obtained in octave bands, which were fitted with three Gaussian distribution curves. The Gaussian distribution curve with the lowest mean value corresponds to a mixture of the technical background noise and audience generated noise, which is named the mixed...... background noise. Finally, the audience noise distribution is extracted by energy subtraction of the technical background noise levels measured in an empty condition from the mixed background noise levels. As a single index, L-90 of the audience noise distribution is named the audience noise level. Empirical...... prediction models were made using the four orchestra concert halls, revealing that the audience noise level is significantly correlated with the technical background noise level. It is therefore concluded that a relaxation of the current background noise recommendations for concert halls is not recommended...

  3. Audience noise in concert halls during musical performances

    DEFF Research Database (Denmark)

    Marie, Pierre; Jeong, Cheol-Ho; Brunskog, Jonas

    2012-01-01

    functions of the sound pressure levels were obtained in octave bands, which were fitted with three Gaussian distribution curves. The Gaussian distribution curve with the lowest mean value corresponds to a mixture of the technical background noise and audience generated noise, which is named the mixed...... background noise. Finally, the audience noise distribution is extracted by energy subtraction of the technical background noise levels measured in an empty condition from the mixed background noise levels. As a single index, L90 of the audience noise distribution is named the audience noise level. Empirical...... prediction models were made using the four orchestra concert halls, revealing that the audience noise level is significantly correlated with the technical background noise level. It is therefore concluded that a relaxation of the current background noise recommendations for concert halls is not recommended....

  4. Standing Concertation Committee: Ordinary Meeting on 1 September 2004

    CERN Document Server

    2004-01-01

    Original: English This meeting was devoted to the main topics summarised below. Preparation for the 5-Yearly Review 2005 The Committee took note that preparatory work had started over the summer months on various topics for the 5-Yearly Review, in line with the internal planning presented to the SCC last June. Concertation process and working procedures Referring to its recent publications, the Staff Association raised this subject in connection with the organization and procedures of the HR study teams and CFO discussion group working on the various topics which are to be covered in the 5-Yearly Review. After some debate, both the Management and the Staff Association underlined the importance that they attach to an efficient concertation process. Both parties agreed to continue the discussion after the meeting. Data collection questionnaire The SCC discussed the content of the questionnaire for the data collection enquiry to be launched this autumn. Subject to some further clarifications and improv...

  5. STANDING CONCERTATION COMMITTEE: ORDINARY MEETING ON 5 FEBRUARY 2004

    CERN Multimedia

    2004-01-01

    Original : English This meeting was devoted to the main topics summarised below. 1-The internal concertation process Responding to various questions in this connection raised by the Staff Association, the Chairman stated that the Management wishes to diminish in no way the role of the SCC in the internal concertation process, as set out in chapter VII of the Staff Rules and Regulations. On the contrary, he underlined the importance of ensuring this process to debate strategic issues concerning employment conditions, prior to decisions taken by the Director-General. On a point of clarification, he confirmed that, as discussed at the January meeting of the Executive Board, the Management wishes to abolish the Long-Term Contract Board and the Senior Staff Advancement Committee; the SCC took note of this intention. Simplified procedures without the Committees would be presented as soon as possible to the SCC, together with amendments to the relevant Administrative Circulars. 2-MAPS The Committee discussed th...

  6. Blind Concert: The World and Its Transformation through Music

    Directory of Open Access Journals (Sweden)

    Nataša Milović

    2015-04-01

    Full Text Available This paper presents an analysis of a Blind Concert held in Belgrade. In a Blind Concert performance, the concept of “space” transforms not for the sake of transformation itself, but because of the effect it strives to achieve. This eliminates the predominance of an institution of art dictating how a musical work should be approached. Accompanying the interpretation of piano compositions, the vocalist let out screams, voices, and noises, which, one may say, could not be summoned inside us, because they have yet to be articulated. I will articulate the effects of the desired transitional forms that have remained trapped and unrepresented in social standardization in terms of Badiou’s inaesthetics.

  7. Practicing perfection: How concert soloists prepare for performance

    Directory of Open Access Journals (Sweden)

    Roger Chaffin

    2006-01-01

    Full Text Available Musical performances by concert soloists in the Western classical tradition are normally memorized. For memory to work reliably under the pressures of the concert stage, the performance must be practiced until it is thoroughly automatic. At the same time, the performance must be fresh and spontaneous in order to communicate emotionally with the audience. The resolution of this apparent contradiction is provided by longitudinal case studies of concert soloists preparing new works for performance. Like expert memorists in other domains, experienced musicians use highly practiced retrieval schemes to accomplish their extraordinary feats of memory. Performers have a mental map of the piece in mind as they perform that tells them where they are and what comes next - a series of landmarks, hierarchically organized by the sections and subsections of the music. The musician attends to these performance cues in order to ensure that the performance unfolds as planned. Performance cues are established by thinking about a particular feature of the music during practice so that it later comes to mind automatically. Performance cues help the soloist consciously monitor and control the rapid, automatic actions of playing, while adjusting to the needs of the moment. During practice, the musician attends mostly to basic performance cues representing critical technical features (e.g., fingerings,andinterpretive performance cues, representing phrasings, and changes in dynamics, tempo, and timbre. During performance, the musician hopes to attend mainly to expressive performance cues representing the musical feelings to be conveyed to the audience (e.g. excitement. We illustrate this analysis with a typical case study of a concert pianist learning J.S. Bach's Italian Concerto (Presto.

  8. Concerted orientation induced unidirectional water transport through nanochannels.

    Science.gov (United States)

    Wan, Rongzheng; Lu, Hangjun; Li, Jinyuan; Bao, Jingdong; Hu, Jun; Fang, Haiping

    2009-11-14

    The dynamics of water inside nanochannels is of great importance for biological activities as well as for the design of molecular sensors, devices, and machines, particularly for sea water desalination. When confined in specially sized nanochannels, water molecules form a single-file structure with concerted dipole orientations, which collectively flip between the directions along and against the nanotube axis. In this paper, by using molecular dynamics simulations, we observed a net flux along the dipole-orientation without any application of an external electric field or external pressure difference during the time period of the particular concerted dipole orientations of the molecules along or against the nanotube axis. We found that this unique special-directional water transportation resulted from the asymmetric potential of water-water interaction along the nanochannel, which originated from the concerted dipole orientation of the water molecules that breaks the symmetry of water orientation distribution along the channel within a finite time period. This finding suggests a new mechanism for achieving high-flux water transportation, which may be useful for nanotechnology and biological applications.

  9. Casein kinases

    DEFF Research Database (Denmark)

    Issinger, O G

    1993-01-01

    The present review on casein kinases focuses mainly on the possible metabolic role of CK-2, with special emphasis on its behavior in pathological tissues. From these data at least three ways to regulate CK-2 activity emerge: (i) CK-2 activity changes during embryogenesis, being high at certain...

  10. Kinases and Cancer

    OpenAIRE

    Jonas Cicenas; Egle Zalyte; Amos Bairoch; Pascale Gaudet

    2018-01-01

    Protein kinases are a large family of enzymes catalyzing protein phosphorylation. The human genome contains 518 protein kinase genes, 478 of which belong to the classical protein kinase family and 40 are atypical protein kinases [...

  11. Host-pathogen interplay of Haemophilus ducreyi.

    Science.gov (United States)

    Janowicz, Diane M; Li, Wei; Bauer, Margaret E

    2010-02-01

    Haemophilus ducreyi, the causative agent of the sexually transmitted infection chancroid, is primarily a pathogen of human skin. During infection, H. ducreyi thrives extracellularly in a milieu of professional phagocytes and other antibacterial components of the innate and adaptive immune responses. This review summarizes our understanding of the interplay between this pathogen and its host that leads to development and persistence of disease. H. ducreyi expresses key virulence mechanisms to resist host defenses. The secreted LspA proteins are tyrosine-phosphorylated by host kinases, which may contribute to their antiphagocytic effector function. The serum resistance and adherence functions of DsrA map to separate domains of this multifunctional virulence factor. An influx transporter protects H. ducreyi from killing by the antimicrobial peptide LL37. Regulatory genes have been identified that may coordinate virulence factor expression during disease. Dendritic cells and natural killer cells respond to H. ducreyi and may be involved in determining the differential outcomes of infection observed in humans. A human model of H. ducreyi infection has provided insights into virulence mechanisms that allow this human-specific pathogen to survive immune pressures. Components of the human innate immune system may also determine the ultimate fate of H. ducreyi infection by driving either clearance of the organism or an ineffective response that allows disease progression.

  12. Statistics regarding the concerted work stoppage of 28 April 2006

    CERN Multimedia

    HR Department

    2006-01-01

    Following the concerted work stoppage of Friday, 28 April, HR Department sent out a questionnaire to all staff members in order to determine the number of those who participated. Questionnaires sent out : 2665 Staff members asked not to return the questionnaire: (on official duty/special leave/sick leave/annual leave) -1006 of which, those who took one day only of annual leave linked to the weekend of 1st May [430] Staff members called upon to perform their duties: -217 Total number of forms expected to be returned 1442 It was presumed that all those who had not returned their forms had not taken part in the work stoppage. After a count and verification of the questionnaires (returned up to 11 May) together with a representative of the Staff Association, the results are the following: Those who specifically indicated that they took part in the concerted work stoppage: 166 11.5% YES Non-participation 1276 88.5% NO of which, those who wanted to indicate that they did not ta...

  13. The European concerted action on air pollution epidemiology

    Energy Technology Data Exchange (ETDEWEB)

    Ackermann-Liebrich, U [Basel Univ. (Switzerland). Inst. for Social and Preventive Medicine

    1996-12-31

    The European Concerted Action on Air Pollution Epidemiology was started in 1990 with the aim of bringing together European researchers in the field and improving research through collaboration and by preparing documents which would help to this end and by organizing workshops. A further aim was to stimulate cooperative research. Air pollution epidemiology investigates human effects of community air pollution by epidemiological methods. Epidemiology in general investigates the distribution and determinants of health-related states and events in populations. Diseases in which air pollution may play a significant role are mainly diseases of the respiratory system, for example chronic non-specific lung disease and lung cancer. Most diseases caused by air pollution can also be caused by other factors. Air pollution epidemiology is therefore specific in the expo variable (community air pollution) rather than in the type of health effects being studied. Air pollution epidemiology is beset with some specially challenging difficulties: ubiquitous exposure and as a consequence limited heterogeneity in exposure, low relative risks, few or specific health end points, and strong confounding. Further on the exposure-effect relationship is complicated by assumptions inherent to different study designs which relate to the exposure duration necessary to produce a certain health effect. In reports and workshops the concerted action tries to propose strategies to deal with these problems. (author)

  14. The European concerted action on air pollution epidemiology

    Energy Technology Data Exchange (ETDEWEB)

    Ackermann-Liebrich, U. [Basel Univ. (Switzerland). Inst. for Social and Preventive Medicine

    1995-12-31

    The European Concerted Action on Air Pollution Epidemiology was started in 1990 with the aim of bringing together European researchers in the field and improving research through collaboration and by preparing documents which would help to this end and by organizing workshops. A further aim was to stimulate cooperative research. Air pollution epidemiology investigates human effects of community air pollution by epidemiological methods. Epidemiology in general investigates the distribution and determinants of health-related states and events in populations. Diseases in which air pollution may play a significant role are mainly diseases of the respiratory system, for example chronic non-specific lung disease and lung cancer. Most diseases caused by air pollution can also be caused by other factors. Air pollution epidemiology is therefore specific in the expo variable (community air pollution) rather than in the type of health effects being studied. Air pollution epidemiology is beset with some specially challenging difficulties: ubiquitous exposure and as a consequence limited heterogeneity in exposure, low relative risks, few or specific health end points, and strong confounding. Further on the exposure-effect relationship is complicated by assumptions inherent to different study designs which relate to the exposure duration necessary to produce a certain health effect. In reports and workshops the concerted action tries to propose strategies to deal with these problems. (author)

  15. Non-concerted ITS evolution in Mammillaria (Cactaceae).

    Science.gov (United States)

    Harpke, Doerte; Peterson, Angela

    2006-12-01

    Molecular studies of 21 species of the large Cactaceae genus Mammillaria representing a variety of intrageneric taxonomic levels revealed a high degree of intra-individual polymorphism of the internal transcribed spacer region (ITS1, 5.8S rDNA, ITS2). Only a few of these ITS copies belong to apparently functional genes, whereas most are probably non-functional (pseudogenes). As a multiple gene family, the ITS region is subjected to concerted evolution. However, the high degree of intra-individual polymorphism of up to 36% in ITS1 and up to 35% in ITS2 suggests a non-concerted evolution of these loci in Mammillaria. Conserved angiosperm motifs of ITS1 and ITS2 were compared between genomic and cDNA ITS clones of Mammillaria. Some of these motifs (e.g., ITS1 motif 1, 'TGGT' within ITS2) in combination with the determination of GC-content, length comparisons of the spacers and ITS2 secondary structure (helices II and III) are helpful in the identification of pseudogene rDNA regions.

  16. Content, Context & Connectivity Persuasive Interplay

    DEFF Research Database (Denmark)

    Sørensen, Christian Grund

    2013-01-01

    -supported research project under EACEA). In the development of this project several categories of content have been implemented in technology enhanced learning tools. These have been designed to support learning in different contexts and eventually the role of the connectivity of these learning objects and tools......The aim of this paper is to discuss the relationship between content, context and connectivity and suggesting a model of Dynamic Interplay. This is done in relation to a specific learning environment concerning cultural mediation, in casu the Kaj Munk Case of the EuroPLOT-project (an EU...... is discussed. Focus is here on The Kaj Munk Study Edition, The Conceptual Pond, Immersive Layers Design, and Generative Learning Objects (GLOs) which are applications affiliated with the Munk case. This paper explores the persuasive potential of the interplay between the different applications for the benefit...

  17. STANDING CONCERTATION COMMMITTEE - ORDINARY MEETING ON 26 JUNE 2007

    CERN Multimedia

    HR Department

    2007-01-01

    The main items discussed at the meeting of the Standing Concertation Committee on 26 June 2007 included: Mutual Aid Fund The Committee took note of the annual report for 2006 by the Chairman of the Mutual Aid Fund and approved contributions to the Fund’s budget from the Management and the Staff Association and thanked the members of the Fund for their work. Administrative Circular No. 12 A (Rev. 1) - Education Fees The Committee agreed to recommend Administrative Circular No. 12 A entitled "Education Fees" to the Director-General for approval. The circular is applicable to staff, fellows and scientific associates recruited from 1st January 2007 and to staff who were recruited as Local Staff before that date. Further details of reimbursement of school fees will shortly be available in the form of Frequently Asked Questions on the HR Department website. Administrative Circular No. 31 (Rev. 1) - International Indemnity and Non-Resident Allowance The Committee agreed to reco...

  18. Standing Concertation Committee - Ordinary Meeting on 3 September 2008

    CERN Multimedia

    HR Department

    2008-01-01

    The main items discussed at the meeting of the Standing Concertation Committee on 3 September 2008 included: Education fees: Indexation of the amounts for accommodation and meals The Committee approved the indexation calculations for accommodation and meals for the academic year 2008-2009. With the indexation of the lump sum payments, accommodation costs for the academic year 2007-2008 will be reimbursed at 529 CHF per month (previously CHF 500). Meals will be reimbursed at 17.50 CHF per meal (unchanged). The ceiling for school transport has been increased from 600 CHF to 622 CHF. Administrative Circular No. 26 (Rev. 8) The Committee took note of the modifications to Administrative Circular No. 26 (Rev. 8) ‘Recognition of merit of staff members’, concerning provision for the award of exceptional advancement outside the annual advancement exercise to recognize, for example, the completion of a major project. HR Survey The Committee took note of the Head of HR Department...

  19. Crisis behavior: An exploration of theories in concert.

    Science.gov (United States)

    McConnell, Jason B; Crudo, Christine

    2015-01-01

    How might prominent existing communication theory better explain behavior in a crisis context, when considered in concert with one another? This theoretical work highlights the insight to be gained using Situational Crisis Communication Theory and Bandura's notions of self-efficacy to heighten the explanatory power of the Theory of Planned Behavior as applied to communication during times of crisis. Situational Crisis Communication Theory better explains how past experience with crisis influences the attitudes and social norms of crisis behavior, while Bandura's notion of self-efficacy speaks more directly to the availability of resources as contributing factors to perceived behavioral control in a crisis situation. As such, the incorporation of these well-developed notions into the broader framework of the Theory of Planned Behavior affords greater understanding of the relationship between communication and behavior during a crisis. Further exploration of this theoretical relationship is warranted.

  20. STANDING CONCERTATION COMMMITTEE - ORDINARY MEETING ON 28 AUGUST 2007

    CERN Multimedia

    HR Department

    2007-01-01

    The main items discussed at the meeting of the Standing Concertation Committee on 28 August 2007 included: Administrative Circular No. 12 A (Rev. 1) - Education Fees The Committee agreed to recommend Administrative Circular No. 12 A, "Education Fees", to the Director-General for approval. The circular is applicable to staff, fellows and scientific associates recruited before 1 January 2007 (except for local staff). Administrative Circular No. 12 B applies to those recruited from 1 January 2007 and was examined by the Committee in June 2007. It was noted that, at the initiative of HR Department, a number of important simplifications have been introduced. These cover, in particular, lump-sum payments to compensate for accommodation, meals and journey expenses. Further details of payment of education fees will shortly be available in the form of Frequently Asked Questions on the HR Department website. The Chairman thanked HR Department as well as "Team 7" members for init...

  1. STANDING CONCERTATION COMMMITTEE - ORDINARY MEETING ON 28 AUGUST 2007

    CERN Document Server

    HR Department

    2007-01-01

    The main items discussed at the meeting of the Standing Concertation Committee on 28 August 2007 included: Administrative Circular No. 12 A (Rev. 1) - Education Fees The committee agreed to recommend Administrative Circular No. 12 A, Education Fees, to the Director-General for approval. The circular is applicable to staff, fellows and scientific associates recruited before 1 January 2007 (except for local staff). Administrative Circular No. 12 B applies to those recruited from 1 January 2007 and was considered by the committee in June 2007. It was noted that, at the initiative of HR Department, a number of important simplifications have been introduced. These cover in particular lump sum payments to compensate for accommodation, meals and journey expenses. Further details of payment of education fees will shortly be available in the form of Frequently Asked Questions on the HR Department website. The Chairman thanked HR Department as well as "Team 7" members for initiating these simp...

  2. Standing Concertation Commmittee - Ordinary meeting on 10 May 2007

    CERN Multimedia

    2007-01-01

    At its meeting on 10 May 2007, the Standing Concertation Committee discussed the Management’s proposal for the revision of Annex A 1 of the Staff Rules and Regulations. Annex A 1 sets out the principles for future periodic reviews of the personnel’s financial and social conditions and the revision reflects the modifications to review methods decided by the CERN Council in December 2006. The aim is to simplify the processes involved and rationalize the use of resources. The data collection process will be outsourced to a greater extent. The new methods also aim to reduce the overall time required to complete future reviews. Details of procedure will be addressed in subsequent discussions. The Committee approved the document for submission to the Tripartite Employment Conditions Forum (TREF) at its meeting on 31 May and 1 June 2007.

  3. Standing Concertation Commmittee - Ordinary meeting on 27 March 2007

    CERN Multimedia

    HR Department

    2007-01-01

    The main items discussed at the meeting of the Standing Concertation Committee on 27 March 2007 included: Merit Recognition Guidelines In the context of the new Merit Appraisal and Recognition Scheme (MARS), the committee took note of the documents entitled 'MARS Guidelines 2007' and the 'Guidelines for Senior Staff Advancement 2007'. Follow-up of Finance Committee and Council meetings The Committee took note of the information provided by S. Lettow, the Director for Finance and Human Resources, including the possibility for a phased increase in Member State contributions from 2008. Registered partnerships It was agreed that staff members with registered partners should be reminded of the social cover available to their partners. Cover is limited to the CERN Health Insurance Scheme and partners may be covered by the Scheme only while the staff member is working. On the staff member's retirement or other change in status, or death, partners are no longer eligible for CHIS cover. Retirement semi...

  4. Standing Concertation Commmittee - Ordinary meeting on 27 March 2007

    CERN Multimedia

    HR Department

    2007-01-01

    The main items discussed at the meeting of the Standing Concertation Committee on 27 March 2007 included: Merit Recognition Guidelines : in the context of the new Merit Appraisal and Recognition Scheme (MARS), the committee took note of the documents entitled MARS Guidelines 2007 and the Guidelines for Senior Staff Advancement 2007. Follow-up of Finance Committee and Council meetings The Committee took note of the information provided by S. Lettow, the Director for Finance and Human Resources, including the possibility for a phased increase in Member State contributions from 2008. Registered partnerships It was agreed that staff members with registered partners should be reminded of the social cover available to their partners. Cover is limited to the CERN Health Insurance Scheme and partners may be covered by the Scheme only while the staff member is working. On the staff members retirement or other change in status, or death, partners are no longer eligible for CHIS cover. Retirement seminars It...

  5. Standing Concertation Commmittee - Ordinary meeting on 10 May 2007

    CERN Multimedia

    HR Department

    2007-01-01

    At its meeting on 10 May 2007, the Standing Concertation Committee discussed the Management's proposal for the revision of Annex A 1 of the Staff Rules and Regulations. Annex A 1 sets out the principles for future periodic reviews of the personnel's financial and social conditions and the revision reflects the modifications to review methods decided by the CERN Council in December 2006. The aim is to simplify the processes involved and rationalize the use of resources. The data collection process will be outsourced to a greater extent. The new methods also aim to reduce the overall time required to complete future reviews. Details of procedure will be addressed in subsequent discussions. The Committee approved the document for submission to the Tripartite Employment Conditions Forum (TREF) at its meeting on 31 May and 1 June 2007.

  6. Concerted diurnal patterns in riverine nutrient concentrations and physical conditions

    International Nuclear Information System (INIS)

    Scholefield, David; Le Goff, Thierry; Braven, Jim; Ebdon, Les; Long, Terry; Butler, Mark

    2005-01-01

    Several long-term sets of hourly nitrate concentration data were obtained through deployment of a nitrate sensor in an upper reach of the River Taw, a small moorland-fed river in the South West of the UK. Examination of the data obtained during periods of low flow and the absence of rainfall in the catchment revealed the presence of marked diurnal cycles, which were in concert and negatively correlated with diurnal cycles in water temperature. After verifying that these cycles were natural, an intensive 90-h field monitoring campaign was conducted, in which river water was sampled hourly and immediately analysed in the laboratory for molybdate-reactive phosphorus (P), nitrate, nitrite, ammonium, and pH. Coincident measurements of water temperature, river discharge and solar energy were also taken at, or close to, the site. All measurements revealed diurnal patterns and all patterns were concerted. The cycles of P, nitrate, nitrite, and discharge had two maxima and minima per 24 h, while the cycle of water temperature had one, with a maximum at 20.00 and a minimum at 08.00. The amplitudes of the cycles of P and nitrate were each about 30% of the mean values, while the amplitude of the nitrite cycle was as great as 80% of the mean value on occasions. Both biological and physical mechanisms for the cycling could operate through water temperature and/or incident radiation to account for the observed phenomenon, but there remains uncertainty of which is the more important. The observations have important implications for both the accuracy of pollution assessment in rivers and the physiological rhythms of riverine organisms

  7. Concerted diurnal patterns in riverine nutrient concentrations and physical conditions.

    Science.gov (United States)

    Scholefield, David; Le Goff, Thierry; Braven, Jim; Ebdon, Les; Long, Terry; Butler, Mark

    2005-05-15

    Several long-term sets of hourly nitrate concentration data were obtained through deployment of a nitrate sensor in an upper reach of the River Taw, a small moorland-fed river in the South West of the UK. Examination of the data obtained during periods of low flow and the absence of rainfall in the catchment revealed the presence of marked diurnal cycles, which were in concert and negatively correlated with diurnal cycles in water temperature. After verifying that these cycles were natural, an intensive 90-h field monitoring campaign was conducted, in which river water was sampled hourly and immediately analysed in the laboratory for molybdate-reactive phosphorus (P), nitrate, nitrite, ammonium, and pH. Coincident measurements of water temperature, river discharge and solar energy were also taken at, or close to, the site. All measurements revealed diurnal patterns and all patterns were concerted. The cycles of P, nitrate, nitrite, and discharge had two maxima and minima per 24 h, while the cycle of water temperature had one, with a maximum at 20.00 and a minimum at 08.00. The amplitudes of the cycles of P and nitrate were each about 30% of the mean values, while the amplitude of the nitrite cycle was as great as 80% of the mean value on occasions. Both biological and physical mechanisms for the cycling could operate through water temperature and/or incident radiation to account for the observed phenomenon, but there remains uncertainty of which is the more important. The observations have important implications for both the accuracy of pollution assessment in rivers and the physiological rhythms of riverine organisms.

  8. PAK4 crystal structures suggest unusual kinase conformational movements.

    Science.gov (United States)

    Zhang, Eric Y; Ha, Byung Hak; Boggon, Titus J

    2018-02-01

    In order for protein kinases to exchange nucleotide they must open and close their catalytic cleft. These motions are associated with rotations of the N-lobe, predominantly around the 'hinge region'. We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077). We find an unusual motion between the N-lobe and C-lobe of PAK4 that manifests as a partial unwinding of helix αC. Principal component analysis of the crystal structures rationalizes these movements into three major states, and analysis of the kinase hydrophobic spines indicates concerted movements that create an accessible back pocket cavity. The conformational changes that we observe for PAK4 differ from previous descriptions of kinase motions, and although we observe these differences in crystal structures there is the possibility that the movements observed may suggest a diversity of kinase conformational changes associated with regulation. Protein kinases are key signaling proteins, and are important drug targets, therefore understanding their regulation is important for both basic research and clinical points of view. In this study, we observe unusual conformational 'hinging' for protein kinases. Hinging, the opening and closing of the kinase sub-domains to allow nucleotide binding and release, is critical for proper kinase regulation and for targeted drug discovery. We determine new crystal structures of PAK4, an important Rho-effector kinase, and conduct analyses of these and previously determined structures. We find that PAK4 crystal structures can be classified into specific conformational groups, and that these groups are associated with previously unobserved hinging motions and an unusual conformation for the kinase hydrophobic core. Our findings therefore indicate that there may be a diversity of kinase hinging motions, and that these may

  9. Muddle or march: China and the 21st century Concert of Powers

    Directory of Open Access Journals (Sweden)

    Weizhun Mao

    2014-01-01

    Full Text Available Concert of Powers has emerged as an attractive modality in global governance. As an emerging power, China must seriously take this template into account. This article seeks to analyze the incentives, possibilities, and uncertainties for China to participate in Concert with reference to China's history memory on Concert, China's intellectual endeavors, as well as China's evolving foreign preferences. It concludes that China is generally qualified and capable of being a key participant in Concert of Powers with increasing willingness. Yet, China's involvement depends on 1 if Concert template can overcome its own deficiencies; 2 if Concert have competitive advantages compared with other governance alternatives for China; and 3 if China can keep its momentum on both willingness and capacity in power transition.

  10. Concerted and stepwise mechanisms in cycloaddition reactions: potential surfaces and isotope effects

    International Nuclear Information System (INIS)

    Houk, K.N.; Yi Li; Storer, Joey; Raimondi, Laura; Beno, Brett

    1994-01-01

    CASSCF/6-31G * calculations have been performed on concerted and stepwise Diels-Alder reactions of butadiene with ethene, the dimerization of butadiene, and the dimerization of cyclobutadiene. The relative energies of concerted and stepwise mechanisms are compared, and the factors influencing these ''energies of concert'' are discussed. The comparison of calculated isotope effects to experimental data provides support for theoretical results. (Author)

  11. Standing Concertation Committee - Ordinary Meeting on 4 December 2007

    CERN Multimedia

    HR Department

    2008-01-01

    The main items discussed at the meeting of the Standing Concertation Committee on 4 December 2007 included: 2006 Medical Service Annual Report The Committee took note of the report by the head of the Medical Service, Dr V. Fassnacht, (see http://sc-me.web.cern.ch/sc-me/index.html) and of a number of points raised during the discussion, including the importance of further prevention measures. The Committee expressed its thanks to all members of the Medical Service for their work in 2006 and over the past year. Short-Term Saved leave Scheme As announced in Weekly Bulletins Nos. 28/2007 and 51/2007, the Saved Leave Scheme will be succeeded from 1 January 2008 by the Short-Term Saved Leave Scheme (see also https://hr-services.web.cern.ch/hr-services/services-Ben/sls_shortterm.asp). The Committee agreed to recommend the Director-General to adopt the relevant procedure. It was noted that staff could apply immediately to participate from 1 January 2008 and that applications to pa...

  12. STANDING CONCERTATION COMMMITTEE - ORDINARY MEETING ON 3 APRIL 2008

    CERN Multimedia

    HR Department

    2008-01-01

    The main items discussed at the meetings of the Standing Concertation Committee on 3 April 2008 included: External mobility The Committee took note of a progress report on external mobility after a run-in period of about six months. Based on the experience gained, it was agreed to broaden the scope of the programme and in particular to extend eligibility conditions to include: All staff members whose limited duration contract will end in less than one year, as well as all those with indefinite contracts; Fellows who have been employed by CERN for more than 18 months; Doctoral students who have been in the CERN doctoral programme for more than 2.5 years; Apprentices in the final year of their apprenticeship; Ex-members of the personnel who are receiving CERN unemployment benefits. An article in the Weekly Bulletin will follow and the relevant web pages will be updated. LHC achievement awards The Committee took note of the outcome of discussions between the Management and t...

  13. STANDING CONCERTATION COMMITTEE: ORDINARY MEETING ON 15 JANUARY 2004

    CERN Document Server

    2004-01-01

    Original: English This meeting was devoted to the main topics summarised below. 1-Introduction by the Director-General Conveying his best wishes for the New Year to SCC members, the Director-General underlined the importance which he attaches to good relations with the staff and their representatives in the Staff Association. He would ensure open dialogue and make every effort to attend the SCC, at the request of the Staff Association or the Management representatives. The concertation process at the SCC and TREF is a most useful and necessary one for the Management in drawing up strategies that are clearly announced and understood by all parties. He trusted that the SCC would play a vital role in realising related programmes and in optimising their implementation. He also wished to pass a message to the staff at large on the importance of good, efficient management, understood in its widest sense and at all levels. The role of supervisors is not only to lead their teams in the scientific and technical doma...

  14. Standing Concertation Committee - Ordinary meeting on 25 June 2008

    CERN Multimedia

    HR Department

    2008-01-01

    The main items discussed at the meetings of the Standing Concertation Committee on 25 June 2008 included: Mutual Aid Fund The committee took note of the annual report for 2007 by the chairman of the Mutual Aid Fund and approved contributions to the Fund’s 2008 budget from the Management and the Staff Association. Results of 2008 MARS exercise and LHC achievement awards The committee took note of the Head of HR Department’s presentation of the results of the 2008 MARS exercise and the distribution of LHC achievement awards. It was noted that these awards would be granted with effect from 1 October 2008 (see Bulletin 18&19). The results show agreement with the 2008 MARS guidelines (see Bulletin 10&11) for the advancement ceilings per career path, the number of awards for extraordinary service, as well as the distribution of steps for the recognition of merit as shown in the SCC of 27 February (see Bulletin 14&15). Follow-up of Finance Committee and Council...

  15. STANDING CONCERTATION COMMITTEE ORDINARY MEETING ON 24 JANUARY 2001

    CERN Multimedia

    2001-01-01

    This meeting was mainly devoted to follow-up from the meetings of the Finance Committee and Council in December 2000, as well as to the work planning of the SCC for 2001. The newly-appointed Chairman of SCC, J. van der Boon, welcomed the Director-General and members to this first meeting of the new year, underlining his objective of maintaining a positive climate of concertation in the best interests of the Organization and its personnel. The President of the Staff Association declared that the latter would actively pursue its role in the same spirit. 1. Follow-up from the meetings of the Finance Committee and Council in December 2000 The Director-General, underlining the positive outcome of the 5-yearly review, conveyed his thanks to all parties that had taken part and, in particular, to the Staff Association for its constructive contribution to reach the compromise accepted by the three parties. After discussion of decisions on the package of measures approved by Council last December and on related impleme...

  16. STANDING CONCERTATION COMMITTEE ORDINARY MEETING ON 4 SEPTEMBER 2003

    CERN Multimedia

    2003-01-01

    This meeting was devoted to the main topics summarised below. 1. Information on the Organization's Human Resources Plan The SCC took note of the Chairman's presentation summarising the content of the HR Plan and the internal process that had been followed in drawing it up for approval by Council at the end of last year. The Staff Association expressed criticism concerning the lack of concertation in this process and, in particular, the Management's declared objective of achieving an overall 2:1 ratio of indefinite contracts to limited contracts of the staff by 2010, which it considers is not based on objective grounds. More importantly, the Staff Association criticised the fact that this ratio can only be arrived at under the assumption that no new project is initiated before 2010. The Management, recalling that planning issues are not in the remit of the SCC, underlined that this ratio concerning staff contracts is indeed the result of an analysis in the Divisions and, in any case, is considered as a guidel...

  17. Standing Concertation Committee - Ordinary Meeting on 30 September 2008

    CERN Multimedia

    HR Department

    2008-01-01

    The main items discussed at the meetings of the Standing Concertation Committee on 30 September 2008 included: Part-time work as a pre-retirement measure The Committee agreed to recommend the Director-General to extend the scheme of part-time work as a pre-retirement measure by one year, i.e. until 31 December 2009. Preparation of TREF on 7 October 2008 The Committee took note that the TREF agenda would cover: Annual salary adjustment; Voluntary programmes; Five-yearly review of financial & social conditions of members of the personnel; Update on 2005 review; Preparation for 2010 review; TREF workplan 2009; Update on CHIS actuarial study. The proposals and presentations which the Management planned to present to TREF were discussed and some clarifications were agreed. Follow-up of Finance Committee and Council The Committee took note of a report by the Chairman of points related to personnel matters discussed in those committees. He mentioned in particular the annu...

  18. Interrupting the Symphony: Unpacking the Importance Placed on Classical Concert Experiences

    Science.gov (United States)

    Hess, Juliet

    2018-01-01

    The Toronto Symphony Orchestra presents a series of youth concerts each year to introduce and attract younger audiences to the symphony. Music teachers often attend these concerts with students, and the importance of such experiences is frequently emphasised and normalised. This article explores the historical roots of the following relations,…

  19. Sound Design in Virtual Reality Concert Experiences using a Wave Field Synthesis Approach

    DEFF Research Database (Denmark)

    Lind, Rasmus Bloustrød; Milesen, Victor; Smed, Dina Madsen

    2017-01-01

    In this paper we propose an experiment that evaluates the influence of audience noise on the feeling of presence and the perceived quality in a virtual reality concert experience delivered using Wave Field Synthesis. A 360 degree video of a live rock concert from a local band was recorded. Single...

  20. Interplay of magnetism and superconductivity

    International Nuclear Information System (INIS)

    Akhavan, M.

    2006-01-01

    After about two decades of intense research since the discovery of high-temperature superconductivity (HTSC) in cuprates, although many aspects of the physics and chemistry of these cuprate superconductors are now well understood, the underlying pairing mechanism remains elusive. Magnetism and superconductivity are usually thought as incompatible, but in number of special materials including HTSCs these two mutually excluding mechanisms are found to coexist. The presence in a system of superconductivity and magnetism, gives rise to a large number of interesting phenomenon. This article provides perspective on recent developments and their implications for our understanding of the interplay between magnetism and superconductivity in new materials. (copyright 2006 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (Abstract Copyright [2006], Wiley Periodicals, Inc.)

  1. Substance use patterns and in-hospital care of adolescents and young adults attending music concerts.

    Science.gov (United States)

    Ruest, Stephanie M; Stephan, Alexander M; Masiakos, Peter T; Biddinger, Paul D; Camargo, Carlos A; Kharasch, Sigmund

    2018-01-09

    Few studies describe medical complaints and substance use patterns related to attending music concerts. As such, the objective of this study is to describe patient demographics, substance use and intoxication patterns, and medical interventions provided to adolescents and young adults assessed in an emergency department (ED) for complaints directly related to concert attendance. A retrospective chart review of patients 13-30 years old who were transported to the ED directly from music concerts between January 2011 and December 2015 was conducted. Descriptive statistics and logistic regression were used to analyze patient demographic, intervention, and substance use data. There were 115 concerts identified, of which 48 (42%) were linked to 142 relevant ED visits; the total number of attendees at each concert is unknown. The mean age of the 142 described patients was 19.5 years (SD 3.3) with 72% pop and electronic dance music concerts was associated with the widest ranges of GCS scores (8-15 and 6-14 respectively), mass casualty incident declarations, and among the highest mean blood alcohol levels (246 and 244 mg/dL, respectively). Substance use is the predominant reason for music concert related ED visits and patients may have serious levels of intoxication, receiving multiple medical interventions. These data demonstrate the need for additional large-scale studies to confirm trends and increase awareness of this important public health problem.

  2. [Public music concerts in a psychiatric hospital: effects on public opinion and as therapy for patients].

    Science.gov (United States)

    Takasaka, Y; Yokota, O; Tanioka, T; Nagata, K; Yasuoka, K; Toda, H

    2001-01-01

    We investigate the effects of music therapy concerts, which were held 60 times over a four year period, 1992 to 1996, in Geiyo Psychiatric Hospital, Kochi Prefecture and found that; 1) Musicians who performed at the concerts were not only from Kochi prefecture but also from other prefectures (10 times) and from four foreign countries (7 times). 2) Live concerts in a small hall had a positive influence on patients and drew the patient's attention and interest away from their hallucinations and delusions to the real world. Moreover, the concerts provided the patients with chances to acquire social graces such as being well-groomed. 3) Explanations by the musicians, interviews with the musicians and the seasonal choruses accompanied by the musicians were helpful to give the patients motives for recovering communication skills and to interact with society. 4) Inquiries to the patients about the concerts indicated discrepancies between the poor observed estimations during the concerts (83.3%) and the good subjective impressions expressed by the patients (82.0%), suggesting that the patients were not good at expressing their internal emotions through facial expressions or attitudes. 5) Many citizens including children came to the concerts and/or gave aid to the hospital because the concerts were open to the public and we suggest that this contributed to improving the general publics' image of psychiatric hospitals. Questionnaires revealed that 90% of people in a control group had a bad image of psychiatric hospitals in Japan, but only 32% of the members of the general public who attended our concerts had a bad image of psychiatric hospitals. In addition, the revolving ratio of the hospital beds rose from 0.4 to 1.2 over the four years, which also suggests a beneficial effect on the patients.

  3. Women's Month 2006 to include a tribute concert to women composers

    OpenAIRE

    Lazenby, Jenna

    2006-01-01

    Virginia Tech will commemorate Women's Month 2006 in March with a variety of events and programs. Festivities will include a special concert to be held Wednesday, March 1 at 8 p.m. in the Squires Student Center Recital Salon. This concert will pay tribute to 400 years of women composers by featuring performances by Virginia Tech faculty, students, and guests. Admission to the concert is free, though a free-will donation will be taken to support the work of the Women's Resource Center of the N...

  4. Nuclear technology and human civilization in interplay

    International Nuclear Information System (INIS)

    Broda, E.

    1979-01-01

    This lecture was held by E. Broda during a series of lectures “Wiener Internationale Hochschulkurse”, organized by the University of Vienna in 1979. The lecture is about nuclear technology and human civilization in interplay. (nowak)

  5. The interplay of theory and experiment

    International Nuclear Information System (INIS)

    Jacob, M.

    1987-01-01

    The author reviews the interplay between theory and experiment in the development of the physics of elementary particles and gives an outlook on the possibilities of the new accelerators to study the yet unexplained phenomena of particle physics. (HSI).

  6. Interplay between tilted and principal axis rotation

    International Nuclear Information System (INIS)

    Datta, Pradip; Roy, Santosh; Chattopadhyay, S.

    2014-01-01

    At IUAC-INGA, our group has studied four neutron rich nuclei of mass-110 region, namely 109,110 Ag and 108,110 Cd. These nuclei provide the unique platform to study the interplay between Tilted and Principal axis rotation since these are moderately deformed and at the same time, shears structures are present at higher spins. The salient features of the high spin behaviors of these nuclei will be discussed which are the signatures of this interplay

  7. Interplay between tilted and principal axis rotation

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Pradip [Ananda Mohan College, 102/1 Raja Rammohan Sarani, Kolkata 700 009 (India); Roy, Santosh; Chattopadhyay, S. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700 064 (India)

    2014-08-14

    At IUAC-INGA, our group has studied four neutron rich nuclei of mass-110 region, namely {sup 109,110}Ag and {sup 108,110}Cd. These nuclei provide the unique platform to study the interplay between Tilted and Principal axis rotation since these are moderately deformed and at the same time, shears structures are present at higher spins. The salient features of the high spin behaviors of these nuclei will be discussed which are the signatures of this interplay.

  8. Thymidine kinases in archaea

    DEFF Research Database (Denmark)

    Clausen, A.R.; Matakos, A.; Sandrini, Michael

    2006-01-01

    Twenty-six fully sequenced archaeal genomes were searched for genes coding for putative deoxyribonucleoside kinases (dNKs). We identified only 5 human-like thymidine kinase 1 genes (TK1s) and none for non-TK1 kinases. Four TK1s were identified in the Euryarchaea and one was found in the Crenarcha...

  9. Motion induced interplay effects for VMAT radiotherapy.

    Science.gov (United States)

    Edvardsson, Anneli; Nordström, Fredrik; Ceberg, Crister; Ceberg, Sofie

    2018-04-19

    The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin 6 breathing motion in the superior-inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD 98% and ΔD 2% ) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD 98% and maximum ΔD 2% being  -16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was

  10. Motion induced interplay effects for VMAT radiotherapy

    Science.gov (United States)

    Edvardsson, Anneli; Nordström, Fredrik; Ceberg, Crister; Ceberg, Sofie

    2018-04-01

    The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin6 breathing motion in the superior–inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD98% and ΔD2%) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD98% and maximum ΔD2% being  ‑16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was

  11. Consumers’ Attitude to the Protest Against Lady Gaga’s Concert: An Exploratory Study

    Directory of Open Access Journals (Sweden)

    Kresno Agus Hendarto

    2013-12-01

    Full Text Available Lady gaga is an American singer who has won 5 Grammy Awards. In the middle of 2012, she was requested to have concert in Jakarta with the contract value of tens billion. The concert was protested by a number of groups. The promoter had approached the pressure groups and negotiated the dressing. However, Lady Gaga’s management canceled the concert for security consideration. The objectives of the study are: (1 to explore consumers’ attitude to the protest for the cancelation of Lady Gaga’s concert; and (2 using classical conditioning and expectancy-value theory, to explain consumers’ attitude to the protest. The study used focus group to collect data. The collected data was then transcribed and analyzed by content analysis. The results show that informants’ opinions can be classified into two groups: agreement and disagreement with the protest for the cancelation of Lady Gaga’s concert. Informants either agree or disagree for some reasons. Classical conditioning theory can explain either consumer’s attitude. The difference is the object of consumers’ attitude who agreed was Lady Gaga herself, while the object of disagreement was the pressure group that sponsored the protest. The attitude of the disagreement can also be explained by expectancy-value theory.

  12. Exploring the impact of music concerts in promoting well-being in dementia care.

    Science.gov (United States)

    Shibazaki, Kagari; Marshall, Nigel A

    2017-05-01

    This study explores the specific effects of live music concerts on the clients with dementia, their families and nursing staff/caregivers. Researchers attended 22 concerts in care facilities in England and Japan. Interviews were carried out with clients with dementia, nursing staff and family members. Observations were also carried out before, during and after the concerts. All observations were recorded in field notes. The effect of the concerts in both countries was seen to be beneficial to all clients and nursing staff, whether or not they attended the concert. Interviews with clients with mild to mid-stage dementia noted increased levels of cooperation, interaction and conversation. Those with more advanced forms of dementia exhibited decreased levels of agitation and anti-social behaviour. Staff members reported increased levels of care, cooperation and opportunities for assessment. Family members noted an increase in the levels of well-being in their partner/parent as well as in themselves. The study also suggested that the knowledge of musical components, an awareness of the rules of music and specific musical preferences appear to remain well beyond the time when other cognitive skills and abilities have disappeared. This initial study provided some further indication in terms of the uses of music as a non-pharmacological intervention for those living with all stages of dementia. These included opportunities for assessment of physical abilities as well as facilitating an increasing level of care.

  13. Peroxisome-mitochondria interplay and disease.

    Science.gov (United States)

    Schrader, Michael; Costello, Joseph; Godinho, Luis F; Islinger, Markus

    2015-07-01

    Peroxisomes and mitochondria are ubiquitous, highly dynamic organelles with an oxidative type of metabolism in eukaryotic cells. Over the years, substantial evidence has been provided that peroxisomes and mitochondria exhibit a close functional interplay which impacts on human health and development. The so-called "peroxisome-mitochondria connection" includes metabolic cooperation in the degradation of fatty acids, a redox-sensitive relationship, an overlap in key components of the membrane fission machineries and cooperation in anti-viral signalling and defence. Furthermore, combined peroxisome-mitochondria disorders with defects in organelle division have been revealed. In this review, we present the latest progress in the emerging field of peroxisomal and mitochondrial interplay in mammals with a particular emphasis on cooperative fatty acid β-oxidation, redox interplay, organelle dynamics, cooperation in anti-viral signalling and the resulting implications for disease.

  14. Between Two Worlds: Concert-giving and Rioting in the Post-Yugoslav Area

    Directory of Open Access Journals (Sweden)

    Ana Petrov

    2015-04-01

    Full Text Available Starting in the late 1990s, some musicians from the territory of former Yugoslavia gradually embarked on the project of giving concerts in Belgrade, the capital of the former country. Others refused to perform in Serbia after the wars, which fuelled a negative attitude toward these musicians. In this paper I deal with the reception of those concerts, pointing to the ways they have become specific affective sites of memory. I focus on two major issues: the discourse produced in the concerts by the performers themselves and members of the audience and the discourse produced by various protest groups (which resulted in the organization of protests in Belgrade against performances by musicians who ‘hate Serbs’.

  15. Christian rock concerts as a meeting between religion and popular culture

    Directory of Open Access Journals (Sweden)

    Andreas Häger

    2003-01-01

    Full Text Available Different forms of artistic expression play a vital role in religious practices of the most diverse traditions. One very important such expression is music. This paper deals with a contemporary form of religious music, Christian rock. Rock or popular music has been used within Christianity as a means for evangelization and worship since the end of the 1960s. The genre of "contemporary Christian music", or Christian rock, stands by definition with one foot in established institutional (in practicality often evangelical Christianity, and the other in the commercial rock musicindustry. The subject of this paper is to study how this intermediate position is manifested and negotiated in Christian rock concerts. Such a performance of Christian rock music is here assumed to be both a rock concert and a religious service. The paper will examine how this duality is expressed in practices at Christian rock concerts.

  16. Interplay of viruses and radiation in carcinogenesis

    International Nuclear Information System (INIS)

    Upton, A.C.

    1975-01-01

    The discovery by Gross and by Lieberman and Kaplan that leukemias induced by irradiation in mice may be transmissible by cell-free filtrates pointed to the existence of an interplay between the effects of radiation and those of an otherwise latent oncogenic virus, which has since been the subject of intensive study. In the years intervening since these pioneer observations, efforts have been made to elucidate the nature and mechanisms of the interplay and to determine whether other neoplasms also may be elicited by an interaction between virus and radiation. The results of these efforts, although still highly preliminary, are surveyed in the light of recent advances in viral oncology

  17. Detecting regular sound changes in linguistics as events of concerted evolution.

    Science.gov (United States)

    Hruschka, Daniel J; Branford, Simon; Smith, Eric D; Wilkins, Jon; Meade, Andrew; Pagel, Mark; Bhattacharya, Tanmoy

    2015-01-05

    Concerted evolution is normally used to describe parallel changes at different sites in a genome, but it is also observed in languages where a specific phoneme changes to the same other phoneme in many words in the lexicon—a phenomenon known as regular sound change. We develop a general statistical model that can detect concerted changes in aligned sequence data and apply it to study regular sound changes in the Turkic language family. Linguistic evolution, unlike the genetic substitutional process, is dominated by events of concerted evolutionary change. Our model identified more than 70 historical events of regular sound change that occurred throughout the evolution of the Turkic language family, while simultaneously inferring a dated phylogenetic tree. Including regular sound changes yielded an approximately 4-fold improvement in the characterization of linguistic change over a simpler model of sporadic change, improved phylogenetic inference, and returned more reliable and plausible dates for events on the phylogenies. The historical timings of the concerted changes closely follow a Poisson process model, and the sound transition networks derived from our model mirror linguistic expectations. We demonstrate that a model with no prior knowledge of complex concerted or regular changes can nevertheless infer the historical timings and genealogical placements of events of concerted change from the signals left in contemporary data. Our model can be applied wherever discrete elements—such as genes, words, cultural trends, technologies, or morphological traits—can change in parallel within an organism or other evolving group. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. “The Concert of Europe” In 20th Century British and American Historiography

    Directory of Open Access Journals (Sweden)

    Ekaterina V. Romanova

    2016-01-01

    Full Text Available The article provides a critical analysis of the interpretations of the Concert of Europe by British and American historians of the XXth century. The interest in the study of this phenomenon is rooted in its relation to the problems of the maintenance of international order and stability. It is not only academic, being partly determined by the fact that throughout the XX century first Britain and then the USA was at the top of the world hierarchy, and accordingly played a leading role in the construction and maintenance of the European order. Current international environment, the experience of the two World Wars of the XXth century determined the angle from which the phenomenon of the Concert of Europe was studied. Whereas in the second half of the 1910s - early 1920s historians pointed to the deficiencies of the international system of the preceding century (and in particular, the institution of the Concert of Europe, the students of the Vienna system working after the Second World War regarded the period of 1815-1914 as relatively stable, compared to the short interwar interlude. The Concert of Europe was named as one of the factors contributing to stability and peace. Certain logic can be discerned in the development of the historiography of the problem, which to some degree reflected the evolution of ideas about international relations management. At the same time, the differences in the interpretations of the Concert of Europe derive from the fact that this very concept in the XIXth century was not fixed and static. Great Powers' readiness to cooperation did not mean that there were no conflicts of interests. They struggled for leadership within the Concert and sought to impart to it their own interpretation.

  19. Music Genre as a Predictor of Resource Utilization at Outdoor Music Concerts.

    Science.gov (United States)

    Westrol, Michael S; Koneru, Susmith; McIntyre, Norah; Caruso, Andrew T; Arshad, Faizan H; Merlin, Mark A

    2017-06-01

    The aim of this study was to examine the various modern music genres and their effect on the utilization of medical resources with analysis and adjustment for potential confounders. A retrospective review of patient logs from an open-air, contemporary amphitheater over a period of 10 years was performed. Variables recorded by the medical personnel for each concert included the attendance, description of the weather, and a patient log in which nature and outcome were recorded. The primary outcomes were associations of genres with the medical usage rate (MUR). Secondary outcomes investigated were the association of confounders and the influences on the level of care provided, the transport rate, and the nature of medical complaint. A total of 2,399,864 concert attendees, of which 4,546 patients presented to venue Emergency Medical Services (EMS) during 403 concerts with an average of 11.4 patients (annual range 7.1-17.4) each concert. Of potential confounders, only the heat index ≥90°F (32.2°C) and whether the event was a festival were significant (P=.027 and .001, respectively). After adjustment, the genres with significantly increased MUR in decreasing order were: alternative rock, hip-hop/rap, modern rock, heavy metal/hard rock, and country music (Pmusic (P=.033). Alternative rock, hip-hop/rap, modern rock, heavy metal/hard rock, and country music concerts had higher levels of medical resource utilization. High heat indices and music festivals also increase the MUR. This information can assist event planners with preparation and resource utilization. Future research should focus on prospective validation of the regression equation. Westrol MS , Koneru S , McIntyre N , Caruso AT , Arshad FH , Merlin MA . Music genre as a predictor of resource utilization at outdoor music concerts. Prehosp Disaster Med. 2017;32(3):289-296.

  20. Trends in preference, programming and design of concert halls for symphonic music

    DEFF Research Database (Denmark)

    Gade, Anders Christian

    2008-01-01

    This paper discusses the evolution in taste regarding concert hall acoustics and how this can be reflected in the new halls being built today. The clients' and listener's preferences are not only based on listening in existing halls; but also on listening to reproduced music recorded with microph......This paper discusses the evolution in taste regarding concert hall acoustics and how this can be reflected in the new halls being built today. The clients' and listener's preferences are not only based on listening in existing halls; but also on listening to reproduced music recorded...

  1. The impact of local government cultural policies on the sales of tickets for private music concerts in Japan

    OpenAIRE

    谷口, みゆき

    2014-01-01

    This paper attempts to examine the effect of public cultural policy on the sales of tickets for private music concerts in Japan. In particular, it focuses on how the introduction of the Designated Manager System (DMS) in 2006 influenced the sales of tickets for private music concerts. The hypothesis that both local governments' cultural investments and the DMS have increased the sales of tickets for private music concerts is examined. Data from the Private Music Live Entertainment 2000-2008 i...

  2. Concerted action on the retrievability of long lived radioactive waste in deep underground repositories - progress to date

    International Nuclear Information System (INIS)

    Dodd, D.H.

    2000-01-01

    Within the EURATOM Framework Programme: Nuclear Fission Safety, a Concerted Action on the retrievability of long lived radioactive waste in deep underground repositories is being carried out. This Concerted Action commenced on the 1st of January 1998 and involves experts from nine different European countries. The Concerted Action will be completed by the 31st of December 1999. This paper gives a brief overview of the objectives of the Concerted Action, the work programme that has been defined to meet these objectives, the work performed to date, and the remaining work programme. (author)

  3. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  4. A tablet app to enrich the live and post-live experience of classical concerts

    NARCIS (Netherlands)

    Melenhorst, M.S.; Van der Sterren, R.; Arzt, A.; Martorell, A.; Liem, C.C.S.

    2015-01-01

    This demonstration paper describes a tablet application that is developed to make classical concerts more accessible and more enjoyable for a broader audience. The app offers interactive visualizations of a symphony’s instrumentation and its score. It also offers timed background information about

  5. Unequal Academic Achievement in High School: The Mediating Roles of Concerted Cultivation and Close Friends

    Science.gov (United States)

    Carolan, Brian V.

    2016-01-01

    Building from the classic Wisconsin model of status attainment, this study examines whether a specific style of parenting, concerted cultivation, and a close friend's school-related attitudes and behaviors mediate the relationship between a family's socioeconomic status and their child's academic achievement in the United States. Using a recursive…

  6. Density functional theory study of the concerted pyrolysis mechanism for lignin models

    Science.gov (United States)

    Thomas Elder; Ariana Beste

    2014-01-01

    ABSTRACT: Studies on the pyrolysis mechanisms of lignin model compounds have largely focused on initial homolytic cleavage reactions. It has been noted, however, that concerted mechanisms may also account for observed product formation. In the current work, the latter processes are examined and compared to the former, by the application of density functional theory...

  7. Stepwise or concerted? DFT study on the mechanism of ionic Diels-Alder reaction of chromanes

    Directory of Open Access Journals (Sweden)

    Haghdadi Mina

    2016-01-01

    Full Text Available The stepwise and concerted Ionic Diels-Alder reaction between phenyl (pyridin-2-ylmethylene oxonium and styrene derivatives are explored using theoretical method. The results support using computational method via persistent intermediates. The DFT method was essential to reproduce a reasonable potential energy surface for these challenging systems.

  8. The virtual reconstruction of the ancient Roman concert hall in Aphrodisias, Turkey

    DEFF Research Database (Denmark)

    Rindel, Jens Holger; Gade, Anders Christian; Nielsen, Martin Lisa

    2006-01-01

    About two thousand years ago one of the world’s earliest and most beautiful concert halls were built in the city Aphrodisias, named after the goddess Aphrodite. It was a rich society, renowned for its marble and mastery in sculptures. Like many other cities in the Roman Empire there was an open...

  9. Statistical relations among architectural features and objective acoustical measurements of concert halls

    DEFF Research Database (Denmark)

    Gade, Anders Christian; Siebein, G. W.; Chiang, W.

    1993-01-01

    as for entire rooms. Measurements data from all three teams were used in the models to assess the sensitivity of the models to expect variations in measurements. The results were compared to the previous work of Barron, Gade, and Hook among others. [Work supported by the National Science Foundation and Concert...

  10. Design of concert hall in uremia based on notification to hidden role ...

    African Journals Online (AJOL)

    The growth of sound in a concert hall is reviewed with emphasis on hearing the direct sound clearly. Architecture in its daily means provides renewed space and is replaced within a larger space and people are moving in it and in it's around. Music is purely mechanical conception, organized and deliberate scattering of ...

  11. An adaptive, data driven sound field control strategy for outdoor concerts

    DEFF Research Database (Denmark)

    Heuchel, Franz Maria; Caviedes Nozal, Diego; Brunskog, Jonas

    2017-01-01

    One challenge of outdoor concerts is to ensure adequate levels for the audience while avoiding disturbance of the surroundings. We outline the initial concept of a sound field control (SFC) system for tackling this issue using sound-zoning. The system uses Bayesian inference to update a sound...

  12. Tightening the Iron Cage: Concertive Control in Self-Managing Teams.

    Science.gov (United States)

    Barker, James R.

    1993-01-01

    Describes how an (industrial) organization's control system evolved in response to a managerial change from hierarchical, bureaucratic control to concertive control via self-management teams. The organization's members developed a system of value-based normative rules that controlled their actions more powerfully and completely than did the former…

  13. A new concert hall for the city of Eindhoven : design and model tests

    NARCIS (Netherlands)

    Braat-Eggen, P.E.; van Luxemburg, Renz; Booy, L.G.; de Lange, P.A.

    1993-01-01

    A music centre containing a large (1300 seats) and a small (400 seats) concert hall has been built in the city of Eindhoven. The music centre is integrated into a larger building complex, called the ‘Heuvel-Galerie’, with shopping area (malls), recreational facilities, parking, offices and

  14. CONCERT. ''European joint programme for the integration of radiation protection research''; CONCERT. Gemeinsame Europaeische Forschungsfoerderung

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt-Hannig, A.; Birschwilks, M.; Jung, T. [Bundesamt fuer Strahlenschutz (Germany)

    2016-07-01

    CONCERT is a joint project of the EU and its member states which assume joint financing: Over the next five years the largest European radiation protection programme so far will have available about 28 Million Euros for research and integrative measures, whereby the European Commission will bear 70 per cent of the costs. Integrative measures include, among others, targeted vocational education and training of junior researchers in radiation protection, better access to research and irradiation facilities for scientists, as well as a stronger connection of universities and research centres in radiation protection research.

  15. Interactive painting. An evolving study to facilitate reduced exclusion from classical music concerts for the deaf community

    DEFF Research Database (Denmark)

    Brooks, Tony

    2005-01-01

    Exclusion from the joy of experiencing music, especially in concert venues, is especially applicable to those with an auditory impairment. There have been limited investigations into how to reduce the exclusion for this community in attending classical orchestra music concerts. Through utilizing ...

  16. Concert Club

    CERN Document Server

    Concert Club

    2010-01-01

    CERN MEYRIN (terminus bus 56-CERN) entrée B - bâtiment 500 - amphithéâtre Mardi 9 Février 2010 à 20 h 30 ”La fontaine aux larmes” Les pays de l’est et le choeur féminin Ensemble vocal féminin Polhymnia Célia Perrard, harpe Camille Girod, flûte Christophe Sturzenegger, piano Quartet Elixir Eléonore Giroud, violon Delphine Touzery, violon Priscille Oehninger, alto Elsa Dorbath, violoncelle Direction : Franck Marcon Au programme : Kodaly – Bartok – Donceanu - Janacek Francesco Hoch (création) ...

  17. Concerts & Opera

    Index Scriptorium Estoniae

    2006-01-01

    Arvo Pärdi teos "Cantus in memoriam Benjamin Britten" esitusel 2. dets. Aldeburghis, Pärdi "Annum per annum" 7. dets. Birminghamis, Kristjan Järvi dirigeerimas 7. dets. Liverpoolis, Neeme Järvi diregeerimas 15. dets. Edinburghis ja 16. dets. Glasgowis

  18. Concerts & Opera

    Index Scriptorium Estoniae

    2006-01-01

    Kammerorkestri Kremerata Baltica kontserdid: 19. apr. Londonis LSO St Lukesis, 21. apr. Oxfordis Sheldonian Theatre'is, 17. apr. Aldeburghis, 20. apr. Manchesteris Bridgewater Hallis, 23. apr. Wales Millennium Centre'is, 22. apr. Edinburghis Usher Hallis

  19. Concert club

    CERN Multimedia

    Concert club

    2010-01-01

    CERN MEYRIN (terminus bus 56-CERN) entrée B - bâtiment 500 - amphithéâtre mardi 23 mars 2010 à 20 h 30 Eric Schmid, clarinette Muriel Slatkine, piano Au programme : Danzi, Delibes, Gounod, Lovreglio (Verdi), Poulenc, Rossini, Schubert * * * * * samedi 27 mars 2010 à 20 h 30 « Quart de ton » Orchestre et solistes Au programme : Leung Xiao, Lan www.myspace.com/lecardethon * * * * * Dimanche 28 mars 2010 à 17 h 00 et 19 h 00 Rachel Kolly d’Alba, violon Au programme : Bach, Ysaïe * * * * * mardi 30 mars 2010 à 20 h 30 ...

  20. Concert club

    CERN Multimedia

    2010-01-01

    CERN MEYRIN (terminus bus 56-CERN) entrée B - bâtiment 500 - amphithéâtre mardi 9 mars 2010 à 20 h 30 Le trio «Impressions» avec Liliane Jaques, flûte traversière Isabelle Martin-Achard, harpe John Devore, violoncelle Au programme : Bolling, Dewey, Ibert, Vellon, Vellones, Molnar, Andres * * * * * mardi 16 mars 2010 à 20 h 30 Irina Chkourindina, piano Au programme : Chopin, Liszt, Schumann * * * * * vendredi 19 mars 2010 à 20 h 30 Pascal Salomon, piano Au programme : J. Brahms, F.Chopin, M. Ravel, S. Rachmaninoff * * * * * ...

  1. Concerts & Opera

    Index Scriptorium Estoniae

    2007-01-01

    Arvo Pärdi muusika esitusel 4. mail Londonis St Giles Cripplegate'is, 14. mail Queen Elizabeth Hallis, 3. mail Oxfordis; Eesti Filharmoonia Kammerkoor esitab Cyrillus Kreegi "Requiemi" 11. mail Manchesteris Bridgewater Hallis; Olari Elts dirigeerimas 10. mail Edinburghis Usher Hallis, 11. mail Glasgowis ja 12. mail Aberdeenis

  2. The multifaceted interplay between lipids and epigenetics.

    Science.gov (United States)

    Dekkers, Koen F; Slagboom, P Eline; Jukema, J Wouter; Heijmans, Bastiaan T

    2016-06-01

    The interplay between lipids and epigenetic mechanisms has recently gained increased interest because of its relevance for common diseases and most notably atherosclerosis. This review discusses recent advances in unravelling this interplay with a particular focus on promising approaches and methods that will be able to establish causal relationships. Complementary approaches uncovered close links between circulating lipids and epigenetic mechanisms at multiple levels. A characterization of lipid-associated genetic variants suggests that these variants exert their influence on lipid levels through epigenetic changes in the liver. Moreover, exposure of monocytes to lipids persistently alters their epigenetic makeup resulting in more proinflammatory cells. Hence, epigenetic changes can both impact on and be induced by lipids. It is the combined application of technological advances to probe epigenetic modifications at a genome-wide scale and methodological advances aimed at causal inference (including Mendelian randomization and integrative genomics) that will elucidate the interplay between circulating lipids and epigenetics. Understanding its role in the development of atherosclerosis holds the promise of identifying a new category of therapeutic targets, since epigenetic changes are amenable to reversal.

  3. Gene-Environment Interplay in Twin Models

    Science.gov (United States)

    Hatemi, Peter K.

    2013-01-01

    In this article, we respond to Shultziner’s critique that argues that identical twins are more alike not because of genetic similarity, but because they select into more similar environments and respond to stimuli in comparable ways, and that these effects bias twin model estimates to such an extent that they are invalid. The essay further argues that the theory and methods that undergird twin models, as well as the empirical studies which rely upon them, are unaware of these potential biases. We correct this and other misunderstandings in the essay and find that gene-environment (GE) interplay is a well-articulated concept in behavior genetics and political science, operationalized as gene-environment correlation and gene-environment interaction. Both are incorporated into interpretations of the classical twin design (CTD) and estimated in numerous empirical studies through extensions of the CTD. We then conduct simulations to quantify the influence of GE interplay on estimates from the CTD. Due to the criticism’s mischaracterization of the CTD and GE interplay, combined with the absence of any empirical evidence to counter what is presented in the extant literature and this article, we conclude that the critique does not enhance our understanding of the processes that drive political traits, genetic or otherwise. PMID:24808718

  4. Pyruvate kinase blood test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003357.htm Pyruvate kinase blood test To use the sharing features on this page, ... energy when oxygen levels are low. How the Test is Performed A blood sample is needed. In the laboratory, white blood ...

  5. Concert | The CERN Choir hits the high notes | Victoria Hall | 30 September

    CERN Multimedia

    2014-01-01

    60 – 40 – 25: a series of numbers that have inspired an exceptional concert. They refer to the 60th anniversary of CERN, the 40th anniversary of the CERN Choir and the 25th anniversary of its direction by Gonzalo Martinez. On the occasion of this collision of anniversaries, the Committee of this CERN club decided to organise an appropriately significant event to celebrate the important worldwide role that CERN has played for 60 years, the fact that the CERN Choir has brought together amateur singers for 40 years, and finally the decisive role in the Choir’s history of its director, Gonzalo Martinez.   The work chosen for this concert also had to be something exceptional. A work which, through its monumental status, its brilliance, its innovation, its originality and its energy, symbolises CERN’s scientific discoveries, reflects the genius of its creator and represents the highest creative ambitions: Beethoven’s Missa Solemnis.  Perfor...

  6. Concert | The CERN Choir hits the high notes | Victoria Hall | 30 September

    CERN Document Server

    2014-01-01

    60 – 40 – 25: a series of numbers that have inspired an exceptional concert. They refer to the 60th anniversary of CERN, the 40th anniversary of the CERN Choir and the 25th anniversary of its direction by Gonzalo Martinez. On the occasion of this collision of anniversaries, the Committee of this CERN club decided to organise an appropriately significant event to celebrate the important worldwide role that CERN has played for 60 years, the fact that the CERN Choir has brought together amateur singers for 40 years, and finally the decisive role in the Choir’s history of its director, Gonzalo Martinez.   The work chosen for this concert also had to be something exceptional. A work which, through its monumental status, its brilliance, its innovation, its originality and its energy, symbolises CERN’s scientific discoveries, reflects the genius of its creator and represents the highest creative ambitions: Beethoven’s Missa Solemnis.  Perfo...

  7. An Interactive Concert Program Based on Infrared Watermark and Audio Synthesis

    Science.gov (United States)

    Wang, Hsi-Chun; Lee, Wen-Pin Hope; Liang, Feng-Ju

    The objective of this research is to propose a video/audio system which allows the user to listen the typical music notes in the concert program under infrared detection. The system synthesizes audio with different pitches and tempi in accordance with the encoded data in a 2-D barcode embedded in the infrared watermark. The digital halftoning technique has been used to fabricate the infrared watermark composed of halftone dots by both amplitude modulation (AM) and frequency modulation (FM). The results show that this interactive system successfully recognizes the barcode and synthesizes audio under infrared detection of a concert program which is also valid for human observation of the contents. This interactive video/audio system has greatly expanded the capability of the printout paper to audio display and also has many potential value-added applications.

  8. Measured Early Lateral Energy Fractions in Concert Halls and Opera Houses

    Science.gov (United States)

    BARRON, M.

    2000-04-01

    In the 30 years since early lateral reflections were first suggested as important for concert halls, spatial impression and source broadening have become almost universally accepted as essential characteristics of halls with good acoustics. Two objective measures of source broadening have been proposed. Measured values of the best defined of these measures, the early lateral energy fraction (LF), are considered here. Results from two independent measurement surveys are discussed. Comparisons of LF values by hall show a significant link between hall mean LF and hall width. There is however considerable overlap between measured LF values in different halls so the relevance of describing halls by their mean early lateral energy fraction values is questionable. The behaviour of LF values within auditoria is discussed for different concert hall plan forms and within opera houses. A measure of source broadening including sound level is proposed and results considered in the context of auditorium design.

  9. The Concert system - Compiler and runtime technology for efficient concurrent object-oriented programming

    Science.gov (United States)

    Chien, Andrew A.; Karamcheti, Vijay; Plevyak, John; Sahrawat, Deepak

    1993-01-01

    Concurrent object-oriented languages, particularly fine-grained approaches, reduce the difficulty of large scale concurrent programming by providing modularity through encapsulation while exposing large degrees of concurrency. Despite these programmability advantages, such languages have historically suffered from poor efficiency. This paper describes the Concert project whose goal is to develop portable, efficient implementations of fine-grained concurrent object-oriented languages. Our approach incorporates aggressive program analysis and program transformation with careful information management at every stage from the compiler to the runtime system. The paper discusses the basic elements of the Concert approach along with a description of the potential payoffs. Initial performance results and specific plans for system development are also detailed.

  10. Optimal Volume for Concert Halls Based on Ando’s Subjective Preference and Barron Revised Theories

    Directory of Open Access Journals (Sweden)

    Salvador Cerdá

    2014-03-01

    Full Text Available The Ando-Beranek’s model, a linear version of Ando’s subjective preference theory, obtained by the authors in a recent work, was combined with Barron revised theory. An optimal volume region for each reverberation time was obtained for classical music in symphony orchestra concert halls. The obtained relation was tested with good agreement with the top rated halls reported by Beranek and other halls with reported anomalies.

  11. Ethanol dehydration in HZSM-5 studied by density functional theory: evidence for a concerted process.

    Science.gov (United States)

    Kim, Seonah; Robichaud, David J; Beckham, Gregg T; Paton, Robert S; Nimlos, Mark R

    2015-04-16

    Dehydration over acidic zeolites is an important reaction class for the upgrading of biomass pyrolysis vapors to hydrocarbon fuels or to precursors for myriad chemical products. Here, we examine the dehydration of ethanol at a Brønsted acid site, T12, found in HZSM-5 using density functional theory (DFT). The geometries of both cluster and mixed quantum mechanics/molecular mechanics (QM:MM) models are prepared from the ZSM-5 crystal structure. Comparisons between these models and different DFT methods are conducted to show similar results among the models and methods used. Inclusion of the full catalyst cavity through a QM:MM approach is found to be important, since activation barriers are computed on average as 7 kcal mol(-1) lower than those obtained with a smaller cluster model. Two different pathways, concerted and stepwise, have been considered when examining dehydration and deprotonation steps. The current study shows that a concerted dehydration process is possible with a lower (4-5 kcal mol(-1)) activation barrier while previous literature studies have focused on a stepwise mechanism. Overall, this work demonstrates that fairly high activation energies (∼50 kcal mol(-1)) are required for ethanol dehydration. A concerted mechanism is favored over a stepwise mechanism because charge separation in the transition state is minimized. QM:MM approaches appear to provide superior results to cluster calculations due to a more accurate representation of charges on framework oxygen atoms.

  12. DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis.

    Science.gov (United States)

    Enriquez-Rios, Vanessa; Dumitrache, Lavinia C; Downing, Susanna M; Li, Yang; Brown, Eric J; Russell, Helen R; McKinnon, Peter J

    2017-01-25

    The DNA damage response (DDR) orchestrates a network of cellular processes that integrates cell-cycle control and DNA repair or apoptosis, which serves to maintain genome stability. DNA-PKcs (the catalytic subunit of the DNA-dependent kinase, encoded by PRKDC), ATM (ataxia telangiectasia, mutated), and ATR (ATM and Rad3-related) are related PI3K-like protein kinases and central regulators of the DDR. Defects in these kinases have been linked to neurodegenerative or neurodevelopmental syndromes. In all cases, the key neuroprotective function of these kinases is uncertain. It also remains unclear how interactions between the three DNA damage-responsive kinases coordinate genome stability, particularly in a physiological context. Here, we used a genetic approach to identify the neural function of DNA-PKcs and the interplay between ATM and ATR during neurogenesis. We found that DNA-PKcs loss in the mouse sensitized neuronal progenitors to apoptosis after ionizing radiation because of excessive DNA damage. DNA-PKcs was also required to prevent endogenous DNA damage accumulation throughout the adult brain. In contrast, ATR coordinated the DDR during neurogenesis to direct apoptosis in cycling neural progenitors, whereas ATM regulated apoptosis in both proliferative and noncycling cells. We also found that ATR controls a DNA damage-induced G 2 /M checkpoint in cortical progenitors, independent of ATM and DNA-PKcs. These nonoverlapping roles were further confirmed via sustained murine embryonic or cortical development after all three kinases were simultaneously inactivated. Thus, our results illustrate how DNA-PKcs, ATM, and ATR have unique and essential roles during the DDR, collectively ensuring comprehensive genome maintenance in the nervous system. The DNA damage response (DDR) is essential for prevention of a broad spectrum of different human neurologic diseases. However, a detailed understanding of the DDR at a physiological level is lacking. In contrast to many in

  13. DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase

    Czech Academy of Sciences Publication Activity Database

    Bražina, Jan; Švadlenka, Jan; Macůrek, Libor; Anděra, Ladislav; Hodný, Zdeněk; Bartek, Jiří; Hanzlíková, Hana

    2015-01-01

    Roč. 14, č. 3 (2015), s. 375-387 ISSN 1538-4101 R&D Projects: GA ČR GPP305/11/P683 Institutional support: RVO:68378050 Keywords : ATM * DAXX * DNA damage * p53 * Wip1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.952, year: 2015

  14. The interplay between a Phytophthora RXLR effector and an Arabidopsis lectin receptor kinase

    NARCIS (Netherlands)

    Bouwmeester, K.

    2010-01-01

    Phytophthora infestans – the causal agent of potato late blight – secretes a plethora of effector proteins to facilitate plant infection. The central subject of this thesis is ipiO, one of the first cloned Phytophthora genes with a putative function in pathogenicity as was anticipated based on its

  15. Phosphorylation of the Yeast Choline Kinase by Protein Kinase C

    Science.gov (United States)

    Choi, Mal-Gi; Kurnov, Vladlen; Kersting, Michael C.; Sreenivas, Avula; Carman, George M.

    2005-01-01

    The Saccharomyces cerevisiae CKI1-encoded choline kinase catalyzes the committed step in phosphatidylcholine synthesis via the Kennedy pathway. The enzyme is phosphorylated on multiple serine residues, and some of this phosphorylation is mediated by protein kinase A. In this work, we examined the hypothesis that choline kinase is also phosphorylated by protein kinase C. Using choline kinase as a substrate, protein kinase C activity was dose- and time-dependent, and dependent on the concentrations of choline kinase (Km = 27 μg/ml) and ATP (Km = 15 μM). This phosphorylation, which occurred on a serine residue, was accompanied by a 1.6-fold stimulation of choline kinase activity. The synthetic peptide SRSSS25QRRHS (Vmax/Km = 17.5 mM-1 μmol min-1 mg-1) that contains the protein kinase C motif for Ser25 was a substrate for protein kinase C. A Ser25 to Ala (S25A) mutation in choline kinase resulted in a 60% decrease in protein kinase C phosphorylation of the enzyme. Phosphopeptide mapping analysis of the S25A mutant enzyme confirmed that Ser25 was a protein kinase C target site. In vivo, the S25A mutation correlated with a decrease (55%) in phosphatidylcholine synthesis via the Kennedy pathway whereas an S25D phosphorylation site mimic correlated with an increase (44%) in phosphatidylcholine synthesis. Whereas the S25A (protein kinase C site) mutation did not affect the phosphorylation of choline kinase by protein kinase A, the S30A (protein kinase A site) mutation caused a 46% reduction in enzyme phosphorylation by protein kinase C. A choline kinase synthetic peptide (SQRRHS30LTRQ) containing Ser30 was a substrate (Vmax/Km = 3.0 mM−1 μmol min−1 mg−1) for protein kinase C. Comparison of phosphopeptide maps of the wild type and S30A mutant choline kinase enzymes phosphorylated by protein kinase C confirmed that Ser30 was also a target site for protein kinase C. PMID:15919656

  16. Enterococcus faecalis phosphomevalonate kinase

    Science.gov (United States)

    Doun, Stephanie S.; Burgner, John W.; Briggs, Scott D.; Rodwell, Victor W.

    2005-01-01

    The six enzymes of the mevalonate pathway of isopentenyl diphosphate biosynthesis represent potential for addressing a pressing human health concern, the development of antibiotics against resistant strains of the Gram-positive streptococci. We previously characterized the first four of the mevalonate pathway enzymes of Enterococcus faecalis, and here characterize the fifth, phosphomevalonate kinase (E.C. 2.7.4.2). E. faecalis genomic DNA and the polymerase chain reaction were used to clone DNA thought to encode phosphomevalonate kinase into pET28b(+). Double-stranded DNA sequencing verified the sequence of the recombinant gene. The encoded N-terminal hexahistidine-tagged protein was expressed in Escherichia coli with induction by isopropylthiogalactoside and purified by Ni++ affinity chromatography, yield 20 mg protein per liter. Analysis of the purified protein by MALDI-TOF mass spectrometry established it as E. faecalis phosphomevalonate kinase. Analytical ultracentrifugation revealed that the kinase exists in solution primarily as a dimer. Assay for phosphomevalonate kinase activity used pyruvate kinase and lactate dehydrogenase to couple the formation of ADP to the oxidation of NADH. Optimal activity occurred at pH 8.0 and at 37°C. The activation energy was ~5.6 kcal/mol. Activity with Mn++, the preferred cation, was optimal at about 4 mM. Relative rates using different phosphoryl donors were 100 (ATP), 3.6 (GTP), 1.6 (TTP), and 0.4 (CTP). Km values were 0.17 mM for ATP and 0.19 mM for (R,S)-5-phosphomevalonate. The specific activity of the purified enzyme was 3.9 μmol substrate converted per minute per milligram protein. Applications to an immobilized enzyme bioreactor and to drug screening and design are discussed. PMID:15802646

  17. Fit, Interplay, and Scale: A Diagnosis

    Directory of Open Access Journals (Sweden)

    Arild Vatn

    2012-12-01

    Full Text Available Developing institutions to handle human-environment interactions well is important. In relation to that, the theory of resource regimes, and the themes of fit, interplay, and scale - as originating not least in the work of Oran Young - are core. His work is very impressive. At the same time we observe two sets of issues where we think further development is needed. The first relates to the ontological underpinning of Young's conceptual framework. The second set of issues concerns the definitions of and the relationships between the concepts of fit, interplay, and scale. Regarding the former, we emphasize issues related to "marrying" different theories about human action. Regarding the latter, we note that while the three concepts have a lot of practical appeal, there are still some important challenges surfacing, not least when using them in empirical research. We analyze three challenges: the definitions of the concepts; their internal overlap; and finally, the way environmental regimes are defined and understood as opposed to the wider institutional context of the economy. Our paper offers some direction for how to move forward on the issues specified.

  18. From Phosphosites to Kinases

    DEFF Research Database (Denmark)

    Munk, Stephanie; Refsgaard, Jan C; Olsen, Jesper V

    2016-01-01

    Kinases play a pivotal role in propagating the phosphorylation-mediated signaling networks in living cells. With the overwhelming quantities of phosphoproteomics data being generated, the number of identified phosphorylation sites (phosphosites) is ever increasing. Often, proteomics investigations...... sequence motifs, mostly based on large scale in vivo and in vitro experiments. The context of the kinase and the phosphorylated proteins in a biological system is equally important for predicting association between the enzymes and substrates, an aspect that is also being tackled with available...

  19. Exposure and materiality of the secondary room and its impact on the impulse response of coupled-volume concert halls

    Science.gov (United States)

    Ermann, Michael; Johnson, Marty

    2005-06-01

    How does sound decay when one room is partially exposed to another (acoustically coupled)? More specifically, this research aims to quantify how operational and design decisions impact sound fields in the design of concert halls with acoustical coupling. By adding a second room to a concert hall, and designing doors to control the sonic transparency between the two rooms, designers can create a new, coupled acoustic. Concert halls use coupling to achieve a variable, longer, and distinct reverberant quality for their musicians and listeners. For this study a coupled-volume shoebox concert hall is conceived with a fixed geometric volume, form, and primary-room sound absorption. Aperture size and secondary-room sound absorption levels are established as variables. Statistical analysis of sound decay in this simulated hall suggests a highly sensitive relationship between the double-sloped condition and (1) architectural composition, as defined by the aperture size exposing the chamber and (2) materiality, as defined by the sound absorptance in the coupled volume. The theoretical, mathematical predictions are compared with coupled-volume concert hall field measurements and guidelines are suggested for future designs of coupled-volume concert halls.

  20. Concerted evolution of sea anemone neurotoxin genes is revealed through analysis of the Nematostella vectensis genome.

    Science.gov (United States)

    Moran, Yehu; Weinberger, Hagar; Sullivan, James C; Reitzel, Adam M; Finnerty, John R; Gurevitz, Michael

    2008-04-01

    Gene families, which encode toxins, are found in many poisonous animals, yet there is limited understanding of their evolution at the nucleotide level. The release of the genome draft sequence for the sea anemone Nematostella vectensis enabled a comprehensive study of a gene family whose neurotoxin products affect voltage-gated sodium channels. All gene family members are clustered in a highly repetitive approximately 30-kb genomic region and encode a single toxin, Nv1. These genes exhibit extreme conservation at the nucleotide level which cannot be explained by purifying selection. This conservation greatly differs from the toxin gene families of other animals (e.g., snakes, scorpions, and cone snails), whose evolution was driven by diversifying selection, thereby generating a high degree of genetic diversity. The low nucleotide diversity at the Nv1 genes is reminiscent of that reported for DNA encoding ribosomal RNA (rDNA) and 2 hsp70 genes from Drosophila, which have evolved via concerted evolution. This evolutionary pattern was experimentally demonstrated in yeast rDNA and was shown to involve unequal crossing-over. Through sequence analysis of toxin genes from multiple N. vectensis populations and 2 other anemone species, Anemonia viridis and Actinia equina, we observed that the toxin genes for each sea anemone species are more similar to one another than to those of other species, suggesting they evolved by manner of concerted evolution. Furthermore, in 2 of the species (A. viridis and A. equina) we found genes that evolved under diversifying selection, suggesting that concerted evolution and accelerated evolution may occur simultaneously.

  1. COELIAC DISEASE IN CENTRAL AND SOUTH AMERICA: time for a concerted approach to its epidemiology

    Directory of Open Access Journals (Sweden)

    Affifa FARRUKH

    2015-06-01

    Full Text Available Central and South America offer an opportunity to resolve some of the current controversies that surround the epidemiology of celiac disease. Through a concerted action which brings together clinicians, researchers and patients there is an opportunity to establish robust data sets which will allow detailed analysis of environmental and genetic factors. In this review available data from the continent together with data from Spain and Italy are drawn together to give a current picture in the hope that it will stimulate further research.

  2. Ventilating plant in the large concert hall of the music centre at Vredenburg/Utrecht, Holland

    Energy Technology Data Exchange (ETDEWEB)

    Brockmeyer, H.; Detzer, R.; van Dijk, A.E.; Kouffeld, R.W.J.

    1979-01-01

    To form an opinion on the thermo-dynamic and flow-pattern conditions in large halls for air conditioning like e.g. concert halls, one will refer to the study of models which normally are prepared in a reduced scale. Comparisons between model studies and the executed object indicate that, even with difficult boundary conditions, reproducible data can be prepared the deviations being only minute. Presented are the results of a model study and the data of the executed plant of a large music centre in the Netherlands.

  3. Early reflection energy in concert halls: how much, how early, and from where (A)

    DEFF Research Database (Denmark)

    Gade, Anders Christian

    2001-01-01

    Today, the importance of distributing early reflection energy to listeners and performers in concert halls is well understood and accepted—also among architects. Still, implementation in the practical design of a large hall is not easy, partly because we still have difficulties quantifying...... to decide how far to promote the good cause on the basis of his/her experience, taste, and talent in influencing the decision process. The aural presentation will focus on the current limitations in our knowledge regarding the musicians' need for early reflections, which is a special challenge in the design...

  4. Interplay between superconductivity and Coulomb blockade

    Energy Technology Data Exchange (ETDEWEB)

    Lorenz, Thomas; Sprenger, Susanne; Scheer, Elke [Universitaet Konstanz (Germany)

    2016-07-01

    Studying the interplay between superconductivity and Coulomb blockade (CB) can be achieved by investigating an all superconducting single electron transistor (SSET) consisting of an island coupled to the leads by two tunneling contacts. The majority of experiments performed so far were using superconducting tunnel contacts made from oxide layers, in which multiple Andreev reflections (MAR) can be excluded. Using a mechanically controlled break junction (MCBJ) made of aluminum enables tuning the contributions of MAR in one junction continuously and thereby addressing different transport regimes within the same sample. Our results offer the possibility to attribute particular features in the transport characteristics to the transmission probabilities of individual modes in the MCBJ contact. We discuss our findings in terms of dynamical CB, SSET behaviour and MAR when continuously opening the MCBJ from the fully closed state to a tunneling contact.

  5. Gene-environment interplay in depressive symptoms

    DEFF Research Database (Denmark)

    Petkus, A. J.; Beam, C. R.; Johnson, W.

    2017-01-01

    that genetic factors play a larger part in the association between depressive symptoms and physical illness for men than for women. For both sexes, across all ages, physical illness may similarly trigger social and health limitations that contribute to depressive symptoms.......Background Numerous factors influence late-life depressive symptoms in adults, many not thoroughly characterized. We addressed whether genetic and environmental influences on depressive symptoms differed by age, sex, and physical illness. Method The analysis sample included 24 436 twins aged 40......-90 years drawn from the Interplay of Genes and Environment across Multiple Studies (IGEMS) Consortium. Biometric analyses tested age, sex, and physical illness moderation of genetic and environmental variance in depressive symptoms. Results Women reported greater depressive symptoms than men. After age 60...

  6. Lepton asymmetry and neutrino oscillations interplay

    Energy Technology Data Exchange (ETDEWEB)

    Kirilova, Daniela, E-mail: dani@astro.bas.bg [Bulgarian Academy of Sciences, Institute of Astronomy and NAO (Bulgaria)

    2013-03-15

    We discuss the interplay between lepton asymmetry L and {nu} oscillations in the early Universe. Neutrino oscillations may suppress or enhance previously existing L. On the other hand L is capable to suppress or enhance neutrino oscillations. The mechanism of L enhancement in MSW resonant {nu} oscillations in the early Universe is numerically analyzed. L cosmological effects through {nu} oscillations are discussed. We discuss how L may change the cosmological BBN constraints on neutrino and show that BBN model with {nu}{sub e}{r_reversible}{nu}{sub s} oscillations is extremely sensitive to L - it allows to obtain the most stringent constraints on L value. We discuss also the cosmological role of active-sterile {nu} mixing and L in connection with the indications about additional relativistic density in the early Universe, pointed out by BBN, CMB and LSS data and the analysis of global {nu} data.

  7. Bringing Astronomy Directly to New Audiences (50,000 People) at Outdoor Concerts and Music Festivals

    Science.gov (United States)

    Lubowich, D.

    2014-07-01

    My NASA-funded Music and Astronomy Under the Stars (MAUS) has brought astronomy to 50,000 music lovers at the National Mall (co-sponsor OSTP); Central Park Jazz, Newport Folk, Ravinia, or Tanglewood music festivals; and classical, folk, pop/rock, opera, Caribbean, or county-western concerts in parks assisted by astronomy clubs (55 events since 2009). Yo-Yo-Ma, the Chicago and Boston Symphony Orchestras, Ravi Coltrane, Esperanza Spalding, Phish, Blood Sweat and Tears, Deep Purple, Tony Orlando, and Wilco performed at these events. MAUS combines solar, optical, and radio telescope observations; large posters/banners (From the Earth to the Universe; Visions of the Universe); videos; hands-on activities (Night Sky Network; Harvard-Smithsonian CfA); imaging with a cell phone mount; and hand-outs (info on science museums, astronomy clubs, and citizen science) before and after the concerts or at intermission. MAUS reached underserved groups and attracted large enthusiastic crowds. Many young children participated in this family learning experience-often the first time they looked through a telescope. Outcomes: While education!

  8. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko

    2011-08-01

    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  9. Helicobacter pylori induces cell migration and invasion through casein kinase 2 in gastric epithelial cells.

    Science.gov (United States)

    Lee, Yeo Song; Lee, Do Yeon; Yu, Da Yeon; Kim, Shin; Lee, Yong Chan

    2014-12-01

    Chronic infection with Helicobacter pylori (H. pylori) is causally linked with gastric carcinogenesis. Virulent H. pylori strains deliver bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA-dependent process. Casein kinase 2 plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition. This study was aimed to investigate the effect of H. pylori infection on the casein kinase 2-mediated migration and invasion in gastric epithelial cells. AGS or MKN28 cells as human gastric epithelial cells and H. pylori strains Hp60190 (ATCC 49503, CagA(+)) and Hp8822 (CagA(-)) were used. Cells were infected with H. pylori at multiplicity of infection of 100 : 1 for various times. We measured in vitro kinase assay to examine casein kinase 2 activity and performed immunofluorescent staining to observe E-cadherin complex. We also examined β-catenin transactivation through promoter assay and MMP7 expression by real-time PCR and ELISA. H. pylori upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H. pylori-infected cells profoundly suppressed cell invasiveness and motility. We confirmed that casein kinase 2 mediates membranous α-catenin depletion through dissociation of the α-/β-catenin complex in H. pylori-infected cells. We also found that H. pylori induces β-catenin nuclear translocation and increases MMP7 expressions mediated through casein kinase 2. We show for the first time that CagA(+) H. pylori upregulates cellular invasiveness and motility through casein kinase 2. The demonstration of a mechanistic interplay between H. pylori and casein kinase 2 provides important insights into the role of CagA(+) H. pylori in the gastric cancer invasion and metastasis. © 2014 John Wiley & Sons Ltd.

  10. Protein Kinase Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Promotes Obesity-induced Hyperinsulinemia.

    Science.gov (United States)

    Roth Flach, Rachel J; Danai, Laura V; DiStefano, Marina T; Kelly, Mark; Menendez, Lorena Garcia; Jurczyk, Agata; Sharma, Rohit B; Jung, Dae Young; Kim, Jong Hun; Kim, Jason K; Bortell, Rita; Alonso, Laura C; Czech, Michael P

    2016-07-29

    Previous studies revealed a paradox whereby mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) acted as a negative regulator of insulin sensitivity in chronically obese mice, yet systemic deletion of Map4k4 did not improve glucose tolerance. Here, we report markedly reduced glucose-responsive plasma insulin and C-peptide levels in whole body Map4k4-depleted mice (M4K4 iKO) as well as an impaired first phase of insulin secretion from islets derived from M4K4 iKO mice ex vivo After long-term high fat diet (HFD), M4K4 iKO mice pancreata also displayed reduced β cell mass, fewer proliferating β cells and reduced islet-specific gene mRNA expression compared with controls, although insulin content was normal. Interestingly, the reduced plasma insulin in M4K4 iKO mice exposed to chronic (16 weeks) HFD was not observed in response to acute HFD challenge or short term treatment with the insulin receptor antagonist S961. Furthermore, the improved insulin sensitivity in obese M4K4 iKO mice was abrogated by high exogenous insulin over the course of a euglycemic clamp study, indicating that hypoinsulinemia promotes insulin sensitivity in chronically obese M4K4 iKO mice. These results demonstrate that protein kinase Map4k4 drives obesity-induced hyperinsulinemia and insulin resistance in part by promoting insulin secretion from β cells in mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. The role of the C8 proton of ATP in the catalysis of shikimate kinase and adenylate kinase

    Directory of Open Access Journals (Sweden)

    Kenyon Colin P

    2012-08-01

    is therefore conceivable that kinase enzymes achieve the observed 2,500-fold variation in KM through a combination of the various conserved “push” and “pull” mechanisms associated with the release of C8-H, the proton transfer cascades unique to the class of kinase in question and the resultant/concomitant creation of a pentavalent species from the γ-phosphate group of ATP. Also demonstrated is the interplay between the role of the C8-H of ATP and the ATP concentration in the observed enzyme activity. The lability of the C8-H mediated by active site residues co-ordinated to the purine ring of ATP therefore plays a significant role in explaining the broad KM range associated with kinase steady state enzyme activities.

  12. Regulation of Autophagy by Kinases

    International Nuclear Information System (INIS)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

    2011-01-01

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets

  13. Regulation of Autophagy by Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda, E-mail: alakananda.basu@unthsc.edu [Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2011-06-09

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  14. Regulation of Autophagy by Kinases

    Science.gov (United States)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

    2011-01-01

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets. PMID:24212825

  15. Regulation of Autophagy by Kinases

    Directory of Open Access Journals (Sweden)

    Savitha Sridharan

    2011-06-01

    Full Text Available Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  16. CONCERT-'European Joint Programme for the Integration at Radiation Protection Research'; CONCERT-''European Joint Programme for the Integration at Radiation Protection Research''

    Energy Technology Data Exchange (ETDEWEB)

    Birschwilks, Mandy; Schmitt-Hannig, Annemarie [Bundesamt fuer Strahlenschutz, Oberschleissheim (Germany). Internationale und Nationale Zusammenarbeit im Strahlenschutz; Jung, Thomas [Bundesamt fuer Strahlenschutz, Oberschleissheim (Germany). Strahlenschutz und Gesundheit

    2016-08-01

    In 2009 the High Level Expert Group (HLEG) on low dose research recommended the development of a scientific platform for low dose radiation research. The foundation of MELODI (Multidisciplinary European Low Dose Initiative) occurred in 2010. In 2015 a new project on radiation protection research was established: CONCERT (European Joint Programme for the Integration at Radiation Protection Research). The aim is the coordination of the already existing scientific platforms MELODI (radiation effects and interactions), ALLIANCE (radioecology), NERIS (nuclear and radiological emergency protection) and EURADOS (radiation dosimetry). With CONCERT an efficient use of this infrastructure for research cooperation and transparency is intended.

  17. Rainforests as concert halls for birds: Are reverberations improving sound transmission of long song elements?

    DEFF Research Database (Denmark)

    Nemeth, Erwin; Dabelsteen, Torben; Pedersen, Simon Boel

    2006-01-01

    that longer sounds are less attenuated. The results indicate that higher sound pressure level is caused by superimposing reflections. It is suggested that this beneficial effect of reverberations explains interspecific birdsong differences in element length. Transmission paths with stronger reverberations......In forests reverberations have probably detrimental and beneficial effects on avian communication. They constrain signal discrimination by masking fast repetitive sounds and they improve signal detection by elongating sounds. This ambivalence of reflections for animal signals in forests is similar...... to the influence of reverberations on speech or music in indoor sound transmission. Since comparisons of sound fields of forests and concert halls have demonstrated that reflections can contribute in both environments a considerable part to the energy of a received sound, it is here assumed that reverberations...

  18. DRAWING MUSIC! ANAL Y Z ING AN EXTRACURRICULAR ACTIVITY OF VISUALI Z ING A CONCERT

    Directory of Open Access Journals (Sweden)

    Váradi, Judit

    2018-01-01

    Full Text Available According to the literature and recent studies, a high number of encounters with classical music during childhood and adolescence in the context of positive feelings closely correlates with the formation of classical music competencies. During the investigation of primary students’ attitudes towards classical music, it has been revealed that those who have more opportunities to enter music education will come closer to understanding classical music. At the University of Debrecen Faculty of Music, we have organised and staged various educational youth performances in the last decades. Our goal is to get elementary school children acquainted with live music, classical instruments. A key element of our mission is to form the preferences of children and young people who do not participate in art education, so that they may become interested and sophisticated adults. In our paper we analysis the creations of the drawing competition what connects in theme with the youth concert.

  19. An analysis of concert saxophone vibrato through the examination of recordings by eight prominent soloists

    Science.gov (United States)

    Zinninger, Thomas

    This study examines concert saxophone vibrato through the analysis of several recordings of standard repertoire by prominent soloists. The vibrato of Vincent Abato, Arno Bornkamp, Claude Delangle, Jean-Marie Londeix, Marcel Mule, Otis Murphy, Sigurd Rascher, and Eugene Rousseau is analyzed with regards to rate, extent, shape, and discretionary use. Examination of these parameters was conducted through both general observation and precise measurements with the aid of a spectrogram. Statistical analyses of the results provide tendencies for overall vibrato use, as well as the effects of certain musical attributes (note length, tempo, dynamic, range) on vibrato. The results of this analysis are also compared among each soloist and against pre-existing theories or findings in vibrato research.

  20. Music Audiences 3.0: Concert-Goers’ Psychological Motivations at the Dawn of Virtual Reality

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Charron

    2017-05-01

    Full Text Available Reviewing consumers’ motivations to attend performances in a continuously evolving social and technological context is essential because live concerts generate an important and growing share of revenues for the music industry. Evolving fans’ preferences and technological innovations constantly alter the way music is distributed and consumed. In a marketing 3.0 era, what consumers do with music is becoming more significant than simply owning or listening to a song. These changes are not only blurring the lines between production and consumption (i.e., co-creation, but also distorting the concept of live attendance altogether. Although mediated performances typically lack presence and authenticity, recent advances in immersive technologies, such as spherical videos and virtual reality goggles, could represent a new form of experiencing live music.

  1. Music Audiences 3.0: Concert-Goers' Psychological Motivations at the Dawn of Virtual Reality.

    Science.gov (United States)

    Charron, Jean-Philippe

    2017-01-01

    Reviewing consumers' motivations to attend performances in a continuously evolving social and technological context is essential because live concerts generate an important and growing share of revenues for the music industry. Evolving fans' preferences and technological innovations constantly alter the way music is distributed and consumed. In a marketing 3.0 era, what consumers do with music is becoming more significant than simply owning or listening to a song. These changes are not only blurring the lines between production and consumption (i.e., co-creation), but also distorting the concept of live attendance altogether. Although mediated performances typically lack presence and authenticity, recent advances in immersive technologies, such as spherical videos and virtual reality goggles, could represent a new form of experiencing live music.

  2. Efficacy of Role Play in Concert with Lecture to Enhance Student Learning of Immunology

    Directory of Open Access Journals (Sweden)

    Samantha L. Elliott

    2010-11-01

    Full Text Available Despite numerous reports that active learning increases student understanding, many barriers still exist that prevent faculty from shedding the traditional passive lecture and adopting active learning strategies in the classroom. This study looks at the use of role play as an active learning technique to convey new material, or as reinforcement to traditional lecture. A pre- and post-test survey was utilized to determine student learning gains, along with an anonymous survey to determine student attitudes about role play. Student learning gains are similar regardless of class size, role-playing participation or learning style, and reflect an increase in lower order cognition. Attitudes and learning gains indicate role play is preferable as a reinforcement technique, although the order does not matter if both lecture and role play are utilized to convey information. These data provide insight into the best practices of role-playing implementation in concert with traditional lecture format.

  3. CONCERT A high power proton accelerator driven multi-application facility concept

    CERN Document Server

    Laclare, J L

    2000-01-01

    A new generation of High Power Proton Accelerator (HPPA) is being made available. It opens new avenues to a long series of scientific applications in fundamental and applied research, which can make use of the boosted flux of secondary particles. Presently, in Europe, several disciplines are preparing their project of dedicated facility, based on the upgraded performances of HPPAs. Given the potential synergies between these different projects, for reasons of cost effectiveness, it was considered appropriate to look into the possibility to group a certain number of these applications around a single HPPA: CONCERT project left bracket 1 right bracket . The ensuing 2-year feasibility study organized in collaboration between the European Spallation Source and the CEA just started. EURISOL left bracket 2 right bracket project and CERN participate in the steering committee.

  4. Parametrization in models of subcritical glass fracture: Activation offset and concerted activation

    Science.gov (United States)

    Rodrigues, Bruno Poletto; Hühn, Carolin; Erlebach, Andreas; Mey, Dorothea; Sierka, Marek; Wondraczek, Lothar

    2017-08-01

    There are two established but fundamentally different empirical approaches to parametrize the rate of subcritical fracture in brittle materials. While both are relying on a thermally activated reaction of bond rupture, the difference lies in the way as to how the externally applied stresses affect the local energy landscape. In the consideration of inorganic glasses, the strain energy is typically taken as an off-set on the activation barrier. As an alternative interpretation, the system’s volumetric strain-energy is added to its thermal energy. Such an interpretation is consistent with the democratic fiber bundle model. Here, we test this approach of concerted activation against macroscopic data of bond cleavage activation energy, and also against ab initio quantum chemical simulation of the energy barrier for cracking in silica. The fact that both models are able to reproduce experimental observation to a remarkable degree highlights the importance of a holistic consideration towards non-empirical understanding.

  5. Hierarchical Oct4 Binding in Concert with Primed Epigenetic Rearrangements during Somatic Cell Reprogramming

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2016-02-01

    Full Text Available The core pluripotency factor Oct4 plays key roles in somatic cell reprogramming through transcriptional control. Here, we profile Oct4 occupancy, epigenetic changes, and gene expression in reprogramming. We find that Oct4 binds in a hierarchical manner to target sites with primed epigenetic modifications. Oct4 binding is temporally continuous and seldom switches between bound and unbound. Oct4 occupancy in most of promoters is maintained throughout the entire reprogramming process. In contrast, somatic cell-specific enhancers are silenced in the early and intermediate stages, whereas stem cell-specific enhancers are activated in the late stage in parallel with cell fate transition. Both epigenetic remodeling and Oct4 binding contribute to the hyperdynamic enhancer signature transitions. The hierarchical Oct4 bindings are associated with distinct functional themes at different stages. Collectively, our results provide a comprehensive molecular roadmap of Oct4 binding in concert with epigenetic rearrangements and rich resources for future reprogramming studies.

  6. Music Audiences 3.0: Concert-Goers’ Psychological Motivations at the Dawn of Virtual Reality

    Science.gov (United States)

    Charron, Jean-Philippe

    2017-01-01

    Reviewing consumers’ motivations to attend performances in a continuously evolving social and technological context is essential because live concerts generate an important and growing share of revenues for the music industry. Evolving fans’ preferences and technological innovations constantly alter the way music is distributed and consumed. In a marketing 3.0 era, what consumers do with music is becoming more significant than simply owning or listening to a song. These changes are not only blurring the lines between production and consumption (i.e., co-creation), but also distorting the concept of live attendance altogether. Although mediated performances typically lack presence and authenticity, recent advances in immersive technologies, such as spherical videos and virtual reality goggles, could represent a new form of experiencing live music. PMID:28588528

  7. Culture and biology interplay: An introduction.

    Science.gov (United States)

    Causadias, José M; Telzer, Eva H; Lee, Richard M

    2017-01-01

    Culture and biology have evolved together, influence each other, and concurrently shape behavior, affect, cognition, and development. This special section highlights 2 major domains of the interplay between culture and biology. The first domain is neurobiology of cultural experiences-how cultural, ethnic, and racial experiences influence limbic systems and neuroendocrine functioning-and the second domain is cultural neuroscience-the connections between cultural processes and brain functioning. We include 3 studies on neurobiology of cultural experiences that examine the associations between racial discrimination and heart rate variability (Hill et al., 2016), economic and sociocultural stressors and cortisol levels (Mendoza, Dmitrieva, Perreira, & Watamura, 2016), and unfair treatment and allostatic load (Ong, Williams, Nwizu, & Gruenewald, 2016). We also include 2 studies on cultural neuroscience that investigate cultural group differences and similarities in beliefs, practices, and neural basis of emotion regulation (Qu & Telzer, 2016), and reflected and direct self-appraisals (Pfeifer et al., 2016). We discuss pending challenges and future directions for this emerging field. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  8. Oxidative Stress, Prooxidants, and Antioxidants: The Interplay

    Directory of Open Access Journals (Sweden)

    Anu Rahal

    2014-01-01

    Full Text Available Oxidative stress is a normal phenomenon in the body. Under normal conditions, the physiologically important intracellular levels of reactive oxygen species (ROS are maintained at low levels by various enzyme systems participating in the in vivo redox homeostasis. Therefore, oxidative stress can also be viewed as an imbalance between the prooxidants and antioxidants in the body. For the last two decades, oxidative stress has been one of the most burning topics among the biological researchers all over the world. Several reasons can be assigned to justify its importance: knowledge about reactive oxygen and nitrogen species production and metabolism; identification of biomarkers for oxidative damage; evidence relating manifestation of chronic and some acute health problems to oxidative stress; identification of various dietary antioxidants present in plant foods as bioactive molecules; and so on. This review discusses the importance of oxidative stress in the body growth and development as well as proteomic and genomic evidences of its relationship with disease development, incidence of malignancies and autoimmune disorders, increased susceptibility to bacterial, viral, and parasitic diseases, and an interplay with prooxidants and antioxidants for maintaining a sound health, which would be helpful in enhancing the knowledge of any biochemist, pathophysiologist, or medical personnel regarding this important issue.

  9. Interplay of a multiplicity of security features

    Science.gov (United States)

    Moser, Jean-Frederic

    2000-04-01

    The great variety of existing security features can cause difficulty in choosing the adequate set for a particular security document. Considering the cost/benefit aspects with respect to the overall protection performance requested, a choice has to be made, for example, between either few features of high-security value or numerous many, less- resistant features. Another choice is the high versus low complexity of one particular features. A study aimed at providing a decision basis is a challenging matter because it involves human factors. Attention, perception, physiology of seeing and habits - to name some of the factors - are intangibles and are subject to evaluations involving normally a great number of experiments, if they are to be representative. The opportunity was given for a case study with the introduction of new Swiss banknotes between 1995 and 1998, because the new banknotes represent a novelty in the sense of the multiplicity and interplay of its optical security features. We have analyzed 652 articles which appeared in the press media concerning the new banknotes, seeking especially for peoples' reaction towards the security features.

  10. Calcium and ROS: A mutual interplay

    Science.gov (United States)

    Görlach, Agnes; Bertram, Katharina; Hudecova, Sona; Krizanova, Olga

    2015-01-01

    Calcium is an important second messenger involved in intra- and extracellular signaling cascades and plays an essential role in cell life and death decisions. The Ca2+ signaling network works in many different ways to regulate cellular processes that function over a wide dynamic range due to the action of buffers, pumps and exchangers on the plasma membrane as well as in internal stores. Calcium signaling pathways interact with other cellular signaling systems such as reactive oxygen species (ROS). Although initially considered to be potentially detrimental byproducts of aerobic metabolism, it is now clear that ROS generated in sub-toxic levels by different intracellular systems act as signaling molecules involved in various cellular processes including growth and cell death. Increasing evidence suggests a mutual interplay between calcium and ROS signaling systems which seems to have important implications for fine tuning cellular signaling networks. However, dysfunction in either of the systems might affect the other system thus potentiating harmful effects which might contribute to the pathogenesis of various disorders. PMID:26296072

  11. An efficient algorithm to perform local concerted movements of a chain molecule.

    Directory of Open Access Journals (Sweden)

    Stefano Zamuner

    Full Text Available The devising of efficient concerted rotation moves that modify only selected local portions of chain molecules is a long studied problem. Possible applications range from speeding the uncorrelated sampling of polymeric dense systems to loop reconstruction and structure refinement in protein modeling. Here, we propose and validate, on a few pedagogical examples, a novel numerical strategy that generalizes the notion of concerted rotation. The usage of the Denavit-Hartenberg parameters for chain description allows all possible choices for the subset of degrees of freedom to be modified in the move. They can be arbitrarily distributed along the chain and can be distanced between consecutive monomers as well. The efficiency of the methodology capitalizes on the inherent geometrical structure of the manifold defined by all chain configurations compatible with the fixed degrees of freedom. The chain portion to be moved is first opened along a direction chosen in the tangent space to the manifold, and then closed in the orthogonal space. As a consequence, in Monte Carlo simulations detailed balance is easily enforced without the need of using Jacobian reweighting. Moreover, the relative fluctuations of the degrees of freedom involved in the move can be easily tuned. We show different applications: the manifold of possible configurations is explored in a very efficient way for a protein fragment and for a cyclic molecule; the "local backbone volume", related to the volume spanned by the manifold, reproduces the mobility profile of all-α helical proteins; the refinement of small protein fragments with different secondary structures is addressed. The presented results suggest our methodology as a valuable exploration and sampling tool in the context of bio-molecular simulations.

  12. Bacterial Protein-Tyrosine Kinases

    DEFF Research Database (Denmark)

    Shi, Lei; Kobir, Ahasanul; Jers, Carsten

    2010-01-01

    in exopolysaccharide production, virulence, DNA metabolism, stress response and other key functions of the bacterial cell. BY-kinases act through autophosphorylation (mainly in exopolysaccharide production) and phosphorylation of other proteins, which have in most cases been shown to be activated by tyrosine......Bacteria and Eukarya share essentially the same family of protein-serine/threonine kinases, also known as the Hanks-type kinases. However, when it comes to protein-tyrosine phosphorylation, bacteria seem to have gone their own way. Bacterial protein-tyrosine kinases (BY-kinases) are bacterial...... and highlighted their importance in bacterial physiology. Having no orthologues in Eukarya, BY-kinases are receiving a growing attention from the biomedical field, since they represent a particularly promising target for anti-bacterial drug design....

  13. Redox interplay between mitochondria and peroxisomes

    Directory of Open Access Journals (Sweden)

    Celien eLismont

    2015-05-01

    Full Text Available Reduction-oxidation or ‘redox’ reactions are an integral part of a broad range of cellular processes such as gene expression, energy metabolism, protein import and folding, and autophagy. As many of these processes are intimately linked with cell fate decisions, transient or chronic changes in cellular redox equilibrium are likely to contribute to the initiation and progression of a plethora of human diseases. Since a long time, it is known that mitochondria are major players in redox regulation and signaling. More recently, it has become clear that also peroxisomes have the capacity to impact redox-linked physiological processes. To serve this function, peroxisomes cooperate with other organelles, including mitochondria. This review provides a comprehensive picture of what is currently known about the redox interplay between mitochondria and peroxisomes in mammals. We first outline the pro- and antioxidant systems of both organelles and how they may function as redox signaling nodes. Next, we critically review and discuss emerging evidence that peroxisomes and mitochondria share an intricate redox-sensitive relationship and cooperate in cell fate decisions. Key issues include possible physiological roles, messengers, and mechanisms. We also provide examples of how data mining of publicly-available datasets from ‘omics’ technologies can be a powerful means to gain additional insights into potential redox signaling pathways between peroxisomes and mitochondria. Finally, we highlight the need for more studies that seek to clarify the mechanisms of how mitochondria may act as dynamic receivers, integrators, and transmitters of peroxisome-derived mediators of oxidative stress. The outcome of such studies may open up exciting new avenues for the community of researchers working on cellular responses to organelle-derived oxidative stress, a research field in which the role of peroxisomes is currently highly underestimated and an issue of

  14. Music and politics after the Holocaust: Menuhin’s Berlin concerts of 1947 and their aftermath

    Directory of Open Access Journals (Sweden)

    Frühauf, Tina

    2011-10-01

    Full Text Available Between September 27 and October 3, 1947, Yehudi Menuhin gave six performances in Berlin, two of them together with Wilhelm Furtwängler, who had just been cleared by the denazification tribunals in Austria and Germany. Because of the German audience and the Furtwängler collaboration, these concerts led to a scandal in the Jewish community and the Displaced Persons camp in Germany as well as Jewish communities abroad. I turn first to the historical background of these performances, specifically the position of Menuhin and Furtwängler toward each other and their roles in postwar Germany. I will then chronicle the events of September and October 1947 through the lenses of Abraham S. Hyman, legal consultant to the American Advisers on Jewish Affairs in Germany, and Yehudi Menuhin and his biographers, to reveal the complexity of the events. Lastly, I will scrutinize the reception of the concerts to shed light on the reasons for and impact of the scandal. I argue that these concerts were mishandled in their organization and aims, in that politics played too large a role in the events during a time when the Jewish people suffered severe trauma in the aftermath of the Holocaust.

    Entre el 27 de septiembre y el 3 de octubre del 1947, Yehudi Menuhin ofreció seis conciertos en Berlín, dos de ellos con Wilhelm Furtwängler, quien acababa de ser declarado inocente por los tribunales de “desnazificación” en Austria y Alemania. Debido a que el público era alemán y a la participación de Furtwängler, estos conciertos provocaron un fuerte escándalo entre la comunidad judía y la población desplazada de los campos en Alemania, así como entre las comunidades judías en el extranjero. Mi investigación se centra, primero, en el contexto histórico de estos conciertos y, concretamente, la posición de Menuhin y Furtwängler hacia el uno al otro, así como sus respectivos papeles en la Alemania de la postguerra. Posteriormente ofrezco una relaci

  15. The American Board of Emergency Medicine ConCert Examination: Emergency Physicians' Perceptions of Learning and Career Benefits.

    Science.gov (United States)

    Marco, Catherine A; Wahl, Robert P; Counselman, Francis L; Heller, Barry N; Harvey, Anne L; Joldersma, Kevin B; Kowalenko, Terry; Coombs, Andrea B; Reisdorff, Earl J

    2016-09-01

    As part of the American Board of Emergency Medicine (ABEM) Maintenance of Certification (MOC) program, ABEM-certified physicians are required to pass the Continuous Certification (ConCert) examination at least every 10 years. With the 2015 ConCert examination, ABEM sought to better understand emergency physicians' perceptions of the benefits of preparing for and taking the examination and the career benefits of staying ABEM-certified. This was a prospective survey study. A voluntary postexamination survey was administered at the end of the 2015 ABEM ConCert examination (September 21-26, 2015). Physicians were asked about the benefits of preparing for the examination and maintaining ABEM certification. Examination performance was compared to perceptions of learning and career benefits. Of the 2,601 on-time test takers, 2,511 respondents participated (96.5% participation rate). The majority of participants (92.0%) identified a benefit to preparing for the ConCert examination, which included reinforced medical knowledge (73.9%), increased knowledge (66.8%), and making them a better clinician (39.4%). The majority of respondents (90.8%) identified a career benefit of maintaining ABEM certification, which included more employment options (73.8%), more positively viewed by other physicians (56.8%), and better financial outcomes (29.8%). There was a statistically significant association between the perception of knowledge reinforcement and examination performance (p Medicine.

  16. Creating personalized memories from social events: community-based support for multi-camera recordings of school concerts

    NARCIS (Netherlands)

    R.L. Guimarães (Rodrigo); P.S. Cesar Garcia (Pablo Santiago); D.C.A. Bulterman (Dick); V. Zsombori; I. Kegel

    2011-01-01

    htmlabstractThe wide availability of relatively high-quality cameras makes it easy for many users to capture video fragments of social events such as concerts, sports events or community gatherings. The wide availability of simple sharing tools makes it nearly as easy to upload individual fragments

  17. "Posh Music Should Equal Posh Dress": An Investigation into the Concert Dress and Physical Appearance of Female Soloists

    Science.gov (United States)

    Griffiths, Noola K.

    2010-01-01

    This study investigates the effects of concert dress and physical appearance on perceptions of female classical soloists' musical abilities over a range of genres. Four female violinists were recorded playing three pieces, in four styles of dress of varying formality. Each combination of performer, piece and dress was recorded twice, once as the…

  18. Warm-Up Activities of Middle and High School Band Directors Participating in State-Level Concert Band Assessments

    Science.gov (United States)

    Ward, Justin P.; Hancock, Carl B.

    2016-01-01

    The purpose of this study was to examine the warm-ups chosen by concert band directors participating in state-level performance assessments. We observed 29 middle and high school bands and coded the frequency and duration of warm-up activities and behaviors. Results indicated that most bands rehearsed music and played scales, long tones, and…

  19. In-situ observations of young contrails – overview and selected results from the CONCERT campaign

    Directory of Open Access Journals (Sweden)

    C. Voigt

    2010-09-01

    Full Text Available Lineshaped contrails were detected with the research aircraft Falcon during the CONCERT – CONtrail and Cirrus ExpeRimenT – campaign in October/November 2008. The Falcon was equipped with a set of instruments to measure the particle size distribution, shape, extinction and chemical composition as well as trace gas mixing ratios of sulfur dioxide (SO2, reactive nitrogen and halogen species (NO, NOy, HNO3, HONO, HCl, ozone (O3 and carbon monoxide (CO. During 12 mission flights over Europe, numerous contrails, cirrus clouds and a volcanic aerosol layer were probed at altitudes between 8.5 and 11.6 km and at temperatures above 213 K. 22 contrails from 11 different aircraft were observed near and below ice saturation. The observed NO mixing ratios, ice crystal and soot number densities are compared to a process based contrail model. On 19 November 2008 the contrail from a CRJ-2 aircraft was penetrated in 10.1 km altitude at a temperature of 221 K. The contrail had mean ice crystal number densities of 125 cm−3 with effective radii reff of 2.6 μm. The presence of particles with r>50 μm in the less than 2 min old contrail suggests that natural cirrus crystals were entrained in the contrail. Mean HONO/NO (HONO/NOy ratios of 0.037 (0.024 and the fuel sulfur conversion efficiency to H2SO4S of 2.9 % observed in the CRJ-2 contrail are in the range of previous measurements in the gaseous aircraft exhaust. On 31 October 2010 aviation NO emissions could have contributed by more than 40% to the regional scale NO levels in the mid-latitude lowest stratosphere. The CONCERT observations help to better quantify the climate impact from contrails and will be used to investigate the chemical processing of trace gases on contrails.

  20. A cross-talk between TrkB and Ret tyrosine kinases receptors mediates neuroblastoma cells differentiation.

    Directory of Open Access Journals (Sweden)

    Carla Lucia Esposito

    Full Text Available Understanding the interplay between intracellular signals initiated by multiple receptor tyrosine kinases (RTKs to give the final cell phenotype is a major pharmacological challenge. Retinoic acid (RA-treatment of neuroblastoma (NB cells implicates activation of Ret and TrkB RTKs as critical step to induce cell differentiation. By studying the signaling interplay between TrkB and Ret as paradigmatic example, here we demonstrate the existence of a cross-talk mechanism between the two unrelated receptors that is needed to induce the cell differentiation. Indeed, we show that TrkB receptor promotes Ret phosphorylation by a mechanism that does not require GDNF. This reveals to be a key mechanism, since blocking either TrkB or Ret by small interfering RNA causes a failure in NB biochemical and morphological differentiation. Our results provide the first evidence that a functional transactivation between distinct tyrosine kinases receptors is required for an important physiological process.

  1. Interplay between topology, gauge fields and gravity

    Science.gov (United States)

    Corichi Rodriguez Gil, Alejandro

    In this thesis we consider several physical systems that illustrate an interesting interplay between quantum theory, connections and knot theory. It can be divided into two parts. In the first one, we consider the quantization of the free Maxwell field. We show that there is an important role played by knot theory, and in particular the Gauss linking number, in the quantum theory. This manifestation is twofold. The first occurs at the level of the algebra of observables given by fluxes of electric and magnetic field across surfaces. The commutator of the operators, and thus the basic uncertainty relations, are given in terms of the linking number of the loops that bound the surfaces. Next, we consider the quantization of the Maxwell field based on self-dual connections in the loop representation. We show that the measure which determines the quantum inner product can be expressed in terms of the self linking number of thickened loops. Therefore, the linking number manifests itself at two key points of the theory: the Heisenberg uncertainty principle and the inner product. In the second part, we bring gravity into play. First we consider quantum test particles on certain stationary space-times. We demonstrate that a geometric phase exists for those space-times and focus on the example of a rotating cosmic string. The geometric phase can be explicitly computed, providing a fully relativistic gravitational Aharonov-Bohm effect. Finally, we consider 3-dimensional gravity with non-vanishing cosmological constant in the connection dynamics formulation. We restrict our attention to Lorentzian gravity with positive cosmological constant and Euclidean signature with negative cosmological constant. A complex transformation is performed in phase space that makes the constraints simple. The reduced phase space is characterized as the moduli space of flat complex connections. We construct the quantization of the theory when the initial hyper-surface is a torus. Two important

  2. Mutational analyses of the core domain of Avian Leukemia and Sarcoma Viruses integrase: critical residues for concerted integration and multimerization

    International Nuclear Information System (INIS)

    Moreau, Karen; Faure, Claudine; Violot, Sebastien; Gouet, Patrice; Verdier, Gerard; Ronfort, Corinne

    2004-01-01

    During replicative cycle of retroviruses, the reverse-transcribed viral DNA is integrated into the cell DNA by the viral integrase (IN) enzyme. The central core domain of IN contains the catalytic site of the enzyme and is involved in binding viral ends and cell DNA as well as dimerization. We previously performed single amino acid substitutions in the core domain of an Avian Leukemia and Sarcoma Virus (ALSV) IN [Arch. Virol. 147 (2002) 1761]. Here, we modeled the resulting IN mutants and analyzed the ability of these mutants to mediate concerted DNA integration in an in vitro assay, and to form dimers by protein-protein cross-linking and size exclusion chromatography. The N197C mutation resulted in the inability of the mutant to perform concerted integration that was concomitant with a loss of IN dimerization. Surprisingly, mutations Q102G and A106V at the dimer interface resulted in mutants with higher efficiencies than the wild-type IN in performing two-ended concerted integration of viral DNA ends. The G139D and A195V mutants had a trend to perform one-ended DNA integration of viral ends instead of two-ended integration. More drastically, the I88L and L135G mutants preferentially mediated nonconcerted DNA integration although the proteins form dimers. Therefore, these mutations may alter the formation of IN complexes of higher molecular size than a dimer that would be required for concerted integration. This study points to the important role of core domain residues in the concerted integration of viral DNA ends as well as in the oligomerization of the enzyme

  3. Receptor-interacting protein (RIP) kinase family

    OpenAIRE

    Zhang, Duanwu; Lin, Juan; Han, Jiahuai

    2010-01-01

    Receptor-interacting protein (RIP) kinases are a group of threonine/serine protein kinases with a relatively conserved kinase domain but distinct non-kinase regions. A number of different domain structures, such as death and caspase activation and recruitment domain (CARD) domains, were found in different RIP family members, and these domains should be keys in determining the specific function of each RIP kinase. It is known that RIP kinases participate in different biological processes, incl...

  4. Concerted Electrodeposition and Alloying of Antimony on Indium Electrodes for Selective Formation of Crystalline Indium Antimonide.

    Science.gov (United States)

    Fahrenkrug, Eli; Rafson, Jessica; Lancaster, Mitchell; Maldonado, Stephen

    2017-09-19

    The direct preparation of crystalline indium antimonide (InSb) by the electrodeposition of antimony (Sb) onto indium (In) working electrodes has been demonstrated. When Sb is electrodeposited from dilute aqueous electrolytes containing dissolved Sb 2 O 3 , an alloying reaction is possible between Sb and In if any surface oxide films are first thoroughly removed from the electrode. The presented Raman spectra detail the interplay between the formation of crystalline InSb and the accumulation of Sb as either amorphous or crystalline aggregates on the electrode surface as a function of time, temperature, potential, and electrolyte composition. Electron and optical microscopies confirm that under a range of conditions, the preparation of a uniform and phase-pure InSb film is possible. The cumulative results highlight this methodology as a simple yet potent strategy for the synthesis of intermetallic compounds of interest.

  5. Radical Abstraction Reactions with Concerted Fragmentation in the Chain Decay of Nitroalkanes

    Science.gov (United States)

    Denisov, E. T.; Shestakov, A. F.

    2018-05-01

    Reactions of the type X• + HCR2CH2NO2 → XH + R2C=CH2 + N•O2 are exothermic, due to the breaking of weak C-N bonds and the formation of energy-intensive C=C bonds. Quantum chemistry calculations of the transition state using the reactions of Et• and EtO• with 2-nitrobutane shows that such reactions can be categorized as one-step, due to the extreme instability of the intermediate nitrobutyl radical toward decay with the formation of N•O2. Kinetic parameters that allow us to calculate the energy of activation and rate constant of such a reaction from its enthalpy are estimated using a model of intersecting parabolas. Enthalpies, energies of activation, and rate constants are calculated for a series of reactions with the participation of Et•, EtO•, RO•2, N•O2 radicals on the one hand and a series of nitroalkanes on the other. A new kinetic scheme of the chain decay of nitroalkanes with the participation of abstraction reactions with concerted fragmentation is proposed on the basis of the obtained data.

  6. Standing Concertation Committee - Meetings held on 6, 20 & 22 May 2008

    CERN Multimedia

    HR Department

    2008-01-01

    The main items discussed at the meeting of the Standing Concertation Committee on 6 May 2008 included: Carry-forward of leave The Committee discussed a proposal to increase, for the period 2008-2009, the carry forward of leave days at the end of the 2008 leave year (30 September 2008) so that staff members working on LHC installation and commissioning do not lose leave. It was agreed that departments would be consulted before finalizing a proposal on the number of extra days of carry-forward. Revision of CHIS Rules The Committee discussed a number of outstanding issues relating to the current revision of the CHIS Rules. This revision should be finalized before a market survey is launched for the service contract for the administration of the CHIS that is foreseen by the end of the year. Preparation for TREF on 28 May The following items were to be discussed at TREF on 28 May 2008: Equal Opportunities Report The Committee took note of the report for 2007 presented by the Equ...

  7. [A concertation experience: prevention of WMSDs in workmanship of Parmigiano-Reggiano].

    Science.gov (United States)

    Zecchi, G

    2012-01-01

    The dairy industry of Parmigiano-Reggiano represents in Emilia a resource and an important source of employment. A Protected Designation of Origin (DOP) regulates all stages of processing of milk into cheese "forms" in excess of 40 kg weight, favouring a "traditional" working which involves various manual steps tiring and stressful. From 2002 to 2008 the Service in charge of the Azienda USL of Reggio Emilia has developed a plan focused on musculoskeletal risks in this sector. The need for comparison on the conservation "craftsmanship" of the complex manufacturing process maintaining high attention to health and safety brought the AUSL of Reggio E. and later the AUSL of Modena and Parma, to choose the path of concertation with the social partners, aiming at substantial and non-formal application of the law. It is thus obtained the adoption of preventive measures in a sector so peculiar, complex and constantly changing. Conciliation remains privileged tool in relations between social partners and AUSL of Reggio E. in dairies.

  8. Folding and membrane insertion of the pore-forming peptide gramicidin occur as a concerted process.

    Science.gov (United States)

    Hicks, Matthew R; Damianoglou, Angeliki; Rodger, Alison; Dafforn, Timothy R

    2008-11-07

    Many antibiotic peptides function by binding and inserting into membranes. Understanding this process provides an insight into the fundamentals of both membrane protein folding and antibiotic peptide function. For the first time, in this work, flow-aligned linear dichroism (LD) is used to study the folding of the antibiotic peptide gramicidin. LD provides insight into the combined processes of peptide folding and insertion and has the advantage over other similar techniques of being insensitive to off-membrane aggregation events. By combining LD data with conventional measurements of protein fluorescence and circular dichroism, the mechanism of gramicidin insertion is elucidated. The mechanism consists of five separately assignable steps that include formation of a water-insoluble gramicidin aggregate, dissociation from the aggregate, partitioning of peptide to the membrane surface, oligomerisation on the surface and concerted insertion and folding of the peptide to the double-helical form of gramicidin. Measurement of the rates of each step shows that although changes in the fluorescence signal cease 10 s after the initiation of the process, the insertion of the peptide into the membrane is actually not complete for a further 60 min. This last membrane insertion phase is only apparent by measurement of LD and circular dichroism signal changes. In summary, this study demonstrates the importance of multi-technique approaches, including LD, in studies of membrane protein folding.

  9. Concerted changes in N and C primary metabolism in alfalfa (Medicago sativa) under water restriction.

    Science.gov (United States)

    Aranjuelo, Iker; Tcherkez, Guillaume; Molero, Gemma; Gilard, Françoise; Avice, Jean-Christophe; Nogués, Salvador

    2013-02-01

    Although the mechanisms of nodule N(2) fixation in legumes are now well documented, some uncertainty remains on the metabolic consequences of water deficit. In most cases, little consideration is given to other organs and, therefore, the coordinated changes in metabolism in leaves, roots, and nodules are not well known. Here, the effect of water restriction on exclusively N(2)-fixing alfalfa (Medicago sativa L.) plants was investigated, and proteomic, metabolomic, and physiological analyses were carried out. It is shown that the inhibition of nitrogenase activity caused by water restriction was accompanied by concerted alterations in metabolic pathways in nodules, leaves, and roots. The data suggest that nodule metabolism and metabolic exchange between plant organs nearly reached homeostasis in asparagine synthesis and partitioning, as well as the N demand from leaves. Typically, there was (i) a stimulation of the anaplerotic pathway to sustain the provision of C skeletons for amino acid (e.g. glutamate and proline) synthesis; (ii) re-allocation of glycolytic products to alanine and serine/glycine; and (iii) subtle changes in redox metabolites suggesting the implication of a slight oxidative stress. Furthermore, water restriction caused little change in both photosynthetic efficiency and respiratory cost of N(2) fixation by nodules. In other words, the results suggest that under water stress, nodule metabolism follows a compromise between physiological imperatives (N demand, oxidative stress) and the lower input to sustain catabolism.

  10. Concerted practice and/or conscious parallelism on an oligopolistic market

    Directory of Open Access Journals (Sweden)

    Đuričić Jovana

    2011-01-01

    Full Text Available The competition represents a desirable state of the market in every society. Putting a lot of effort in trying to be better than each other, the competitors of the market, where there is a fair competition, contribute to making that market more advanced than the other one with the weaker competition. However it has become quite frequent to come across the violation of the competition in modern society. It is usually done by making different agreements or with explicit or tacit coordination of conduct on the market. Apart from these, there are many other ways for doing so, with the aim of getting certain benefits, especially making extra profit. In addition to that, there are some restrictions on the competition on oligopolistic markets too, yet, those markets are covered with different market forms which cannot be easily distinguished from the forbidden ones. This paper defines the relation between the concerted practice and conscious parallelism on an oligopolistic market, which is the example of a restricted market conduct, and the one which just seems to be legal, according to the practice of the European Court of Justice.

  11. Conditioning Methodologies for DanceSport: Lessons from Gymnastics, Figure Skating, and Concert Dance Research.

    Science.gov (United States)

    Outevsky, David; Martin, Blake Cw

    2015-12-01

    Dancesport, the competitive branch of ballroom dancing, places high physiological and psychological demands on its practitioners, but pedagogical resources in these areas for this dance form are limited. Dancesport competitors could benefit from strategies used in other aesthetic sports. In this review, we identify conditioning methodologies from gymnastics, figure skating, and contemporary, modern, and ballet dance forms that could have relevance and suitability for dancesport training, and propose several strategies for inclusion in the current dancesport curriculum. We reviewed articles derived from Google Scholar, PubMed, ScienceDirect, Taylor & Francis Online, and Web of Science search engines and databases, with publication dates from 1979 to 2013. The keywords included MeSH terms: dancing, gymnastics, physiology, energy metabolism, physical endurance, and range of motion. Out of 47 papers examined, 41 papers met the inclusion criteria (validity of scientific methods, topic relevance, transferability to dancesport, publication date). Quality and validity of the data were assessed by examining the methodologies in each study and comparing studies on similar populations as well as across time using the PRISMA 2009 checklist and flowchart. The relevant research suggests that macro-cycle periodization planning, aerobic and anaerobic conditioning, range of motion and muscular endurance training, and performance psychology methods have potential for adaptation for dancesport training. Dancesport coaches may help their students fulfill their ambitions as competitive athletes and dance artists by adapting the relevant performance enhancement strategies from gymnastics, figure skating, and concert dance forms presented in this paper.

  12. The Interplay Between Saline Fluid Flow and Dynamic Permeability in Magmatic-Hydrothermal Systems

    Science.gov (United States)

    Weis, P.

    2014-12-01

    Magmatic-hydrothermal ore deposits document the interplay between saline fluid flow and rock permeability. Numerical simulations of multi-phase flow of variably miscible, compressible H20-NaCl fluids in concert with a dynamic permeability model can reproduce characteristics of porphyry copper and epithermal gold systems. This dynamic permeability model incorporates depth-dependent permeability profiles characteristic for tectonically active crust as well as pressure- and temperature-dependent relationships describing hydraulic fracturing and the transition from brittle to ductile rock behavior. In response to focused expulsion of magmatic fluids from a crystallizing upper crustal magma chamber, the hydrothermal system self-organizes into a hydrological divide, separating an inner part dominated by ascending magmatic fluids under near-lithostatic pressures from a surrounding outer part dominated by convection of colder meteoric fluids under near-hydrostatic pressures. This hydrological divide also provides a mechanism to transport magmatic salt through the crust, and prevents the hydrothermal system to become "clogged" by precipitation of solid halite due to depressurization of saline, high-temperature magmatic fluids. The same physical processes at similar permeability ranges, crustal depths and flow rates are relevant for a number of active systems, including geothermal resources and excess degassing at volcanos. The simulations further suggest that the described mechanism can separate the base of free convection in high-enthalpy geothermal systems from the magma chamber as a driving heat source by several kilometers in the vertical direction in tectonic settings with hydrous magmatism. This hydrology would be in contrast to settings with anhydrous magmatism, where the base of the geothermal systems may be closer to the magma chamber.

  13. Interplay between apoptosis and autophagy in colorectal cancer.

    Science.gov (United States)

    Qian, Hao-Ran; Shi, Zhao-Qi; Zhu, He-Pan; Gu, Li-Hu; Wang, Xian-Fa; Yang, Yi

    2017-09-22

    Autophagy and apoptosis are two pivotal mechanisms in mediating cell survival and death. Cross-talk of autophagy and apoptosis has been documented in the tumorigenesis and progression of cancer, while the interplay between the two pathways in colorectal cancer (CRC) has not yet been comprehensively summarized. In this study, we outlined the basis of apoptosis and autophagy machinery firstly, and then reviewed the recent evidence in cellular settings or animal studies regarding the interplay between them in CRC. In addition, several key factors that modulate the cross-talk between autophagy and apoptosis as well as its significance in clinical practice were discussed. Understanding of the interplay between the cell death mechanisms may benefit the translation of CRC treatment from basic research to clinical use.

  14. Evidence for concerted ring opening and C–Br bond breaking in UV-excited bromocyclopropane

    Energy Technology Data Exchange (ETDEWEB)

    Pandit, Shubhrangshu; Preston, Thomas J.; Orr-Ewing, Andrew J., E-mail: a.orr-ewing@bristol.ac.uk [School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS (United Kingdom); King, Simon J.; Vallance, Claire [Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA (United Kingdom)

    2016-06-28

    Photodissociation of gaseous bromocyclopropane via its A-band continuum has been studied at excitation wavelengths ranging from 230 nm to 267 nm. Velocity-map images of ground-state bromine atoms (Br), spin-orbit excited bromine atoms (Br{sup ∗}), and C{sub 3}H{sub 5} hydrocarbon radicals reveal the kinetic energies of these various photofragments. Both Br and Br{sup ∗} atoms are predominantly generated via repulsive excited electronic states in a prompt photodissociation process in which the hydrocarbon co-fragment is a cyclopropyl radical. However, the images obtained at the mass of the hydrocarbon radical fragment identify a channel with total kinetic energy greater than that deduced from the Br and Br{sup ∗} images, and with a kinetic energy distribution that exceeds the energetic limit for Br + cyclopropyl radical products. The velocity-map images of these C{sub 3}H{sub 5} fragments have lower angular anisotropies than measured for Br and Br{sup ∗}, indicating molecular restructuring during dissociation. The high kinetic energy C{sub 3}H{sub 5} signals are assigned to allyl radicals generated by a minor photochemical pathway which involves concerted C–Br bond dissociation and cyclopropyl ring-opening following single ultraviolet (UV)-photon absorption. Slow photofragments also contribute to the velocity map images obtained at the C{sub 3}H{sub 5} radical mass, but the corresponding slow Br atoms are not observed. These features in the images are attributed to C{sub 3}H{sub 5}{sup +} from the photodissociation of the C{sub 3}H{sub 5}Br{sup +} molecular cation following two-photon ionization of the parent compound. This assignment is confirmed by 118-nm vacuum ultraviolet ionization studies that prepare the molecular cation in its ground electronic state prior to UV photodissociation.

  15. Evidence for concerted ring opening and C-Br bond breaking in UV-excited bromocyclopropane.

    Science.gov (United States)

    Pandit, Shubhrangshu; Preston, Thomas J; King, Simon J; Vallance, Claire; Orr-Ewing, Andrew J

    2016-06-28

    Photodissociation of gaseous bromocyclopropane via its A-band continuum has been studied at excitation wavelengths ranging from 230 nm to 267 nm. Velocity-map images of ground-state bromine atoms (Br), spin-orbit excited bromine atoms (Br(∗)), and C3H5 hydrocarbon radicals reveal the kinetic energies of these various photofragments. Both Br and Br(∗) atoms are predominantly generated via repulsive excited electronic states in a prompt photodissociation process in which the hydrocarbon co-fragment is a cyclopropyl radical. However, the images obtained at the mass of the hydrocarbon radical fragment identify a channel with total kinetic energy greater than that deduced from the Br and Br(∗) images, and with a kinetic energy distribution that exceeds the energetic limit for Br + cyclopropyl radical products. The velocity-map images of these C3H5 fragments have lower angular anisotropies than measured for Br and Br(∗), indicating molecular restructuring during dissociation. The high kinetic energy C3H5 signals are assigned to allyl radicals generated by a minor photochemical pathway which involves concerted C-Br bond dissociation and cyclopropyl ring-opening following single ultraviolet (UV)-photon absorption. Slow photofragments also contribute to the velocity map images obtained at the C3H5 radical mass, but the corresponding slow Br atoms are not observed. These features in the images are attributed to C3H5 (+) from the photodissociation of the C3H5Br(+) molecular cation following two-photon ionization of the parent compound. This assignment is confirmed by 118-nm vacuum ultraviolet ionization studies that prepare the molecular cation in its ground electronic state prior to UV photodissociation.

  16. Concerted bis-alkylating reactivity of clerocidin towards unpaired cytosine residues in DNA

    Science.gov (United States)

    Richter, Sara N.; Menegazzo, Ileana; Fabris, Daniele; Palumbo, Manlio

    2004-01-01

    Clerocidin (CL) is a topoisomerase II poison, which cleaves DNA irreversibly at guanines (G) and reversibly at cytosines (C). Furthermore, the drug can induce enzyme-independent strand breaks at the G and C level. It has been previously shown that G-damage is induced by alkylation of the guanine N7, followed by spontaneous depurination and nucleic acid cleavage, whereas scission at C is obtained only after treatment with hot alkali, and no information is available to explain the nature of this damage. We present here a systematic study on the reactivity of CL towards C both in the DNA environment and in solution. Selected synthetic derivatives were employed to evaluate the role of each chemical group of the drug. The structure of CL–dC adduct was then characterized by tandem mass spectrometry and NMR: the adduct is a stable condensed ring system resulting from a concerted electrophilic attack of the adjacent carbonyl and epoxide groups of CL towards the exposed NH2 and N3, respectively. This reaction mechanism, shown here for the first time, is characterized by faster kinetic rates than alkylation at G, due to the fact that the rate-determining step, alkylation at the epoxide, is an intramolecular process, provided a Schiff base linking CL and C can rapidly form, whereas the corresponding reaction of G N7 is intermolecular. These results provide helpful hints to explain the reversible/irreversible nature of topoisomerase II mediated DNA damage produced by CL at C/G steps. PMID:15494453

  17. Following Musical Shows: A Study with Focal Groups on Satisfaction of Musical Concerts Regular Visitors and Socialization between Them

    Directory of Open Access Journals (Sweden)

    Lúmia Massa Garcia Pires

    2017-06-01

    Full Text Available This article aimed to identify which attributes impact more significantly on the satisfaction of concerts’ regular visitors and socialization between them when inserted in these kinds of events. Thus, we used a qualitative methodology, performing focus groups. Among the main results of this study, we found, regarding satisfaction of concerts’ visitors, the attributes that most influence the public are related to services - especially for beverage supply, cleaning of bathrooms and lines formed inside the event - organization, show infrastructure and performance artists. Furthermore, considering the socialization of the visitors, we found that most respondents often go to concerts together with other people, but some did not exclude the possibility to attend the concerts alone when it comes to a familiar artist.

  18. Chinese Dream——Concert in Commemoration of 115th Birth Anniversary of Premier Zhou Enlai Held

    Institute of Scientific and Technical Information of China (English)

    Our; Staff; Reporter

    2013-01-01

    <正>The theme song of the film The Founding of a Republic sung by male vocalists Dai Yuqiang and Wei Song reverberated in the Opera Hall at the National Center for the Performing Arts on the `evening of March 14. It marked the start of the concert in commemoration of the 115th anniversary of the birth of Premier Zhou Enlai, with "Chinese Dream" as the theme.

  19. Creating personalized memories from social events: Community-based support for multi-camera recordings of school concerts

    OpenAIRE

    Guimaraes R.L.; Cesar P.; Bulterman D.C.A.; Zsombori V.; Kegel I.

    2011-01-01

    htmlabstractThe wide availability of relatively high-quality cameras makes it easy for many users to capture video fragments of social events such as concerts, sports events or community gatherings. The wide availability of simple sharing tools makes it nearly as easy to upload individual fragments to on-line video sites. Current work on video mashups focuses on the creation of a video summary based on the characteristics of individual media fragments, but it fails to address the interpersona...

  20. SPECIFIC FEATURES OF THE MUSICAL LANGUAGE AND TEXTURE IN THE CONCERT WALTZ FOR TWO PIANOS BY OLEG NEGRUTA

    Directory of Open Access Journals (Sweden)

    MAMALÂGA MARINA

    2017-06-01

    Full Text Available The article analyzes the Concert Waltz by Oleg Negruta written for piano duet. This work is considered in terms of form and content. Special attention is given to identifying the specificity of the musical language and texture. As a result, the conclusion is that the originality of the composer’s style is manifested in bright melody, relying on the classic-romantic harmony, enriched by jazz elements.

  1. GENESIS OF KHARKOV MUSIC CULTURE IN THE HIGHLIGHT OF THE CITY’S EDUCATION AND CONCERT LIFE FORMATION

    Directory of Open Access Journals (Sweden)

    Olena Kononova

    2016-02-01

    Full Text Available The article highlights the genesis of Kharkov musical culture from the late 18th to the first half of the 19th century, studying it in terms of two aspects, the formation of education and the emergence of the city’s concert life.The relevance of the research subject chosen by the author is determined by the wish to give the fullest description of the multi-layered process of formation of Kharkov musical culture which played one of the leading roles in the history of Ukrainian culture, and to acquaint the Western public with the most interesting facts of the formation and development of a reputable East-European centre. The main range of issues discussed in the article covers the period of the innitial foundation of artistic education, and its influence on the expansion and perception of music in different social circles, presenting the structures and forms of the nascent musical life of Kharkov. The section "Specific features of the Ukrainian system of education" brings out the facts which indicate the progressive tendencies in education, especially, on the territory of Sloboda Ukraine. The formation of artistic education in the religious schools of the city is covered in the section "Genesis of musical education in Kharkov". One of the most productive periods of the city’s cultivation of concert life associated with the functioning of the University is analyzed in the section "The impact of the University music activities on the city's concert going." The Conclusion emphasizes the interaction of traditional and nontraditional in the musical culture of Kharkov that was clearly manifested in the concert activities of the University, in particular, in popularization of oratorios. Furthermore, it discusses the factors which participated in the development in the field of compositional achievement as well as the performing arts and opened new perspectives in the dynamics of the artistic life of the Ukrainian city.

  2. “AGREEMENTS”, “DECISIONS” AND “CONCERTED PRACTICES”: KEY CONCEPTS IN THE ANALYSIS OF ANTICOMPETITIVE AGREEMENTS

    Directory of Open Access Journals (Sweden)

    CRISTINA CUCU

    2013-05-01

    Full Text Available In their economic activity, undertakings conclude many agreements between them. But agreements between undertakings which can distort the competition -anticompetitive agreements- are prohibited. The Romanian and EU law prohibit “all agreements between undertakings, decisions by associations of undertakings and concerted practices which have as their object or effect the prevention, restriction or distortion of competition”. However, the terms ”agreements”, ”decisions” or ”concerted practices” are nowhere defined in the EU Treaties or in the Romanian law. These terms are key concepts in the analysis of anticompetitive agreements which can distort the competition. In the lack of a legal definition, these concepts have generated a complex body of jurisprudence, which has to be identified. The analysis of these key concepts necessarily entails the conceptual delimitation of the notions. On this purpose, the relevant legal provisions will be identified in the Romanian and EU law, as well as the decisions of the European Court of Justice in this matter. The present paper intends to present the conceptual evolution of the analysed notions, paying special attention to concerted practices and to parallel behaviour in price fixing on the market.

  3. Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.

    Science.gov (United States)

    Caligiore, Daniele; Pezzulo, Giovanni; Baldassarre, Gianluca; Bostan, Andreea C; Strick, Peter L; Doya, Kenji; Helmich, Rick C; Dirkx, Michiel; Houk, James; Jörntell, Henrik; Lago-Rodriguez, Angel; Galea, Joseph M; Miall, R Chris; Popa, Traian; Kishore, Asha; Verschure, Paul F M J; Zucca, Riccardo; Herreros, Ivan

    2017-02-01

    Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.

  4. Cooperative DNA Recognition Modulated by an Interplay between Protein-Protein Interactions and DNA-Mediated Allostery.

    Directory of Open Access Journals (Sweden)

    Felipe Merino

    2015-06-01

    Full Text Available Highly specific transcriptional regulation depends on the cooperative association of transcription factors into enhanceosomes. Usually, their DNA-binding cooperativity originates from either direct interactions or DNA-mediated allostery. Here, we performed unbiased molecular simulations followed by simulations of protein-DNA unbinding and free energy profiling to study the cooperative DNA recognition by OCT4 and SOX2, key components of enhanceosomes in pluripotent cells. We found that SOX2 influences the orientation and dynamics of the DNA-bound configuration of OCT4. In addition SOX2 modifies the unbinding free energy profiles of both DNA-binding domains of OCT4, the POU specific and POU homeodomain, despite interacting directly only with the first. Thus, we demonstrate that the OCT4-SOX2 cooperativity is modulated by an interplay between protein-protein interactions and DNA-mediated allostery. Further, we estimated the change in OCT4-DNA binding free energy due to the cooperativity with SOX2, observed a good agreement with experimental measurements, and found that SOX2 affects the relative DNA-binding strength of the two OCT4 domains. Based on these findings, we propose that available interaction partners in different biological contexts modulate the DNA exploration routes of multi-domain transcription factors such as OCT4. We consider the OCT4-SOX2 cooperativity as a paradigm of how specificity of transcriptional regulation is achieved through concerted modulation of protein-DNA recognition by different types of interactions.

  5. Gene-Environment Interplay, Family Relationships, and Child Adjustment

    Science.gov (United States)

    Horwitz, Briana N.; Neiderhiser, Jenae M.

    2011-01-01

    This paper reviews behavioral genetic research from the past decade that has moved beyond simply studying the independent influences of genes and environments. The studies considered in this review have instead focused on understanding gene-environment interplay, including genotype-environment correlation (rGE) and genotype x environment…

  6. Improving the Interplay between Usability Evaluation and User Interface Design

    DEFF Research Database (Denmark)

    Hornbæk, K.; Stage, Jan

    2004-01-01

    of the workshop are motivated and an outline of the contents of the papers that were presented in the workshop is given. In addition we summarize some challenges to the interplay between usability evaluation and user interface design agreed upon at the workshop, as well as some solutions that were debated....

  7. Understanding the interplay of cancer patients' instrumental concerns and emotions.

    Science.gov (United States)

    Brandes, Kim; van der Goot, Margot J; Smit, Edith G; van Weert, Julia C M; Linn, Annemiek J

    2017-05-01

    1) to assess patients' descriptions of concerns, and 2) to inform a conceptual framework in which the impact of the nature of concerns on doctor-patient communication is specified. Six focus groups were conducted with 39 cancer patients and survivors. In these focus groups participants were asked to describe their concerns during and after their illness. Concerns were described as instrumental concerns (e.g., receiving insufficient information) and emotions (e.g., sadness). Patients frequently explained their concerns as an interplay of instrumental concerns and emotions. Examples of the interplay were "receiving incorrect information" and "frustration", and "difficulties with searching, finding and judging of information" and "fear". Instrumental concerns need to be taken into account in the operationalization of concerns in research. Based on the interplay, the conceptual framework suggests that patients can express instrumental concerns as emotions and emotions as instrumental concerns. Consequently, providers can respond with instrumental and emotional communication when patients express an interplay of concerns. The results of this study can be used to support providers in recognizing concerns that are expressed by patients in consultations. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Interplay between Colloids and Interfaces : Emulsions, Foams and Microtubes

    NARCIS (Netherlands)

    de Folter, J.W.J.

    2013-01-01

    The central theme of this thesis is the interplay between colloids and interfaces. The adsorption of colloids at fluid-fluid interfaces is the main topic and covers Chapters 2-6. Pickering emulsions where colloidal particles act as emulsion stabilizers in the absence of surfactants are studied in a

  9. Beyond Conflict: Functional Facets of the Work-Family Interplay

    Science.gov (United States)

    Wiese, Bettina S.; Seiger, Christine P.; Schmid, Christian M.; Freund, Alexandra M.

    2010-01-01

    The present paper deals with three positive facets of the work-family interplay, i.e., transfer of competencies, transfer of positive mood, and cross-domain compensation. The latter refers to the experience that engagement in one domain helps dealing with failures in the other domain. In two correlational studies (N[subscript 1] = 107 working…

  10. Collaborative Improvement – Interplay but not a Game

    DEFF Research Database (Denmark)

    Kaltoft, Rasmus; Boer, Harry; Chapman, Ross

    2006-01-01

    improvement. This article reports research aimed at developing a deeper understanding of that interplay. Ten relationships between ten factors are presented and discussed. It appears that vision, approach, trust and commercial reality are the strongest factors. These factors are, however, influenced by...

  11. A note on the interplay between symmetries, reduction and ...

    Indian Academy of Sciences (India)

    A note on the interplay between symmetries, reduction and conservation laws of Stokes' first problem for third-grade rotating fluids ... Department of Mathematics, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Skudai, Johor, Malaysia; Ibnu Sina Institute for Fundamental Science Studies, Universiti Teknologi ...

  12. Information concerning the results of the concerted work stoppage on 22 June 2011 (from 8-30 to 12-30)

    CERN Multimedia

    Human Resources Department

    2011-01-01

     Following the concerted work stoppage called by the Staff Association for 22 June 2011 concerning the measures aimed at restoring the financial equilibrium of the Pension Fund, HR Department invited staff members and fellows to declare whether or not they had participated in this action. As indicated in the communication sent to the persons concerned, it was assumed that those who did not complete the electronic declaration form did not take part in the work stoppage. The results are as follows:     Staff and fellows Declarations: Yes (took part in the concerted work stoppage) 373 Declarations: No (did not take part in the concerted work stoppage) 386 Those requisitioned 120 Those not able to participate in the concerted work stoppage (leave, absence, training…) ...

  13. Chitin and stress induced protein kinase activation

    DEFF Research Database (Denmark)

    Kenchappa, Chandra Shekar; Azevedo da Silva, Raquel; Bressendorff, Simon

    2017-01-01

    The assays described here are pertinent to protein kinase studies in any plant. They include an immunoblot phosphorylation/activation assay and an in-gel activity assay for MAP kinases (MPKs) using the general protein kinase substrate myelin basic protein. They also include a novel in-gel peptide...... substrate assay for Snf1-related kinase family 2 members (SnRK2s). This kinase family-specific assay overcomes some limitations of in-gel assays and permits the identification of different types of kinase activities in total protein extracts....

  14. Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes

    DEFF Research Database (Denmark)

    Petersen, Rasmus Koefoed; Madsen, Lise; Pedersen, Lone Møller

    2008-01-01

    AMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho......-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of c......AMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response....

  15. Trophoblast cell fusion and differentiation are mediated by both the protein kinase C and a pathways.

    Directory of Open Access Journals (Sweden)

    Waka Omata

    Full Text Available The syncytiotrophoblast of the human placenta is an epithelial barrier that interacts with maternal blood and is a key for the transfer of nutrients and other solutes to the developing fetus. The syncytiotrophoblast is a true syncytium and fusion of progenitor cytotrophoblasts is the cardinal event leading to the formation of this layer. BeWo cells are often used as a surrogate for cytotrophoblasts, since they can be induced to fuse, and then express certain differentiation markers associated with trophoblast syncytialization. Dysferlin, a syncytiotrophoblast membrane repair protein, is up-regulated in BeWo cells induced to fuse by treatment with forskolin; this fusion is thought to occur through cAMP/protein kinase A-dependent mechanisms. We hypothesized that dysferlin may also be up-regulated in response to fusion through other pathways. Here, we show that BeWo cells can also be induced to fuse by treatment with an activator of protein kinase C, and that this fusion is accompanied by increased expression of dysferlin. Moreover, a dramatic synergistic increase in dysferlin expression is observed when both the protein kinase A and protein kinase C pathways are activated in BeWo cells. This synergy in fusion is also accompanied by dramatic increases in mRNA for the placental fusion proteins syncytin 1, syncytin 2, as well as dysferlin. Dysferlin, however, was shown to be dispensable for stimulus-induced BeWo cell syncytialization, since dysferlin knockdown lines fused to the same extent as control cells. The classical trophoblast differentiation marker human chorionic gonadotropin was also monitored and changes in the expression closely parallel that of dysferlin in all of the experimental conditions employed. Thus different biochemical markers of trophoblast fusion behave in concert supporting the hypothesis that activation of both protein kinase C and A pathways lead to trophoblastic differentiation.

  16. Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

    International Nuclear Information System (INIS)

    Park, In-Hyun; Erbay, Ebru; Nuzzi, Paul; Chen Jie

    2005-01-01

    The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

  17. Les concerts européens à la radio dans l'entre-deux-guerres : mise en ondes d'une métaphore diplomatique

    NARCIS (Netherlands)

    Laborie, L.; Lommers, S.B.

    2008-01-01

    L’expression « concert européen » s’applique à la fois aux relations diplomatiques tissées entre les Etats au xixe siècle et à la diffusion d’émissions musicales à l’échelle continentale entre 1929 et 1939. Au-delà des prouesses techniques, l’ambition culturelle et pacifiste de ces concerts

  18. A bipolar clamp mechanism for activation of Jak-family protein tyrosine kinases.

    Directory of Open Access Journals (Sweden)

    Dipak Barua

    2009-04-01

    Full Text Available Most cell surface receptors for growth factors and cytokines dimerize in order to mediate signal transduction. For many such receptors, the Janus kinase (Jak family of non-receptor protein tyrosine kinases are recruited in pairs and juxtaposed by dimerized receptor complexes in order to activate one another by trans-phosphorylation. An alternative mechanism for Jak trans-phosphorylation has been proposed in which the phosphorylated kinase interacts with the Src homology 2 (SH2 domain of SH2-B, a unique adaptor protein with the capacity to homo-dimerize. Building on a rule-based kinetic modeling approach that considers the concerted nature and combinatorial complexity of modular protein domain interactions, we examine these mechanisms in detail, focusing on the growth hormone (GH receptor/Jak2/SH2-Bbeta system. The modeling results suggest that, whereas Jak2-(SH2-Bbeta(2-Jak2 heterotetramers are scarcely expected to affect Jak2 phosphorylation, SH2-Bbeta and dimerized receptors synergistically promote Jak2 trans-activation in the context of intracellular signaling. Analysis of the results revealed a unique mechanism whereby SH2-B and receptor dimers constitute a bipolar 'clamp' that stabilizes the active configuration of two Jak2 molecules in the same macro-complex.

  19. Outreach for Families and Girls- Astronomy at Outdoor Concerts and at Super Bowl or Halloween Star Parties

    Science.gov (United States)

    Lubowich, Donald A.

    2011-05-01

    Bring telescope to where the people are! Music and Astronomy Under the Stars (MAUS) is a NASA-funded as astronomy outreach program at community parks and music festivals (1000 - 25,000 people/event). While there have been many astronomy outreach activities and telescope observations at sidewalks and parks, this program targets a different audience - music lovers who are attending concerts in community parks or festivals. These music lovers who may not have visited science museums, planetariums, or star parties are exposed to telescope observations and astronomy information with no additional travel costs. MAUS includes solar observing, telescope observations including a live imaging system, an astronomical video, astronomy banners/posters, and hands-on activities. MAUS increased awareness, engagement, and interest in astronomy at classical, pop, rock, and ethnic music concerts. Since 2009 over 50,000 people have participated in these outreach activities including a significant number of families and young girls. In addition to concerts in local Long Island parks, there were MUAS events at Tanglewood (summer home of the Boston Symphony Orchestra), Jazz in Central Park, and Astronomy Night on the National Mall (co-sponsored by the White House Office of Science and Technology Policy). In 2011 MUAS will be expanded to include Ravinia (summer home of the Chicago Symphony Orchestra), the Newport Folk Festival, and the Bethel Woods Center for the Arts (site of the 1969 Woodstock festival). According to our survey results, music lovers became more informed about astronomy. Expanding Hofstra University's successful outreach programs, I propose the creation of a National Halloween Stars event targeting children and a National Super Bowl Star Party targeting girls, women, and the 2/3 of Americans who do not watch the Super Bowl. This can be combined with astronomers or amateur astronomers bringing telescopes to Super Bowl parties for football fans to stargaze during

  20. CONCERT. ''European joint programme for the integration of radiation protection research''

    International Nuclear Information System (INIS)

    Schmitt-Hannig, A.; Birschwilks, M.; Jung, T.

    2016-01-01

    CONCERT is a joint project of the EU and its member states which assume joint financing: Over the next five years the largest European radiation protection programme so far will have available about 28 Million Euros for research and integrative measures, whereby the European Commission will bear 70 per cent of the costs. Integrative measures include, among others, targeted vocational education and training of junior researchers in radiation protection, better access to research and irradiation facilities for scientists, as well as a stronger connection of universities and research centres in radiation protection research.

  1. Variants of Interplay as Drivers of Media Change

    Directory of Open Access Journals (Sweden)

    Tilo Grenz

    2017-09-01

    Full Text Available This article conceptualizes acting on media in terms of different interplays between focal actors, users, and user communities. It is argued that—in times of mediated visibility, the increasing entanglement of social and technological change, and accelerated feedback loops—arenas of negotiation emerge and therewith the complexities of relations between producers and users increases. Using insights from the fields of Wii hacking, Circuit Bending, and online poker tools, three variants of interplay are presented and discussed: integration, segregation, and permanent confrontation. Whilst a process-oriented perspective on reciprocal action is developed the paper contributes (a to a balanced perspective on what is often a one-sided discussion regarding the actions leading to media change, and (b to the understanding of the relation between media change and reflexive modernity.

  2. Top partner-resonance interplay in a composite Higgs framework

    Science.gov (United States)

    Yepes, Juan; Zerwekh, Alfonso

    2018-04-01

    Guided us by the scenario of weak scale naturalness and the possible existence of exotic resonances, we have explored in a SO(5) Composite Higgs setup the interplay among three matter sectors: elementary, top partners and vector resonances. We parametrize it through explicit interactions of spin-1 SO(4)-resonances, coupled to the SO(5)-invariant fermionic currents and tensors presented in this work. Such invariants are built upon the Standard Model fermion sector as well as top partners sourced by the unbroken SO(4). The mass scales entailed by the top partner and vector resonance sectors will control the low energy effects emerging from our interplaying model. Its phenomenological impact and parameter spaces have been considered via flavor-dijet processes and electric dipole moments bounds. Finally, the strength of the Nambu-Goldstone symmetry breaking and the extra couplings implied by the top partner mass scales are measured in accordance with expected estimations.

  3. Flag varieties an interplay of geometry, combinatorics, and representation theory

    CERN Document Server

    Lakshmibai, V

    2009-01-01

    Flag varieties are important geometric objects and their study involves an interplay of geometry, combinatorics, and representation theory. This book is detailed account of this interplay. In the area of representation theory, the book presents a discussion of complex semisimple Lie algebras and of semisimple algebraic groups; in addition, the representation theory of symmetric groups is also discussed. In the area of algebraic geometry, the book gives a detailed account of the Grassmannian varieties, flag varieties, and their Schubert subvarieties. Because of the connections with root systems, many of the geometric results admit elegant combinatorial description, a typical example being the description of the singular locus of a Schubert variety. This is shown to be a consequence of standard monomial theory (abbreviated SMT). Thus the book includes SMT and some important applications - singular loci of Schubert varieties, toric degenerations of Schubert varieties, and the relationship between Schubert variet...

  4. Mechanism of adenylate kinase: Site-directed mutagenesis versus x-ray and NMR

    International Nuclear Information System (INIS)

    Tsai, Mingdaw; Yan, Honggao

    1991-01-01

    Controversy is an integral part of scientific research and is often a precursor to the truth. However, this lesson has been learned in a very hard way in the case of the structure-function relationship of adenylate kinase (AK), which catalyzes the interconversion between MgATP+AMP and MgADP+ADP. While this small kinase has been considered a model kinase and the enzyme-substrate interaction of AK was among the first investigated by X-ray crystallography and NMR the substrate binding sites deduced from the early studies by these two powerful techniques (termed the X-ray model and the NMR model, respectively) were dramatically different. Ironically, both models have had substantial impact on researchers in related fields. The problems have finally been dealt with since 1987 by the interplay between site-directed mutagenesis, X-ray, and NMR. The purpose of this review is not only to summarize the current knowledge in the structure-function relationship of adenylate kinase but also to accurately document and critically analyze historical developments in the hope that history will not be repeated

  5. Interplay of gravitation and linear superposition of different mass eigenstates

    International Nuclear Information System (INIS)

    Ahluwalia, D.V.

    1998-01-01

    The interplay of gravitation and the quantum-mechanical principle of linear superposition induces a new set of neutrino oscillation phases. These ensure that the flavor-oscillation clocks, inherent in the phenomenon of neutrino oscillations, redshift precisely as required by Einstein close-quote s theory of gravitation. The physical observability of these phases in the context of the solar neutrino anomaly, type-II supernova, and certain atomic systems is briefly discussed. copyright 1998 The American Physical Society

  6. Active intestinal drug absorption and the solubility-permeability interplay.

    Science.gov (United States)

    Porat, Daniel; Dahan, Arik

    2018-02-15

    The solubility-permeability interplay deals with the question: what is the concomitant effect on the drug's apparent permeability when increasing the apparent solubility with a solubility-enabling formulation? The solubility and the permeability are closely related, exhibit certain interplay between them, and ongoing research throughout the past decade shows that treating the one irrespectively of the other may be insufficient. The aim of this article is to provide an overview of the current knowledge on the solubility-permeability interplay when using solubility-enabling formulations for oral lipophilic drugs, highlighting active permeability aspects. A solubility-enabling formulation may affect the permeability in opposite directions; the passive permeability may decrease as a result of the apparent solubility increase, according to the solubility-permeability tradeoff, but at the same time, certain components of the formulation may inhibit/saturate efflux transporters (when relevant), resulting in significant apparent permeability increase. In these cases, excipients with both solubilizing and e.g. P-gp inhibitory properties may lead to concomitant increase of both the solubility and the permeability. Intelligent development of such formulation will account for the simultaneous effects of the excipients' nature/concentrations on the two arms composing the overall permeability: the passive and the active arms. Overall, thorough mechanistic understanding of the various factors involved in the solubility-permeability interplay may allow developing better solubility-enabling formulations, thereby exploiting the advantages analyzed in this article, offering oral delivery solution even for BCS class IV drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Interplay between endogenous and exogenous fluctuations in financial markets

    OpenAIRE

    Gontis, Vygintas

    2016-01-01

    We address microscopic, agent based, and macroscopic, stochastic, modeling of the financial markets combining it with the exogenous noise. The interplay between the endogenous dynamics of agents and the exogenous noise is the primary mechanism responsible for the observed long-range dependence and statistical properties of high volatility return intervals. By exogenous noise we mean information flow or/and order flow fluctuations. Numerical results based on the proposed model reveal that the ...

  8. Interplay between Candida albicans and the Mammalian Innate Host Defense

    Science.gov (United States)

    Cheng, Shih-Chin; Joosten, Leo A. B.; Kullberg, Bart-Jan

    2012-01-01

    Candida albicans is both the most common fungal commensal microorganism in healthy individuals and the major fungal pathogen causing high mortality in at-risk populations, especially immunocompromised patients. In this review, we summarize the interplay between the host innate system and C. albicans, ranging from how the host recognizes, responds, and clears C. albicans infection to how C. albicans evades, dampens, and escapes from host innate immunity. PMID:22252867

  9. Problematising the interplay between employment relations, migration and mobility

    OpenAIRE

    Rodriguez, Jenny; Mearns, Lesley

    2012-01-01

    The purpose of this paper is to introduce the special issue by problematising labour agency, precariousness, and labour fragmentation as defining themes of the interplay between employment relations, migration and mobility. Drawing from discussions about the impact of globalisation on changes in features of work and employment, and bringing together theory and research on employment relations and labour migration, the paper discusses the relational spatial and temporal nature of agency, the d...

  10. Non-Viral Deoxyribonucleoside Kinases

    DEFF Research Database (Denmark)

    Christiansen, Louise Slot; Munch-Petersen, Birgitte; Knecht, Wolfgang

    2015-01-01

    Deoxyribonucleoside kinases (dNKs) phosphorylate deoxyribonucleosides to their corresponding monophosphate compounds. dNks also phosphorylate deoxyribonucleoside analogues that are used in the treatment of cancer or viral infections. The study of the mammalian dNKs has therefore always been of gr...

  11. Nonequilibrium localization and the interplay between disorder and interactions

    International Nuclear Information System (INIS)

    Mascarenhas, Eduardo; Bragança, Helena; Aguiar, M C O; França Santos, M; Drumond, R

    2016-01-01

    We study the nonequilibrium interplay between disorder and interactions in a closed quantum system. We base our analysis on the notion of dynamical state-space localization, calculated via the Loschmidt echo. Although real-space and state-space localization are independent concepts in general, we show that both perspectives may be directly connected through a specific choice of initial states, namely, maximally localized states (ML-states). We show numerically that in the noninteracting case the average echo is found to be monotonically increasing with increasing disorder; these results are in agreement with an analytical evaluation in the single particle case in which the echo is found to be inversely proportional to the localization length. We also show that for interacting systems, the length scale under which equilibration may occur is upper bounded and such bound is smaller the greater the average echo of ML-states. When disorder and interactions, both being localization mechanisms, are simultaneously at play the echo features a non-monotonic behaviour indicating a non-trivial interplay of the two processes. This interplay induces delocalization of the dynamics which is accompanied by delocalization in real-space. This non-monotonic behaviour is also present in the effective integrability which we show by evaluating the gap statistics. (paper)

  12. Transcription factor interplay in T helper cell differentiation

    Science.gov (United States)

    Evans, Catherine M.

    2013-01-01

    The differentiation of CD4 helper T cells into specialized effector lineages has provided a powerful model for understanding immune cell differentiation. Distinct lineages have been defined by differential expression of signature cytokines and the lineage-specifying transcription factors necessary and sufficient for their production. The traditional paradigm of differentiation towards Th1 and Th2 subtypes driven by T-bet and GATA3, respectively, has been extended to incorporate additional T cell lineages and transcriptional regulators. Technological advances have expanded our view of these lineage-specifying transcription factors to the whole genome and revealed unexpected interplay between them. From these data, it is becoming clear that lineage specification is more complex and plastic than previous models might have suggested. Here, we present an overview of the different forms of transcription factor interplay that have been identified and how T cell phenotypes arise as a product of this interplay within complex regulatory networks. We also suggest experimental strategies that will provide further insight into the mechanisms that underlie T cell lineage specification and plasticity. PMID:23878131

  13. Interplay of hot electrons from localized and propagating plasmons.

    Science.gov (United States)

    Hoang, Chung V; Hayashi, Koki; Ito, Yasuo; Gorai, Naoki; Allison, Giles; Shi, Xu; Sun, Quan; Cheng, Zhenzhou; Ueno, Kosei; Goda, Keisuke; Misawa, Hiroaki

    2017-10-03

    Plasmon-induced hot-electron generation has recently received considerable interest and has been studied to develop novel applications in optoelectronics, photovoltaics and green chemistry. Such hot electrons are typically generated from either localized plasmons in metal nanoparticles or propagating plasmons in patterned metal nanostructures. Here we simultaneously generate these heterogeneous plasmon-induced hot electrons and exploit their cooperative interplay in a single metal-semiconductor device to demonstrate, as an example, wavelength-controlled polarity-switchable photoconductivity. Specifically, the dual-plasmon device produces a net photocurrent whose polarity is determined by the balance in population and directionality between the hot electrons from localized and propagating plasmons. The current responsivity and polarity-switching wavelength of the device can be varied over the entire visible spectrum by tailoring the hot-electron interplay in various ways. This phenomenon may provide flexibility to manipulate the electrical output from light-matter interaction and offer opportunities for biosensors, long-distance communications, and photoconversion applications.Plasmon-induced hot electrons have potential applications spanning photodetection and photocatalysis. Here, Hoang et al. study the interplay between hot electrons generated by localized and propagating plasmons, and demonstrate wavelength-controlled polarity-switchable photoconductivity.

  14. Nonequilibrium localization and the interplay between disorder and interactions.

    Science.gov (United States)

    Mascarenhas, Eduardo; Bragança, Helena; Drumond, R; Aguiar, M C O; França Santos, M

    2016-05-18

    We study the nonequilibrium interplay between disorder and interactions in a closed quantum system. We base our analysis on the notion of dynamical state-space localization, calculated via the Loschmidt echo. Although real-space and state-space localization are independent concepts in general, we show that both perspectives may be directly connected through a specific choice of initial states, namely, maximally localized states (ML-states). We show numerically that in the noninteracting case the average echo is found to be monotonically increasing with increasing disorder; these results are in agreement with an analytical evaluation in the single particle case in which the echo is found to be inversely proportional to the localization length. We also show that for interacting systems, the length scale under which equilibration may occur is upper bounded and such bound is smaller the greater the average echo of ML-states. When disorder and interactions, both being localization mechanisms, are simultaneously at play the echo features a non-monotonic behaviour indicating a non-trivial interplay of the two processes. This interplay induces delocalization of the dynamics which is accompanied by delocalization in real-space. This non-monotonic behaviour is also present in the effective integrability which we show by evaluating the gap statistics.

  15. Transcription factor interplay in T helper cell differentiation.

    Science.gov (United States)

    Evans, Catherine M; Jenner, Richard G

    2013-11-01

    The differentiation of CD4 helper T cells into specialized effector lineages has provided a powerful model for understanding immune cell differentiation. Distinct lineages have been defined by differential expression of signature cytokines and the lineage-specifying transcription factors necessary and sufficient for their production. The traditional paradigm of differentiation towards Th1 and Th2 subtypes driven by T-bet and GATA3, respectively, has been extended to incorporate additional T cell lineages and transcriptional regulators. Technological advances have expanded our view of these lineage-specifying transcription factors to the whole genome and revealed unexpected interplay between them. From these data, it is becoming clear that lineage specification is more complex and plastic than previous models might have suggested. Here, we present an overview of the different forms of transcription factor interplay that have been identified and how T cell phenotypes arise as a product of this interplay within complex regulatory networks. We also suggest experimental strategies that will provide further insight into the mechanisms that underlie T cell lineage specification and plasticity.

  16. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. There are two paralog catalytic subunits, i.e. alpha (A1) and alpha' (A2). The alpha and alpha' subunits are linked to two beta subunits to produce a heterotetrameric structure...

  17. Autoregulation of kinase dephosphorylation by ATP binding in AGC protein kinases.

    Science.gov (United States)

    Chan, Tung O; Pascal, John M; Armen, Roger S; Rodeck, Ulrich

    2012-02-01

    AGC kinases, including the three Akt (protein kinase B) isoforms, protein kinase A (PKA) and all protein kinase C (PKC) isoforms, require activation loop phosphorylation (threonine 308 in Akt1) as well as phosphorylation of a C-terminal residue (serine 473 in Akt1) for catalytic activity and phosphorylation of downstream targets. Conversely, phosphatases reverse these phosphorylations. Virtually all cellular processes are affected by AGC kinases, a circumstance that has led to intense scrutiny of the molecular mechanisms that regulate phosphorylation of these kinases. Here, we review a new layer of control of phosphorylation in Akt, PKA and PKC pointing to ATP binding pocket occupancy as a means to decelerate dephosphorylation of these and, potentially, other kinases. This additional level of kinase regulation opens the door to search for new functional motifs for the rational design of non- ATP-competitive kinase inhibitors that discriminate within and between protein kinase families.

  18. Autoregulation of kinase dephosphorylation by ATP binding to AGC protein kinases

    Science.gov (United States)

    Pascal, John M; Armen, Roger S

    2012-01-01

    AGC kinases, including the three Akt (protein kinase B) isoforms, protein kinase A (PKA) and all protein kinase C (PKC) isoforms, require activation loop phosphorylation (threonine 308 in Akt1) as well as phosphorylation of a C-terminal residue (serine 473 in Akt1) for catalytic activity and phosphorylation of downstream targets. Conversely, phosphatases reverse these phosphorylations. Virtually all cellular processes are affected by AGC kinases, a circumstance that has led to intense scrutiny of the molecular mechanisms that regulate phosphorylation of these kinases. Here, we review a new layer of control of phosphorylation in Akt, PKA and PKC pointing to ATP binding pocket occupancy as a means to decelerate dephosphorylation of these and, potentially, other kinases. This additional level of kinase regulation opens the door to search for new functional motifs for the rational design of non-ATP-competitive kinase inhibitors that discriminate within and between protein kinase families. PMID:22262182

  19. Computations on the primary photoreaction of Br2 with CO2: stepwise vs concerted addition of Br atoms.

    Science.gov (United States)

    Xu, Kewei; Korter, Timothy M; Braiman, Mark S

    2015-04-09

    It was proposed previously that Br2-sensitized photolysis of liquid CO2 proceeds through a metastable primary photoproduct, CO2Br2. Possible mechanisms for such a photoreaction are explored here computationally. First, it is shown that the CO2Br radical is not stable in any geometry. This rules out a free-radical mechanism, for example, photochemical splitting of Br2 followed by stepwise addition of Br atoms to CO2-which in turn accounts for the lack of previously observed Br2+CO2 photochemistry in gas phases. A possible alternative mechanism in liquid phase is formation of a weakly bound CO2:Br2 complex, followed by concerted photoaddition of Br2. This hypothesis is suggested by the previously published spectroscopic detection of a binary CO2:Br2 complex in the supersonically cooled gas phase. We compute a global binding-energy minimum of -6.2 kJ mol(-1) for such complexes, in a linear geometry. Two additional local minima were computed for perpendicular (C2v) and nearly parallel asymmetric planar geometries, both with binding energies near -5.4 kJ mol(-1). In these two latter geometries, C-Br and O-Br bond distances are simultaneously in the range of 3.5-3.8 Å, that is, perhaps suitable for a concerted photoaddition under the temperature and pressure conditions where Br2 + CO2 photochemistry has been observed.

  20. Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains.

    Science.gov (United States)

    Nakamura, Yuki; Hibino, Kayo; Yanagida, Toshio; Sako, Yasushi

    2016-01-01

    Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS.

  1. Conference-concert with Frédéric Bernachon on Thursday, 8 March at 6 pm

    CERN Multimedia

    Staff Association

    2018-01-01

    The Staff Association is pleased to invite you to an educational conference-concert of classical piano by Frédéric Bernachon « Beethoven : sa vie et son destin au cœur de la sonate Pathétique » on Thursday, 8 March at 6 pm Main Auditorium (500-1-001) Length: 60-90 minutes. Free entrance, cocktails served after the concert. External visitors, please contact the Staff Association for a visitor card: staff.association@cern.ch or +41 22 76 63738 With the help of a piano, Frédéric Bernachon proposes to explain the tragedy of Beethoven, as transmitted in his musical legacy. The listeners will get to experience Ludwig van Beethoven's destiny, suspense, drama and great questions in all their range and variety. After a careful introduction to listening to Sonate Pathétique, Frédéric Bernachon himself interprets this unique piece, through which Beethowen has chosen...

  2. Src kinase regulation by phosphorylation and dephosphorylation

    International Nuclear Information System (INIS)

    Roskoski, Robert

    2005-01-01

    Src and Src-family protein-tyrosine kinases are regulatory proteins that play key roles in cell differentiation, motility, proliferation, and survival. The initially described phosphorylation sites of Src include an activating phosphotyrosine 416 that results from autophosphorylation, and an inhibiting phosphotyrosine 527 that results from phosphorylation by C-terminal Src kinase (Csk) and Csk homologous kinase. Dephosphorylation of phosphotyrosine 527 increases Src kinase activity. Candidate phosphotyrosine 527 phosphatases include cytoplasmic PTP1B, Shp1 and Shp2, and transmembrane enzymes include CD45, PTPα, PTPε, and PTPλ. Dephosphorylation of phosphotyrosine 416 decreases Src kinase activity. Thus far PTP-BL, the mouse homologue of human PTP-BAS, has been shown to dephosphorylate phosphotyrosine 416 in a regulatory fashion. The platelet-derived growth factor receptor protein-tyrosine kinase mediates the phosphorylation of Src Tyr138; this phosphorylation has no direct effect on Src kinase activity. The platelet-derived growth factor receptor and the ErbB2/HER2 growth factor receptor protein-tyrosine kinases mediate the phosphorylation of Src Tyr213 and activation of Src kinase activity. Src kinase is also a substrate for protein-serine/threonine kinases including protein kinase C (Ser12), protein kinase A (Ser17), and CDK1/cdc2 (Thr34, Thr46, and Ser72). Of the three protein-serine/threonine kinases, only phosphorylation by CDK1/cdc2 has been demonstrated to increase Src kinase activity. Although considerable information on the phosphoprotein phosphatases that catalyze the hydrolysis of Src phosphotyrosine 527 is at hand, the nature of the phosphatases that mediate the hydrolysis of phosphotyrosine 138 and 213, and phosphoserine and phosphothreonine residues has not been determined

  3. Signaling network of the Btk family kinases.

    Science.gov (United States)

    Qiu, Y; Kung, H J

    2000-11-20

    The Btk family kinases represent new members of non-receptor tyrosine kinases, which include Btk/Atk, Itk/Emt/Tsk, Bmx/Etk, and Tec. They are characterized by having four structural modules: PH (pleckstrin homology) domain, SH3 (Src homology 3) domain, SH2 (Src homology 2) domain and kinase (Src homology 1) domain. Increasing evidence suggests that, like Src-family kinases, Btk family kinases play central but diverse modulatory roles in various cellular processes. They participate in signal transduction in response to virtually all types of extracellular stimuli which are transmitted by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen-receptors and integrins. They are regulated by many non-receptor tyrosine kinases such as Src, Jak, Syk and FAK family kinases. In turn, they regulate many of major signaling pathways including those of PI3K, PLCgamma and PKC. Both genetic and biochemical approaches have been used to dissect the signaling pathways and elucidate their roles in growth, differentiation and apoptosis. An emerging new role of this family of kinases is cytoskeletal reorganization and cell motility. The physiological importance of these kinases was amply demonstrated by their link to the development of immunodeficiency diseases, due to germ-line mutations. The present article attempts to review the structure and functions of Btk family kinases by summarizing our current knowledge on the interacting partners associated with the different modules of the kinases and the diverse signaling pathways in which they are involved.

  4. Receptor-interacting protein (RIP) kinase family

    Science.gov (United States)

    Zhang, Duanwu; Lin, Juan; Han, Jiahuai

    2010-01-01

    Receptor-interacting protein (RIP) kinases are a group of threonine/serine protein kinases with a relatively conserved kinase domain but distinct non-kinase regions. A number of different domain structures, such as death and caspase activation and recruitment domain (CARD) domains, were found in different RIP family members, and these domains should be keys in determining the specific function of each RIP kinase. It is known that RIP kinases participate in different biological processes, including those in innate immunity, but their downstream substrates are largely unknown. This review will give an overview of the structures and functions of RIP family members, and an update of recent progress in RIP kinase research. PMID:20383176

  5. Oncoprotein protein kinase antibody kit

    Science.gov (United States)

    Karin, Michael [San Diego, CA; Hibi, Masahiko [San Diego, CA; Lin, Anning [La Jolla, CA

    2008-12-23

    An isolated polypeptide (JNK) characterized by having a molecular weight of 46 kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.

  6. Thymidine kinase diversity in bacteria

    DEFF Research Database (Denmark)

    Sandrini, Michael; Clausen, A.R.; Munch-Petersen, B.

    2006-01-01

    Thymidine kinases (TKs) appear to be almost ubiquitous and are found in nearly all prokaryotes, eukaryotes, and several viruses. They are the key enzymes in thymidine salvage and activation of several anti-cancer and antiviral drugs. We show that bacterial TKs can be subdivided into 2 groups. The....... The TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria....

  7. Protein Kinase C Inhibitors as Modulators of Vascular Function and Their Application in Vascular Disease

    Directory of Open Access Journals (Sweden)

    Raouf A. Khalil

    2013-03-01

    Full Text Available Blood pressure (BP is regulated by multiple neuronal, hormonal, renal and vascular control mechanisms. Changes in signaling mechanisms in the endothelium, vascular smooth muscle (VSM and extracellular matrix cause alterations in vascular tone and blood vessel remodeling and may lead to persistent increases in vascular resistance and hypertension (HTN. In VSM, activation of surface receptors by vasoconstrictor stimuli causes an increase in intracellular free Ca2+ concentration ([Ca2+]i, which forms a complex with calmodulin, activates myosin light chain (MLC kinase and leads to MLC phosphorylation, actin-myosin interaction and VSM contraction. Vasoconstrictor agonists could also increase the production of diacylglycerol which activates protein kinase C (PKC. PKC is a family of Ca2+-dependent and Ca2+-independent isozymes that have different distributions in various blood vessels, and undergo translocation from the cytosol to the plasma membrane, cytoskeleton or the nucleus during cell activation. In VSM, PKC translocation to the cell surface may trigger a cascade of biochemical events leading to activation of mitogen-activated protein kinase (MAPK and MAPK kinase (MEK, a pathway that ultimately increases the myofilament force sensitivity to [Ca2+]i, and enhances actin-myosin interaction and VSM contraction. PKC translocation to the nucleus may induce transactivation of various genes and promote VSM growth and proliferation. PKC could also affect endothelium-derived relaxing and contracting factors as well as matrix metalloproteinases (MMPs in the extracellular matrix further affecting vascular reactivity and remodeling. In addition to vasoactive factors, reactive oxygen species, inflammatory cytokines and other metabolic factors could affect PKC activity. Increased PKC expression and activity have been observed in vascular disease and in certain forms of experimental and human HTN. Targeting of vascular PKC using PKC inhibitors may function in

  8. A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase.

    Directory of Open Access Journals (Sweden)

    Mutsuki Amano

    Full Text Available BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity.

  9. Nonmonotonic Thermal Casimir Force from Geometry-Temperature Interplay

    International Nuclear Information System (INIS)

    Weber, Alexej; Gies, Holger

    2010-01-01

    The geometry dependence of Casimir forces is significantly more pronounced in the presence of thermal fluctuations due to a generic geometry-temperature interplay. We show that the thermal force for standard sphere-plate or cylinder-plate geometries develops a nonmonotonic behavior already in the simple case of a fluctuating Dirichlet scalar. In particular, the attractive thermal force can increase for increasing distances below a critical temperature. This anomalous behavior is triggered by a reweighting of relevant fluctuations on the scale of the thermal wavelength. The essence of the phenomenon becomes transparent within the worldline picture of the Casimir effect.

  10. Particle trapping induced by the interplay between coherence and decoherence

    International Nuclear Information System (INIS)

    Yi Sangyong; Choi, Mahn-Soo; Kim, Sang Wook

    2009-01-01

    We propose a novel scheme to trap a particle based on a delicate interplay between coherence and decoherence. If the decoherence occurs as a particle is located in the scattering region and subsequently the appropriate destructive interference takes place, the particle can be trapped in the scattering area. We consider two possible experimental realizations of such trapping: a ring attached to a single lead and a ring attached to two leads. Our scheme has nothing to do with a quasi-bound state of the system, but has a close analogy with the weak localization phenomena in disordered conductors.

  11. The Interplay Between Online and Offline Community Culture

    DEFF Research Database (Denmark)

    Kornum, Niels; Gyrd-Jones, Richard; Al Zagir, Nadia

    This study examines the interplay between online and offline community cultures based on identifying the distinct features of both. Studying this interaction explicitly and in empirical analysis is new to community literature and brands can through this better know the communities to which...... they relate. The findings reveal that without a thorough understanding of both online and offline cultures and their interaction, companies or brands may get a misleading picture of these cultures. For instance, if only looking at the culture online and not core values offline, the company might intervene...

  12. Collisional width of giant resonances and interplay with Landau damping

    International Nuclear Information System (INIS)

    Bonasera, A.; Burgio, G.F.; Di Toro, M.; Wolter, H.H.

    1989-01-01

    We present a semiclassical method to calculate the widths of giant resonances. We solve a mean-field kinetic equation (Vlasov equation) with collision terms treated within the relaxation time approximation to construct a damped strength distribution for collective motions. The relaxation time is evaluated from the time evolution of distortions in the nucleon momentum distribution using a test-particle approach. The importance of an energy dependent nucleon-nucleon cross section is stressed. Results are shown for isoscalar giant quadrupole and octupole motions. A quite important interplay between self-consistent (Landau) and collisional damping is revealed

  13. Coulomb interaction from the interplay between confinement and screening

    International Nuclear Information System (INIS)

    Gaete, P.; Guendelman, E.I.

    2004-01-01

    It has been noticed that confinement effects can be described by the addition of a √(-F μν a F aμν ) term in the Lagrangian density. We now study the combined effect of such 'confinement term' and that of a mass term. The surprising result is that the interplay between these two terms gives rise to a Coulomb interaction. Our picture has a certain correspondence with the quasiconfinement picture described by Giles, Jaffe and de Rujula for QCD with symmetry breaking

  14. Superconductivity and magnetism: From antagonism to mutual interplay

    International Nuclear Information System (INIS)

    Steglich, Frank

    2007-01-01

    In this paper, a brief survey is given on a number of research activities devoted to exploring the relationship between superconductivity and magnetism in f-electron systems. The starting point for these activities has been the pioneering work of 1958 by Matthias and coworkers illustrating the antagonistic nature of the two phenomena. Subsequent efforts concerned the investigation of Kondo superconductors and Kondo-lattice systems (in the 1970s), heavy-fermion metals (in the 1980s and 90s) and quantum critical materials (in the last decade). The latter systems are especially interesting as they promise a deeper insight into the mutual interplay between unconventional superconductivity and magnetism

  15. Interplay of drug metabolizing enzymes with cellular transporters.

    Science.gov (United States)

    Böhmdorfer, Michaela; Maier-Salamon, Alexandra; Riha, Juliane; Brenner, Stefan; Höferl, Martina; Jäger, Walter

    2014-11-01

    Many endogenous and xenobiotic substances and their metabolites are substrates for drug metabolizing enzymes and cellular transporters. These proteins may not only contribute to bioavailability of molecules but also to uptake into organs and, consequently, to overall elimination. The coordinated action of uptake transporters, metabolizing enzymes, and efflux pumps, therefore, is a precondition for detoxification and elimination of drugs. As the understanding of the underlying mechanisms is important to predict alterations in drug disposal, adverse drug reactions and, finally, drug-drug interactions, this review illustrates the interplay between selected uptake/efflux transporters and phase I/II metabolizing enzymes.

  16. Molecular Cogs: Interplay between Circadian Clock and Cell Cycle.

    Science.gov (United States)

    Gaucher, Jonathan; Montellier, Emilie; Sassone-Corsi, Paolo

    2018-05-01

    The cell cycle and the circadian clock operate as biological oscillators whose timed functions are tightly regulated. Accumulating evidence illustrates the presence of molecular links between these two oscillators. This mutual interplay utilizes various coupling mechanisms, such as the use of common regulators. The connection between these two cyclic systems has unique interest in the context of aberrant cell proliferation since both of these oscillators are frequently misregulated in cancer cells. Further studies will provide deeper understanding of the detailed molecular connections between the cell cycle and the circadian clock and may also serve as a basis for the design of innovative therapeutic strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Visualization of multivalent histone modification in a single cell reveals highly concerted epigenetic changes on differentiation of embryonic stem cells

    DEFF Research Database (Denmark)

    Hattori, Naoko; Niwa, Tohru; Kimura, Kana

    2013-01-01

    . Bivalent modification was clearly visualized by iChmo in wild-type embryonic stem cells (ESCs) known to have it, whereas rarely in Suz12 knockout ESCs and mouse embryonic fibroblasts known to have little of it. iChmo was applied to analysis of epigenetic and phenotypic changes of heterogeneous cell......Combinations of histone modifications have significant biological roles, such as maintenance of pluripotency and cancer development, but cannot be analyzed at the single cell level. Here, we visualized a combination of histone modifications by applying the in situ proximity ligation assay, which...... population, namely, ESCs at an early stage of differentiation, and this revealed that the bivalent modification disappeared in a highly concerted manner, whereas phenotypic differentiation proceeded with large variations among cells. Also, using this method, we were able to visualize a combination...

  18. Human breast cancer: concerted role of diet, prolactin and adrenal C19-delta 5-steroids in tumorigenesis.

    Science.gov (United States)

    Adams, J B

    1992-04-01

    The low incidence of breast cancer in Japan disappears within 2 generations in migrant Japanese in the USA. This is of fundamental importance if we are to understand, and perhaps reverse, the high rate seen in Western countries. Diet is the most likely factor involved, and a review of the topic of diet, body mass index, and gain in adult body mass, supports a relationship between these factors and breast-cancer risk in post-menopausal, but not pre-menopausal, women. A direct link between nutritional factors and secretion of the hormones prolactin and dehydroepiandrosterone sulfate is proposed. An estrogen 5-androstene-3 beta, 17 beta-diol is formed peripherally from the latter steroid, and in Western women attains a blood concentration at which it is biologically active. Thus diet/fat provides factors, viz., fatty acids, prolactin and estrogen, which in concerted fashion provide a milieu conducive to mammary tumorigenesis.

  19. Concerted in vitro trimming of viral HLA-B27-restricted ligands by human ERAP1 and ERAP2 aminopeptidases.

    Science.gov (United States)

    Lorente, Elena; Barriga, Alejandro; Johnstone, Carolina; Mir, Carmen; Jiménez, Mercedes; López, Daniel

    2013-01-01

    In the classical human leukocyte antigen (HLA) class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases) and transported to the endoplasmic reticulum (ER) lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. In this study, the possible cooperative effect of generating five naturally processed HLA-B27 ligands by both proteases was analyzed. We identified differences in the products obtained with increased detection of natural HLA-B27 ligands by comparing double versus single enzyme digestions by mass spectrometry analysis. These in vitro data suggest that each enzyme can use the degradation products of the other as a substrate for new N-terminal trimming, indicating concerted aminoproteolytic activity of ERAP 1 and ERAP2.

  20. Kinases Involved in Both Autophagy and Mitosis.

    Science.gov (United States)

    Li, Zhiyuan; Zhang, Xin

    2017-08-31

    Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases), Aurora kinases, PLK-1 (polo-like kinase 1), BUB1 (budding uninhibited by benzimidazoles 1), MAPKs (mitogen-activated protein kinases), mTORC1 (mechanistic target of rapamycin complex 1), AMPK (AMP-activated protein kinase), PI3K (phosphoinositide-3 kinase) and protein kinase B (AKT). By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

  1. Kinases Involved in Both Autophagy and Mitosis

    Directory of Open Access Journals (Sweden)

    Zhiyuan Li

    2017-08-01

    Full Text Available Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases, Aurora kinases, PLK-1 (polo-like kinase 1, BUB1 (budding uninhibited by benzimidazoles 1, MAPKs (mitogen-activated protein kinases, mTORC1 (mechanistic target of rapamycin complex 1, AMPK (AMP-activated protein kinase, PI3K (phosphoinositide-3 kinase and protein kinase B (AKT. By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

  2. Interplay Between Politics and Sport in Political Science Theories

    Directory of Open Access Journals (Sweden)

    Simona Kustec Lipicer

    2010-01-01

    Full Text Available Times when relations between politics and sports did not exist – be it in everyday practices or within scientific research – is definitely long gone, if they ever even existed. Nevertheless, it seems today that, especially within scientific research, these relations do not receive appropriate attention in the territories of former socialist sports superpowers, being a priori denied and considered as unimportant. That is why the key motive of this article is to initiate a discussion about the relevance of knowledge and research of the relations between politics and sport from two perspectives – the existing world-wide political science research experiences gained so far and already conducted researches in the territory of former Yugoslavia. In doing so, we first theoretically define the context of sports and politics, and then with the use of the literature review method analyse their mutual connectivity in the world and, more narrowly, within the work of the scientific community in the region of former Yugoslavia. Based on the gained conclusions which confirm a tight and constant, but also often abstract and flat-rate understood interplay between both analysed phenomena, a special typology for their in-depth and political-science-focused study is delivered. It is believed that distinctions between political, polity and policy approaches to sport decisively influence the mode of their future interplay.

  3. The dynamic interplay between DNA topoisomerases and DNA topology.

    Science.gov (United States)

    Seol, Yeonee; Neuman, Keir C

    2016-11-01

    Topological properties of DNA influence its structure and biochemical interactions. Within the cell, DNA topology is constantly in flux. Transcription and other essential processes, including DNA replication and repair, not only alter the topology of the genome but also introduce additional complications associated with DNA knotting and catenation. These topological perturbations are counteracted by the action of topoisomerases, a specialized class of highly conserved and essential enzymes that actively regulate the topological state of the genome. This dynamic interplay among DNA topology, DNA processing enzymes, and DNA topoisomerases is a pervasive factor that influences DNA metabolism in vivo. Building on the extensive structural and biochemical characterization over the past four decades that has established the fundamental mechanistic basis of topoisomerase activity, scientists have begun to explore the unique roles played by DNA topology in modulating and influencing the activity of topoisomerases. In this review we survey established and emerging DNA topology-dependent protein-DNA interactions with a focus on in vitro measurements of the dynamic interplay between DNA topology and topoisomerase activity.

  4. Interplay between electron-phonon and electron-electron interactions

    International Nuclear Information System (INIS)

    Roesch, O.; Gunnarsson, O.; Han, J.E.; Crespi, V.H.

    2005-01-01

    We discuss the interplay between electron-electron and electron-phonon interactions for alkali-doped fullerides and high temperature superconductors. Due to the similarity of the electron and phonon energy scales, retardation effects are small for fullerides. This raises questions about the origin of superconductivity, since retardation effects are believed to be crucial for reducing effects of the Coulomb repulsion in conventional superconductors. We demonstrate that by treating the electron-electron and electron-phonon interactions on an equal footing, superconductivity can be understood in terms of a local pairing. The Jahn-Teller character of the important phonons in fullerides plays a crucial role for this result. To describe effects of phonons in cuprates, we derive a t-J model with phonons from the three-band model. Using exact diagonalization for small clusters, we find that the anomalous softening of the half-breathing phonon as well as its doping dependence can be explained. By comparing the solution of the t-J model with the Hartree-Fock approximation for the three-band model, we address results obtained in the local-density approximation for cuprates. We find that genuine many-body results, due to the interplay between the electron-electron and electron-phonon interactions, play an important role for the the results in the t-J model. (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  5. Immunomodulatory interplay of the microbiome and therapy of rheumatic diseases.

    Science.gov (United States)

    Ostrov, Barbara E; Amsterdam, Daniel

    2017-11-01

    Modulation of the immune system by microbes, especially from the gastrointestinal tract, is increasingly considered a key factor in the onset, course and outcome of rheumatic diseases. The interplay of the microbiome, along with genetic predisposition and environmental exposure, is thought to be an important trigger for rheumatic diseases. Improved identification of the relationship of disease-specific genetic alterations and rheumatic diseases has potential diagnostic and therapeutic applications. Treatment of rheumatic disorders is influenced by microbial actions but this interplay can be challenging due to variable and unpredictable responses to therapies. Expanded knowledge of the microbiome now allows clinicians to more precisely select ideal medication regimens and to predict response to and toxicity from drugs. Rheumatic diseases and associated therapies were among the earliest microbiome interactions investigated, yet it is notable that current research is focused on clinical and immunological associations but, in comparison, a limited number of studies regarding the microbiome's impact on treatment for rheumatic diseases have been published. In the coming years, further knowledge of immunomodulating interactions between the microbiome and the immune system will aid our understanding of autoimmunity and will be increasingly important in selection of therapeutic agents for patients with autoimmune and rheumatic diseases. In this review, recent literature regarding the bidirectional immunomodulatory effects of the microbiome with rheumatic diseases and current understanding and gaps regarding the drug-microbiome interface in the management of these disorders is presented.

  6. The interplay between HIF-1 and calcium signalling in cancer.

    Science.gov (United States)

    Azimi, Iman

    2018-04-01

    The interplay between hypoxia-inducible factor-1 (HIF-1) and calcium in cancer has begun to be unravelled with recent findings demonstrating the relationships between the two in different cancer types. This is an area of significance considering the crucial roles of both HIF-1 and calcium signalling in cancer progression and metastasis. This review summarises the experimental evidence of the crosstalk between HIF-1 and specific calcium channels, pumps and regulators in the context of cancer. HIF-1 as a master regulator of hypoxic transcriptional responses, mediates transcription of several calcium modulators. On the other hand, specific calcium channels and pumps regulate HIF-1 activity through controlling its transcription, translation, stabilisation, or nuclear translocation. Identifying the interplay between HIF-1 and components of the calcium signal will give new insights into mechanisms underlying cellular responses to physiological and pathophysiological cues, and may provide novel and more efficient therapeutic strategies for the control of cancer progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. The interplay between noncoding RNAs and insulin in diabetes.

    Science.gov (United States)

    Tian, Yan; Xu, Jia; Du, Xiao; Fu, Xianghui

    2018-04-10

    Noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs and circular RNAs, regulate various biological processes and are involved in the initiation and progression of human diseases. Insulin, a predominant hormone secreted from pancreatic β cells, is an essential factor in regulation of systemic metabolism through multifunctional insulin signaling. Insulin production and action are tightly controlled. Dysregulations of insulin production and action can impair metabolic homeostasis, and eventually lead to the development of multiple metabolic diseases, especially diabetes. Accumulating data indicates that ncRNAs modulate β cell mass, insulin synthesis, secretion and signaling, and their role in diabetes is dramatically emerging. This review summarizes our current knowledge of ncRNAs as regulators of insulin, with particular emphasis on the implications of this interplay in the development of diabetes. We outline the role of ncRNAs in pancreatic β cell mass and function, which is critical for insulin production and secretion. We also highlight the involvement of ncRNAs in insulin signaling in peripheral tissues including liver, muscle and adipose, and discuss ncRNA-mediated inter-organ crosstalk under diabetic conditions. A more in-depth understanding of the interplay between ncRNAs and insulin may afford valuable insights and novel therapeutic strategies for treatment of diabetes, as well as other human diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Interplay between the lung microbiome and lung cancer.

    Science.gov (United States)

    Mao, Qixing; Jiang, Feng; Yin, Rong; Wang, Jie; Xia, Wenjie; Dong, Gaochao; Ma, Weidong; Yang, Yao; Xu, Lin; Hu, Jianzhong

    2018-02-28

    The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Compositional disorder, magnetism, and their interplay in metallic alloys

    International Nuclear Information System (INIS)

    Johnson, D.D.; Staunton, J.B.; Pinski, F.J.; Gyorffy, B.L.; Stocks, G.M.

    1992-01-01

    Chemical disorder leads to a variety of intriguing phenomena in alloys which have yet to be fully understood, particularly those phenomena occurring when chemical and magnetic effects interplay with one another. For example, magnetic order gives rise to chemical ordering in alloys, as in Ni-rich NiFe alloys. Two examples of the interplay of chemical disorder and magnetism will be discussed. Our recently developed ab-initio Landau (mean-field) theory for calculating the chemical-chemical, magneto-chemical, and magnetic-magnetic correlation functions in substitutional random alloys is used to describe electronic/magnetic mechanisms (e.g. in FeV) which give rise to the chemical short-range order as determined by neutron, X-ray, or electron diffuse scattering intensities. New developments within this approach that account for charge rearrangement effect will be mentioned. These calculations are performed within the multiple-scattering framework, developed by Korringa, Kohn, and Rostoker (KKR), combined with the coherent potential approximation (CPA) to describe the disorder. This approach allows a first-principles description of the electronic structure of the high-temperature, chemically disordered state and its instability to ordering a low temperatures. This paper reports that this method provides not only a direct comparison of diffuse scattering data with theory but a means to understand more fully the underlying mechanisms which drive chemical and/or magnetic ordering

  10. Receptor Tyrosine Kinases in Drosophila Development

    Science.gov (United States)

    Sopko, Richelle; Perrimon, Norbert

    2013-01-01

    Tyrosine phosphorylation plays a significant role in a wide range of cellular processes. The Drosophila genome encodes more than 20 receptor tyrosine kinases and extensive studies in the past 20 years have illustrated their diverse roles and complex signaling mechanisms. Although some receptor tyrosine kinases have highly specific functions, others strikingly are used in rather ubiquitous manners. Receptor tyrosine kinases regulate a broad expanse of processes, ranging from cell survival and proliferation to differentiation and patterning. Remarkably, different receptor tyrosine kinases share many of the same effectors and their hierarchical organization is retained in disparate biological contexts. In this comprehensive review, we summarize what is known regarding each receptor tyrosine kinase during Drosophila development. Astonishingly, very little is known for approximately half of all Drosophila receptor tyrosine kinases. PMID:23732470

  11. Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains

    KAUST Repository

    Diaz Galicia, Miriam Escarlet

    2018-01-01

    is then translated into a FRET (Fluorescence Resonance Energy Transfer) signal is here proposed. To this end, DNA constructs for interaction amplification (split kinases), positive controls (intact kinase domains), scaffolding proteins and phosphopeptide - SH2-domain

  12. Phosphorylation-induced changes in the energetic frustration in human Tank binding kinase 1.

    Science.gov (United States)

    Husain, Shahrukh; Kumar, Vijay; Hassan, Md Imtaiyaz

    2018-07-14

    Tank binding kinase 1 (TBK-1) plays an important role in immunity, inflammation, autophagy, cell growth and proliferation. Nevertheless, a key molecular and structural detail of TBK-1 phosphorylation and activation has been largely unknown. Here we investigated the energy landscape of phosphorylated (active) and unphosphorylated (inactive) forms of human TBK-1 to characterize the interplay between phosphorylation and local frustration. By employing the algorithm equipped with energy function and implemented in Frustratometer web-server (http://www.frustratometer.tk), we quantify the role of frustration in the activation of TBK-1. Accordingly, the conformational changes were observed in phosphoregulated active and inactive TBK-1. Substantial changes in frustration, flexibility and interatomic motions were observed among different forms of TBK-1. Structurally rigid kinase domain constitutes a minimally frustrated hub in the core of the catalytic domain, and highly frustrated clusters mainly at the C-lobe might enable the conformational transitions during activation. Also, a large network of highly frustrated interactions is found in the SDD domain of TBK-1 involved in protein-protein interactions and dimerization. The contact maps of the activation loop and α-C helix of kinase domain showed significant changes upon phosphorylation. Cross correlation analysis indicate that both intra and inter subunit correlated motions increases with phosphorylation of TBK-1. Phosphorylation thus introduces subtle changes in long-range contacts that might lead to significant conformational change of TBK-1. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Measuring Kinase Activity-A Global Challenge.

    Science.gov (United States)

    Cann, Marissa L; McDonald, Ian M; East, Michael P; Johnson, Gary L; Graves, Lee M

    2017-11-01

    The kinase enzymes within a cell, known collectively as the kinome, play crucial roles in many signaling pathways, including survival, motility, differentiation, stress response, and many more. Aberrant signaling through kinase pathways is often linked to cancer, among other diseases. A major area of scientific research involves understanding the relationships between kinases, their targets, and how the kinome adapts to perturbations of the cellular system. This review will discuss many of the current and developing methods for studying kinase activity, and evaluate their applications, advantages, and disadvantages. J. Cell. Biochem. 118: 3595-3606, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Recent Advances in Understanding of Kinetic Interplay Between Phase II Metabolism and Efflux Transport.

    Science.gov (United States)

    Wang, Shuai; Xing, Huijie; Zhao, Mengjing; Lu, Danyi; Li, Zhijie; Dong, Dong; Wu, Baojian

    2016-01-01

    Mechanistic understanding of the metabolism-transport interplay assumes great importance in pharmaceutical fields because the knowledge can help to interpret drug/xenobiotic metabolism and disposition studies as well as the drug-drug interactions in vivo. About 10 years ago, it started to recognize that cellular phase II metabolism is strongly influenced by the excretion (efflux transport) of generated metabolites, a kinetic phenomenon termed "phase II metabolism-transport interplay". This interplay is believed to have significant effects on the pharmacokinetics (bioavailability) of drugs/chemicals undergoing phase II metabolism. In this article, we review the studies investigating the phase II metabolism-transport interplay using cell models, perfused rat intestine, and intact rats. The potential confounding factors in exploring such interplay is also summarized. Moreover, the mechanism underlying the phase II metabolism-transport interplay is discussed. Various studies with engineered cells and rodents have demonstrated that there is an interaction (interplay) between phase II enzymes and efflux transporters. This type of interplay mainly refers to the dependence of phase II (conjugative) metabolism on the activities of efflux transporters. In general, inhibiting efflux transporters or decreasing their expression causes the reductions in metabolite excretion, apparent excretion clearance (CLapp) and total metabolism (fmet), as well as an increase in the intracellular level of metabolite (Ci). The deconjugation mediated by hydrolase (acting as a "bridge") is essential for the interplay to play out based on pharmacokinetic modeling/simulations, cell and animal studies. The hydrolases bridge the two processes (i.e., metabolite formation and excretion) and enable the interplay thereof (a bridging effect). Without the bridge, metabolite formation is independent on its downstream process excretion, thus impact of metabolite excretion on its formation is impossible

  15. Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains

    KAUST Repository

    Diaz Galicia, Miriam Escarlet

    2018-05-01

    Protein-protein interactions modulate cellular processes in health and disease. However, tracing weak or rare associations or dissociations of proteins is not a trivial task. Kinases are often regulated through interaction partners and, at the same time, themselves regulate cellular interaction networks. The use of kinase domains for creating a synthetic sensor device that reads low concentration protein-protein interactions and amplifies them to a higher concentration interaction which is then translated into a FRET (Fluorescence Resonance Energy Transfer) signal is here proposed. To this end, DNA constructs for interaction amplification (split kinases), positive controls (intact kinase domains), scaffolding proteins and phosphopeptide - SH2-domain modules for the reading of kinase activity were assembled and expression protocols for fusion proteins containing Lyn, Src, and Fak kinase domains in bacterial and in cell-free systems were optimized. Also, two non-overlapping methods for measuring the kinase activity of these proteins were stablished and, finally, a protein-fragment complementation assay with the split-kinase constructs was tested. In conclusion, it has been demonstrated that features such as codon optimization, vector design and expression conditions have an impact on the expression yield and activity of kinase-based proteins. Furthermore, it has been found that the defined PURE cell-free system is insufficient for the active expression of catalytic kinase domains. In contrast, the bacterial co-expression with phosphatases produced active kinase fusion proteins for two out of the three tested Tyrosine kinase domains.

  16. COMMUNICATIONAL THINKING IN THE STATE ORCHESTRA OF MATO GROSSO AND THE FIELD OF CONCERT MUSIC IN CUIABÁ

    Directory of Open Access Journals (Sweden)

    Yuji Gushiken

    2016-12-01

    Full Text Available Na perspectiva da “comunicação como cultura”, este artigo tem como questão central a relação entre pensamento comunicacional e a formação da música de concerto como campo artístico-cultural, num estudo de caso da Orquestra do Estado de Mato Grosso (OEMT. Criada em 2005, a OEMT instituiu um novo momento para a música de concerto em Cuiabá, capital de Mato Grosso, estado do Centro-Oeste com parte de seu território na Amazônia Legal. O funcionamento da OEMT na primeira década de atividade (2005-2015 atualiza-se com o desenvolvimento paralelo de estratégias de comunicação organizacional que redimensionam as relações da orquestra junto a seus diversos públicos. A interface entre distintos campos profissionais evidencia a dimensão comunicacional das práticas artísticas e culturais na contemporaneidade.   PALAVRAS-CHAVE: Comunicação; Música de concerto; Orquestra do Estado de Mato Grosso; Cuiabá.     ABSTRACT In the perspective of “communication as culture”, this article has as its central question the relationship between communicational thinking and the formation of concert music as an artistic-cultural field, in a case study of the State Orchestra of Mato Grosso (OEMT. Created in 2005, OEMT instituted a new moment for concert music in Cuiabá, capital of Mato Grosso, state of the Midwest with part of its territory in the Legal Amazon. The operation of OEMT in the first decade of activity (2005-2015 is updated with the parallel development of organizational communication strategies that reshape the relations of the orchestra with its different audiences. The interface between different professional fields evidences the communicational dimension of the artistic and cultural practices in the contemporaneity.   KEYWORDS: Communication; Concert music; State Orchestra of  Mato Grosso; Cuiabá.     RESUMEN Desde la perspectiva de la “comunicación como cultura”, este artículo tiene como cuestión central la

  17. An European concerted action investigating the validity of perinatal mortality as an outcome indicator for the quality of antenatal and perinatal care

    NARCIS (Netherlands)

    Richardus, J.H.; Graafmans, W.C.; Pal-de Bruin, K.M. van der; Amelink-Verburg, M.P.; Verloove-Vanhorick, S.P.; Mackenbach, J.P.

    1997-01-01

    In this paper the concepts, objectives, design, and data analysis procedures of the EuroNatal study are described. This sutdy started in 1996 and is a concerted action including 14 countries in Europe. The EuroNatal study aims at determining the validity of national perinatal mortality rates as an

  18. Pilot study: Exposure and materiality of the secondary room and its impact in the impulse response of coupled-volume concert halls

    Science.gov (United States)

    Ermann, Michael; Johnson, Marty E.

    2002-05-01

    What does one room sound like when it is partially exposed to another (acoustically coupled)? More specifically, this research aims to quantify how operational and design decisions impact aural impressions in the design of concert halls with acoustical coupling. By adding a second room to a concert hall, and designing doors to control the sonic transparency between the two rooms, designers can create a new, coupled acoustic. Concert halls use coupling to achieve a variable, longer, and distinct reverberant quality for their musicians and listeners. For this study, a coupled-volume shoebox concert hall was conceived with a fixed geometric volume, form, and primary-room sound absorption. Aperture size and secondary-room sound-absorption levels were established as variables. Statistical analysis of sound decay in this simulated hall suggests a highly sensitive relationship between the double-sloped condition and (1) Architectural composition, as defined by the aperture size exposing the chamber and (2) Materiality, as defined by the sound absorbance in the coupled volume. Preliminary calculations indicate that the double-sloped sound decay condition only appears when the total aperture area is less than 1.5% of the total shoebox surface area and the average absorption coefficient of the coupled volume is less than 0.07.

  19. Oscillations and NMDA Receptors: Their Interplay Create Memories

    Directory of Open Access Journals (Sweden)

    Chris Cadonic

    2014-06-01

    Full Text Available Oscillatory activity is inherent in many types of normal cellular function. Importantly, oscillations contribute to cellular network activity and cellular decision making, which are driving forces for cognition. Theta oscillations have been correlated with learning and memory encoding and gamma oscillations have been associated with attention and working memory. NMDA receptors are also implicated in oscillatory activity and contribute to normal function and in disease-related pathology. The interplay between oscillatory activity and NMDA receptors are intellectually curious and a fascinating dimension of inquiry. In this review we introduce some of the essential mathematical characteristics of oscillatory activity in order to provide a platform for additional discussion on recent studies concerning oscillations involving neuronal firing and NMDA receptor activity, and the effect of these dynamic mechanisms on cognitive processing in health and disease.

  20. Complex Interplay of Hormonal Signals during Grape Berry Ripening

    Directory of Open Access Journals (Sweden)

    Ana Margarida Fortes

    2015-05-01

    Full Text Available Grape and wine production and quality is extremely dependent on the fruit ripening process. Sensory and nutritional characteristics are important aspects for consumers and their development during fruit ripening involves complex hormonal control. In this review, we explored data already published on grape ripening and compared it with the hormonal regulation of ripening of other climacteric and non-climacteric fruits. The roles of abscisic acid, ethylene, and brassinosteroids as promoters of ripening are discussed, as well as the role of auxins, cytokinins, gibberellins, jasmonates, and polyamines as inhibitors of ripening. In particular, the recently described role of polyamine catabolism in grape ripening is discussed, together with its putative interaction with other hormones. Furthermore, other recent examples of cross-talk among the different hormones are presented, revealing a complex interplay of signals during grape development and ripening.

  1. Interplay of delay and multiplexing: Impact on cluster synchronization

    Science.gov (United States)

    Singh, Aradhana; Jalan, Sarika; Boccaletti, Stefano

    2017-04-01

    Communication delays and multiplexing are ubiquitous features of real-world network systems. We here introduce a simple model where these two features are simultaneously present and report the rich phenomenology which is actually due to their interplay on cluster synchronization. A delay in one layer has non trivial impacts on the collective dynamics of the other layers, enhancing or suppressing synchronization. At the same time, multiplexing may also enhance cluster synchronization of delayed layers. We elucidate several nontrivial (and anti-intuitive) scenarios, which are of interest and potential application in various real-world systems, where the introduction of a delay may render synchronization of a layer robust against changes in the properties of the other layers.

  2. Interplay of Laser-Plasma Interactions and Inertial Fusion Hydrodynamics

    International Nuclear Information System (INIS)

    Strozzi, D. J.; Bailey, D. S.; Michel, P.; Divol, L.; Sepke, S. M.

    2017-01-01

    The effects of laser-plasma interactions (LPI) on the dynamics of inertial confinement fusion hohlraums are investigated in this work via a new approach that self-consistently couples reduced LPI models into radiation-hydrodynamics numerical codes. The interplay between hydrodynamics and LPI—specifically stimulated Raman scatter and crossed-beam energy transfer (CBET)—mostly occurs via momentum and energy deposition into Langmuir and ion acoustic waves. This spatially redistributes energy coupling to the target, which affects the background plasma conditions and thus, modifies laser propagation. In conclusion, this model shows reduced CBET and significant laser energy depletion by Langmuir waves, which reduce the discrepancy between modeling and data from hohlraum experiments on wall x-ray emission and capsule implosion shape.

  3. Interplay between transparency and efficiency in dye sensitized solar cells.

    Science.gov (United States)

    Tagliaferro, Roberto; Colonna, Daniele; Brown, Thomas M; Reale, Andrea; Di Carlo, Aldo

    2013-02-11

    In this paper we analyze the interplay between transparency and efficiency in dye sensitized solar cells by varying fabrication parameters such as the thickness of the nano-crystalline TiO(2) layer, the dye loading and the dye type. Both transparency and efficiency show a saturation trend when plotted versus dye loading. By introducing the transparency-efficiency plot, we show that the relation between transparency and efficiency is linear and is almost independent on the TiO(2) thickness for a certain thickness range. On the contrary, the relation between transparency and efficiency depends strongly on the type of the dye. Moreover, we show that co-sensitization techniques can be effectively used to access regions of the transparency-efficiency space that are forbidden for single dye sensitization. The relation found between transparency and efficiency (T&E) can be the general guide for optimization of Dye Solar Cells in building integration applications.

  4. Interplay between geometry and temperature for inclined Casimir plates

    International Nuclear Information System (INIS)

    Weber, Alexej; Gies, Holger

    2009-01-01

    We provide further evidence for the nontrivial interplay between geometry and temperature in the Casimir effect. We investigate the temperature dependence of the Casimir force between an inclined semi-infinite plate above an infinite plate in D dimensions using the worldline formalism. Whereas the high-temperature behavior is always found to be linear in T in accordance with dimensional-reduction arguments, different power-law behaviors at small temperatures emerge. Unlike the case of infinite parallel plates, which shows the well-known T D behavior of the force, we find a T D-1 behavior for inclined plates, and a ∼T D-0.3 behavior for the edge effect in the limit where the plates become parallel. The strongest temperature dependence ∼T D-2 occurs for the Casimir torque of inclined plates. Numerical as well as analytical worldline results are presented.

  5. The interplay of management accounting research and NPM health initiatives

    DEFF Research Database (Denmark)

    Malmmose, Margit

    This paper investigates the development of management accounting research in the context of New Public Management (NPM) initiatives in health care. Drawing on concepts from diffusion theory and earlier literature reviews, the paper examines the interplay between management accounting research...... and health care reforms in relation to country of origin, development, theoretical approach, research method and topic. The study thus establishes a different focus; namely the interrelationship between the development of management accounting research and practical socio-political NPM innovations. The study...... shows that management accounting techniques are increasingly adopted in governmental health reforms and diffused across nations, themes and initiatives through time with the result that wider social practices become more and more integrated in management accounting research themes...

  6. Reciprocal Supportive Interplay between Glioblastoma and Tumor-Associated Macrophages

    International Nuclear Information System (INIS)

    Zhou, Wenchao; Bao, Shideng

    2014-01-01

    Glioblastoma multiforme (GBM) is the most lethal and aggressive type of primary brain malignancy. Failures of the traditional therapies in treating GBMs raise the urgent requirement to develop new approaches with more responsive targets. The phenomenon of the high infiltration of tumor-associated macrophages (TAMs) into GBMs has been observed for a long time. Regardless of the limited knowledge about TAMs, the high percentage of supportive TAM in GBM tumor mass makes it possible to be a good target for GBM treatment. In this review, we discussed the unique features of TAMs in GBMs, including their origin, the tumor-supportive properties, the secreted cytokines, and the relevant mechanisms. In addition, we tried to interpret the current understandings about the interplay between GBM cancer cells and TAMs. Finally, the translational studies of targeting TAMs were also described

  7. Reciprocal Supportive Interplay between Glioblastoma and Tumor-Associated Macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Wenchao; Bao, Shideng, E-mail: baos@ccf.org [Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (United States)

    2014-03-26

    Glioblastoma multiforme (GBM) is the most lethal and aggressive type of primary brain malignancy. Failures of the traditional therapies in treating GBMs raise the urgent requirement to develop new approaches with more responsive targets. The phenomenon of the high infiltration of tumor-associated macrophages (TAMs) into GBMs has been observed for a long time. Regardless of the limited knowledge about TAMs, the high percentage of supportive TAM in GBM tumor mass makes it possible to be a good target for GBM treatment. In this review, we discussed the unique features of TAMs in GBMs, including their origin, the tumor-supportive properties, the secreted cytokines, and the relevant mechanisms. In addition, we tried to interpret the current understandings about the interplay between GBM cancer cells and TAMs. Finally, the translational studies of targeting TAMs were also described.

  8. Interplay between parametric instabilities in fusion - relevant laser plasmas

    International Nuclear Information System (INIS)

    Huller, St.

    2003-01-01

    The control of parametric instabilities plays an important role in laser fusion. They are driven by the incident laser beams in the underdense plasma surrounding a fusion capsule and hinder the absorption process of incident laser light which is necessary to heat the fusion target. Due to its high intensity and power, the laser light modifies the plasma density dynamically, such that two or more parametric instabilities compete, in particular stimulated Brillouin scattering and the filamentation instability. The complicated interplay between these parametric instabilities is studied in detail by developing an adequate model accompanied by numerical simulations with multidimensional codes. The model is applied to generic and to smoothed laser beams, which are necessary to limit parametric instabilities, with parameters close to experimental conditions. (author)

  9. Imaging of the host/parasite interplay in cutaneous leishmaniasis.

    Science.gov (United States)

    Millington, Owain R; Myburgh, Elmarie; Mottram, Jeremy C; Alexander, James

    2010-11-01

    An understanding of host-parasite interplay is essential for the development of therapeutics and vaccines. Immunoparasitologists have learned a great deal from 'conventional'in vitro and in vivo approaches, but recent developments in imaging technologies have provided us (immunologists and parasitologists) with the ability to ask new and exciting questions about the dynamic nature of the parasite-immune system interface. These studies are providing us with new insights into the mechanisms involved in the initiation of a Leishmania infection and the consequent induction and regulation of the immune response. Here, we review some of the recent developments and discuss how these observations can be further developed to understand the immunology of cutaneous Leishmania infection in vivo. (c) 2010 Elsevier Inc. All rights reserved.

  10. The interplay of immunotherapy and chemotherapy: harnessing potential synergies.

    Science.gov (United States)

    Emens, Leisha A; Middleton, Gary

    2015-05-01

    Although cancer chemotherapy has historically been considered immune suppressive, it is now accepted that certain chemotherapies can augment tumor immunity. The recent success of immune checkpoint inhibitors has renewed interest in immunotherapies, and in combining them with chemotherapy to achieve additive or synergistic clinical activity. Two major ways that chemotherapy promotes tumor immunity are by inducing immunogenic cell death as part of its intended therapeutic effect and by disrupting strategies that tumors use to evade immune recognition. This second strategy, in particular, is dependent on the drug, its dose, and the schedule of chemotherapy administration in relation to antigen exposure or release. In this Cancer Immunology at the Crossroads article, we focus on cancer vaccines and immune checkpoint blockade as a forum for reviewing preclinical and clinical data demonstrating the interplay between immunotherapy and chemotherapy. ©2015 American Association for Cancer Research.

  11. Flavour and collider interplay for SUSY at LHC7

    International Nuclear Information System (INIS)

    Calibbi, L.; Hodgkinson, R.N.; Vives, O.; Jones Perez, J.; Masiero, A.

    2012-01-01

    The current 7 TeV run of the LHC experiment shall be able to probe gluino and squark masses up to values larger than 1 TeV. Assuming that hints for SUSY are found in the jets plus missing energy channel by the end of a 5 fb -1 run, we explore the flavour constraints on three models with a CMSSM-like spectrum: the CMSSM itself, a seesaw extension of the CMSSM, and Flavoured CMSSM. In particular, we focus on decays that might have been measured by the time the run is concluded, such as B s →μμ and μ→e γ. We also analyse constraints imposed by neutral meson bounds and electric dipole moments. The interplay between collider and flavour experiments is explored through the use of three benchmark scenarios, finding the flavour feedback useful in order to determine the model parameters and to test the consistency of the different models. (orig.)

  12. Genome interplay in the grain transcriptome of hexaploid bread wheat.

    Science.gov (United States)

    Pfeifer, Matthias; Kugler, Karl G; Sandve, Simen R; Zhan, Bujie; Rudi, Heidi; Hvidsten, Torgeir R; Mayer, Klaus F X; Olsen, Odd-Arne

    2014-07-18

    Allohexaploid bread wheat (Triticum aestivum L.) provides approximately 20% of calories consumed by humans. Lack of genome sequence for the three homeologous and highly similar bread wheat genomes (A, B, and D) has impeded expression analysis of the grain transcriptome. We used previously unknown genome information to analyze the cell type-specific expression of homeologous genes in the developing wheat grain and identified distinct co-expression clusters reflecting the spatiotemporal progression during endosperm development. We observed no global but cell type- and stage-dependent genome dominance, organization of the wheat genome into transcriptionally active chromosomal regions, and asymmetric expression in gene families related to baking quality. Our findings give insight into the transcriptional dynamics and genome interplay among individual grain cell types in a polyploid cereal genome. Copyright © 2014, American Association for the Advancement of Science.

  13. Interplay of DNA repair with transcription: from structures to mechanisms.

    Science.gov (United States)

    Deaconescu, Alexandra M; Artsimovitch, Irina; Grigorieff, Nikolaus

    2012-12-01

    Many DNA transactions are crucial for maintaining genomic integrity and faithful transfer of genetic information but remain poorly understood. An example is the interplay between nucleotide excision repair (NER) and transcription, also known as transcription-coupled DNA repair (TCR). Discovered decades ago, the mechanisms for TCR have remained elusive, not in small part due to the scarcity of structural studies of key players. Here we summarize recent structural information on NER/TCR factors, focusing on bacterial systems, and integrate it with existing genetic, biochemical, and biophysical data to delineate the mechanisms at play. We also review emerging, alternative modalities for recruitment of NER proteins to DNA lesions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Physics and information technology an interplay between science and engineering

    CERN Multimedia

    Hagstrom, S B

    1999-01-01

    In the last decade of this century and millennium, the computer and communication revolution has shown its power to transform the society. In this talk I will reflect on my personal experience of witnessing this revolution from an observation post in Silicon Valley. In particular, I will emphasize the role of physics and the interplay between science and engineering in this development. Information technology is often viewed as based on some physics discoveries and inventions such as the transistor and the semiconductor laser. Much of the subsequent development, the integrated circuit being a good example, has been an engineering feat. With shrinking dimensions of the circuits we are approaching the quantum limitations, requiring new types of computer architectures based on fundamental physics concepts. In this context we may ask if we should include the basic concepts of information and information handling as part of physics. Finally I will include some remarks on the views of physics as seen in the eyes of...

  15. Analysis tools for the interplay between genome layout and regulation.

    Science.gov (United States)

    Bouyioukos, Costas; Elati, Mohamed; Képès, François

    2016-06-06

    Genome layout and gene regulation appear to be interdependent. Understanding this interdependence is key to exploring the dynamic nature of chromosome conformation and to engineering functional genomes. Evidence for non-random genome layout, defined as the relative positioning of either co-functional or co-regulated genes, stems from two main approaches. Firstly, the analysis of contiguous genome segments across species, has highlighted the conservation of gene arrangement (synteny) along chromosomal regions. Secondly, the study of long-range interactions along a chromosome has emphasised regularities in the positioning of microbial genes that are co-regulated, co-expressed or evolutionarily correlated. While one-dimensional pattern analysis is a mature field, it is often powerless on biological datasets which tend to be incomplete, and partly incorrect. Moreover, there is a lack of comprehensive, user-friendly tools to systematically analyse, visualise, integrate and exploit regularities along genomes. Here we present the Genome REgulatory and Architecture Tools SCAN (GREAT:SCAN) software for the systematic study of the interplay between genome layout and gene expression regulation. SCAN is a collection of related and interconnected applications currently able to perform systematic analyses of genome regularities as well as to improve transcription factor binding sites (TFBS) and gene regulatory network predictions based on gene positional information. We demonstrate the capabilities of these tools by studying on one hand the regular patterns of genome layout in the major regulons of the bacterium Escherichia coli. On the other hand, we demonstrate the capabilities to improve TFBS prediction in microbes. Finally, we highlight, by visualisation of multivariate techniques, the interplay between position and sequence information for effective transcription regulation.

  16. When chocolate seeking becomes compulsion: gene-environment interplay.

    Directory of Open Access Journals (Sweden)

    Enrico Patrono

    Full Text Available Eating disorders appear to be caused by a complex interaction between environmental and genetic factors, and compulsive eating in response to adverse circumstances characterizes many eating disorders.We compared compulsion-like eating in the form of conditioned suppression of palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J mice, two well-characterized inbred strains, to determine the influence of gene-environment interplay on this behavioral phenotype. Moreover, we tested the hypothesis that low accumbal D2 receptor (R availability is a genetic risk factor of food compulsion-like behavior and that environmental conditions that induce compulsive eating alter D2R expression in the striatum. To this end, we measured D1R and D2R expression in the striatum and D1R, D2R and α1R levels in the medial prefrontal cortex, respectively, by western blot.Exposure to environmental conditions induces compulsion-like eating behavior, depending on genetic background. This behavioral pattern is linked to decreased availability of accumbal D2R. Moreover, exposure to certain environmental conditions upregulates D2R and downregulates α1R in the striatum and medial prefrontal cortex, respectively, of compulsive animals. These findings confirm the function of gene-environment interplay in the manifestation of compulsive eating and support the hypothesis that low accumbal D2R availability is a "constitutive" genetic risk factor for compulsion-like eating behavior. Finally, D2R upregulation and α1R downregulation in the striatum and medial prefrontal cortex, respectively, are potential neuroadaptive responses that parallel the shift from motivated to compulsive eating.

  17. Oncogenic Receptor Tyrosine Kinases Directly Phosphorylate Focal Adhesion Kinase (FAK) as a Resistance Mechanism to FAK-Kinase Inhibitors.

    Science.gov (United States)

    Marlowe, Timothy A; Lenzo, Felicia L; Figel, Sheila A; Grapes, Abigail T; Cance, William G

    2016-12-01

    Focal adhesion kinase (FAK) is a major drug target in cancer and current inhibitors targeted to the ATP-binding pocket of the kinase domain have entered clinical trials. However, preliminary results have shown limited single-agent efficacy in patients. Despite these unfavorable data, the molecular mechanisms that drive intrinsic and acquired resistance to FAK-kinase inhibitors are largely unknown. We have demonstrated that receptor tyrosine kinases (RTK) can directly bypass FAK-kinase inhibition in cancer cells through phosphorylation of FAK's critical tyrosine 397 (Y397). We also showed that HER2 forms a direct protein-protein interaction with the FAK-FERM-F1 lobe, promoting direct phosphorylation of Y397. In addition, FAK-kinase inhibition induced two forms of compensatory RTK reprogramming: (i) the rapid phosphorylation and activation of RTK signaling pathways in RTK High cells and (ii) the long-term acquisition of RTKs novel to the parental cell line in RTK Low cells. Finally, HER2 +: cancer cells displayed resistance to FAK-kinase inhibition in 3D growth assays using a HER2 isogenic system and HER2 + cancer cell lines. Our data indicate a novel drug resistance mechanism to FAK-kinase inhibitors whereby HER2 and other RTKs can rescue and maintain FAK activation (pY397) even in the presence of FAK-kinase inhibition. These data may have important ramifications for existing clinical trials of FAK inhibitors and suggest that individual tumor stratification by RTK expression would be important to predict patient response to FAK-kinase inhibitors. Mol Cancer Ther; 15(12); 3028-39. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. The interplay between formal and informal contracting in integrated project delivery

    NARCIS (Netherlands)

    Bygballe, L.E.; Dewulf, Geert P.M.R.; Levitt, R.

    2015-01-01

    This research examines the interplay between formal and informal contracting in integrated project delivery (IPD). It investigates how the interplay enables parties in health-care construction projects to cope with uncertainty and complexities, due to, among others, changing demands. New delivery

  19. Teaching and Learning the Interplay between Chance and Determinism in Nonlinear Systems

    Science.gov (United States)

    Stavrou, Dimitrios; Duit, Reinders

    2014-01-01

    That the interplay of random and deterministic processes may result in both the limited predictability of nonlinear systems and the formation of structures seems to be a most valuable general insight into the nature of science. This study investigates the possibility of teaching and learning the interplay of chance and determinism in nonlinear…

  20. The Next Steps in Our Understanding of Gene-Peer Interplay: A Commentary

    Science.gov (United States)

    Burt, S. Alexandra

    2014-01-01

    The studies included in this special issue on gene-peer interplay in child and adolescent outcomes can uniformly be described as cutting edge and methodologically sophisticated. When viewed together, they all but conclusively document the presence and importance of gene-peer interplay in child and adolescent outcomes. Nevertheless, more work on…

  1. Electronic Interplay between TTF and Extended-TCNQ Electrophores along a Ruthenium Bis(acetylide) Linker.

    Science.gov (United States)

    Vacher, Antoine; Auffray, Morgan; Barrière, Frédéric; Roisnel, Thierry; Lorcy, Dominique

    2017-11-17

    A bis(TTF-butadiynyl) ruthenium D-D'-D complex, with intramolecular electronic interplay between the three electron-donating electrophores, was easily converted through a cycloaddition-retroelectrocyclization with TCNQ into a D-A-D'-A-D pentad complex, which exhibits an intense intramolecular charge transfer together with an electronic interplay between the two acceptors along the conjugated organometallic bridge.

  2. Interplay of Drug-Metabolizing Enzymes and Transporters in Drug Absorption and Disposition.

    Science.gov (United States)

    Shi, Shaojun; Li, Yunqiao

    2014-01-01

    In recent years, the functional interplay between drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in drug absorption and disposition, as well as the complex drug interactions (DIs), has become an intriguing contention, which has also been termed the "transport-metabolism interplay". The current mechanistic understanding for this interplay is first discussed. In the present article, studies investigating the interplay between cytochrome P450 enzymes (CYPs) and efflux transporters have been systematically reviewed in vitro, in situ, in silico, in animals and humans, followed by CYPs-uptake transporters, CYPs-uptake transporters-efflux transporters, and phase II metabolic enzymes-transporters interplay studies. Although several cellular, isolated organ and whole animal studies, in conjunction with simulation and modelling, have addressed the issue that DMEs and DTs can work cooperatively to affect the bioavailability of shared substrate drugs, convincing evidences in human studies are still lacking. Furthermore, the functional interplay between DMEs and DTs will be highly substrate- and dose- dependent. Additionally, we review recent studies to evaluate the influence of genetic variations in the interplay between DMEs and DTs, which might be helpful for the prediction of pharmacokinetics (PK) and possible DIs in human more correctly. There is strong evidence of coordinately regulated DEMs and DTs gene expression and protein activity (e.g. nuclear receptors). Taken together, further investigations and analysis are urgently needed to explore the functional interplay of DMEs and DTs and to delineate the underlying mechanisms.

  3. The interplay of parental monitoring and socioeconomic status in predicting minor delinquency between and within adolescents

    NARCIS (Netherlands)

    Rekker, Roderik; Keijsers, Loes; Branje, Susan; Koot, Hans M.; Meeus, Wim

    2017-01-01

    This six-wave multi-informant longitudinal study on Dutch adolescents (N = 824; age 12–18) examined the interplay of socioeconomic status with parental monitoring in predicting minor delinquency. Fixed-effects negative binomial regression analyses revealed that this interplay is different within

  4. IGEMS: The Consortium on Interplay of Genes and Environment Across Multiple Studies

    DEFF Research Database (Denmark)

    Pedersen, Nancy L; Christensen, Kaare; Dahl, Anna K

    2013-01-01

    The Interplay of Genes and Environment across Multiple Studies (IGEMS) group is a consortium of eight longitudinal twin studies established to explore the nature of social context effects and gene-environment interplay in late-life functioning. The resulting analysis of the combined data from ove...

  5. The interplay of parental monitoring and socioeconomic status in predicting minor delinquency between and within adolescents

    NARCIS (Netherlands)

    Rekker, Roderik; Keijsers, L.G.M.T.; Branje, Susan; Koot, Hans; Meeus, W.H.J.

    This six-wave multi-informant longitudinal study on Dutch adolescents (N = 824; age 12 18) examined the interplay of socioeconomic status with parental monitoring in predicting minor delinquency. Fixed-effects negative binomial regression analyses revealed that this interplay is different within

  6. A rice kinase-protein interaction map.

    Science.gov (United States)

    Ding, Xiaodong; Richter, Todd; Chen, Mei; Fujii, Hiroaki; Seo, Young Su; Xie, Mingtang; Zheng, Xianwu; Kanrar, Siddhartha; Stevenson, Rebecca A; Dardick, Christopher; Li, Ying; Jiang, Hao; Zhang, Yan; Yu, Fahong; Bartley, Laura E; Chern, Mawsheng; Bart, Rebecca; Chen, Xiuhua; Zhu, Lihuang; Farmerie, William G; Gribskov, Michael; Zhu, Jian-Kang; Fromm, Michael E; Ronald, Pamela C; Song, Wen-Yuan

    2009-03-01

    Plants uniquely contain large numbers of protein kinases, and for the vast majority of the 1,429 kinases predicted in the rice (Oryza sativa) genome, little is known of their functions. Genetic approaches often fail to produce observable phenotypes; thus, new strategies are needed to delineate kinase function. We previously developed a cost-effective high-throughput yeast two-hybrid system. Using this system, we have generated a protein interaction map of 116 representative rice kinases and 254 of their interacting proteins. Overall, the resulting interaction map supports a large number of known or predicted kinase-protein interactions from both plants and animals and reveals many new functional insights. Notably, we found a potential widespread role for E3 ubiquitin ligases in pathogen defense signaling mediated by receptor-like kinases, particularly by the kinases that may have evolved from recently expanded kinase subfamilies in rice. We anticipate that the data provided here will serve as a foundation for targeted functional studies in rice and other plants. The application of yeast two-hybrid and TAPtag analyses for large-scale plant protein interaction studies is also discussed.

  7. Discovery of inhibitors of bacterial histidine kinases

    NARCIS (Netherlands)

    Velikova, N.R.

    2014-01-01

    Discovery of Inhibitors of Bacterial Histidine Kinases Summary

    The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based drug discovery approach, we have identified small-molecule histidine-kinase

  8. dependent/calmodulin- stimulated protein kinase from moss

    Indian Academy of Sciences (India)

    Unknown

    stimulated protein kinase; CDPK, calmodulin domain-like protein kinase; KM14, 14 amino acid synthetic peptide; .... used were obtained from Sigma Chemical Company, USA, ..... Plant chimeric Ca2+/Calmodulin-dependent protein kinase.

  9. The Protein Kinase RSK Family - Roles in Prostate Cancer

    National Research Council Canada - National Science Library

    Lannigan, Deborah

    2006-01-01

    The Ser/Thr protein kinase p90-kDa ribosomal S6 kinase (RSK) is an important downstream effector of mitogen-activated protein kinase but its roles in prostate cancer have not been previously examined...

  10. On the interplay between working memory consolidation and attentional selection in controlling conscious access : Parallel processing at a cost-a comment on 'The interplay of attention and consciousness in visual search, attentional blink and working memory consolidation'

    NARCIS (Netherlands)

    Wyble, Brad; Bowman, Howard; Nieuwenstein, Mark

    On the interplay between working memory consolidation and attentional selection in controlling conscious access: parallel processing at a cost-a comment on 'The interplay of attention and consciousness in visual search, attentional blink and working memory consolidation'

  11. Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.

    Science.gov (United States)

    Filippakopoulos, Panagis; Kofler, Michael; Hantschel, Oliver; Gish, Gerald D; Grebien, Florian; Salah, Eidarus; Neudecker, Philipp; Kay, Lewis E; Turk, Benjamin E; Superti-Furga, Giulio; Pawson, Tony; Knapp, Stefan

    2008-09-05

    The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved the structure of the prototypic SH2-kinase unit of the human Fes tyrosine kinase, which appears specialized for positive signaling. In its active conformation, the SH2 domain tightly interacts with the kinase N-terminal lobe and positions the kinase alphaC helix in an active configuration through essential packing and electrostatic interactions. This interaction is stabilized by ligand binding to the SH2 domain. Our data indicate that Fes kinase activation is closely coupled to substrate recognition through cooperative SH2-kinase-substrate interactions. Similarly, we find that the SH2 domain of the active Abl kinase stimulates catalytic activity and substrate phosphorylation through a distinct SH2-kinase interface. Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling.

  12. Glycogen Synthase Kinase-3β

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Lenskjold, Toke; Jacoby, Anne Sophie

    2016-01-01

    cells were quantitated using enzyme immunometric assays. The activity of GSK-3β (serine-9-phosphorylated GSK-3β/total GSK-3β) was lower at baseline compared with follow-up. No significant mean change over time was observed in levels of total GSK-3β and serine-9-phosphorylated GSK-3β. Exploratory......Evidence indicates a role for glycogen synthase kinase-3β (GSK-3β) in the pathophysiology of mood disorders and in cognitive disturbances; however, the natural variation in GSK-3β activity over time is unknown. We aimed to investigate GSK-3β activity over time and its possible correlation...... with emotional lability, subjective mood fluctuations and cognitive function in healthy individuals. Thirty-seven healthy subjects were evaluated with neuropsychological tests and blood samples at baseline and 12-week follow-up. Total GSK-3β and serine-9-phosphorylated GSK-3β in peripheral blood mononuclear...

  13. TYROSINE KINASE INHIBITORS AND PREGNANCY

    Directory of Open Access Journals (Sweden)

    Elisabetta Abruzzese

    2014-04-01

    Full Text Available The management of patients with chronic myeloid leukemia (CML during pregnancy has became recently a matter of continuous debate.  The introduction of the Tyrosine Kinase Inhibitors (TKIs in clinical practice has dramatically changed the prognosis of CML patients.  Patients diagnosed in chronic phase can reasonably expect many years of excellent disease control and good quality of life, as well as a normal life expectancy.  This fact has come the necessity to address issues relating to fertility and pregnancy. Physicians are not infrequently being asked for advice regarding the need for, and or the appropriateness of, stopping treatment in order to conceive. In this report we will review the data published in terms of fertility, conception, pregnancy, pregnancy outcome and illness control for all the approved TKIs, as well as suggest how to manage a planned and/or unplanned pregnancy.

  14. European concerted action on offshore wind energy deployment: inventory and analysis of power transmission barriers in eight member states

    International Nuclear Information System (INIS)

    Woyte, Achim; Gardner, Paul; Snodin, Helen

    2007-01-01

    The European Concerted Action for Offshore Wind Energy Deployment (COD) was carried out by eight sea-bordering European Union member states, with the objective to remove not explicitly technical barriers to offshore wind energy. Within the COD, an inventory of relevant aspects affecting the grid integration of offshore wind energy on a large scale in the eight countries has been made. Collected data items for this inventory are national plans and prospects for offshore wind energy, information about the transmission system, possibilities for grid connection, aspects of the grid codes, balancing, connection and energy pricing. The comprehensive COD reports were published and presented in October 2005 during the Copenhagen Offshore wind conference. This paper provides a short description of the situation for each country. Thereafter, country-specific information is grouped based on geography and membership in a synchronous zone. Additionally, a view is developed on the desirable facilities for the trans-European exchange of power from large wind farms. Finally, we elaborate overall conclusions in order to arrive at generalized observations, recommendations for policy makers and issues that will emerge in the near future. As a general conclusion, many things need to be done on a technical level in order to integrate large amounts of offshore wind power into our power systems. However, none of these measures is technically unknown. Therefore, the feasibility of integrating large amounts of offshore wind power is mainly a question of finance and hence based on political decisions. (Author)

  15. Offshore Wind Energy Ready to Power a Sustainable Europe. Final Report. Concerted Action on Offshore Wind Energy in Europe

    International Nuclear Information System (INIS)

    2001-12-01

    The objective of the project Concerted Action on Offshore Wind Energy in Europe [CA-OWEE] is to define the current state of the art of offshore wind energy in Europe through gathering and evaluation of information from across Europe and to disseminate the resulting knowledge to all interested, in order to help stimulate the development of the industry. The project is being funded by the European Commission and will be completed at the end of 2001. The knowledge gathered will be freely available through an internet site, a workshop and a printed report. This project divides offshore wind energy into five clusters of subjects and reviews the recent history and summarise the current state of affairs, relating to: Cluster 1 offshore technology, of the wind turbines and the support structures, Cluster 2 grid integration, energy supply and financing, Cluster 3 resources and economics, Cluster 4 activities and prospects, Cluster 5 social acceptance, environmental impact and politics. The conclusions from these surveys are then used to define recommendations for the future RTD strategy for Europe. The project's 17 partners come from 13 countries, thus covering the majority of the European Community's coastline. The partners cover a wide range of expertise and include developers, utilities, consultants, research institutes and universities

  16. Acetic Acid Can Catalyze Succinimide Formation from Aspartic Acid Residues by a Concerted Bond Reorganization Mechanism: A Computational Study

    Directory of Open Access Journals (Sweden)

    Ohgi Takahashi

    2015-01-01

    Full Text Available Succinimide formation from aspartic acid (Asp residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe as a model compound, we propose the possibility that acetic acid (AA, which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism.

  17. Concerted in vitro trimming of viral HLA-B27-restricted ligands by human ERAP1 and ERAP2 aminopeptidases.

    Directory of Open Access Journals (Sweden)

    Elena Lorente

    Full Text Available In the classical human leukocyte antigen (HLA class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases and transported to the endoplasmic reticulum (ER lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. In this study, the possible cooperative effect of generating five naturally processed HLA-B27 ligands by both proteases was analyzed. We identified differences in the products obtained with increased detection of natural HLA-B27 ligands by comparing double versus single enzyme digestions by mass spectrometry analysis. These in vitro data suggest that each enzyme can use the degradation products of the other as a substrate for new N-terminal trimming, indicating concerted aminoproteolytic activity of ERAP 1 and ERAP2.

  18. Paul Wittgenstein's right arm and his phantom: the saga of a famous concert pianist and his amputation.

    Science.gov (United States)

    Boller, François; Bogousslavsky, Julien

    2015-01-01

    Reports of postamputation pain and problems linked to phantom limbs have increased in recent years, particularly in relation to war-related amputations. These problems are still poorly understood and are considered rather mysterious, and they are difficult to treat. In addition, they may shed light on brain physiology and neuropsychology. Functional neuroimaging techniques now enable us to better understand their pathophysiology and to consider new rehabilitation techniques. Several artists have suffered from postamputation complications and this has influenced not only their personal life but also their artistic work. Paul Wittgenstein (1887-1961), a pianist whose right arm was amputated during the First World War, became a famous left-handed concert performer. His case provides insight into Post-World War I musical and political history. More specifically, the impact on the artistic life of this pianist illustrates various postamputation complications, such as phantom limb, stump pain, and especially moving phantom. The phantom movements of his right hand helped him develop the dexterity of his left hand. Wittgenstein played piano works that were written especially for him (the most famous being Ravel's Concerto for the Left Hand) and composed some of his own. Additionally, several famous composers had previously written for the left hand. © 2015 Elsevier B.V. All rights reserved.

  19. The evolution of increased competitive ability, innate competitive advantages, and novel biochemical weapons act in concert for a tropical invader.

    Science.gov (United States)

    Qin, Rui-Min; Zheng, Yu-Long; Valiente-Banuet, Alfonso; Callaway, Ragan M; Barclay, Gregor F; Pereyra, Carlos Silva; Feng, Yu-Long

    2013-02-01

    There are many non-mutually exclusive mechanisms for exotic invasions but few studies have concurrently tested more than one hypothesis for the same species. Here, we tested the evolution of increased competitive ability (EICA) hypothesis in two common garden experiments in which Chromolaena odorata plants originating from native and nonnative ranges were grown in competition with natives from each range, and the novel weapons hypothesis in laboratory experiments with leachates from C. odorata. Compared with conspecifics originating from the native range, C. odorata plants from the nonnative range were stronger competitors at high nutrient concentrations in the nonnative range in China and experienced far more herbivore damage in the native range in Mexico. In both China and Mexico, C. odorata was more suppressed by species native to Mexico than by species native to China. Species native to China were much more inhibited by leaf extracts from C. odorata than species from Mexico, and this difference in allelopathic effects may provide a possible explanation for the biogeographic differences in competitive ability. Our results indicate that EICA, innate competitive advantages, and novel biochemical weapons may act in concert to promote invasion by C. odorata, and emphasize the importance of exploring multiple, non-mutually exclusive mechanisms for invasions. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  20. Protein crystal growth on board Shenzhou 3: a concerted effort improves crystal diffraction quality and facilitates structure determination

    International Nuclear Information System (INIS)

    Han, Y.; Cang, H.-X.; Zhou, J.-X.; Wang, Y.-P.; Bi, R.-C.; Colelesage, J.; Delbaere, L.T.J.; Nahoum, V.; Shi, R.; Zhou, M.; Zhu, D.-W.; Lin, S.-X.

    2004-01-01

    The crystallization of 16 proteins was carried out using 60 wells on board Shenzhou 3 in 2002. Although the mission was only 7 days, careful and concerted planning at all stages made it possible to obtain crystals of improved quality compared to their ground controls for some of the proteins. Significantly improved resolutions were obtained from diffracted crystals of 4 proteins. A complete data set from a space crystal of the PEP carboxykinase yielded significantly higher resolution (1.46 A vs. 1.87 A), I/sigma (22.4 vs. 15.5), and a lower average temperature factor (29.2 A 2 vs. 42.9 A 2 ) than the best ground-based control crystal. The 3-D structure of the enzyme is well improved with significant ligand density. It has been postulated that the reduced convection and absence of macromolecule sedimentation under microgravity have advantages/benefits for protein crystal growth. Improvements in experimental design for protein crystal growth in microgravity are ongoing

  1. Acetic acid can catalyze succinimide formation from aspartic acid residues by a concerted bond reorganization mechanism: a computational study.

    Science.gov (United States)

    Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi

    2015-01-12

    Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition) to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds) occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism.

  2. The interplay of BDNF-TrkB with NMDA receptor in propofol-induced cognition dysfunction : Mechanism for the effects of propofol on cognitive function.

    Science.gov (United States)

    Zhou, Junfei; Wang, Fang; Zhang, Jun; Li, Jianfeng; Ma, Li; Dong, Tieli; Zhuang, Zhigang

    2018-04-05

    The aim of the present study was to verify whether propofol impaired learning and memory through the interplay of N-methyl-D-aspartate (NMDA) receptor with brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling pathway. 120 Sprague-Dawley (SD) rats were randomly assigned into eight groups. Experimental drugs including saline, intralipid, propofol, N-methyl-D-aspartate (NMDA), 7,8-dihydroxyflavone (7,8-DHF), K252a and MK-801. Spatial learning and memory of rats were tested by the Morris water maze (MWM) test. The mRNA and protein expression were determined by immunohistochemistry, RT-PCR and western blot. Finally, hippocampus cells proliferation and apoptosis were examined by PCNA immunohistochemistry and TUNEL respectively. The memory and learning was diminished in the propofol exposure group, however, the impaired memory and learning of rats were improved with the addition of NMDA and 7,8-DHF, while the improvement of memory and learning of rats were reversed with the addition of K252a and MK-801. In addition, the mRNA and protein expression levels and hippocampus cells proliferation were the same trend with the results of the MWM test, while apoptosis in hippocampus was reversed. The propofol can impair memory and learning of rats and induce cognition dysfunction through the interplay of NMDA receptor and BDNF-TrkB-CREB signaling pathway.

  3. Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

    Directory of Open Access Journals (Sweden)

    Stephanie Munk

    2017-10-01

    Full Text Available The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essential role for SUMOs (small ubiquitin-like modifiers has also been established. Here, we investigate the global interplay between phosphorylation and SUMOylation in response to replication stress. Using SUMO and phosphoproteomic technologies, we identify thousands of regulated modification sites. We find co-regulation of central DNA damage and replication stress responders, of which the ATR-activating factor TOPBP1 is the most highly regulated. Using pharmacological inhibition of the DNA damage response kinases ATR and ATM, we find that these factors regulate global protein SUMOylation in the protein networks that protect DNA upon replication stress and fork breakage, pointing to integration between phosphorylation and SUMOylation in the cellular systems that protect DNA integrity.

  4. Standing Concertation Committee

    CERN Document Server

    HR Department

    2009-01-01

    Main points examined at the meeting of 24 June 2009 Results of the 2009 MARS exercise The Committee took note of the results of the 2009 MARS exercise presented by the Head of the HR Department, expressing satisfaction for the early availability of the statistics and for the fact that the analysis of the results covered the last three years. Status report on the work on the five-yearly review The Committee took note of a presentation by P. Gildemyn on the data collection procedure for the 2010 five-yearly review (staff, fellows, associate members of the personnel, CHIS) and of the proposed work schedule. Implications for employment conditions of the discussions at the Finance Committee and Council on 17 and 18 June 2009 The Chairman briefly reported on the discussions at the meetings of the Finance Committee and Council in June 2009, on the 2010-2014 medium-term plan and the 2010 preliminary draft budget, as well as on the modified strategy and goals for 2009. The Committee ...

  5. Towards a Concerted Effort

    DEFF Research Database (Denmark)

    Johansen, Mette-Louise; Mouritsen, Tina; Montgomery, Edith

    2006-01-01

    This book contains a method model for the prevention of youth crime in Danish municipalities. The method model consists of instructions for conducting processual network meetings between traumatized refugee parents and the professional specialists working with their children on an intermunicipal...

  6. Thinking-in-Concert

    Science.gov (United States)

    O'Donnell, Aislinn

    2012-01-01

    In this essay, I examine the concept of thinking in Hannah Arendt's writings. Arendt's interest in the experience of thinking allowed her to develop a concept of thinking that is distinct from other forms of mental activity such as cognition and problem solving. For her, thinking is an unending, unpredictable and destructive activity without fixed…

  7. AIDA: concerted calorimeter development

    CERN Multimedia

    Felix Sefkow

    2013-01-01

    AIDA – the EU-funded project bringing together more than 80 institutes worldwide – aims at developing new detector solutions for future accelerators. Among the highlights reported at AIDA’s recent annual meeting in Frascati was the completion of an impressive calorimeter test beam programme, conducted by the CALICE collaboration over the past two years at CERN’s PS and SPS beam lines.   The CALICE tungsten calorimeter prototype under test at CERN. This cubic-metre hadron calorimeter prototype has almost 500,000 individually read-out electronics channels – more than all the calorimeters of ATLAS and CMS put together. Calorimeter development in AIDA is mainly motivated by experiments at possible future electron-positron colliders, namely ILC or CLIC. The physics requirements of such future machines demand extremely high-performance calorimetry. This is best achieved using a finely segmented system that reconstructs events using the so-called pa...

  8. Interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.

    Science.gov (United States)

    Yang, Ke-Ke; Sui, Yi; Zhou, Hui-Rong; Zhao, Hai-Lu

    2017-05-01

    Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate-activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate-activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate-activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate-activated protein kinase signaling pathway resulted in hyperlipidemia and

  9. Spice: discovery of phenotype-determining component interplays

    Directory of Open Access Journals (Sweden)

    Chen Zhengzhang

    2012-05-01

    Full Text Available Abstract Background A latent behavior of a biological cell is complex. Deriving the underlying simplicity, or the fundamental rules governing this behavior has been the Holy Grail of systems biology. Data-driven prediction of the system components and their component interplays that are responsible for the target system’s phenotype is a key and challenging step in this endeavor. Results The proposed approach, which we call System Phenotype-related Interplaying Components Enumerator (Spice, iteratively enumerates statistically significant system components that are hypothesized (1 to play an important role in defining the specificity of the target system’s phenotype(s; (2 to exhibit a functionally coherent behavior, namely, act in a coordinated manner to perform the phenotype-specific function; and (3 to improve the predictive skill of the system’s phenotype(s when used collectively in the ensemble of predictive models. Spice can be applied to both instance-based data and network-based data. When validated, Spice effectively identified system components related to three target phenotypes: biohydrogen production, motility, and cancer. Manual results curation agreed with the known phenotype-related system components reported in literature. Additionally, using the identified system components as discriminatory features improved the prediction accuracy by 10% on the phenotype-classification task when compared to a number of state-of-the-art methods applied to eight benchmark microarray data sets. Conclusion We formulate a problem—enumeration of phenotype-determining system component interplays—and propose an effective methodology (Spice to address this problem. Spice improved identification of cancer-related groups of genes from various microarray data sets and detected groups of genes associated with microbial biohydrogen production and motility, many of which were reported in literature. Spice also improved the predictive skill of the

  10. The heterothallic sugarbeet pathogen Cercospora beticola contains exon fragments of both MAT genes that are homogenized by concerted evolution.

    Science.gov (United States)

    Bolton, Melvin D; de Jonge, Ronnie; Inderbitzin, Patrik; Liu, Zhaohui; Birla, Keshav; Van de Peer, Yves; Subbarao, Krishna V; Thomma, Bart P H J; Secor, Gary A

    2014-01-01

    Dothideomycetes is one of the most ecologically diverse and economically important classes of fungi. Sexual reproduction in this group is governed by mating type (MAT) genes at the MAT1 locus. Self-sterile (heterothallic) species contain one of two genes at MAT1 (MAT1-1-1 or MAT1-2-1) and only isolates of opposite mating type are sexually compatible. In contrast, self-fertile (homothallic) species contain both MAT genes at MAT1. Knowledge of the reproductive capacities of plant pathogens are of particular interest because recombining populations tend to be more difficult to manage in agricultural settings. In this study, we sequenced MAT1 in the heterothallic Dothideomycete fungus Cercospora beticola to gain insight into the reproductive capabilities of this important plant pathogen. In addition to the expected MAT gene at MAT1, each isolate contained fragments of both MAT1-1-1 and MAT1-2-1 at ostensibly random loci across the genome. When MAT fragments from each locus were manually assembled, they reconstituted MAT1-1-1 and MAT1-2-1 exons with high identity, suggesting a retroposition event occurred in a homothallic ancestor in which both MAT genes were fused. The genome sequences of related taxa revealed that MAT gene fragment pattern of Cercospora zeae-maydis was analogous to C. beticola. In contrast, the genome of more distantly related Mycosphaerella graminicola did not contain MAT fragments. Although fragments occurred in syntenic regions of the C. beticola and C. zeae-maydis genomes, each MAT fragment was more closely related to the intact MAT gene of the same species. Taken together, these data suggest MAT genes fragmented after divergence of M. graminicola from the remaining taxa, and concerted evolution functioned to homogenize MAT fragments and MAT genes in each species. Published by Elsevier Inc.

  11. Stakeholder Analysis for Sharing Agro-environment Issues Towards Concerted Action: A Case Study on Diffuse Nitrate Pollution

    Directory of Open Access Journals (Sweden)

    Pier Paolo Roggero

    2006-12-01

    Full Text Available There is increasing need for participatory approaches to support the development of sustainable farming systems, based on the active involvement of stakeholders in the definition of research objectives and priorities. This paper reports the experience of a team of agronomy researchers involved in the SLIM project (http://slim.open.ac.uk, around a case study of nitrate pollution. The agro-ecosystem analysis included biophysical processes at microcatchment scale and the stakeholders’ perceptions, interests and practices related to the nitrate issue (stakeholders analysis. The conceptual SLIM framework model supported new interactions among stakeholders, that were facilitated by researchers, using dialogical tools to enable them to use scientific data and to integrate their own knowledge on the farming system. The agro-environment policies, based on compulsory prescriptions, revealed weak assumptions and insufficient integration of scientific knowledge. The stakeholder analysis contributed to the identification of priorities both for scientific research and agro-environment policies. Researchers provided the site-specific scientific knowledge, in a way that enabled stakeholders to identify the relationships between agricultural practices, landscape values and the nitrate pollution issue and to elaborate shared strategies to develop concerted actions. New spaces for interaction between researchers and stakeholders should be created to face complex agro-environment issues at catchment scale, such as the nitrate pollution of groundwater. The implication for agronomy research is that the experiments should be designed to produce suitable results to facilitate participatory sessions and that it is worthwhile to invest in specific skills of communication science and group dynamics management within the agronomy researchers’ community, in order to integrate agronomy knowledge into high quality participatory processes.

  12. Stakeholder Analysis for Sharing Agro-environment Issues Towards Concerted Action: A Case Study on Diffuse Nitrate Pollution

    Directory of Open Access Journals (Sweden)

    Marco Toderi

    2011-02-01

    Full Text Available There is increasing need for participatory approaches to support the development of sustainable farming systems, based on the active involvement of stakeholders in the definition of research objectives and priorities. This paper reports the experience of a team of agronomy researchers involved in the SLIM project (http://slim.open.ac.uk, around a case study of nitrate pollution. The agro-ecosystem analysis included biophysical processes at microcatchment scale and the stakeholders’ perceptions, interests and practices related to the nitrate issue (stakeholders analysis. The conceptual SLIM framework model supported new interactions among stakeholders, that were facilitated by researchers, using dialogical tools to enable them to use scientific data and to integrate their own knowledge on the farming system. The agro-environment policies, based on compulsory prescriptions, revealed weak assumptions and insufficient integration of scientific knowledge. The stakeholder analysis contributed to the identification of priorities both for scientific research and agro-environment policies. Researchers provided the site-specific scientific knowledge, in a way that enabled stakeholders to identify the relationships between agricultural practices, landscape values and the nitrate pollution issue and to elaborate shared strategies to develop concerted actions. New spaces for interaction between researchers and stakeholders should be created to face complex agro-environment issues at catchment scale, such as the nitrate pollution of groundwater. The implication for agronomy research is that the experiments should be designed to produce suitable results to facilitate participatory sessions and that it is worthwhile to invest in specific skills of communication science and group dynamics management within the agronomy researchers’ community, in order to integrate agronomy knowledge into high quality participatory processes.

  13. Epigenetic silencing of BTB and CNC homology 2 and concerted promoter CpG methylation in gastric cancer.

    Science.gov (United States)

    Haam, Keeok; Kim, Hee-Jin; Lee, Kyung-Tae; Kim, Jeong-Hwan; Kim, Mirang; Kim, Seon-Young; Noh, Seung-Moo; Song, Kyu-Sang; Kim, Yong Sung

    2014-09-01

    BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription factor with a prominent role in B-cell development. Genetic polymorphisms within a single locus encoding BACH2 are associated with various autoimmune diseases and allergies. In this study, restriction landmark genomic scanning revealed methylation at a NotI site in a CpG island covering the BACH2 promoter in gastric cancer cell lines and primary gastric tumors. Increased methylation of the BACH2 promoter was observed in 52% (43/83) of primary gastric tumors, and BACH2 hypermethylation was significantly associated with decreased gene expression. Treatment with 5-aza-2'-deoxycytidine and/or trichostatin. A restored BACH2 expression in BACH2-silenced gastric cancer cell lines, and knockdown of BACH2 using short hairpin RNA (i.e. RNA interference) increased cell proliferation in gastric cancer cells. Clinicopathologic data showed that decreased BACH2 expression occurred significantly more frequently in intestinal-type (27/44, 61%) compared with diffuse-type (13/50, 26%) gastric cancers (P<0.001). Furthermore, BACH2 promoter methylation paralleled that of previously identified targets, such as LRRC3B, LIMS2, PRKD1 and POPDC3, in a given set of gastric tumors. We propose that concerted methylation in many promoters plays a role in accelerating gastric tumor formation and that methylated promoter loci may be targets for therapeutic treatment, such as the recently introduced technique of epigenetic editing. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. The concerted impact of galaxies and QSOs on the ionization and thermal state of the intergalactic medium

    Science.gov (United States)

    Kakiichi, Koki; Graziani, Luca; Ciardi, Benedetta; Meiksin, Avery; Compostella, Michele; Eide, Marius B.; Zaroubi, Saleem

    2017-07-01

    We present a detailed analysis of the ionization and thermal structure of the intergalactic medium (IGM) around a high-redshift (z = 10) QSO, using a large suite of cosmological, multifrequency radiative transfer simulations, exploring the contribution from galaxies as well as the QSO, and the effect of X-rays and secondary ionization. We show that in high-z QSO environments both the central QSO and the surrounding galaxies concertedly control the reionization morphology of hydrogen and helium and have a non-linear impact on the thermal structure of the IGM. A QSO imprints a distinctive morphology on H II regions if its total ionizing photon budget exceeds that of the surrounding galaxies since the onset of hydrogen reionization; otherwise, the morphology shows little difference from that of H II regions produced only by galaxies. In addition, the spectral shape of the collective radiation field from galaxies and QSOs controls the thickness of the I-fronts. While a UV-obscured QSO can broaden the I-front, the contribution from other UV sources, either galaxies or unobscured QSOs, is sufficient to maintain a sharp I-front. X-ray photons from the QSO are responsible for a prominent extended tail of partial ionization ahead of the I-front. QSOs leave a unique imprint on the morphology of He II/He III regions. We suggest that, while the physical state of the IGM is modified by QSOs, the most direct test to understand the role of galaxies and QSOs during reionization is to perform galaxy surveys in a region of sky imaged by 21 cm tomography.

  15. Interplay of static and dynamic features in biomimetic smart ears.

    Science.gov (United States)

    Pannala, Mittu; Meymand, Sajjad Zeinoddini; Müller, Rolf

    2013-06-01

    Horseshoe bats (family Rhinolophidae) have sophisticated biosonar systems with outer ears (pinnae) that are characterized by static local shape features as well as dynamic non-rigid changes to their overall shapes. Here, biomimetic prototypes fabricated from elastic rubber sheets have been used to study the impact of these static and dynamic features on the acoustic device characteristics. The basic shape of the prototypes was an obliquely truncated horn augmented with three static local shape features: vertical ridge, pinna-rim incision and frontal flap (antitragus). The prototype shape was deformed dynamically using a one-point actuation mechanism to produce a biomimetic bending of the prototype's tip. In isolation, the local shape features had little impact on the device beampattern. However, strong interactions were observed between these features and the overall deformation. The further the prototype tip was bent down, the stronger the beampatterns associated with combinations of multiple features differed from the upright configuration in the prominence of sidelobes. This behavior was qualitatively similar to numerical predictions for horseshoe bats. Hence, the interplay between static and dynamic features could be a bioinspired principle for affecting large changes through the dynamic manipulations of interactions that are sensitive to small geometrical changes.

  16. Physics Interplay of the LHC and the ILC

    Energy Technology Data Exchange (ETDEWEB)

    Weiglein, G.

    2004-12-17

    Physics at the Large Hadron Collider (LHC) and the International e{sup +}e{sup -} Linear Collider (ILC)will be complementary in many respects, as has been demonstrated at previous generations of hadron and lepton colliders. This report addresses the possible interplay between the LHC and ILC in testing the Standard Model and in discovering and determining the origin of new physics. Mutual benefits for the physics programme at both machines can occur both at the level of a combined interpretation of Hadron Collider and Linear Collider data and at the level of combined analyses of the data, where results obtained at one machine can directly influence the way analyses are carried out at the other machine. Topics under study comprise the physics of weak and strong electroweak symmetry breaking, supersymmetric models, new gauge theories, models with extra dimensions, and electroweak and QCD precision physics. The status of the work that has been carried out within the LHC/LC Study Group so far is summarized in this report. Possible topics for future studies are outlined.

  17. Representing Space through the Interplay between Attention and Multisensory Integration

    Directory of Open Access Journals (Sweden)

    Emiliano Macaluso

    2011-10-01

    Full Text Available Multisensory integration has been traditionally thought to rely on a restricted set of multisensory brain areas, and to occur automatically and pre-attentively. More recently, it has become evident that multisensory interactions can be found almost everywhere in the brain, including areas involved in attention control and areas modulated by attention. In a series of fMRI experiments, we manipulated concurrently the position of multisensory stimuli and the distribution of spatial attention. This enabled us to highlight the role of high-order fronto-parietal areas, as well as sensory-specific occipital cortex, for multisensory processing and spatial attention control. We found that specific task constraints regarding the nature of attentional deployment (endogenous vs. exogenous, the spatial relationship between stimulus position and attended location, and attentional load shape the interplay between attention and multisensory processing. We suggest that multisensory integration acts as a saliency-defining process that can interact with attentional control beyond any within-modality mechanism. We propose that an anatomically-distributed, but functionally-integrated, representation of space makes use of multisensory interactions to help attention selecting relevant spatial locations. Stimuli at the attended location undergo enhanced processing, including boosting of multisensory signals there. In this perspective, attention and multisensory integration operate in an interactive manner jointly determining the activity of a wide-spread network that includes high-order fronto-parietal regions and sensory-specific areas.

  18. Microscopic interplay of superconducting and magnetic order parameters in ferropnictides

    Energy Technology Data Exchange (ETDEWEB)

    Maeter, H.; Goltz, T.; Spehling, J.; Klauss, H.H. [Institut fuer Festkoerperphysik, TU Dresden (Germany); Bendele, M.; Luetkens, H.; Khasanov, R.; Pascua, G.; Shermadini, Z.; Amato, A. [Laboratory for Muon-Spin Spectroscopy, Paul Scherrer Institut, Villigen (Switzerland); Aswartham, S.; Hamann-Borrero, J.E.; Kondrat, A.; Hess, C.; Wolter, A.; Wurmehl, S.; Behr, G.; Buechner, B. [Leibniz-Institut fuer Festkoerper- und Werkstoffforschung Dresden (Germany); Wiesenmayer, E.; Johrendt, D. [Department Chemie, Ludwig-Maximilians-Universitaet Muenchen (Germany); Potts, H.; Banusch, B. [Swiss Nanoscience Institute, Universitaet Basel (Switzerland)

    2012-07-01

    We present results of {mu}SR experiments of Ba{sub 1-x}Na{sub x}Fe{sub 2}As{sub 2} that show a large coupling of the superconducting and magnetic order parameters. This is unexpected in light of the phase separation in Ba{sub 1-x}K{sub x}Fe{sub 2}As{sub 2}. However, in a {mu}SR study of Ba{sub 1-x}K{sub x}Fe{sub 2}As{sub 2} we unambiguously showed microscopic coexistence, even though there are many reports of phase separation in this system. In FeSe{sub 1-x} the interplay of phase separation and microscopic coexistence is also evident, here pressure can induce a change from microscopic coexistence to a combination of both. In light of the {mu}SR results it seems likely that phase separation and microscopic coexistence depend on the microscopic properties much more than on disorder.

  19. Lactobacillus acidophilus-Rutin Interplay Investigated by Proteomics.

    Directory of Open Access Journals (Sweden)

    Maria Fiorella Mazzeo

    Full Text Available Dietary polyphenols are bioactive molecules that beneficially affect human health, due to their anti-oxidant, anti-inflammatory, cardio-protective and chemopreventive properties. They are absorbed in a very low percentage in the small intestine and reach intact the colon, where they are metabolized by the gut microbiota. Although it is well documented a key role of microbial metabolism in the absorption of polyphenols and modulation of their biological activity, molecular mechanisms at the basis of the bacteria-polyphenols interplay are still poorly understood. In this context, differential proteomics was applied to reveal adaptive response mechanisms that enabled a potential probiotic Lactobacillus acidophilus strain to survive in the presence of the dietary polyphenol rutin. The response to rutin mainly modulated the expression level of proteins involved in general stress response mechanisms and, in particular, induced the activation of protein quality control systems, and affected carbohydrate and amino acid metabolism, protein synthesis and cell wall integrity. Moreover, rutin triggered the expression of proteins involved in oxidation-reduction processes.This study provides a first general view of the impact of dietary polyphenols on metabolic and biological processes of L. acidophilus.

  20. The Interplay between Feedback and Buffering in Cellular Homeostasis.

    Science.gov (United States)

    Hancock, Edward J; Ang, Jordan; Papachristodoulou, Antonis; Stan, Guy-Bart

    2017-11-22

    Buffering, the use of reservoirs of molecules to maintain concentrations of key molecular species, and negative feedback are the primary known mechanisms for robust homeostatic regulation. To our knowledge, however, the fundamental principles behind their combined effect have not been elucidated. Here, we study the interplay between buffering and negative feedback in the context of cellular homeostasis. We show that negative feedback counteracts slow-changing disturbances, whereas buffering counteracts fast-changing disturbances. Furthermore, feedback and buffering have limitations that create trade-offs for regulation: instability in the case of feedback and molecular noise in the case of buffering. However, because buffering stabilizes feedback and feedback attenuates noise from slower-acting buffering, their combined effect on homeostasis can be synergistic. These effects can be explained within a traditional control theory framework and are consistent with experimental observations of both ATP homeostasis and pH regulation in vivo. These principles are critical for studying robustness and homeostasis in biology and biotechnology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Interplay between Kondo and Majorana Interactions in Quantum Dots

    Directory of Open Access Journals (Sweden)

    Meng Cheng

    2014-09-01

    Full Text Available We study the properties of a quantum dot coupled to a topological superconductor and a normal lead and discuss the interplay between Kondo-and Majorana-induced couplings in quantum dots. The latter appears due to the presence of Majorana zero-energy modes localized, for example, at the ends of the one-dimensional superconductor. We investigate the phase diagram of the system as a function of Kondo and Majorana interactions using a renormalization-group analysis, a slave-boson mean-field theory, and numerical simulations using the density-matrix renormalization-group method. We show that, in addition to the well-known Kondo fixed point, the system may flow to a new fixed point controlled by the Majorana-induced coupling, which is characterized by nontrivial correlations between a localized spin on the dot and the fermion parity of the topological superconductor and the normal lead. We compute several measurable quantities, such as differential tunneling conductance and impurity-spin susceptibility, which highlight some peculiar features characteristic to the Majorana fixed point.

  2. Gene-environment interplay in the etiology of psychosis.

    Science.gov (United States)

    Zwicker, Alyson; Denovan-Wright, Eileen M; Uher, Rudolf

    2018-01-15

    Schizophrenia and other types of psychosis incur suffering, high health care costs and loss of human potential, due to the combination of early onset and poor response to treatment. Our ability to prevent or cure psychosis depends on knowledge of causal mechanisms. Molecular genetic studies show that thousands of common and rare variants contribute to the genetic risk for psychosis. Epidemiological studies have identified many environmental factors associated with increased risk of psychosis. However, no single genetic or environmental factor is sufficient to cause psychosis on its own. The risk of developing psychosis increases with the accumulation of many genetic risk variants and exposures to multiple adverse environmental factors. Additionally, the impact of environmental exposures likely depends on genetic factors, through gene-environment interactions. Only a few specific gene-environment combinations that lead to increased risk of psychosis have been identified to date. An example of replicable gene-environment interaction is a common polymorphism in the AKT1 gene that makes its carriers sensitive to developing psychosis with regular cannabis use. A synthesis of results from twin studies, molecular genetics, and epidemiological research outlines the many genetic and environmental factors contributing to psychosis. The interplay between these factors needs to be considered to draw a complete picture of etiology. To reach a more complete explanation of psychosis that can inform preventive strategies, future research should focus on longitudinal assessments of multiple environmental exposures within large, genotyped cohorts beginning early in life.

  3. Interplay of light and heavy impurities in a fusion plasma

    Energy Technology Data Exchange (ETDEWEB)

    Gaja, Mustafa [IPP, Garching (Germany); Tokar, Mikhail [IEK4, Juelich FZ, Juelich (Germany)

    2016-07-01

    Radiation from impurities eroded from the walls can lead to a broad spectrum of spectacular phenomena in fusion devices An example of such events are breathing oscillations observed in the large helical device (LHD), in long pulse discharges with a stainless steel divertor. They were characterized with oscillations of a period of a second in various plasma parameters. By optimizing magnetic geometry this operation mode, leading to a deteriorate plasma performance, can be avoided. Nonetheless it is of interest and practical importance to understand and firmly predict conditions for breathing phenomenon, in particular, in view of similar impurity environment in W-7 X stellarator. A qualitative explanation for breathing oscillations proposed earlier presumes that they arise due to non-linear synergetic interplay of diverse physical processes. A one-dimensional non-stationary model, describing the generation and transport of main, impurity particles and heat by including the radiation of high-Z (Fe) and low-Z (C and O) impurities is elaborated here. The calculations predict the appearance of oscillations in the relevant range of plasma parameters, reproduce well experimentally observed amplitudes and period of oscillations. It demonstrates that the smaller the fraction of the plasma interaction with a stainless steel surface, the higher the light impurity concentration needed to excite the breathing oscillations. This shows a way to avoid oscillations in future experiments.

  4. Interplay between Peptide Bond Geometrical Parameters in Nonglobular Structural Contexts

    Directory of Open Access Journals (Sweden)

    Luciana Esposito

    2013-01-01

    Full Text Available Several investigations performed in the last two decades have unveiled that geometrical parameters of protein backbone show a remarkable variability. Although these studies have provided interesting insights into one of the basic aspects of protein structure, they have been conducted on globular and water-soluble proteins. We report here a detailed analysis of backbone geometrical parameters in nonglobular proteins/peptides. We considered membrane proteins and two distinct fibrous systems (amyloid-forming and collagen-like peptides. Present data show that in these systems the local conformation plays a major role in dictating the amplitude of the bond angle N-Cα-C and the propensity of the peptide bond to adopt planar/nonplanar states. Since the trends detected here are in line with the concept of the mutual influence of local geometry and conformation previously established for globular and water-soluble proteins, our analysis demonstrates that the interplay of backbone geometrical parameters is an intrinsic and general property of protein/peptide structures that is preserved also in nonglobular contexts. For amyloid-forming peptides significant distortions of the N-Cα-C bond angle, indicative of sterical hidden strain, may occur in correspondence with side chain interdigitation. The correlation between the dihedral angles Δω/ψ in collagen-like models may have interesting implications for triple helix stability.

  5. Interplay between peptide bond geometrical parameters in nonglobular structural contexts.

    Science.gov (United States)

    Esposito, Luciana; Balasco, Nicole; De Simone, Alfonso; Berisio, Rita; Vitagliano, Luigi

    2013-01-01

    Several investigations performed in the last two decades have unveiled that geometrical parameters of protein backbone show a remarkable variability. Although these studies have provided interesting insights into one of the basic aspects of protein structure, they have been conducted on globular and water-soluble proteins. We report here a detailed analysis of backbone geometrical parameters in nonglobular proteins/peptides. We considered membrane proteins and two distinct fibrous systems (amyloid-forming and collagen-like peptides). Present data show that in these systems the local conformation plays a major role in dictating the amplitude of the bond angle N-C(α)-C and the propensity of the peptide bond to adopt planar/nonplanar states. Since the trends detected here are in line with the concept of the mutual influence of local geometry and conformation previously established for globular and water-soluble proteins, our analysis demonstrates that the interplay of backbone geometrical parameters is an intrinsic and general property of protein/peptide structures that is preserved also in nonglobular contexts. For amyloid-forming peptides significant distortions of the N-C(α)-C bond angle, indicative of sterical hidden strain, may occur in correspondence with side chain interdigitation. The correlation between the dihedral angles Δω/ψ in collagen-like models may have interesting implications for triple helix stability.

  6. Interplay of Anderson localization and strong interaction in disordered systems

    International Nuclear Information System (INIS)

    Henseler, Peter

    2010-01-01

    We study the interplay of disorder localization and strong local interactions within the Anderson-Hubbard model. Taking into account local Mott-Hubbard physics and static screening of the disorder potential, the system is mapped onto an effective single-particle Anderson model, which is studied within the self-consistent theory of electron localization. For fermions, we find rich nonmonotonic behavior of the localization length ξ, particularly in two-dimensional systems, including an interaction-induced exponential enhancement of ξ for small and intermediate disorders and a strong reduction of ξ due to hopping suppression by strong interactions. In three dimensions, we identify for half filling a Mott-Hubbard-assisted Anderson localized phase existing between the metallic and the Mott-Hubbard-gapped phases. For small U there is re-entrant behavior from the Anderson localized phase to the metallic phase. For bosons, the unrestricted particle occupation number per lattice site yields a monotonic enhancement of ξ as a function of decreasing interaction, which we assume to persist until the superfluid Bose-Einstein condensate phase is entered. Besides, we study cold atomic gases expanding, by a diffusion process, in a weak random potential. We show that the density-density correlation function of the expanding gas is strongly affected by disorder and we estimate the typical size of a speckle spot, i.e., a region of enhanced or depleted density. Both a Fermi gas and a Bose-Einstein condensate (in a mean-field approach) are considered. (orig.)

  7. Synthetic microbial ecology and the dynamic interplay between microbial genotypes.

    Science.gov (United States)

    Dolinšek, Jan; Goldschmidt, Felix; Johnson, David R

    2016-11-01

    Assemblages of microbial genotypes growing together can display surprisingly complex and unexpected dynamics and result in community-level functions and behaviors that are not readily expected from analyzing each genotype in isolation. This complexity has, at least in part, inspired a discipline of synthetic microbial ecology. Synthetic microbial ecology focuses on designing, building and analyzing the dynamic behavior of ‘ecological circuits’ (i.e. a set of interacting microbial genotypes) and understanding how community-level properties emerge as a consequence of those interactions. In this review, we discuss typical objectives of synthetic microbial ecology and the main advantages and rationales of using synthetic microbial assemblages. We then summarize recent findings of current synthetic microbial ecology investigations. In particular, we focus on the causes and consequences of the interplay between different microbial genotypes and illustrate how simple interactions can create complex dynamics and promote unexpected community-level properties. We finally propose that distinguishing between active and passive interactions and accounting for the pervasiveness of competition can improve existing frameworks for designing and predicting the dynamics of microbial assemblages.

  8. Interplay of Anderson localization and strong interaction in disordered systems

    Energy Technology Data Exchange (ETDEWEB)

    Henseler, Peter

    2010-01-15

    We study the interplay of disorder localization and strong local interactions within the Anderson-Hubbard model. Taking into account local Mott-Hubbard physics and static screening of the disorder potential, the system is mapped onto an effective single-particle Anderson model, which is studied within the self-consistent theory of electron localization. For fermions, we find rich nonmonotonic behavior of the localization length {xi}, particularly in two-dimensional systems, including an interaction-induced exponential enhancement of {xi} for small and intermediate disorders and a strong reduction of {xi} due to hopping suppression by strong interactions. In three dimensions, we identify for half filling a Mott-Hubbard-assisted Anderson localized phase existing between the metallic and the Mott-Hubbard-gapped phases. For small U there is re-entrant behavior from the Anderson localized phase to the metallic phase. For bosons, the unrestricted particle occupation number per lattice site yields a monotonic enhancement of {xi} as a function of decreasing interaction, which we assume to persist until the superfluid Bose-Einstein condensate phase is entered. Besides, we study cold atomic gases expanding, by a diffusion process, in a weak random potential. We show that the density-density correlation function of the expanding gas is strongly affected by disorder and we estimate the typical size of a speckle spot, i.e., a region of enhanced or depleted density. Both a Fermi gas and a Bose-Einstein condensate (in a mean-field approach) are considered. (orig.)

  9. Interplay of bistable kinetics of gene expression during cellular growth

    International Nuclear Information System (INIS)

    Zhdanov, Vladimir P

    2009-01-01

    In cells, the bistable kinetics of gene expression can be observed on the level of (i) one gene with positive feedback between protein and mRNA production, (ii) two genes with negative mutual feedback between protein and mRNA production, or (iii) in more complex cases. We analyse the interplay of two genes of type (ii) governed by a gene of type (i) during cellular growth. In particular, using kinetic Monte Carlo simulations, we show that in the case where gene 1, operating in the bistable regime, regulates mutually inhibiting genes 2 and 3, also operating in the bistable regime, the latter genes may eventually be trapped either to the state with high transcriptional activity of gene 2 and low activity of gene 3 or to the state with high transcriptional activity of gene 3 and low activity of gene 2. The probability to get to one of these states depends on the values of the model parameters. If genes 2 and 3 are kinetically equivalent, the probability is equal to 0.5. Thus, our model illustrates how different intracellular states can be chosen at random with predetermined probabilities. This type of kinetics of gene expression may be behind complex processes occurring in cells, e.g., behind the choice of the fate by stem cells

  10. Interplay between inhibited transport and reaction in nanoporous materials

    Energy Technology Data Exchange (ETDEWEB)

    Ackerman, David Michael [Iowa State Univ., Ames, IA (United States)

    2013-01-01

    This work presents a detailed formulation of reaction and diffusion dynamics of molecules in confined pores such as mesoporous silica and zeolites. A general reaction-diffusion model and discrete Monte Carlo simulations are presented. Both transient and steady state behavior is covered. Failure of previous mean-field models for these systems is explained and discussed. A coarse-grained, generalized hydrodynamic model is developed that accurately captures the interplay between reaction and restricted transport in these systems. This method incorporates the non-uniform chemical diffusion behavior present in finite pores with multi-component diffusion. Two methods of calculating these diffusion values are developed: a random walk based approach and a driven diffusion model based on an extension of Fick's law. The effects of reaction, diffusion, pore length, and catalytic site distribution are investigated. In addition to strictly single file motion, quasi-single file diffusion is incorporated into the model to match a range of experimental systems. The connection between these experimental systems and model parameters is made through Langevin dynamics modeling of particles in confined pores.

  11. PIC Activation through Functional Interplay between Mediator and TFIIH.

    Science.gov (United States)

    Malik, Sohail; Molina, Henrik; Xue, Zhu

    2017-01-06

    The multiprotein Mediator coactivator complex functions in large part by controlling the formation and function of the promoter-bound preinitiation complex (PIC), which consists of RNA polymerase II and general transcription factors. However, precisely how Mediator impacts the PIC, especially post-recruitment, has remained unclear. Here, we have studied Mediator effects on basal transcription in an in vitro transcription system reconstituted from purified components. Our results reveal a close functional interplay between Mediator and TFIIH in the early stages of PIC development. We find that under conditions when TFIIH is not normally required for transcription, Mediator actually represses transcription. TFIIH, whose recruitment to the PIC is known to be facilitated by the Mediator, then acts to relieve Mediator-induced repression to generate an active form of the PIC. Gel mobility shift analyses of PICs and characterization of TFIIH preparations carrying mutant XPB translocase subunit further indicate that this relief of repression is achieved through expending energy via ATP hydrolysis, suggesting that it is coupled to TFIIH's established promoter melting activity. Our interpretation of these results is that Mediator functions as an assembly factor that facilitates PIC maturation through its various stages. Whereas the overall effect of the Mediator is to stimulate basal transcription, its initial engagement with the PIC generates a transcriptionally inert PIC intermediate, which necessitates energy expenditure to complete the process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Vitamin D in Fibromyalgia: A Causative or Confounding Biological Interplay?

    Directory of Open Access Journals (Sweden)

    Spyridon Karras

    2016-06-01

    Full Text Available Fibromyalgia (FM is a chronic syndrome with an increasing prevalence, characterized by widespread musculoskeletal pain in combination with a variety of cognitive symptoms and fatigue. A plethora of scientific evidence that has accumulated during the last decades, resulted in a significant improvement of the understanding of the pathophysiology of the disease. However, current therapeutic approaches in patients with FM remains a multidimensional approach including patient education, behavioral therapy, exercise, pain management, and relief of chronic symptoms, rather than the use drug therapies, based on the mechanisms of disease development. Vitamin D, a fat-soluble vitamin derived mainly from skin synthesis through ultraviolet radiation, has been recognized to manifest a plethora of extraskeletal actions, apart from its fundamental role in skeletal and calcium homeostasis, including modulation of cell growth, neuromuscular actions, and potential anti-inflammatory properties. Recent findings indicate that hypovitaminosis D to be highly prevalent in patients with FM. Supplementation studies are limited so far, indicating potential beneficial effects on pain and severity of the disease, however specific recommendations are lacking. This review aims to summarize and critically appraise data regarding the pathophysiological interplay between vitamin D and FM, available results from observational and supplementation studies so far, with a clinical discourse on current knowledge gaps and future research agenda.

  13. Lamin B Receptor: Interplay between Structure, Function and Localization

    Directory of Open Access Journals (Sweden)

    Eleni Nikolakaki

    2017-08-01

    Full Text Available Lamin B receptor (LBR is an integral protein of the inner nuclear membrane, containing a hydrophilic N-terminal end protruding into the nucleoplasm, eight hydrophobic segments that span the membrane and a short, nucleoplasmic C-terminal tail. Two seemingly unrelated functions have been attributed to LBR. Its N-terminal domain tethers heterochromatin to the nuclear periphery, thus contributing to the shape of interphase nuclear architecture, while its transmembrane domains exhibit sterol reductase activity. Mutations within the transmembrane segments result in defects in cholesterol synthesis and are associated with diseases such as the Pelger–Huët anomaly and Greenberg skeletal dysplasia, whereas no such harmful mutations related to the anchoring properties of LBR have been reported so far. Recent evidence suggests a dynamic regulation of LBR expression levels, structural organization, localization and function, in response to various signals. The molecular mechanisms underlying this dynamic behavior have not yet been fully unraveled. Here, we provide an overview of the current knowledge of the interplay between the structure, function and localization of LBR, and hint at the interconnection of the two distinct functions of LBR.

  14. Segregation in ternary alloys: an interplay of driving forces

    International Nuclear Information System (INIS)

    Luyten, J.; Helfensteyn, S.; Creemers, C.

    2003-01-01

    Monte Carlo (MC) simulations combined with the constant bond energy (CBE) model are set up to explore and understand the general segregation behaviour in ternary alloys as a function of composition and more in particular the segregation to Cu-Ni-Al (1 0 0) surfaces. Besides its simplicity, allowing swift simulations, which are necessary for a first general survey over all possible compositions, one of the advantages of the CBE model lies in the possibility to clearly identify the different driving forces for segregation. All simulations are performed in the Grand Canonical Ensemble, using a new algorithm to determine the chemical potential of the components. Notwithstanding the simplicity of the CBE model, one extra feature is evidenced: depending on the values of the interatomic interaction parameters, in some regions of the ternary diagram, a single solid solution becomes thermodynamically unstable, leading to demixing into two conjugate phases. The simulations are first done for three hypothetical systems that are however representative for real alloy systems. The three systems are characterised by different sets of interatomic interaction parameters. These extensive simulations over the entire composition range of the ternary alloy yield a 'topographical' segregation map, showing distinct regions where different species segregate. These distinct domains originate from a variable interplay between the driving forces for segregation and attractive/repulsive interactions in the bulk of the alloy. The results on these hypothetical systems are very helpful for a better understanding of the segregation behaviour in Cu-Ni-Al and other ternary alloys

  15. Interplay between geometry and temperature in the Casimir effect

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Alexej

    2010-06-23

    In this thesis, we investigate the interplay between geometry and temperature in the Casimir effect for the inclined-plates, sphere-plate and cylinder-plate configurations. We use the worldline approach, which combines the string-inspired quantum field theoretical formalism with Monte Carlo techniques. The approach allows the precise computation of Casimir energies in arbitrary geometries. We analyze the dependence of the Casimir energy, force and torque on the separation parameter and temperature T, and find Casimir phenomena which are dominated by long-range fluctuations. We demonstrate that for open geometries, thermal energy densities are typically distributed on scales of thermal wavelengths. As an important consequence, approximation methods for thermal corrections based on local energy-density estimates, such as the proximity-force approximation, are found to become unreliable even at small surface-separations. Whereas the hightemperature behavior is always found to be linear in T, richer power-law behaviors at small temperatures emerge. In particular, thermal forces can develop a non-monotonic behavior. Many novel numerical as well as analytical results are presented. (orig.)

  16. Interplay between geometry and temperature in the Casimir effect

    International Nuclear Information System (INIS)

    Weber, Alexej

    2010-01-01

    In this thesis, we investigate the interplay between geometry and temperature in the Casimir effect for the inclined-plates, sphere-plate and cylinder-plate configurations. We use the worldline approach, which combines the string-inspired quantum field theoretical formalism with Monte Carlo techniques. The approach allows the precise computation of Casimir energies in arbitrary geometries. We analyze the dependence of the Casimir energy, force and torque on the separation parameter and temperature T, and find Casimir phenomena which are dominated by long-range fluctuations. We demonstrate that for open geometries, thermal energy densities are typically distributed on scales of thermal wavelengths. As an important consequence, approximation methods for thermal corrections based on local energy-density estimates, such as the proximity-force approximation, are found to become unreliable even at small surface-separations. Whereas the hightemperature behavior is always found to be linear in T, richer power-law behaviors at small temperatures emerge. In particular, thermal forces can develop a non-monotonic behavior. Many novel numerical as well as analytical results are presented. (orig.)

  17. Protein Kinase A in Cancer

    International Nuclear Information System (INIS)

    Caretta, Antonio; Mucignat-Caretta, Carla

    2011-01-01

    In the past, many chromosomal and genetic alterations have been examined as possible causes of cancer. However, some tumors do not display a clear molecular and/or genetic signature. Therefore, other cellular processes may be involved in carcinogenesis. Genetic alterations of proteins involved in signal transduction have been extensively studied, for example oncogenes, while modifications in intracellular compartmentalization of these molecules, or changes in the expression of unmodified genes have received less attention. Yet, epigenetic modulation of second messenger systems can deeply modify cellular functioning and in the end may cause instability of many processes, including cell mitosis. It is important to understand the functional meaning of modifications in second messenger intracellular pathways and unravel the role of downstream proteins in the initiation and growth of tumors. Within this framework, the cAMP system has been examined. cAMP is a second messenger involved in regulation of a variety of cellular functions. It acts mainly through its binding to cAMP-activated protein kinases (PKA), that were suggested to participate in the onset and progression of various tumors. PKA may represent a biomarker for tumor detection, identification and staging, and may be a potential target for pharmacological treatment of tumors

  18. Protein Kinase A in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Caretta, Antonio; Mucignat-Caretta, Carla, E-mail: carla.mucignat@unipd.it [Department of Human Anatomy and Physiology, University of Padova, Via Marzolo 3, 35131 Padova (Italy)

    2011-02-28

    In the past, many chromosomal and genetic alterations have been examined as possible causes of cancer. However, some tumors do not display a clear molecular and/or genetic signature. Therefore, other cellular processes may be involved in carcinogenesis. Genetic alterations of proteins involved in signal transduction have been extensively studied, for example oncogenes, while modifications in intracellular compartmentalization of these molecules, or changes in the expression of unmodified genes have received less attention. Yet, epigenetic modulation of second messenger systems can deeply modify cellular functioning and in the end may cause instability of many processes, including cell mitosis. It is important to understand the functional meaning of modifications in second messenger intracellular pathways and unravel the role of downstream proteins in the initiation and growth of tumors. Within this framework, the cAMP system has been examined. cAMP is a second messenger involved in regulation of a variety of cellular functions. It acts mainly through its binding to cAMP-activated protein kinases (PKA), that were suggested to participate in the onset and progression of various tumors. PKA may represent a biomarker for tumor detection, identification and staging, and may be a potential target for pharmacological treatment of tumors.

  19. Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)

    DEFF Research Database (Denmark)

    Dettori, Rosalia; Sonzogni, Silvina; Meyer, Lucas

    2009-01-01

    of numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites......, the activation loop and the Z/TM in the C-terminal extension. We provide evidence that phosphorylation of the Z/TM site of PRK2 inhibits its interaction with PDK1. Our studies further provide a mechanistic model to explain different steps in the docking interaction and regulation. Interestingly, we found...... that the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2 and do...

  20. Isoprenoid biosynthesis and mevalonate kinase deficiency

    NARCIS (Netherlands)

    Henneman, L.

    2011-01-01

    Mevalonaat Kinase Deficiëntie (MKD) is een aangeboren ziekte geassocieerd met heftige koortsaanvallen die drie tot vier dagen aanhouden en gepaard gaan met koude rillingen, gewrichtsklachten, huiduitslag, hoofdpijn, duizeligheid, buikpijn, braken en diarree. De koortsaanvallen treden gemiddeld eens

  1. Expression Profiling of Tyrosine Kinase Genes

    National Research Council Canada - National Science Library

    Weier, Heinz

    2000-01-01

    ... of these genes parallels the progression of tumors to a more malignant phenotype. We developed a DNA micro-array based screening system to monitor the level of expression of tyrosine kinase (tk...

  2. MAP kinase cascades in Arabidopsis innate immunity

    DEFF Research Database (Denmark)

    Rasmussen, Magnus Wohlfahrt; Roux, Milena Edna; Petersen, Morten

    2012-01-01

    Plant mitogen-activated protein kinase (MAPK) cascades generally transduce extracellular stimuli into cellular responses. These stimuli include the perception of pathogen-associated molecular patterns (PAMPs) by host transmembrane pattern recognition receptors which trigger MAPK-dependent innate ...

  3. Protein Kinases in Human Breast Carcinoma

    National Research Council Canada - National Science Library

    Cane, William

    1998-01-01

    .... Rak is a novel nuclear tyrosine that our group has identified in breast cancer tissues and cell lines that has structural homology to the Src tyrosine kinase, with SH2 and SH3 domains at its amino terminus...

  4. Concerted evolution rapidly eliminates sequence variation in rDNA coding regions but not in intergenic spacers in Nicotiana tabacum allotetraploid

    Czech Academy of Sciences Publication Activity Database

    Lunerová Bedřichová, Jana; Renny-Byfield, S.; Matyášek, Roman; Leitch, A.; Kovařík, Aleš

    2017-01-01

    Roč. 303, č. 8 (2017), s. 1043-1060 ISSN 0378-2697 R&D Projects: GA ČR(CZ) GA17-11642S; GA ČR(CZ) GC16-02149J Institutional support: RVO:68081707 Keywords : Concerted evolution * Immunomodulation * Neutrophils Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 1.239, year: 2016

  5. Ror receptor tyrosine kinases: orphans no more

    OpenAIRE

    Green, Jennifer L.; Kuntz, Steven G.; Sternberg, Paul W.

    2008-01-01

    Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either act...

  6. Mediator kinase module and human tumorigenesis.

    Science.gov (United States)

    Clark, Alison D; Oldenbroek, Marieke; Boyer, Thomas G

    2015-01-01

    Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways.

  7. Evolutionary and polymorphism analyses reveal the central role of BTN3A2 in the concerted evolution of the BTN3 gene family.

    Science.gov (United States)

    Afrache, Hassnae; Pontarotti, Pierre; Abi-Rached, Laurent; Olive, Daniel

    2017-06-01

    The butyrophilin 3 (BTN3) receptors are implicated in the T lymphocytes regulation and present a wide plasticity in mammals. In order to understand how these genes have been diversified, we studied their evolution and show that the three human BTN3 are the result of two successive duplications in Primates and that the three genes are present in Hominoids and the Old World Monkey groups. A thorough phylogenetic analysis reveals a concerted evolution of BTN3 characterized by a strong and recurrent homogenization of the region encoding the signal peptide and the immunoglobulin variable (IgV) domain in Hominoids, where the sequences of BTN3A1 or BTN3A3 are replaced by BTN3A2 sequence. In human, the analysis of the diversity of these genes in 1683 individuals representing 26 worldwide populations shows that the three genes are polymorphic, with more than 46 alleles for each gene, and marked by extreme homogenization of the IgV sequences. The same analysis performed for the BTN2 genes shows also a concerted evolution; however, it is not as strong and recurrent as for BTN3. This study shows that BTN3 receptors are marked by extreme concerted evolution at the IgV domain and that BTN3A2 plays a central role in this evolution.

  8. Computational Investigation of the Competition between the Concerted Diels-Alder Reaction and Formation of Diradicals in Reactions of Acrylonitrile with Non-Polar Dienes

    Science.gov (United States)

    James, Natalie C.; Um, Joann M.; Padias, Anne B.; Hall, H. K.; Houk, K. N.

    2013-01-01

    The energetics of the Diels-Alder cycloaddition reactions of several 1,3-dienes with acrylonitrile, and the energetics of formation of diradicals, were investigated with density functional theory (B3LYP and M06-2X) and compared to experimental data. For the reaction of 2,3-dimethyl-1,3-butadiene with acrylonitrile, the concerted reaction is favored over the diradical pathway by 2.5 kcal/mol using B3LYP/6-31G(d); experimentally this reaction gives both cycloadduct and copolymer. The concerted cycloaddition of cyclopentadiene with acrylonitrile is preferred computationally over the stepwise pathway by 5.9 kcal/mol; experimentally, only the Diels-Alder adduct is formed. For the reactions of (E)-1,3-pentadiene and acrylonitrile, both cycloaddition and copolymerization were observed experimentally; these trends were mimicked by the computational results, which showed only a 1.2 kcal/mol preference for the concerted pathway. For the reactions of (Z)-1,3-pentadiene and acrylonitrile, the stepwise pathway is preferred by 3.9 kcal/mol, in agreement with previous experimental findings that only polymerization occurs. M06-2X is known to give more accurate activation and reaction energetics but the energies of diradicals are too high. PMID:23758325

  9. Aperture size, materiality of the secondary room and listener location: Impact on the simulated impulse response of a coupled-volume concert hall

    Science.gov (United States)

    Ermann, Michael; Johnson, Marty E.; Harrison, Byron W.

    2003-04-01

    By adding a second room to a concert hall, and designing doors to control the sonic transparency between the two rooms, designers can create a new, coupled acoustic. Concert halls use coupling to achieve a variable, longer and distinct reverberant quality for their musicians and listeners. For this study, a coupled-volume concert hall based on an existing performing arts center is conceived and computer-modeled. It has a fixed geometric volume, form and primary-room sound absorption. Ray-tracing software simulates impulse responses, varying both aperture size and secondary-room sound absorption level, across a grid of receiver (listener) locations. The results are compared with statistical analysis that suggests a highly sensitive relationship between the double-sloped condition and the architecture of the space. This line of study aims to quantitatively and spatially correlate the double-sloped condition with (1) aperture size exposing the chamber, (2) sound absorptance in the coupled volume, and (3) listener location.

  10. Fibronectin phosphorylation by ecto-protein kinase

    International Nuclear Information System (INIS)

    Imada, Sumi; Sugiyama, Yayoi; Imada, Masaru

    1988-01-01

    The presence of membrane-associated, extracellular protein kinase (ecto-protein kinase) and its substrate proteins was examined with serum-free cultures of Swiss 3T3 fibroblast. When cells were incubated with [γ- 32 ]ATP for 10 min at 37 degree C, four proteins with apparent molecular weights between 150 and 220 kDa were prominently phosphorylated. These proteins were also radiolabeled by lactoperoxidase catalyzed iodination and were sensitive to mild tryptic digestion, suggesting that they localized on the cell surface or in the extracellular matrix. Phosphorylation of extracellular proteins with [γ- 32 P]ATP in intact cell culture is consistent with the existence of ecto-protein kinase. Anti-fibronectin antibody immunoprecipitated one of the phosphoproteins which comigrated with a monomer and a dimer form of fibronectin under reducing and nonreducing conditions of electrophoresis, respectively. The protein had affinity for gelatin as demonstrated by retention with gelatin-conjugated agarose. This protein substrate of ecto-protein kinase was thus concluded to be fibronectin. The sites of phosphorylation by ecto-protein kinase were compared with those of intracellularly phosphorylated fibronectin by the analysis of radiolabeled amino acids and peptides. Ecto-protein kinase phosphorylated fibronectin at serine and threonine residues which were distinct from the sites of intracellular fibronectin phosphorylation

  11. The PIM kinases in hematological cancers.

    Science.gov (United States)

    Alvarado, Yesid; Giles, Francis J; Swords, Ronan T

    2012-02-01

    The PIM genes represent a family of proto-oncogenes that encode three different serine/threonine protein kinases (PIM1, PIM2 and PIM3) with essential roles in the regulation of signal transduction cascades, which promote cell survival, proliferation and drug resistance. PIM kinases are overexpressed in several hematopoietic tumors and support in vitro and in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. PIM kinases do not have an identified regulatory domain, which means that these proteins are constitutively active once transcribed. They appear to be critical downstream effectors of important oncoproteins and, when overexpressed, can mediate drug resistance to available agents, such as rapamycin. Recent crystallography studies reveal that, unlike other kinases, they possess a hinge region, which creates a unique binding pocket for ATP, offering a target for an increasing number of potent small-molecule PIM kinase inhibitors. Preclinical studies in models of various hematologic cancers indicate that these novel agents show promising activity and some of them are currently being evaluated in a clinical setting. In this review, we profile the PIM kinases as targets for therapeutics in hematologic malignancies.

  12. Deglaciation in the tropical Indian Ocean driven by interplay between the regional monsoon and global teleconnections

    Digital Repository Service at National Institute of Oceanography (India)

    Saraswat, R.; Lea, D.W.; Nigam, R.; Mackensen, A.; Naik, Dinesh K.

    High resolution climate records of the ice age terminations from monsoon-dominated regions reveal the interplay of regional and global driving forces. Speleothem records from Chinese caves indicate that glacial terminations were interrupted...

  13. An update on the role of serotonin and its interplay with dopamine for reward

    NARCIS (Netherlands)

    Fischer, A.G.; Ullsperger, M.

    2017-01-01

    The specific role of serotonin and its interplay with dopamine in adaptive, reward guided behavior as well as drug dependence, still remains elusive. Recently, novel methods allowed cell type specific anatomical, functional, and interventional analyses of serotonergic and dopaminergic circuits,

  14. In one harness: the interplay of cellular responses and subsequent cell fate after quantum dot uptake

    KAUST Repository

    Gladkovskaya, Olga; Gun'Ko, Yuri K.; O'Connor, Gerard M.; Gogvadze, Vladimir; Rochev, Yury

    2016-01-01

    is to organize existing knowledge into lucid biological and mathematical models. In our review we aim to describe the interplay of various cell death mechanisms triggered by quantum dots as a consequence of particle parameters and experimental conditions.

  15. The interplay between tissue growth and scaffold degradation in engineered tissue constructs

    KAUST Repository

    O’ Dea, R. D.; Osborne, J. M.; El Haj, A. J.; Byrne, H. M.; Waters, S. L.

    2012-01-01

    of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. In this paper, we use a

  16. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

    Science.gov (United States)

    Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2013-09-01

    The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect

  17. The interplay between experiential and traditional learning for competency development

    Directory of Open Access Journals (Sweden)

    Sara eBonesso

    2015-09-01

    Full Text Available Extensive research demonstrated that firms may pursue several advantages in hiring individuals with the set of emotional, social, and cognitive (ESC competencies that are most critical for business success. Therefore, the role of education for competency development is becoming paramount. Prior studies have questioned the traditional methods, grounded in the lecture format, as a way to effectively develop ESC competencies. Alternatively, they propose experiential learning techniques that involve participants in dedicated courses or activities. Despite the insights provided by these studies, they do not take into account a comprehensive set of learning methods and their combined effect on the individual’s competency portfolio within educational programs that aim to transfer primarily professional skills. Our study aims to fill these gaps by investigating the impact of the interplay between different learning methods on ESC competencies through a sample of students enrolled in the first year of a master’s degree program. After providing a classification of three learning methods (traditional learning, individual experiential learning, and social experiential learning, the study delves into their combined influence on ESC competencies, adopting the Artificial Neural Network. Contrary to prior studies, our results provide counterintuitive evidence, suggesting that traditional learning needs to be implemented together, on the one hand, with individual experiential learning to achieve a significant effect on emotional competencies and, on the other hand, with social experiential learning to have an impact on social competencies. Moreover, individual experiential learning plays a prominent role in stimulating cognitive competencies. Our research contributes to educational literature by providing new insights on the effective combination of learning methods that can be adopted into programs that transfer technical knowledge and skills to promote

  18. Biochar–macrofauna interplay: Searching for new bioindicators

    Energy Technology Data Exchange (ETDEWEB)

    Castracani, C., E-mail: cristina.castracani@unipr.it [Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/a, 43124 Parma (Italy); Maienza, A., E-mail: a.maienza@ibimet.cnr.it [Institute of Biometeorology, National Research Council (IBIMET-CNR), Via G. Caproni 8, 50145 Firenze (Italy); Grasso, D.A., E-mail: donato.grasso@unipr.it [Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/a, 43124 Parma (Italy); Genesio, L., E-mail: l.genesio@ibimet.cnr.it [Institute of Biometeorology, National Research Council (IBIMET-CNR), Via G. Caproni 8, 50145 Firenze (Italy); Malcevschi, A., E-mail: alessio.malcevschi@unipr.it [Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/a, 43124 Parma (Italy); Miglietta, F., E-mail: f.miglietta@ibimet.cnr.it [Institute of Biometeorology, National Research Council (IBIMET-CNR), Via G. Caproni 8, 50145 Firenze (Italy); Vaccari, F.P., E-mail: f.vaccari@ibimet.cnr.it [Institute of Biometeorology, National Research Council (IBIMET-CNR), Via G. Caproni 8, 50145 Firenze (Italy); Mori, A., E-mail: alessandra.mori@unipr.it [Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/a, 43124 Parma (Italy)

    2015-12-01

    Biochar incorporation in agricultural soils has been proposed as a climate change mitigation strategy and has proved to substantially increase crop productivity via physical, chemical and biological mechanisms. The changes induced in soil properties are known to have a direct impact on soil ecosystem with consequences for soil biota community that, in turn, can influence biochar aging in soil. Despite several studies investigated in the interplay between biochar and soil microbiology, there is a clear lack of information on groups that live in the most superficial ground layers: soil meso and macro fauna. These groups are of great importance if we consider that biochar application should ideally be located in the soil's surface layer (0–30 cm). Our study is the first attempt to investigate the interactions between biochar soil amendments and aboveground soil macro-meso fauna in a field crop. This was made setting-up a randomized-block experiment on a processing tomato crop in northern Italy, using three different biochar types and periodically monitoring soil parameters and fauna abundances along the crop growing cycle in summer 2013. Results show that the impact of biochar application on soil fauna as a whole is small when compared to that of agricultural management, suggesting that this amendment does not have short-term ecological interferences. Nevertheless, ants exhibited variations in abundances and distribution connected to properties of amended soils such as temperature, pH and humidity, proving that they can be effectively used as a target group in the study of interactions between biochar and soil biota. - Highlights: • We use a field study to evaluate the effects of biochar on aboveground fauna. • We focus on ants as useful bioindicators for biochar environmental safety. • Biochar has less impact on soil fauna compared to agricultural management. • Ant distribution can be connected to properties of amended soils.

  19. On the interplay between cosmological shock waves and their environment

    Science.gov (United States)

    Martin-Alvarez, Sergio; Planelles, Susana; Quilis, Vicent

    2017-05-01

    Cosmological shock waves are tracers of the thermal history of the structures in the Universe. They play a crucial role in redistributing the energy within the cosmic structures and are also amongst the main ingredients of galaxy and galaxy cluster formation. Understanding this important function requires a proper description of the interplay between shocks and the different environments where they can be found. In this paper, an Adaptive Mesh Refinement (AMR) Eulerian cosmological simulation is analysed by means of a shock-finding algorithm that allows to generate shock wave maps. Based on the population of dark matter halos and on the distribution of density contrast in the simulation, we classify the shocks in five different environments. These range from galaxy clusters to voids. The shock distribution function and the shocks power spectrum are studied for these environments dynamics. We find that shock waves on different environments undergo different formation and evolution processes, showing as well different characteristics. We identify three different phases of formation, evolution and dissipation of these shock waves, and an intricate migration between distinct environments and scales. Shock waves initially form at external, low density regions and are merged and amplified through the collapse of structures. Shock waves and cosmic structures follow a parallel evolution. Later on, shocks start to detach from them and dissipate. We also find that most of the power that shock waves dissipate is found at scales of k ˜0.5 Mpc^{-1}, with a secondary peak at k ˜8 Mpc^{-1}. The evolution of the shocks power spectrum confirms that shock waves evolution is coupled and conditioned by their environment.

  20. Biochar–macrofauna interplay: Searching for new bioindicators

    International Nuclear Information System (INIS)

    Castracani, C.; Maienza, A.; Grasso, D.A.; Genesio, L.; Malcevschi, A.; Miglietta, F.; Vaccari, F.P.; Mori, A.

    2015-01-01

    Biochar incorporation in agricultural soils has been proposed as a climate change mitigation strategy and has proved to substantially increase crop productivity via physical, chemical and biological mechanisms. The changes induced in soil properties are known to have a direct impact on soil ecosystem with consequences for soil biota community that, in turn, can influence biochar aging in soil. Despite several studies investigated in the interplay between biochar and soil microbiology, there is a clear lack of information on groups that live in the most superficial ground layers: soil meso and macro fauna. These groups are of great importance if we consider that biochar application should ideally be located in the soil's surface layer (0–30 cm). Our study is the first attempt to investigate the interactions between biochar soil amendments and aboveground soil macro-meso fauna in a field crop. This was made setting-up a randomized-block experiment on a processing tomato crop in northern Italy, using three different biochar types and periodically monitoring soil parameters and fauna abundances along the crop growing cycle in summer 2013. Results show that the impact of biochar application on soil fauna as a whole is small when compared to that of agricultural management, suggesting that this amendment does not have short-term ecological interferences. Nevertheless, ants exhibited variations in abundances and distribution connected to properties of amended soils such as temperature, pH and humidity, proving that they can be effectively used as a target group in the study of interactions between biochar and soil biota. - Highlights: • We use a field study to evaluate the effects of biochar on aboveground fauna. • We focus on ants as useful bioindicators for biochar environmental safety. • Biochar has less impact on soil fauna compared to agricultural management. • Ant distribution can be connected to properties of amended soils

  1. Biochar-macrofauna interplay: Searching for new bioindicators.

    Science.gov (United States)

    Castracani, C; Maienza, A; Grasso, D A; Genesio, L; Malcevschi, A; Miglietta, F; Vaccari, F P; Mori, A

    2015-12-01

    Biochar incorporation in agricultural soils has been proposed as a climate change mitigation strategy and has proved to substantially increase crop productivity via physical, chemical and biological mechanisms. The changes induced in soil properties are known to have a direct impact on soil ecosystem with consequences for soil biota community that, in turn, can influence biochar aging in soil. Despite several studies investigated in the interplay between biochar and soil microbiology, there is a clear lack of information on groups that live in the most superficial ground layers: soil meso and macro fauna. These groups are of great importance if we consider that biochar application should ideally be located in the soil's surface layer (0-30 cm). Our study is the first attempt to investigate the interactions between biochar soil amendments and aboveground soil macro-meso fauna in a field crop. This was made setting-up a randomized-block experiment on a processing tomato crop in northern Italy, using three different biochar types and periodically monitoring soil parameters and fauna abundances along the crop growing cycle in summer 2013. Results show that the impact of biochar application on soil fauna as a whole is small when compared to that of agricultural management, suggesting that this amendment does not have short-term ecological interferences. Nevertheless, ants exhibited variations in abundances and distribution connected to properties of amended soils such as temperature, pH and humidity, proving that they can be effectively used as a target group in the study of interactions between biochar and soil biota. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Dentifrice fluoride and abrasivity interplay on artificial caries lesions.

    Science.gov (United States)

    Nassar, Hani M; Lippert, Frank; Eckert, George J; Hara, Anderson T

    2014-01-01

    Incipient caries lesions on smooth surfaces may be subjected to toothbrushing, potentially leading to remineralization and/or abrasive wear. The interplay of dentifrice abrasivity and fluoride on this process is largely unknown and was investigated on three artificially created lesions with different mineral content/distribution. 120 bovine enamel specimens were randomly allocated to 12 groups (n = 10), resulting from the association of (1) lesion type [methylcellulose acid gel (MeC); carboxymethylcellulose solution (CMC); hydroxyethylcellulose gel (HEC)], (2) slurry abrasive level [low (REA 4/ RDA 69); high (REA 7/RDA 208)], and (3) fluoride concentration [0/275 ppm (14.5 mM) F as NaF]. After lesion creation, specimens were brushed in an automated brushing machine with the test slurries (50 strokes 2×/day). Specimens were kept in artificial saliva in between brushings and overnight. Enamel surface loss (SL) was determined by optical profilometry after lesion creation, 1, 3 and 5 days. Two enamel sections (from baseline and post-brushing areas) were obtained and analyzed microradiographically. Data were analyzed by analysis of variance and Tukey's tests (α = 5%). Brushing with high-abrasive slurry caused more SL than brushing with low-abrasive slurry. For MeC and CMC lesions, fluoride had a protective effect on SL from day 3 on. Furthermore, for MeC and CMC, there was a significant mineral gain in the remaining lesions except when brushed with high-abrasive slurries and 0 ppm F. For HEC, a significant mineral gain took place when low-abrasive slurry was used with fluoride. The tested lesions responded differently to the toothbrushing procedures. Both slurry fluoride content and abrasivity directly impacted SL and mineral gain of enamel caries lesions.

  3. The interplay between experiential and traditional learning for competency development.

    Science.gov (United States)

    Bonesso, Sara; Gerli, Fabrizio; Pizzi, Claudio

    2015-01-01

    Extensive research demonstrated that firms may pursue several advantages in hiring individuals with the set of emotional, social, and cognitive (ESC) competencies that are most critical for business success. Therefore, the role of education for competency development is becoming paramount. Prior studies have questioned the traditional methods, grounded in the lecture format, as a way to effectively develop ESC competencies. Alternatively, they propose experiential learning techniques that involve participants in dedicated courses or activities. Despite the insights provided by these studies, they do not take into account a comprehensive set of learning methods and their combined effect on the individual's competency portfolio within educational programs that aim to transfer primarily professional skills. Our study aims to fill these gaps by investigating the impact of the interplay between different learning methods on ESC competencies through a sample of students enrolled in the first year of a master's degree program. After providing a classification of three learning methods [traditional learning (TL), individual experiential learning (IEL), and social experiential learning (SEL)], the study delves into their combined influence on ESC competencies, adopting the Artificial Neural Network. Contrary to prior studies, our results provide counterintuitive evidence, suggesting that TL needs to be implemented together, on the one hand, with IEL to achieve a significant effect on emotional competencies and, on the other hand, with SEL to have an impact on social competencies. Moreover, IEL plays a prominent role in stimulating cognitive competencies. Our research contributes to educational literature by providing new insights on the effective combination of learning methods that can be adopted into programs that transfer technical knowledge and skills to promote behavioral competencies.

  4. The interplay of stress and sleep impacts BDNF level.

    Science.gov (United States)

    Giese, Maria; Unternaehrer, Eva; Brand, Serge; Calabrese, Pasquale; Holsboer-Trachsler, Edith; Eckert, Anne

    2013-01-01

    Sleep plays a pivotal role in normal biological functions. Sleep loss results in higher stress vulnerability and is often found in mental disorders. There is evidence that brain-derived neurotrophic factor (BDNF) could be a central player in this relationship. Recently, we could demonstrate that subjects suffering from current symptoms of insomnia exhibited significantly decreased serum BDNF levels compared with sleep-healthy controls. In accordance with the paradigm indicating a link between sleep and BDNF, we aimed to investigate if the stress system influences the association between sleep and BDNF. Participants with current symptoms of insomnia plus a former diagnosis of Restless Legs Syndrome (RLS) and/or Periodic Limb Movement (PLM) and sleep healthy controls were included in the study. They completed questionnaires on sleep (ISI, Insomnia Severity Index) and stress (PSS, Perceived Stress Scale) and provided a blood sample for determination of serum BDNF. We found a significant interaction between stress and insomnia with an impact on serum BDNF levels. Moreover, insomnia severity groups and score on the PSS each revealed a significant main effect on serum BDNF levels. Insomnia severity was associated with increased stress experience affecting serum BDNF levels. Of note, the association between stress and BDNF was only observed in subjects without insomnia. Using a mediation model, sleep was revealed as a mediator of the association between stress experience and serum BDNF levels. This is the first study to show that the interplay between stress and sleep impacts BDNF levels, suggesting an important role of this relationship in the pathogenesis of stress-associated mental disorders. Hence, we suggest sleep as a key mediator at the connection between stress and BDNF. Whether sleep is maintained or disturbed might explain why some individuals are able to handle a certain stress load while others develop a mental disorder.

  5. The interplay of stress and sleep impacts BDNF level.

    Directory of Open Access Journals (Sweden)

    Maria Giese

    Full Text Available BACKGROUND: Sleep plays a pivotal role in normal biological functions. Sleep loss results in higher stress vulnerability and is often found in mental disorders. There is evidence that brain-derived neurotrophic factor (BDNF could be a central player in this relationship. Recently, we could demonstrate that subjects suffering from current symptoms of insomnia exhibited significantly decreased serum BDNF levels compared with sleep-healthy controls. In accordance with the paradigm indicating a link between sleep and BDNF, we aimed to investigate if the stress system influences the association between sleep and BDNF. METHODOLOGY/PRINCIPAL FINDINGS: Participants with current symptoms of insomnia plus a former diagnosis of Restless Legs Syndrome (RLS and/or Periodic Limb Movement (PLM and sleep healthy controls were included in the study. They completed questionnaires on sleep (ISI, Insomnia Severity Index and stress (PSS, Perceived Stress Scale and provided a blood sample for determination of serum BDNF. We found a significant interaction between stress and insomnia with an impact on serum BDNF levels. Moreover, insomnia severity groups and score on the PSS each revealed a significant main effect on serum BDNF levels. Insomnia severity was associated with increased stress experience affecting serum BDNF levels. Of note, the association between stress and BDNF was only observed in subjects without insomnia. Using a mediation model, sleep was revealed as a mediator of the association between stress experience and serum BDNF levels. CONCLUSIONS: This is the first study to show that the interplay between stress and sleep impacts BDNF levels, suggesting an important role of this relationship in the pathogenesis of stress-associated mental disorders. Hence, we suggest sleep as a key mediator at the connection between stress and BDNF. Whether sleep is maintained or disturbed might explain why some individuals are able to handle a certain stress load while

  6. The interplay between perceptual organization and object recognition: Temporal dynamics and neuropsychology

    OpenAIRE

    Torfs, Katrien

    2012-01-01

    The ease and efficiency with which we perceive objects in daily life masks the complexity of the processes involved. The main goal of my doctoral research was to enhance our understanding of the complex interplay between perceptual organization and object recognition. To this end, we investigated the dynamic interplay between different component processes of object recognition, and their temporal dynamics. In the first part of this thesis, I present three behavioral studies focusing on the ro...

  7. Computer simulation of the interplay between fractal structures and surrounding heterogeneous multifractal distributions. Applications

    OpenAIRE

    Martin Martin, Miguel Angel; Reyes Castro, Miguel E.; Taguas Coejo, Fco. Javier

    2014-01-01

    In a large number of physical, biological and environmental processes interfaces with high irregular geometry appear separating media (phases) in which the heterogeneity of constituents is present. In this work the quantification of the interplay between irregular structures and surrounding heterogeneous distributions in the plane is made For a geometric set image and a mass distribution (measure) image supported in image, being image, the mass image gives account of the interplay between th...

  8. Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis

    DEFF Research Database (Denmark)

    Cao, Renhai; Ji, Hong; Feng, Ninghan

    2012-01-01

    Interplay between various lymphangiogenic factors in promoting lymphangiogenesis and lymphatic metastasis remains poorly understood. Here we show that FGF-2 and VEGF-C, two lymphangiogenic factors, collaboratively promote angiogenesis and lymphangiogenesis in the tumor microenvironment, leading...... endothelial cell tip cell formation is a prerequisite for FGF-2-stimulated lymphangiogenesis. In the tumor microenvironment, the reciprocal interplay between FGF-2 and VEGF-C collaboratively stimulated tumor growth, angiogenesis, intratumoral lymphangiogenesis, and metastasis. Thus, intervention and targeting...

  9. Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival.

    Directory of Open Access Journals (Sweden)

    Daniel Thomas

    Full Text Available The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K, promotes growth factor-mediated cell survival and is frequently deregulated in cancer. However, in contrast to canonical lipid-kinase functions, the role of PI3K protein kinase activity in regulating cell survival is unknown. We have employed a novel approach to purify and pharmacologically profile protein kinases from primary human acute myeloid leukemia (AML cells that phosphorylate serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. We have isolated a kinase activity that is able to directly phosphorylate Ser585 in the cytoplasmic domain of the interleukin 3 (IL-3 and granulocyte macrophage colony stimulating factor (GM-CSF receptors and shown it to be PI3K. Physiological concentrations of cytokine in the picomolar range were sufficient for activating the protein kinase activity of PI3K leading to Ser585 phosphorylation and hemopoietic cell survival but did not activate PI3K lipid kinase signaling or promote proliferation. Blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1 had no significant impact on the ability of picomolar concentrations of cytokine to promote hemopoietic cell survival. Furthermore, inducible expression of a mutant form of PI3K that is defective in lipid kinase activity but retains protein kinase activity was able to promote Ser585 phosphorylation and hemopoietic cell survival in the absence of cytokine. Blockade of p110α by RNA interference or multiple independent PI3K inhibitors not only blocked Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also resulted in a block in survival signaling and cell death. Our findings demonstrate a new role for the protein kinase activity of PI3K in phosphorylating the cytoplasmic tail of the GM-CSF and IL-3 receptors to selectively regulate cell survival highlighting the importance of targeting

  10. Computational model to simulate the interplay effect in dynamic IMRT delivery

    International Nuclear Information System (INIS)

    Yoganathan, S A; Maria Das, K J; Kumar, Shaleen

    2014-01-01

    The purpose of this study was to develop and experimentally verify a patient specific model for simulating the interplay effect in a DMLC based IMRT delivery. A computational model was developed using MATLAB program to incorporate the interplay effect in a 2D beams eye view fluence of dynamic IMRT fields. To simulate interplay effect, the model requires two inputs: IMRT field (DMLC file with dose rate and MU) and the patient specific respiratory motion. The interplay between the DMLC leaf motion and target was simulated for three lung patients. The target trajectory data was acquired using RPM system during the treatment simulation. The model was verified experimentally for the same patients using Imatrix 2D array device placed over QUASAR motion platform in CL2100 linac. The simulated fluences and measured fluences were compared with the TPS generated static fluence (no motion) using an in-house developed gamma evaluation program (2%/2mm). The simulated results were well within agreement with the measured. Comparison of the simulated and measured fluences with the TPS static fluence resulted 55.3% and 58.5% pixels passed the gamma criteria. A patient specific model was developed and validated for simulating the interplay effect in the dynamic IMRT delivery. This model can be clinically used to quantify the dosimetric uncertainty due to the interplay effect prior to the treatment delivery.

  11. Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Wittmann Christoph

    2008-03-01

    Full Text Available Abstract Background Pyruvate kinase is an important element in flux control of the intermediate metabolism. It catalyzes the irreversible conversion of phosphoenolpyruvate into pyruvate and is under allosteric control. In Corynebacterium glutamicum, this enzyme was regarded as promising target for improved production of lysine, one of the major amino acids in animal nutrition. In pyruvate kinase deficient strains the required equimolar ratio of the two lysine precursors oxaloacetate and pyruvate can be achieved through concerted action of the phosphotransferase system (PTS and phosphoenolpyruvate carboxylase (PEPC, whereby a reduced amount of carbon may be lost as CO2 due to reduced flux into the tricarboxylic acid (TCA cycle. In previous studies, deletion of pyruvate kinase in lysine-producing C. glutamicum, however, did not yield a clear picture and the exact metabolic consequences are not fully understood. Results In this work, deletion of the pyk gene, encoding pyruvate kinase, was carried out in the lysine-producing strain C. glutamicum lysCfbr, expressing a feedback resistant aspartokinase, to investigate the cellular response to deletion of this central glycolytic enzyme. Pyk deletion was achieved by allelic replacement, verified by PCR analysis and the lack of in vitro enzyme activity. The deletion mutant showed an overall growth behavior (specific growth rate, glucose uptake rate, biomass yield which was very similar to that of the parent strain, but differed in slightly reduced lysine formation, increased formation of the overflow metabolites dihydroxyacetone and glycerol and in metabolic fluxes around the pyruvate node. The latter involved a flux shift from pyruvate carboxylase (PC to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle. This created a metabolic by-pass from PEP to pyruvate via malic enzyme demonstrating its contribution to metabolic flexibility of C. glutamicum on glucose. Conclusion The metabolic

  12. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution.

    Directory of Open Access Journals (Sweden)

    Amanda Tse

    Full Text Available Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib and promiscuous (Bosutinib, Dasatinib kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations

  13. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution

    Science.gov (United States)

    Tse, Amanda; Verkhivker, Gennady M.

    2015-01-01

    Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib) and promiscuous (Bosutinib, Dasatinib) kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations of key mediating

  14. ATR-Chk1-APC/C-dependent stabilization of Cdc7-ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress

    DEFF Research Database (Denmark)

    Yamada, M.; Watanabe, K.; Mistrik, M.

    2013-01-01

    replication. Stalled DNA replication evoked stabilization of the Cdc7-ASK (Dbf4) complex in a manner dependent on ATR-Chk1-mediated checkpoint signaling and its interplay with the anaphase-promoting complex/cyclosomeCdh1 (APC/C) ubiquitin ligase. Mechanistically, Chk1 kinase inactivates APC/C through...... degradation of Cdh1 upon replication block, thereby stabilizing APC/C substrates, including Cdc7-ASK (Dbf4). Furthermore, motif C of ASK (Dbf4) interacts with the N-terminal region of RAD18 ubiquitin ligase, and this interaction is required for chromatin binding of RAD18. Impaired interaction of ASK (Dbf4...

  15. Non-degradative Ubiquitination of Protein Kinases.

    Directory of Open Access Journals (Sweden)

    K Aurelia Ball

    2016-06-01

    Full Text Available Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichment and quantitative mass spectrometry to identify ubiquitinated kinases and the sites of ubiquitination in Jurkat and HEK293 cells. We find that, unlike phosphorylation, ubiquitination most commonly occurs in structured domains, and on the kinase domain, ubiquitination is concentrated in regions known to be important for regulating activity. We hypothesized that ubiquitination, like other post-translational modifications, may alter the conformational equilibrium of the modified protein. We chose one human kinase, ZAP-70, to simulate using molecular dynamics with and without a monoubiquitin modification. In Jurkat cells, ZAP-70 is ubiquitinated at several sites that are not sensitive to proteasome inhibition and thus may have other regulatory roles. Our simulations show that ubiquitination influences the conformational ensemble of ZAP-70 in a site-dependent manner. When monoubiquitinated at K377, near the C-helix, the active conformation of the ZAP-70 C-helix is disrupted. In contrast, when monoubiquitinated at K476, near the kinase hinge region, an active-like ZAP-70 C-helix conformation is stabilized. These results lead to testable hypotheses that ubiquitination directly modulates kinase activity, and that ubiquitination is likely to alter structure, dynamics, and function in other protein classes as well.

  16. Crystal structure of Cryptosporidium parvum pyruvate kinase.

    Directory of Open Access Journals (Sweden)

    William J Cook

    Full Text Available Pyruvate kinase plays a critical role in cellular metabolism of glucose by serving as a major regulator of glycolysis. This tetrameric enzyme is allosterically regulated by different effector molecules, mainly phosphosugars. In response to binding of effector molecules and substrates, significant structural changes have been identified in various pyruvate kinase structures. Pyruvate kinase of Cryptosporidium parvum is exceptional among known enzymes of protozoan origin in that it exhibits no allosteric property in the presence of commonly known effector molecules. The crystal structure of pyruvate kinase from C. parvum has been solved by molecular replacement techniques and refined to 2.5 Å resolution. In the active site a glycerol molecule is located near the γ-phosphate site of ATP, and the protein structure displays a partially closed active site. However, unlike other structures where the active site is closed, the α6' helix in C. parvum pyruvate kinase unwinds and assumes an extended conformation. In the crystal structure a sulfate ion is found at a site that is occupied by a phosphate of the effector molecule in many pyruvate kinase structures. A new feature of the C. parvum pyruvate kinase structure is the presence of a disulfide bond cross-linking the two monomers in the asymmetric unit. The disulfide bond is formed between cysteine residue 26 in the short N-helix of one monomer with cysteine residue 312 in a long helix (residues 303-320 of the second monomer at the interface of these monomers. Both cysteine residues are unique to C. parvum, and the disulfide bond remained intact in a reduced environment. However, the significance of this bond, if any, remains unknown at this time.

  17. A systematic evaluation of protein kinase a-a-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P|info:eu-repo/dai/nl/341566551; van der Heyden, Marcel A G; Kok, Bart; Heck, Albert J R|info:eu-repo/dai/nl/105189332; Scholten, Arjen|info:eu-repo/dai/nl/313939780

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  18. A systematic evaluation of protein kinase A-A-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P; van der Heyden, MAG; Kok, Bart; Heck, Albert J R; Scholten, Arjen

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  19. Role of adiponectin/phosphatidylinositol 3-kinase/protein kinase B ...

    African Journals Online (AJOL)

    The adiponectin/phosphatidylinositol 3-kinase/protein kinase B (ADP/PI3k/Akt) signal transduction pathway has an important role in promoting cell survival. This study was designed to determine if the ADP/PI3K/Akt signaling pathway has a role in the mechanism of ischemia–reperfusion injury in vivo. Sprague–Dawley rats ...

  20. Phosphorylation of nm23/nucleoside diphosphate kinase by casein kinase 2 in vitro

    DEFF Research Database (Denmark)

    Engel, M; Issinger, O G; Lascu, I

    1994-01-01

    We have investigated phosphorylation of human nucleoside diphosphate kinase (NDPK) and of homologous NDPK from different species by human casein kinase 2 (CK-2). The human NDPK isotypes A and B were phosphorylated by CK-2 in vitro both when the purified proteins and total lysate of HL-60 leukemia...

  1. Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Ting-Lei Gu

    Full Text Available Cholangiocarcinoma, also known as bile duct cancer, is the second most common primary hepatic carcinoma with a median survival of less than 2 years. The molecular mechanisms underlying the development of this disease are not clear. To survey activated tyrosine kinases signaling in cholangiocarcinoma, we employed immunoaffinity profiling coupled to mass spectrometry and identified DDR1, EPHA2, EGFR, and ROS tyrosine kinases, along with over 1,000 tyrosine phosphorylation sites from about 750 different proteins in primary cholangiocarcinoma patients. Furthermore, we confirmed the presence of ROS kinase fusions in 8.7% (2 out of 23 of cholangiocarcinoma patients. Expression of the ROS fusions in 3T3 cells confers transforming ability both in vitro and in vivo, and is responsive to its kinase inhibitor. Our data demonstrate that ROS kinase is a promising candidate for a therapeutic target and for a diagnostic molecular marker in cholangiocarcinoma. The identification of ROS tyrosine kinase fusions in cholangiocarcinoma, along with the presence of other ROS kinase fusions in lung cancer and glioblastoma, suggests that a more broadly based screen for activated ROS kinase in cancer is warranted.

  2. The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

    Science.gov (United States)

    Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I.; Hantschel, Oliver

    2014-11-01

    The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

  3. The Link between Protein Kinase CK2 and Atypical Kinase Rio1

    Directory of Open Access Journals (Sweden)

    Konrad Kubiński

    2017-02-01

    Full Text Available The atypical kinase Rio1 is widespread in many organisms, ranging from Archaebacteria to humans, and is an essential factor in ribosome biogenesis. Little is known about the protein substrates of the enzyme and small-molecule inhibitors of the kinase. Protein kinase CK2 was the first interaction partner of Rio1, identified in yeast cells. The enzyme from various sources undergoes CK2-mediated phosphorylation at several sites and this modification regulates the activity of Rio1. The aim of this review is to present studies of the relationship between the two different kinases, with respect to CK2-mediated phosphorylation of Rio1, regulation of Rio1 activity, and similar susceptibility of the kinases to benzimidazole inhibitors.

  4. syk kinase activation by a src kinase-initiated activation loop phosphorylation chain reaction

    Science.gov (United States)

    El-Hillal, O.; Kurosaki, T.; Yamamura, H.; Kinet, J.-P.; Scharenberg, A. M.

    1997-01-01

    Activation of the syk tyrosine kinase occurs almost immediately following engagement of many types of antigen receptors, including Fc receptors, but the mechanism through which syk is activated is currently unclear. Here we demonstrate that Fc receptor-induced syk activation occurs as the result of phosphorylation of the syk activation loop by both src family kinases and other molecules of activated syk, suggesting that syk activation occurs as the result of a src kinase-initiated activation loop phosphorylation chain reaction. This type of activation mechanism predicts that syk activation would exhibit exponential kinetics, providing a potential explanation for its rapid and robust activation by even weak antigen receptor stimuli. We propose that a similar mechanism may be responsible for generating rapid activation of other cytoplasmic tyrosine kinases, such as those of the Bruton tyrosine kinase/tec family, as well. PMID:9050880

  5. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments

    International Nuclear Information System (INIS)

    Stambaugh, Cassandra; Nelms, Benjamin E.; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2013-01-01

    Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D 99% ), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from the

  6. Molecular Cloning and Characterization of a P38-Like Mitogen-Activated Protein Kinase from Echinococcus granulosus.

    Science.gov (United States)

    Lü, Guodong; Li, Jing; Zhang, Chuanshan; Li, Liang; Bi, Xiaojuan; Li, Chaowang; Fan, Jinliang; Lu, Xiaomei; Vuitton, Dominique A; Wen, Hao; Lin, Renyong

    2016-12-01

    Cystic echinococcosis (CE) treatment urgently requires a novel drug. The p38 mitogen-activated protein kinases (MAPKs) are a family of Ser/Thr protein kinases, but still have to be characterized in Echinococcus granulosus . We identified a 1,107 bp cDNA encoding a 368 amino acid MAPK protein (Egp38) in E. granulosus . Egp38 exhibits 2 distinguishing features of p38-like kinases: a highly conserved T-X-Y motif and an activation loop segment. Structural homology modeling indicated a conserved structure among Egp38, EmMPK2, and H. sapiens p38α, implying a common binding mechanism for the ligand domain and downstream signal transduction processing similar to that described for p38α. Egp38 and its phosphorylated form are expressed in the E. granulosus larval stages vesicle and protoscolices during intermediate host infection of an intermediate host. Treatment of in vitro cultivated protoscolices with the p38-MAPK inhibitor ML3403 effectively suppressed Egp38 activity and led to significant protoscolices death within 5 days. Treatment of in vitro-cultivated protoscolices with TGF-β1 effectively induced Egp38 phosphorylation. In summary, the MAPK, Egp38, was identified in E. granulosus , as an anti-CE drug target and participates in the interplay between the host and E. granulosus via human TGF-β1.

  7. Mechanism of polyphosphate kinase from Propionibacterium shermanii

    International Nuclear Information System (INIS)

    Robinson, N.A.

    1986-01-01

    Polyphosphate kinase, which catalyzes the reaction shown below, is one of two enzymes which have been reported to catalyze the synthesis of polyphosphate. Purification performed by ammonium sulfate precipitation (0-40% fraction) was followed by chromatography. The enzyme represents 70% of the protein in the hydroxylapatite pool and is stable at this level of purity. The subunit molecular weight was determined by SDS polyacrylamide gel analysis, (83,000 +/- 3000), nondenaturing polyacrylamide gel electrophoresis, (80,000 and 86,000 daltons), gel filtration (Biogel A 0.5m column was 85,000 +/- 4000.) Polyphosphate kinase appears to be a monomeric enzyme of ∼83,000 daltons. Four assays were developed for polyphosphate kinase. Basic proteins such as polylysine stimulate the synthesis of polyphosphate, these proteins cause precipitation of polyphosphate kinase from relatively impure enzyme extracts: Synthesized polyphosphate interacts noncovalently with the basic protein-enzyme precipitate. Efficient synthesis of polyphosphate requires the addition of either phosphate or short chain polyphosphate. Synthesis did occur at 1/10 the rate when neither of these two compounds were included. Initiation, elongation, and termination events of polyphosphate synthesis were examined. Short chain polyphosphate acts as a primer, with [ 32 P] short-chain polyphosphate incorporation into long chain polyphosphate by the kinase

  8. Radioimmunoassay of bovine heart protein kinase

    International Nuclear Information System (INIS)

    Fleischer, N.; Rosen, O.M.; Reichlin, M.

    1976-01-01

    Immunization of guinea pigs with bovine cardiac cAMP-dependent protein kinase (ATP : protein phosphotransferase, EC 2.7.1.37) resulted in the development of precipitating antibodies to the cAMP-binding subunit of the enzyme. Both the phosphorylated and nonphosphorylated cAMP-binding protein of the protein kinase reacted with the antiserum. A radioimmunoassay was developed that detects 10 ng of holoenzyme and permits measurement of enzyme concentrations in bovine cardiac muscle. Bovine liver, kidney, brain, and skeletal muscle contain protein kinases which are immunologically identical to those found in bovine cardiac muscle. However, the proportion of immunoreactive enzyme activity differed for each tissue. All of the immunologically nonreactive enzyme in skeletal muscle and heart was separable from immunoreactive enzyme by chromatography on DEAE-cellulose. Rat tissues and pig heart contained protein kinase activity that cross reacted immunologically in a nonparallel fashion with bovine cardiac enzyme. These results indicate that cAMP-dependent protein kinases within and between species are immunologically heterogeneous

  9. The target landscape of clinical kinase drugs.

    Science.gov (United States)

    Klaeger, Susan; Heinzlmeir, Stephanie; Wilhelm, Mathias; Polzer, Harald; Vick, Binje; Koenig, Paul-Albert; Reinecke, Maria; Ruprecht, Benjamin; Petzoldt, Svenja; Meng, Chen; Zecha, Jana; Reiter, Katrin; Qiao, Huichao; Helm, Dominic; Koch, Heiner; Schoof, Melanie; Canevari, Giulia; Casale, Elena; Depaolini, Stefania Re; Feuchtinger, Annette; Wu, Zhixiang; Schmidt, Tobias; Rueckert, Lars; Becker, Wilhelm; Huenges, Jan; Garz, Anne-Kathrin; Gohlke, Bjoern-Oliver; Zolg, Daniel Paul; Kayser, Gian; Vooder, Tonu; Preissner, Robert; Hahne, Hannes; Tõnisson, Neeme; Kramer, Karl; Götze, Katharina; Bassermann, Florian; Schlegl, Judith; Ehrlich, Hans-Christian; Aiche, Stephan; Walch, Axel; Greif, Philipp A; Schneider, Sabine; Felder, Eduard Rudolf; Ruland, Juergen; Médard, Guillaume; Jeremias, Irmela; Spiekermann, Karsten; Kuster, Bernhard

    2017-12-01

    Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  10. Janus kinase inhibitors: jackpot or potluck?

    Directory of Open Access Journals (Sweden)

    Pavithran Keechilat

    2012-06-01

    Full Text Available The reports of a unique mutation in the Janus kinase-2 gene (JAK2 in polycythemia vera by several independent groups in 2005 quickly spurred the development of the Janus kinase inhibitors. In one of the great victories of translational research in recent times, the first smallmolecule Janus kinase inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the management of a subset of myeloproliferative neoplasms (MPN: primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only covers high-risk and intermediate-2 risk myelofibrosis, inhibitors with greater potency are likely to offer better disease control and survival advantage in patients belonging to these categories, and possibly to the low-risk and intermediate-1 risk categories of MPN as well. But use of the Janus kinase inhibitors also probably has certain disadvantages, such as toxicity, resistance, withdrawal phenomenon, non-reversal of histology, and an implausible goal of disease clone eradication, some of which could offset the gains. In spite of this, Janus kinase inhibitors are here to stay, and for use in more than just myeloproliferative neoplasms.

  11. Interplay between superconductivity and magnetism in iron-based superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Chubukov, Andrey V [University of Wisconsin

    2015-06-10

    This proposal is for theoretical work on strongly correlated electron systems, which are at the center of experimental and theoretical activities in condensed-matter physics. The interest to this field is driven fascinating variety of observed effects, universality of underlying theoretical ideas, and practical applications. I propose to do research on Iron-based superconductors (FeSCs), which currently attract high attention in the physics community. My goal is to understand superconductivity and magnetism in these materials at various dopings, the interplay between the two, and the physics in the phase in which magnetism and superconductivity co-exist. A related goal is to understand the origin of the observed pseudogap-like behavior in the normal state. My research explores the idea that superconductivity is of electronic origin and is caused by the exchange of spin-fluctuations, enhanced due to close proximity to antiferromagnetism. The multi-orbital/multi-band nature of FeSCs opens routes for qualitatively new superconducting states, particularly the ones which break time-reversal symmetry. By all accounts, the coupling in pnictdes is below the threshold for Mott physics and I intend to analyze these systems within the itinerant approach. My plan is to do research in two stages. I first plan to address several problems within weak-coupling approach. Among them: (i) what sets stripe magnetic order at small doping, (ii) is there a preemptive instability into a spin-nematic state, and how stripe order affects fermions; (iii) is there a co-existence between magnetism and superconductivity and what are the system properties in the co-existence state; (iv) how superconductivity emerges despite strong Coulomb repulsion and can the gap be s-wave but with nodes along electron FSs, (v) are there complex superconducting states, like s+id, which break time reversal symmetry. My second goal is to go beyond weak coupling and derive spin-mediated, dynamic interaction between

  12. Interplay between structural symmetry and magnetism in Ag–Cu

    Energy Technology Data Exchange (ETDEWEB)

    Yen, Tsung-Wen; Lai, S.K., E-mail: sklai@coll.phy.ncu.edu.tw

    2016-01-01

    occupy different molecular orbital energy levels. - Highlights: • Interpretation of the interplay between cluster symmetry and magnetism. • Spin unrestricted DFT calculations within restricted and unrestricted symmetries. • Structural optimization of bimetallic clusters Ag{sub n}Cu{sub 38−n}.

  13. Protocols for the Design of Kinase-focused Compound Libraries.

    Science.gov (United States)

    Jacoby, Edgar; Wroblowski, Berthold; Buyck, Christophe; Neefs, Jean-Marc; Meyer, Christophe; Cummings, Maxwell D; van Vlijmen, Herman

    2018-05-01

    Protocols for the design of kinase-focused compound libraries are presented. Kinase-focused compound libraries can be differentiated based on the design goal. Depending on whether the library should be a discovery library specific for one particular kinase, a general discovery library for multiple distinct kinase projects, or even phenotypic screening, there exists today a variety of in silico methods to design candidate compound libraries. We address the following scenarios: 1) Datamining of SAR databases and kinase focused vendor catalogues; 2) Predictions and virtual screening; 3) Structure-based design of combinatorial kinase inhibitors; 4) Design of covalent kinase inhibitors; 5) Design of macrocyclic kinase inhibitors; and 6) Design of allosteric kinase inhibitors and activators. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Phosphatidylinositol 3-Kinase (PI3K) and phosphatidylinositol 3-kinase-related kinase (PIKK) inhibitors: importance of the morpholine ring

    Czech Academy of Sciences Publication Activity Database

    Andrs, M.; Kobarecny, J.; Jun, D.; Hodný, Zdeněk; Bartek, Jiří; Kuca, K.

    2015-01-01

    Roč. 58, č. 1 (2015), s. 41-71 ISSN 0022-2623 R&D Projects: GA MŠk(CZ) CZ.1.07/2.3.00/30.0044 Grant - others:University Hospital Hradec Kralove(CZ) 00179906; Faculty of Military Health Sciences, University of Defence(CZ) SV/FVZ201402 Institutional support: RVO:68378050 Keywords : DEPENDENT PROTEIN-KINASE * STRAND BREAK REPAIR * SELECTIVE PI3K-BETA INHIBITORS * TELANGIECTASIA MUTATED KINASE Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.589, year: 2015

  15. Protein Kinases in Shaping Plant Architecture.

    Science.gov (United States)

    Wu, Juan; Wang, Bo; Xin, Xiaoyun; Ren, Dongtao

    2018-02-13

    Plant architecture, the three-dimensional organization of the plant body, includes the branching pattern and the size, shape, and position of organs. Plant architecture is genetically controlled and is influenced by environmental conditions. The regulations occur at most of the stages from the first division of the fertilized eggs to the final establishment of plant architecture. Among the various endogenous regulators, protein kinases and their associated signaling pathways have been shown to play important roles in regulating the process of plant architecture establishment. In this review, we summarize recent progress in the understanding of the mechanisms by which plant architecture formation is regulated by protein kinases, especially mitogen-activated protein kinase (MAPK). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. The Concert of Europe and Great Power Governance Today: What Can the Order of 19th-Century Europe Teach Policymakers About International Order in the 21st Century

    Science.gov (United States)

    2017-01-01

    13 These differences became alarmingly clear once liberal revolutions broke out across multiple European polities in 1820.61 The eastern powers ...dealings with that eastern power that they had so often worked with in concert. For in that treat- ment, the western powers ultimately “ broke the first...KYLE LASCURETTES The Concert of Europe and Great- Power Governance Today What Can the Order of 19th-Century Europe Teach Policymakers About

  17. The Role of PAS Kinase in PASsing the Glucose Signal

    Directory of Open Access Journals (Sweden)

    Julianne H. Grose

    2010-06-01

    Full Text Available PAS kinase is an evolutionarily conserved nutrient responsive protein kinase that regulates glucose homeostasis. Mammalian PAS kinase is activated by glucose in pancreatic beta cells, and knockout mice are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet. Yeast PAS kinase is regulated by both carbon source and cell integrity stress and stimulates the partitioning of glucose toward structural carbohydrate biosynthesis. In our current model for PAS kinase regulation, a small molecule metabolite binds the sensory PAS domain and activates the enzyme. Although bona fide PAS kinase substrates are scarce, in vitro substrate searches provide putative targets for exploration.

  18. Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

    International Nuclear Information System (INIS)

    Grose, C.; Jackson, W.; Traugh, J.A.

    1989-01-01

    Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [γ- 32 P]ATP. The same glycoprotein was phosphorylated when [ 32 P]GTP was substituted for [ 32 P]ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein

  19. 2-Aminobenzimidazoles as potent Aurora kinase inhibitors.

    Science.gov (United States)

    Zhong, Min; Bui, Minna; Shen, Wang; Baskaran, Subramanian; Allen, Darin A; Elling, Robert A; Flanagan, W Michael; Fung, Amy D; Hanan, Emily J; Harris, Shannon O; Heumann, Stacey A; Hoch, Ute; Ivy, Sheryl N; Jacobs, Jeffrey W; Lam, Stuart; Lee, Heman; McDowell, Robert S; Oslob, Johan D; Purkey, Hans E; Romanowski, Michael J; Silverman, Jeffrey A; Tangonan, Bradley T; Taverna, Pietro; Yang, Wenjin; Yoburn, Josh C; Yu, Chul H; Zimmerman, Kristin M; O'Brien, Tom; Lew, Willard

    2009-09-01

    This Letter describes the discovery and key structure-activity relationship (SAR) of a series of 2-aminobenzimidazoles as potent Aurora kinase inhibitors. 2-Aminobenzimidazole serves as a bioisostere of the biaryl urea residue of SNS-314 (1c), which is a potent Aurora kinase inhibitor and entered clinical testing in patients with solid tumors. Compared to SNS-314, this series of compounds offers better aqueous solubility while retaining comparable in vitro potency in biochemical and cell-based assays; in particular, 6m has also demonstrated a comparable mouse iv PK profile to SNS-314.

  20. Mapping sound intensities by seating position in a university concert band: A risk of hearing loss, temporary threshold shifts, and comparisons with standards of OSHA and NIOSH

    Science.gov (United States)

    Holland, Nicholas Vedder, III

    Exposure to loud sounds is one of the leading causes of hearing loss in the United States. The purpose of the current research was to measure the sound pressure levels generated within a university concert band and determine if those levels exceeded permissible sound limits for exposure according to criteria set by the Occupational Safety and Health Administration (OSHA) and the National Institute of Occupational Safety and Health (NIOSH). Time-weighted averages (TWA) were obtained via a dosimeter during six rehearsals for nine members of the ensemble (plus the conductor), who were seated in frontal proximity to "instruments of power" (trumpets, trombones, and percussion; (Backus, 1977). Subjects received audiometer tests prior to and after each rehearsal to determine any temporary threshold shifts (TTS). Single sample t tests were calculated to compare TWA means and the maximum sound intensity exposures set by OSHA and NIOSH. Correlations were calculated between TWAs and TTSs, as well as TTSs and the number of semesters subjects reported being seated in proximity to instruments of power. The TWA-OSHA mean of 90.2 dBA was not significantly greater than the specified OSHA maximum standard of 90.0 dBA (p > .05). The TWA-NIOSH mean of 93.1 dBA was, however, significantly greater than the NIOSH specified maximum standard of 85.0 dBA (p OSHA, r = .20 for NIOSH); the correlation between TTSs and semesters of proximity to instruments of power was also considered weak (r = .13). TWAs cumulatively exceeded both association's sound exposure limits at 11 specified locations (nine subjects and both ears of the conductor) throughout the concert band's rehearsals. In addition, hearing acuity, as determined by TTSs, was substantially affected negatively by the intensities produced in the concert band. The researcher concluded that conductors, as well as their performers, must be aware of possible damaging sound intensities in rehearsals or performances.

  1. The 5S rDNA family evolves through concerted and birth-and-death evolution in fish genomes: an example from freshwater stingrays

    Science.gov (United States)

    2011-01-01

    Background Ribosomal 5S genes are well known for the critical role they play in ribosome folding and functionality. These genes are thought to evolve in a concerted fashion, with high rates of homogenization of gene copies. However, the majority of previous analyses regarding the evolutionary process of rDNA repeats were conducted in invertebrates and plants. Studies have also been conducted on vertebrates, but these analyses were usually restricted to the 18S, 5.8S and 28S rRNA genes. The recent identification of divergent 5S rRNA gene paralogs in the genomes of elasmobranches and teleost fishes indicate that the eukaryotic 5S rRNA gene family has a more complex genomic organization than previously thought. The availability of new sequence data from lower vertebrates such as teleosts and elasmobranches enables an enhanced evolutionary characterization of 5S rDNA among vertebrates. Results We identified two variant classes of 5S rDNA sequences in the genomes of Potamotrygonidae stingrays, similar to the genomes of other vertebrates. One class of 5S rRNA genes was shared only by elasmobranches. A broad comparative survey among 100 vertebrate species suggests that the 5S rRNA gene variants in fishes originated from rounds of genome duplication. These variants were then maintained or eliminated by birth-and-death mechanisms, under intense purifying selection. Clustered multiple copies of 5S rDNA variants could have arisen due to unequal crossing over mechanisms. Simultaneously, the distinct genome clusters were independently homogenized, resulting in the maintenance of clusters of highly similar repeats through concerted evolution. Conclusions We believe that 5S rDNA molecular evolution in fish genomes is driven by a mixed mechanism that integrates birth-and-death and concerted evolution. PMID:21627815

  2. Purification and characterization of a casein kinase 2-type protein kinase from pea nuclei

    Science.gov (United States)

    Li, H.; Roux, S. J.

    1992-01-01

    Almost all the polyamine-stimulated protein kinase activity associated with the chromatin fraction of nuclei purified from etiolated pea (Pisum sativum L.) plumules is present in a single enzyme that can be extracted from chromatin by 0.35 molar NaCl. This protein kinase can be further purified over 2000-fold by salt fractionation and anion-exchange and casein-agarose column chromatography, after which it is more than 90% pure. The purified kinase has a specific activity of about 650 nanomoles per minute per milligram protein in the absence of polyamines, with either ATP or GTP as phosphoryl donor. Spermidine can stimulate its activity fourfold, with half-maximal activation at about 2 millimolar. Spermine and putrescine also stimulate activity, although somewhat less effectively. This kinase has a tetrameric alpha 2 beta 2 structure with a native molecular weight of 130,000, and subunit molecular weights of 36,000 for the catalytic subunit (alpha) and 29,000 for the regulatory subunit (beta). In western blot analyses, only the alpha subunit reacts strongly with polyclonal antibodies to a Drosophila casein kinase II. The pea kinase can use casein and phosvitin as artificial substrates, phosphorylating both the serine and threonine residues of casein. It has a pH optimum near 8.0, a Vmax of 1.5 micromoles per minute per milligram protein, and a Km for ATP of approximately 75 micromolar. Its activity can be almost completely inhibited by heparin at 5 micrograms per milliliter, but is relatively insensitive to concentrations of staurosporine, K252a, and chlorpromazine that strongly antagonize Ca(2+) -regulated protein kinases. These results are discussed in relation to recent findings that casein kinase 2-type kinases may phosphorylate trans-acting factors that bind to light-regulated promoters in plants.

  3. CZK3, a MAP kinase kinase kinase homolog in Cercospora zeae-maydis, regulates cercosporin biosynthesis, fungal development, and pathogenesis.

    Science.gov (United States)

    Shim, Won-Bo; Dunkle, Larry D

    2003-09-01

    The fungus Cercospora zeae-maydis causes gray leaf spot of maize and produces cercosporin, a photosensitizing perylenequinone with toxic activity against a broad spectrum of organisms. However, little is known about the biosynthetic pathway or factors that regulate cercosporin production. Analysis of a cDNA subtraction library comprised of genes that are up-regulated during cercosporin synthesis revealed a sequence highly similar to mitogen-activated protein (MAP) kinases in other fungi. Sequencing and conceptual translation of the full-length genomic sequence indicated that the gene, which we designated CZK3, contains a 4,119-bp open reading frame devoid of introns and encodes a 1,373-amino acid sequence that is highly similar to Wis4, a MAP kinase kinase kinase in Schizosaccharomyces pombe. Targeted disruption of CZK3 suppressed expression of genes predicted to participate in cercosporin biosynthesis and abolished cercosporin production. The disrupted mutants grew faster on agar media than the wild type but were deficient in conidiation and elicited only small chlorotic spots on inoculated maize leaves compared with rectangular necrotic lesions incited by the wild type. Complementation of disruptants with the CZK3 open reading frame and flanking sequences restored wild-type levels of conidiation, growth rate, and virulence as well as the ability to produce cercosporin. The results suggest that cercosporin is a virulence factor in C. zeae-maydis during maize pathogenesis, but the pleiotropic effects of CZK3 disruption precluded definitive conclusions.

  4. Control of concerted two bond versus single bond dissociation in CH3Co(CO)4 via an intermediate state using pump-dump laser pulses

    Science.gov (United States)

    Ambrosek, David; González, Leticia

    2007-10-01

    Wavepacket propagations on ab initio multiconfigurational two-dimensional potential energy surfaces for CH3Co(CO)4 indicate that after irradiation to the lowest first and second electronic excited states, concerted dissociation of CH3 and the axial CO ligand takes place. We employ a pump-dump sequence of pulses with appropriate frequencies and time delays to achieve the selective breakage of a single bond by controlling the dissociation angle. The pump and dump pulse sequence exploits the unbound surface where dissociation occurs in a counterintuitive fashion; stretching of one bond in an intermediate state enhances the single dissociation of the other bond.

  5. Control of concerted two bond versus single bond dissociation in CH(3)Co(CO)(4) via an intermediate state using pump-dump laser pulses.

    Science.gov (United States)

    Ambrosek, David; González, Leticia

    2007-10-07

    Wavepacket propagations on ab initio multiconfigurational two-dimensional potential energy surfaces for CH(3)Co(CO)(4) indicate that after irradiation to the lowest first and second electronic excited states, concerted dissociation of CH(3) and the axial CO ligand takes place. We employ a pump-dump sequence of pulses with appropriate frequencies and time delays to achieve the selective breakage of a single bond by controlling the dissociation angle. The pump and dump pulse sequence exploits the unbound surface where dissociation occurs in a counterintuitive fashion; stretching of one bond in an intermediate state enhances the single dissociation of the other bond.

  6. Myosin light chain kinase phosphorylation in tracheal smooth muscle

    International Nuclear Information System (INIS)

    Stull, J.T.; Hsu, L.C.; Tansey, M.G.; Kamm, K.E.

    1990-01-01

    Purified myosin light chain kinase from smooth muscle is phosphorylated by cyclic AMP-dependent protein kinase, protein kinase C, and the multifunctional calmodulin-dependent protein kinase II. Because phosphorylation in a specific site (site A) by any one of these kinases desensitizes myosin light chain kinase to activation by Ca2+/calmodulin, kinase phosphorylation could play an important role in regulating smooth muscle contractility. This possibility was investigated in 32 P-labeled bovine tracheal smooth muscle. Treatment of tissues with carbachol, KCl, isoproterenol, or phorbol 12,13-dibutyrate increased the extent of kinase phosphorylation. Six primary phosphopeptides (A-F) of myosin light chain kinase were identified. Site A was phosphorylated to an appreciable extent only with carbachol or KCl, agents which contract tracheal smooth muscle. The extent of site A phosphorylation correlated to increases in the concentration of Ca2+/calmodulin required for activation. These results show that cyclic AMP-dependent protein kinase and protein kinase C do not affect smooth muscle contractility by phosphorylating site A in myosin light chain kinase. It is proposed that phosphorylation of myosin light chain kinase in site A in contracting tracheal smooth muscle may play a role in the reported desensitization of contractile elements to activation by Ca2+

  7. Study of the IMRT interplay effect using a 4DCT Monte Carlo dose calculation.

    Science.gov (United States)

    Jensen, Michael D; Abdellatif, Ady; Chen, Jeff; Wong, Eugene

    2012-04-21

    Respiratory motion may lead to dose errors when treating thoracic and abdominal tumours with radiotherapy. The interplay between complex multileaf collimator patterns and patient respiratory motion could result in unintuitive dose changes. We have developed a treatment reconstruction simulation computer code that accounts for interplay effects by combining multileaf collimator controller log files, respiratory trace log files, 4DCT images and a Monte Carlo dose calculator. Two three-dimensional (3D) IMRT step-and-shoot plans, a concave target and integrated boost were delivered to a 1D rigid motion phantom. Three sets of experiments were performed with 100%, 50% and 25% duty cycle gating. The log files were collected, and five simulation types were performed on each data set: continuous isocentre shift, discrete isocentre shift, 4DCT, 4DCT delivery average and 4DCT plan average. Analysis was performed using 3D gamma analysis with passing criteria of 2%, 2 mm. The simulation framework was able to demonstrate that a single fraction of the integrated boost plan was more sensitive to interplay effects than the concave target. Gating was shown to reduce the interplay effects. We have developed a 4DCT Monte Carlo simulation method that accounts for IMRT interplay effects with respiratory motion by utilizing delivery log files.

  8. Protein kinase CK2 in health and disease: Protein kinase CK2: from structures to insights

    DEFF Research Database (Denmark)

    Niefind, K; Raaf, J; Issinger, Olaf-Georg

    2009-01-01

    the critical region of CK2alpha recruitment is pre-formed in the unbound state. In CK2alpha the activation segment - a key element of protein kinase regulation - adapts invariably the typical conformation of the active enzymes. Recent structures of human CK2alpha revealed a surprising plasticity in the ATP......Within the last decade, 40 crystal structures corresponding to protein kinase CK2 (former name 'casein kinase 2'), to its catalytic subunit CK2alpha and to its regulatory subunit CK2beta were published. Together they provide a valuable, yet by far not complete basis to rationalize the biochemical...

  9. Modulation of Cyclins, p53 and Mitogen-Activated Protein Kinases Signaling in Breast Cancer Cell Lines by 4-(3,4,5-Trimethoxyphenoxybenzoic Acid

    Directory of Open Access Journals (Sweden)

    Kuan-Han Lee

    2014-01-01

    Full Text Available Despite the advances in cancer therapy and early detection, breast cancer remains a leading cause of cancer-related deaths among females worldwide. The aim of the current study was to investigate the antitumor activity of a novel compound, 4-(3,4,5-trimethoxyphenoxybenzoic acid (TMPBA and its mechanism of action, in breast cancer. Results indicated the relatively high sensitivity of human breast cancer cell-7 and MDA-468 cells towards TMPBA with IC50 values of 5.9 and 7.9 µM, respectively compared to hepatocarcinoma cell line Huh-7, hepatocarcinoma cell line HepG2, and cervical cancer cell line Hela cells. Mechanistically, TMPBA induced apoptotic cell death in MCF-7 cells as indicated by 4',6-diamidino-2-phenylindole (DAPI nuclear staining, cell cycle analysis and the activation of caspase-3. Western blot analysis revealed the ability of TMPBA to target pathways mediated by mitogen-activated protein (MAP kinases, 5' adenosine monophosphate-activated protein kinase (AMPK, and p53, of which the concerted action underlined its antitumor efficacy. In addition, TMPBA induced alteration of cyclin proteins’ expression and consequently modulated the cell cycle. Taken together, the current study underscores evidence that TMPBA induces apoptosis in breast cancer cells via the modulation of cyclins and p53 expression as well as the modulation of AMPK and mitogen-activated protein kinases (MAPK signaling. These findings support TMPBA’s clinical promise as a potential candidate for breast cancer therapy.

  10. Side-effects of protein kinase inhibitors on ion channels

    Indian Academy of Sciences (India)

    2013-11-06

    Nov 6, 2013 ... with aberrant kinase activity, including cancers, arthritis and cardiovascular disorders. Several strategies .... family, the β-adrenergic receptor kinase (βARK), the ribosomal S6 ..... urinary bladder smooth muscle cells. While no ...

  11. Creatine kinase activity is associated with blood pressure

    NARCIS (Netherlands)

    Brewster, Lizzy M.; Mairuhu, Gideon; Bindraban, Navin R.; Koopmans, Richard P.; Clark, Joseph F.; van Montfrans, Gert A.

    2006-01-01

    BACKGROUND: We previously hypothesized that high activity of creatine kinase, the central regulatory enzyme of energy metabolism, facilitates the development of high blood pressure. Creatine kinase rapidly provides adenosine triphosphate to highly energy-demanding processes, including cardiovascular

  12. Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

    DEFF Research Database (Denmark)

    Knecht, Wolfgang; Mikkelsen, N.E.; Clausen, A.R.

    2009-01-01

    Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) can additionally sensitize human cancer cell lines towards the anti-cancer drug gemcitabine. We show that this property is based on the Dm-dNK ability to efficiently phosphorylate gemcitabine. The 2.2 angstrom resolution...

  13. Deoxyribonucleoside kinases in mitochondrial DNA depletion.

    Science.gov (United States)

    Saada-Reisch, Ann

    2004-10-01

    Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a heterogeneous group of mitochondrial disorders, manifested by a decreased mtDNA copy number and respiratory chain dysfunction. Primary MDS are inherited autosomally and may affect a single organ or multiple tissues. Mutated mitochondrial deoxyribonucleoside kinases; deoxyguanosine kinase (dGK) and thymidine kinase 2 (TK2), were associated with the hepatocerebral and myopathic forms of MDS respectively. dGK and TK2 are key enzymes in the mitochondrial nucleotide salvage pathway, providing the mitochondria with deoxyribonucleotides (dNP) essential for mtDNA synthesis. Although the mitochondrial dNP pool is physically separated from the cytosolic one, dNP's may still be imported through specific transport. Non-replicating tissues, where cytosolic dNP supply is down regulated, are thus particularly vulnerable to dGK and TK2 deficiency. The overlapping substrate specificity of deoxycytidine kinase (dCK) may explain the relative sparing of muscle in dGK deficiency, while low basal TK2 activity render this tissue susceptible to TK2 deficiency. The precise pathophysiological mechanisms of mtDNA depletion due to dGK and TK2 deficiencies remain to be determined, though recent findings confirm that it is attributed to imbalanced dNTP pools.

  14. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    current barriers of kinase inhibitors, including poor selectivity and emergence of drug resistance. In spite of the small number of identified allosteric inhibitors in comparison with that of inhibitors targeting the ATP pocket, encouraging results, such as the FDA-approval of the first small...

  15. Plant PA signaling via diacylglycerol kinase

    NARCIS (Netherlands)

    Arisz, S.A.; Testerink, C.; Munnik, T.

    2009-01-01

    Accumulating evidence suggests that phosphatidic acid (PA) plays a pivotal role in the plant's response to environmental signals. Besides phospholipase D (PLD) activity, PA can also be generated by diacylglycerol kinase (DGK). To establish which metabolic route is activated, a differential

  16. Nonorthologous gene displacement of phosphomevalonate kinase

    NARCIS (Netherlands)

    Houten, S. M.; Waterham, H. R.

    2001-01-01

    Phosphomevalonate kinase (PMK; EC 2.7.4.2) catalyzes the phosphorylation of 5-phosphomevalonate into 5-diphosphomevalonate, an essential step in isoprenoid biosynthesis via the mevalonate pathway. So far, two nonorthologous genes encoding PMK have been described, the Saccharomyces cerevisiae ERG8

  17. Casein kinase-2 structure-function relationship

    DEFF Research Database (Denmark)

    Boldyreff, B; Meggio, F; Pinna, L A

    1992-01-01

    Nine mutants of human casein kinase-2 beta subunit have been created and assayed for their ability to assemble with the catalytic alpha subunit to give, at a 1:1 molar ratio, a fully competent CK-2 holoenzyme as judged by the following criteria: 1) the generation of an active heterotetrameric form...

  18. Mitogen-activated protein kinases mediate Mycobacterium ...

    Indian Academy of Sciences (India)

    2012-01-19

    Jan 19, 2012 ... CD44, an adhesion molecule, has been reported to be a binding site for ... receptors in mediating mitogen-activated protein kinase activation. ... surface expression and tumour necrosis factor-alpha levels, ... Abbreviations used: Abs, antibodies; ANOVA, analysis of variance; AP-1, activator protein -1; BCG, ...

  19. Kinase-Centric Computational Drug Development

    NARCIS (Netherlands)

    Kooistra, Albert J.; Volkamer, Andrea

    2017-01-01

    Kinases are among the most studied drug targets in industry and academia, due to their involvement in a majority of cellular processes and, upon dysregulation, in a variety of diseases including cancer, inflammation, and autoimmune disorders. The high interest in this druggable protein family

  20. Kinases involved in Rec8 phosphorylation revealed

    Czech Academy of Sciences Publication Activity Database

    Anger, Martin

    2010-01-01

    Roč. 9, č. 14 (2010), s. 2708-2708 ISSN 1538-4101 Institutional research plan: CEZ:AV0Z50450515 Keywords : kinases * Rec8 * meisosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.999, year: 2010

  1. Gene regulation by MAP kinase cascades

    DEFF Research Database (Denmark)

    Fiil, Berthe Katrine; Petersen, Klaus; Petersen, Morten

    2009-01-01

    Mitogen-activated protein kinase (MAPK) cascades are signaling modules that transduce extracellular stimuli to a range of cellular responses. Research in yeast and metazoans has shown that MAPK-mediated phosphorylation directly or indirectly regulates the activity of transcription factors. Plant ...

  2. Nitric oxide-sphingolipid interplays in plant signalling: a new enigma from the Sphinx?

    Directory of Open Access Journals (Sweden)

    Isabelle eGuillas

    2013-09-01

    Full Text Available Nitric oxide (NO emerged as one of the major signalling molecules operating during plant development and plant responses to its environment. Beyond the identification of the direct molecular targets of NO, a series of studies considered its interplay with other actors of signal transduction and the integration of nitric oxide into complex signalling networks. Beside the close relationships between NO and calcium or phosphatidic acid signalling pathways that are now well-established, recent reports paved the way for interplays between NO and sphingolipids. This mini-review summarises our current knowledge of the influence NO and sphingolipids might exert on each other in plant physiology. Based on comparisons with examples from the animal field, it further indicates that, although sphingolipid-NO interplays are common features in signalling networks of eukaryotic cells, the underlying mechanisms and molecular targets significantly differ.

  3. Nitric oxide-sphingolipid interplays in plant signalling: a new enigma from the Sphinx?

    Science.gov (United States)

    Guillas, Isabelle; Puyaubert, Juliette; Baudouin, Emmanuel

    2013-09-12

    Nitric oxide (NO) emerged as one of the major signaling molecules operating during plant development and plant responses to its environment. Beyond the identification of the direct molecular targets of NO, a series of studies considered its interplay with other actors of signal transduction and the integration of NO into complex signaling networks. Beside the close relationships between NO and calcium or phosphatidic acid signaling pathways that are now well-established, recent reports paved the way for interplays between NO and sphingolipids (SLs). This mini-review summarizes our current knowledge of the influence NO and SLs might exert on each other in plant physiology. Based on comparisons with examples from the animal field, it further indicates that, although SL-NO interplays are common features in signaling networks of eukaryotic cells, the underlying mechanisms and molecular targets significantly differ.

  4. Interplay of charge density wave and spin density wave in high-T{sub c} superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Pradhan, B. [Government Science College, Malkangiri 764 048 (India)], E-mail: brunda@iopb.res.in; Raj, B.K. [B.J.B. College, Bhubaneswar 751 014 (India); Rout, G.C. [Condensed Matter Physics Group, P.G. Department of Applied Physics and Ballistics, F.M. University, Balasore 756 019 (India)], E-mail: gcr@iopb.res.in

    2008-12-01

    We present a mean-field theory theoretical model study for the coexistence of the two strongly interacting charge density wave (CDW) and spin density wave (SDW) for high-T{sub c} cuprates in the underdoped region before the onset of the superconductivity in the system. The analytic expressions for the temperature dependence of the CDW and SDW order parameters are derived and solved self-consistently. Their interplay is studied by varying their respective coupling constants. It is observed that in the interplay region both the gap parameters exhibit very strong dependence of their gap values for the coupling constants. Further, the electronic density of states (DOS) for the conduction electrons, which represents the scanning tunneling data, show two gap parameters in the interplay region from these experimental data. Our model can help to determine separately the CDW and SDW parameters.

  5. Interplay of charge density wave and spin density wave in high-Tc superconductors

    International Nuclear Information System (INIS)

    Pradhan, B.; Raj, B.K.; Rout, G.C.

    2008-01-01

    We present a mean-field theory theoretical model study for the coexistence of the two strongly interacting charge density wave (CDW) and spin density wave (SDW) for high-T c cuprates in the underdoped region before the onset of the superconductivity in the system. The analytic expressions for the temperature dependence of the CDW and SDW order parameters are derived and solved self-consistently. Their interplay is studied by varying their respective coupling constants. It is observed that in the interplay region both the gap parameters exhibit very strong dependence of their gap values for the coupling constants. Further, the electronic density of states (DOS) for the conduction electrons, which represents the scanning tunneling data, show two gap parameters in the interplay region from these experimental data. Our model can help to determine separately the CDW and SDW parameters

  6. Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets.

    Science.gov (United States)

    Lai, Justine Y Q; Langston, Steven; Adams, Ruth; Beevers, Rebekah E; Boyce, Richard; Burckhardt, Svenja; Cobb, James; Ferguson, Yvonne; Figueroa, Eva; Grimster, Neil; Henry, Andrew H; Khan, Nawaz; Jenkins, Kerry; Jones, Mark W; Judkins, Robert; Major, Jeremy; Masood, Abid; Nally, James; Payne, Helen; Payne, Lloyd; Raphy, Gilles; Raynham, Tony; Reader, John; Reader, Valérie; Reid, Alison; Ruprah, Parminder; Shaw, Michael; Sore, Hannah; Stirling, Matthew; Talbot, Adam; Taylor, Jess; Thompson, Stephen; Wada, Hiroki; Walker, David

    2005-05-01

    This work describes the preparation of approximately 13,000 compounds for rapid identification of hits in high-throughput screening (HTS). These compounds were designed as potential serine/threonine or tyrosine kinase inhibitors. The library consists of various scaffolds, e.g., purines, oxindoles, and imidazoles, whereby each core scaffold generally includes the hydrogen bond acceptor/donor properties known to be important for kinase binding. Several of these are based upon literature kinase templates, or adaptations of them to provide novelty. The routes to their preparation are outlined. A variety of automation techniques were used to prepare >500 compounds per scaffold. Where applicable, scavenger resins were employed to remove excess reagents and when necessary, preparative high performance liquid chromatography (HPLC) was used for purification. These compounds were screened against an 'in-house' kinase panel. The success rate in HTS was significantly higher than the corporate compound collection. Copyright (c) 2004 Wiley Periodicals, Inc.

  7. Kinase detection with gallium nitride based high electron mobility transistors.

    Science.gov (United States)

    Makowski, Matthew S; Bryan, Isaac; Sitar, Zlatko; Arellano, Consuelo; Xie, Jinqiao; Collazo, Ramon; Ivanisevic, Albena

    2013-07-01

    A label-free kinase detection system was fabricated by the adsorption of gold nanoparticles functionalized with kinase inhibitor onto AlGaN/GaN high electron mobility transistors (HEMTs). The HEMTs were operated near threshold voltage due to the greatest sensitivity in this operational region. The Au NP/HEMT biosensor system electrically detected 1 pM SRC kinase in ionic solutions. These results are pertinent to drug development applications associated with kinase sensing.

  8. Diversity, classification and function of the plant protein kinase superfamily

    OpenAIRE

    Lehti-Shiu, Melissa D.; Shiu, Shin-Han

    2012-01-01

    Eukaryotic protein kinases belong to a large superfamily with hundreds to thousands of copies and are components of essentially all cellular functions. The goals of this study are to classify protein kinases from 25 plant species and to assess their evolutionary history in conjunction with consideration of their molecular functions. The protein kinase superfamily has expanded in the flowering plant lineage, in part through recent duplications. As a result, the flowering plant protein kinase r...

  9. Pharmacokinetic interplay of phase II metabolism and transport: a theoretical study.

    Science.gov (United States)

    Wu, Baojian

    2012-01-01

    Understanding of the interdependence of cytochrome P450 enzymes and P-glycoprotein in disposition of drugs (also termed "transport-metabolism interplay") has been significantly advanced in recent years. However, whether such "interplay" exists between phase II metabolic enzymes and efflux transporters remains largely unknown. The objective of this article is to explore the role of efflux transporters (acting on the phase II metabolites) in disposition of the parent drug in Caco-2 cells, liver, and intestine via simulations utilizing a catenary model (for Caco-2 system) and physiologically based pharmacokinetic (PBPK) models (for the liver and intestine). In all three models, "transport-metabolism interplay" (i.e., inhibition of metabolite efflux decreases the metabolism) can be observed only when futile recycling (or deconjugation) occurred. Futile recycling appeared to bridge the two processes (i.e., metabolite formation and excretion) and enable the interplay thereof. Without futile recycling, metabolite formation was independent on its downstream process excretion, thus impact of metabolite excretion on its formation was impossible. Moreover, in liver PBPK model with futile recycling, impact of biliary metabolite excretion on the exposure of parent drug [(systemic (reservoir) area under the concentration-time curve (AUC(R1))] was limited; a complete inhibition of efflux resulted in AUC(R1) increases of less than 1-fold only. In intestine PBPK model with futile recycling, even though a complete inhibition of efflux could result in large elevations (e.g., 3.5-6.0-fold) in AUC(R1), an incomplete inhibition of efflux (e.g., with a residual activity of ≥ 20% metabolic clearance) saw negligible increases (interplay between phase II enzymes and efflux transporters. Those studying such "interplay" are encouraged to adequately consider potential consequences of inhibition of efflux transporters in humans. Copyright © 2011 Wiley-Liss, Inc.

  10. p21-activated Kinase1(PAK1) can promote ERK activation in a kinase independent manner

    DEFF Research Database (Denmark)

    Wang, Zhipeng; Fu, Meng; Wang, Lifeng

    2013-01-01

    204) although phosphorylation of b-Raf (Ser445) and c-Raf (Ser 338) remained unchanged. Furthermore, increased activation of the PAK1 activator Rac1 induced the formation of a triple complex of Rac1, PAK1 and Mek1, independent of the kinase activity of PAK1. These data suggest that PAK1 can stimulate...... MEK activity in a kinase independent manner, probably by serving as a scaffold to facilitate interaction of c-Raf....

  11. Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure.

    Science.gov (United States)

    Laurent, Olivier; Gomolka, Maria; Haylock, Richard; Blanchardon, Eric; Giussani, Augusto; Atkinson, Will; Baatout, Sarah; Bingham, Derek; Cardis, Elisabeth; Hall, Janet; Tomasek, Ladislav; Ancelet, Sophie; Badie, Christophe; Bethel, Gary; Bertho, Jean-Marc; Bouet, Ségolène; Bull, Richard; Challeton-de Vathaire, Cécile; Cockerill, Rupert; Davesne, Estelle; Ebrahimian, Teni; Engels, Hilde; Gillies, Michael; Grellier, James; Grison, Stephane; Gueguen, Yann; Hornhardt, Sabine; Ibanez, Chrystelle; Kabacik, Sylwia; Kotik, Lukas; Kreuzer, Michaela; Lebacq, Anne Laure; Marsh, James; Nosske, Dietmar; O'Hagan, Jackie; Pernot, Eileen; Puncher, Matthew; Rage, Estelle; Riddell, Tony; Roy, Laurence; Samson, Eric; Souidi, Maamar; Turner, Michelle C; Zhivin, Sergey; Laurier, Dominique

    2016-06-01

    The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation.

  12. Concerted Practice-Based Actions in Intimate Partner and Family Violence: When the Children’s Well-Being Is the Central Concern

    Directory of Open Access Journals (Sweden)

    Geneviève Lessard

    2014-09-01

    Full Text Available In Canada, the exposure of children to intimate partner violence is, along with negligence, one of the most frequent forms of maltreatment. Intimate partner violence raises important issues with regard to child custody and to the exercising of parental roles. The aid provided for children exposed to intimate partner violence covers a range of programs, in particular community services specializing in intimate partner violence, frontline social and health services, and child protection. However, these resource services do not share the same missions, or the same understanding of the problems and possible solutions, since they often operate in parallel networks. The complex situations of families confronted with intimate partner violence present considerable challenges in terms of collaboration between the different organizations. Action research was employed to develop an innovative concertation strategy that fostered collaboration between practitioners from different family resource services. The strategy, which was implemented in the Québec City region between 2011 and 2013, was then evaluated. This article presents the results of this evaluation as well as the positive outcomes that the concertation strategy had for the practitioners’ practice and for the improvement of family services.

  13. The Roles of Protein Kinases in Learning and Memory

    Science.gov (United States)

    Giese, Karl Peter; Mizuno, Keiko

    2013-01-01

    In the adult mammalian brain, more than 250 protein kinases are expressed, but only a few of these kinases are currently known to enable learning and memory. Based on this information it appears that learning and memory-related kinases either impact on synaptic transmission by altering ion channel properties or ion channel density, or regulate…

  14. Interplay between usability evaluation and software development (I-USED 2009)

    DEFF Research Database (Denmark)

    Abrahão, S.; Hornbæk, Kasper Anders Søren; Law, E.

    2009-01-01

    This workshop is aimed at bringing together researchers and practitioners from the Human-Computer Interaction (HCI) and Software Engineering (SE) fields to determine the state-of-the-art in the interplay between usability evaluation and software development and to generate ideas for new...... and improved relations between these activities. The aim is to base the determination of the current state on empirical studies. Presentations of new ideas on how to improve the interplay between HCI & SE to the design of usable software systems should also be based on empirical studies....

  15. A teaching and learning sequence about the interplay of chance and determinism in nonlinear systems

    International Nuclear Information System (INIS)

    Stavrou, D; Duit, R; Komorek, M

    2008-01-01

    A teaching and learning sequence aimed at introducing upper secondary school students to the interplay between chance and determinism in nonlinear systems is presented. Three experiments concerning nonlinear systems (deterministic chaos, self-organization and fractals) and one experiment concerning linear systems are introduced. Thirty upper secondary students' capabilities and difficulties in understanding the scientific point of view were investigated, using a teaching experiment design. The results show that most students were capable of sound explanations concerning the interplay of chance and determinism in nonlinear systems

  16. Realtime Interaction Analysis of Social Interplay in a Multimodal Musical-Sonic Interaction Context

    DEFF Research Database (Denmark)

    Hansen, Anne-Marie

    2010-01-01

    This paper presents an approach to the analysis of social interplay among users in a multimodal interaction and musical performance situation. The approach consists of a combined method of realtime sensor data analysis for the description and interpretation of player gestures and video micro......-analysis methods used to describe the interaction situation and the context in which the social interplay takes place. This combined method is used in an iterative process, where the design of interactive games with musical-sonic feedback is improved according to newly discovered understandings and interpretations...

  17. Activation of protein kinase A and exchange protein directly activated by cAMP promotes adipocyte differentiation of human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Jia, Bingbing; Madsen, Lise; Petersen, Rasmus Koefoed

    2012-01-01

    ) and exchange protein directly activated by cAMP (Epac) in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS). We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical for this process even in the presence......Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA...... results emphasize the need for cAMP signaling in concert with treatment with a PPARγ or PPARδ agonist to secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells....

  18. Kinase impact assessment in the landscape of fusion genes that retain kinase domains: a pan-cancer study

    Science.gov (United States)

    Kim, Pora; Jia, Peilin; Zhao, Zhongming

    2018-01-01

    Abstract Assessing the impact of kinase in gene fusion is essential for both identifying driver fusion genes (FGs) and developing molecular targeted therapies. Kinase domain retention is a crucial factor in kinase fusion genes (KFGs), but such a systematic investigation has not been done yet. To this end, we analyzed kinase domain retention (KDR) status in chimeric protein sequences of 914 KFGs covering 312 kinases across 13 major cancer types. Based on 171 kinase domain-retained KFGs including 101 kinases, we studied their recurrence, kinase groups, fusion partners, exon-based expression depth, short DNA motifs around the break points and networks. Our results, such as more KDR than 5′-kinase fusion genes, combinatorial effects between 3′-KDR kinases and their 5′-partners and a signal transduction-specific DNA sequence motif in the break point intronic sequences, supported positive selection on 3′-kinase fusion genes in cancer. We introduced a degree-of-frequency (DoF) score to measure the possible number of KFGs of a kinase. Interestingly, kinases with high DoF scores tended to undergo strong gene expression alteration at the break points. Furthermore, our KDR gene fusion network analysis revealed six of the seven kinases with the highest DoF scores (ALK, BRAF, MET, NTRK1, NTRK3 and RET) were all observed in thyroid carcinoma. Finally, we summarized common features of ‘effective’ (highly recurrent) kinases in gene fusions such as expression alteration at break point, redundant usage in multiple cancer types and 3′-location tendency. Collectively, our findings are useful for prioritizing driver kinases and FGs and provided insights into KFGs’ clinical implications. PMID:28013235

  19. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments

    Energy Technology Data Exchange (ETDEWEB)

    Stambaugh, Cassandra [Department of Physics, University of South Florida, Tampa, Florida 33612 (United States); Nelms, Benjamin E. [Canis Lupus LLC, Merrimac, Wisconsin 53561 (United States); Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida 33612 (United States)

    2013-09-15

    Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D{sub 99%}), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from

  20. Roles of Apicomplexan protein kinases at each life cycle stage.

    Science.gov (United States)

    Kato, Kentaro; Sugi, Tatsuki; Iwanaga, Tatsuya

    2012-06-01

    Inhibitors of cellular protein kinases have been reported to inhibit the development of Apicomplexan parasites, suggesting that the functions of protozoan protein kinases are critical for their life cycle. However, the specific roles of these protein kinases cannot be determined using only these inhibitors without molecular analysis, including gene disruption. In this report, we describe the functions of Apicomplexan protein kinases in each parasite life stage and the potential of pre-existing protein kinase inhibitors as Apicomplexan drugs against, mainly, Plasmodium and Toxoplasma. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling.

    Science.gov (United States)

    Nyati, Shyam; Schinske-Sebolt, Katrina; Pitchiaya, Sethuramasundaram; Chekhovskiy, Katerina; Chator, Areeb; Chaudhry, Nauman; Dosch, Joseph; Van Dort, Marcian E; Varambally, Sooryanarayana; Kumar-Sinha, Chandan; Nyati, Mukesh Kumar; Ray, Dipankar; Walter, Nils G; Yu, Hongtao; Ross, Brian Dale; Rehemtulla, Alnawaz

    2015-01-06

    Transforming growth factor-β (TGF-β) signaling regulates cell proliferation and differentiation, which contributes to development and disease. Upon binding TGF-β, the type I receptor (TGFBRI) binds TGFBRII, leading to the activation of the transcription factors SMAD2 and SMAD3. Using an RNA interference screen of the human kinome and a live-cell reporter for TGFBR activity, we identified the kinase BUB1 (budding uninhibited by benzimidazoles-1) as a key mediator of TGF-β signaling. BUB1 interacted with TGFBRI in the presence of TGF-β and promoted the heterodimerization of TGFBRI and TGFBRII. Additionally, BUB1 interacted with TGFBRII, suggesting the formation of a ternary complex. Knocking down BUB1 prevented the recruitment of SMAD3 to the receptor complex, the phosphorylation of SMAD2 and SMAD3 and their interaction with SMAD4, SMAD-dependent transcription, and TGF-β-mediated changes in cellular phenotype including epithelial-mesenchymal transition (EMT), migration, and invasion. Knockdown of BUB1 also impaired noncanonical TGF-β signaling mediated by the kinases AKT and p38 MAPK (mitogen-activated protein kinase). The ability of BUB1 to promote TGF-β signaling depended on the kinase activity of BUB1. A small-molecule inhibitor of the kinase activity of BUB1 (2OH-BNPP1) and a kinase-deficient mutant of BUB1 suppressed TGF-β signaling and formation of the ternary complex in various normal and cancer cell lines. 2OH-BNPP1 administration to mice bearing lung carcinoma xenografts reduced the amount of phosphorylated SMAD2 in tumor tissue. These findings indicated that BUB1 functions as a kinase in the TGF-β pathway in a role beyond its established function in cell cycle regulation and chromosome cohesion. Copyright © 2015, American Association for the Advancement of Science.

  2. Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase*S⃞

    Science.gov (United States)

    Kang, Nam Joo; Lee, Ki Won; Lee, Dong Eun; Rogozin, Evgeny A.; Bode, Ann M.; Lee, Hyong Joo; Dong, Zigang

    2008-01-01

    Cocoa was shown to inhibit chemically induced carcinogenesis in animals and exert antioxidant activity in humans. However, the molecular mechanisms of the chemopreventive potential of cocoa and its active ingredient(s) remain unknown. Here we report that cocoa procyanidins inhibit neoplastic cell transformation by suppressing the kinase activity of mitogen-activated protein kinase kinase (MEK). A cocoa procyanidin fraction (CPF) and procyanidin B2 at 5 μg/ml and 40 μm, respectively, inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ mouse epidermal (JB6 P+) cells by 47 and 93%, respectively. The TPA-induced promoter activity and expression of cyclooxygenase-2, which is involved in tumor promotion and inflammation, were dose-dependently inhibited by CPF or procyanidin B2. The activation of activator protein-1 and nuclear factor-κB induced by TPA was also attenuated by CPF or procyanidin B2. The TPA-induced phosphorylation of MEK, extracellular signal-regulated kinase, and p90 ribosomal s6 kinase was suppressed by CPF or procyanidin B2. In vitro and ex vivo kinase assay data demonstrated that CPF or procyanidin B2 inhibited the kinase activity of MEK1 and directly bound with MEK1. CPF or procyanidin B2 suppressed JB6 P+ cell transformation induced by epidermal growth factor or H-Ras, both of which are known to be involved in MEK/ERK signal activation. In contrast, theobromine (up to 80 μm) had no effect on TPA-induced transformation, cyclooxygenase-2 expression, the transactivation of activator protein-1 or nuclear factor-κB, or MEK. Notably, procyanidin B2 exerted stronger inhibitory effects compared with PD098059 (a well known pharmacological inhibitor of MEK) on MEK1 activity and neoplastic cell transformation. PMID:18519570

  3. Tyrosine kinase inhibitors: Multi-targeted or single-targeted?

    Science.gov (United States)

    Broekman, Fleur; Giovannetti, Elisa; Peters, Godefridus J

    2011-02-10

    Since in most tumors multiple signaling pathways are involved, many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases. The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL, SCR, platelet derived growth factor, vascular endothelial growth factor receptor and epidermal growth factor receptor families. Both multi-kinase inhibitors and single-kinase inhibitors have advantages and disadvantages, which are related to potential resistance mechanisms, pharmacokinetics, selectivity and tumor environment. In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist. Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor. Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity, while differences in gene expression exist between tumor and stromal cells. Considering these aspects, one type of inhibitor can generally not be preferred above the other, but will depend on the specific genetic constitution of the patient and the tumor, allowing personalized therapy. The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered (epi)genetics of the tumor. This strategy might result in treatment by a single multi kinase inhibitor for one patient, but in treatment by a couple of single kinase inhibitors for other patients.

  4. A Global Protein Kinase and Phosphatase Interaction Network in Yeast

    Science.gov (United States)

    Breitkreutz, Ashton; Choi, Hyungwon; Sharom, Jeffrey R.; Boucher, Lorrie; Neduva, Victor; Larsen, Brett; Lin, Zhen-Yuan; Breitkreutz, Bobby-Joe; Stark, Chris; Liu, Guomin; Ahn, Jessica; Dewar-Darch, Danielle; Reguly, Teresa; Tang, Xiaojing; Almeida, Ricardo; Qin, Zhaohui Steve; Pawson, Tony; Gingras, Anne-Claude; Nesvizhskii, Alexey I.; Tyers, Mike

    2011-01-01

    The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses. PMID:20489023

  5. Protein phosphatases active on acetyl-CoA carboxylase phosphorylated by casein kinase I, casein kinase II and the cAMP-dependent protein kinase

    International Nuclear Information System (INIS)

    Witters, L.A.; Bacon, G.W.

    1985-01-01

    The protein phosphatases in rat liver cytosol, active on rat liver acetyl-CoA carboxylase (ACC) phosphorylated by casein kinase I, casein kinase II and the cAMP-dependent protein kinase, have been partially purified by anion-exchange and gel filtration chromatography. The major phosphatase activities against all three substrates copurify through fractionation and appear to be identical to protein phosphatases 2A1 and 2A2. No unique protein phosphatase active on 32 P-ACC phosphorylated by the casein kinases was identified

  6. A Third Revolution in Linguistics: The Interplay between the Verbal and Non-Verbal

    Science.gov (United States)

    Liu, Jun

    2009-01-01

    This article regards Saussure's social, static and structural perspective and Chomsky's individual, generative and formal perspective as two revolutions in linguistics in the 20th century. A third revolution is already on the way. This is characterised by considering the individual's mental mechanisms in relation to the interplay between verbal…

  7. Fostering Students' Moderation Competence: The Interplay between Social Relatedness and Perceived Competence

    Science.gov (United States)

    Bürgermeister, Anika; Ringeisen, Tobias; Raufelder, Diana

    2016-01-01

    Using a longitudinal design, the present study examined whether two teaching concepts that varied in their capacity to foster students' self-determination affected students' sense of social relatedness and their perceived moderation competence, as well as the interplay between these two components and the students' performance during a moderation…

  8. Road pricing policy process : The interplay between policy actors, the media and public

    NARCIS (Netherlands)

    Ardiç, O.

    2015-01-01

    Although road pricing policies are generally seen as an effective measure to deal with transport related problems (e.g. congestion), the number of implemented road pricing schemes is relatively limited. The thesis aims to gain insights into complex interplay between policy actors, media and public

  9. The dynamic interplay of microbiota and mucosa drives establishment of homeostasis in conventionalized mice

    NARCIS (Netherlands)

    Aidy, El S.F.

    2012-01-01

    The intimate interplay between gut microbiota, host, and nutrient flow is crucial in defining the health status of the host. During microbial conventionalization of germfree mice, tightly regulated molecular responses assure the establishment of homeostasis and immune tolerance towards the

  10. A light scalar-HLQBS interplay and a HLQBS weak decay test

    International Nuclear Information System (INIS)

    Kozlov, G.A.

    1993-01-01

    The interplay between a light scalar boson (Higgs) and a heavy-light quark bound system (HLQBS) in the flavour-changing of the heavy quarks is presented. The estimations of the transition form-factors in the weak leptonic decays of the pseudoscalar HLQBS are proposed. (orig.)

  11. Interplay between MRP Inhibition and Metabolism of MRP Inhibitors: The Case of Curcumin

    NARCIS (Netherlands)

    Wortelboer, H.M.; Usta, M.; Velde, A.E. van der; Boersma, M.G.; Spenkelink, B.; Zanden, J.J. van; Rietjens, I.M.C.M.; Bladeren, P.J. van; Cnubben, N.H.P.

    2003-01-01

    The multidrug resistance proteins MRP1 and MRP2 are efflux transporters with broad substrate specificity, including glutathione, glucuronide, and sulfate conjugates. In the present study, the interaction of the dietary polyphenol curcumin with MRP1 and MRP2 and the interplay between

  12. Interplay between MRP-inhibition and metabolism of MRP-inhibitors: the case of curcumin

    NARCIS (Netherlands)

    Wortelboer, H.M.; Usta, M.; Velde, van der A.E.; Boersma, M.G.; Spenkelink, A.; Zanden, van J.J.; Rietjens, I.M.C.M.; Bladeren, van P.J.; Cnubben, N.H.P.

    2003-01-01

    The multidrug resistance proteins MRP1 and MRP2 are efflux transporters with broad substrate specificity, including glutathione, glucuronide, and sulfate conjugates. In the present study, the interaction of the dietary polyphenol curcumin with MRP1 and MRP2 and the interplay between

  13. The Interplay of Occupational Motivation and Well-Being during the Transition from University to Work

    Science.gov (United States)

    Haase, Claudia M.; Heckhausen, Jutta; Silbereisen, Rainer K.

    2012-01-01

    A successful entry into work is one of the key developmental tasks in young adulthood. The present 4-wave longitudinal study examined the interplay between occupational motivation (i.e., goal engagement and goal disengagement) and well-being (i.e., satisfaction with life, satisfaction with work, satisfaction with partnership, positive affect,…

  14. Dialectics of Development: Teacher Identity Formation in the Interplay of Ideal Ego and Ego Ideal

    Science.gov (United States)

    Clarke, Matthew; Michell, Michael; Ellis, Neville John

    2017-01-01

    This paper results from research examining pre-service teacher development in relation to experiences of mentoring during the Professional Experience component of their programme. The paper focuses on the interplay between pre-service teachers' personal aspirations for their own practice and identity and their perceptions of more socialized and…

  15. A Teaching and Learning Sequence about the Interplay of Chance and Determinism in Nonlinear Systems

    Science.gov (United States)

    Stavrou, D.; Duit, R.; Komorek, M.

    2008-01-01

    A teaching and learning sequence aimed at introducing upper secondary school students to the interplay between chance and determinism in nonlinear systems is presented. Three experiments concerning nonlinear systems (deterministic chaos, self-organization and fractals) and one experiment concerning linear systems are introduced. Thirty upper…

  16. Can we adequately represent the spatial interplay between humans and nature?

    Science.gov (United States)

    One of the challenges remaining before ecosystem services assessments can become part of mainstream decision making is how to spatially represent the interplay of nature as a whole and humans. Nature’s ecosystems act as natural capital by producing things (i.e. stocks and ...

  17. The interplay of demography and selection during maize domestication and expansion

    Science.gov (United States)

    The history of maize has been characterized by major demographic events including changes in population size associated with domestication and subsequent range expansion as well as gene flow with wild relatives. This complex demographic history and its interplay with selection have shaped diversity ...

  18. How Spatial Abilities and Dynamic Visualizations Interplay When Learning Functional Anatomy with 3D Anatomical Models

    Science.gov (United States)

    Berney, Sandra; Bétrancourt, Mireille; Molinari, Gaëlle; Hoyek, Nady

    2015-01-01

    The emergence of dynamic visualizations of three-dimensional (3D) models in anatomy curricula may be an adequate solution for spatial difficulties encountered with traditional static learning, as they provide direct visualization of change throughout the viewpoints. However, little research has explored the interplay between learning material…

  19. Quantification of interplay and gradient effects for lung stereotactic ablative radiotherapy (SABR) treatments.

    Science.gov (United States)

    Tyler, Madelaine K

    2016-01-08

    This study quantified the interplay and gradient effects on GTV dose coverage for 3D CRT, dMLC IMRT, and VMAT SABR treatments for target amplitudes of 5-30 mm using 3DVH v3.1 software incorporating 4D Respiratory MotionSim (4D RMS) module. For clinically relevant motion periods (5 s), the interplay effect was small, with deviations in the minimum dose covering the target volume (D99%) of less than ± 2.5% for target amplitudes up to 30 mm. Increasing the period to 60 s resulted in interplay effects of up to ± 15.0% on target D99% dose coverage. The gradient effect introduced by target motion resulted in deviations of up to ± 3.5% in D99% target dose coverage. VMAT treatments showed the largest deviation in dose metrics, which was attributed to the long delivery times in comparison to dMLC IMRT. Retrospective patient analysis indicated minimal interplay and gradient effects for patients treated with dMLC IMRT at the NCCI.

  20. The Interplay of Spatial Attentional Biases and Mental Codes in VSTM: Developmentally Informed Hypotheses

    Science.gov (United States)

    Shimi, Andria; Scerif, Gaia

    2015-01-01

    What cognitive processes influence how well we maintain information in visual short-term memory (VSTM)? We used a developmentally informed design to delve into the interplay of top-down spatial biases with the nature of the internal memory codes, motivated by documented changes for both factors over childhood. Seven-year-olds, 11-year-olds, and…