WorldWideScience

Sample records for kandahar generally met

  1. Water/Pasture Assessment of Registan Desert (Kandahar and Helmand Provinces)

    OpenAIRE

    Toderich, Kristina; Tsukatani, Tsuneo

    2005-01-01

    The desolate desert in Afghanistan's Kandahar and Helmand Provinces was previously populated by thousands of pastoralists until a devastating drought decimated animal herds and forced them to live as IDPs (Internally Displaced Persons) on land bordering the desert. Through funding from UNAMA (United Nations Assistance Mission in Afghanistan), this report assesses conditions in the Registan Desert and border regions to devise solutions to the problems facing Registan Kuchi nomads. A work plan ...

  2. Preservation of general intelligence following traumatic brain injury: contributions of the Met66 brain-derived neurotrophic factor.

    Directory of Open Access Journals (Sweden)

    Aron K Barbey

    Full Text Available Brain-derived neurotrophic factor (BDNF promotes survival and synaptic plasticity in the human brain. The Val66Met polymorphism of the BDNF gene interferes with intracellular trafficking, packaging, and regulated secretion of this neurotrophin. The human prefrontal cortex (PFC shows lifelong neuroplastic adaption implicating the Val66Met BDNF polymorphism in the recovery of higher-order executive functions after traumatic brain injury (TBI. In this study, we examined the effect of this BDNF polymorphism on the preservation of general intelligence following TBI. We genotyped a sample of male Vietnam combat veterans (n = 156 consisting of a frontal lobe lesion group with focal penetrating head injuries for the Val66Met BDNF polymorphism. Val/Met did not differ from Val/Val genotypes in general cognitive ability before TBI. However, we found substantial average differences between these groups in general intelligence (≈ half a standard deviation or 8 IQ points, verbal comprehension (6 IQ points, perceptual organization (6 IQ points, working memory (8 IQ points, and processing speed (8 IQ points after TBI. These results support the conclusion that Val/Met genotypes preserve general cognitive functioning, whereas Val/Val genotypes are largely susceptible to TBI.

  3. The impact of the Catechol-O-methyltransferase Val158Met polymorphism on survival in the general population – the HUNT study

    Directory of Open Access Journals (Sweden)

    Skorpen Frank

    2007-06-01

    Full Text Available Abstract Background The catechol-O-methyltransferase (COMT gene contains a functional polymorphism, Val158Met which has been related to common diseases like cancer, psychiatric illness and myocardial infarction. Whether the Val158Met polymorphism is associated with survival has not been evaluated in the general population. The aim of this prospective study was to evaluate the impact of codon 158 COMT gene polymorphism on survival in a population-based cohort. Methods The sample comprised 2979 non-diabetic individuals who participated in the Nord-Trøndelag Health Study (HUNT in the period 1995–97. The subjects were followed up with respect to mortality throughout year 2004. Results 212 men and 183 women died during the follow up. No association between codon 158 COMT gene polymorphism and survival was found. The unadjusted relative risk of death by non-ischemic heart diseases with Met/Met or Met/Val genotypes was 3.27 (95% confidence interval, 1.19–9.00 compared to Val/Val genotype. When we adjusted for age, gender, smoking, coffee intake and body mass index the relative risk decreased to 2.89 (95% confidence interval, 1.04–8.00. Conclusion During 10 year of follow-up, the Val158Met polymorphism had no impact on survival in a general population. Difference in mortality rates from non-ischemic heart diseases may be incidental and should be evaluated in other studies.

  4. Estructura metálica del edificio social de la Mutua General de Seguros Barcelona – España

    Directory of Open Access Journals (Sweden)

    Busquets, Xavier

    1977-10-01

    Full Text Available This describes the solution adopted for the Mutua General de Seguros structure on the Diagonal in Barcelona. The building consists of six general basements and two elevated wings, one of thirteen stories and another of four, joined together on the third and second floors. The problems which had to be overcome were various in nature: from anchoring the concrete blocks in the underground floors to achieving maximum clear space —there are no intermediate supports on the office floors— this was achieved satisfactorily, on the higher floors by means of large span porticos, made up of two well-defined parts (the ground floor portico and the upper floor assembly], from both a structural and esthetic point of view.Se describe la solución adoptada para estructura de la Mutua General de Seguros, en la Diagonal de Barcelona. El edificio se compone de seis sótanos generales y dos bloques elevados, uno de trece plantas y otro de cuatro, debidamente enlazados por la segunda y tercera. Los problemas planteados fueron de muy diversa índole: desde la sujeción de las pantallas de hormigón de las plantas enterradas, hasta la consecución de la máxima diafanidad —en todas las plantas de oficinas no existen soportes intermedios— en las plantas altas a base de pórticos de gran luz, compuestos de dos partes bien definidas (el pórtico de planta baja y el conjunto de las superiores y acertadamente resueltos, desde el doble punto de vista estructural y estético.

  5. Topographic Map of Quadrangle 3164, Lashkargah (605) and Kandahar (606) Quadrangles, Afghanistan

    Science.gov (United States)

    Bohannon, Robert G.

    2006-01-01

    This map was produced from several larger digital datasets. Topography was derived from Shuttle Radar Topography Mission (SRTM) 85-meter digital data. Gaps in the original dataset were filled with data digitized from contours on 1:200,000-scale Soviet General Staff Sheets (1978-1997). Contours were generated by cubic convolution averaged over four pixels using TNTmips surface-modeling capabilities. Minor artifacts resulting from the auto-contouring technique are present. Streams were auto-generated from the SRTM data in TNTmips as flow paths. Flow paths were limited in number by their Horton value on a quadrangle-by-quadrangle basis. Peak elevations were averaged over an area measuring 85 m by 85 m (represented by one pixel), and they are slightly lower than the highest corresponding point on the ground. Cultural data were extracted from files downloaded from the Afghanistan Information Management Service (AIMS) Web site (http://www.aims.org.af). The AIMS files were originally derived from maps produced by the Afghanistan Geodesy and Cartography Head Office (AGCHO). Because cultural features were not derived from the SRTM base, they do not match it precisely. Province boundaries are not exactly located. This map is part of a series that includes a geologic map, a topographic map, a Landsat natural-color-image map, and a Landsat false-color-image map for the USGS/AGS (Afghan Geological Survey) quadrangles covering Afghanistan. The maps for any given quadrangle have the same open-file number but a different letter suffix, namely, -A, -B, -C, and -D for the geologic, topographic, Landsat natural-color, and Landsat false-color maps, respectively. The open-file report (OFR) numbers for each quadrangle range in sequence from 1092 - 1123. The present map series is to be followed by a second series, in which the geology is reinterpreted on the basis of analysis of remote-sensing data, limited fieldwork, and library research. The second series is to be produced by the USGS

  6. Local-area-enhanced, 2.5-meter resolution natural-color and color-infrared satellite-image mosaics of the Kandahar mineral district in Afghanistan: Chapter Z in Local-area-enhanced, high-resolution natural-color and color-infrared satellite-image mosaics of mineral districts in Afghanistan

    Science.gov (United States)

    Davis, Philip A.

    2013-01-01

    -squares analysis. The resolution of the multispectral image mosaic was then increased to that of the panchromatic image mosaic using the SPARKLE logic, which is described in Davis (2006). Each of the four-band images within the resolution-enhanced image mosaic was individually subjected to a local-area histogram stretch algorithm (described in Davis, 2007), which stretches each band's picture element based on the digital values of all picture elements within a 500-m radius. The final databases, which are provided in this DS, are three-band, color-composite images of the local-area- enhanced, natural-color data (the blue, green, and red wavelength bands) and color-infrared data (the green, red, and near-infrared wavelength bands). All image data were initially projected and maintained in Universal Transverse Mercator (UTM) map projection using the target area's local zone (42 for Kandahar) and the WGS84 datum. The final image mosaics were subdivided into eight overlapping tiles or quadrants because of the large size of the target area. The eight image tiles (or quadrants) for the Kandahar area are provided as embedded geotiff images, which can be read and used by most geographic information system (GIS) and image-processing software. The tiff world files (tfw) are provided, even though they are generally not needed for most software to read an embedded geotiff image. Within the Kandahar study area, two subareas were designated for detailed field investigations (that is, the Obatu-Shela and Sekhab-Zamto Kalay subareas); these subareas were extracted from the area's image mosaic and are provided as separate embedded geotiff images.

  7. Fatty acid dietary intake in the general French population: are the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) national recommendations met?

    Science.gov (United States)

    Tressou, Jessica; Moulin, Philippe; Vergès, Bruno; Le Guillou, Céline; Simon, Noémie; Pasteau, Stéphane

    2016-12-01

    Quantity and quality of fatty acids (FA) in diet influence CVD risk. Consequently, health authorities promote recommended dietary intakes for FA, looking for optimal intakes in a primary prevention of CVD perspective. In parallel, a few data are available detailing intakes in national populations. The objective of the present study was to perform a large analysis combining the data of the French National Survey INCA 2 on food consumption performed in 2006 and 2007, and the nutritional content of food consumed in France updated in 2013 by the French Information Centre on Food Quality, to explore in details the FA intakes in French adults using the most recent available data. To compare the discrepancies in the observed intake levels with the French recommended levels, a weighted fat adherence score was built combining intakes of the different FA. Individual scores were computed in relation to official recommendations, and potential explanatory factors were identified. These data show that SFA intakes are persistently higher than national recommendations, combined with low intakes of MUFA and PUFA, particularly long-chain n-3 FA. Only 14·6 % of the French population met DHA intake recommendation, 7·8 % for EPA and 21·6 % for SFA. This situation remains unfavourable in terms of primary prevention of CVD. Consuming fish and other sources of n-3 FA, living in the south of France, being female, having a higher education level, and low alcohol consumption were associated with a healthier fat adherence score.

  8. Sereniteit met een dip

    NARCIS (Netherlands)

    dr Ed de Jonge

    2015-01-01

    Boekbespreking van Serendipiteit. De ongezochte vondst. Het boek opent met een verzameling van citaten die direct of indirect met het onderwerp samenhangen. Daarna volgt een kort voorwoord van Hans Clevers, de toenmalige president van de KNAW, die een lans breekt voor serendipiteit in de biologie.

  9. Ervaringen met beeldverwerking.

    NARCIS (Netherlands)

    Meuleman, J.

    1989-01-01

    Verslag van een werkbezoek aan het Franse instituut Cemagref, met nadruk op beeldverwerking. Toepassingen van beeldverwerking zijn onder andere: een plukrobot voor appels; het detecteren van oppervlaktebeschadigingen bij appels; het detecteren van breuk in eieren; remote sensing

  10. Nisine geholpen met hordentechnologie

    NARCIS (Netherlands)

    Jong, de L.S.

    2001-01-01

    Een combinatie van nisine met carvacrol, thymol of carvon leidde tot een synergistische reductie van het aantal levensvatbare cellen van Listeria monocytogenes en Bacillus cereus. Verslag van een promotieonderzoek

  11. Autorijden met ADHD

    NARCIS (Netherlands)

    Fuermaier, Anselm B.M.; Tucha, Lara; de Vries, Stefanie M.; Koerts, Janneke; de Waard, Dick; Brookhuis, Karel; Tucha, Oliver

    Volwassenen met attention deficit hyperactivity disorder (ADHD) hebben uiteenlopende cognitieve beperkingen, die een aanzienlijke invloed kunnen hebben op verschillende aspecten van het dagelijks leven. Een van deze aspecten is het besturen van een auto. Autorijden is een belangrijke activiteit in

  12. When Historiography Met Epistemology

    Directory of Open Access Journals (Sweden)

    Jean-François Stoffel

    2017-06-01

    Full Text Available Review of Bordoni, Stefano. When historiography met epistemology: Sophisticated histories and philosophies of science in French-speaking countries in the second half of the nineteenth century. Reviewed by Jean-François Stoffel.

  13. Jeugd met beperkingen

    NARCIS (Netherlands)

    Sjoerd Kooiker

    2006-01-01

    Voor kinderen en jongeren met een lichamelijke of verstandelijke beperking is 'gewoon meedoen' in de samenleving geen vanzelfsprekendheid.  Zij ervaren vaak meer obstakels bij het naar school gaan, het vinden van een baan en in hun vrijetijdsbesteding dan andere kinderen en jongeren. Ook

  14. Studeren met Hans Rosenberg

    NARCIS (Netherlands)

    Rutten, R.J.

    2001-01-01

    Hoe was het om in de jaren zestig te studeren? Laat ik een terugblik ophangen aan een studiemakker, Hans Rosenberg. We vormden samen de sterrekundejaar- gang 1961. Hans studeerde af in 1966 met hoofdvak wiskunde, promoveerde op radiostralingsprocessen in de zonnecorona in 1973, verliet de

  15. SPSS met syntax

    NARCIS (Netherlands)

    Grotenhuis, H.F. te; Visscher, C.A.M.

    2007-01-01

    Dit boekje wijkt af van de gebruikelijke statistiekboeken omdat het sec gaat over het bekende statistische computerprogramma SPSS, en dan alleen nog de oorspronkelijke variant waarin wordt gewerkt met syntax (intypen commando's -zoals bij DOS) i.p.v. de later ontwikkelde 'Windows-schil' (aanklikken

  16. Met kerse op met -konstruksies 1 : 'n Verwysingspuntperspektief ...

    African Journals Online (AJOL)

    Met kerse op met-konstruksies1: 'n Verwysingspuntperspektief. Johanna Messerschmidt, Luna Bergh. Abstract. This article analyses the usage of the Afrikaans preposition met ('with'). The analysis is done within the framework of Cognitive Linguistics and more specifically within the model proposed by Langacker (1993) ...

  17. MMPM - Mars MetNet Precursor Mission

    Science.gov (United States)

    Harri, A.-M.; Schmidt, W.; Pichkhadze, K.; Linkin, V.; Vazquez, L.; Uspensky, M.; Polkko, J.; Genzer, M.; Lipatov, A.; Guerrero, H.; Alexashkin, S.; Haukka, H.; Savijarvi, H.; Kauhanen, J.

    2008-09-01

    MetNet Mars Mission will provide a crucial support for the safety of large landing missions in general and manned Mars missions in particular. Accurate knowledge of atmospheric conditions and weather data is essential to guarantee safe landings of the forthcoming Mars mission elements. The MetNet Mars Mission is exactly this type of tool that is needed both for the Martian atmospheric science as well as for the mission safety issues.

  18. Gezondheidsrisico's in verband met het werken met Pentachloorfenol : een onderzoek

    NARCIS (Netherlands)

    Geuskens, R.B.M.; Nossent, S.M.; Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A.; Zielhuis, R.l.

    1989-01-01

    De gezondheidsrisico's i.v.m. het werken met pentachloorfenol (PCP) wordt geevalueerd. Het gebruik van PCP in Nederlandse arbeidssituaties neemt sterk af en is beperkt tot de formulering van emeltenkorrels en de, met name preventieve, houtverduurzaming. De totale risicopopulatie is niet omvangrijk

  19. Microbewerking met behulp van lasers

    NARCIS (Netherlands)

    Ezendam, M.M.M.

    1994-01-01

    Het bewerken van materialen met behulp van lasers staat momenteel enorm in de belangstelling, en terecht. De ontwikkeling van bestaande en nieuwe typen lasers staat alles behalve stil. Ontwikkelingen bevinden zich met name in het gebied van hogere vermogens, betere bundelkwaliteit en hogere

  20. Gezondheidsrisico's in verband met het werken met Polychloorbifenylen : een onderzoek

    NARCIS (Netherlands)

    Geuskens, R.B.M.; Nossent, S.M.; Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A.; Zielhuis, R.L.

    1989-01-01

    Met behulp van gegevens verkregen uit een werkplekinventarisatie naar gegevens over produktie/gebruik, risicopopulatie en (mogelijke) blootstelling aan polychloorbifenylen (PCB's), en een literatuurstudie naar mogelijke schadelijke eigenschappen van PCB's op het reproductiesysteem en/of nageslacht

  1. Cesar-therapie tijdelijk effectiever dan standaardbehandeling door de huisarts bij patiënten met chronische aspecifieke lage rugklachten : gerandomiseerd, gecontroleerd en geblindeerd onderzoek met 1 jaar follow-up [Cesar therapy is temporarily more effective than a standard treatment from the general practitioner in patients with chronic aspecific lower back pain; randomized, controlled and blinded study with a I year follow-up

    NARCIS (Netherlands)

    Hildebrandt, V.H.; Proper, K.I.; Berg, R. van den; Douwes, M.; Heuvel, S.G. van den; Buuren, S. van

    2000-01-01

    Doel van dit onderzoek was het vaststellen van korte- en langetermijneffecten van Cesar-therapie op zelfgerapporteerd herstel en op houdingsverandering bij patiënten met chronische aspecifieke lage rugklachten. Patiënten met chronische aspecifieke lage rugklachten werden, nadat 'informed consent'

  2. La metáfora

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2007-01-01

    2002 y principios de 2003, anteriores a la proclamación de las Juntas de Buen Gobierno. Nuestro objetivo es comprobar cómo las metáforas crean nuevas significaciones, que intentan deshacer una lógica comúnmente asumida, y promover otros modos de comprender la acción y la realidad político-social. Este...

  3. Reactions of Met-Cars

    International Nuclear Information System (INIS)

    Castleman, A.W. Jr.; Guo, B.C.

    1993-01-01

    A new class of metal-carbon complexes, termed metallo-carbohedrenes (Met-Cars), have been discovered to form in a plasma reactor in which early transition metals are vaporized into a stream carrying small hydrocarbon molecules. The initial discovery involved the species Ti 8 c 12 + , while subsequent studies revealed the stability of the anion and, most importantly, the neutral species. Subsequent investigations show that similar molecules, predicted to have a pentagonal dodecahedral structure, can also be formed with vanadium, hafnium, and zirconium. In the case of the latter, more recent investigations have displaced an interesting growth pattern. In particular, pentagonal dodecahedrons with dangling carbon atoms can undergo further growth, adding at least a second and third cage. The latest results on the properties and reactivities of these new cage-like molecular clusters will be discussed

  4. Proef met duurzaam watergebruik in de bollenstreek

    NARCIS (Netherlands)

    Fliegenthart, F.; Dik, P.E.; Groenendijk, P.

    2009-01-01

    In 2007 begon in de Wieringermeer een praktijkproef met alternatieve waterbeheersystemen voor de bollenteelt. Met drie verschillende teeltsystemen wordt onderzoek verricht naar zo optimaal mogelijk gebruik van zoet water door recirculatie en hergebruik. Ook loopt onderzoek naar de emissie van

  5. Differences in MetS marker prevalence between black African and ...

    African Journals Online (AJOL)

    Multiple linear regression analysis, independent of covariates, showed that the albumin:creatinine ratio is explained only by glucose in Africans. Conclusion: African women, as a group, present with few MetS risk factors, and glucose is associated with renal function risk in Africans. Keywords: MetS, metabolic syndrome, ...

  6. Requirements to be met by the operation manual

    International Nuclear Information System (INIS)

    1981-03-01

    The rule applies to the contents and the lay-out of the operating manual for stationary nuclear power plants. The draft contains: 1. General requirement to be met by the contents of the operating manual. The operating manual to be arranged in 4 parts (part 1: internal rules and regulations; part 2: operation overall plant; part 3: incidents; part 4: operation systems). Safety specifications to be included in the manual, the exemption being the system of technical documentation. 2. General requirements to be met by the lay-out of the operating manual. Comprehensibility; legibility; structure and subdivisions; arrangement of the instructions and design of the manuals cover. 3. Requirements to be met by part 1. Defining the various internal rules and regulations (personnel management); rules and regulations concerning inspections and shift work; maintenance and repair; radiation protection; guard duty and admission; alarm; fire protection; first aid. 4. Requirements to be met by part 2. Provisions and operational limitations; limit values important from the point of view of safety; normal operation; anomalous operation; in-service inspections. 6. Requirements to be met by part 3. 7. Annex: Rules, regulations and stipulations mentioned in the rule draft. (orig.)

  7. Vulvair basaalcelcarcinoom met destructieve gevolgen

    NARCIS (Netherlands)

    Blok, Janine L; Reesink-Peters, Nathalie; Diercks, Gilles F H; Reyners, An K L; Terra, Jorrit B

    2012-01-01

    BACKGROUND: Basal cell carcinoma is the most common form of skin cancer. Generally, the prognosis is relatively good and curative surgical treatment is accomplished in the great majority of patients. CASE DESCRIPTION: Here we report a case that illustrates the natural course of a vulvar basal cell

  8. 17 CFR 230.502 - General conditions to be met.

    Science.gov (United States)

    2010-04-01

    ... advertising, including, but not limited to, the following: (1) Any advertisement, article, notice or other communication published in any newspaper, magazine, or similar media or broadcast over television or radio; and... advertising; Provided, however, that publication by an issuer of a notice in accordance with § 230.135c or...

  9. Metsämaisema ulkoilijoiden kokemana

    OpenAIRE

    Vuohijoki, Jaana

    2010-01-01

    Työn aiheena oli tutkia, miten ulkoilijat kokevat metsämaiseman Tampereella. Tavoitteena oli selvittää ulkoilijoiden maisema-arvostuksia sekä suhtautumista metsänhoidon toimenpiteisiin. Tutkimus toteutettiin maastohaastatteluina Tampereella kolmella eri asuinalueella: Hallilassa, Leinolassa ja Tesomajärvellä. Otoskooksi muodostui kymmenen haastattelua aluetta kohti, mutta yhdeltä vastaajalta ei ehditty kysyä kaikkia kysymyksiä. Vastaajat olivat yleisesti ottaen tyytyväisiä alueiden metsän...

  10. Is neurofeedback effectief bij kinderen met ADHD?

    NARCIS (Netherlands)

    de Hen, M.H.; Geurts, H.M.

    2008-01-01

    Kan neurofeedback verantwoord ingezet worden bij de behandeling van kinderen met ADHD? Omdeze vraag te beantwoorden worden zeven recente onderzoeken naar de effectiviteit van neurofeedback bij kinderen met ADHD geanalyseerd. Ondanks dat de resultaten in eerste instantie lijken te suggereren dat

  11. Coriocarcinoma con metástasis pulmonar

    Directory of Open Access Journals (Sweden)

    Vicia Sánchez Abalos

    2014-05-01

    Full Text Available Se presenta el caso clínico de una fémina de 44 años de edad, con 32 semanas de embarazo, la cual fuera ingresada en la Unidad de Cuidados Intensivos del Hospital General Docente "Dr. Juan Bruno Zayas Alfonso" de Santiago de Cuba, por presentar insuficiencia respiratoria aguda como consecuencia de una sepsis. La paciente fue tratada con cefalosporina de tercera generación y ventilación mecánica no invasiva, pero se mantuvieron las características gasométricas de hipoxemia y una mala reacción terapéutica, por lo que se requirió instrumentación de las vías respiratorias y soporte hemodinámico, sin lograr regresión del cuadro clínico, lo cual condujo a un paro cardiorrespiratorio y, con ello, a la muerte. La necropsia mostró un coriocarcinoma del endometrio con metástasis pulmonar

  12. Word je met Donkey Konga een betere muzikant? : Muziek leren spelen met de spelcomputer

    NARCIS (Netherlands)

    Tom Langhorst

    2010-01-01

    Kan de spelcomputer behulpzaam zijn bij de ontwikkeling van het muzikale gevoel? Met die vraag in het achterhoofd bekijkt Tom Langhorst hier kritisch het Nintendo-spel Donkey Konga, waarin de speler mee kan drummen met bekende popsongs.

  13. Met1-linked Ubiquitination in Immune Signalling

    DEFF Research Database (Denmark)

    Fiil, Berthe Katrine; Gyrd-Hansen, Mads

    2014-01-01

    Methionine 1-linked ubiquitin chains (Met1-Ub), or linear ubiquitin, has emerged as a central post-translational modification in innate immune signalling. Molecular machinery that assembles, senses and, more recently, disassembles Met1-Ub has been identified, and technical advances have enabled...... identification of physiological substrates for Met1-Ub in response to activation of innate immune receptors. These discoveries have significantly advanced our understanding of how non-degradative ubiquitin modifications control pro-inflammatory responses mediated by nuclear factor κB and mitogen...

  14. Mars MetNet Mission Payload Overview

    Science.gov (United States)

    Harri, A.-M.; Haukka, H.; Alexashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.

    2012-09-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide crucial scientific data about the Martian atmospheric phenomena.

  15. Gesloten kringloop met omgekeerde osmose of membraandestilatie

    NARCIS (Netherlands)

    Stijger, H.; Os, van E.A.

    2011-01-01

    TNO heeft samen met Wageningen UR Glastuinbouw een inventarisatie uitgevoerd naar geschikte zuiveringstechnieken om de waterstroom op tuinbouwbedrijven gesloten te krijgen. Uit de haalbaarheidstudie komen twee veelbelovende technieken naar voren die op vrij korte termijn inzetbaar zijn: omgekeerde

  16. Mars MetNet Mission Status

    Science.gov (United States)

    Harri, A.-M.; Aleksashkin, S.; Arruego, I.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.; Palin, M.; Nikkanen, T.

    2015-10-01

    New kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semihard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  17. Mars MetNet Precursor Mission Status

    Science.gov (United States)

    Harri, A.-M.; Aleksashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.

    2013-09-01

    We are developing a new kind of planetary exploration mission for Mars in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  18. Bio-composiet : Thermoplastische kunsstof met natuurvezels

    NARCIS (Netherlands)

    Beurden, van K.M.M. (Karin); Goselink, E.A. (Erik)

    2013-01-01

    Een biocomposiet wordt samengesteld uit een vezel en een hars. In dit document worden twee verwerkingsvormen van biocomposieten behandeld: - Vezel/poeder versterkt kunststof (granulaat); - Kunststof plaatmateriaal versterkt met een weefsel (laminaat), ook wel Sizopreg® genoemd. Door een

  19. Intern transport beter te plannen met computer

    NARCIS (Netherlands)

    Annevelink, E.

    1999-01-01

    Verbetering van intern transport in de potplantenteelt. Door getoetste vuistregels te combineren met toegepaste wiskunde is automatische planning van het intern transport binnen handbereik. Dit leidt tot minder transportbewegingen en tijdsbesparing bij het plannen

  20. Fosfaatwerking ogranische meststoffen vergelijkbaar met kunstmest

    NARCIS (Netherlands)

    Ehlert, P.A.I.; Pasterkamp, H.P.

    2000-01-01

    Gegevens in bijgaande tabel: Indicatieve fosfaatgehalten en de relatieve verdeling over mineraalfosfaat en organisch gebonden fosfaat in meststoffen met per mestsoort gegevens over het totaal fosfaatgehalte, het percentage mineraal fosfaat en het percentage organisch fosfaat

  1. Technisch lego met een Duplo-interface

    NARCIS (Netherlands)

    Pimentel, A.; Schipper, D.

    2008-01-01

    Daedalus is een ontwerpflow op systeemniveau waarmee techneuten snel kunnen experimenteren met verschillende multiprocessorarchitecturen tijdens de vroege stadia van het ontwerptraject. Het is het resultaat van tien jaar onderzoek en ontwikkeling binnen de Progress-projecten Artemis en Artemisia.

  2. Extraboard performance : TriMet case study.

    Science.gov (United States)

    2012-02-01

    This paper examines extraboard operations and management at TriMet, the transit provider for the Portland Oregon metropolitan area. The : extraboard consists of a pool of operators who fill open work resulting from absences and other causes. The pape...

  3. Mars MetNet Mission Status

    Science.gov (United States)

    Harri, Ari-Matti; Aleksashkin, Sergei; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Haukka, Harri

    2015-04-01

    New kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. 1. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. 2. Scientific Payload The payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: 1. MetBaro Pressure device 2. MetHumi Humidity device 3. MetTemp Temperature sensors Optical devices: 1. PanCam Panoramic 2. MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer 3. DS Dust sensor The descent processes dynamic properties are monitored by a special 3-axis accelerometer combined with a 3-axis gyrometer. The data will be sent via auxiliary beacon antenna throughout the

  4. MetBaro - Pressure Device for Mars MetNet Lander

    Science.gov (United States)

    Haukka, Harri; Polkko, Jouni; Harri, Ari-Matti; Schmidt, Walter; Leinonen, Jussi; Genzer, Maria; Mäkinen, Teemu

    2010-05-01

    MetNet Mars Mission focused for Martian atmospheric science is based on a new semihard landing vehicle called the MetNet Lander (MNL). The MNL will have a versatile science payload focused on the atmospheric science of Mars. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. MetBaro is the pressure sensor of MetNet Lander designed to work on Martian surface. It is based on Barocap® technology developed by Vaisala, Inc. MetBaro is a capacitive type of sensing device where capasitor plates are moved by ambient pressure. MetBaro device consists of two pressure transducers including a total of 4 Barocap® sensor heads of high-stability and high-resolution types. The long-term stability of MetBaro is in order of 20…50 µBar and resolution a few µBar. MetBaro is small, lightweighed and has low power consumption. It weighs about 50g without wires and controlling FPGA, and consumes 15 mW of power. A similar device has successfully flown in Phoenix mission, where it performed months of measurements on Martian ground. Another device is also part of the Mars Science Laboratory REMS instrument (to be launched in 2011).

  5. MetHumi - Humidity Device for Mars MetNet Lander

    Science.gov (United States)

    Genzer, Maria; Polkko, Jouni; Harri, Ari-Matti; Schmidt, Walter; Leinonen, Jussi; Mäkinen, Teemu; Haukka, Harri

    2010-05-01

    MetNet Mars Mission focused for Martian atmospheric science is based on a new semihard landing vehicle called the MetNet Lander (MNL). The MNL will have a versatile science payload focused on the atmospheric science of Mars. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. MetHumi is the humidity sensor of MetNet Lander designed to work on Martian surface. It is based on Humicap® technology developed by Vaisala, Inc. MetHumi is a capacitive type of sensing device where an active polymer film changes capacitance as function of relative humidity. One MetHumi device package consists of one humidity transducer including three Humicap® sensor heads, an accurate temperature sensor head (Thermocap® by Vaisala, Inc.) and constant reference channels. MetHumi is very small, lightweighed and has low power consumption. It weighs only about 15 g without wires, and consumes 15 mW of power. MetHumi can make meaningful relative humidity measurements in range of 0 - 100%RH down to -70°C ambient temperature, but it survives even -135°C ambient temperature.

  6. Special Inspector General for Afghanistan Reconstruction

    Science.gov (United States)

    2012-04-30

    Kandahar and Bagram airfi elds, Camp Stone , Camp Leatherneck, Forward Operating Base Salerno, USFOR-A headquarters in Kabul, and the U.S. Consulate in... marble , chromite, and placer gold.414 U.S. Assistance This quarter, the MoM and the TFBSO attended two conferences on mining:415 • Mining Indaba Cape

  7. C-MET overexpression and amplification in gliomas.

    Science.gov (United States)

    Kwak, Yoonjin; Kim, Seong-Ik; Park, Chul-Kee; Paek, Sun Ha; Lee, Soon-Tae; Park, Sung-Hye

    2015-01-01

    We investigated c-Met overexpression and MET gene amplification in gliomas to determine their incidence and prognostic significance. c-Met immunohistochemistry and MET gene fluorescence in situ hybridization were carried out on tissue microarrays from 250 patients with gliomas (137 grade IV GBMs and 113 grade II and III diffuse gliomas). Clinicopathological features of these cases were reviewed. c-Met overexpression and MET gene amplification were detected in 13.1% and 5.1% of the GBMs, respectively. All the MET-amplified cases showed c-Met overexpression, but MET amplification was not always concordant with c-Met overexpression. None of grade II and III gliomas demonstrated c-Met overexpression or MET gene amplification. Mean survival of the GBM patients with MET amplification was not significantly different from patients without MET amplification (P=0.155). However, GBM patients with c-Met overexpression survived longer than patients without c-Met overexpression (P=0.035). Although MET amplification was not related to poor GBM prognosis, it is partially associated with the aggressiveness of gliomas, as MET amplification was found only in grade IV, not in grade II and III gliomas. We suggest that MET inhibitor therapy may be beneficial in about 5% GBMs, which was the incidence of MET gene amplification found in the patients included in this study.

  8. Samen in Zee met Zelfregulatie: Een Design-Based Aanpak met Vmbo Leraren

    NARCIS (Netherlands)

    Jossberger, Helen; Brand-Gruwel, Saskia; Boshuizen, Els; Van de Wiel, Margje

    2010-01-01

    Jossberger, H., Brand-Gruwel, S., Boshuizen, H. P. A., & Van der Wiel, M. (2010, June). Samen in Zee met Zelfregulatie: Een Design-Based Aanpak met Vmbo Leraren. Poster presented at the 37th Onderwijs Research Dagen (ORD), Enschede, Nederland.

  9. MetBaro - Pressure Instrument for Mars MetNet Lander

    Science.gov (United States)

    Polkko, J.; Haukka, H.; Harri, A.-M.; Schmidt, W.; Leinonen, J.; Mäkinen, T.

    2009-04-01

    THE METNET MISSION FOCUSED ON THE Martian atmospheric science is based on a new semihard landing vehicle called the MetNet Lander (MNL). The MNL will have a versatile science payload focused on the atmospheric science of Mars. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. MetBaro is the pressure instrument of MetNet Lander designed to work on Martian surface. It is based on Barocap® technology developed by Vaisala, Inc. MetBaro is a capacitic type of sensing device where capasitor plates are moved by ambient pressure. MetBaro device consists of two pressure transducers including a total of 6 Barocap® sensor heads of high-stability and high-resolution types. The long-term stability of MetBaro is in order of 20…50 µBar and resolution a few µBar. MetBaro is small, lightweighed and has low power consumption. It weighs about 50g without wires and controlling FPGA, and consumes 15 mW of power. A similar device has successfully flown in Phoenix mission, where it performed months of measurements on Martian ground. Another device is also part of the Mars Science Laboratory REMS instrument (to be launched in 2011).

  10. Inhaken met sociale media in 60 minuten

    NARCIS (Netherlands)

    Thijs Waardenburg; Komala Mazerant

    2018-01-01

    Met creatieve content die slim inhaakt op actuele gebeurtenissen kun je elke dag nieuwe mensen bereiken. Goedkoper dan adverteren op sociale media, en sympathieker bovendien.Thijs Waardenburg en Komala Mazerant leggen uit hoe je kansrijke inhakers bedenkt en communiceert om je bereik op sociale

  11. Varroabestrijding met bijenbroed als mijtenval (2)

    NARCIS (Netherlands)

    Calis, J.; Beetsma, J.; Boot, W.J.; Eijnde, van den J.; Ruijter, de A.

    1994-01-01

    Bij deze bestrijdingsmethode worden belegde darreraten uit een moergoede veger overgehangen naar het moerloze en later broedloze hoofdvolk. Hier worden de mijten die zich op de bijen bevinden gevangen. Nadat de laatste darreraat uit een hoofdvolk is verwijderd, wordt het bijenvolk met Perizine

  12. Beeldverwerking met de Micron Automatic Processor

    OpenAIRE

    Goyens, Frank

    2017-01-01

    Deze thesis is een onderzoek naar toepassingen binnen beeldverwerking op de Micron Automata Processor hardware. De hardware wordt vergeleken met populaire hedendaagse hardware. Ook bevat dit onderzoek nuttige informatie en strategieën voor het ontwikkelen van nieuwe toepassingen. Bevindingen in dit onderzoek omvatten proof of concept algoritmes en een praktische toepassing.

  13. Groen proceswater: zuivering brouwerijprocesafvalwater met microalgen

    NARCIS (Netherlands)

    Dijk, van W.; Weide, van der R.Y.; Kroon, A.

    2016-01-01

    In 2012 is het project Groen Proceswater gestart. Hierin worden de mogelijkheden van zuivering van brouwerijprocesafvalwater met behulp van microalgen onderzocht. Dit is gedaan in een samenwerkingsverband van Heineken Nederland BV, Algae Food & Fuel en WUR-ACRRES. De resultaten behaald in 2012

  14. Evangelisch Commando, onze omgamg met de buitenkerkelijke ...

    African Journals Online (AJOL)

    Test

    Of J. en E. dus interkerklik is, bly 'n vraag! Die gedeelte oor die „Oorzaken van buitenkerklijkheid is prikkelend en interessant. Die vraag is net of dit nie nog dieper gesoek moet word, nl. in die herontwaking van die Heidendom wat sig sins die Renaissance hardnekkig deur sit met die outonomie van die mens in die sentrum.

  15. Risicoanalyse voor buisleidingen met brandbare vloeistoffen

    NARCIS (Netherlands)

    van Vliet AAC; Laheij GMH; Wolting AG; CEV

    2006-01-01

    De minimale veiligheidsafstanden tussen buisleidingen met brandbare vloeistoffen en bebouwingen kunnen gelijk blijven of iets verkleind worden. Dit is de conclusie na een herberekening van de afstanden uit een circulaire uit 1991. In Nederland ligt zo'n 1850 kilometer aan ondergrondse buisleiding

  16. A brief report on mets system

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, W.A.

    Mets system is basically a gas monitoring system, used for the detection of underwater gas. The system consists of a sensor, datalogger and energy module. The sensor works on the diffusion techniques. The system can be deployed to a water depth...

  17. De Doop met de Heilige Geest

    Directory of Open Access Journals (Sweden)

    S. C.W. Duvenage.

    1965-03-01

    Full Text Available Ds. Molenaar begin sy boek, waarvan hy self die publikasienie beleef het nie, deur te wys op 'n groot tekort, ’n manko,nie alleen in die Gereformeerde vroomheid of lewe nie maarook in die Gereformeerde teologie. Hy beskou dit as hoogsmerkwaardig dat die Gereformeerde teologie in die verledeso goed as niks raakgesien het van die groot betekenis vandie sogenaamde doop met die Heilige Gees nie. Daarby meenhy dat die Gereformeerde predikante verleë sit met die Pinkterfees.Talle probleme meen hy vir die Gereformeerde teoloograak te sien, veral ten aansien van die moontlikhede van dieGees teenoor die so tasbare „onmoontIikhede” in ons lewe. Dieprobleme is syns insiens nie onoplosbaar nie, as mens maardie moontlikhede van die Gees nie beperk tot die verlede nie.

  18. MET and Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Gelsomino

    2014-10-01

    Full Text Available Small-cell lung cancer (SCLC is one of the most aggressive lung tumors. The majority of patients with SCLC are diagnosed at an advanced stage. This tumor type is highly sensitive to chemo-radiation treatment, with very high response rates, but invariably relapses. At this time, treatment options are still limited and the prognosis of these patients is poor. A better knowledge of the molecular biology of SCLC allowed us to identify potential druggable targets. Among these, the MET/HGF axis seems to be one of the most aberrant signaling pathways involved in SCLC invasiveness and progression. In this review, we describe briefly all recent literature on the different molecular profiling in SCLC; in particular, we discuss the specific alterations involving c-MET gene and their implications as a potential target in SCLC.

  19. Metáfora y estructura conceptual

    Directory of Open Access Journals (Sweden)

    Emilia Castaño

    2012-01-01

    Full Text Available La lingüística cognitiva siempre ha argumentado que la metáfora no pertenece exclusivamente al lenguaje, sino que es una competencia que se basa en la habilidad humana de concebir un dominio de experiencia en términos de otro. Entendida así, la metáfora no puede ser otra cosa que un fenómeno conceptual. No obstante, pocos adeptos de la lingüística cognitiva han concentrados sus esfuerzos en catalogar manifestaciones metafóricas en ámbitos no lingüísticos. En este trabajo, sugerimos que es factible encontrar pruebas de que la metáfora es un proceso conceptual y, como tal, se manifiesta en esferas que no son estrictamente lingüísticas. Para ello, aportamos un seguido de evidencias muy diversas, como por ejemplo su papel en el razonamiento lógico-matemático de los niños en la fase preoperacional del desarrollo cognitivo, la programación de interfaces para aplicaciones informáticas y los resultados de tres estudios empíricos realizados recientemente en el campo  de la psicología cognitiva que analizan los efectos whorfianos en la conceptualización del tiempo y los efectos del espacio en la memoria emocional.

  20. Lipid ratio as a suitable tool to identify individuals with MetS risk: A case- control study.

    Science.gov (United States)

    Abbasian, Maryam; Delvarianzadeh, Mehri; Ebrahimi, Hossein; Khosravi, Farideh

    2017-11-01

    This study aimed to compare the serum lipids ratio in staff with and without metabolic syndrome (MetS) who were working in Shahroud University of Medical Sciences. This case-control study was conducted in 2015 on 499 personnel aged 30-60 years old. ATP III criteria were used to diagnose patients with MetS. The data were analyzed by using logistic regression and ROC curve. Mean lipid ratio was higher in individuals having the MetS in both sexes compared with those without. In addition, the mean levels of lipid ratios significantly increased with increasing number of MetS components in both sexes. Also it could be concluded that TG/HDL-C ratio is the best marker for the diagnosis of MetS in men and women. Moreover, the cut-off point for the TG/HDL-C was 2.86 in women and 4.03 in men. It was found that for any unit of increases in the TG/HDL-C, the risk of developing the MetS will increase by 2.12 times. TG/HDL-C ratio is found to be the best clinical marker for the diagnosis of MetS compare with other lipid ratios, therefore it is recommended to be used as a feasible tool to identify individuals with MetS risk. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  1. Metáfora y conceptos abstractos

    OpenAIRE

    Danesi, Marcel

    2006-01-01

    La gran cantidad de datos recolectados sobre la metáfora sugiere enfáticamente que muchos de los conceptos abstractos, si no la mayoría, son codificables y reconocibles primordialmente como «ideas metaforizadas», es decir como conceptos que se derivan cognitivamente mediante el razonamiento metafórico y un proceso de asociación metafórica que en este artículo se denominará estratificación [layering] (Gibbs, 1994; Goatley, 1997). La literatura más actualizada sobre lo que se ha denominado Teor...

  2. Dissection of combinatorial control by the Met4 transcriptional complex.

    Science.gov (United States)

    Lee, Traci A; Jorgensen, Paul; Bognar, Andrew L; Peyraud, Caroline; Thomas, Dominique; Tyers, Mike

    2010-02-01

    Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.

  3. Advanced CerMet ceramic composites for medical applications.

    Science.gov (United States)

    Dittmer, Robert; Schaefer, Christian M; Fischer, Jean-Francois; Hausch, Ulrich; Troetzschel, Jens; Specht, Heiko

    2017-11-01

    Implantable active devices such as pacemakers are facing rigorous requirements. Because they reside within the body for years, materials applied in this surrounding must exhibit biocompatibility and extraordinary reliability. They also have to provide a number of functional properties. In this work we present a method that enables the realization of a highly complex profile of properties by means of a dual composite approach. Using multilayer technology, an electrical conductor is embedded into a ceramic matrix, thus, creating conductive paths that are insulated from each other. In addition to this macroscopically hybrid architecture, this approach features a second composite aspect: the conductor is not composed of a single metallic phase, but is a ceramic-metal mixture. Owing to its interpenetrating microstructure, this CerMet allows for a strong and hermetic integration of the conductor into the ceramic matrix otherwise impossible due to mismatch in thermal expansion. In fact, the CerMet ceramic composite exhibits a higher strength than the pure ceramic as revealed by a three-point bending test study. At the same time, the CerMet offers high and virtually metal-like conductor properties, enabling a down-scaling of the conductive paths to 150µm diameter and smaller. Furthermore, the described composite is biocompatible, non-magnetic, and chemically inert, which is vital for the application in active, implantable, medical devices. Beside the general fabrication route, we present the microstructural, functional, and mechanical properties of this newly developed class of dual composites. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Saving energy with paint. Coating with ceramic globules; Energie besparen met verf. Coating met keramische bolletjes

    Energy Technology Data Exchange (ETDEWEB)

    Willemse, R. [Coateq Coatings, Haarlem (Netherlands)

    2011-07-01

    The special paint coating of ThermoShield saves energy. The coating consists for 50% of hollow, vacuum ceramic globules. The waterborne damp-open coating with capillary function resists rain water and removes redundant water in case of draught and it reflects sunlight. [Dutch] Met de speciale verfcoating ThermoShield kan energie worden bespaard. De coating bestaat voor 50% uit holle, vacuum getrokken keramische bolletjes. De watergedragen damp-open coating met capillaire werking stoot bij regen water af en voert bij droogte overtollig vocht af en reflecteert zonlicht.

  5. MET Standards for Electro-Technical Officers

    Directory of Open Access Journals (Sweden)

    Janusz Mindykowski

    2014-12-01

    Full Text Available The paper deals with one of the most important changes in the STCW 1978 as amended in 2010 Convention, from the point of view of the watchkeeping officers responsible for control, maintenance, diagnostic and repair of electrical and electronic installations on board of ships. Some reasons, why the MET Standards for Electro-Technical had to be developed and implemented are shortly analyzed and described. A legislative way towards and a short description of the minimum standards competence for ETO are presented. Next, new tools supporting ETO’s standards implementation are appointed. Finally, the future works as well as the concluding remarks concerning discussed issue are formulated and commented on.

  6. Tidal analysis of Met rocket wind data

    Science.gov (United States)

    Bedinger, J. F.; Constantinides, E.

    1976-01-01

    A method of analyzing Met Rocket wind data is described. Modern tidal theory and specialized analytical techniques were used to resolve specific tidal modes and prevailing components in observed wind data. A representation of the wind which is continuous in both space and time was formulated. Such a representation allows direct comparison with theory, allows the derivation of other quantities such as temperature and pressure which in turn may be compared with observed values, and allows the formation of a wind model which extends over a broader range of space and time. Significant diurnal tidal modes with wavelengths of 10 and 7 km were present in the data and were resolved by the analytical technique.

  7. Metástasis hipofisaria Hypophyseal metastasis

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Yanes Quesada

    2009-04-01

    Full Text Available mayoría son lesiones silentes descubiertas accidentalmente en las autopsia. La aparición de metástasis sintomáticas es, en cambio, excepcional. DESARROLLO: se describen aquí los hallazgos clínicos y radiológicos de una paciente femenina de 69 años, con un carcinoma indiferenciado del pulmón, diagnosticado hace 2 años y medio, que comenzó con cefalea y trastornos visuales sin hipopituitarismo ni diabetes insípida. Se le realizó resonancia magnética nuclear y se le diagnosticó una lesión hipofisaria, que fue operada por vía tranesfenoidal, y se informó por anatomía patológica una metástasis del carcinoma del pulmón. CONCLUSIONES: la paciente se encuentra en estos momentos recibiendo quimioterapia, radioterapia y anticuerpo monoclonal con evolución favorable.INTRODUCTION: metastatic tumors of hypophyseal gland are infrequent. Most are silent lesions discovered accidentally in necropsy. Appearance of symptomatic metastasis is however, exceptional. DEVELOPMENT: we describe here clinical and radiological findings in a female patient aged 69, presenting with a non-differential carcinoma of lung, diagnosed two years a half ago, starting with headache and visual disorders without hypopituitarism and insipidus diabetes. We made a nuclear magnetic resonance and diagnosis was a hypophyseal lesion operated on by trans-esphenoidal route, and Pathological Anatomy Service reports a metastasis of lung carcinoma. CONCLUSIONS: patient receives chemotherapy, radiotherapy, and monoclonal antibody with a favorable evolution.

  8. Resultaten boomkorsurvey 2013: BTS met onderzoeksvaartuigen Isis en Tridens (interview met Ingeborg de Boois)

    NARCIS (Netherlands)

    Boois, de I.J.

    2013-01-01

    Van begin augustus tot half september heeft IMARES de boomkorsurvey (BTS) uitgevoerd met de onderzoeksschepen Isis en Tridens. Op 29 maart 2014 wordt een bijeenkomst georganiseerd voor geinteresseerden, waar de resultaten van zowel de BTS als de bedrijfssurvey gepresenteerd worden. De BTS wordt

  9. Pastoors naar de PFA: nieuwe impuls voor samenwerking met de wetenschap (interview met Martin Pastoors)

    NARCIS (Netherlands)

    Pastoors, M.A.

    2014-01-01

    De Pelagic Freezer-trawler Association (PFA) heeft visserijonderzoeler Martin Pastoors aangenomen als 'Chief Science Officer'. De afgelopen tien jaar is de PFA zich steeds meer bezig gaan houden met wetenschappelijk onderzoek. Bijvoorbeeld door het ontwikkelen van nieuwe manieren om data te

  10. MetNet - In situ observational Network and Orbital platform to investigate the Martian environment

    Science.gov (United States)

    Harri, Ari-Matti; Leinonen, Jussi; Merikallio, Sini; Paton, Mark; Haukka, Harri; Polkko, Jouni

    2007-09-01

    MetNet Mars Mission is an in situ observational network and orbital platform mission to investigate the Martian environment and it has been proposed to European Space Agency in response to Call for proposals for the first planning cycle of Cosmic Vision 2015-2025 D/SCI/DJS/SV/val/21851. The MetNet Mars Mission is to be implemented in collaboration with ESA, FMI, LA, IKI and the payload providing science teams. The scope of the MetNet Mission is to deploy 16 MetNet Landers (MNLs) on the Martian surface by using inflatable descent system structures accompanied by an atmospheric sounder and data relay onboard the MetNet Orbiter (MNO), which is based on ESA Mars Express satellite platform. The MNLs are attached on the three sides of the satellite and most of the MNLs are deployed to Mars separately a few weeks prior to the arrival to Mars. The MetNet Orbiter will perform continuous atmospheric soundings thus complementing the accurate in situ observations at the Martian ground produced by the MetNet observation network, as well as the orbiter will serve as the primary data relay between the MetNet Landers and the Earth. The MNLs are equipped with a versatile science payload focused on the atmospheric science of Mars. Detailed characterisation of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatological cycles, as well as interior investigations, require simultaneous in situ meteorological, seismic and magnetic measurements from networks of stations on the Martian surface. MetNet Mars Mission will also provide a crucial support for the safety of large landing missions in general and manned Mars missions in particular. Accurate knowledge of atmospheric conditions and weather data is essential to guarantee safe landings of the forthcoming Mars mission elements.

  11. Milde voedselverwerkingstechnologie II : milde conservering met hoge druk : nieuwe ontwikkelingen

    NARCIS (Netherlands)

    Matser, A.M.; Ven, van der C.; Berg, van den R.

    2004-01-01

    Met behulp van hogedruktechnologie kunnen producten langer houdbaar worden gemaakt. Deze bekende techniek kent de laatste tijd nieuwe ontwikkelingen en toepassingen . Naast pasteuriseren door een hogedrukbehandeling bij kamertemperatuur is het nu ook mogelijk om te steriliseren met hoge druk. Ook

  12. MetNet Network Mission for Martian Atmospheric Investigations

    Science.gov (United States)

    Harri, A.-M.; Alexashkin, S.; Arrugeo, I.; Schmidt, W.; Vazquez, L.; Genzer, M.; Haukka, H.

    2014-07-01

    A new kind of planetary exploration mission for Mars called MetNet is being developed for martian atmospheric investigations. The eventual scope of the MetNet Mission is to deploy tens of small landers on the martian surface.

  13. Dimensionering van de Uniqfill chemischer wasser met lamellen

    NARCIS (Netherlands)

    Starmans, D.A.J.

    2006-01-01

    In dit rapport wordt een eerste aanzet gegeven tot de modellering van een kruisstroom chemische wasser met lamellen. Met behulp van bestaande metingen is de stofoverdrachtscoëfficiënt afgeschat, waarna scenario's voor nieuwe wassers doorgerekend konden worden.

  14. Klimaatverandering en de stadsboom (interview met Jitze Kopinga)

    NARCIS (Netherlands)

    Bennink, P.; Kopinga, J.

    2010-01-01

    Bomen in de stad staan vaak op warme plaatsen met een gebrekkige waterhuishouding. Volgens het KNMI zal Nederland in de toekomst steeds vaker met hitte en droogte te maken hebben. Wat betekent dat voor onze stadsbomen?

  15. Association between the catechol-o-methyltransferase val158met polymorphism with susceptibility and severity of carpal tunnel syndrome

    Directory of Open Access Journals (Sweden)

    Erkol İnal E

    2015-12-01

    Full Text Available Carpal tunnel syndrome (CTS is the most common entrapment neuropathy of the upper extremity. In this study, we aimed to clarify the relationships between the catechol-O-methyltransferase (COMT gene Val158Met (rs4680 polymorphism and development, functional and clinical status of CTS. Ninety-five women with electro diagnostically confirmed CTS and 95 healthy controls were enrolled in the study. The functional and clinical status of the patients was measured by the Turkish version of the Boston Questionnaire and intensity of pain related to the past 2 weeks was evaluated on a visual analog scale (VAS. The Val158Met polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP, method. We divided patients according to the genotypes of the Val158Met polymorphism as Val/Val, Val/Met and Met/Met. There were not any significant differences in terms of Val158Met polymorphisms between patients and healthy controls (p >0.05. We also did not find any relationships between the Val158Met polymorphism and CTS (p >0.05. In conclusion, although we did not find any relationships between CTS and the Val158Met polymorphism, we could not generalize this result to the general population. Future studies are warranted to conclude precise associations.

  16. MET amplification, expression, and exon 14 mutations in colorectal adenocarcinoma.

    Science.gov (United States)

    Zhang, Meng; Li, Guichao; Sun, Xiangjie; Ni, Shujuan; Tan, Cong; Xu, Midie; Huang, Dan; Ren, Fei; Li, Dawei; Wei, Ping; Du, Xiang

    2018-04-08

    MET amplification, expression, and splice mutations at exon 14 result in dysregulation of the MET signaling pathway. The aim of this study was to identify the relationship between MET amplification, protein or mRNA expression, and mutations in colorectal cancer (CRC). MET immunohistochemistry (IHC) was used for MET protein expression analysis and fluorescence in situ hybridization (FISH) was used for MET amplification detection. Both analyses were performed in tissue microarrays (TMA) containing 294 of colorectal adenocarcinoma tissue samples and 131 samples of adjacent normal epithelial tissue. MET mRNA expression was examined by real-time quantitative polymerase chain reaction (qRT-PCR) in 72 fresh colorectal adenocarcinoma tissue samples and adjacent normal colon tissue. PCR sequencing was performed to screen for MET exon 14 splice mutations in 59 fresh CRC tissue samples. Our results showed that MET protein expression was higher in colorectal tumor tissue than in adjacent normal intestinal epithelium. Positive MET protein expression was associated with significantly poorer overall survival (OS) and disease-free survival (DFS). Multivariate analysis revealed that positive MET protein expression was an independent risk factor for DFS, but not for OS. MET mRNA expression was upregulated in tumor tissues compared with the adjacent normal tissues. The incidence of MET amplification was 4.4%. None of the patients was positive for MET mutation. Collectively, MET was overexpressed in colorectal adenocarcinoma, and its positive protein expression predicted a poorer outcome in CRC patients. Furthermore, according to our results, MET amplification and 14 exon mutation are extremely rare events in colorectal adenocarcinoma. Copyright © 2018. Published by Elsevier Inc.

  17. Effect of MET on formation and vigor of wheat roots

    International Nuclear Information System (INIS)

    Wang Bingkui; Jin Ziyu; Zhao Miaozhen; Zhao Yanshen

    1993-01-01

    Effect of MET on the formation and vigor of roots of wheat seedlings were studied. The results showed that 50 ∼ 200 ppm MET inhibited vertical elongation of roots, increased root, shoot ratio and enhanced the formation and vigor of roots. But MET had no effect on the dry weight of roots. The activity of peroxidase was decreased and the proportion of assimilates in roots was increased by MET treatment compared with the control

  18. Innoveren met serious games : Wat is serious gaming?

    NARCIS (Netherlands)

    Werkhoven, P.J.

    2008-01-01

    Het begrip serious gaming is inmiddels gekaapt door vele aanbieders van wat vroeger simulatie en virtual reality technologie genoemd werd. Met die technologie kunnen we mensen laten rondlopen in virtuele gebouwen en landschappen, al dan niet met grote projectieschermen of met brillen op. Maar dat is

  19. Groen proceswater: zuivering brouwerijprocesafvalwater met microalgen : Resultaten onderzoek 2013

    NARCIS (Netherlands)

    Dijk, van W.; Diem, van A.; Doornbusch, P.; Grobben-Gaastra, S.A.; Kleinhout, G.; Kroon, A.; Weide, van der R.Y.

    2014-01-01

    Afgelopen jaar is de pilot met het kweken van algen met afvalwater van de brouwerijlocatie Zoeterwoude geslaagd. Dit is gedaan in een samenwerkingsverband van Heineken Nederland BV, Algae Food & Fuel en WUR-Acrres. Dit is de eerste inline pilot in de wereld waarbij met LED verlichting op 1000 L

  20. Erlotinib e metástases cerebrais

    Directory of Open Access Journals (Sweden)

    Fernando Barata

    2008-10-01

    Full Text Available Resumo: Relatamos dois casos de carcinoma pulmonar de não pequenas células (CPNPC com metástases cerebrais que após quimioterapia sistémica receberam em segunda e terceira linha erlotinib 150 mg/dia, oral, com resposta completa das lesões secundárias cerebrais e franca resposta parcial das lesões torácicas.A metastização cerebral, bastante prevalente no contexto do CPNPC, está associada a escassas opções terapêuticas eficazes e, consequentemente, a uma sobre-vida mediana de 4 a 6 meses.Estes casos alertam para o erlotinib como uma excelente opção terapêutica para estes doentes. Os autores propõem um ensaio clínico com este fármaco neste grupo de doentes, procurando determinar da resposta objectiva.Rev Port Pneumol 2008; XIV (Supl 3: S35-S42 Abstract: We report two cases of brain metastases in context of non small cell lung cancer (NSCLC. After having progressed to chemotherapy they received erlotinib 150 mg/m2 orally daily, with complete response of brain metastasis and partial response of thoracic lesions.Brain metastases are both prevalent and a major cause of mortality in NSCLC, with few systemic treatment options. Median survival after whole brain radiotherapy is 4-6 months and the role of systemic therapy for brain metastases is limited with the most drugs use to stage IV disease ineffective in this setting.This case demonstrates that brain metastases may be sensitive to erlotinib and give to us growing body of evidence that EGFR-associated tyrosine kinase inhibition is a feasible strategy in the management of NSCLC patients with brain metastasesWe propose further study into the continued use of this drug in the situation where there is a differential response.Rev Port Pneumol 2008; XIV (Supl 3: S35-S42 Palavras-chave: Erlotinib, metástase cerebral, cancro do pulmão, Key-words: Erlotinib, brain metastasis, lung cancer

  1. Phase I Trial of Anti-MET Monoclonal Antibody in MET-Overexpressed Refractory Cancer.

    Science.gov (United States)

    Lee, Jeeyun; Kim, Seung Tae; Park, Sungju; Lee, Sujin; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Ahn, Hongmo; Bok, Haesook; Kim, Kyoung-Mee; Ahn, Myung Ju; Kang, Won Ki; Park, Young Suk

    2018-06-01

    Samsung Advance Institute of Technology-301 (SAIT301) is a human immunoglobulin G2 antibody that can specifically target mesenchymal epithelial transition factor (c-MET). This novel antibody has higher priority over hepatocyte growth factors when binding to the Sema domain of c-MET and accelerates the internalization and degradation of c-MET, proving its powerful antitumor activities in intra- as well as extracellular areas. SAIT301 was administered intravenously once every 3 weeks in c-MET overexpressed solid tumor patients, focusing on metastatic colorectal cancer (CRC) according to common clinical phase I criteria. Dose escalation was performed according to a modified Fibonacci design, following the conventional 3+3 design. The purpose of this phase I study was to assess the safety profile, to establish the recommended dose for clinical phase II studies and to assess potential anticancer activity of the compound. Sixteen patients with a median age of 56 (range, 39-69) years were enrolled in the study. The most common adverse events were decreased appetite (50.0%), hypophosphatemia, fatigue and dizziness (25.0%, respectively), and diarrhea, blood alkaline phosphatase increased and dyspnea (18.8%, respectively). For tumor response, no patients achieved complete response. One (9.1%) CRC patient had a partial response in the 1.23 mg/kg group, 4 (36.4%) patients achieved stable disease (2 in the 0.41 mg/kg group, 2 in the 1.23 mg/kg group, 0 in the 3.69 mg/kg group, and 1 in the 8.61 mg/kg group). Because of the increase in dose-limiting toxicities (DLTs) at 8.61 mg/kg, the 3.69 mg/kg dose was considered the maximum tolerated dose and selected for further assessment in phase II. We successfully completed a phase I trial with MET antibody in a MET-overexpressed patient population focusing on CRC, and found that the DLTs were alkaline phosphatase elevation or hypophosphatemia. The recommended dose of SAIT301 for phase II is the dose of 3.69 mg/kg. Copyright © 2018

  2. 3D RoboMET Characterization

    Energy Technology Data Exchange (ETDEWEB)

    Madison, Jonathan D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Susan, Donald F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kilgo, Alice C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-10-01

    The goal of this project is to generate 3D microstructural data by destructive and non-destructive means and provide accompanying characterization and quantitative analysis of such data. This work is a continuing part of a larger effort to relate material performance variability to microstructural variability. That larger effort is called “Predicting Performance Margins” or PPM. In conjunction with that overarching initiative, the RoboMET.3D™ is a specific asset of Center 1800 and is an automated serialsectioning system for destructive analysis of microstructure, which is called upon to provide direct customer support to 1800 and non-1800 customers. To that end, data collection, 3d reconstruction and analysis of typical and atypical microstructures have been pursued for the purposes of qualitative and quantitative characterization with a goal toward linking microstructural defects and/or microstructural features with mechanical response. Material systems examined in FY15 include precipitation hardened 17-4 steel, laser-welds of 304L stainless steel, thermal spray coatings of 304L and geological samples of sandstone.

  3. Progress in switching technology for METS systems

    International Nuclear Information System (INIS)

    Honig, E.M.; Swannack, C.E.; Warren, R.W.; Whitaker, D.H.

    1977-01-01

    Three distinct sets of switching requirements have emerged from design optimization studies of large superconducting magnetic energy storage systems, such as the METS system to power the adiabatic plasma compression field in the proposed theta-pinch SFTR. Extremely low joule loss cryogenic disconnects are required between storage coils in the liquid helium environment to allow charging the coils in series over a prolonged time, then to isolate the coils for parallel fast discharging into the load. Another switch must break the current in the series charging loop and absorb the energy from the stray inductance. This action will allow the subsequent opening of the cryogenic disconnects under near zero current condition. The current now has been transferred to the many paralleled circuits, each containing a high current, high voltage interrupter. The opening and arc commutation of the interrupter starts the energy transfer into the load. The primary activities associated with cryogenic disconnect have been testing and development of contact materials, configurations, and closing forces for carrying 26 kA with a resistance less than 40 nΩ, and development of an actuating system that is both reliable and fast acting in a liquid helium environment. The charging loop switch will include a continuous duty switch and a vacuum interrupter. The continuous duty switch resistance can be an order of magnitude larger than that of the cryogenic disconnect because it does not present a refrigeration load. The HVDC interrupter must break 26 kA and withstand 60 kV during the energy transfer time of 700 μs. Testing in progress already has shown successful interruption using single vacuum interrupters up to 31 kA and 66 kV

  4. Research progress in c-Met and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    WANG Changqing

    2015-06-01

    Full Text Available c-Met plays a pivotal role in the development and progression of hepatocellular carcinoma (HCC, which can lead to proliferation, survival, cytoskeleton reorganization, separation and diffusion, and angiogenesis of tumor cells. Moreover, c-Met is an important prognostic factor for HCC. In HCC, c-Met acts as an activator of a series of signaling pathways, including PI3K/AKT/mTOR, ERK/MAPK, and Rac-Pak. In recent years, it has been reported that small-molecule kinase inhibitors can abolish phosphorylation at the intracellular carboxyl terminal of c-Met, and then inhibit the recruitment of signal convertors and downstream signaling pathways, which finally achieve anti-tumor activities. Based on the carcinogenic activity of c-Met in HCC, this paper points out that selective inhibitors of c-Met hold promise for targeted therapies for HCC.

  5. Design and Implementation of Image Research for the Columbia Mets

    Science.gov (United States)

    1992-01-01

    the other hand, developed an unusual camaraderie through identifying with their underdog Mets." (7) Teams are finding good public relations programs do...supports the club. Question 24 was designed to measure brand loyalty by respondents to Mets sponsors versus non-Mets sponsors. Finally, question 27...be done to attract crowds. Especially with a brand new stadium. The Carolinas, in my opinion, are big minor league baseball states. Let’s get people

  6. Effective implementation of novel MET pharmacodynamic assays in translational studies.

    Science.gov (United States)

    Srivastava, Apurva K; Navas, Tony; Herrick, William G; Hollingshead, Melinda G; Bottaro, Donald P; Doroshow, James H; Parchment, Ralph E

    2017-01-01

    MET tyrosine kinase (TK) dysregulation is significantly implicated in many types of cancer. Despite over 20 years of drug development to target MET in cancers, a pure anti-MET therapeutic has not yet received market approval. The failure of two recently concluded phase III trials point to a major weakness in biomarker strategies to identify patients who will benefit most from MET therapies. The capability to interrogate oncogenic mutations in MET via circulating tumor DNA (ctDNA) provides an important advancement in identification and stratification of patients for MET therapy. However, a wide range in type and frequency of these mutations suggest there is a need to carefully link these mutations to MET dysregulation, at least in proof-of-concept studies. In this review, we elaborate how we can utilize recently developed and validated pharmacodynamic biomarkers of MET not only to show target engagement, but more importantly to quantitatively measure MET dysregulation in tumor tissues. The MET assay endpoints provide evidence of both canonical and non-canonical MET signaling, can be used as "effect markers" to define biologically effective doses (BEDs) for molecularly targeted drugs, confirm mechanism-of-action in testing combination of drugs, and establish whether a diagnostic test is reporting MET dysregulation. We have established standard operating procedures for tumor biopsy collections to control pre-analytical variables that have produced valid results in proof-of-concept studies. The reagents and procedures are made available to the research community for potential implementation on multiple platforms such as ELISA, quantitative immunofluorescence assay (qIFA), and immuno-MRM assays.

  7. Targeting MET Amplification as a New Oncogenic Driver

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Hisato [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Okamoto, Isamu, E-mail: okamotoi@kokyu.med.kyushu-u.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582 (Japan); Okamoto, Wataru [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Division of Transrlational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577 (Japan); Tanizaki, Junko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, HIM223, 450 Brookline Avenue, Boston, MA 02215 (United States); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan)

    2014-07-22

    Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy.

  8. Targeting MET Amplification as a New Oncogenic Driver

    International Nuclear Information System (INIS)

    Kawakami, Hisato; Okamoto, Isamu; Okamoto, Wataru; Tanizaki, Junko; Nakagawa, Kazuhiko; Nishio, Kazuto

    2014-01-01

    Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy

  9. Preproghrelin Leu72Met polymorphism in obese Korean children.

    Science.gov (United States)

    Jo, Dae-Sun; Kim, Se-Lim; Kim, Sun-Young; Hwang, Pyoung Han; Lee, Kee-Hyoung; Lee, Dae-Yeol

    2005-11-01

    Ghrelin is a novel gut-brain peptide that has somatotropic, orexigenic, and adipogenic effects. We examined the preproghrelin Leu72Met polymorphism in 222 obese Korean children to determine whether it is associated with obesity. The frequencies of the Leu72Met polymorphism were 29.3% in obese, 32.3% in overweight, and 32.5% in lean Korean children. No significant difference was found between Met72 carrier and non-carrier obese children with respect to BMI, total body fat, serum triglycerides, total cholesterol, or LDL-cholesterol levels. Our data suggest that the preproghrelin Leu72Met polymorphism is not associated with obesity in children.

  10. Mars MetNet Mission Pressure and Humidity Devices

    Science.gov (United States)

    Haukka, H.; Harri, A.-M.; Schmidt, W.; Genzer, M.; Polkko, J.; Kemppinen, O.; Leinonen, J.

    2012-09-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). MetBaro and MetHumi are part of the scientific payload of the MNL. Main scientific goal of both devices is to measure the meteorological phenomena (pressure and humidity) of the Martian atmosphere and complement the previous Mars mission atmospheric measurements (Viking and Phoenix) for better understanding of the Martian atmospheric conditions.

  11. MetR and CRP bind to the Vibrio harveyi lux promoters and regulate luminescence.

    Science.gov (United States)

    Chatterjee, Jaidip; Miyamoto, Carol M; Zouzoulas, Athina; Lang, B Franz; Skouris, Nicolas; Meighen, Edward A

    2002-10-01

    The induction of luminescence in Vibrio harveyi at the later stages of growth is controlled by a quorum-sensing mechanism in addition to nutritional signals. However, the mechanism of transmission of these signals directly to the lux promoters is unknown and only one regulatory protein, LuxR, has been shown to bind directly to lux promoter DNA. In this report, we have cloned and sequenced two genes, crp and metR, coding for the nutritional regulators, CRP (cAMP receptor protein) and MetR (a LysR homologue), involved in catabolite repression and methionine biosynthesis respectively. The metR gene was cloned based on a general strategy to detect lux DNA-binding proteins expressed from a genomic library, whereas the crp gene was cloned based on its complementation of an Escherichia coli crp mutant. Both CRP and MetR were shown to bind to lux promoter DNA, with CRP being dependent on the presence of cAMP. Expression studies indicated that the two regulators had opposite effects on luminescence: CRP was an activator and MetR a repressor. Disruption of crp decreased luminescence by about 1,000-fold showing that CRP is a major activator of luminescence the same as LuxR, whereas disruption of MetR resulted in activation of luminescence over 10-fold, confirming its function as a repressor. Comparison of the levels of the autoinducers involved in quorum sensing excreted by V. harveyi, and the crp and metR mutants, showed that autoinducer production was not significantly different, thus indicating that the nutritional signals do not affect luminescence by changing the levels of the signals required for quorum sensing. Indeed, the large effects of these nutritional sensors show that luminescence is controlled by multiple signals related to the environment and the cell density which must be integrated at the molecular level to control expression at the lux promoters.

  12. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

    Directory of Open Access Journals (Sweden)

    Brian Shuch

    2015-01-01

    Full Text Available Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1. MET expression weakly correlated between primary and matched metastatic sites (R=0.5 and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39. Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

  13. Genetic Correlates of Maladaptive Beliefs: COMT VAL(158)MET and Irrational Cognitions Linked Depending on Distress.

    Science.gov (United States)

    Podina, Ioana; Popp, Radu; Pop, Ioan; David, Daniel

    2015-11-01

    Maladaptive/irrational beliefs are significant cognitive vulnerability mechanisms in psychopathology. They are more likely to be associated with a genetic vulnerability marker under conditions of emotional distress when irrational beliefs are more salient. Therefore, in the current study we investigated the COMT Val(158)Met gene variation in relation to irrational beliefs, assuming this relationship depended on the level of emotional distress. Two hundred and sixty-seven genotyped volunteers were assessed for core/general maladaptive beliefs, as well as trait emotional distress. We focused on context-independent measures of irrational beliefs and emotional distress in the absence of a stressor. As expected, the relationship between COMT Val(158)Met and irrational beliefs depended on the level of emotional distress (f(2)=.314). The COMT Val(158)Met-irrationality association was significant only when individuals fell in the average to above average range of emotional distress. Furthermore, within this range the Met allele seemed to relate to higher irrational beliefs. These results were significant for overall irrational beliefs and its subtypes, but not for rational beliefs, the functional counterpart of irrationality. In light of the study's limitations, the results should be considered as preliminary. If replicable, these findings have potential implications for therapygenetics, changing the view that COMT Val(158)Met might be of greater relevance when treatment modality does not rely on cognitive variables. Copyright © 2015. Published by Elsevier Ltd.

  14. Aptamers Binding to c-Met Inhibiting Tumor Cell Migration.

    Directory of Open Access Journals (Sweden)

    Birgit Piater

    Full Text Available The human receptor tyrosine kinase c-Met plays an important role in the control of critical cellular processes. Since c-Met is frequently over expressed or deregulated in human malignancies, blocking its activation is of special interest for therapy. In normal conditions, the c-Met receptor is activated by its bivalent ligand hepatocyte growth factor (HGF. Also bivalent antibodies can activate the receptor by cross linking, limiting therapeutic applications. We report the generation of the RNA aptamer CLN64 containing 2'-fluoro pyrimidine modifications by systematic evolution of ligands by exponential enrichment (SELEX. CLN64 and a previously described single-stranded DNA (ssDNA aptamer CLN3 exhibited high specificities and affinities to recombinant and cellular expressed c-Met. Both aptamers effectively inhibited HGF-dependent c-Met activation, signaling and cell migration. We showed that these aptamers did not induce c-Met activation, revealing an advantage over bivalent therapeutic molecules. Both aptamers were shown to bind overlapping epitopes but only CLN3 competed with HGF binding to cMet. In addition to their therapeutic and diagnostic potential, CLN3 and CLN64 aptamers exhibit valuable tools to further understand the structural and functional basis for c-Met activation or inhibition by synthetic ligands and their interplay with HGF binding.

  15. Alternative Fuels Data Center: Workplace Charging Success: MetLife

    Science.gov (United States)

    future." Several others noted that their decision to purchase or lease a PEV was based on MetLife's : MetLife " By making PEV charging stations more readily available to employees, we can encourage more promote alternative transportation. By making PEV charging stations more readily available to employees

  16. Invloed krachtvoerniveau op vleesproduktiekenmerken van Piemontese met zwartbont kruislingstieren

    NARCIS (Netherlands)

    Hanekamp, W.J.A.

    1989-01-01

    Met 3 ronden van elk 36 Piemontese X zwartbonte kruislingstieren is het effect van extra krachtvoer vergeleken met de normaal gangbare gift naast onbeperkt snijmaoskuil. De stieren waren gehuisvest in een natuurlijk geventileerde stal (space-boarding)en op een volledige roostervloer.

  17. Interview met Leon Deben: van tegenstellingen leer je het meeste

    NARCIS (Netherlands)

    van Diepen, A.; Huisman, C.

    2008-01-01

    Wat in de jaren zeventig begonnen is als Sociologie van bouwen en wonen is uitgegroeid tot Stadssociologie. Leon Deben heeft het medeopgebouwd. Hij nam onlangs afscheid van de universiteit met een rede over de openbare ruimte. "Het centrale bestuur van de stad is druk met de waan van de dag en dan

  18. Mindfulness voor volwassenen met een licht verstandelijke beperking

    NARCIS (Netherlands)

    Punt, M.; Helmond, P.E.; Meirmans, M.; Otten, R.; Speckens, A.E.M.

    2016-01-01

    Mensen met een licht verstandelijke beperking (LVB) hebben veelal te maken met een opeenstapeling van verschillende biologische, psychologische en sociale factoren, waardoor zij vijf tot zes keer meer kans hebben op het ontwikkelen van psychopathologie dan normaal begaafden (Allen, 2008; Buckles,

  19. 'Epistemology models ontology'− In gesprek met John Polkinghorne

    African Journals Online (AJOL)

    Test

    7 Jun 2011 ... maar met die aard daarvan. Polkinghorne wil met sy boek One World (1996) presies sê wat die titel suggereer. Hiervoor kry hy die oplossing by sy mentor en latere kollega, Paul Dirac. Vir meer as 30 jaar het Dirac dieselfde leerstoel in Fisika aan Cambridge beklee as Isaac Newton (Polkinghorne 2005:34).

  20. Efficacy of c-Met inhibitor for advanced prostate cancer

    International Nuclear Information System (INIS)

    Tu, William H; Zhu, Chunfang; Clark, Curtis; Christensen, James G; Sun, Zijie

    2010-01-01

    Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer

  1. Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks

    DEFF Research Database (Denmark)

    Dodds, Chris M; Henson, Richard N; Suckling, John

    2013-01-01

    It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activatio...

  2. Modulating effect of COMT Val(158)Met polymorphism on interference resolution during a working memory task.

    Science.gov (United States)

    Jaspar, Mathieu; Dideberg, Vinciane; Bours, Vincent; Maquet, Pierre; Collette, Fabienne

    2015-04-01

    Genetic variability related to the catechol-O-methyltransferase (COMT) gene has received increasing attention in the last 15years, in particular as a potential modulator of the neural substrates underlying inhibitory processes and updating in working memory (WM). In an event-related functional magnetic resonance imaging (fMRI) study, we administered a modified version of the Sternberg probe recency task (Sternberg, 1966) to 43 young healthy volunteers, varying the level of interference across successive items. The task was divided into two parts (high vs. low interference) to induce either proactive or reactive control processes. The participants were separated into three groups according to their COMT Val(158)Met genotype [Val/Val (VV); Val/Met (VM); Met/Met (MM)]. The general aim of the study was to determine whether COMT polymorphism has a modulating effect on the neural substrates of interference resolution during WM processing. Results indicate that interfering trials were associated with greater involvement of frontal cortices (bilateral medial frontal gyrus, left precentral and superior frontal gyri, right inferior frontal gyrus) in VV homozygous subjects (by comparison to Met allele carriers) only in the proactive condition of the task. In addition, analysis of peristimulus haemodynamic responses (PSTH) revealed that the genotype-related difference observed in the left SFG was specifically driven by a larger increase in activity from the storage to the recognition phase of the interfering trials in VV homozygous subjects. These results confirm the impact of COMT genotype on inhibitory processes during a WM task, with an advantage for Met allele carriers. Interestingly, this impact on frontal areas is present only when the level of interference is high, and especially during the transition from storage to recognition in the left superior frontal gyrus. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks.

    Science.gov (United States)

    Dodds, Chris M; Henson, Richard N; Suckling, John; Miskowiak, Kamilla W; Ooi, Cinly; Tait, Roger; Soltesz, Fruzsina; Lawrence, Phil; Bentley, Graham; Maltby, Kay; Skeggs, Andrew; Miller, Sam R; McHugh, Simon; Bullmore, Edward T; Nathan, Pradeep J

    2013-01-01

    It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

  4. Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks.

    Directory of Open Access Journals (Sweden)

    Chris M Dodds

    Full Text Available It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

  5. Role of Met Axis in Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yiru, E-mail: xuyiru@umich.edu; Fisher, Gary J., E-mail: xuyiru@umich.edu [Department of Dermatology, University of Michigan, Ann Arbor, MI 48109 (United States)

    2013-11-26

    Head and neck cancer is the sixth most common type of cancer worldwide. Despite advances in aggressive multidisciplinary treatments, the 5-year survival rate for this dreadful disease is only 50%, mostly due to high rate of recurrence and early involvement of regional lymph nodes and subsequent metastasis. Understanding the molecular mechanisms responsible for invasion and metastasis is one of the most pressing goals in the field of head and neck cancer. Met, also known as hepatocyte growth factor receptor (HGFR), is a member of the receptor protein tyrosine kinase (RPTK) family. There is compelling evidence that Met axis is dysregulated and plays important roles in tumorigenesis, progression, metastasis, angiogenesis, and drug resistance in head and neck cancer. We describe in this review current understanding of Met axis in head and neck cancer biology and development of therapeutic inhibitors targeting Met axis.

  6. Met flora meer fauna de stad in trekken

    NARCIS (Netherlands)

    Hoffman, M.H.A.

    2010-01-01

    Meer flora en fauna in de stedelijke omgeving begint met de aanplant van gevarieerd groen. Plant Publicity Holland geeft in een overzicht aan welke bomen, heesters en vaste planten daarvoor geschikt zijn.

  7. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Science.gov (United States)

    Harri, A.-M.; Haukka, H.; Aleksashkin, S.; Arruego, I.; Schmidt, W.; Genzer, M.; Vazquez, L.; Siikonen, T.; Palin, M.

    2017-09-01

    A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  8. Leven met de varroamijt in de 21ste eeuw

    NARCIS (Netherlands)

    Blacquiere, T.; Cornelissen, B.; Smeekens, C.C.; Steen, van der J.J.M.

    2002-01-01

    Overzicht van voorhanden bestrijdingsmethoden tegen Varroa destructor op de korte termijn en vooruitzichten voor de bestrijding op langere termijn. In de nabije toekomst gaat het om bestrijding met diergeneesmiddelen van natuurlijke oorsprong (mierenzuur, oxaalzuur, thymol) in het kader van een

  9. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Science.gov (United States)

    Hari, Ari-Matti; Haukka, Harri; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Siikonen, Timo; Palin, Matti

    2017-04-01

    A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. 1. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. 2. Strawman Scientific Payload The strawman payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: - MetBaro Pressure device - MetHumi Humidity device - MetTemp Temperature sensors Optical devices: - PanCam Panoramic - MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer - DS Dust sensor Composition and Structure Devices: Tri-axial magnetometer MOURA Tri-axial System Accelerometer The descent processes dynamic properties are monitored by a special 3-axis

  10. Military Training: DOD Met Annual Reporting Requirements in Its 2016 Sustainable Ranges Report

    Science.gov (United States)

    2016-06-01

    copyrighted images or other material , permission from the copyright holder may be necessary if you wish to reproduce this material separately...which the report met mandated statutory requirements and whether DOD faced challenges in preparing its report. We conducted this performance audit ...from March 2016 to June 2016 in accordance with generally accepted government auditing standards. Those standards require that we plan and perform

  11. Effects of the BDNF Val66Met Polymorphism and Met Allele Load on Declarative Memory Related Neural Networks

    OpenAIRE

    Dodds, Chris M.; Henson, Richard N.; Suckling, John; Miskowiak, Kamilla W.; Ooi, Cinly; Tait, Roger; Soltesz, Fruzsina; Lawrence, Phil; Bentley, Graham; Maltby, Kay; Skeggs, Andrew; Miller, Sam R.; McHugh, Simon; Bullmore, Edward T.; Nathan, Pradeep J.

    2013-01-01

    It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including...

  12. Special Inspector General for Afghanistan Reconstruction Quarterly Report to the United States Congress

    Science.gov (United States)

    2011-04-30

    kilo- meter road will connect the country’s major cities.321 This project aligns with a key goal of the GIRoA’s Silk Road Initiative—to improve...Nangarhar, Nuristan, Ghazni, Paktika, Logar, Nimroz, Kandahar, Zabul AVIPA 74,168 vouchers redeemed for melon, legume, okra, vegetable, corn , and forage

  13. COMT (Val158Met and BDNF (Val66Met Genes Polymorphism in Schizophrenia: A Case-Control Report

    Directory of Open Access Journals (Sweden)

    ramin saravani

    2017-10-01

    Full Text Available Objective: The effects of human brain-derived neurotropic factor (BDNF Val66Met (G>A and the human Catechol-O-methylTransferase (COMT Val158Met (G>A polymorphisms on Schizophrenia (SCZ risk were evaluated.Methods: This case control study included 92 SCZ patients and 92 healthy controls (HCs. Genotyping of both variants were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR.Results: The findings showed that BDNF Val66Met (G>A variant increased the risk of SCZ (OR=2.008 95%CI=1.008-4.00, P=0.047, GA vs. GG, OR=3.876 95%CI=1.001-14.925, P=0.049. AA vs. GG, OR=2.272. 95%CI=1.204-4.347, P=0.011, GA+AA vs. GG, OR=2.22 95%CI=1.29-3.82. P=0.005, A vs. G. COMT Val158Met (G>A polymorphism was not associated with the risk/protective of SCZ.Conclusion: The results proposed that BDNF Val66Met (G>A polymorphism may increase the risk of SCZ development and did not support an association between COMT Val158Met (G>A variant and risk/protective of SCZ. Further studies and different ethnicities are recommended to confirm the findings.

  14. A comparison of metabolic syndrome (MetS) risk factors in Filipino women and Filipino American women: a pilot study.

    Science.gov (United States)

    Ancheta, Irma B; Battie, Cynthia A; Tuason, Teresa; Ancheta, Christine V

    2012-01-01

    Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in women of Filipino ethnicity. The objective of our work was to determine if metabolic syndrome (MetS), a modifiable CVD risk factor, differs in women as a function of country of residency and to determine if, CVD prevention strategies need to differ for these groups of Filipino women. Data were collected in community-based health screenings for this cross-sectional study. PARTICIPANTS were recruited at places of worship in southeast United States (n=60) and Central Visayas, Philippines (n=56). Prevalence of MetS and its component factors as defined by the International Diabetes Federation criteria. The prevalence of MetS in Filipino women (FW) and Filipino American women (FAW) groups was similar (52% vs 55%, P=.08) although the prevalence of elevated waist circumference was greater for FAW (78% vs 59%, P=.03). Conversely, the percentage of FW women with risk-associated high-density lipoprotein (HDL) levels was higher than the FAW group (84% vs 42%, PFilipino women regardless of the country of residency although the FAW tended to have higher rates of central obesity while the FW tended to have higher rates of risk-associated HDL levels. Further research should examine the cause of these differences in order to develop better cardiovascular screening and intervention strategies.

  15. Hydrogen storage capacity of titanium met-cars

    International Nuclear Information System (INIS)

    Akman, N; Durgun, E; Yildirim, T; Ciraci, S

    2006-01-01

    The adsorption of hydrogen molecules on the titanium metallocarbohedryne (met-car) cluster has been investigated by using the first-principles plane wave method. We have found that, while a single Ti atom at the corner can bind up to three hydrogen molecules, a single Ti atom on the surface of the cluster can bind only one hydrogen molecule. Accordingly, a Ti 8 C 12 met-car can bind up to 16 H 2 molecules and hence can be considered as a high-capacity hydrogen storage medium. Strong interaction between two met-car clusters leading to the dimer formation can affect H 2 storage capacity slightly. Increasing the storage capacity by directly inserting H 2 into the met-car or by functionalizing it with an Na atom have been explored. It is found that the insertion of neither an H 2 molecule nor an Na atom could further promote the H 2 storage capacity of a Ti 8 C 12 cluster. We have also tested the stability of the H 2 -adsorbed Ti 8 C 12 met-car with ab initio molecular dynamics calculations which have been carried out at room temperature

  16. MetReS, an Efficient Database for Genomic Applications.

    Science.gov (United States)

    Vilaplana, Jordi; Alves, Rui; Solsona, Francesc; Mateo, Jordi; Teixidó, Ivan; Pifarré, Marc

    2018-02-01

    MetReS (Metabolic Reconstruction Server) is a genomic database that is shared between two software applications that address important biological problems. Biblio-MetReS is a data-mining tool that enables the reconstruction of molecular networks based on automated text-mining analysis of published scientific literature. Homol-MetReS allows functional (re)annotation of proteomes, to properly identify both the individual proteins involved in the processes of interest and their function. The main goal of this work was to identify the areas where the performance of the MetReS database performance could be improved and to test whether this improvement would scale to larger datasets and more complex types of analysis. The study was started with a relational database, MySQL, which is the current database server used by the applications. We also tested the performance of an alternative data-handling framework, Apache Hadoop. Hadoop is currently used for large-scale data processing. We found that this data handling framework is likely to greatly improve the efficiency of the MetReS applications as the dataset and the processing needs increase by several orders of magnitude, as expected to happen in the near future.

  17. A Meteorological Distribution System for High Resolution Terrestrial Modeling (MicroMet)

    Science.gov (United States)

    Liston, G. E.; Elder, K.

    2004-12-01

    Spatially distributed terrestrial models generally require atmospheric forcing data on horizontal grids that are of higher resolution than available meteorological data. Furthermore, the meteorological data collected may not necessarily represent the area of interest's meteorological variability. To address these deficiencies, computationally efficient and physically realistic methods must be developed to take available meteorological data sets (e.g., meteorological tower observations) and generate high-resolution atmospheric-forcing distributions. This poster describes MicroMet, a quasi-physically-based, but simple meteorological distribution model designed to produce high-resolution (e.g., 5-m to 1-km horizontal grid increments) meteorological data distributions required to run spatially distributed terrestrial models over a wide variety of landscapes. The model produces distributions of the seven fundamental atmospheric forcing variables required to run most terrestrial models: air temperature, relative humidity, wind speed, wind direction, incoming solar radiation, incoming longwave radiation, and precipitation. MicroMet includes a preprocessor that analyzes meteorological station data and identifies and repairs potential data deficiencies. The model uses known relationships between meteorological variables and the surrounding area (primarily topography) to distribute those variables over any given landscape. MicroMet performs two kinds of adjustments to available meteorological data: 1) when there are data at more than one location, at a given time, the data are spatially interpolated over the domain using a Barnes objective analysis scheme, and 2) physical sub-models are applied to each MicroMet variable to improve its realism at a given point in space and time with respect to the terrain. The three, 25-km by 25-km, Cold Land Processes Experiment (CLPX) mesoscale study areas (MSAs: Fraser, North Park, and Rabbit Ears) will be used as example MicroMet

  18. Rocket experiment METS - Microwave Energy Transmission in Space

    Science.gov (United States)

    Kaya, N.; Matsumoto, H.; Akiba, R.

    A Microwave Energy Transmission in Space (METS) rocket experiment is being planned by the Solar Power Satellite Working Group at the Institute of Space and Astronautical Science in Japan for the forthcoming International Space Year, 1992. The METS experiment is an advanced version of the previous MINIX rocket experiment (Matsumoto et al., 1990). This paper describes a conceptual design of the METS rocket experiment. It aims at verifying a newly developed microwave energy transmission system for space use and to study nonlinear effects of the microwave energy beam in the space plasma environment. A high power microwave of 936 W will be transmitted by the new phased-array antenna from a mother rocket to a separated target (daughter rocket) through the ionospheric plasma. The active phased-array system has a capability of focusing the microwave energy around any spatial point by controlling the digital phase shifters individually.

  19. Rocket experiment METS Microwave Energy Transmission in Space

    Science.gov (United States)

    Kaya, N.; Matsumoto, H.; Akiba, R.

    A METS (Microwave Energy Transmission in Space) rocket experiment is being planned by the SPS (Solar Power Satellite) Working Group at the Institute of Space and Astronautical Science (ISAS) in Japan for the forthcoming International Space Year (ISY), 1992. The METS experiment is an advanced version of our MINIX rocket experiment. This paper describes the conceptual design for the METS rocket experiment. Aims are to verify the feasibility of a newly developed microwave energy transmission system designed for use in space and to study nonlinear effects of the microwave energy beam on space plasma. A high power microwave (936 W) will be transmitted by a new phase-array antenna from a mother rocket to a separate target (daughter rocket) through the Earth's ionospheric plasma. The active phased-array system has the capability of being able to focus the microwave energy at any spatial point by individually controlling the digital phase shifters.

  20. El acertijo de la metáfora visual

    OpenAIRE

    De la Rosa Alzate, Adriana; Universidad Autónoma de Occidente

    2016-01-01

    En este artículo se presentan los resultados de la investigación sobre el proceso de interpretación de la metáfora visual, en niños entre tres y cuatro años de edad. El propósito de la investigación fue dar cuenta del proceso de interpretación de la metáfora visual y del razonamiento involucrado. La metáfora visual se entiende como un fenómeno en el que los objetos representados presentan transformaciones que traen como consecuencia la emergencia de nuevas categorías e incluso la ambigüedad, ...

  1. Met Ed gets reprieve: banks lend tax money

    International Nuclear Information System (INIS)

    Utroska, D.

    1981-01-01

    A consortium of banks agreed to loan Metropolitan Edison $23 million to pay its April 15 state taxes and temporarily relieve a cash-flow problem that is leading to default after the Pennsylvania Public Utility Commission expedited a rate request. The continued solvency of Met Ed is a matter of speculation because the present credit formula is based on liquid assets which the PUC did not address. While the action taken by the bankers gives Met Ed a reprieve, it does not provide a long-term solution. The Revolving Credit Agreement will expire on October 1. Met Ed is still faced with the problem of relicensing Three Mile Island-1 unit and the cost of underwriting the cleanup of the No. 2 unit

  2. Remembering the early days of the Met Lab

    International Nuclear Information System (INIS)

    Katz, J.J.

    1990-01-01

    The Met Lab was set up by the war-time Manhattan District, US Corp of Engineers to (i) find a system using normal uranium in which a chain reaction would occur; (ii) to show that if such a chain reaction did occur, it would be possible to separate plutonium chemically from the uranium matrix and the fission products formed in the chain reactions; and (iii) to prepare plans for the large-scale production of plutonium. Chemistry Section C-1 of the Met Lab was assigned the responsibility for developing separation methods for plutonium production on the industrial scale. This report describes some aspects of daily life in Section C-1

  3. Sustainable energy with thermochemical storage; Duurzame energie met thermochemische opslag

    Energy Technology Data Exchange (ETDEWEB)

    Bakker, M. [ECN Efficiency and Infrastructure, Petten (Netherlands)

    2010-03-15

    The Energy research Centre of the Netherlands ECN) foresees an important role for heat in sustainable construction of buildings. Using salt hydrates the surplus of heat can be stored in the summer which then can be used in the winter. By means of thermochemical storage natural gas for heating tap water or houses is no longer necessary. [Dutch] Energieonderzoek Centrum Nederland (ECN) ziet voor warmteopslag een belangrijke rol weggelegd in het duurzaam bouwen. Met behulp van zouthydraten kan de overtollige warmte in de zomer opgeslagen worden om deze in de winter weer vrij te maken. Met deze thermochemische opslag is in de nabije toekomst aardgas overbodig voor de verwarming van kraanwater of woonhuis.

  4. Physiological Signaling and Structure of the HGF Receptor MET

    Directory of Open Access Journals (Sweden)

    Gianluca Baldanzi

    2014-12-01

    Full Text Available The “hepatocyte growth factor” also known as “scatter factor”, is a multifunctional cytokine with the peculiar ability of simultaneously triggering epithelial cell proliferation, movement and survival. The combination of those proprieties results in the induction of an epithelial to mesenchymal transition in target cells, fundamental for embryogenesis but also exploited by tumor cells during metastatization. The hepatocyte growth factor receptor, MET, is a proto-oncogene and a prototypical transmembrane tyrosine kinase receptor. Inhere we discuss the MET molecular structure and the hepatocyte growth factor driven physiological signaling which coordinates epithelial proliferation, motility and morphogenesis.

  5. The MetSkill Program — Rapidly Developing Effective Young Engineers in the Workplace

    Science.gov (United States)

    Drinkwater, Diana; Bianco, Nina

    MetSkill is a professional development program for metallurgical engineers that integrates with normal duties in their first one or two years of service. Graduates work together on a structured technical project, facilitated by specialists and supported by formal learning, and ultimately reported to their technical managers. The program enables graduates to "fill the gaps" in their undergraduate education, which is increasingly pertinent as engineering degrees become more general. Participants report that they enjoy the focus on more challenging (rewarding) aspects of their jobs and feel more confident about problem solving. Sponsor companies add that the relationships developed with external technical specialists enhances opportunities for innovation and development. MetSkill was delivered to two major resource companies in Australia in 2012. This paper provides an outline of the program and the reasons for its success, and demonstrates how the learning model could be applied to groups of graduates in other engineering disciplines.

  6. Zuivering brouwerijprocesafvalwater met behulp van microalgen: Resultaten onderzoek 2012

    NARCIS (Netherlands)

    Dijk, van W.; Schipperus, R.; Grobben, S.A.; Weide, van der R.Y.

    2013-01-01

    In een samenwerkingsverband van Heineken Nederland BV, Algae Food & Fuel en WUR (Acrres) is in 2012 een onderzoeksproject gestart om de mogelijkheden van zuivering van procesafvalwater van de brouwerijen met behulp van algen te onderzoeken. In het kader van dit project is in 2012 een

  7. Christus' offer bij Paulus vergeleken met de offeropvattingen van Philo

    NARCIS (Netherlands)

    Stelma, Juurd Hari

    1938-01-01

    Een vergelijking der offeropvattingen van Paulus en Philo brengt ons in aanraking met twee principieel verschillende voorstellingen aangaande het offer. Het offer van Christus is voor Paulus de gave Gods, waardoor de macht van de zonde en dood vernietigd en de schuld verzoend is. Door de

  8. Constant Cremer, voetballer in Tilburg met Afrikaanse wortels

    NARCIS (Netherlands)

    Drs. Thijs Kemmeren

    2012-01-01

    Constant Cremer is de eerste zwarte voetballer in Nederland. Hij is geboren in Belgisch Congo. Hij speelde bij Willem II in het seizoen 1904 -1905 en werd met Willem II Brabvants kampioen. Constant werd, als een donkere mulat een held in Tilburg. Hij kwam uiteindelijk terecht in Nederland Indie en

  9. Workshop ALOUD 'Onderzoek voor, door en met de OU'

    NARCIS (Netherlands)

    Gijselaers, Jérôme; De Groot, Renate

    2015-01-01

    Vraagt u zich wel eens af wat de doorsnee kenmerken zijn van de OU-student? Hoeveel studenten daadwerkelijk starten met de studeren? Wie van deze groep succesvol zijn? En welke verschillen er zitten tussen de faculteiten? En wilt u meedenken over wat voor details we van studenten willen weten voor

  10. Beoordeling gezondheidsrisico's door sporten op kunstgrasvelden met rubbergranulaat

    NARCIS (Netherlands)

    Oomen AG; de Groot GM; CPV; M&V

    2016-01-01

    Uit nieuw onderzoek van het RIVM blijkt dat het risico voor de gezondheid van sporten op kunstgrasvelden die zijn ingestrooid met rubbergranulaat, praktisch verwaarloosbaar is. Dat betekent dat het verantwoord is om op deze velden te sporten. Aanleiding voor het onderzoek is de maatschappelijke

  11. Van Weel: "Werken met minimumbuis de gebruikelijke, maar foute weg"

    NARCIS (Netherlands)

    Staalduinen, van J.; Weel, van P.A.

    2008-01-01

    Door het aanzuigen en in de kas brengen van relatief droge, voorverwarmde buitenlucht is de RV in de kas te verlagen en beter te beheersen. Omdat ook de verticale temperatuurverschillen afnemen, is het mogelijk om intensiever te schermen. Met Aircobreezeventilatoren, die via kieren of gaten lucht

  12. Ervaringen met ICT-onderzoek in het HBO.

    NARCIS (Netherlands)

    van Leeuwen, H.; Teeuw, W.J.; Tangelder, R.; Griffioen, P.; Krose, B.; Schouten, B.

    2011-01-01

    In dit artikel wordt het belang aangegeven van onderzoeksvaardigheden in het HBO. Met de komst van de lectoraten en de nieuwe positionering van het HBO is het belangrijk om een antwoord te vinden hoe het onderzoek binnen het HBO vormgegeven moet worden. Hierbij wordt gekeken naar de bruikbaarheid

  13. Imidacloprid of niet? (interview met Sjef van der Steen)

    NARCIS (Netherlands)

    Kleis, R.; Steen, van der J.J.M.

    2014-01-01

    Is bijensterfte het werk van neonicotinoïden? Ja, zeggen en denken velen. Volgens hen zijn de neo’s rechtstreeks verantwoordelijk voor de hoge sterfte onder bijen. Nee, toont Wagenings onderzoek aan. Intussen lijkt het met de sterfte voorzichtig de goede kant op te gaan.

  14. Vers bloed voor spinazie (interview met C. Kik)

    NARCIS (Netherlands)

    Nijland, R.; Kik, C.

    2011-01-01

    Chris Kik van het Centrum voor Genetische Bronnen Nederland (CGN) keerde afgelopen weekend terug van een eenmansexpeditie door Azerbeidzjan, Georgië en Armenië. Resultaat van de reis: een koffer volgepropt met 53 witte linnen zakjes zaad van wilde en lokaal geteelde spinazie. Dat materiaal gaat

  15. Slim in het verkeer met open data : adviesrapport

    NARCIS (Netherlands)

    Boelens, Danny; Plasmeyer, Luuk; van Heesewijk, Nick; Smeenge, Tetiana; Hoekzema, Niek; McCreesh, Séamus

    2013-01-01

    Rapport in opdracht van de gemeente Groningen. Aanleiding voor het schrijven van dit rapport is dat de gemeente Groningen graag wil weten hoe ze met het gebruik van open data het (openbaar) vervoer voor studenten in en naar de stad Groningen kunnen verbeteren. Het onderzoek richtte zich daarom op

  16. Een bepalingsmethode voor thallium in regenwater met behulp van voltammetrie

    NARCIS (Netherlands)

    Struijs; J.; Wolfs; P.M.; Esseveld; F.G.van

    1985-01-01

    In dit rapport wordt een bepalingmethode beschreven voor thallium in het nanogram/liter-gebied, waarbij gebruik wordt gemaakt van differentiele pulse-anodic stripping voltammetry (DPASV) aan de dunne kwikfilm. Met deze techniek blijkt het mogelijk om de concentratie van dit element rechtstreeks

  17. Subtiel verleiden met nudging : Verhogen van enquêterespons

    NARCIS (Netherlands)

    V. Versluis; dr. A.F. de Wild

    2015-01-01

    De nonrespons op enquêtes onder studenten is vaak hoog, waardoor verkregen informatie niet altijd betrouwbaar en valide is. Met nudges, subtiele interventies die gebaseerd zijn op inzichten uit de psychologie en sociologie, kan de respons op enquêtes aanzienlijk worden verhoogd. Bij de uitrol van

  18. Aan de slag met honors : praktijklessen uit Europa

    NARCIS (Netherlands)

    Wolfensberger, Marca; Hogenstijn, Maarten

    2015-01-01

    In de brochure ‘Aan de slag met honors’ worden onderzoeksresultaten van het onderzoeksproject Honors in Europe hertaald naar tips voor succesvol en inspirerend honorsonderwijs. De brochure is grotendeels gebaseerd op het boek Talent Development in European Higher Education – Honors programs in the

  19. San Diego Met High School: Personalization as a Foundation

    Science.gov (United States)

    Principal Leadership, 2010

    2010-01-01

    The mission of San Diego Met High School is to prepare students for college and the workforce through active learning, academic rigor, and community involvement in a small school setting. Because personalization is a key component of the school culture, advisories of 20-25 students work with the same teachers for all four years. Advisers, parents,…

  20. Randvoorwaarden ontwerp happy games voor ouderen met dementie

    NARCIS (Netherlands)

    Dr. A.L. Cordia

    2014-01-01

    Deze publicatie is in twee fasen tot stand gekomen tijdens het In Touch onderzoek. De eerste fase had als doel de randvoorwaarden te bepalen voor het ontwerpen van drie nieuwe iPad spellen voor ouderen met dementie en betrof een beperkt literatuuronderzoek op gerelateerde onderwerpen, daar

  1. Stalboekje varkens : natuurlijk gezond met kruiden en andere natuurproducten

    NARCIS (Netherlands)

    Groot, M.J.; Kleijer-Ligtenberg, G.; Asseldonk, van T.

    2014-01-01

    Het streven om het gebruik van antibiotica terug te dringen vraagt om een ander management. Goede voeding, huisvesting en hygiëne zijn hierbij belangrijk. In dit boekje worden handvaten gegeven om met natuurlijke middelen de gezondheid van de dieren te bevorderen en zo ziektes te voorkomen. Tevens

  2. Met hard werken alleen is niets mis : werkdruk en stress

    NARCIS (Netherlands)

    Klein Hesselink, J.; Man, M. de; Heeten, W. den

    1996-01-01

    Als men continu onder flinke druk werkt en die druk ook als last wordt ervaren, ontstaan klachten. Omgaan met werkdruk en werkstress is te leren. De cursus 'Anders werken' biedt die mogelijkheid. Dit artikel geeft na enige statische gevens over stress een nadere definiëring van het begrip

  3. Kenmerken en recidivecijfers van ex-terbeschikkinggestelden met een zedendelict

    NARCIS (Netherlands)

    Schönberger, H.J.M.; Kogel, C.H. de; Bregman, I.M.

    2012-01-01

    Dit rapport beschrijft de omvang, achtergrondkenmerken en recidivegegevens van tbs-gestelden met een zedendelict als indexdelict. Het indexdelict is het delict waarvoor de tbs-maatregel is opgelegd. Twee populaties zedendelinquenten komen aan de orde. De eerste populatie, de 'uitstroompopulatie',

  4. Praktijkervaringen met de Venlow energy kas 2010-2012

    NARCIS (Netherlands)

    Kempkes, F.L.K.; Janse, J.

    2013-01-01

    NL De energiebesparing bij het nieuwe telen werd tot nu toe altijd bereikt door meer schermen te gebruiken. Een alternatief is toepassing van isolatieglas dat door de komst van coatings zoals Anti Refl ectie een vergelijkbare transmissie heeft als standaard enkel glas. Met een aangepast

  5. MET-RODOS: A comprehensive atmospheric dispersion module

    DEFF Research Database (Denmark)

    Mikkelsen, T.; Thykier-Nielsen, S.; Astrup, P.

    1997-01-01

    A comprehensive meteorological dispersion module called MET-RODOS is being developed to serve the real-time RODOS(1-3) decision support system with an integrated prediction capability for airborne radioactive spread, deposition and gamma radiation exposure on all scales. Deposition, ground level ...

  6. Vakansiehuis met swembad. Herman Koch. Vertaal deur Daniel ...

    African Journals Online (AJOL)

    - tig minuten (“my verkoopspunt”), maar. “[p]asiënte verwar tyd met aandag”. Marc luistert niet echt, want een huisarts. “hoef mense nie gesond te maak nie” (12). En als ze zich niet laten afschepen, doet hij maar een rectaal touché, want “hulle.

  7. MetAssimulo:Simulation of Realistic NMR Metabolic Profiles

    Directory of Open Access Journals (Sweden)

    De Iorio Maria

    2010-10-01

    Full Text Available Abstract Background Probing the complex fusion of genetic and environmental interactions, metabolic profiling (or metabolomics/metabonomics, the study of small molecules involved in metabolic reactions, is a rapidly expanding 'omics' field. A major technique for capturing metabolite data is 1H-NMR spectroscopy and this yields highly complex profiles that require sophisticated statistical analysis methods. However, experimental data is difficult to control and expensive to obtain. Thus data simulation is a productive route to aid algorithm development. Results MetAssimulo is a MATLAB-based package that has been developed to simulate 1H-NMR spectra of complex mixtures such as metabolic profiles. Drawing data from a metabolite standard spectral database in conjunction with concentration information input by the user or constructed automatically from the Human Metabolome Database, MetAssimulo is able to create realistic metabolic profiles containing large numbers of metabolites with a range of user-defined properties. Current features include the simulation of two groups ('case' and 'control' specified by means and standard deviations of concentrations for each metabolite. The software enables addition of spectral noise with a realistic autocorrelation structure at user controllable levels. A crucial feature of the algorithm is its ability to simulate both intra- and inter-metabolite correlations, the analysis of which is fundamental to many techniques in the field. Further, MetAssimulo is able to simulate shifts in NMR peak positions that result from matrix effects such as pH differences which are often observed in metabolic NMR spectra and pose serious challenges for statistical algorithms. Conclusions No other software is currently able to simulate NMR metabolic profiles with such complexity and flexibility. This paper describes the algorithm behind MetAssimulo and demonstrates how it can be used to simulate realistic NMR metabolic profiles with

  8. 75 FR 1007 - MetLife, Inc. and MetLife Capital Trust V; Notice of Application

    Science.gov (United States)

    2010-01-07

    ... the definition of investment company by section 3(b) of the Act or by the rules or regulations under... Act for an exclusion from the definition of an investment company. To the extent MetLife or another... definition of a ``parent company'' in rule 3a-5(b)(2)(i) solely because it is an ``insurance company'' or...

  9. Activating mutation in MET oncogene in familial colorectal cancer

    Directory of Open Access Journals (Sweden)

    Schildkraut Joellen M

    2011-10-01

    Full Text Available Abstract Background In developed countries, the lifetime risk of developing colorectal cancer (CRC is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The MET proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility. Methods MET exons were amplified by PCR from germline DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered sequence were detected with high-resolution melt-curve analysis using a LightScanner (Idaho Technologies. Samples demonstrating alternative melt curves were sequenced. A TaqMan assay for the specific c.2975C >T change was used to confirm this mutation in a cohort of 299 colorectal cancer cases and to look for allelic amplification in tumors. Results Here we report a germline non-synonymous change in the MET proto-oncogene at amino acid position T992I (also reported as MET p.T1010I in 5.2% of a cohort of sibling pairs affected with CRC. This genetic variant was then confirmed in a second cohort of individuals diagnosed with CRC and having a first degree relative with CRC at prevalence of 4.1%. This mutation has been reported in cancer cells of multiple origins, including 2.5% of colon cancers, and in Conclusions Although the MET p.T992I genetic mutation is commonly found in somatic colorectal cancer tissues, this is the first report also implicating this MET genetic mutation as a germline inherited risk factor for familial colorectal cancer. Future studies on the cancer risks associated with this mutation and the prevalence in different at-risk populations will

  10. BDNF val66met polymorphism is associated with age at onset and intensity of symptoms of paranoid schizophrenia in a Polish population.

    Science.gov (United States)

    Suchanek, Renata; Owczarek, Aleksander; Paul-Samojedny, Monika; Kowalczyk, Małgorzata; Kucia, Krzysztof; Kowalski, Jan

    2013-01-01

    The brain-derived neurotrophic factor (BDNF) is one of the candidate genes for schizophrenia. There is evidence that val66met polymorphism may be involved in the pathophysiology of schizophrenia. The authors genotyped val66met (rs6265) polymorphism of the BDNF gene in 208 inpatients with paranoid schizophrenia and 254 control subjects in a Polish population. There was no association between val66met polymorphism and development of paranoid schizophrenia in either men or women. However, an association was found between this polymorphism and age at onset and psychopathology of paranoid schizophrenia. Men with the val/met genotype had an earlier age at onset, and the val/val genotype predisposed to more severe symptoms, particularly on the General Psychopathology Scale of the Positive and Negative Symptoms Scale (PANSS-G). The analysis of PANSS single items has shown that patients with the val/met genotype had higher scores on a hallucinatory behavior item than those with other genotypes.

  11. Remote Sensing of Volcanic ASH at the Met Office

    Directory of Open Access Journals (Sweden)

    Marenco F.

    2016-01-01

    Full Text Available The eruption of Eyjafjallajökull in 2010 has triggered the rapid development of volcanic ash remote sensing activities at the Met Office. Volcanic ash qualitative and quantitative mapping have been achieved using lidar on board the Facility for Airborne Atmospheric Measurements (FAAM research aircraft, and using improved satellite retrieval algorithms. After the eruption, a new aircraft facility, the Met Office Civil Contingencies Aircraft (MOCCA, has been set up to enable a rapid response, and a network of ground-based remote sensing sites with lidars and sunphotometers is currently being developed. Thanks to these efforts, the United Kingdom (UK will be much better equipped to deal with such a crisis, should it happen in the future.

  12. Operational Use of OGC Web Services at the Met Office

    Science.gov (United States)

    Wright, Bruce

    2010-05-01

    The Met Office has adopted the Service-Orientated Architecture paradigm to deliver services to a range of customers through Rich Internet Applications (RIAs). The approach uses standard Open Geospatial Consortium (OGC) web services to provide information to web-based applications through a range of generic data services. "Invent", the Met Office beta site, is used to showcase Met Office future plans for presenting web-based weather forecasts, product and information to the public. This currently hosts a freely accessible Weather Map Viewer, written in JavaScript, which accesses a Web Map Service (WMS), to deliver innovative web-based visualizations of weather and its potential impacts to the public. The intention is to engage the public in the development of new web-based services that more accurately meet their needs. As the service is intended for public use within the UK, it has been designed to support a user base of 5 million, the analysed level of UK web traffic reaching the Met Office's public weather information site. The required scalability has been realised through the use of multi-tier tile caching: - WMS requests are made for 256x256 tiles for fixed areas and zoom levels; - a Tile Cache, developed in house, efficiently serves tiles on demand, managing WMS request for the new tiles; - Edge Servers, externally hosted by Akamai, provide a highly scalable (UK-centric) service for pre-cached tiles, passing new requests to the Tile Cache; - the Invent Weather Map Viewer uses the Google Maps API to request tiles from Edge Servers. (We would expect to make use of the Web Map Tiling Service, when it becomes an OGC standard.) The Met Office delivers specialist commercial products to market sectors such as transport, utilities and defence, which exploit a Web Feature Service (WFS) for data relating forecasts and observations to specific geographic features, and a Web Coverage Service (WCS) for sub-selections of gridded data. These are locally rendered as maps or

  13. Estimation of METs by Accelerometers while Walking and Running

    Science.gov (United States)

    Kurihara, Yosuke; Watanabe, Kajiro; Yoneyama, Mitsuru

    It is quite important for Japan to maintain or promote the health condition of elderly citizens. Given the circumstances, the Ministry of Health, Labour and Welfare has established the standards for the activities and exercises for promoting the health, and quantitatively determined the exercise intensity on 107 items of activities. This exercise intensity, however, requires recording the type and the duration of the activity to be calculated. In this paper, the exercise intensities are surmised using 3D accelerometer while the subjects are walking and running. As the result, the exercise intensities were surmised to be within the root mean square error of 1.2[METs] for walking and 3.2[METs] for running respectively.

  14. Testing ATLAS Z+MET excess with LHC run 2

    International Nuclear Information System (INIS)

    Lu, Xiaochuan; Terada, Takahiro

    2016-05-01

    The ATLAS collaboration reported a 3σ excess in the search of events containing on-Z dilepton, jets, and large missing momentum (MET) in the 8 TeV LHC run. Motivated by this excess, many models of new physics have been proposed. Recently, the ATLAS and CMS collaborations reported new results for similar Z+MET channels in the 13 TeV run. In this paper, we comprehensively discuss the consistency between the proposed models and the LHC results of Run 1 and Run 2. We find that in models with heavy gluino production, there is generically some tension between the 8 TeV and 13 TeV results. On the other hand, models with light squark production provide relatively better fitting to both results.

  15. Cetuximab-Induced MET Activation Acts as a Novel Resistance Mechanism in Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Na Song

    2014-04-01

    Full Text Available Aberrant MET expression and hepatocyte growth factor (HGF signaling are implicated in promoting resistance to targeted agents; however, the induced MET activation by epidermal growth factor receptor (EGFR inhibitors mediating resistance to targeted therapy remains elusive. In this study, we identified that cetuximab-induced MET activation contributed to cetuximab resistance in Caco-2 colon cancer cells. MET inhibition or knockdown sensitized Caco-2 cells to cetuximab-mediated growth inhibition. Additionally, SRC activation promoted cetuximab resistance by interacting with MET. Pretreatment with SRC inhibitors abolished cetuximab-mediated MET activation and rendered Caco-2 cells sensitive to cetuximab. Notably, cetuximab induced MET/SRC/EGFR complex formation. MET inhibitor or SRC inhibitor suppressed phosphorylation of MET and SRC in the complex, and MET inhibitor singly led to disruption of complex formation. These results implicate alternative targeting of MET or SRC as rational strategies for reversing cetuximab resistance in colon cancer.

  16. MetWAMer: eukaryotic translation initiation site prediction

    Directory of Open Access Journals (Sweden)

    Brendel Volker

    2008-09-01

    Full Text Available Abstract Background Translation initiation site (TIS identification is an important aspect of the gene annotation process, requisite for the accurate delineation of protein sequences from transcript data. We have developed the MetWAMer package for TIS prediction in eukaryotic open reading frames of non-viral origin. MetWAMer can be used as a stand-alone, third-party tool for post-processing gene structure annotations generated by external computational programs and/or pipelines, or directly integrated into gene structure prediction software implementations. Results MetWAMer currently implements five distinct methods for TIS prediction, the most accurate of which is a routine that combines weighted, signal-based translation initiation site scores and the contrast in coding potential of sequences flanking TISs using a perceptron. Also, our program implements clustering capabilities through use of the k-medoids algorithm, thereby enabling cluster-specific TIS parameter utilization. In practice, our static weight array matrix-based indexing method for parameter set lookup can be used with good results in data sets exhibiting moderate levels of 5'-complete coverage. Conclusion We demonstrate that improvements in statistically-based models for TIS prediction can be achieved by taking the class of each potential start-methionine into account pending certain testing conditions, and that our perceptron-based model is suitable for the TIS identification task. MetWAMer represents a well-documented, extensible, and freely available software system that can be readily re-trained for differing target applications and/or extended with existing and novel TIS prediction methods, to support further research efforts in this area.

  17. El sexo de las metáforas

    Directory of Open Access Journals (Sweden)

    Pérez Sedeño, Eulalia

    2011-02-01

    Full Text Available The hypothesis that states metaphors are structurally determinant in our social relations, routines, and experience has been accepted broadly in the last decades. Moreover, metaphors are to be found in many different levels of scientific practices, and have a diverse set of functions in science. Therefore, they impregnate all scientific enterprise. In this work we examine selected gender metaphors used in biology. We show metaphors are effective precisely because its effectiveness depends on shared social conventions, kinship relations and, authority that, by convention, is given to those that use them.

    La tesis de que las metáforas estructuran gran parte de nuestras relaciones sociales y nuestra experiencia cotidiana ha sido ampliamente aceptada en las últimas décadas. En la ciencia, además, aparecen en muchos niveles y desempeñan diversas funciones, impregnando todo el quehacer científico. En este trabajo se examinan algunas metáforas de género usadas en biología. Se muestra que las metáforas eficaces lo son porque su efectividad depende de las convenciones sociales compartidas, los parecidos de familia ya vigentes y de la autoridad que, por convención, se otorga a quienes las usan.

  18. The EGFR/ErbB3 Pathway Acts as a Compensatory Survival Mechanism upon c-Met Inhibition in Human c-Met+ Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Steven N Steinway

    Full Text Available c-Met, a high-affinity receptor for Hepatocyte Growth Factor (HGF, plays a critical role in tumor growth, invasion, and metastasis. Hepatocellular carcinoma (HCC patients with activated HGF/c-Met signaling have a significantly worse prognosis. Targeted therapies using c-Met tyrosine kinase inhibitors are currently in clinical trials for HCC, although receptor tyrosine kinase inhibition in other cancers has demonstrated early success. Unfortunately, therapeutic effect is frequently not durable due to acquired resistance.We utilized the human MHCC97-H c-Met positive (c-Met+ HCC cell line to explore the compensatory survival mechanisms that are acquired after c-Met inhibition. MHCC97-H cells with stable c-Met knockdown (MHCC97-H c-Met KD cells were generated using a c-Met shRNA vector with puromycin selection and stably transfected scrambled shRNA as a control. Gene expression profiling was conducted, and protein expression was analyzed to characterize MHCC97-H cells after blockade of the c-Met oncogene. A high-throughput siRNA screen was performed to find putative compensatory survival proteins, which could drive HCC growth in the absence of c-Met. Findings from this screen were validated through subsequent analyses.We have previously demonstrated that treatment of MHCC97-H cells with a c-Met inhibitor, PHA665752, results in stasis of tumor growth in vivo. MHCC97-H c-Met KD cells demonstrate slower growth kinetics, similar to c-Met inhibitor treated tumors. Using gene expression profiling and siRNA screening against 873 kinases and phosphatases, we identified ErbB3 and TGF-α as compensatory survival factors that are upregulated after c-Met inhibition. Suppressing these factors in c-Met KD MHCC97-H cells suppresses tumor growth in vitro. In addition, we found that the PI3K/Akt signaling pathway serves as a negative feedback signal responsible for the ErbB3 upregulation after c-Met inhibition. Furthermore, in vitro studies demonstrate that

  19. Intracerebral beta-endorphin, met-enkephalin and morphine: kindling of seizures and handling-induced potentiation of epileptiform effects.

    Science.gov (United States)

    Cain, D P; Corcoran, M E

    1984-06-18

    The effects of repeated infusion of small, initially subconvulsive amounts of beta-endorphin, met-enkephalin or morphine sulfate into the amygdala and hippocampus were investigated. beta-endorphin and met-enkephalin evoked epileptiform spiking when infused into the posterior amygdala or ventral hippocampus. Morphine evoked epileptiform spiking when infused into the anterior amygdala. Naloxone blocked or terminated the spiking. Repetition of the infusions led to the gradual development of bilateral generalized convulsions by beta-endorphin and met-enkephalin and to the development of tolerance to morphine. An unexpected observation was that handling, immobilization or conspecific threat potentiated the epileptiform effects of beta-endorphin and morphine in many cases. These results suggest that endogenous opiate mechanisms might play a role in convulsive seizures and that stressful stimuli can exacerbate opiate seizures.

  20. Generalized Superconductivity. Generalized Levitation

    International Nuclear Information System (INIS)

    Ciobanu, B.; Agop, M.

    2004-01-01

    In the recent papers, the gravitational superconductivity is described. We introduce the concept of generalized superconductivity observing that any nongeodesic motion and, in particular, the motion in an electromagnetic field, can be transformed in a geodesic motion by a suitable choice of the connection. In the present paper, the gravitoelectromagnetic London equations have been obtained from the generalized Helmholtz vortex theorem using the generalized local equivalence principle. In this context, the gravitoelectromagnetic Meissner effect and, implicitly, the gravitoelectromagnetic levitation are given. (authors)

  1. Deelname aan de samenleving van mensen met een beperking: participatiemonitor 2007.

    NARCIS (Netherlands)

    Hoogen, P. van den; Cardol, M.; Speet, M.; Spreeuwenberg, P.; Rijken, M.

    2008-01-01

    Hoe doen mensen met een beperking mee in de maatschappij? Mensen met een lichamelijke beperking wonen en werken meestal net als iedereen, en ook zij zijn niet altijd tevreden met hun werk. Mensen met een verstandelijke beperking wonen en werken vaak in een speciale omgeving. Het overheidsbeleid

  2. 32 CFR 154.40 - General.

    Science.gov (United States)

    2010-07-01

    ... PROGRAM REGULATION Adjudication § 154.40 General. (a) The standard which must be met for clearance or assignment to sensitive duties is that, based on all available information, the person's loyalty, reliability...

  3. MET gene exon 14 deletion created using the CRISPR/Cas9 system enhances cellular growth and sensitivity to a MET inhibitor.

    Science.gov (United States)

    Togashi, Yosuke; Mizuuchi, Hiroshi; Tomida, Shuta; Terashima, Masato; Hayashi, Hidetoshi; Nishio, Kazuto; Mitsudomi, Tetsuya

    2015-12-01

    MET splice site mutations resulting in an exon 14 deletion have been reported to be present in about 3% of all lung adenocarcinomas. Patients with lung adenocarcinoma and a MET splice site mutation who have responded to MET inhibitors have been reported. The CRISPR/Cas9 system is a recently developed genome-engineering tool that can easily and rapidly cause small insertions or deletions. We created an in vitro model for MET exon 14 deletion using the CRISPR/Cas9 system and the HEK293 cell line. The phenotype, which included MET inhibitor sensitivity, was then investigated in vitro. Additionally, MET splice site mutations were analyzed in several cancers included in The Cancer Genome Atlas (TCGA) dataset. An HEK293 cell line with a MET exon 14 deletion was easily and rapidly created; this cell line had a higher MET protein expression level, enhanced MET phosphorylation, and prolonged MET activation. In addition, a direct comparison of phenotypes using this system demonstrated enhanced cellular growth, colony formation, and MET inhibitor sensitivity. In the TCGA dataset, lung adenocarcinomas had the highest incidence of MET exon 14 deletions, while other cancers rarely carried such mutations. Approximately 10% of the lung adenocarcinoma samples without any of driver gene alterations carried the MET exon 14 deletion. These findings suggested that this system may be useful for experiments requiring the creation of specific mutations, and the present experimental findings encourage the development of MET-targeted therapy against lung cancer carrying the MET exon 14 deletion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Deelname aan de samenleving van mensen met een beperking: participatiemonitor 2007.

    OpenAIRE

    Hoogen, P. van den; Cardol, M.; Speet, M.; Spreeuwenberg, P.; Rijken, M.

    2008-01-01

    Hoe doen mensen met een beperking mee in de maatschappij? Mensen met een lichamelijke beperking wonen en werken meestal net als iedereen, en ook zij zijn niet altijd tevreden met hun werk. Mensen met een verstandelijke beperking wonen en werken vaak in een speciale omgeving. Het overheidsbeleid is erop gericht dat iedereen – dus ook mensen met een beperking – zoveel mogelijk ‘gewoon mee kan doen’ in de maatschappij. Bijvoorbeeld werken bij een gewone werkgever, schoolgaan op een gewone school...

  5. Sandscape - engaging people in Met Office science through sand sculpture

    Science.gov (United States)

    Liggins, Felicity; Dowell, Ellen; Wardley, Jamie; Jamieson, Claire

    2017-04-01

    In 2015, the Met Office's award-winning outreach programme, designed to inspire the next generation of scientists and engineers, delivered one of its most ambitious and creative activities to date. It explored how scientists and artists can come together to create an engaging experience for young people and families. This activity was called Sandscape. Sandscape is an interactive sand sculpture workshop exploring how weather and climate affect our health. Budding sand sculptors are shown how to fashion elaborate structures from sand and water - creating a landscape with bridges, skyscrapers, forests and factories. As they work, participants are encouraged by the scientists delivering the activity to reflect on what makes a healthy city, considering how the natural and built environments influence air quality and circulation and how this impacts our health. Topics discussed include urban heat islands, air pollution and dispersion modelling, pollen forecasting and predicting the wind-borne spread of animal diseases. Each hour long workshop culminates in a dramatic demonstration that uses dry ice to represent clean air circulating from mountains, along rivers and into cities. Here we present an overview of Sandscape, identify the strengths and challenges of such a collaborative, innovative and playful approach to public engagement and share the results of our evaluation. Sandscape was originally supported by the Met Office and the Wellcome Trust, and produced by Einstein's Garden in collaboration with the Met Office, scientists from the University of Exeter and sand sculptors from Sand in Your Eye. It was first presented in Einstein's Garden at Green Man festival 2015, an independent music and arts festival held annually in Wales, and has since been invited to run at the 2015 Bournemouth Arts By the Sea Festival and Teignmouth's TRAIL Sculpture Festival in the summer of 2016.

  6. Met receptor inhibitor SU11274 localizes in the endoplasmic reticulum.

    Science.gov (United States)

    Wiest, Edwin J; Smith, Heather Jensen; Hollingsworth, Michael A

    2018-07-02

    We discovered that SU11274, a class I c-Met inhibitor, fluoresces when excited by 488 nm laser light and showed rapid specific accumulation in distinct subcellular compartments. Given that SU11274 reduces cancer cell viability, we exploited these newly identified spectral properties to determine SU11274 intracellular distribution and accumulation in human pancreatic cancer cells. The aim of the studies reported here was to identify organelle(s) to which SU11274 is trafficked. We conclude that SU11274 rapidly and predominantly accumulates in the endoplasmic reticulum. Copyright © 2018. Published by Elsevier Inc.

  7. A Comparative Study of virtual and operational met mast data

    International Nuclear Information System (INIS)

    Orhan, Dr Ö Emre; Ahmet, Gökhan

    2014-01-01

    Performance of wind assessment studies depend on the adequacy and duration of the wind data. For a reasonable wind assessment, at least one full year wind data is needed so that, all the variations throughout the year are represented. On the other hand, it is always a question of time and cost how to get the wind data. On-site measurements are the most common way of obtaining wind data but it is the most expensive and time consuming as well. Apart from onsite data, there are also reanalysis long term data sources like MERRA, NCAR, etc. Time and spatial resolution of these long term data are lower compared to on-site measurements but in cases where on-site measurements are not available, they are also utilized. On top of on-site and reanalysis wind data, weather forecasting models like WRF, MM5 are available. Although, these models mainly are used for forecasting services, flexibility of the models makes them suitable for preliminary resource assessment purposes. In this study, comparisons of annual energy production estimations are computed using virtual and on-site met mast data separately for a specific time range. The widely used weather research and forecasting model (WRF) is used to provide virtual met mast data. Once WRF simulations are completed, interpolation routines are employed in order to extract data for a specific location. The on-site met mast is located inside a wind farm project area which is under development. Project site is located in the south of Turkey. There are four different met masts, three of them recording wind data presently. On-site measurements together with WRF results are used to obtain energy yields for the project area. The performance of both methodologies is compared. It has been observed that WRF can as well serve as a preliminary model in cases where no other data source is available but the model has to be implemented with great care depending on the project site conditions

  8. General general game AI

    OpenAIRE

    Togelius, Julian; Yannakakis, Georgios N.; 2016 IEEE Conference on Computational Intelligence and Games (CIG)

    2016-01-01

    Arguably the grand goal of artificial intelligence research is to produce machines with general intelligence: the capacity to solve multiple problems, not just one. Artificial intelligence (AI) has investigated the general intelligence capacity of machines within the domain of games more than any other domain given the ideal properties of games for that purpose: controlled yet interesting and computationally hard problems. This line of research, however, has so far focuse...

  9. Alkaline transition of pseudoazurin Met16X mutant proteins: protein stability influenced by the substitution of Met16 in the second sphere coordination.

    Science.gov (United States)

    Abdelhamid, Rehab F; Obara, Yuji; Kohzuma, Takamitsu

    2008-01-01

    Several blue copper proteins are known to change the active site structure at alkaline pH (alkaline transition). Spectroscopic studies of Met16Phe, Met16Tyr, Met16Trp, and Met16Val pseudoazurin variants were performed to investigate the second sphere role through alkaline transition. The visible electronic absorption and resonance Raman spectra of Met16Phe, Met16Tyr, and Met16Trp variants showed the increasing of axial component at pH approximately 11 like wild-type PAz. The visible electronic absorption and far-UV CD spectra of Met16Val demonstrated that the destabilization of the protein structure was triggered at pH>11. Resonance Raman (RR) spectra of PAz showed that the intensity-weighted averaged Cu-S(Cys) stretching frequency was shifted to higher frequency region at pH approximately 11. The higher frequency shift of Cu-S(Cys) bond is implied the stronger Cu-S(Cys) bond at alkaline transition pH approximately 11. The visible electronic absorption and far-UV CD spectra of Met16X PAz revealed that the Met16Val variant is denatured at pH>11, but Met16Phe, Met16Tyr, and Met16Trp mutant proteins are not denatured even at pH>11. These observations suggest that Met16 is important to maintain the protein structure through the possible weak interaction between methionine -SCH3 part and coordinated histidine imidazole moiety. The introduction of pi-pi interaction in the second coordination sphere may be contributed to the enhancement of protein structure stability.

  10. A first-in-human phase I study of SAR125844, a selective MET tyrosine kinase inhibitor, in patients with advanced solid tumours with MET amplification.

    Science.gov (United States)

    Angevin, Eric; Spitaleri, Gianluca; Rodon, Jordi; Dotti, Katia; Isambert, Nicolas; Salvagni, Stefania; Moreno, Victor; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hollebecque, Antoine; Azaro, Analia; Hervieu, Alice; Rihawi, Karim; De Marinis, Filippo

    2017-12-01

    Dysregulated MET signalling is implicated in oncogenesis. The safety and preliminary efficacy of a highly selective MET kinase inhibitor (SAR125844) was investigated in patients with advanced solid tumours and MET dysregulation. This was a phase I dose-escalation (3 + 3 design [50-740 mg/m 2 ]) and dose-expansion study. In the dose escalation, patients had high total MET (t-MET) expression by immunohistochemistry (IHC) or MET amplification by fluorescence in situ hybridisation. In the dose expansion, patients had MET amplification (including a subset of patients with non-small cell lung cancer [NSCLC]) or phosphorylated-MET (p-MET) expression (IHC). Objectives were determination of maximum tolerated dose (MTD) of once-weekly intravenous SAR125844 based on dose-limiting toxicities; safety and pharmacokinetic profile; preliminary efficacy of SAR125844 MTD in the expansion cohort. In total, 72 patients were enrolled: dose escalation, N = 33; dose expansion, N = 39; 570 mg/m 2 was established as the MTD. Most frequent treatment-emergent adverse events (AEs) were asthenia/fatigue (58.3%), nausea (31.9%), and abdominal pain, constipation, and dyspnea (27.8% for each); 58.3% of patients reported grade 3 AEs (19.4% were treatment related). Of the 29 evaluable patients with MET amplification treated at 570 mg/m 2 , five achieved a partial response, including four of 22 with NSCLC; 17 patients had stable disease. No response was observed in patients with high p-MET solid tumours. There was no correlation between tumour response and t-MET status or MET gene copy number. The MTD of once-weekly SAR125844 was 570 mg/m 2 ; SAR125844 was well tolerated, with significant antitumour activity in patients with MET-amplified NSCLC. NCT01391533. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  11. Verification of space weather forecasts at the UK Met Office

    Science.gov (United States)

    Bingham, S.; Sharpe, M.; Jackson, D.; Murray, S.

    2017-12-01

    The UK Met Office Space Weather Operations Centre (MOSWOC) has produced space weather guidance twice a day since its official opening in 2014. Guidance includes 4-day probabilistic forecasts of X-ray flares, geomagnetic storms, high-energy electron events and high-energy proton events. Evaluation of such forecasts is important to forecasters, stakeholders, model developers and users to understand the performance of these forecasts and also strengths and weaknesses to enable further development. Met Office terrestrial near real-time verification systems have been adapted to provide verification of X-ray flare and geomagnetic storm forecasts. Verification is updated daily to produce Relative Operating Characteristic (ROC) curves and Reliability diagrams, and rolling Ranked Probability Skill Scores (RPSSs) thus providing understanding of forecast performance and skill. Results suggest that the MOSWOC issued X-ray flare forecasts are usually not statistically significantly better than a benchmark climatological forecast (where the climatology is based on observations from the previous few months). By contrast, the issued geomagnetic storm activity forecast typically performs better against this climatological benchmark.

  12. The performance of FLake in the Met Office Unified Model

    Directory of Open Access Journals (Sweden)

    Gabriel Gerard Rooney

    2013-12-01

    Full Text Available We present results from the coupling of FLake to the Met Office Unified Model (MetUM. The coupling and initialisation are first described, and the results of testing the coupled model in local and global model configurations are presented. These show that FLake has a small statistical impact on screen temperature, but has the potential to modify the weather in the vicinity of areas of significant inland water. Examination of FLake lake ice has revealed that the behaviour of lakes in the coupled model is unrealistic in some areas of significant sub-grid orography. Tests of various modifications to ameliorate this behaviour are presented. The results indicate which of the possible model changes best improve the annual cycle of lake ice. As FLake has been developed and tuned entirely outside the Unified Model system, these results can be interpreted as a useful objective measure of the performance of the Unified Model in terms of its near-surface characteristics.

  13. La metáfora como proceso cognitivo

    Directory of Open Access Journals (Sweden)

    Luz Amparo Fajardo Uribe

    2006-01-01

    Full Text Available La metáfora es un mecanismo que hace posible conceptualizar y reconceptualizar el mundo a partir de la traslación de rasgos de un dominio de origen a un dominio de llegada. En esa medida, la metáfora no necesita inventar nuevos términos para referirse a la realidad, sino que a partir de los ya existentes brinda una visión diferente de ésta en tanto que ha sido enriquecida con la afectividad y la emotividad del sujeto cognoscente. Por esa razón, la comprensión y producción metafórica requiere más de la competencia comunicativa que de la competencia lingüística, dado que el sentido que éste adopta depende del contexto comunicativo y no de la constitución léxica, morfológica sintáctica del enunciado.

  14. Higher Levels of c-Met Expression and Phosphorylation Identify Cell Lines With Increased Sensitivity to AMG-458, a Novel Selective c-Met Inhibitor With Radiosensitizing Effects

    International Nuclear Information System (INIS)

    Li Bo; Torossian, Artour; Sun, Yunguang; Du, Ruihong; Dicker, Adam P.; Lu Bo

    2012-01-01

    Purpose: c-Met is overexpressed in some non-small cell lung cancer (NSCLC) cell lines and tissues. Cell lines with higher levels of c-Met expression and phosphorylation depend on this receptor for survival. We studied the effects of AMG-458 on 2 NSCLC cell lines. Methods and Materials: 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium assays assessed the sensitivities of the cells to AMG-458. Clonogenic survival assays illustrated the radiosensitizing effects of AMG-458. Western blot for cleaved caspase 3 measured apoptosis. Immunoblotting for c-Met, phospho-Met (p-Met), Akt/p-Akt, and Erk/p-Erk was performed to observe downstream signaling. Results: AMG-458 enhanced radiosensitivity in H441 but not in A549. H441 showed constitutive phosphorylation of c-Met. A549 expressed low levels of c-Met, which were phosphorylated only in the presence of exogenous hepatocyte growth factor. The combination of radiation therapy and AMG-458 treatment was found to synergistically increase apoptosis in the H441 cell line but not in A549. Radiation therapy, AMG-458, and combination treatment were found to reduce p-Akt and p-Erk levels in H441 but not in A549. H441 became less sensitive to AMG-458 after small interfering RNA knockdown of c-Met; there was no change in A549. After overexpression of c-Met, A549 became more sensitive, while H441 became less sensitive to AMG-458. Conclusions: AMG-458 was more effective in cells that expressed higher levels of c-Met/p-Met, suggesting that higher levels of c-Met and p-Met in NSCLC tissue may classify a subset of tumors that are more sensitive to molecular therapies against this receptor.

  15. The new Met Office strategy for seasonal forecasts

    Science.gov (United States)

    Hewson, T. D.

    2012-04-01

    In October 2011 the Met Office began issuing a new-format UK seasonal forecast, called "The 3-month Outlook". Government interest in a UK-relevant product had been heightened by infrastructure issues arising during the severe cold of previous winters. At the same time there was evidence that the Met Office's "GLOSEA4" long range forecasting system exhibited some hindcast skill for the UK, that was comparable to its hindcast skill for the larger (and therefore less useful) 'northern Europe' region. Also, the NAO- and AO- signals prevailing in the previous two winters had been highlighted by the GLOSEA4 model well in advance. This presentation will initially give a brief overview of GLOSEA4, describing key features such as evolving sea-ice, a well-resolved stratosphere, and the perturbation strategy. Skill measures will be shown, along with forecasts for the last 3 winters. The new structure 3-month outlook will then be described and presented. Previously, our seasonal forecasts had been based on a tercile approach. The new format outlook aims to substantially improve upon this by illustrating graphically, and with text, the full range of possible outcomes, and by placing those outcomes in the context of climatology. In one key component the forecast pdfs (probability density functions) are displayed alongside climatological pdfs. To generate the forecast pdf we take the bias-corrected GLOSEA4 output (42 members), and then incorporate, via expert team, all other relevant information. Firstly model forecasts from other centres are examined. Then external 'forcing factors', such as solar, and the state of the land-ocean-ice system, are referenced, assessing how well the models represent their influence, and bringing in statistical relationships where appropriate. The expert team thereby decides upon any changes to the GLOSEA4 data, employing an interactive tool to shift, expand or contract the forecast pdfs accordingly. The full modification process will be illustrated

  16. PHA665752, a small-molecule inhibitor of c-Met, inhibits hepatocyte growth factor-stimulated migration and proliferation of c-Met-positive neuroblastoma cells

    International Nuclear Information System (INIS)

    Crosswell, Hal E; Dasgupta, Anindya; Alvarado, Carlos S; Watt, Tanya; Christensen, James G; De, Pradip; Durden, Donald L; Findley, Harry W

    2009-01-01

    c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), and both c-Met and its ligand are expressed in a variety of tissues. C-Met/HGF/SF signaling is essential for normal embryogenesis, organogenesis, and tissue regeneration. Abnormal c-Met/HGF/SF signaling has been demonstrated in different tumors and linked to aggressive and metastatic tumor phenotypes. In vitro and in vivo studies have demonstrated inhibition of c-Met/HGF/SF signaling by the small-molecule inhibitor PHA665752. This study investigated c-Met and HGF expression in two neuroblastoma (NBL) cell lines and tumor tissue from patients with NBL, as well as the effects of PHA665752 on growth and motility of NBL cell lines. The effect of the tumor suppressor protein PTEN on migration and proliferation of tumor cells treated with PHA665752 was also evaluated. Expression of c-Met and HGF in NBL cell lines SH-EP and SH-SY5Y and primary tumor tissue was assessed by immunohistochemistry and quantitative RT-PCR. The effect of PHA665752 on c-Met/HGF signaling involved in NBL cell proliferation and migration was evaluated in c-Met-positive cells and c-Met-transfected cells. The transwell chemotaxis assay and the MTT assay were used to measure migration and proliferation/cell-survival of tumor cells, respectively. The PPAR-γ agonist rosiglitazone was used to assess the effect of PTEN on PHA665752-induced inhibition of NBL cell proliferation/cell-survival and migration High c-Met expression was detected in SH-EP cells and primary tumors from patients with advanced-stage disease. C-Met/HGF signaling induced both migration and proliferation of SH-EP cells. Migration and proliferation/cell-survival were inhibited by PHA665752 in a dose-dependent manner. We also found that induced overexpression of PTEN following treatment with rosiglitazone significantly enhanced the inhibitory effect of PHA665752 on NBL-cell migration and proliferation. c-Met is highly expressed in most tumors from

  17. Metallography at the Met Lab -- The first fifty years

    International Nuclear Information System (INIS)

    Lee, R.H.

    1995-01-01

    The Met Lab at the University of Chicago was established to build the world's first nuclear reactor. The object was to see if a pile (CP-1) could be built to create a sustained chain reaction, i.e., controlled nuclear fission. New materials of the very best quality were needed and people of many skills worked together to achieve the goal as quickly as possible. This is the story of a select group of people who were scientific and engineering pioneers in this new field. Research continued at new sites on more advanced reactors and cooling systems. Many problems were encountered in the fabrication of reactor components, and metallography was a crucial method of analyzing the reactions and quality of consolidation. 1996 will be the 50th anniversary of the beginning of the National Laboratories, so it is appropriate to commemorate and recall some pioneering achievements

  18. The MeteoMet2 project—highlights and results

    Science.gov (United States)

    Merlone, A.; Sanna, F.; Beges, G.; Bell, S.; Beltramino, G.; Bojkovski, J.; Brunet, M.; del Campo, D.; Castrillo, A.; Chiodo, N.; Colli, M.; Coppa, G.; Cuccaro, R.; Dobre, M.; Drnovsek, J.; Ebert, V.; Fernicola, V.; Garcia-Benadí, A.; Garcia-Izquierdo, C.; Gardiner, T.; Georgin, E.; Gonzalez, A.; Groselj, D.; Heinonen, M.; Hernandez, S.; Högström, R.; Hudoklin, D.; Kalemci, M.; Kowal, A.; Lanza, L.; Miao, P.; Musacchio, C.; Nielsen, J.; Nogueras-Cervera, M.; Oguz Aytekin, S.; Pavlasek, P.; de Podesta, M.; Rasmussen, M. K.; del-Río-Fernández, J.; Rosso, L.; Sairanen, H.; Salminen, J.; Sestan, D.; Šindelářová, L.; Smorgon, D.; Sparasci, F.; Strnad, R.; Underwood, R.; Uytun, A.; Voldan, M.

    2018-02-01

    Launched in 2011 within the European Metrology Research Programme (EMRP) of EURAMET, the joint research project ‘MeteoMet’—Metrology for Meteorology—is the largest EMRP consortium; national metrology institutes, universities, meteorological and climate agencies, research institutes, collaborators and manufacturers are working together, developing new metrological techniques, as well as improving existing ones, for use in meteorological observations and climate records. The project focuses on humidity in the upper and surface atmosphere, air temperature, surface and deep-sea temperatures, soil moisture, salinity, permafrost temperature, precipitation, and the snow albedo effect on air temperature. All tasks are performed using a rigorous metrological approach and include the design and study of new sensors, new calibration facilities, the investigation of sensor characteristics, improved techniques for measurements of essential climate variables with uncertainty evaluation, traceability, laboratory proficiency and the inclusion of field influencing parameters, long-lasting measurements, and campaigns in remote and extreme areas. The vision for MeteoMet is to take a step further towards establishing full data comparability, coherency, consistency, and long-term continuity, through a comprehensive evaluation of the measurement uncertainties for the quantities involved in the global climate observing systems and the derived observations. The improvement in quality of essential climate variables records, through the inclusion of measurement uncertainty budgets, will also highlight possible strategies for the reduction of the uncertainty. This contribution presents selected highlights of the MeteoMet project and reviews the main ongoing activities, tasks and deliverables, with a view to its possible future evolution and extended impact.

  19. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

    Science.gov (United States)

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo J A; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-06-03

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

  20. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target

    International Nuclear Information System (INIS)

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo JA; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-01-01

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression. The online version of this article (doi:10.1186/s12885-015-1450-3) contains supplementary material, which is available to authorized users

  1. Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease.

    Science.gov (United States)

    Gomar, Jesus J; Conejero-Goldberg, Concepcion; Huey, Edward D; Davies, Peter; Goldberg, Terry E

    2016-03-01

    Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e., APOE gene) may influence brain-derived neurotrophic factor (BDNF) val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied 2 cohorts from Alzheimer's Disease Neuroimaging Initiative: 175 healthy subjects and 222 with prodromal and established Alzheimer's disease. Yearly structural magnetic resonance imaging and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers' (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices was detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes, respectively. The mild cognitive impairment/Alzheimer's disease cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. In addition, an effect of BDNF genotype was found in APOE E4 carriers for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers and APOE E4 carriers in healthy and pathological aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Radiation Chemical Studies of Gly-Met-Gly in Aqueous Solution

    NARCIS (Netherlands)

    Barata-Vallejo, Sebastian; Ferreri, Carla; Zhang, Tao; Permentier, Hjalmar; Bischoff, Rainer; Bobrowski, Krzysztof; Chatgilialoglu, Chryssostomos

    2016-01-01

    Important biological consequences are related to the reaction of HO(•) radicals with methionine (Met). Several fundamental aspects remain to be defined when Met is an amino acid residue incorporated in the interior of peptides and proteins. The present study focuses on Gly-Met-Gly, the simplest

  3. Muziektherapie voor kinderen en jongeren met ASS : En overzicht van de relevante literatuur

    NARCIS (Netherlands)

    Pater, Mathieu; van Yperen, Tom

    Muziektherapie wordt met grote regelmaat toegepast bij kinderen en jongeren met een autismespectrumstoornis (ASS). De vraag is of dit effect heeft. Dit artikel geeft een overzicht van de recente literatuur op dit vlak. Over de periode 1990 tot en met 2016 zijn 33 studies gevonden naar de inzet en

  4. Met .naturalis in zee: Nederlands koraalrifonderzoek in de Indo-Pacific

    NARCIS (Netherlands)

    Hoeksema, B.W.

    2003-01-01

    In een serie arikelen onder de naam 'Met Naturalis in zee', zal Onderwatersport in samenwerking met het Leidse museum Naturalis met enige regelmaat aandacht besteden aan Nederlands biologisch koraalrifonderzoek in de Indische en de Stille Oceaan. Bert Hoeksema schreef de introductie van de serie.

  5. The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Luis J. Herrera

    2005-01-01

    Full Text Available The hepatocyte growth factor (HGF receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE, and normal esophagus (NE using immunohistochemistry (IHC and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100% EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2-overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted.

  6. Mogelijkheden om vroeg tijdig bladrandproblemen te signaleren met MIPS bij Hortensia

    NARCIS (Netherlands)

    Noort, van F.R.; Jalink, H.

    2010-01-01

    Met geavanceerde camera technieken zijn beelden vast te leggen van fotosynthese activiteit en het is ook mogelijk gebleken om bladgedeelten met stress vast te leggen, zonder dat deze stress met het blote oog al te zien is. Dit opent perspectieven om monitorringonderzoek te doen naar het ontstaan van

  7. The COMT Val158Met Polymorphism Is Associated With Response to Add-on Dextromethorphan Treatment in Bipolar Disorder.

    Science.gov (United States)

    Lee, Sheng-Yu; Chen, Shiou-Lan; Wang, Tzu-Yun; Chang, Yun-Hsuan; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Chen, Kao Ching; Yang, Yen Kuang; Lu, Ru-Band

    2017-02-01

    We previously conducted a randomized, double-blind, controlled, 12-week study evaluating the effect of add-on dextromethorphan (DM), a noncompetitive N-methyl-D-aspartate receptor antagonist, on patients with bipolar disorder (BD) treated using valproate (VPA), which showed negative clinical differences. The genetic variation between each individual may be responsible for interindividual differences. The catechol-O-methyltransferase (COMT) gene has been a candidate gene for BD. In the current study, we investigated whether the COMT Val158Met polymorphism predicts treatment response to VPA + add-on DM and to VPA + placebo. Patients with BD (n = 309) undergoing regular VPA treatments were randomly assigned to groups given either add-on DM (30 mg/d) (n = 102), DM (60 mg/d) (n = 101), or placebo (n = 106) for 12 weeks. The Hamilton Depression Rating Scale and Young Mania Rating Scale were used to evaluate clinical response during weeks 0, 1, 2, 4, 8, and 12. The genotypes of the COMT Val158Met polymorphism were determined using polymerase chain reaction plus restriction fragment length polymorphism analysis. To adjust for within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used. When stratified by the COMT Val158Met genotypes, significantly greater decreases in Hamilton Depression Rating Scale scores were found in the VPA + DM (30 mg/d) group in patients with the Val/Met genotype (P = 0.008). We conclude that the COMT Val158Met polymorphism may influence responses to DM (30 mg/d) by decreasing depressive symptoms in BD patients.

  8. AKT-ions with a TWIST between EMT and MET.

    Science.gov (United States)

    Tang, Huifang; Massi, Daniela; Hemmings, Brian A; Mandalà, Mario; Hu, Zhengqiang; Wicki, Andreas; Xue, Gongda

    2016-09-20

    The transcription factor Twist is an important regulator of cranial suture during embryogenesis. Closure of the neural tube is achieved via Twist-triggered cellular transition from an epithelial to mesenchymal phenotype, a process known as epithelial-mesenchymal transition (EMT), characterized by a remarkable increase in cell motility. In the absence of Twist activity, EMT and associated phenotypic changes in cell morphology and motility can also be induced, albeit moderately, by other transcription factor families, including Snail and Zeb. Aberrant EMT triggered by Twist in human mammary tumour cells was first reported to drive metastasis to the lung in a metastatic breast cancer model. Subsequent analysis of many types of carcinoma demonstrated overexpression of these unique EMT transcription factors, which statistically correlated with worse outcome, indicating their potential as biomarkers in the clinic. However, the mechanisms underlying their activation remain unclear. Interestingly, increasing evidence indicates they are selectively activated by distinct intracellular kinases, thereby acting as downstream effectors facilitating transduction of cytoplasmic signals into nucleus and reprogramming EMT and mesenchymal-epithelial transition (MET) transcription to control cell plasticity. Understanding these relationships and emerging data indicating differential phosphorylation of Twist leads to complex and even paradoxical functionalities, will be vital to unlocking their potential in clinical settings.

  9. Mecanismo cognitivos en la memoria; la Metáfora

    Directory of Open Access Journals (Sweden)

    Francisco José Ruiz de Mendoza Ibañez

    2010-12-01

    Full Text Available La Lingüística Cognitiva (LC es una disciplina que, pese a su juventud, ha experimentado un desarrollo vertiginoso en los últimos treinta años1. Uno de los mayores logros de la LC (que la distingue de enfoques anteriores sobre el lenguaje como el estructuralismo y el generativismo chomskyano radica en no considerar el lenguaje como un sistema autosuficiente, sino más bien como una facultad cognitiva que interactúa con otras capacidades como son la percepción, la atención, la memoria, la emoción y el razonamiento. Por tanto, en LC los significados son parte de nuestro mundo conceptual. En la versión más temprana de la TMC Lakoff y Johnson defienden que tanto el lenguaje como el pensamiento están ligados y se estructuran de acuerdo con la experiencia corpórea (embodied experience. Así, la experiencia perceptual y espacial es la base para la categorización del mundo de manera que estas categorías (que pertenecen a dominios concretos se hacen corresponder con dominios más abstractos como los de la emoción, el tiempo o la estructura. Por tanto, la metáfora queda definida como un conjunto de correspondencias (conceptual mapping entre un dominio fuente (más concreto y un dominio meta (más abstracto.

  10. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Granito, Alessandro; Guidetti, Elena; Gramantieri, Laura

    2015-01-01

    c-MET is the membrane receptor for hepatocyte growth factor (HGF), also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC). In particular, c-MET amplification is a rare event, accounting for 4%-5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC.

  11. Prognostic impact of tumor MET expression among patients with stage IV gastric cancer

    DEFF Research Database (Denmark)

    Erichsen, Rune; Kelsh, Michael A; Oliner, Kelly S

    2016-01-01

    PURPOSE: We aimed to investigate the prevalence and prognostic impact of tumor mesenchymal epithelial transition factor (MET) expression in stage IV gastric cancers in a real-world clinical setting because existing evidence is sparse. METHODS: The study included archived cancer specimens from 103...... stage IV gastric cancer patients (2003-2010). We analyzed MET-protein expression by immunohistochemistry (MET-positive if ≥25% of tumor cells showed MET expression). We calculated overall survival using the Kaplan-Meier method and hazard ratios comparing mortality among MET-positive and MET.......6 months), corresponding to an adjusted hazard ratio of 2.2 (95% confidence interval, 1.3-3.7). CONCLUSIONS: Tumor MET expression is prevalent and has substantial prognostic impact in stage IV gastric cancer patients....

  12. A protective effect of the BDNF Met/Met genotype in obesity in healthy Caucasian subjects but not in patients with coronary heart disease.

    Science.gov (United States)

    Sustar, A; Nikolac Perkovic, M; Nedic Erjavec, G; Svob Strac, D; Pivac, N

    2016-08-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor with an important role in the regulation of body weight, body mass index (BMI) and obesity. Increased BMI that leads to obesity is a substantial risk factor for coronary heart disease (CHD). The functional BDNF Val66Met polymorphism (rs6265) has been associated with CHD, obesity and BMI. The aim of the study was to determine the association between BDNF rs6265 polymorphism and CHD and/or BMI in patients with CHD and healthy control subjects. The study included 704 Caucasian subjects: 206 subjects with CHD and 498 healthy control subjects. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. BDNF rs6265 polymorphism was not associated with a diagnosis of CHD or with BMI categories among patients with CHD. In contrast, healthy Caucasians, carriers of the BDNF Met/Met genotype, had more

  13. 29 CFR 785.27 - General.

    Science.gov (United States)

    2010-07-01

    ... to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS OF GENERAL POLICY OR... Training Programs § 785.27 General. Attendance at lectures, meetings, training programs and similar activities need not be counted as working time if the following four criteria are met: (a) Attendance is...

  14. The BDNF-Val66Met polymorphism modulates parental rearing effects on adult psychiatric symptoms: a community twin-based study.

    Science.gov (United States)

    Ibarra, P; Alemany, S; Fatjó-Vilas, M; Córdova-Palomera, A; Goldberg, X; Arias, B; González-Ortega, I; González-Pinto, A; Nenadic, I; Fañanás, L

    2014-06-01

    To test whether firstly, different parental rearing components were associated with different dimensions of psychiatric symptoms in adulthood, secondly BDNF-Val66Met polymorphism moderated this association and thirdly, this association was due to genetic confounding. Perceived parental rearing according to Parental Bonding Instrument (PBI), psychiatric symptoms evaluated with the Brief Symptom Inventory (BSI) and the BDNF-Val66Met polymorphism were analyzed in a sample of 232 adult twins from the general population. In the whole sample, paternal care was negatively associated with depression. Maternal overprotection was positively associated with paranoid ideation, obsession-compulsion and somatization. Gene-environment interaction effects were detected between the BDNF-Val66Met polymorphism and maternal care on phobic anxiety, paternal care on hostility, maternal overprotection on somatization and paternal overprotection also in somatization. In the subsample of MZ twins, intrapair differences in maternal care were associated with anxiety, paranoid ideation and somatization. Met carriers were, in general, more sensitive to the effects of parental rearing compared to Val/Val carriers in relation to anxiety and somatization. Contra-intuitively, our findings suggest that high rates of maternal care might be of risk for Met carriers regarding anxiety. Results from analyses controlling for genetic confounding were in line with this finding. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. In vivo detection of c-Met expression in a rat C6 glioma model.

    Science.gov (United States)

    Towner, R A; Smith, N; Doblas, S; Tesiram, Y; Garteiser, P; Saunders, D; Cranford, R; Silasi-Mansat, R; Herlea, O; Ivanciu, L; Wu, D; Lupu, F

    2008-01-01

    The tyrosine kinase receptor, c-Met, and its substrate, the hepatocyte growth factor (HGF), are implicated in the malignant progression of glioblastomas. In vivo detection of c-Met expression may be helpful in the diagnosis of malignant tumours. The C6 rat glioma model is a widely used intracranial brain tumour model used to study gliomas experimentally. We used a magnetic resonance imaging (MRI) molecular targeting agent to specifically tag the cell surface receptor, c-Met, with an anti-c-Met antibody (Ab) linked to biotinylated Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-albumin in rat gliomas to detect overexpression of this antigen in vivo. The anti-c-Met probe (anti-c-Met-Gd-DTPA-albumin) was administered intravenously, and as determined by an increase in MRI signal intensity and a corresponding decrease in regional T(1) relaxation values, this probe was found to detect increased expression of c-Met protein levels in C6 gliomas. In addition, specificity for the binding of the anti-c-Met contrast agent was determined by using fluorescence microscopic imaging of the biotinylated portion of the targeting agent within neoplastic and 'normal'brain tissues following in vivo administration of the anti-c-Met probe. Controls with no Ab or with a normal rat IgG attached to the contrast agent component indicated no non-specific binding to glioma tissue. This is the first successful visualization of in vivo overexpression of c-Met in gliomas.

  16. The potential roles of hepatocyte growth factor (HGF-MET pathway inhibitors in cancer treatment

    Directory of Open Access Journals (Sweden)

    Parikh RA

    2014-06-01

    Full Text Available Rahul A Parikh,1 Peng Wang,2 Jan H Beumer,3 Edward Chu,1 Leonard J Appleman11Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; 2Division of Medical Oncology, University of Kentucky College of Medicine, Markey Cancer Center, Lexington, KY, USA; 3University of Pittsburgh School of Pharmacy, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USAAbstract: MET is located on chromosome 7q31 and is a proto-oncogene that encodes for hepatocyte growth factor (HGF receptor, a member of the receptor tyrosine kinase (RTK family. HGF, also known as scatter factor (SF, is the only known ligand for MET. MET is a master regulator of cell growth and division (mitogenesis, mobility (motogenesis, and differentiation (morphogenesis; it plays an important role in normal development and tissue regeneration. The HGF-MET axis is frequently dysregulated in cancer by MET gene amplification, translocation, and mutation, or by MET or HGF protein overexpression. MET dysregulation is associated with an increased propensity for metastatic disease and poor overall prognosis across multiple tumor types. Targeting the dysregulated HGF-MET pathway is an area of active research; a number of monoclonal antibodies to HGF and MET, as well as small molecule inhibitors of MET, are under development. This review summarizes the key biological features of the HGF-MET axis, its dysregulation in cancer, and the therapeutic agents targeting the HGF-MET axis, which are in development.Keywords: MET inhibitor, HGF inhibitor, cancer

  17. I Met Lucky People: The Story of the Romani Gypsies. By Yaron Matras. London: Allen Lane, Penguin Books, 2014, 276 pp.; ISBN 978-1-846-14481-3.

    Directory of Open Access Journals (Sweden)

    Victor A Friedman

    2015-09-01

    Full Text Available This is a book review of I met lucky people: The story of the Romani Gypsies, by Yaron Matras. The work is oriented for a general reading public, but it can be highly recommended for academics and policy makers as well.

  18. Stoppen met roken: hoe pakken wij dat aan?

    NARCIS (Netherlands)

    Jacobs-van der Bruggen, M.; Donker, G.; Verkleij, H.; Baan, C.

    2007-01-01

    Background: Smoking is the cause of a great deal of morbidity and mortality. General practitioners (GPs) can help prevent smoking-related diseases by following an active anti-smoking policy, i.e. by taking the initiative to discuss stopping smoking with their patients. The aim of our research is to

  19. Kwantitatief gevoeligheidsonderzoek met intra- en extramurale isolaten van Escherichia coli

    NARCIS (Netherlands)

    de Neeling AJ; de Jong J; Overbeek BP; de Bruin RW; Dessens-Kroon M; van Klingeren B

    1990-01-01

    Three Dutch laboratories for medical microbiology collected a total number of 1432 strains of Escherichia coli. Of these 995 were obtained from routine samples taken in clinic and policlinic, 290 had been sent spontaneously by general practitioners for microbiological examination and 147 had been

  20. The Met receptor tyrosine kinase prevents zebrafish primary motoneurons from expressing an incorrect neurotransmitter

    Directory of Open Access Journals (Sweden)

    Eisen Judith S

    2008-07-01

    Full Text Available Abstract Background Expression of correct neurotransmitters is crucial for normal nervous system function. How neurotransmitter expression is regulated is not well-understood; however, previous studies provide evidence that both environmental signals and intrinsic differentiation programs are involved. One environmental signal known to regulate neurotransmitter expression in vertebrate motoneurons is Hepatocyte growth factor, which acts through the Met receptor tyrosine kinase and also affects other aspects of motoneuron differentiation, including axonal extension. Here we test the role of Met in development of motoneurons in embryonic zebrafish. Results We found that met is expressed in all early developing, individually identified primary motoneurons and in at least some later developing secondary motoneurons. We used morpholino antisense oligonucleotides to knock down Met function and found that Met has distinct roles in primary and secondary motoneurons. Most secondary motoneurons were absent from met morpholino-injected embryos, suggesting that Met is required for their formation. We used chemical inhibitors to test several downstream pathways activated by Met and found that secondary motoneuron development may depend on the p38 and/or Akt pathways. In contrast, primary motoneurons were present in met morpholino-injected embryos. However, a significant fraction of them had truncated axons. Surprisingly, some CaPs in met morpholino antisense oligonucleotide (MO-injected embryos developed a hybrid morphology in which they had both a peripheral axon innervating muscle and an interneuron-like axon within the spinal cord. In addition, in met MO-injected embryos primary motoneurons co-expressed mRNA encoding Choline acetyltransferase, the synthetic enzyme for their normal neurotransmitter, acetylcholine, and mRNA encoding Glutamate decarboxylase 1, the synthetic enzyme for GABA, a neurotransmitter never normally found in these motoneurons, but

  1. Samen leven met ME/CVS : Een onderzoek naar de rol van partnersteun en ziekterepresentaties bij coping met en adaptatie aan ME/CVS.

    NARCIS (Netherlands)

    Marleen Hofman, [No Value

    2013-01-01

    Achtergrond: Het chronisch vermoeidheidssyndroom (CVS) is een chronische ziekte die wordt gekenmerkt door ernstige vermoeidheid die vaak gepaard gaat met reumatische, infectieuze en neuropsychiatrische klachten. Het is een ernstig invaliderende aandoening waar tot nog toe geen genezende behandeling

  2. VIGS in afrika, met spesiale verwysing na Suid-Afrika

    Directory of Open Access Journals (Sweden)

    A. T. Viljoen

    1990-03-01

    Full Text Available It is generally accepted that Africa is the continent that is most seriously affected by the AIDS epidemic. As a result of under-reporting, the actual incidence of AIDS may be more than ten times higher than indicated by the official figures. The majority of females of child-bearing age can be infected within the next 4-6 years. Infant mortality is expected to increase dramatically. Up to 50% of babies born to HIV-infected mothers are also infected. Most of these babies will develop an AIDS-related illness and die at a very young age. Twelve factors have been identified which place the black population of South-Africa among the highest risk groups in the world. No vaccine or cure is available at this stage. Education of the general population, with the aim to bring about a change in sexual practices, is the only way to prevent a demographic catastrophe in this country.

  3. Physics and Women: A Challenge Being Successfully Met in Cuba

    Science.gov (United States)

    Arias de Fuentes, Olimpia

    The history of physics in Cuba, like all the country's educational and scientific development, cannot be understood without taking into account its close relationship with the social changes that took place in Cuba during the five decades elapsed since 1959. This should include due consideration to the role played by women in this process, all the more since the link between science and gender is now generally regarded as a subject of growing special interest

  4. The modulatory influence of the functional COMT Val158Met polymorphism on lexical decisions and semantic priming.

    Science.gov (United States)

    Reuter, Martin; Montag, Christian; Peters, Kristina; Kocher, Anne; Kiefer, Markus

    2009-01-01

    The role of the prefrontal Cortex (PFC) in higher cognitive functions - including working memory, conflict resolution, set shifting and semantic processing - has been demonstrated unequivocally. Despite the great heterogeneity among tasks measuring these phenotypes, due in part to the different cognitive sub-processes implied and the specificity of the stimulus material used, there is agreement that all of these tasks recruit an executive control system located in the PFC. On a biochemical level it is known that the dopaminergic system plays an important role in executive control functions. Evidence comes from molecular genetics relating the functional COMT Val158Met polymorphism to working memory and set shifting. In order determine whether this pattern of findings generalises to linguistic and semantic processing, we investigated the effects of the COMT Val158Met polymorphism in lexical decision making using masked and unmasked versions of the semantic priming paradigm on N = 104 healthy subjects. Although we observed strong priming effects in all conditions (masked priming, unmasked priming with short/long stimulus asynchronies (SOAs), direct and indirect priming), COMT was not significantly related to priming, suggesting no reliable influence on semantic processing. However, COMT Val158Met was strongly associated with lexical decision latencies in all priming conditions if considered separately, explaining between 9 and 14.5% of the variance. Therefore, the findings indicate that COMT mainly influences more general executive control functions in the PFC supporting the speed of lexical decisions.

  5. The brain-derived neurotrophic factor Val66Met polymorphism is associated with age-related change in reasoning skills.

    Science.gov (United States)

    Harris, S E; Fox, H; Wright, A F; Hayward, C; Starr, J M; Whalley, L J; Deary, I J

    2006-05-01

    A polymorphism (Val66Met) in the gene encoding brain-derived neurotrophic factor (BDNF) has previously been associated with impaired hippocampal function and scores on the Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R). Despite its widespread expression in the brain, there have been few studies examining the role of BDNF on cognitive domains, other than memory. We examined the association between BDNF Val66Met genotype and non-verbal reasoning, as measured by Raven's standard progressive matrices (Raven), in two cohorts of relatively healthy older people, one aged 79 (LBC1921) and the other aged 64 (ABC1936) years. LBC1921 and ABC1936 subjects had reasoning measured at age 11 years, using the Moray House Test (MHT), in the Scottish Mental Surveys of 1932 and 1947, respectively. BDNF genotype was significantly associated with later life Raven scores, controlling for sex, age 11 MHT score and cohort (P = 0.001). MHT, Verbal Fluency and Logical Memory scores were available, in later life, for LBC1921 only. BDNF genotype was significantly associated with age 79 MHT score, controlling for sex and age 11 MHT score (P = 0.016). In both significant associations, Met homozygotes scored significantly higher than heterozygotes and Val homozygotes. This study indicates that BDNF genotype contributes to age-related changes in reasoning skills, which are closely related to general intelligence.

  6. The modulatory influence of the functional COMT Val158Met polymorphism on lexical decisions and semantic priming

    Directory of Open Access Journals (Sweden)

    Martin Reuter

    2009-08-01

    Full Text Available The role of the prefrontal Cortex (PFC in higher cognitive functions - including working memory, conflict resolution, set shifting and semantic processing - has been demonstrated unequivocally. Despite the great heterogeneity among tasks measuring these phenotypes, due in part to the different cognitive sub-processes implied and the specificity of the stimulus material used, there is agreement that all of these tasks recruit an executive control system located in the PFC. On a biochemical level it is known that the dopaminergic system plays an important role in executive control functions. Evidence comes from molecular genetics relating the functional COMT Val158Met polymorphism to working memory and set shifting. In order determine whether this pattern of findings generalises to linguistic and semantic processing, we investigated the effects of the COMT Val158Met polymorphism in lexical decision making using masked and unmasked versions of the semantic priming paradigm on N=104 healthy subjects. Although we observed strong priming effects in all conditions (masked priming, unmasked priming with short/long stimulus asynchronies (SOAs, direct and indirect priming, COMT was not significantly related to masked priming, suggesting no reliable influence on semantic processing. However, COMT Val158Met was strongly associated with lexical decision latencies in all priming conditions if considered separately, explaining between 9 to 14.5 % of the variance. Therefore, the findings indicate that COMT mainly influences more general executive control functions in the PFC supporting the speed of lexical decisions.

  7. Anti-c-MET Nanobody - a new potential drug in multiple myeloma treatment.

    Science.gov (United States)

    Slørdahl, Tobias Schmidt; Denayer, Tinneke; Moen, Siv Helen; Standal, Therese; Børset, Magne; Ververken, Cedric; Rø, Torstein Baade

    2013-11-01

    c-MET is the tyrosine kinase receptor of the hepatocyte growth factor (HGF). HGF-c-MET signaling is involved in many human malignancies, including multiple myeloma (MM). Recently, multiple agents have been developed directed to interfere at different levels in HGF-c-MET signaling pathway. Nanobodies are therapeutic proteins based on the smallest functional fragments of heavy-chain-only antibodies. In this study, we wanted to determine the anticancer effect of a novel anti-c-MET Nanobody in MM. We examined the effects of an anti-c-MET Nanobody on thymidine incorporation, migration, adhesion of MM cells, and osteoblastogenesis in vitro. Furthermore, we investigated the effects of the Nanobody on HGF-dependent c-MET signaling by Western blotting. We show that the anti-c-MET Nanobody effectively inhibited thymidine incorporation of ANBL-6 MM cells via inhibition of an HGF autocrine growth loop and thymidine incorporation in INA-6 MM cells induced by exogenous HGF. HGF-induced migration and adhesion of INA-6 were completely and specifically blocked by the Nanobody. Furthermore, the Nanobody abolished the inhibiting effect of HGF on bone morphogenetic protein-2-induced alkaline phosphatase activity and the mineralization of human mesenchymal stem cells. Finally, we show that the Nanobody reduced phosphorylation of tyrosine residues in c-MET, MAPK, and Akt. We also compared the Nanobody with anti-c-MET monoclonal antibodies and revealed the similar or better effect. The anti-c-MET Nanobody inhibited MM cell migration, thymidine incorporation, and adhesion, and blocked the HGF-mediated inhibition of osteoblastogenesis. The anti-c-MET Nanobody might represent a novel therapeutic agent in the treatment of MM and other cancers driven by HGF-c-MET signaling. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis.

    Science.gov (United States)

    Bozkaya, Giray; Korhan, Peyda; Cokaklı, Murat; Erdal, Esra; Sağol, Ozgül; Karademir, Sedat; Korch, Christopher; Atabey, Neşe

    2012-09-11

    Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis. MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  9. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Granito A

    2015-04-01

    Full Text Available Alessandro Granito,1 Elena Guidetti,1 Laura Gramantieri2,3 1Dipartimento di Scienze Mediche e Chirurgiche Università di Bologna, Bologna, Italy; 2Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3Centro di Ricerca Biomedica Applicata (CRBA, Azienda Ospedaliero-Universitaria Policlinico S Orsola-Malpighi e Università di Bologna, Bologna, Italy Abstract: c-MET is the membrane receptor for hepatocyte growth factor (HGF, also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC. In particular, c-MET amplification is a rare event, accounting for 4%–5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC. Keywords: hepatocellular carcinoma, c-MET, clinical trials

  10. De betekenis van Paulus' oproep tot de groet met de heilige kus

    NARCIS (Netherlands)

    Voogd, Joanna Bernarda

    Dit boek is een studie naar de betekenis van de Paulijnse oproep tot de groet met de heilige kus. In vier passages in het Nieuwe Testament is deze oproep vindbaar: “Groet alle broeders (en zusters) met de heilige kus” (1 Tes 5:26) of “groet elkaar met de heilige kus” (1 Kor 16:20; 2 Kor 13:12 en

  11. User-Defined Meteorological (MET) Profiles from Climatological and Extreme Condition Data

    Science.gov (United States)

    2018-04-01

    ARL-TN-0876 ● MAR 2018 US Army Research Laboratory User-Defined Meteorological (MET) Profiles from Climatological and Extreme...needed. Do not return it to the originator. ARL-TN-0876 ● MAR 2018 US Army Research Laboratory User-Defined Meteorological (MET...User-Defined Meteorological (MET) Profiles from Climatological and Extreme Condition Data 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

  12. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Bozkaya Giray

    2012-09-01

    Full Text Available Abstract Background Hepatocyte growth factor (HGF induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC. MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s is in hepatocarcinogenesis. Results MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. Conclusions These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  13. Lipoprotein lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS

    Science.gov (United States)

    Previous analysis clustered 1,238 individuals from the general population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of their fasting very low-density, low-density and high-density lipoproteins (VLDL, LDL, HDL) using latent class analysis. From two of the eight identified gro...

  14. MET overexpression, gene amplification and relevant clinicopathological features in gastric adenocarcinoma.

    Science.gov (United States)

    Zhang, Jing; Guo, Lei; Liu, Xiuyun; Li, Wenbin; Ying, Jianming

    2017-02-07

    This study was conducted to investigate the expression of MET in Chinese gastric adenocarcinoma cohort, the correlation between MET overexpression and clinical pathological features, HER2 expression and MET gene amplification. A total of 816 gastric adenocarcinoma patients were included and MET and HER2 immunohistochemical (IHC) staining were performed. IHC and dual-color silver in situ hybridization analysis were performed in the tissue microarrays, constructed from the 240 patients who were randomly selected. MET overexpression (IHC 3+) was observed in 6.0% (49/816) of the cohort. MET overexpression rate was higher in patients with poor prognostic factors, such as clinical stages III/IV (p =0.012) and pathologic stages T3/T4 (p =0.027). The HER2 overexpression (IHC 3+) rate was 8.8% (72/816) and MET overexpression rate was higher in HER2 positive patients (9.7%, 7/72). A high concordance rate (94.6%) between MET overexpression and gene amplification was demonstrated. Therefore, MET overexpression could serve as a prognostic biomarker and a potential therapeutic target for gastric cancer.

  15. Design and synthesis of 3,3'-biscoumarin-based c-Met inhibitors.

    Science.gov (United States)

    Xu, Jimin; Ai, Jing; Liu, Sheng; Peng, Xia; Yu, Linqian; Geng, Meiyu; Nan, Fajun

    2014-06-14

    A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3'-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells.

  16. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young H. [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Agarwal, Piyush K.; Bottaro, Donald P., E-mail: dbottaro@helix.nih.gov [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2014-11-25

    There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

  17. Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

    International Nuclear Information System (INIS)

    Dietz, Marina S; Haße, Daniel; Ferraris, Davide M; Göhler, Antonia; Niemann, Hartmut H; Heilemann, Mike

    2013-01-01

    The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.

  18. Recent advances in the discovery of small molecule c-Met Kinase inhibitors.

    Science.gov (United States)

    Parikh, Palak K; Ghate, Manjunath D

    2018-01-01

    c-Met is a prototype member of a subfamily of heterodimeric receptor tyrosine kinases (RTKs) and is the receptor for hepatocyte growth factor (HGF). Binding of HGF to its receptor c-Met, initiates a wide range of cellular signalling, including those involved in proliferation, motility, migration and invasion. Importantly, dysregulated HGF/c-Met signalling is a driving factor for numerous malignancies and promotes tumour growth, invasion, dissemination and/or angiogenesis. Dysregulated HGF/c-Met signalling has also been associated with poor clinical outcomes and resistance acquisition to some approved targeted therapies. Thus, c-Met kinase has emerged as a promising target for cancer drug development. Different therapeutic approaches targeting the HGF/c-Met signalling pathway are under development for targeted cancer therapy, among which small molecule inhibitors of c-Met kinase constitute the largest effort within the pharmaceutical industry. The review is an effort to summarize recent advancements in medicinal chemistry development of small molecule c-Met kinase inhibitors as potential anti-cancer agents which would certainly help future researchers to bring further developments in the discovery of small molecule c-Met kinase inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Preproghrelin Leu72Met polymorphism in Chinese subjects with coronary artery disease and controls.

    Science.gov (United States)

    Tang, Na-Ping; Wang, Lian-Sheng; Yang, Li; Gu, Hai-Juan; Zhu, Huai-Jun; Zhou, Bo; Sun, Qing-Min; Cong, Ri-Hong; Wang, Bin

    2008-01-01

    Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to exert a protective effect against atherosclerosis. The Leu72Met (+408C>A) polymorphic variant of the preproghrelin, the gene for the ghrelin precursor, has been linked to obesity, diabetes and metabolic syndrome. However, it is unclear whether this polymorphism is associated with coronary artery disease (CAD). We conducted a case-control study with 317 CAD patients and 323 controls to investigate the potential association of the Leu72Met polymorphism with the occurrence of CAD and CAD-related phenotypes in Chinese population. No significant difference in the Leu72Met genotype frequency was observed between CAD patients and controls (P=NS). The Leu72Met polymorphism was not associated with hypertension, diabetes, dyslipidemia, the number of diseased vessels, plasma total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol or fasting glucose levels in CAD patients. However, among CAD patients, those with variant genotypes (Leu72Met and Met72Met) had lower BMI (24.4+/-0.3 kg/m(2)) than Leu72Leu carriers (25.4+/-0.2 kg/m(2), adjusted P=0.033). Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with CAD in Chinese population. However, the Leu72Met variant is associated with BMI among CAD patients.

  20. Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus.

    Science.gov (United States)

    Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Park, Ji Hyun; Park, Sung Kwang; Yi, Ho Keun; Lee, Dae-Yeol

    2006-03-01

    Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.

  1. Ran GTPase promotes cancer progression via Met receptor-mediated downstream signaling

    Science.gov (United States)

    Yuen, Hiu-Fung; Chan, Ka-Kui; Platt-Higgins, Angela; Dakir, El-Habib; Matchett, Kyle B.; Haggag, Yusuf Ahmed; Jithesh, Puthen V.; Habib, Tanwir; Faheem, Ahmed; Dean, Fennell A.; Morgan, Richard; Rudland, Philip S.; El-Tanani, Mohamed

    2016-01-01

    It has been shown previously that cancer cells with an activated oncogenic pathway, including Met activation, require Ran for growth and survival. Here, we show that knockdown of Ran leads to a reduction of Met receptor expression in several breast and lung cancer cell lines. This, in turn suppressed HGF expression and the Met-mediated activation of the Akt pathway, as well as cell adhesion, migration, and invasion. In a cell line model where Met amplification has previously been shown to contribute to gefitinib resistance, Ran knockdown sensitized cells to gefitinib-mediated inhibition of Akt and ERK1/2 phosphorylation and consequently reduced cell proliferation. We further demonstrate that Met reduction-mediated by knockdown of Ran, occurs at the post-transcriptional level, probably via a matrix metalloproteinase. Moreover, the level of immunoreactive Ran and Met are positively associated in human breast cancer specimens, suggesting that a high level of Ran may be a pre-requisite for Met overexpression. Interestingly, a high level of immunoreactive Ran dictates the prognostic significance of Met, indicating that the co-overexpression of Met and Ran may be associated with cancer progression and could be used in combination as a prognostic indicator. PMID:27716616

  2. Role of Methoprene-tolerant (Met in adult morphogenesis and in adult ecdysis of Blattella germanica.

    Directory of Open Access Journals (Sweden)

    Jesus Lozano

    Full Text Available Juvenile Hormone (JH represses metamorphosis of young instars in insects. One of the main players in hormonal signalling is Methoprene-tolerant (Met, which plays the role of JH receptor. Using the Polyneopteran insect Blattella germanica as the model and RNAi for transcript depletion, we have confirmed that Met transduces the antimetamorphic signal of JH in young nymphs and plays a role in the last nymphal instar moult in this species. Previously, the function of Met as the JH receptor had been demonstrated in the Eumetabola clade, with experiments in Holometabola (in the beetle Tribolium castaneum and in their sister group Paraneoptera (in the bug Pyrrhocoris apterus. Our result shows that the function of Met as JH receptor is also conserved in the more basal Polyneoptera. The function of Met as JH transducer might thus predate the evolutionary innovation of metamorphosis. Moreover, expression of Met was also found in last nymphal instar of B. germanica, when JH is absent. Depletion of Met in this stage provoked deficiencies in wing growth and ecdysis problems in the imaginal moult. Down-regulation of the ecdysone-inducible gene E75A and Insulin-Like-Peptide 1 in these Met-depleted specimens suggest that Met is involved in the ecdysone and insulin signalling pathways in last nymphal instar, when JH is virtually absent.

  3. Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

    Science.gov (United States)

    Korhan, Peyda; Erdal, Esra; Kandemiş, Emine; Cokaklı, Murat; Nart, Deniz; Yılmaz, Funda; Can, Alp; Atabey, Neşe

    2014-01-01

    c-Met, the receptor for Hepatocyte Growth Factor (HGF), overexpressed and deregulated in Hepatocellular Carcinoma (HCC). Caveolin 1 (CAV1), a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

  4. Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Peyda Korhan

    Full Text Available c-Met, the receptor for Hepatocyte Growth Factor (HGF, overexpressed and deregulated in Hepatocellular Carcinoma (HCC. Caveolin 1 (CAV1, a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

  5. OTULIN antagonizes LUBAC signaling by specifically hydrolyzing met1-linked polyubiquitin

    DEFF Research Database (Denmark)

    Keusekotten, K.; Elliott, P.R.; Kulathu, Y.

    2013-01-01

    The linear ubiquitin (Ub) chain assembly complex (LUBAC) is an E3 ligase that specifically assembles Met1-linked (also known as linear) Ub chains that regulate nuclear factor κB (NF-κB) signaling. Deubiquitinases (DUBs) are key regulators of Ub signaling, but a dedicated DUB for Met1 linkages has...... not been identified. Here, we reveal a previously unannotated human DUB, OTULIN (also known as FAM105B), which is exquisitely specific for Met1 linkages. Crystal structures of the OTULIN catalytic domain in complex with diubiquitin reveal Met1-specific Ub-binding sites and a mechanism of substrate...

  6. Generalized functions

    CERN Document Server

    Gelfand, I M; Graev, M I; Vilenkin, N Y; Pyatetskii-Shapiro, I I

    Volume 1 is devoted to basics of the theory of generalized functions. The first chapter contains main definitions and most important properties of generalized functions as functional on the space of smooth functions with compact support. The second chapter talks about the Fourier transform of generalized functions. In Chapter 3, definitions and properties of some important classes of generalized functions are discussed; in particular, generalized functions supported on submanifolds of lower dimension, generalized functions associated with quadratic forms, and homogeneous generalized functions are studied in detail. Many simple basic examples make this book an excellent place for a novice to get acquainted with the theory of generalized functions. A long appendix presents basics of generalized functions of complex variables.

  7. MET signalling in primary colon epithelial cells leads to increased transformation irrespective of aberrant Wnt signalling

    Science.gov (United States)

    Boon, E M J; Kovarikova, M; Derksen, P W B; van der Neut, R

    2005-01-01

    It has been shown that in hereditary and most sporadic colon tumours, components of the Wnt pathway are mutated. The Wnt target MET has been implicated in the development of colon cancer. Here, we show that overexpression of wild-type or a constitutively activated form of MET in colon epithelial cells leads to increased transformation irrespective of Wnt signalling. Fetal human colon epithelial cells without aberrant Wnt signalling were transfected with wild-type or mutated MET constructs. Expression of these constructs leads to increased phosphorylation of MET and its downstream targets PKB and MAPK. Upon stimulation with HGF, the expression of E-cadherin is downregulated in wild-type MET-transfected cells, whereas cells expressing mutated MET show low E-cadherin levels independent of stimulation with ligand. This implies a higher migratory propensity of these cells. Furthermore, fetal human colon epithelial cells expressing the mutated form of MET have colony-forming capacity in soft agar, while cells expressing wild-type MET show an intermediate phenotype. Subcutaneous injection of mutated MET-transfected cells in nude mice leads to the formation of tumours within 12 days in all mice injected. At this time point, mock-transfected cells do not form tumours, while wild-type MET-transfected cells form subcutaneous tumours in one out of five mice. We thus show that MET signalling can lead to increased transformation of colon epithelial cells independent of Wnt signalling and in this way could play an essential role in the onset and progression of colorectal cancer. PMID:15785735

  8. Psychosocial Care Needs of Melanoma Survivors: Are They Being Met?

    Directory of Open Access Journals (Sweden)

    Sabine Fischbeck

    Full Text Available Patients who have survived malignant melanoma for more than five years may lack the opportunity to talk about their burden. As a consequence their psychosocial care needs remain undetected and available supportive interventions may not be utilised. Therefore, the psychosocial burden of this patient group needs to be assessed using specific screening instruments. The aim of this study was to investigate the psychosocial burden of long-term melanoma survivors, their psychosocial care needs and the determinants of these needs. We wanted to find out if the use of professional support corresponds to the care needs defined by experts. Using the cancer registry of Rhineland-Palatinate, melanoma patients diagnosed at least 5 years before the survey were contacted by physicians. N = 689 former patients completed the Hornheide Questionnaire (short form HQ-S to identify psychosocial support need (scale cut off ≥ 16 or item-based cut-off score and the potential psychosocial determinants of these needs. Additionally, they were asked about their utilisation of the professional support system. More than one third (36% of them was in need for professional psychosocial support. The highest burden scores concerned worry about tumour progression. Younger age (< 50, higher general fatigue, higher symptom burden, lower general health, negative social interactions and unfulfilled information needs were significant predictors of the need for psychosocial intervention. Related to the percentage of survivors identified as 'in need', the professional support system was underused. Further studies should investigate whether using the HQ-S to routinely identify burdened melanoma patients could lead to better fulfilment of their intervention needs, ultimately enhancing health-related quality of life.

  9. Onderzoekers sluiten jaar af met nieuwe inzichten; teelt de grond uit ook waardevol voor vollegrond

    NARCIS (Netherlands)

    Maas, van der M.P.; Elk, van P.J.H.; Voogt, W.; Dijk, van P.; Douven, F.

    2013-01-01

    Geslaagde groeiregulatie; vertraagde opbouw schadelijke aaltjes bij appel; goede resultaten met nieuwe substraten bij blauwe bes. Dat zijn de belangrijkste nieuwe inzichten van 2012 in het onderzoek naar Teelt de grond uit. De bevinding met aaltjes is ook relevant voor de teelt in de vollegrond. Het

  10. Anxiolytic effect of music exposure on BDNFMet/Met transgenic mice.

    Science.gov (United States)

    Li, Wen-Jing; Yu, Hui; Yang, Jian-Min; Gao, Jing; Jiang, Hong; Feng, Min; Zhao, Yu-Xia; Chen, Zhe-Yu

    2010-08-06

    Brain-derived neurotrophic factor (BDNF) has been reported to play important roles in the modulation of anxiety, mood stabilizers, and pathophysiology of affective disorders. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (Val66Met) has been found to be associated with depression and anxiety disorders. The humanized BDNF(Met/Met) knock-in transgenic mice exhibited increased anxiety-related behaviors that were unresponsive to serotonin reuptake inhibitors, fluoxetine. Music is known to be able to elicit emotional changes, including anxiolytic effects. In this study, we found that music treatment could significantly decrease anxiety state in BDNF(Met/Met) mice, but not in BDNF(+/)(-), mice compared with white noise exposure in open field and elevated plus maze test. Moreover, in contrast to white noise exposure, BDNF expression levels in the prefrontal cortex (PFC), amygdala and hippocampus were significantly increased in music-exposed adult BDNF(Met/Met) mice. However, music treatment could not upregulate BDNF levels in the PFC, amygdala, and hippocampus in BDNF(+/)(-) mice, which suggests the essential role of BDNF in the anxiolytic effect of music. Together, our results imply that music may provide an effective therapeutic intervention for anxiety disorders in humans with this genetic BDNF(Met) variant. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Activation of the JNK pathway is essential for transformation by the Met oncogene.

    Science.gov (United States)

    Rodrigues, G A; Park, M; Schlessinger, J

    1997-05-15

    The Met/Hepatocyte Growth Factor (HGF) receptor tyrosine kinase is oncogenically activated through a rearrangement that creates a hybrid gene Tpr-Met. The resultant chimeric p65(Tpr-Met) protein is constitutively phosphorylated on tyrosine residues in vivo and associates with a number of SH2-containing signaling molecules including the p85 subunit of PI-3 kinase and the Grb2 adaptor protein, which couples receptor tyrosine kinases to the Ras signaling pathway. Mutation of the binding site for Grb2 impairs the ability of Tpr-Met oncoprotein to transform fibroblasts, suggesting that the activation of the Ras/MAP kinase signaling pathway through Grb2 may be essential for cellular transformation. To test this hypothesis dominant-negative mutants of Grb2 with deletions of the SH3 domains were introduced into Tpr-Met transformed fibroblasts. Cells overexpressing the mutants were found to be morphologically reverted and exhibited reduced growth in soft agar. Surprisingly, the Grb2 mutants blocked activation of the JNK/SAPK but not MAP kinase activity induced by the Tpr-Met oncoprotein. Additionally, cells expressing dominant-negative Grb2 mutants had reduced PI-3-kinase activity and dominant-negative mutants of Rac1 blocked both Tpr-Met-induced transformation and activation of JNK. These experiments reveal a novel link between Met and the JNK pathway, which is essential for transformation by this oncogene.

  12. De dansmug Psectrocladius schlienzi nieuw voor Nederland, met een beschrijving van de larve (Diptera: Chironomidae)

    NARCIS (Netherlands)

    Beauvesère-Storm, de A.; Tempelman, D.

    2009-01-01

    De meeste soorten Chironomidae (dans- of vedermuggen) zijn dieren met een aquatische larve. Ze zijn een belangrijk onderdeel van de macrofaunagemeenschap van het zoete water, waarbij ze goede indicatoren zijn voor de milieukwaliteit. Veel soorten zijn met enige moeite goed tot soort of soortgroep te

  13. Recurrent MET fusion genes represent a drug target in pediatric glioblastoma

    DEFF Research Database (Denmark)

    Sehested, Astrid Marie

    2016-01-01

    Pediatric glioblastoma is one of the most common and most deadly brain tumors in childhood. Using an integrative genetic analysis of 53 pediatric glioblastomas and five in vitro model systems, we identified previously unidentified gene fusions involving the MET oncogene in ∼10% of cases. These MET...

  14. Betere en efficiëntere zorg met Lean Six Sigma

    NARCIS (Netherlands)

    Trip, A.; Jong, L.J.; Does, R.J.M.M.

    2009-01-01

    Zorgaanbieders moeten steeds meer met elkaar concurreren. De wetten van de markteconomie worden daarom meer en meer van toepassing in de zorgsector die dat tot voor kort helemaal niet gewend was. Dat vergt veranderingen, zowel in het besturen van deze organisaties, als in de omgang met patiënten en

  15. BDNF Val66Met homozygosity does not influence plasma BDNF levels in healthy human subjects

    NARCIS (Netherlands)

    Luykx, J.J.; Boks, M.P.M.; Breetvelt, E.J.; Aukes, M.F.; Strengman, E.; da Pozzo, E.; Dell'osso, L.; Marazziti, D.; van Leeuwen, A.; Vreeker, A.; Abramovic, L.; Martini, C.; Numans, M.E.; Kahn, R. S.; Ophoff, R. A.

    2013-01-01

    A putative pathway by which the BDNF Val66Met polymorphism (rs6265) leads to aberrant phenotypes is its influence on plasma BDNF. Research into the impact of rs6265 on plasma BDNF has given rise to conflicting results. Moreover, most such studies have compared Met-carriers with Val-homozygous

  16. Patienten met diabetes Mellitus type 1 screenen op coeliakie; Ja of nee

    NARCIS (Netherlands)

    Greijdanus, T.

    2005-01-01

    Diabetes mellitus type 1 is een veelvoorkomende ziekte. Deze ziekte blijkt niet op zichzelf te staan maar is onder andere geassocieerd met coeliakie. Coeliakie wordt behandeld middels een glutenvrij dieet. De diabetespatiënten die aan coeliakie lijden blijken zich niet altijd bij de huisarts met

  17. Kas Eesti Mets on vanim praegu ilmuv eestikeelne ajakiri? / Rosmarii Kurvits

    Index Scriptorium Estoniae

    Kurvits, Roosmarii, 1969-

    2015-01-01

    Artiklist selgub, et vanim tänini ilmuv eestikeelne ajakiri on baptistide häälekandja Teekäija. Kuid vanuselt järgmine ongi 1921. aastast ilmuv Eesti Mets. Ühtlasi on Eesti Mets vanim kodumaine loodusajakiri

  18. De natuur en de honingbij (interview met o.a. T. Blacquière)

    NARCIS (Netherlands)

    Versluis, K.; Blacquiere, T.

    2009-01-01

    Op het hoogtepunt van de bijenhouderij (in 1850) telde Nederland waarschijnlijk wel 200.000 volken. Nu zijn er nog 40.000 over. Met de wilde bij is het sinds de intensivering van de landbouw snel bergafwaarts gegaan. De nekslag kwam waarschijnlijk met de komst van de varroamijt, een parasiet uit

  19. 34 CFR 692.101 - What requirements must be met by a State partnership?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What requirements must be met by a State partnership...) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION LEVERAGING EDUCATIONAL ASSISTANCE PARTNERSHIP... What requirements must be met by a State partnership? (a) State. A State that is receiving an allotment...

  20. Cliëntgebonden samenwerking met mantelzorgers en vrijwilligers verbonden aan een andere organisatie: tabellen.

    NARCIS (Netherlands)

    Dieteren, C.M.; Veer, A.J.E. de; Groot, K. de

    2017-01-01

    Begin 2017 ontvingen 1756 deelnemers van het NIVEL Panel Verpleging & Verzorging via de mail een vragenlijst over cliëntgebonden samenwerking met zorgverleners of vrijwilligers uit andere organisaties. Is de mantelzorger een samenwerkingspartner? En hoe verloopt de afstemming en samenwerking met

  1. Evaluatie van individuele happy games op de iPad voor mensen met dementie

    NARCIS (Netherlands)

    Dr. J.H. Groenewoud; Dr. J. de Lange

    2014-01-01

    Er is veel belangstelling voor de kwaliteit van zorg voor mensen met dementie. Ook hun kwaliteit van leven krijgt steeds meer aandacht. Een zinvolle en plezierige dagbesteding hoort daarbij. Zorgprofessionals willen mensen met dementie graag ondersteunen bij het doen van activiteiten. Het huidige

  2. The MetLife Survey of the American Teacher: Listening to Teachers in Rural Schools

    Science.gov (United States)

    MetLife, Inc., 2013

    2013-01-01

    MetLife has sponsored and Harris Interactive has conducted the annual MetLife Survey of the American Teacher series since 1984 to share the voices of teachers with educators, policymakers and the public. The series examines significant changes and trends over time, highlights important current issues, and explores topics relevant to the future of…

  3. Voice: Reflections on an Artist-Led Program at the Met

    Science.gov (United States)

    Valladares, Maya

    2017-01-01

    This article explores an education project in which artist Fred Wilson, poets from Lincoln Center's Poet-Linc program, and the Met Museum Education Department collaborated to produce a teen-led spoken-word poetry performance in the Met's galleries. Wilson drew from his own knowledge of the collection to facilitate a group dialogue about objects…

  4. The COMT val158met polymorphism and brain morphometry in healthy young adults

    NARCIS (Netherlands)

    Zinkstok, Janneke; Schmitz, Nicole; van Amelsvoort, Therese; de Win, Maartje; van den Brink, Wim; Baas, Frank; Linszen, Don

    2006-01-01

    Catechol-O-methyltransferase (COMT) is the most important mechanism for dopamine degradation in the prefrontal cortex and contains a functional polymorphism (val(158)met) influencing enzyme activity. The low-activity met allele has been associated with better performance on cognitive tasks relying

  5. COMT Val158Met genotype as a risk factor for problem behaviors in youth

    NARCIS (Netherlands)

    M.D. Albaugh (Matthew); V.S. Harder (Valerie); R.R. Althoff (Robert); D.C. Rettew (David); E.A. Ehli (Erik); T. Lengyel-Nelson (Timea); G.E. Davies (Gareth); L. Ayer (Lynsay); J. Sulman (Julie); C. Stanger (Catherine); J.J. Hudziak (James)

    2010-01-01

    textabstractObjective: To test the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and both aggressive behavior and attention problems in youth. We hypothesized that youth carrying a Met allele would have greater average aggressive behavior scores, and that youth

  6. 'Mastspuit met sensoren brengt middel effectiever aan' (onderzoek praktijkproeven PRI en PPO)

    NARCIS (Netherlands)

    Engels, A.; PPO BBF Boomkwekerij,; PRI,; Nieuwenhuizen, A.T.

    2011-01-01

    In mei 2011 starten Plant Research International (PRI), PPO Boomkwekerij en Damcon de eerste praktijkproeven met sensoren op de mastspuit. Dit prototype spuit alleen als het bladeren detecteert. Projectleider Ard Nieuwenhuizen van PRI is ervan overtuigd dat kwekers met zo'n type spuit middelen

  7. Pepino overdraagbaar via zaad (interview met René van der Vlugt)

    NARCIS (Netherlands)

    Boonekamp, G.; Vlugt, van der R.A.A.

    2008-01-01

    Zaad geoogst van planten met pepinomozaïekvirus vormt een risico voor de overdracht van het virus naar teeltbedrijven. Dit blijkt uit resultaten van het Europees onderzoeksproject Pereira. Al langer bestonden er vermoedens dat pepino met zaad wordt overgebracht. Nu blijkt inderdaad dat het virus,

  8. The MetLife Survey of the American Teacher: Challenges for School Leadership

    Science.gov (United States)

    MetLife, Inc., 2013

    2013-01-01

    "The MetLife Survey of the American Teacher: Challenges for School Leadership" (2012) was conducted by Harris Interactive and is the twenty-ninth in a series sponsored annually by MetLife since 1984 to give voice to those closest to the classroom. This report examines the views of teachers and principals on the responsibilities and challenges…

  9. Met zorg ondernemen: Bouwstenen voor succesvolle samenwerking tussen ondernemers en langdurige zorg

    NARCIS (Netherlands)

    Mogendorff, K.

    2007-01-01

    Het project Samenwerking tussen langdurige zorg en leidinggevenden (in het bedrijfsleven) wil relevante partijen inspireren en stimuleren om meer met elkaar te gaan samenwerken om zo doelstellingen als het vergroten van de maatschappelijke participatie van mensen met een langdurige zorgbehoefte te

  10. "Met" Made Simple: Building Research-Based Teacher Evaluations. Issue Analysis Report

    Science.gov (United States)

    New Teacher Project, 2012

    2012-01-01

    Groundbreaking new findings from the Bill and Melinda Gates Foundation's Measures of Effective Teaching (MET) project hold the potential to answer crucial questions about how to assess teachers' performance. For the past two years, MET researchers have conducted a research project of unprecedented scope, involving 3,000 teachers in six school…

  11. Working with Teachers to Develop Fair and Reliable Measures of Effective Teaching. MET Project

    Science.gov (United States)

    Bill & Melinda Gates Foundation, 2010

    2010-01-01

    In fall 2009, the Bill & Melinda Gates Foundation launched the Measures of Effective Teaching (MET) project to develop and test multiple measures of teacher effectiveness. The goal of the MET project is to improve the quality of information about teaching effectiveness available to education professionals within states and districts--information…

  12. Depression, the Val66Met polymorphism, age, and gender influence the serum BDNF level

    DEFF Research Database (Denmark)

    Elfving, Betina; Buttenschøn, Henriette Nørmølle; Foldager, Leslie

    2012-01-01

    , depression, gender, the Val66Met polymorphism, and the interaction between Val66Met and gender were identified as significant determinants of the serum BDNF level. In conclusion, our data demonstrate that other factors than a diagnosis of depression influence the serum BDNF level and the importance...

  13. Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical cancer.

    Science.gov (United States)

    Boromand, Nadia; Hasanzadeh, Malihe; ShahidSales, Soodabeh; Farazestanian, Marjaneh; Gharib, Masoumeh; Fiuji, Hamid; Behboodi, Negin; Ghobadi, Niloofar; Hassanian, Seyed Mahdi; Ferns, Gordon A; Avan, Amir

    2018-06-01

    Aberrant activation of the HGF/c-Met signalling pathway is reported to be associated with cell proliferation, progression, and metastasis features of several tumor types, including cervical cancer, suggesting that it may be of potential value as a novel therapeutic target. Furthermore, HPV-positive patients had a higher serum level of HGF or c-Met protein, compared with HPV-negative patients. c-Met or HGF overexpression in lesions of cervical cancer is reported to be related to a poorer prognosis, and hence this may be of value as a prognostic and predictive biomarker. Several approaches have been developed for targeting HGF and/or c-Met. One of these is crizotinib (a dual c-Met/ALK inhibitor). This has been approved by FDA for the treatment of lung-cancer. Further investigations are required to evaluate and optimize the use of c-Met inhibitors in cervical cancer or parallel targeting signalling pathway associated/activated via MET/HGF pathway. The main aim of current review was to give an overview of the potential of the c-Met/HGF pathway as a prognostic, or predictive biomarker in cervical cancer. © 2017 Wiley Periodicals, Inc.

  14. Genetic contribution of catechol-O-methyltransferase polymorphism (Val158Met) in children with chronic tension-type headache.

    Science.gov (United States)

    Fernández-de-las-Peñas, César; Ambite-Quesada, Silvia; Rivas-Martínez, Inés; Ortega-Santiago, Ricardo; de-la-Llave-Rincón, Ana Isabel; Fernández-Mayoralas, Daniel M; Pareja, Juan A

    2011-10-01

    Our aim was to investigate the relationship between Val158Met polymorphisms, headache, and pressure hypersensitivity in children with chronic tension-type headache (CTTH). A case-control study with blinded assessor was conducted. Seventy children with CTTH associated with pericranial tenderness and 70 healthy children participated. After amplifying Val158Met polymorphism by polymerase chain reactions, we assessed genotype frequencies and allele distributions. We classified children according to their Val158Met polymorphism: Val/Val, Val/Met, Met/Met. Pressure pain thresholds (PPT) were bilaterally assessed over the temporalis, upper trapezius, second metacarpal, and tibialis anterior muscles. The distribution of Val158Met genotypes was not significantly different (p = 0.335), between children with CTTH and healthy children, and between boys and girls (p = 0.872). Children with CTTH with the Met/Met genotype showed a longer headache history compared with those with Met/Val (p = 0.001) or Val/Val (p = 0.002) genotype. Children with CTTH with Met/Met genotype showed lower PPT over upper trapezius and temporalis muscles than children with CTTH with Met/Val or Val/Val genotype (p < 0.01). The Val158Met catechol-O-methyltransferase (COMT) polymorphism does not appear to be involved in predisposition to suffer from CTTH in children; nevertheless, this genetic factor may be involved in the phenotypic expression, as pressure hypersensitivity was greater in those CTTH children with the Met/Met genotype.

  15. {sup 89}Zr-Onartuzumab PET imaging of c-MET receptor dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Pool, Martin; Kol, Arjan; Giesen, Danique; Vries, Elisabeth G.E. de [University of Groningen, Department of Medical Oncology, University Medical Center Groningen, Groningen (Netherlands); Terwisscha van Scheltinga, Anton G.T. [University of Groningen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen (Netherlands); Lub-de Hooge, Marjolijn N. [University of Groningen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen (Netherlands); University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen (Netherlands)

    2017-08-15

    c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of {sup 89}Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts. In vitro membrane c-MET levels were determined by flow cytometry. HCC827ErlRes, an erlotinib-resistant clone with c-MET upregulation, was generated from the exon-19 EGFR-mutant human NSCLC cell line HCC827. Mice bearing HCC827 and HCC827ErlRes tumours in opposite flanks underwent {sup 89}Zr-onartuzumab PET scans. The HCC827-xenografted mice underwent {sup 89}Zr-onartuzumab PET scans before treatment and while receiving biweekly intraperitoneal injections of 100 mg/kg NVP-AUY-922 or vehicle. Ex vivo, tumour c-MET immunohistochemistry was correlated with the imaging results. In vitro, membrane c-MET was upregulated in HCC827ErlRes tumours by 213 ± 44% in relation to the level in HCC827 tumours, while c-MET was downregulated by 69 ± 9% in HCC827 tumours following treatment with NVP-AUY-922. In vivo, {sup 89}Zr-onartuzumab uptake was 26% higher (P < 0.05) in erlotinib-resistant HCC827ErlRes than in HCC827 xenografts, while HCC827 tumour uptake was 33% lower (P < 0.001) following NVP-AUY-922 treatment. The results show that {sup 89}Zr-onartuzumab PET effectively discriminates relevant changes in c-MET levels and could potentially be used clinically to monitor c-MET status. (orig.)

  16. General Editorial

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. General Editorial. Articles in Resonance – Journal of Science Education. Volume 19 Issue 1 January 2014 pp 1-2 General Editorial. General Editorial on Publication Ethics · R Ramaswamy · More Details Fulltext PDF. Volume 19 Issue 1 January 2014 pp 3-3 ...

  17. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    International Nuclear Information System (INIS)

    Stiene-Martin, A.; Hauser, K.F.

    1990-01-01

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 μM met-enkephalin, 1 μM met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined [ 3 H]-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in [ 3 H]-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture

  18. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    Energy Technology Data Exchange (ETDEWEB)

    Stiene-Martin, A.; Hauser, K.F. (Univ. of Kentucky, Lexington (USA))

    1990-01-01

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 {mu}M met-enkephalin, 1 {mu}M met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined ({sup 3}H)-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in ({sup 3}H)-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture.

  19. De ontwikkeling van een met onderzoek onderbouwde methodiek voor het meidenwerk

    Directory of Open Access Journals (Sweden)

    Judith Metz

    2016-03-01

    Full Text Available The development of a method substantiated by research for girls’ workThis article reports on a study into the possibility of developing a method substantiated by research for girls’ work. It provides an insight into the opportunities and difficulties in building up a knowledge base for open approach methods in the practice of social work. The study was carried out in response to a request by Amsterdam girls’ workers for help in developing an open approach method for this diverse and dynamic practice, which has a history of almost 90 years. A notable characteristic in the practice of girls’ work is that it involves an open approach method. This implies that the professional does not follow a fixed step-by-step plan from a to b. Rather, it involves professional interventions in the social domain with a goal-oriented, process-based, moral and dialogical character.The background forms the discussion about the knowledge base of the social work. Current models, such as Evidence Based Practice, Practice Based Evidence and Common Factors, are unsuitable for developing a method that is substantiated by research into open approach methods. Neither does the limitation of Evidence Based Practice to a causal series of actions do justice to the complexity and dynamics of open approach methods. Practice Based Evidence does offer sufficient scope for this, but there is insufficient guidance on how the diversity of working methods, target groups, goals and contexts can be captured in one denominator and how this can be substantiated with empirical research. The Common Factors model is interesting as an example of how exactly those factors can be identified as communal within various working methods, target groups, goals and contexts and can be substantiated with research. The problem with this model is that the factors identified, such as the working relationship or the method, are too general to describe and substantiate specifically how girls’ work

  20. c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival.

    Science.gov (United States)

    Lee, Su Jin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Kim, Seung Tae

    2018-03-02

    Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features and survival. Primary tumor sites were 67 right-sided colon, 98 left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%) exhibited c-MET overexpression. There was no significant difference in the prevalence of c-MET overexpression according to primary site, histologic differentiation, molecular markers, or metastatic sites. In a comparison of the tumor response to first-line chemotherapy according to the level of c-MET expression, we found no significant difference in either partial response or disease control rate. In the survival analysis, patients with c-MET overexpression had significantly shorter overall survival (39 vs. 27 months; P = .018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7 months; P = .024). c-MET overexpression, which was detected in 39 CRC patients (15.3%) irrespective of primary sites or molecular markers, indicated a poor survival prognosis and predicted shorter PFS during bevacizumab treatment in patients with CRC. Further studies are warranted to elucidate the value of c-MET-targeted therapy in CRC patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Mice with GFAP-targeted loss of neurofibromin demonstrate increased axonal MET expression with aging.

    Science.gov (United States)

    Su, Weiping; Xing, Rubing; Guha, Abhijit; Gutmann, David H; Sherman, Larry S

    2007-05-01

    Neurofibromatosis 1 (NF1) is a common genetic disease that predisposes patients to peripheral nerve tumors and central nervous system (CNS) abnormalities including low-grade astrocytomas and cognitive disabilities. Using mice with glial fibrillary acidic protein (GFAP)-targeted Nf1 loss (Nf1(GFAP)CKO mice), we found that Nf1(-/-) astrocytes proliferate faster and are more invasive than wild-type astrocytes. In light of our previous finding that aberrant expression of the MET receptor tyrosine kinase contributes to the invasiveness of human NF1-associated malignant peripheral nerve sheath tumors, we sought to determine whether MET expression is aberrant in the brains of Nf1 mutant mice. We found that Nf1(-/-) astrocytes express slightly more MET than wild-type cells in vitro, but do not express elevated MET in situ. However, fiber tracts containing myelinated axons in the hippocampus, midbrain, cerebral cortex, and cerebellum express higher than normal levels of MET in older (> or =6 months) Nf1(GFAP)CKO mice. Both Nf1(GFAP)CKO and wild-type astrocytes induced MET expression in neurites of wild-type hippocampal neurons in vitro, suggesting that astrocyte-derived signals may induce MET in Nf1 mutant mice. Because the Nf1 gene product functions as a RAS GTPase, we examined MET expression in the brains of mice with GFAP-targeted constitutively active forms of RAS. MET was elevated in axonal fiber tracts in mice with active K-RAS but not H-RAS. Collectively, these data suggest that loss of Nf1 in either astrocytes or GFAP(+) neural progenitor cells results in increased axonal MET expression, which may contribute to the CNS abnormalities in children and adults with NF1. (c) 2007 Wiley-Liss, Inc.

  2. Jong lesers se identifisering met karakters: skryfteorie en -praktyk

    Directory of Open Access Journals (Sweden)

    F. Greyling

    2005-07-01

    Full Text Available Young readers’ identification with characters: the theory and practice of creative writing It is generally acknowledged that reader identification with characters contributes to readers’ involvement in the text and the subsequent pleasure derived from reading stories. It seems that establishing a relationship with the implied reader of the text comes naturally for successful authors. There is, however, a lack of coherent theory on reader identification with characters which can be used in the teaching of creative writing. This article combines insights gained from various disciplines in order to develop a coherent theory of the phenomenon of reader identification. Of special interest are the results of reader-response research regarding the relation between individuals’ development phase and identification with characters. Some of the possibilities which the writer can utilise to establish a relationship with the reader and influence the nature of reader identification with characters are the choice of characters and their depiction in the text, the narrative strategy and the use of viewpoint.

  3. The autism associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain

    OpenAIRE

    Peng, Yun; Lu, Zhongming; Li, Guohui; Piechowicz, Mariel; Anderson, Miranda; Uddin, Yasin; Wu, Jie; Qiu, Shenfeng

    2016-01-01

    The human MET gene imparts a replicated risk for autism spectrum disorder (ASD), and is implicated in the structural and functional integrity of brain. MET encodes a receptor tyrosine kinase, MET, which plays a pleiotropic role in embryogenesis and modifies a large number of neurodevelopmental events. Very little is known, however, on how MET signaling engages distinct cellular events to collectively affect brain development in ASD-relevant disease domains. Here, we show that MET protein expr...

  4. Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study

    OpenAIRE

    Saravani, Ramin; Galavi, Hamid Reza; Lotfian Sargazi, Marzieh

    2017-01-01

    Objective: Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. Method: This case- contro...

  5. Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study.

    Science.gov (United States)

    Saravani, Ramin; Galavi, Hamid Reza; Lotfian Sargazi, Marzieh

    2017-10-01

    Objective: Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. Method: This case- control study included 92 SCZ patients and 92 healthy controls (HCs). Genotyping of both variants (COMT Val158Met (G>A) and BDNF Val66Met (G>A)) were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Results: The findings revealed that the COMT Val158Met (G>A) polymorphism was not associated with the risk/protective of SCZ in all models (OR=0.630, 95%CI=0.299-1.326, P=0.224, GA vs. GG, OR=1.416, 95%CI=0.719-2.793, P=0.314, AA vs. GG, OR=1.00, 95%CI=0.56-1.79, P=1.00 GA+AA vs. GG, OR=1.667, 95%CI=0.885-3.125, P=0.11, AA vs. GG+GA, OR=1.247, 95%CI=0.825-1.885, P=0.343, A vs. G,). However, BDNF Val66Met (G>A) variant increased the risk of SCZ (OR = 2.008 95%CI = 1.008-4.00, P = 0.047, GA vs. GG, OR = 3.876 95%CI = 1.001-14.925, P = 0.049. AA vs. GG, OR = 2.272. 95%CI = 1.204-4.347, P = 0.011, GA+AA vs. GG, OR = 2.22 95%CI = 1.29-3.82. P = 0.005, A vs. G). Conclusion: The results did not support an association between COMT Val158Met (G>A) variant and risk/protective of SCZ. Moreover, it was found that BDNF Val66Met (G>A) polymorphism may increase the risk of SCZ development. Further studies and different ethnicities are recommended to confirm the findings.

  6. Role of cMET in the Development and Progression of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Ilaria Bossi

    2013-09-01

    Full Text Available Mesenchymal-epithelial transition (MET is a member of a distinct subfamily of heterodimeric receptor tyrosine kinase receptors that specifically binds the hepatocyte growth factor (HGF. Binding to HGF leads to receptor dimerization/multimerization and phosphorylation, resulting in its catalytic activation. MET activation drives the malignant progression of several tumor types, including colorectal cancer (CRC, by promoting signaling cascades that mainly result in alterations of cell motility, survival, and proliferation. MET is aberrantly activated in many human cancers through various mechanisms, including point mutations, gene amplification, transcriptional up-regulation, or ligand autocrine loops. MET promotes cell scattering, invasion, and protection from apoptosis, thereby acting as an adjuvant pro-metastatic gene for many tumor types. In CRC, MET expression confers more aggressiveness and worse clinical prognosis. With all of this rationale, inhibitors that target the HGF/MET axis with different types of response have been developed. HGF and MET are new promising targets to understand the pathogenesis of CRC and for the development of new, targeted therapies.

  7. ROCK I Has More Accurate Prognostic Value than MET in Predicting Patient Survival in Colorectal Cancer.

    Science.gov (United States)

    Li, Jian; Bharadwaj, Shruthi S; Guzman, Grace; Vishnubhotla, Ramana; Glover, Sarah C

    2015-06-01

    Colorectal cancer remains the second leading cause of death in the United States despite improvements in incidence rates and advancements in screening. The present study evaluated the prognostic value of two tumor markers, MET and ROCK I, which have been noted in other cancers to provide more accurate prognoses of patient outcomes than tumor staging alone. We constructed a tissue microarray from surgical specimens of adenocarcinomas from 108 colorectal cancer patients. Using immunohistochemistry, we examined the expression levels of tumor markers MET and ROCK I, with a pathologist blinded to patient identities and clinical outcomes providing the scoring of MET and ROCK I expression. We then used retrospective analysis of patients' survival data to provide correlations with expression levels of MET and ROCK I. Both MET and ROCK I were significantly over-expressed in colorectal cancer tissues, relative to the unaffected adjacent mucosa. Kaplan-Meier survival analysis revealed that patients' 5-year survival was inversely correlated with levels of expression of ROCK I. In contrast, MET was less strongly correlated with five-year survival. ROCK I provides better efficacy in predicting patient outcomes, compared to either tumor staging or MET expression. As a result, ROCK I may provide a less invasive method of assessing patient prognoses and directing therapeutic interventions. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. Effects of the BDNF Val66Met polymorphism on neural responses to facial emotion.

    Science.gov (United States)

    Mukherjee, Prerona; Whalley, Heather C; McKirdy, James W; McIntosh, Andrew M; Johnstone, Eve C; Lawrie, Stephen M; Hall, Jeremy

    2011-03-31

    The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with affective disorders, but its role in emotion processing has not been fully established. Due to the clinically heterogeneous nature of these disorders, studying the effect of genetic variation in the BDNF gene on a common attribute such as fear processing may elucidate how the BDNF Val66Met polymorphism impacts brain function. Here we use functional magnetic resonance imaging examine the effect of the BDNF Val66Met genotype on neural activity for fear processing. Forty healthy participants performed an implicit fear task during scanning, where subjects made gender judgments from facial images with neutral or fearful emotion. Subjects were tested for facial emotion recognition post-scan. Functional connectivity was investigated using psycho-physiological interactions. Subjects were genotyped for the BDNF Val66Met polymorphism and the measures compared between genotype groups. Met carriers showed overactivation in the anterior cingulate cortex (ACC), brainstem and insula bilaterally for fear processing, along with reduced functional connectivity from the ACC to the left hippocampus, and impaired fear recognition ability. The results show that during fear processing, Met allele carriers show an increased neural response in regions previously implicated in mediating autonomic arousal. Further, the Met carriers show decreased functional connectivity with the hippocampus, which may reflect differential retrieval of emotional associations. Together, these effects show significant differences in the neural substrate for fear processing with genetic variation in BDNF. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  9. COMT Val158Met polymorphism, cognitive stability and cognitive flexibility: an experimental examination

    Directory of Open Access Journals (Sweden)

    Rosa Elise C

    2010-09-01

    Full Text Available Abstract Background Dopamine in prefrontal cortex (PFC modulates core cognitive processes, notably working memory and executive control. Dopamine regulating genes and polymorphisms affecting PFC - including Catechol-O-Methyltransferase (COMT Val158Met - are crucial to understanding the molecular genetics of cognitive function and dysfunction. A mechanistic account of the COMT Val158Met effect associates the Met allele with increased tonic dopamine transmission underlying maintenance of relevant information, and the Val allele with increased phasic dopamine transmission underlying the flexibility of updating new information. Thus, consistent with some earlier work, we predicted that Val carriers would display poorer performance when the maintenance component was taxed, while Met carriers would be less efficient when rapid updating was required. Methods Using a Stroop task that manipulated level of required cognitive stability and flexibility, we examined reaction time performance of patients with schizophrenia (n = 67 and healthy controls (n = 186 genotyped for the Val/Met variation. Results In both groups we found a Met advantage for tasks requiring cognitive stability, but no COMT effect when a moderate level of cognitive flexibility was required, or when a conflict cost measure was calculated. Conclusions Our results do not support a simple stability/flexibility model of dopamine COMT Val/Met effects and suggest a somewhat different conceptualization and experimental operationalization of these cognitive components.

  10. Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Kathryn T Hall

    Full Text Available Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT, an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS. The three treatment arms from this study were: no-treatment ("waitlist", placebo treatment alone ("limited" and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035. The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

  11. Benchmarking and gap analysis of faculty mentorship priorities and how well they are met.

    Science.gov (United States)

    Bruner, Deborah Watkins; Dunbar, Sandra; Higgins, Melinda; Martyn, Kristy

    2016-01-01

    There is little consensus among faculty mentoring programs as to best practices. While there are recommendations in the literature to base faculty development programs on gap analyses of faculty ratings of actual and preferred performance in teaching, scholarship and service, no gap analysis was found in the literature. Thus, the purpose of this study was to develop a survey tool to benchmark school of nursing (SON) faculty mentorship priorities and conduct a gap analysis of how well they were being addressed. Senior faculty who lead mentorship as part of their roles in the SON (associate and assistant deans and director of mentorship) developed a survey through (a) asking faculty members for priorities at in-person mentorship seminars, (b) a review of current nursing literature, and (c) input from the SON mentorship advisory board. The final survey included 37 items focused on general job duties, structure of the mentoring program, time management, as well as skills needed for research, teaching, practice, writing and team science. Responses (rated from 0-not important to 5-very high priority) were requested in 4 areas: the first area focused on how high a priority the respondent rated a given item and areas 2 to 4 focused on how well the need was met by one of three resources: their SON primary assigned mentor, other SON resources, or other university resources. There were 63 eligible SON faculty to whom the survey was e-mailed with a 60% (n = 38) response rate. Most of the respondents were clinical track (42.1%) followed by tenure track (39.5%) and research track (15.8%). Half were assistant professors. The percentage of respondents giving a rating of 4 to 5 were calculated and then ranked. Almost all the faculty responding, regardless of track or rank, desired formal mentorship. Among all faculty, the top five priorities were guidance on producing timely publications (70.4%), mentorship on work-life balance (68%), mentorship on putting together a promotion

  12. Generalized product

    OpenAIRE

    Greco, Salvatore; Mesiar, Radko; Rindone, Fabio

    2014-01-01

    Aggregation functions on [0,1] with annihilator 0 can be seen as a generalized product on [0,1]. We study the generalized product on the bipolar scale [–1,1], stressing the axiomatic point of view. Based on newly introduced bipolar properties, such as the bipolar increasingness, bipolar unit element, bipolar idempotent element, several kinds of generalized bipolar product are introduced and studied. A special stress is put on bipolar semicopulas, bipolar quasi-copulas and bipolar copulas.

  13. The c-Met Inhibitor MSC2156119J Effectively Inhibits Tumor Growth in Liver Cancer Models

    Energy Technology Data Exchange (ETDEWEB)

    Bladt, Friedhelm, E-mail: Friedhelm.Bladt@merckgroup.com; Friese-Hamim, Manja; Ihling, Christian; Wilm, Claudia; Blaukat, Andree [EMD Serono, and Merck Serono Research and Development, Merck KGaA, Darmstadt 64293 (Germany)

    2014-08-19

    The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling.

  14. Metaphor and Corpus Linguistics Metáfora e linguística de corpus

    Directory of Open Access Journals (Sweden)

    Tony Berber Sardinha

    2011-01-01

    Full Text Available In this paper, I look at four different aspects of metaphor research from a corpus linguistic perspective, namely: (1 the lexicogrammar of metaphors, which refers to the patterning of linguistic metaphor revealed by corpus analysis; (2 metaphor probabilities, which is a facet of metaphor that emerges from frequency-based studies of metaphor; (3 dimensions of metaphor variation, or the search for systematic parameters of variation in metaphor use across different registers; and (4 automated metaphor retrieval, which relates to the development of software to help identify metaphors in corpora. I argue that these four aspects are interrelated, and that advances in one of them can drive changes in the others.Neste artigo discuto quarto aspectos da pesquisa sobre metáfora do ponto de vista da linguística de corpus: (1 a lexicogramática das metáforas, que se refere aos padrões da metáfora linguística revelados pela análise de corpus; (2 probabilidades metafóricas, que é uma faceta da metáfora que emerge a partir dos estudos relacionados à freqüência de metáforas; (3 dimensões da variação de metáforas, ou a busca por parâmetros sistemáticos de variação de uso de metáfora em diferentes gêneros; e (4 captura automática de metáfora, que está relacionada ao desenvolvimento de softwares que auxiliam na identificação de metáforas em corpora. I defendo que esses quatro aspectos são interrelacionados, e que progressos em um deles podem acarretar mudanças nos outros.

  15. The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism.

    Science.gov (United States)

    Eagleson, Kathie L; Xie, Zhihui; Levitt, Pat

    2017-03-01

    People with autism spectrum disorder and other neurodevelopmental disorders (NDDs) are behaviorally and medically heterogeneous. The combination of polygenicity and gene pleiotropy-the influence of one gene on distinct phenotypes-raises questions of how specific genes and their protein products interact to contribute to NDDs. A preponderance of evidence supports developmental and pathophysiological roles for the MET receptor tyrosine kinase, a multifunctional receptor that mediates distinct biological responses depending upon cell context. MET influences neuron architecture and synapse maturation in the forebrain and regulates homeostasis in gastrointestinal and immune systems, both commonly disrupted in NDDs. Peak expression of synapse-enriched MET is conserved across rodent and primate forebrain, yet regional differences in primate neocortex are pronounced, with enrichment in circuits that participate in social information processing. A functional risk allele in the MET promoter, enriched in subgroups of children with autism spectrum disorder, reduces transcription and disrupts socially relevant neural circuits structurally and functionally. In mice, circuit-specific deletion of Met causes distinct atypical behaviors. MET activation increases dendritic complexity and nascent synapse number, but synapse maturation requires reductions in MET. MET mediates its specific biological effects through different intracellular signaling pathways and has a complex protein interactome that is enriched in autism spectrum disorder and other NDD candidates. The interactome is coregulated in developing human neocortex. We suggest that a gene as pleiotropic and highly regulated as MET, together with its interactome, is biologically relevant in normal and pathophysiological contexts, affecting central and peripheral phenotypes that contribute to NDD risk and clinical symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Isolation and characterization of anti c-met single chain fragment variable (scFv) antibodies.

    Science.gov (United States)

    Qamsari, Elmira Safaie; Sharifzadeh, Zahra; Bagheri, Salman; Riazi-Rad, Farhad; Younesi, Vahid; Abolhassani, Mohsen; Ghaderi, Sepideh Safaei; Baradaran, Behzad; Somi, Mohammad Hossein; Yousefi, Mehdi

    2017-12-01

    The receptor tyrosine kinase (RTK) Met is the cell surface receptor for hepatocyte growth factor (HGF) involved in invasive growth programs during embryogenesis and tumorgenesis. There is compelling evidence suggesting important roles for c-Met in colorectal cancer proliferation, migration, invasion, angiogenesis, and survival. Hence, a molecular inhibitor of an extracellular domain of c-Met receptor that blocks c-Met-cell surface interactions could be of great thera-peutic importance. In an attempt to develop molecular inhibitors of c-Met, single chain variable fragment (scFv) phage display libraries Tomlinson I + J against a specific synthetic oligopeptide from the extracellular domain of c-Met receptor were screened; selected scFv were then characterized using various immune techniques. Three c-Met specific scFv (ES1, ES2, and ES3) were selected following five rounds of panning procedures. The scFv showed specific binding to c-Met receptor, and significantly inhibited proliferation responses of a human colorectal carcinoma cell line (HCT-116). Moreover, anti- apoptotic effects of selected scFv antibodies on the HCT-116 cell line were also evaluated using Annexin V/PI assays. The results demonstrated rates of apoptotic cell death of 46.0, 25.5, and 37.8% among these cells were induced by use of ES1, ES2, and ES3, respectively. The results demonstrated ability to successfully isolate/char-acterize specific c-Met scFv that could ultimately have a great therapeutic potential in immuno-therapies against (colorectal) cancers.

  17. Waarom volwassenen met ADHD vaak te laat komen op afspraken – is het een beperking in de tijdwaarneming of het geheugen?

    NARCIS (Netherlands)

    Mette, Christian; Zielke, Annika; Groen, Yvonne

    Volwassenen met aandachtstekortstoornis met hyperactiviteit (ADHD) hebben vaak moeite met tijdmanagement en het nakomen van afspraken. Een belangrijke functie voor tijdmanagement is tijdwaarneming, die weer samenhangt met de werking van het kortetermijn- en het werkgeheugen. De onderliggende

  18. 34 CFR 76.530 - General cost principles.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false General cost principles. 76.530 Section 76.530... Be Met by the State and Its Subgrantees? Allowable Costs § 76.530 General cost principles. Both 34 CFR 74.27 and 34 CFR 80.22 reference the general cost principles that apply to grants, subgrants and...

  19. 34 CFR 75.530 - General cost principles.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false General cost principles. 75.530 Section 75.530 Education Office of the Secretary, Department of Education DIRECT GRANT PROGRAMS What Conditions Must Be Met by a Grantee? Allowable Costs § 75.530 General cost principles. The general principles to be used in...

  20. Vigas de madera laminada Glulam reforzadas con pletinas metálicas dentadas

    OpenAIRE

    Cañola, Hernán Darío

    2015-01-01

    En esta tesis se estudian las propiedades mecánicas de vigas de madera maciza y de madera laminada Glulam reforzadas con pletinas metálicas dentadas. Se fabricaron y analizaron experimentalmente cuatro grupos diferentes de vigas: 30 vigas de madera maciza no reforzadas, 30 vigas de madera maciza reforzadas con pletinas metálicas dentadas, 30 vigas de madera laminada Glulam no reforzadas y 30 vigas de madera laminada Glulam reforzadas con pletinas metálicas dentadas. Las vigas de madera ...

  1. The applications of 11C-MET PET in brain tumor

    International Nuclear Information System (INIS)

    Hua Fengchun

    2002-01-01

    11 C-methionine (MET), an amino acid, is the most widely used radio pharmaceutics which can reflect transport metabolism of amino acid in vivo, and synthesis of protein in tumor. 11 C-MET PET can be used for evaluation of brain tumor: detection of tumor, differential diagnosis between recurrence and radiation necrosis and early evaluation of response to treatment. Especially, for the definition of tumor margin and detection of low-grade tumors, PET with 11 C-MET is better than PET with 18 F-FDG or other modalities such as CT and MRI

  2. Bepaling van glycyrrhetinezuur in humaan plasma met hoge-druk vloeistofchromatografie ; methode-ontwikkeling en monsteranalyse

    NARCIS (Netherlands)

    Somers HHJ; Stolker AAM; Gelderen CEM van; Savelkoul TJF; Ginkel LA van; ARO; VIC

    1995-01-01

    Dit rapport beschrijft een snelle vloeistofchromatografische methode voor de bepaling van glycyrrhetinezuur in monsters humaan plasma. Na denaturatie van de plasma-eiwitten door toevoegen van ureum, wordt het glycyrrhetinezuur uit plasma geextraheerd met ionpaar vaste-fase extractie. Het

  3. Nieuwe technieken om spuiwater te zuiveren zijn veelbelovend (interview met o.a. Erik van Os)

    NARCIS (Netherlands)

    Arkesteijn, M.; Os, van E.A.

    2012-01-01

    TNO en Wageningen UR Glastuinbouw hebben samen een proefproject gedaan met twee veelbelovende technieken om spuiwater te zuiveren: omgekeerde osmose en membraandestillatie. Deze test vond plaats bij Olij Rozen in De Kwakel. Technisch gezien voldoen beide technieken.

  4. Over ontmoetingen tussen mensen met en zonder verstandelijke beperking in omgekeerde-integratiesettingen

    Directory of Open Access Journals (Sweden)

    Gerda Scholtens

    2016-09-01

    Full Text Available Gustaaf Bos. Antwoorden op andersheid. Over ontmoetingen tussen mensen met en zonder verstandelijke beperking in omgekeerde-integratiesettingen. Nieuwegein: EPC, 2016, 379 p. ISBN: 9789462287358

  5. Bepaling van enkele neurotransmitters, monoaminen, en metabolieten, met behulp van Continuous Flowapparatuur

    NARCIS (Netherlands)

    Eigeman L; Schonewille F; Borst M; van der Laan JW

    1986-01-01

    Bij het onderzoek in de psychofarmacologie kan kennis van de effecten van stoffen op de omzettingssnelheid van neurotransmitters een belangrijk aspect zijn. Met de huidige psychofarmaca lijken vooral de klassieke neurotransmitters zoals de monoaminen, noradrenaline, dopamine en serotonine van

  6. Bemiddelen bij conflicten tussen buren : Een sociaal-wetenschappelijke evaluatie van experimenten met Buurtbemiddeling in Nederland

    NARCIS (Netherlands)

    Peper, Bram; Spierings, Frans; Jong, Wiebe de; Blad, John; Hogenhuis, Stijn; Altena, Vanessa van

    1999-01-01

    In dit boek worden initiatieven geanalyseerd die vanaf 1996 zijn gestart in Rotterdam, Zwolle, en Gouda met vrijwillige bemiddelaars bij burenruzies. Deze vrijwillige bemiddelaars vormen een afspiegeling van de sociale en etnische samenstelling van de betreffende buurten. Naast een procesanalyse,

  7. 75 FR 16205 - MetLife Insurance Company of Connecticut, et al.

    Science.gov (United States)

    2010-03-31

    ... Board of Directors/Trustees without shareholder approval. However, Met Series Fund and MIST represent... remuneration will be paid to any party in connection with the proposed in kind purchase transactions. 27. The...

  8. 76 FR 401 - MetLife Insurance Company of Connecticut, et al.

    Science.gov (United States)

    2011-01-04

    ... Board of Directors/Trustees without shareholder approval. However, Met Series Fund and MIST represent... brokerage commission, fee, or other remuneration will be paid to any party in connection with the proposed...

  9. Statistical forecasting of met-ocean parameters in the Cochin estuarine system, southwest coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Srinivas, K.; Revichandran, C.; DineshKumar, P.K.

    Three different statistical forecasting techniques - autoregressive, sinusoidal and exponentially weighted moving average (EWMA) were used to forecast monthly values of meteorological and oceanographic (met-ocean) parameters viz. sea surface...

  10. A sequential EMT-MET mechanism drives the differentiation of human embryonic stem cells towards hepatocytes.

    Science.gov (United States)

    Li, Qiuhong; Hutchins, Andrew P; Chen, Yong; Li, Shengbiao; Shan, Yongli; Liao, Baojian; Zheng, Dejin; Shi, Xi; Li, Yinxiong; Chan, Wai-Yee; Pan, Guangjin; Wei, Shicheng; Shu, Xiaodong; Pei, Duanqing

    2017-05-03

    Reprogramming has been shown to involve EMT-MET; however, its role in cell differentiation is unclear. We report here that in vitro differentiation of hESCs to hepatic lineage undergoes a sequential EMT-MET with an obligatory intermediate mesenchymal phase. Gene expression analysis reveals that Activin A-induced formation of definitive endoderm (DE) accompanies a synchronous EMT mediated by autocrine TGFβ signalling followed by a MET process. Pharmacological inhibition of TGFβ signalling blocks the EMT as well as DE formation. We then identify SNAI1 as the key EMT transcriptional factor required for the specification of DE. Genetic ablation of SNAI1 in hESCs does not affect the maintenance of pluripotency or neural differentiation, but completely disrupts the formation of DE. These results reveal a critical mesenchymal phase during the acquisition of DE, highlighting a role for sequential EMT-METs in both differentiation and reprogramming.

  11. Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice

    Directory of Open Access Journals (Sweden)

    Roko Martinić

    2014-08-01

    Full Text Available Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.5 mg/kg, which corresponds to the protective dose reported for several different animal disease models. In this group plasma alanine aminotransferase and aspartate aminotransferase enzyme activities, as well as liver necrosis score were significantly reduced in comparison to control animals treated with physiological saline (p > 0.01. The specificity of the peptide hepatoprotection was investigated from the standpoint of the receptor and peptide blockade. It was concluded that Met-enkephalin effects on the liver were mediated via δ and ζ opioid receptors. Genotoxic testing of Met-enkephalin confirmed the safety of the peptide.

  12. Techniek moet rijtaak ondersteunen : interview met Fred Wegman, directeur SWOV, over verkeersveiligheid.

    NARCIS (Netherlands)

    Ohm, R.

    2010-01-01

    Het gaat nog steeds goed, maar het kan altijd beter. Helaas is de problematiek ingewikkelder geworden en zijn er geen snelle oplossingen met veel effect meer voorhanden. Daarom moet het karakter van de aanpak van verkeersonveiligheid veranderen. (Author/publisher)

  13. Ervaringen met camouflage- en afleidingstrategieën in Woonzorgcentra Flevoland : Een kwalitatief onderzoek

    NARCIS (Netherlands)

    Dumisevic, S.; Mourits, P.M.C.; Schreuder, E.J.A.

    2012-01-01

    Woonzorgcentra Flevoland (verder WZF) is een zorginstelling die verpleeghuiszorg, verzorgingshuiszorg, dagverzorging en thuiszorg levert in Lelystad. Er zijn twee locaties, De Uiterton en Hanzeborg. Voor ouderen met dementie heeft WZF kleinschalige woongroepen gerealiseerd waarbij een open deuren

  14. Kaliumfosfiet helpt kalanchoë tegen phytophthora (interview met Filip van Noort)

    NARCIS (Netherlands)

    Neefjes, H.; Noort, van F.R.

    2009-01-01

    Toevoegen van plantversterker kaliumfosfiet maakt kalanchoë weerbaar tegen phytophthora. Onderzoek bij WUR Glastuinbouw heeft dit aangetoond in een deel van een proef. De praktijk is voorzichtig met het middel

  15. Influence of Met-Ocean Condition Forecasting Uncertainties on Weather Window Predictions for Offshore Operations

    DEFF Research Database (Denmark)

    Gintautas, Tomas; Sørensen, John Dalsgaard

    2017-01-01

    The article briefly presents a novel methodology of weather window estimation for offshore operations and mainly focuses on effects of met-ocean condition forecasting uncertainties on weather window predictions when using the proposed methodology. It is demonstrated that the proposed methodology...... to include stochastic variables, representing met-ocean forecasting uncertainties and the results of such modification are given in terms of predicted weather windows for a selected test case....

  16. The BDNF Val66Met Polymorphism Affects the Vulnerability of the Brain Structural Network

    Directory of Open Access Journals (Sweden)

    Chang-hyun Park

    2017-08-01

    Full Text Available Val66Met, a naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF gene resulting in a valine (Val to methionine (Met substitution at codon 66, plays an important role in neuroplasticity. While the effect of the BDNF Val66Met polymorphism on local brain structures has previously been examined, its impact on the configuration of the graph-based white matter structural networks is yet to be investigated. In the current study, we assessed the effect of the BDNF polymorphism on the network properties and robustness of the graph-based white matter structural networks. Graph theory was employed to investigate the structural connectivity derived from white matter tractography in two groups, Val homozygotes (n = 18 and Met-allele carriers (n = 55. Although there were no differences in the global network measures including global efficiency, local efficiency, and modularity between the two genotype groups, we found the effect of the BDNF Val66Met polymorphism on the robustness properties of the white matter structural networks. Specifically, the white matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygote group. These findings suggest that the central role of the BDNF Val66Met polymorphism in regards to neuroplasticity may be associated with inherent differences in the robustness of the white matter structural network according to the genetic variants. Furthermore, greater susceptibility to brain disorders in Met-allele carriers may be understood as being due to their limited stability in white matter structural connectivity.

  17. Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived melanocyte development.

    Science.gov (United States)

    Kos, L; Aronzon, A; Takayama, H; Maina, F; Ponzetto, C; Merlino, G; Pavan, W

    1999-02-01

    The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met-/-) were analysed. In Met-/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro.

  18. Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice

    OpenAIRE

    Martinić, Roko; Šošić, Hrvoje; Turčić, Petra; Konjevoda, Paško; Fučić, Aleksandra; Stojković, Ranko; Aralica, Gorana; Gabričević, Mario; Weitner, Tin; Štambuk, Nikola

    2014-01-01

    Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.5 mg/kg, which corresponds to the protective dose reported for se...

  19. Structural Basis for Selective Small Molecule Kinase Inhibition of Activated c-Met

    Energy Technology Data Exchange (ETDEWEB)

    Rickert, Keith W.; Patel, Sangita B.; Allison, Timothy J.; Byrne, Noel J.; Darke, Paul L.; Ford, Rachael E.; Guerin, David J.; Hall, Dawn L.; Kornienko, Maria; Lu, Jun; Munshi, Sanjeev K.; Reid, John C.; Shipman, Jennifer M.; Stanton, Elizabeth F.; Wilson, Kevin J.; Young, Jonathon R.; Soisson, Stephen M.; Lumb, Kevin J. (Merck)

    2012-03-15

    The receptor tyrosine kinase c-Met is implicated in oncogenesis and is the target for several small molecule and biologic agents in clinical trials for the treatment of cancer. Binding of the hepatocyte growth factor to the cell surface receptor of c-Met induces activation via autophosphorylation of the kinase domain. Here we describe the structural basis of c-Met activation upon autophosphorylation and the selective small molecule inhibiton of autophosphorylated c-Met. MK-2461 is a potent c-Met inhibitor that is selective for the phosphorylated state of the enzyme. Compound 1 is an MK-2461 analog with a 20-fold enthalpy-driven preference for the autophosphorylated over unphosphorylated c-Met kinase domain. The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix {alpha}C and the G loop to generate a viable active site. Helix {alpha}C adopts a orientation different from that seen in activation loop mutants. The crystal structure of the complex formed by the autophosphorylated c-Met kinase domain and compound 1 reveals a significant induced fit conformational change of the G loop and ordering of the activation loop, explaining the selectivity of compound 1 for the autophosphorylated state. The results highlight the role of structural plasticity within the kinase domain in imparting the specificity of ligand binding and provide the framework for structure-guided design of activated c-Met inhibitors.

  20. Activated HGF-c-Met Axis in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Levi Arnold

    2017-12-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is a highly morbid disease. Recent developments including Food and Drug Administration (FDA approved molecular targeted agent’s pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal–epithelial transition factor (c-Met and its ligand hepatocyte growth factor (HGF are overexpressed in head and neck squamous cell carcinoma (HNSCC; and regulates tumor progression and response to therapy. The c-Met pathway has been shown to regulate many cellular processes such as cell proliferation, invasion, and angiogenesis. The c-Met pathway is involved in cross-talk, activation, and perpetuation of other signaling pathways, curbing the cogency of a blockade molecule on a single pathway. The receptor and its ligand act on several downstream effectors including phospholipase C gamma (PLCγ, cellular Src kinase (c-Src, phosphotidylinsitol-3-OH kinase (PI3K alpha serine/threonine-protein kinase (Akt, mitogen activate protein kinase (MAPK, and wingless-related integration site (Wnt pathways. They are also known to cross-talk with other receptors; namely epidermal growth factor receptor (EGFR and vascular endothelial growth factor receptor (VEGFR and specifically contribute to treatment resistance. Clinical trials targeting the c-Met axis in HNSCC have been undertaken because of significant preclinical work demonstrating a relationship between HGF/c-Met signaling and cancer cell survival. Here we focus on HGF/c-Met impact on cellular signaling in HNSCC to potentiate tumor growth and disrupt therapeutic efficacy. Herein we summarize the current understanding of HGF/c-Met signaling and its effects on HNSCC. The intertwining of c-Met signaling with other signaling pathways provides opportunities for more robust and specific therapies, leading to better clinical outcomes.

  1. PS O kke Jager : Interview met de Tijdgeest, JH Kok, NV, Kampen ...

    African Journals Online (AJOL)

    Test

    humor. Hy is nie suinig met die kritiek nie. Wie dit wil ervaar moet “ Een reis langs de Kerken” maar eens lees. Die skrywer sê dat hy „zo nog wel een tijd zou kunnen doorgaan. Maar het is beter dat wij eindigen.” Gelukkig is sy Interview met de Tijdgeest na die hoofstuk nog nie beeïndig nie. Alle fasette van die lewe — nie ...

  2. DrugMetZ DB: an anthology of human drug metabolizing Chytochrome P450 enzymes.

    Science.gov (United States)

    Antony, Tresa Remya Thomas; Nagarajan, Shanthi

    2006-11-14

    Understandings the basics of Cytochrome P450 (P450 or CYP) will help to discern drug metabolism. CYP, a super-family of heme-thiolate proteins, are found in almost all living organisms and is involved in the biotransformation of a diverse range of xenobiotics, therapeutic drugs and toxins. Here, we describe DrugMetZ DB, a database for CYP metabolizing drugs. The DB is implemented in MySQL, PHP and HTML. www.bicpu.edu.in/DrugMetZDB/

  3. General relativity

    International Nuclear Information System (INIS)

    Kenyon, I.R.

    1990-01-01

    General relativity is discussed in this book at a level appropriate to undergraduate students of physics and astronomy. It describes concepts and experimental results, and provides a succinct account of the formalism. A brief review of special relativity is followed by a discussion of the equivalence principle and its implications. Other topics covered include the concepts of curvature and the Schwarzschild metric, test of the general theory, black holes and their properties, gravitational radiation and methods for its detection, the impact of general relativity on cosmology, and the continuing search for a quantum theory of gravity. (author)

  4. Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a

    OpenAIRE

    Schiering, Nikolaus; Knapp, Stefan; Marconi, Marina; Flocco, Maria M.; Cui, Jean; Perego, Rita; Rusconi, Luisa; Cristiani, Cinzia

    2003-01-01

    The protooncogene c-met codes for the hepatocyte growth factor receptor tyrosine kinase. Binding of its ligand, hepatocyte growth factor/scatter factor, stimulates receptor autophosphorylation, which leads to pleiotropic downstream signaling events in epithelial cells, including cell growth, motility, and invasion. These events are mediated by interaction of cytoplasmic effectors, generally through Src homology 2 (SH2) domains, with two phosphotyrosine-containing sequence motifs in the unique...

  5. Induction of epigenetic variation in Arabidopsis by over-expression of DNA METHYLTRANSFERASE1 (MET1.

    Directory of Open Access Journals (Sweden)

    Samuel Brocklehurst

    Full Text Available Epigenetic marks such as DNA methylation and histone modification can vary among plant accessions creating epi-alleles with different levels of expression competence. Mutations in epigenetic pathway functions are powerful tools to induce epigenetic variation. As an alternative approach, we investigated the potential of over-expressing an epigenetic function, using DNA METHYLTRANSFERASE1 (MET1 for proof-of-concept. In Arabidopsis thaliana, MET1 controls maintenance of cytosine methylation at symmetrical CG positions. At some loci, which contain dense DNA methylation in CG- and non-CG context, loss of MET1 causes joint loss of all cytosines methylation marks. We find that over-expression of both catalytically active and inactive versions of MET1 stochastically generates new epi-alleles at loci encoding transposable elements, non-coding RNAs and proteins, which results for most loci in an increase in expression. Individual transformants share some common phenotypes and genes with altered gene expression. Altered expression states can be transmitted to the next generation, which does not require the continuous presence of the MET1 transgene. Long-term stability and epigenetic features differ for individual loci. Our data show that over-expression of MET1, and potentially of other genes encoding epigenetic factors, offers an alternative strategy to identify epigenetic target genes and to create novel epi-alleles.

  6. Regulation of HGF and c-MET Interaction in Normal Ovary and Ovarian Cancer.

    Science.gov (United States)

    Kwon, Youngjoo; Godwin, Andrew K

    2017-04-01

    Binding of hepatocyte growth factor (HGF) to the c-MET receptor has mitogenic, motogenic, and morphogenic effects on cells. The versatile biological effects of HGF and c-MET interactions make them important contributors to the development of malignant tumors. We and others have demonstrated a therapeutic value in targeting the interaction of c-MET and HGF in epithelial ovarian cancer (EOC). However, both HGF and c-MET are expressed in the normal ovary as well. Therefore, it is important to understand the differences in mechanisms that control HGF signaling activation and its functional role in the normal ovary and EOC. In the normal ovary, HGF signaling may be under hormonal regulation. During ovulation, HGF-converting proteases are secreted and the subsequent activation of HGF signaling enhances the proliferation of ovarian surface epithelium in order to replenish the area damaged due to expulsion of the ovum. In contrast, EOC cells that exhibit epithelial characteristics constitutively express both c-MET and HGF-converting proteases such as urokinase-type plasminogen activator. In EOC, mechanisms to control the activation of HGF signaling are absent since HGF is provided locally from the tissue microenvironment as well as remotely throughout the body. Potential incessant HGF signaling in EOC may lead to an increase in proliferation, invasion through the stroma, and migration to other tissues of cancer cells. Therefore, targeting the interaction of c-MET and HGF would be beneficial in treating EOC.

  7. Metáforas metalinguísticas de Euclides da Cunha

    Directory of Open Access Journals (Sweden)

    Carlos Antônio Magalhães Guedelha

    2016-03-01

    Full Text Available Este artigo apresenta uma leitura das metáforas metalinguísticas do escritor Euclides da Cunha, ou seja, as metáforas que ele utilizou para se referir aos seus dois principais livros, Os Sertões (sobre a guerra de Canudos e Um paraíso perdido (sobre a Amazônia. O conceito de metalinguagem estabelecido por Jakobson foi fundamental para a pesquisa, que teve como suporte teórico básico o postulado da metáfora conceptual, proposta por Lakoff e Johnson. As metáforas analisados neste artigo (VINGAR-SE É ESCREVER e UM LIVRO É UM FILHO foram colhidas de ensaios do escritor e de cartas que ele escreveu a amigos e familiares, “escriturando” a sua escrita por meio da metalinguagem. A análise das metáforas assume, com base em Lakoff e Johnson, que a metáfora não é uma questão apenas de linguagem. Ela é também – e fundamentalmente – uma questão de pensamento e ação.

  8. Association of ghrelin Leu72Met polymorphism with type 2 diabetes mellitus in Chinese population.

    Science.gov (United States)

    Liu, Jing; Liu, Jia; Tian, Li-min; Liu, Ju-xiang; Bing, Ya-jun; Zhang, Ji-ping; Wang, Yun-Fang; Zhang, Lu-yan

    2012-08-10

    Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to implicate the development of the type 2 diabetes mellitus (T2DM). The Leu72Met (+408C>A) polymorphism of the preproghrelin, has been linked to obesity, insulin resistance and diabetes. To investigate the distribution of ghrelin gene Leu72Met polymorphism and its association with the type 2 diabetes mellitus in Chinese population. We conducted a case-control study on 877 patients with T2DM and 864 controls, which were genotyped by the polymerase chain reaction (PCR) technique, denaturing high performance liquid chromatography (DHPLC) and DNA sequence analysis. Laboratory analyses were carried out in the hospital laboratory. No significant difference in the Leu72Met genotype distributions and allele frequency was observed between type 2 diabetes mellitus and controls (both P>0.05). The polymorphism was not associated with T2DM. However, among the T2DM group, the patients carrying Leu72Leu genotype had significantly increased levels of FPG and serum creatinine compared with variant genotypes (Leu72Met and Met72Met) (Ppolymorphism of the preproghrelin gene was not associated with T2DM in Chinese population. However, it may have some roles in the etiology of insulin resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. BDNF Val66Met Polymorphism Influences Visuomotor Associative Learning and the Sensitivity to Action Observation

    Science.gov (United States)

    Taschereau-Dumouchel, Vincent; Hétu, Sébastien; Michon, Pierre-Emmanuel; Vachon-Presseau, Etienne; Massicotte, Elsa; De Beaumont, Louis; Fecteau, Shirley; Poirier, Judes; Mercier, Catherine; Chagnon, Yvon C.; Jackson, Philip L.

    2016-01-01

    Motor representations in the human mirror neuron system are tuned to respond to specific observed actions. This ability is widely believed to be influenced by genetic factors, but no study has reported a genetic variant affecting this system so far. One possibility is that genetic variants might interact with visuomotor associative learning to configure the system to respond to novel observed actions. In this perspective, we conducted a candidate gene study on the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, a genetic variant linked to motor learning in regions of the mirror neuron system, and tested the effect of this polymorphism on motor facilitation and visuomotor associative learning. In a single-pulse TMS study carried on 16 Met (Val/Met and Met/Met) and 16 Val/Val participants selected from a large pool of healthy volunteers, Met participants showed significantly less muscle-specific corticospinal sensitivity during action observation, as well as reduced visuomotor associative learning, compared to Val homozygotes. These results are the first evidence of a genetic variant tuning sensitivity to action observation and bring to light the importance of considering the intricate relation between genetics and associative learning in order to further understand the origin and function of the human mirror neuron system. PMID:27703276

  10. Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

    Science.gov (United States)

    Perez-Rodriguez, M Mercedes; New, Antonia S; Goldstein, Kim E; Rosell, Daniel; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David; Siever, Larry J; Hazlett, Erin A

    2017-05-30

    A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype. Copyright © 2017. Published by Elsevier B.V.

  11. BDNFval66met affects neural activation pattern during fear conditioning and 24 h delayed fear recall.

    Science.gov (United States)

    Lonsdorf, Tina B; Golkar, Armita; Lindström, Kara M; Haaker, Jan; Öhman, Arne; Schalling, Martin; Ingvar, Martin

    2015-05-01

    Brain-derived neurotrophic factor (BDNF), the most abundant neutrophin in the mammalian central nervous system, is critically involved in synaptic plasticity. In both rodents and humans, BDNF has been implicated in hippocampus- and amygdala-dependent learning and memory and has more recently been linked to fear extinction processes. Fifty-nine healthy participants, genotyped for the functional BDNFval66met polymorphism, underwent a fear conditioning and 24h-delayed extinction protocol while skin conductance and blood oxygenation level dependent (BOLD) responses (functional magnetic resonance imaging) were acquired. We present the first report of neural activation pattern during fear acquisition 'and' extinction for the BDNFval66met polymorphism using a differential conditioned stimulus (CS)+ > CS- comparison. During conditioning, we observed heightened allele dose-dependent responses in the amygdala and reduced responses in the subgenual anterior cingulate cortex in BDNFval66met met-carriers. During early extinction, 24h later, we again observed heightened responses in several regions ascribed to the fear network in met-carriers as opposed to val-carriers (insula, amygdala, hippocampus), which likely reflects fear memory recall. No differences were observed during late extinction, which likely reflects learned extinction. Our data thus support previous associations of the BDNFval66met polymorphism with neural activation in the fear and extinction network, but speak against a specific association with fear extinction processes. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  12. The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.

    Science.gov (United States)

    İşcan, Evin; Güneş, Aysim; Korhan, Peyda; Yılmaz, Yeliz; Erdal, Esra; Atabey, Neşe

    2017-06-01

    The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)-induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c-Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c-Met receptor dimerization and activated c-Met signaling in an HGF independent manner. Heparin-induced c-Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c-Met signaling reversed heparin-induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c-Met signaling in HCC.

  13. General problems

    International Nuclear Information System (INIS)

    2005-01-01

    This article presents the general problems as natural disasters, consequences of global climate change, public health, the danger of criminal actions, the availability to information about problems of environment

  14. Generalized Recovery

    DEFF Research Database (Denmark)

    Jensen, Christian Skov; Lando, David; Pedersen, Lasse Heje

    We characterize when physical probabilities, marginal utilities, and the discount rate can be recovered from observed state prices for several future time periods. Our characterization makes no assumptions of the probability distribution, thus generalizing the time-homogeneous stationary model...

  15. General Conformity

    Science.gov (United States)

    The General Conformity requirements ensure that the actions taken by federal agencies in nonattainment and maintenance areas do not interfere with a state’s plans to meet national standards for air quality.

  16. Relationship between Metabolic Syndrome Components and Periodontal Disease in a Japanese General Population: the Suita Study.

    Science.gov (United States)

    Kikui, Miki; Kokubo, Yoshihiro; Ono, Takahiro; Kida, Momoyo; Kosaka, Takayuki; Yamamoto, Masaaki; Watanabe, Makoto; Maeda, Yoshinobu; Miyamoto, Yoshihiro

    2017-05-01

    A positive association between metabolic syndrome (MetS) and periodontal status has recently been noted. However, no study has evaluated the relationship by sex and in a general urban population using the uniform definition proposed in the 2009 Joint Interim Statement. The aim of this study was to clarify the relationship between MetS and periodontal status using the uniform definition in a general urban Japanese population. A total of 1,856 Japanese men and women (mean age: 66.4 years) were studied using data from the Suita study. Periodontal status was evaluated by the Community Periodontal Index (CPI). MetS was defined using the 2009 Joint Interim Statement. The associations of the MetS and its components with periodontal disease were investigated using multiple logistic regression analysis adjusting for age, drinking, and smoking. Among the components of the MetS, low HDL cholesterol level was significantly associated with periodontal disease in men and women [odds ratios (OR)=2.39 and 1.53; 95% confidence intervals=1.36-4.19 and 1.06-2.19]. Furthermore, the risk of periodontal disease showed 1.43-, 1.42-, and 1.89-fold increases in those with 2, 3, and ≥4 components, respectively, compared with those having no components (P trend <0.001). For the analysis by sex, the risk of periodontal disease was increased 2.27- and 1.76-fold in those with ≥4 components in men and women, respectively (both P trend =0.001). These findings suggest that MetS and lower HDL cholesterol are associated with periodontal disease. Subjects with two or more MetS components had a significantly higher prevalence of periodontal disease.

  17. 11C-MET PET/MRI for detection of recurrent glioma.

    Science.gov (United States)

    Deuschl, C; Kirchner, J; Poeppel, T D; Schaarschmidt, B; Kebir, S; El Hindy, N; Hense, J; Quick, H H; Glas, M; Herrmann, K; Umutlu, L; Moenninghoff, C; Radbruch, A; Forsting, M; Schlamann, M

    2018-04-01

    Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid 11 C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid 11 C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid 11 C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. Hybrid 11 C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for 11 C-MET PET (96.77% and 73.68%), and for hybrid 11 C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid 11 C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing 11 C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). This feasibility study showed that hybrid PET/MRI might strengthen

  18. {sup 11}C-MET PET/MRI for detection of recurrent glioma

    Energy Technology Data Exchange (ETDEWEB)

    Deuschl, C. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Kirchner, J.; Schaarschmidt, B. [University Duesseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Duesseldorf (Germany); Poeppel, T.D.; Herrmann, K. [University Hospital Essen, Clinic for Nuclear Medicine, Essen (Germany); Kebir, S.; Glas, M. [University Hospital Essen, Division of Clinical Neurooncology, Department of Neurology, Essen (Germany); El Hindy, N. [University Hospital Essen, Department of Neurosurgery, Essen (Germany); Hense, J. [University Hospital Essen, Department of Medical Oncology, West German Cancer Center, Essen (Germany); Quick, H.H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); Umutlu, L.; Moenninghoff, C.; Radbruch, A.; Forsting, M. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Schlamann, M. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Hospital Cologne, Department of Diagnostic and Interventional Radiology, Cologne (Germany)

    2018-04-15

    Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid {sup 11}C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid {sup 11}C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid {sup 11}C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. Hybrid {sup 11}C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for {sup 11}C-MET PET (96.77% and 73.68%), and for hybrid {sup 11}C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid {sup 11}C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing {sup 11}C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). This feasibility study showed that hybrid

  19. Generalized polygons

    CERN Document Server

    Van Maldeghem, Hendrik

    1998-01-01

    Generalized Polygons is the first book to cover, in a coherent manner, the theory of polygons from scratch. In particular, it fills elementary gaps in the literature and gives an up-to-date account of current research in this area, including most proofs, which are often unified and streamlined in comparison to the versions generally known. Generalized Polygons will be welcomed both by the student seeking an introduction to the subject as well as the researcher who will value the work as a reference. In particular, it will be of great value for specialists working in the field of generalized polygons (which are, incidentally, the rank 2 Tits-buildings) or in fields directly related to Tits-buildings, incidence geometry and finite geometry. The approach taken in the book is of geometric nature, but algebraic results are included and proven (in a geometric way!). A noteworthy feature is that the book unifies and generalizes notions, definitions and results that exist for quadrangles, hexagons, octagons - in the ...

  20. Variant BDNF Val66Met polymorphism affects extinction of conditioned aversive memory.

    Science.gov (United States)

    Yu, Hui; Wang, Yue; Pattwell, Siobhan; Jing, Deqiang; Liu, Ting; Zhang, Yun; Bath, Kevin G; Lee, Francis S; Chen, Zhe-Yu

    2009-04-01

    Brain-derived neurotrophic factor (BDNF) plays important roles in activity-dependent plasticity processes, such as long-term potentiation, learning, and memory. The recently reported human BDNF Val66Met (BDNF(Met)) polymorphism has been shown to lead to altered hippocampal volume and impaired hippocampal-dependent memory and is associated with a variety of neuropsychiatric disorders. There are few studies, however, that investigate the effect of the BDNF(Met) polymorphism on hippocampal-independent memory processes. A conditioned taste aversion (CTA) task was used for studying the mechanisms of long-term, hippocampal-independent, nondeclarative memory in the mammalian brain. Using the CTA paradigm, we found a novel impairment in extinction learning, but not acquisition or retention, of aversive memories resulting from the variant BDNF(Met). BDNF(Met) mice were slower to extinguish an aversive CTA memory compared with wild-type counterparts. Moreover, the BDNF(Met) was associated with smaller volume and decreased neuronal dendritic complexity in the ventromedial prefrontal cortex (vmPFC), which plays a significant role in extinction of CTA. Finally, this delay in extinction learning could be rescued pharmacologically with a cognitive enhancer, d-cycloserine (DCS). To our knowledge, this is the first evidence that the BDNF(Met) polymorphism contributes to abnormalities in memory extinction. This abnormality in extinction learning may be explained by alterations in neuronal morphology, as well as decreased neural activity in the vmPFC. Importantly, DCS was effective in rescuing this delay in extinction, suggesting that when coupled with behavior therapy, DCS may be an effective treatment option for anxiety disorders in humans with this genetic variant BDNF.

  1. No association of the BDNF val66met polymorphism with implicit associative vocabulary and motor learning.

    Directory of Open Access Journals (Sweden)

    Nils Freundlieb

    Full Text Available Brain-derived neurotrophic factor (BDNF has been suggested to play a major role in plasticity, neurogenesis and learning in the adult brain. The BDNF gene contains a common val66met polymorphism associated with decreased activity-dependent excretion of BDNF and a potential influence on behaviour, more specifically, on motor learning. The objective of this study was to determine the influence of the BDNF val66met polymorphism on short-term implicit associative learning and whether its influence is cognitive domain-specific (motor vs. language. A sample of 38 young healthy participants was genotyped, screened for background and neuropsychological differences, and tested with two associative implicit learning paradigms in two different cognitive domains, i.e., motor and vocabulary learning. Subjects performed the serial reaction time task (SRTT to determine implicit motor learning and a recently established associative vocabulary learning task (AVL for implicit learning of action and object words. To determine the influence of the BDNF polymorphism on domain-specific implicit learning, behavioural improvements in the two tasks were compared between val/val (n = 22 and met carriers (val/met: n = 15 and met/met: n = 1. There was no evidence for an impact of the BDNF val66met polymorphism on the behavioural outcome in implicit short-term learning paradigms in young healthy subjects. Whether this polymorphism plays a relevant role in long-term training paradigms or in subjects with impaired neuronal plasticity or reduced learning capacity, such as aged individuals, demented patients or patients with brain lesions, has to be determined in future studies.

  2. METs in adults while playing active video games: a metabolic chamber study.

    Science.gov (United States)

    Miyachi, Motohiko; Yamamoto, Kenta; Ohkawara, Kazunori; Tanaka, Shigeho

    2010-06-01

    Active video game systems controlled through arm gestures and motions (Nintendo Wii Sports) and video games controlled through force plate (Wii Fit Plus) are becoming increasingly popular. This study was performed to determine the energy expenditure (EE) during Wii Fit Plus and Wii Sports game activities. Twelve adult men and women performed all the activities of Wii Sports (five activities: golf, bowling, tennis, baseball, and boxing) and Wii Fit Plus (63 activities classified as yoga, resistance, balance, and aerobic exercises). Each activity was continued for at least 8 min to obtain a steady-state EE. Because EE was assessed in an open-circuit indirect metabolic chamber consisting of an airtight room (20,000 or 15,000 L), subjects were freed of apparatus to collect expired gas while playing the games. MET value was calculated from resting EE and steady-state EE during activity. The mean MET values of all 68 activities were distributed over a wide range from 1.3 METs (Lotus Focus) to 5.6 METs (single-arm stand). The mean MET values in yoga, balance, resistance, and aerobic exercise of Wii Fit Plus and Wii Sports were 2.1, 2.0, 3.2, 3.4, and 3.0 METs, respectively. Forty-six activities (67%) were classified as light intensity (6.0 METs). Time spent playing one-third of the activities supplied by motion- and gesture-controlled video games can count toward the daily amount of exercise required according to the guidelines provided by the American College of Sports Medicine and the American Heart Association, which focus on 30 min of moderate-intensity daily physical activity 5 d x wk(-1).

  3. The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

    Directory of Open Access Journals (Sweden)

    Kaja K Jasińska

    Full Text Available Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265 is associated with children's (age 6-10 neural activation patterns during a reading task (n = 81 using functional magnetic resonance imaging (fMRI, genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

  4. The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

    Science.gov (United States)

    Jasińska, Kaja K; Molfese, Peter J; Kornilov, Sergey A; Mencl, W Einar; Frost, Stephen J; Lee, Maria; Pugh, Kenneth R; Grigorenko, Elena L; Landi, Nicole

    2016-01-01

    Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

  5. De werkzame bestanddelen van de hulpverlening aan gezinnen met meervoudige problematiek

    Directory of Open Access Journals (Sweden)

    Isolde Driesen

    2016-09-01

    assistance. They state that a good working relationship with the client plays a decisive role in a successful assistance process. The basic attitude of the social worker is essential for achieving a successful working relationship with the client. This basic attitude is characterized by involvement and transparency.The social workers state that the degree to which they take control of the client’s situation also plays a decisive role in the working relationship. According to them, the client is initially in control and this is most effective. But if the social worker assesses the living conditions of the client as seriously compromised, it can be more effective for the social worker to take control temporarily.In general, social workers devote considerable attention to promoting the motivation of parents in families with multiple issues. They consider this motivation to be one of the most important factors for successful assistance. The targeted use of interventions to promote this motivation is considered essential, with a distinction made between intrinsic and extrinsic motivation. In terms of taking control, if the social worker assesses that parents in families with multiple problems are sufficiently motivated, they can retain control of the situation. However, if there is little intrinsic motivation and living conditions are seriously compromised, it is more effective for the social worker to take control temporarily in order to (first and foremost promote extrinsic motivation.Social workers state that targeted assistance to parents in families with multiple problems must include all facets of life. They do not believe that problems can be resolved through a fragmented approach. An integrated approach is needed to be able to provide effective support. According to the social workers, the financial problems should be assigned the highest priority. It is important that the financial situation is first stabilized as much as possible before dealing with problems in other

  6. General conclusions

    International Nuclear Information System (INIS)

    Tubiana, M.

    1993-01-01

    In conclusion, a general consensus of a number of points which the author endeavours to summarize in this article: -doctors are an excellent channel for passing on information to the public -doctors feel that they do not know enough about the subject and a training on radiobiology and radiation protection is a necessity for them -communication between doctors and the general public is poor in this field -research should be encouraged in numerous areas such as: carcinogenic effect of low doses of radiation, pedagogy and risk perception

  7. Extreme Partnership in Afghanistan: Arghandab District, Kandahar Province, 2010-2011

    Science.gov (United States)

    2012-04-01

    pomegranate orchards typical of the Arghandab. They were in the midst of the population they were there to protect, but had no Afghan partners. Their...system for the Kandak mullah to announce the call to prayer five times a day. The local population and many farmers in the area could hear the mosque...know the villagers and farmers of Arghandab as well as the fields the farmers owned, the houses where they lived, how many children they had, and

  8. Voor elk-ander. Ervaringsdeskundigen met een lichte verstandelijke beperking en coaches over betekenisvolle samenwerking

    Directory of Open Access Journals (Sweden)

    Maaike Hermsen

    2017-06-01

    Full Text Available For each other. Experience experts with a mild intellectual disability and coaches on meaningful cooperation Collaboration with experience experts, particularly in mental healthcare, has flourished in recent years. The positive results of cooperating with experience experts in mental healthcare have led to more initiatives in other healthcare sectors too, such as in care for people with intellectual disabilities. Daily cooperation with experience experts with intellectual disabilities requires structural support, however, which is often provided by coaches in the workplace. This qualitative study aims to answer the question which knowledge, skills and attitudes are needed by coaches in order to support experience experts with intellectual disabilities. In addition, we look at what makes the cooperation with experience experts with an intellectual disability a meaningful process for all those involved. To answer these questions, individual interviews with experience experts with an intellectual disability and with coaches were conducted, as well as group interviews with teachers and researchers working with experience experts in practice. Current coaching guidelines emphasize responsibility, self-control and reflection on the part of the person being coached. However, this research shows that these basic principles are not sufficient for the specific nature of coaching experience experts with a mild intellectual disability. Voor elk-ander. Ervaringsdeskundigen met een lichte verstandelijke beperking en coaches over betekenisvolle samenwerkingSamenwerken met ervaringsdeskundigen neemt de laatste jaren, met name in de GGZ, een hoge vlucht. De positieve resultaten van de samenwerking met ervaringsdeskundigen in de GGZ hebben ertoe geleid dat er meer initiatieven komen in andere zorgsectoren, zo ook in de zorg aan mensen met een verstandelijke beperking. Samenwerking met ervaringsdeskundigen met een verstandelijke beperking vraagt in de dagelijkse

  9. Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-08-01

    Full Text Available Yuanyuan Zhao,1,* Jing Zhang,2,* Ying Tian,1,* Cong Xue,1 Zhihuang Hu,1 Li Zhang1,3 1Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, the First Affiliated Hospital of Guang Zhou Traditional Chinese Medicine University, 3National Anti-Cancer Drug Research Centre, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this work Purpose: We explored the effect of hepatocyte growth factor (HGF/Met signaling pathway on nasopharyngeal carcinoma (NPC cells in vitro and in vivo, and investigated the ability of Met tyrosine kinase inhibitor (TKI to block HGF-induced biological signaling.Experimental design: Met TKI inhibitor PF-2341066 alone, or in combination with cisplatin, was investigated for its ability to block HGF-induced signaling and biological effects in vitro and in vivo. HGF/Met expression and activation of signaling in NPC cells were detected by using Western blot and immunohistochemistry. Biological evaluation, including wound healing, cell proliferation, and invasion of NPC cells, was also examined, and the correlation between HGF/Met expression of primary and metastatic tumor in NPC patients and clinical prognosis were also analyzed.Results: Met TKI inhibitor, PF-2341066, inhibited growth of NPC cells in vivo with half maximal inhibitory concentration of 0.79±0.21 µmol/L, and suppressed invasion and migration of NPC cells; also, the inhibition of PF-2341066 was synergized with cisplatin treatment. Compared with the control group, Met TKI inhibited metastasis of transplanted NPC in nude mice (the number of live metastases [mean ± SD]: 5.8±2.2 versus 11.8±2.2, P=0.03; the number of lung metastases: 2.3±1.5 versus

  10. GENERAL Iarticle

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 2. Supersymmetry. Akshay Kulkarni P Ramadevi. General Article Volume 8 Issue 2 February 2003 pp 28-41 ... Author Affiliations. Akshay Kulkarni1 P Ramadevi1. Physics Department, Indian Institute of Technology, Mumbai 400 076, India.

  11. General indicators

    International Nuclear Information System (INIS)

    2003-01-01

    This document summarizes the main 2002 energy indicators for France. A first table lists the evolution of general indicators between 1973 and 2002: energy bill, price of imported crude oil, energy independence, primary and final energy consumption. The main 2002 results are detailed separately for natural gas, petroleum and coal (consumption, imports, exports, production, stocks, prices). (J.S.)

  12. Generalized Recovery

    DEFF Research Database (Denmark)

    Jensen, Christian Skov; Lando, David; Pedersen, Lasse Heje

    We characterize when physical probabilities, marginal utilities, and the discount rate can be recovered from observed state prices for several future time periods. We make no assumptions of the probability distribution, thus generalizing the time-homogeneous stationary model of Ross (2015). Recov...

  13. GENERAL SURGERY

    African Journals Online (AJOL)

    Department of Surgery, University of Cape Town Health Sciences Faculty, Groote Schuur Hospital, Observatory, Cape Town,. South Africa ... included all district, regional and tertiary hospitals in the nine provinces. Clinics and so-called ..... large contingency of senior general surgeons from countries such as Cuba, who have ...

  14. GENERAL SURGERY

    African Journals Online (AJOL)

    effect of fatigue on patient safety, and owing to increasing emphasis on lifestyle issues .... increasing emphasis on an appropriate work-life balance in professional life.10 ... experience, were the most negative about the EWTD in general.3,13 ...

  15. GENERAL SURGERY

    African Journals Online (AJOL)

    in the endoscopy room. GENERAL SURGERY. T du Toit, O C Buchel, S J A Smit. Department of Surgery, University of the Free State, Bloemfontein, ... The lack of video instrumentation in developing countries: Redundant fibre-optic instruments (the old. “eye scope”) are still being used. This instrument brings endoscopists ...

  16. General Assembly

    CERN Multimedia

    Staff Association

    2016-01-01

    5th April, 2016 – Ordinary General Assembly of the Staff Association! In the first semester of each year, the Staff Association (SA) invites its members to attend and participate in the Ordinary General Assembly (OGA). This year the OGA will be held on Tuesday, April 5th 2016 from 11:00 to 12:00 in BE Auditorium, Meyrin (6-2-024). During the Ordinary General Assembly, the activity and financial reports of the SA are presented and submitted for approval to the members. This is the occasion to get a global view on the activities of the SA, its financial management, and an opportunity to express one’s opinion, including taking part in the votes. Other points are listed on the agenda, as proposed by the Staff Council. Who can vote? Only “ordinary” members (MPE) of the SA can vote. Associated members (MPA) of the SA and/or affiliated pensioners have a right to vote on those topics that are of direct interest to them. Who can give his/her opinion? The Ordinary General Asse...

  17. GENERAL SURGERY

    African Journals Online (AJOL)

    could cripple the global economy. Greater attention ... Africa and 5.7 general surgeons per 100 000 in the US.12 One of the key ... 100 000 insured population working in the private sector, which is comparable with the United States (US).

  18. Necklaces: Generalizations

    Indian Academy of Sciences (India)

    IAS Admin

    . A q-ary necklace of length n is an equivalence class of q-coloured strings of length n under rota- tion. In this article, we study various generaliza- tions and derive analytical expressions to count the number of these generalized necklaces.

  19. Generalized Recovery

    DEFF Research Database (Denmark)

    Lando, David; Pedersen, Lasse Heje; Jensen, Christian Skov

    We characterize when physical probabilities, marginal utilities, and the discount rate can be recovered from observed state prices for several future time periods. We make no assumptions of the probability distribution, thus generalizing the time-homogeneous stationary model of Ross (2015...... our model empirically, testing the predictive power of the recovered expected return and other recovered statistics....

  20. General Relativity

    CERN Document Server

    Straumann, Norbert

    2013-01-01

    This book provides a completely revised and expanded version of the previous classic edition ‘General Relativity and Relativistic Astrophysics’. In Part I the foundations of general relativity are thoroughly developed, while Part II is devoted to tests of general relativity and many of its applications. Binary pulsars – our best laboratories for general relativity – are studied in considerable detail. An introduction to gravitational lensing theory is included as well, so as to make the current literature on the subject accessible to readers. Considerable attention is devoted to the study of compact objects, especially to black holes. This includes a detailed derivation of the Kerr solution, Israel’s proof of his uniqueness theorem, and a derivation of the basic laws of black hole physics. Part II ends with Witten’s proof of the positive energy theorem, which is presented in detail, together with the required tools on spin structures and spinor analysis. In Part III, all of the differential geomet...

  1. Preproghrelin Leu72Met polymorphism in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Ukkola, O; Kesäniemi, Y A

    2003-10-01

    The association between the Leu72Met polymorphism of the preproghrelin gene and diabetic complications was examined in patients with type 2 diabetes mellitus. A total of 258 patients with type 2 diabetes mellitus and 522 control subjects were screened. Genotypes were determined by polymerase chain reaction technique. The diagnosis of coronary heart disease was based on clinical and ECG criteria. Laboratory analyses were carried out in the hospital laboratory. No differences in the genotype distributions and allele frequencies of the preproghrelin Leu72Met polymorphism were found between type 2 diabetes mellitus patients and controls. The polymorphism was not associated with macro- or micro-angiopathy or hypertension. However, Leu72Met polymorphism was associated with serum creatinine (P = 0.006) and lipoprotein(a) [Lp(a)] levels (P = 0.006) with Leu72Leu subjects showing the highest values. This association was observed only amongst diabetic group. The Leu72Met polymorphism of the preproghrelin gene was not related to cardiovascular disease in type 2 diabetes mellitus patients. Leu72Met polymorphism was, however, associated with serum creatinine and Lp(a) levels in diabetic patients. The mechanism might be associated with a possible change in ghrelin product and its somatotropic effect.

  2. BDNF Val66Met polymorphism moderates the link between child maltreatment and reappraisal ability.

    Science.gov (United States)

    Miu, A C; Cărnuţă, M; Vulturar, R; Szekely-Copîndean, R D; Bîlc, M I; Chiş, A; Cioară, M; Fernandez, K C; Szentágotai-Tătar, A; Gross, J J

    2017-04-01

    Child maltreatment is associated with increased risk for virtually all common mental disorders, but it is not yet clear why. One possible mechanism is emotion regulation ability. The present study investigated for the first time the influence of a BDNF Val66Met genotype × child maltreatment interaction on emotion regulation, and compared differential susceptibility and diathesis-stress models. A sample of N = 254 healthy volunteers were genotyped for the BDNF Val66Met polymorphism and underwent an experimental assessment of reappraisal ability (i.e. the success of using reappraisal to downregulate negative affect). A self-report instrument previously validated against a clinical interview was used to investigate child maltreatment. There was a significant BDNF Val66Met genotype × child maltreatment interaction (B = -0.31, P maltreated participants, and the highest level of reappraisal ability in non-maltreated participants. By assessing alternative models, we found that the best fitting model was in line with strong differential susceptibility. As expected, reappraisal ability was negatively correlated with depressive symptoms. Therefore, the BDNF Val66Met polymorphism moderates the link between child maltreatment and emotion regulation ability. Future studies could investigate whether improving reappraisal in maltreated BDNF Met carriers results in reduced risk for mental disorders. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  3. MET network in PubMed: a text-mined network visualization and curation system.

    Science.gov (United States)

    Dai, Hong-Jie; Su, Chu-Hsien; Lai, Po-Ting; Huang, Ming-Siang; Jonnagaddala, Jitendra; Rose Jue, Toni; Rao, Shruti; Chou, Hui-Jou; Milacic, Marija; Singh, Onkar; Syed-Abdul, Shabbir; Hsu, Wen-Lian

    2016-01-01

    Metastasis is the dissemination of a cancer/tumor from one organ to another, and it is the most dangerous stage during cancer progression, causing more than 90% of cancer deaths. Improving the understanding of the complicated cellular mechanisms underlying metastasis requires investigations of the signaling pathways. To this end, we developed a METastasis (MET) network visualization and curation tool to assist metastasis researchers retrieve network information of interest while browsing through the large volume of studies in PubMed. MET can recognize relations among genes, cancers, tissues and organs of metastasis mentioned in the literature through text-mining techniques, and then produce a visualization of all mined relations in a metastasis network. To facilitate the curation process, MET is developed as a browser extension that allows curators to review and edit concepts and relations related to metastasis directly in PubMed. PubMed users can also view the metastatic networks integrated from the large collection of research papers directly through MET. For the BioCreative 2015 interactive track (IAT), a curation task was proposed to curate metastatic networks among PubMed abstracts. Six curators participated in the proposed task and a post-IAT task, curating 963 unique metastatic relations from 174 PubMed abstracts using MET.Database URL: http://btm.tmu.edu.tw/metastasisway. © The Author(s) 2016. Published by Oxford University Press.

  4. Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma.

    Science.gov (United States)

    Karagonlar, Zeynep F; Korhan, Peyda; Atabey, Neşe

    2015-11-01

    Preclinical Research Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference-mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c-Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. © 2015 Wiley Periodicals, Inc.

  5. Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction.

    Science.gov (United States)

    Anastasia, Agustin; Deinhardt, Katrin; Chao, Moses V; Will, Nathan E; Irmady, Krithi; Lee, Francis S; Hempstead, Barbara L; Bracken, Clay

    2013-01-01

    A common single-nucleotide polymorphism (SNP) in the human brain-derived neurotrophic factor (BDNF) gene results in a Val66Met substitution in the BDNF prodomain region. This SNP is associated with alterations in memory and with enhanced risk to develop depression and anxiety disorders in humans. Here we show that the isolated BDNF prodomain is detected in the hippocampus and that it can be secreted from neurons in an activity-dependent manner. Using nuclear magnetic resonance spectroscopy and circular dichroism, we find that the prodomain is intrinsically disordered, and the Val66Met substitution induces structural changes. Surprisingly, application of Met66 (but not Val66) BDNF prodomain induces acute growth cone retraction and a decrease in Rac activity in hippocampal neurons. Expression of p75(NTR) and differential engagement of the Met66 prodomain to the SorCS2 receptor are required for this effect. These results identify the Met66 prodomain as a new active ligand, which modulates neuronal morphology.

  6. The divergent impact of catechol-O-methyltransferase (COMT) Val158Met genetic polymorphisms on executive function in adolescents with discrete patterns of childhood adversity.

    Science.gov (United States)

    Zhang, Huihui; Li, Jie; Yang, Bei; Ji, Tao; Long, Zhouting; Xing, Qiquan; Shao, Di; Bai, Huayu; Sun, Jiwei; Cao, Fenglin

    2018-02-01

    Catechol-O-methyltransferase (COMT) Val 158 Met functional polymorphisms play a crucial role in the development of executive function (EF), but their effect may be moderated by environmental factors such as childhood adversity. The present study aimed at testing the divergent impact of the COMT Val 158 Met genotype on EF in non-clinical adolescents with discrete patterns of childhood adversity. A total of 341 participants completed the Childhood Trauma Questionnaire, the self-reported version of the Behavior Rating Inventory of Executive Function, and self-administered questionnaires on familial function. The participants' COMT Val 158 Met genotype was determined. Associations among the variables were explored using latent class analysis and general linear models. We found that Val/Val homozygotes showed significantly worse performance on behavioral shift, relative to Met allele carriers (F=5.921, p=0.015, Partial η 2 =0.018). Moreover, three typical patterns of childhood adversity, namely, low childhood adversity (23.5%), childhood neglect (59.8%), and high childhood adversity (16.7%), were found. Both childhood neglect and high childhood adversity had a negative impact on each aspect of EF and on global EF performance. Importantly, these results provided evidence for significant interaction effects, as adolescents with the Val/Val genotype showed inferior behavioral shift performance than Met carriers (F=6.647, p=0.010, Partial η 2 =0.020) in the presence of high childhood adversity. Furthermore, there were no differences between the genotypes for childhood neglect and low childhood adversity. Overall, this is the first study to show that an interaction between the COMT genotype and childhood adversity affects EF in non-clinical adolescents. These results suggest that the COMT genotype may operate as a susceptibility gene vulnerable to an adverse environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a.

    Science.gov (United States)

    Schiering, Nikolaus; Knapp, Stefan; Marconi, Marina; Flocco, Maria M; Cui, Jean; Perego, Rita; Rusconi, Luisa; Cristiani, Cinzia

    2003-10-28

    The protooncogene c-met codes for the hepatocyte growth factor receptor tyrosine kinase. Binding of its ligand, hepatocyte growth factor/scatter factor, stimulates receptor autophosphorylation, which leads to pleiotropic downstream signaling events in epithelial cells, including cell growth, motility, and invasion. These events are mediated by interaction of cytoplasmic effectors, generally through Src homology 2 (SH2) domains, with two phosphotyrosine-containing sequence motifs in the unique C-terminal tail of c-Met (supersite). There is a strong link between aberrant c-Met activity and oncogenesis, which makes this kinase an important cancer drug target. The furanosylated indolocarbazole K-252a belongs to a family of microbial alkaloids that also includes staurosporine. It was recently shown to be a potent inhibitor of c-Met. Here we report the crystal structures of an unphosphorylated c-Met kinase domain harboring a human cancer mutation and its complex with K-252a at 1.8-A resolution. The structure follows the well established architecture of protein kinases. It adopts a unique, inhibitory conformation of the activation loop, a catalytically noncompetent orientation of helix alphaC, and reveals the complete C-terminal docking site. The first SH2-binding motif (1349YVHV) adopts an extended conformation, whereas the second motif (1356YVNV), a binding site for Grb2-SH2, folds as a type II Beta-turn. The intermediate portion of the supersite (1353NATY) assumes a type I Beta-turn conformation as in an Shc-phosphotyrosine binding domain peptide complex. K-252a is bound in the adenosine pocket with an analogous binding mode to those observed in previously reported structures of protein kinases in complex with staurosporine.

  8. Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis.

    Science.gov (United States)

    Lee, Young Ho; Kim, Jae-Hoon; Song, Gwan Gyu

    2015-01-01

    The aim of this study was to explore whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with susceptibility to fibromyalgia and fibromyalgia impact questionnaire (FIQ) score in fibromyalgia patients. We conducted a meta-analysis of the associations of the COMT Val158Met polymorphism with fibromyalgia risk as well as FIQ score in fibromyalgia patients. A total of 993 fibromyalgia patients and 778 controls from 10 studies on the COMT Val158Met polymorphism and 538 fibromyalgia patients from 5 studies on the COMT Val158Met polymorphism and FIQ score were included in this meta-analysis. The meta-analysis revealed an association between fibromyalgia and the COMT Met/Met + Val/Met genotype in all study subjects (odds ratio (OR) 1.635, 95 % confidence interval (CI) 1.029-2.597, p = 0.037). However, stratification by ethnicity indicated no association between the Met/Met + Val/Met genotype and fibromyalgia in the European and Turkish populations (OR 1.202, 95 % CI 0.876-1.649, p = 0.255; OR 2.132, 95 % CI 0.764-5.949, p = 0.148, respectively). Analysis using other genetic models showed no association between the COMT Val158Met polymorphism and fibromyalgia. The meta-analysis also revealed that the FIQ score was significantly higher in individuals with the COMT Met/Met genotype than in those with the Val/Val genotype [weighted mean difference (WMD) = 14.39, 95 % CI 3.316-25.48, p = 0.011] and the Val/Met genotype (WMD = 5.108, 95 % CI 2.212-4.891, p = 0.021). This meta-analysis identified an association between fibromyalgia risk and the COMT Val158Met polymorphism as well as the FIQ score in fibromyalgia patients.

  9. The MET/AXL/FGFR Inhibitor S49076 Impairs Aurora B Activity and Improves the Antitumor Efficacy of Radiotherapy.

    Science.gov (United States)

    Clémenson, Céline; Chargari, Cyrus; Liu, Winchygn; Mondini, Michele; Ferté, Charles; Burbridge, Mike F; Cattan, Valérie; Jacquet-Bescond, Anne; Deutsch, Eric

    2017-10-01

    Several therapeutic agents targeting HGF/MET signaling are under clinical development as single agents or in combination, notably with anti-EGFR therapies in non-small cell lung cancer (NSCLC). However, despite increasing data supporting a link between MET, irradiation, and cancer progression, no data regarding the combination of MET-targeting agents and radiotherapy are available from the clinic. S49076 is an oral ATP-competitive inhibitor of MET, AXL, and FGFR1-3 receptors that is currently in phase I/II clinical trials in combination with gefitinib in NSCLC patients whose tumors show resistance to EGFR inhibitors. Here, we studied the impact of S49076 on MET signaling, cell proliferation, and clonogenic survival in MET-dependent (GTL16 and U87-MG) and MET-independent (H441, H460, and A549) cells. Our data show that S49076 exerts its cytotoxic activity at low doses on MET-dependent cells through MET inhibition, whereas it inhibits growth of MET-independent cells at higher but clinically relevant doses by targeting Aurora B. Furthermore, we found that S49076 improves the antitumor efficacy of radiotherapy in both MET-dependent and MET-independent cell lines in vitro and in subcutaneous and orthotopic tumor models in vivo In conclusion, our study demonstrates that S49076 has dual antitumor activity and can be used in combination with radiotherapy for the treatment of both MET-dependent and MET-independent tumors. These results support the evaluation of combined treatment of S49076 with radiation in clinical trials without patient selection based on the tumor MET dependency status. Mol Cancer Ther; 16(10); 2107-19. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. Global Distributions of Temperature Variances At Different Stratospheric Altitudes From Gps/met Data

    Science.gov (United States)

    Gavrilov, N. M.; Karpova, N. V.; Jacobi, Ch.

    The GPS/MET measurements at altitudes 5 - 35 km are used to obtain global distribu- tions of small-scale temperature variances at different stratospheric altitudes. Individ- ual temperature profiles are smoothed using second order polynomial approximations in 5 - 7 km thick layers centered at 10, 20 and 30 km. Temperature inclinations from the averaged values and their variances obtained for each profile are averaged for each month of year during the GPS/MET experiment. Global distributions of temperature variances have inhomogeneous structure. Locations and latitude distributions of the maxima and minima of the variances depend on altitudes and season. One of the rea- sons for the small-scale temperature perturbations in the stratosphere could be internal gravity waves (IGWs). Some assumptions are made about peculiarities of IGW gener- ation and propagation in the tropo-stratosphere based on the results of GPS/MET data analysis.

  11. Data driven polypharmacological drug design for lung cancer: analyses for targeting ALK, MET, and EGFR

    DEFF Research Database (Denmark)

    Narayanan, Dilip; Gani, Osman ABSM; Gruber, Franz XE

    2017-01-01

    encoded into molecular mechanics force fields. Cheminformatics analyses of binding data show EGFR to be dissimilar to ALK and MET, but its structure shows how it may be co-targeted with the addition of a covalent trap. This suggests a strategy for the design of a focussed chemical library based on a pan......Drug design of protein kinase inhibitors is now greatly enabled by thousands of publicly available X-ray structures, extensive ligand binding data, and optimized scaffolds coming off patent. The extensive data begin to enable design against a spectrum of targets (polypharmacology); however...... consider polypharmacological targeting of protein kinases ALK, MET, and EGFR (and its drug resistant mutant T790M) in non small cell lung cancer as an example. Both EGFR and ALK represent sources of primary oncogenic lesions, while drug resistance arises from MET amplification and EGFR mutation. A drug...

  12. Cooling concept with energy storage for ICT; Koelconcept met energieopslag voor ICT

    Energy Technology Data Exchange (ETDEWEB)

    Van der Wilt, P. [Compertius, Amsterdam (Netherlands)

    2009-12-15

    Renewable energy concepts with energy storage in the soil are not only about technique. To ensure successful implementation of energy storage in the soil for various branches cooperation needs to be sought with parties who know specific branches very well. In addition to the technical aspects, it is at least as important that the needs and working methods of a market segment are thoroughly known to ensure optimal linkage of source systems to the systems and operational processes of the client. [Dutch] Bij ontwikkelde duurzame energieconcepten met inzet van energieopslag in de bodem gaat het niet alleen om techniek, Om energieopslag in de bodem voor verschillende branches met succes in te zetten, is samenwerking nodig met partijen die een specifieke branche goed kennen. Naast de techniek is het minstens zo belangrijk ook de behoeftes en werkwijzen van een marktsegment door en door te kennen, om bronsystemen zo optimaal te koppelen aan de systemen en bedrijfsprocessen van de klant.

  13. CoMET: A Mesquite package for comparing models of continuous character evolution on phylogenies

    Directory of Open Access Journals (Sweden)

    Chunghau Lee

    2006-01-01

    Full Text Available Continuously varying traits such as body size or gene expression level evolve during the history of species or gene lineages. To test hypotheses about the evolution of such traits, the maximum likelihood (ML method is often used. Here we introduce CoMET (Continuous-character Model Evaluation and Testing, which is module for Mesquite that automates likelihood computations for nine different models of trait evolution. Due to its few restrictions on input data, CoMET is applicable to testing a wide range of character evolution hypotheses. The CoMET homepage, which links to freely available software and more detailed usage instructions, is located at http://www.lifesci.ucsb.edu/eemb/labs/oakley/software/comet.htm.

  14. Generalizing entanglement

    Science.gov (United States)

    Jia, Ding

    2017-12-01

    The expected indefinite causal structure in quantum gravity poses a challenge to the notion of entanglement: If two parties are in an indefinite causal relation of being causally connected and not, can they still be entangled? If so, how does one measure the amount of entanglement? We propose to generalize the notions of entanglement and entanglement measure to address these questions. Importantly, the generalization opens the path to study quantum entanglement of states, channels, networks, and processes with definite or indefinite causal structure in a unified fashion, e.g., we show that the entanglement distillation capacity of a state, the quantum communication capacity of a channel, and the entanglement generation capacity of a network or a process are different manifestations of one and the same entanglement measure.

  15. General topology

    CERN Document Server

    Willard, Stephen

    2004-01-01

    Among the best available reference introductions to general topology, this volume is appropriate for advanced undergraduate and beginning graduate students. Its treatment encompasses two broad areas of topology: ""continuous topology,"" represented by sections on convergence, compactness, metrization and complete metric spaces, uniform spaces, and function spaces; and ""geometric topology,"" covered by nine sections on connectivity properties, topological characterization theorems, and homotopy theory. Many standard spaces are introduced in the related problems that accompany each section (340

  16. Transmission of epi-alleles with MET1-dependent dense methylation in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Michael Watson

    Full Text Available DNA methylation in plants targets cytosines in three sequence contexts, CG, CHG and CHH (H representing A, C or T. Each of these patterns has traditionally been associated with distinct DNA methylation pathways with CHH methylation being controlled by the RNA dependent DNA methylation (RdDM pathway employing small RNAs as a guide for the de novo DOMAINS REARRANGED METHYLTRANSFERASE (DRM2, and maintenance DNA METHYLTRANSFERASE1 (MET1 being responsible for faithful propagation of CG methylation. Here we report an unusual 'dense methylation' pattern under the control of MET1, with methylation in all three sequence contexts. We identified epi-alleles of dense methylation at a non coding RNA locus (At4g15242 in Arabidopsis ecotypes, with distinct dense methylation and expression characteristics, which are stably maintained and transmitted in genetic crosses and which can be heritably altered by depletion of MET1. This suggests that, in addition to its classical CG maintenance function, at certain loci MET1 plays a role in creating transcriptional diversity based on the generation of independent epi-alleles. Database inspection identified several other loci with MET1-dependent dense methylation patterns. Arabidopsis ecotypes contain distinct epi-alleles of these loci with expression patterns that inversely correlate with methylation density, predominantly within the transcribed region. In Arabidopsis, dense methylation appears to be an exception as it is only found at a small number of loci. Its presence does, however, highlight the potential for MET1 as a contributor to epigenetic diversity, and it will be interesting to investigate the representation of dense methylation in other plant species.

  17. BDNF val66met polymorphism affects aging of multiple types of memory.

    Science.gov (United States)

    Kennedy, Kristen M; Reese, Elizabeth D; Horn, Marci M; Sizemore, April N; Unni, Asha K; Meerbrey, Michael E; Kalich, Allan G; Rodrigue, Karen M

    2015-07-01

    The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age×BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (pmemory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory - in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). This article is part of a Special Issue entitled Memory & Aging. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses.

    Science.gov (United States)

    Aas, Monica; Haukvik, Unn K; Djurovic, Srdjan; Bergmann, Ørjan; Athanasiu, Lavinia; Tesli, Martin S; Hellvin, Tone; Steen, Nils Eiel; Agartz, Ingrid; Lorentzen, Steinar; Sundet, Kjetil; Andreassen, Ole A; Melle, Ingrid

    2013-10-01

    Brain derived neurotrophic factor (BDNF) is important for brain development and plasticity, and here we tested if the functional BDNF val66met variant modulates the association between high levels of childhood abuse, cognitive function, and brain abnormalities in psychoses. 249 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited to the TOP research study (mean±age: 30.7±10.9; gender: 49% males). History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Cognitive function was assessed through a standardized neuropsychological test battery. BDNF val66met was genotyped using standardized procedures. A sub-sample of n=106 Caucasians with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder (mean±age: 32.67±10.85; 49% males) had data on sMRI. Carriers of the Methionine (met) allele exposed to high level of childhood abuse demonstrated significantly poorer cognitive functioning compared to homozygotic Valine (val/val) carriers. Taking in consideration multiple testing, using a more conservative p value, this was still shown for physical abuse and emotional abuse, as well as a trend level for sexual abuse. Further, met carriers exposed to high level of childhood sexual abuse showed reduced right hippocampal volume (r(2)=0.43; p=0.008), and larger right and left lateral ventricles (r(2)=0.37; p=0.002, and r(2)=0.27; p=0.009, respectively). Our findings were independent of age, gender, diagnosis and intracranial volume. Our data demonstrate that in patients with psychoses, met carriers of the BDNF val66met with high level of childhood abuse have more cognitive and brain abnormalities than all other groups. © 2013.

  19. Anomalous inhibition of c-Met by the kinesin inhibitor aurintricarboxylic acid.

    Science.gov (United States)

    Milanovic, Mina; Radtke, Simone; Peel, Nick; Howell, Michael; Carrière, Virginie; Joffre, Carine; Kermorgant, Stéphanie; Parker, Peter J

    2012-03-01

    c-Met [the hepatocyte growth factor (HGF) receptor] is a receptor tyrosine kinase playing a role in various biological events. Overexpression of the receptor has been observed in a number of cancers, correlating with increased metastatic tendency and poor prognosis. Additionally, activating mutations in c-Met kinase domain have been reported in a subset of familial cancers causing resistance to treatment. Receptor trafficking, relying on the integrity of the microtubule network, plays an important role in activation of downstream targets and initiation of signalling events. Aurintricarboxylic acid (ATA) is a triphenylmethane derivative that has been reported to inhibit microtubule motor proteins kinesins. Additional reported properties of this inhibitor include inhibition of protein tyrosine phosphatases, nucleases and members of the Jak family. Here we demonstrate that ATA prevents HGF-induced c-Met phosphorylation, internalisation, subsequent receptor trafficking and degradation. In addition, ATA prevented HGF-induced downstream signalling which also affected cellular function, as assayed by collective cell migration of A549 cells. Surprisingly, the inhibitory effect of ATA on HGF-induced phosphorylation and signalling in vivo was associated with an increase in basal c-Met kinase activity in vitro. It is concluded that the inhibitory effects of ATA on c-Met in vivo is an allosteric effect mediated through the kinase domain of the receptor. As the currently tested adenosine triphosphate competitive tyrosine kinase inhibitors (TKIs) may lead to tumor resistance (McDermott U, et al., Cancer Res 2010;70:1625-34), our findings suggest that novel anti-c-Met therapies could be developed in the future for cancer treatment. Copyright © 2011 UICC.

  20. Association study between COMT 158Met and creativity scores in bipolar disorder and healthy controls

    Directory of Open Access Journals (Sweden)

    Márcio Gerhardt Soeiro-de-Souza

    2014-03-01

    Full Text Available Background Bipolar disorder (BD patients have been reported to be associated higher creativity abilities, and recent data tend to support the hypothesis that dopaminergic system that could be associated with creativity. Catechol-O-methyltransferase (COMT is one of the major enzymes involved in the metabolic degradation of dopamine. The COMT gene polymorphism (rs4680 or Val158Met Met allele is reported to cause decreased activity of this enzyme in prefrontal cortex and improve performance in several cognitive domains. Objective The objective of this study was to evaluate the influence of Val158Met on creativity in BD type I and healthy controls. Methods Ninety-seven healthy volunteers and 120 BD type I were genotyped for COMT rs4680 and tested for creativity (Barrow Welsh Art Scale – BWAS and intelligence Wechsler Abbreviated Scale of Intelligence (WASI. Results COMT Met allele positively influenced creativity scores in healthy controls but not in BD subjects during mood episodes and euthymia. The presence of allele Met did not influence IQ scores. No influence of IQ total score on creativity was observed. Limitations control group presented higher IQ scores and euthymic group was under medication use. Discussion Our research suggests positive effect of COMT rs4680 (allele Met on creativity scores in healthy controls. One possible interpretation is that creativity is more likely to be associated with lesser degrees of bipolarity. The fact that the same results were not observed in BD may be associated to dysfunctions in the dopaminergic system that characterizes this disorder. Further studies with larger samples and other types of BD should explore the role of the dopaminergic system in creativity.

  1. Generalized polygons

    CERN Document Server

    Maldeghem, Hendrik

    1998-01-01

    This book is intended to be an introduction to the fascinating theory ofgeneralized polygons for both the graduate student and the specialized researcher in the field. It gathers together a lot of basic properties (some of which are usually referred to in research papers as belonging to folklore) and very recent and sometimes deep results. I have chosen a fairly strict geometrical approach, which requires some knowledge of basic projective geometry. Yet, it enables one to prove some typically group-theoretical results such as the determination of the automorphism groups of certain Moufang polygons. As such, some basic group-theoretical knowledge is required of the reader. The notion of a generalized polygon is a relatively recent one. But it is one of the most important concepts in incidence geometry. Generalized polygons are the building bricks of Tits buildings. They are the prototypes and precursors of more general geometries such as partial geometries, partial quadrangles, semi-partial ge­ ometries, near...

  2. 34 CFR 75.620 - General conditions on publication.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false General conditions on publication. 75.620 Section 75... Must Be Met by a Grantee? Publications and Copyrights § 75.620 General conditions on publication. (a...) Required statement. The grantee shall ensure that any publication that contains project materials also...

  3. 45 CFR 1180.48 - General conditions on publications.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false General conditions on publications. 1180.48... Conditions Which Must Be Met by a Grantee Publications and Copyrights § 1180.48 General conditions on publications. (a) Content of materials. Subject to any specific requirements that apply to its grant, a grantee...

  4. Cerebro y metáfora en la novela "Pedro Páramo", de Juan Rulfo

    Directory of Open Access Journals (Sweden)

    CECILIA EDILMA DÍAZ DÍAZ

    2010-01-01

    Full Text Available Se trata de un avance de investigación que aplica la teoría neurolingüística de Omar Parra Rozo para leer y comprender la metáfora en un texto literario. Se toma como objeto de estudio la novela "Pedro Páramo" de Juan Rulfo, específicamente los fragmentos que hablan acerca de la imagen compleja (religión-poder y muerte. El ejercicio de investigación alcanzó a establecer la relación que existe entre imagen- cerebro y metáfora, en el discurso de esta novela.

  5. Saving energy with fiscal benefit of EIA; Energie besparen met fiscaal voordeel van EIA

    Energy Technology Data Exchange (ETDEWEB)

    Smit, R.

    2007-04-15

    A brief overview is given for installers to benefit from the fiscal advantages of the Energy Investment Deduction (EIA in Dutch) incentive, by means of which investments for energy saving technologies and renewable energy sources can be reimbursed. [Dutch] Het kabinet trekt 500 miljoen euro uit voor energiebesparing en duurzaamheid waarmee deze onderwerpen weer in het middelpunt van de belangstelling staan. Daarmee worden samen met de markt grote stappen gezet in de transitie naar een van de duurzaamste en efficientste energievoorzieningen in Europa. Voor installateurs het moment om energiebesparing, met de fiscale voordelen die deze biedt, bij de klant op tafel te leggen.

  6. Excretion tendency of zinc from 65Zn-Met in feces and urine of goats

    International Nuclear Information System (INIS)

    Li Lili; Zhang Bin; Huang Jianliang; Li Hesong

    1998-01-01

    An experiment was conducted to evaluate excretion tendency of zinc in feces and urine with 8 goats groups fed with diet I (basal diet + 65 Zn-Met) and diet II (basal diet + 65 ZnSo 4 ) respectively. The results showed that 65 Zn concentration in feces of the goats fed with diet I was lower than that of the goats fed with diet II, and the absorptivity of zinc from Zn-Met was significantly higher than that from 65 ZnSO 4 (P<0.05)

  7. Gas‒phase reactions of NO+ with Glu and γ‒Glu–Met

    OpenAIRE

    Wincel, H.; Fokkens, R. H.; Nibbering, N. M. M.

    2000-01-01

    The reactivity of the nitrosonium ion, NO+, with the amino acid Glu and the dipeptide γ‒Glu–Met in the gas phase has been investigated using the combination of chemical ionisation mass spectrometry and MS/MS. It is shown that NO+ reacts efficiently with both Glu and Glu–Met leading to the formation of the nitroso‒group containing ions at m/z 159 and 288.The formation of m/z 159, (GluNO‒18)+, is rationalized by a mechanism involving an electrophilic attack of NO+ upon the carbonyl oxygen atom ...

  8. BDNF val66met association with serotonin transporter binding in healthy humans

    DEFF Research Database (Denmark)

    Fisher, P. M.; Ozenne, B.; Svarer, C.

    2017-01-01

    The serotonin transporter (5-HTT) is a key feature of the serotonin system, which is involved in behavior, cognition and personality and implicated in neuropsychiatric illnesses including depression. The brain-derived neurotrophic factor (BDNF) val66met and 5-HTTLPR polymorphisms have predicted......-carriers have increased subcortical 5-HTT binding. The small difference suggests limited statistical power may explain previously reported null effects. Our finding adds to emerging evidence that BDNF val66met contributes to differences in the human brain serotonin system, informing how variability in the 5-HTT...

  9. Meanings of being received and met by others as experienced by women with MS

    Directory of Open Access Journals (Sweden)

    Malin Olsson

    2011-03-01

    Full Text Available In order to elucidate meanings of being received and met by others as experienced by women with multiple sclerosis (MS we conducted a qualitative inquiry. We interviewed 15 women with MS and analysed the interviews with a phenomenological hermeneutic interpretation. The findings were presented in two themes: experiencing oneself as a valuable person and experiencing oneself as diminished. Meanings of being received and met by others, as experienced by women with MS, can be understood as containing two dimensions where treatment from others can mean recognising oneself through confirmation, as well as being ignored due to missing togetherness with others.

  10. Meanings of being received and met by others as experienced by women with MS

    Science.gov (United States)

    Olsson, Malin; Skär, Lisa; Söderberg, Siv

    2011-01-01

    In order to elucidate meanings of being received and met by others as experienced by women with multiple sclerosis (MS) we conducted a qualitative inquiry. We interviewed 15 women with MS and analysed the interviews with a phenomenological hermeneutic interpretation. The findings were presented in two themes: experiencing oneself as a valuable person and experiencing oneself as diminished. Meanings of being received and met by others, as experienced by women with MS, can be understood as containing two dimensions where treatment from others can mean recognising oneself through confirmation, as well as being ignored due to missing togetherness with others. PMID:21394245

  11. Activation of c-MET induces a stem-like phenotype in human prostate cancer.

    Directory of Open Access Journals (Sweden)

    Geert J L H van Leenders

    Full Text Available Prostate cancer consists of secretory cells and a population of immature cells. The function of immature cells and their mutual relation with secretory cells are still poorly understood. Immature cells either have a hierarchical relation to secretory cells (stem cell model or represent an inducible population emerging upon appropriate stimulation of differentiated cells. Hepatocyte Growth Factor (HGF receptor c-MET is specifically expressed in immature prostate cells. Our objective is to determine the role of immature cells in prostate cancer by analysis of the HGF/c-MET pathway.Gene-expression profiling of DU145 prostate cancer cells stimulated with HGF revealed induction of a molecular signature associated with stem cells, characterized by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 ('stem-like signature'. We confirmed the acquisition of a stem-like phenotype by quantitative PCR, FACS analysis and Western blotting. Further, HGF led to activation of the stem cell related Notch pathway by up-regulation of its ligands Jagged-1 and Delta-like 4. Small molecules SU11274 and PHA665752 targeting c-MET activity were both able to block the molecular and biologic effects of HGF. Knock-down of c-MET by shRNA infection resulted in significant reduction and delay of orthotopic tumour-formation in male NMRI mice. Immunohistochemical analysis in prostatectomies revealed significant enrichment of c-MET positive cells at the invasive front, and demonstrated co-expression of c-MET with stem-like markers CD49b and CD49f.In conclusion, activation of c-MET in prostate cancer cells induced a stem-like phenotype, indicating a dynamic relation between differentiated and stem-like cells in this malignancy. Its mediation of efficient tumour-formation in vivo and predominant receptor expression at the invasive front implicate that c-MET regulates tumour infiltration in surrounding tissues putatively by acquisition of a stem-like phenotype.

  12. Genetic modulation of training and transfer in older adults:BDNF Val66Met polymorphism is associated with wider useful field of view

    Directory of Open Access Journals (Sweden)

    Lorenza S Colzato

    2011-09-01

    Full Text Available Western society has an increasing proportion of older adults. Increasing age is associated with a general decrease in the control over task-relevant mental processes. In the present study we investigated the possibility that successful transfer of game-based cognitive improvements to untrained tasks in elderly people is modulated by preexisting neuro-developmental factors as genetic variability related to levels of the brain-derived neurotrophic factor (BDNF, an important neuromodulator underlying cognitive processes. We trained participants, genotyped for the BDNF Val66Met polymorphism, on cognitive tasks developed to improve dynamic attention. Pre-training (baseline and post-training measures of attentional processes (divided and selective attention were acquired by means of the Useful Field of View (UFOV task. As expected, Val/Val homozygous individuals showed larger beneficial transfer effects than Met/-carriers. Our findings support the idea that genetic predisposition modulates transfer effects.

  13. Association of Catechol-O-methyltransferase polymorphism Val158Met and mammographic density: A meta-analysis.

    Science.gov (United States)

    Kallionpää, Roope A; Uusitalo, Elina; Peltonen, Juha

    2017-08-15

    The Val158Met polymorphism in catechol-O-methyltransferase (COMT) enzyme reduces the methylation of catechol estrogens, which may affect mammographic density. High mammographic density is a known risk factor of breast cancer. Our aim was to perform meta-analysis of the effect of COMT Val158Met polymorphism on mammographic density. Original studies reporting data on mammographic density, stratified by the presence of COMT Val158Met polymorphism, were identified and combined using genetic models Met/Val vs. Val/Val, Met/Met vs. Val/Val, Val/Met+Met/Met vs. Val/Val (dominant model) and Met/Met vs. Val/Met+Val/Val (recessive model). Subgroup analyses by breast cancer status, menopausal status and use of hormone replacement therapy (HRT) were also performed. Eight studies were included in the meta-analysis. The overall effect in percent mammographic density was -1.41 (CI -2.86 to 0.05; P=0.06) in the recessive model. Exclusion of breast cancer patients increased the effect size to -1.93 (CI -3.49 to -0.37; P=0.02). The results suggested opposite effect of COMT Val158Met for postmenopausal users of HRT versus premenopausal women or postmenopausal non-users of HRT. COMT Val158Met polymorphism may be associated with mammographic density at least in healthy women. Menopausal status and HRT should be taken into account in future studies to avoid masking of the underlying effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody-"decoy" strategy.

    Science.gov (United States)

    Basilico, Cristina; Modica, Chiara; Maione, Federica; Vigna, Elisa; Comoglio, Paolo M

    2018-04-25

    MET, a master gene sustaining "invasive growth," is a relevant target for cancer precision therapy. In the vast majority of tumors, wild-type MET behaves as a "stress-response" gene and relies on the ligand (HGF) to sustain cell "scattering," invasive growth and apoptosis protection (oncogene "expedience"). In this context, concomitant targeting of MET and HGF could be crucial to reach effective inhibition. To test this hypothesis, we combined an anti-MET antibody (MvDN30) inducing "shedding" (i.e., removal of MET from the cell surface), with a "decoy" (i.e., the soluble extracellular domain of the MET receptor) endowed with HGF-sequestering ability. To avoid antibody/decoy interaction-and subsequent neutralization-we identified a single aminoacid in the extracellular domain of MET-lysine 842-that is critical for MvDN30 binding and engineered the corresponding recombinant decoyMET (K842E). DecoyMET K842E retains the ability to bind HGF with high affinity and inhibits HGF-induced MET phosphorylation. In HGF-dependent cellular models, MvDN30 antibody and decoyMET K842E used in combination cooperate in restraining invasive growth, and synergize in blocking cancer cell "scattering." The antibody and the decoy unbridle apoptosis of colon cancer stem cells grown in vitro as spheroids. In a preclinical model, built by orthotopic transplantation of a human pancreatic carcinoma in SCID mice engineered to express human HGF, concomitant treatment with antibody and decoy significantly reduces metastatic spread. The data reported indicate that vertical targeting of the MET/HGF axis results in powerful inhibition of ligand-dependent MET activation, providing proof of concept in favor of combined target therapy of MET "expedience." © 2018 UICC.

  15. Complete or partial reduction of the Met receptor tyrosine kinase in distinct circuits differentially impacts mouse behavior.

    Science.gov (United States)

    Thompson, Barbara L; Levitt, Pat

    2015-01-01

    Our laboratory discovered that the gene encoding the receptor tyrosine kinase, MET, contributes to autism risk. Expression of MET is reduced in human postmortem temporal lobe in autism and Rett Syndrome. Subsequent studies revealed a role for MET in human and mouse functional and structural cortical connectivity. To further understand the contribution of Met to brain development and its impact on behavior, we generated two conditional mouse lines in which Met is deleted from select populations of central nervous system neurons. Mice were then tested to determine the consequences of disrupting Met expression. Mating of Emx1 (cre) and Met (fx/fx) mice eliminates receptor signaling from all cells arising from the dorsal pallium. Met (fx/fx) and Nestin (cre) crosses result in receptor signaling elimination from all neural cells. Behavioral tests were performed to assess cognitive, emotional, and social impairments that are observed in multiple neurodevelopmental disorders and that are in part subserved by circuits that express Met. Met (fx/fx) /Emx1 (cre) null mice displayed significant hypoactivity in the activity chamber and in the T-maze despite superior performance on the rotarod. Additionally, these animals showed a deficit in spontaneous alternation. Surprisingly, Met (fx/fx; fx/+) /Nestin (cre) null and heterozygous mice exhibited deficits in contextual fear conditioning, and Met (fx/+) /Nestin (cre) heterozygous mice spent less time in the closed arms of the elevated plus maze. These data suggest a complex contribution of Met in the development of circuits mediating social, emotional, and cognitive behavior. The impact of disrupting developmental Met expression is dependent upon circuit-specific deletion patterns and levels of receptor activity.

  16. More with thermal energy storage. Report 1. Coupling with policy. Coupling of research results MMB with policy aspects. Final report; Meer met bodemenergie. Rapport 1. Koppeling met beleid. Koppeling onderzoeksresultaten MMB met beleidsaspecten. Eindrapport

    Energy Technology Data Exchange (ETDEWEB)

    Luitwieler, M. [Bioclear, Groningen (Netherlands); Van Beek, D.; De Boer, S.; Koenders, M. [IF Technology, Arnhem (Netherlands)

    2012-06-25

    The project More With Thermal Energy Storage (MMB, abbreviated in Dutch) focuses on knowledge gaps and potential opportunities regarding open systems. The main questions to be answered are: (1) What effects (hydrological, thermal, microbiological and chemical) occur in the soil system by application of thermal energy storage; (2) Which technical options are available for a sustainable integration of thermal energy storage in the water and energy chain?; (3) Is it possible to achieve multiple objectives by using smart combinations? The project is organized in different work packages. In work package 2, the effects of individual and collective thermal energy storage storage systems on subsoils and the environment are determined. In work package 3 the opportunities for thermal energy storage and soil remediation are examined, while in work package 4 the focus is on new sustainable combinations of heat and cold storage. Work package is the umbrella part where communication and policy of and participation in MMB are the main subjects. This final report provides (a) an overview of the activities that have taken place in the context of work package 1, (b) the results of the other work packages in the light of four policy frameworks, and (c) a view on future policy [Dutch] Het project Meer Met Bodemenergie (MMB) richt zich op het invullen van kennisleemtes en mogelijke kansen ten aanzien van open systemen. De belangrijkste vragen waarop het onderzoeksprogramma MMB antwoord geeft zijn: (1) Welke effecten (hydrologisch, thermisch, microbiologisch en chemisch) treden op in het bodemsysteem bij toepassing van bodemenergie?; (2) Welke technische mogelijkheden zijn er voor het duurzaam inpassen van bodem-energie in de water- en energieketen?; (3) Is het mogelijk om meerdere doelstellingen tegelijk te verwezenlijken door slimme combinaties te maken? Het project is ingericht met verschillende werkpakketten. In werkpakket 2 worden de effecten van individuele en collectieve

  17. OCRA radiometric cloud fractions for GOME-2 on MetOp-A/B

    Science.gov (United States)

    Lutz, Ronny; Loyola, Diego; Gimeno García, Sebastián; Romahn, Fabian

    2016-05-01

    This paper describes an approach for cloud parameter retrieval (radiometric cloud-fraction estimation) using the polarization measurements of the Global Ozone Monitoring Experiment-2 (GOME-2) onboard the MetOp-A/B satellites. The core component of the Optical Cloud Recognition Algorithm (OCRA) is the calculation of monthly cloud-free reflectances for a global grid (resolution of 0.2° in longitude and 0.2° in latitude) to derive radiometric cloud fractions. These cloud fractions will serve as a priori information for the retrieval of cloud-top height (CTH), cloud-top pressure (CTP), cloud-top albedo (CTA) and cloud optical thickness (COT) with the Retrieval Of Cloud Information using Neural Networks (ROCINN) algorithm. This approach is already being implemented operationally for the GOME/ERS-2 and SCIAMACHY/ENVISAT sensors and here we present version 3.0 of the OCRA algorithm applied to the GOME-2 sensors. Based on more than five years of GOME-2A data (April 2008 to June 2013), reflectances are calculated for ≈ 35 000 orbits. For each measurement a degradation correction as well as a viewing-angle-dependent and latitude-dependent correction is applied. In addition, an empirical correction scheme is introduced in order to remove the effect of oceanic sun glint. A comparison of the GOME-2A/B OCRA cloud fractions with colocated AVHRR (Advanced Very High Resolution Radiometer) geometrical cloud fractions shows a general good agreement with a mean difference of -0.15 ± 0.20. From an operational point of view, an advantage of the OCRA algorithm is its very fast computational time and its straightforward transferability to similar sensors like OMI (Ozone Monitoring Instrument), TROPOMI (TROPOspheric Monitoring Instrument) on Sentinel 5 Precursor, as well as Sentinel 4 and Sentinel 5. In conclusion, it is shown that a robust, accurate and fast radiometric cloud-fraction estimation for GOME-2 can be achieved with OCRA using polarization measurement devices (PMDs).

  18. Mercuralismo metálico crônico ocupacional Chronic occupational metallic mercurialism

    Directory of Open Access Journals (Sweden)

    Marcília de Araújo Medrado Faria

    2003-02-01

    Full Text Available Revisão que analisa os conhecimento atuais das manifestações do mercuralismo crônico ocupacional. Avaliaram-se os principais estudos e revisões científicas concernentes às formas clínicas e fisiopatogenia desta intoxicação. Foram pesquisadas, entre outras fontes, as bases de dados Medline e Lilacs. O eretismo ou a síndrome neuropsíquica caracterizada por sintomas de irritabilidade, ansiedade, mudanças de comportamento, apatia, perda da auto-estima e de memória, depressão, insônia, delírio, cefaléia, dores musculares e tremores é observada após a exposição ao mercúrio metálico. Manifestações de hipertensão arterial, renais, imunológicas e alérgicas são freqüentes. A falta de medidas preventivas aumenta o risco da doença em indústrias, no garimpo e consultórios odontológicos. A legislação brasileira assinala 16 manifestações clínicas determinadas pela intoxicação, todavia ocorre subdiagnóstico. O diagnóstico clínico é importante e as novas tecnologias médicas podem detectar alterações do sistema nervoso central, renal e imunológico, proporcionando avanços no conhecimento neuro-imuno-toxicológico e nas medidas de prevenção do mercuralismo.This is a review on current knowledge of chronic occupational mercurialism syndrome. Major scientific studies and reviews on clinical manifestation and physiopathology of mercury poisoning were evaluated. The search was complemented using Medline and Lilacs data. Erethism or neuropsychological syndrome, characterized by irritability, personality change, loss of self-confidence, depression, delirium, insomnia, apathy, loss of memory, headaches, general pain, and tremors, is seen after exposure to metallic mercury. Hypertension, renal disturbances, allergies and immunological conditions are also common. Mercury is found in many different work processes: industries, gold mining, and dentistry. As prevention measures are not often adopted there is an increasing

  19. General chemistry

    International Nuclear Information System (INIS)

    Kwon, Yeong Sik; Lee, Dong Seop; Ryu, Haung Ryong; Jang, Cheol Hyeon; Choi, Bong Jong; Choi, Sang Won

    1993-07-01

    The book concentrates on the latest general chemistry, which is divided int twenty-three chapters. It deals with basic conception and stoichiometry, nature of gas, structure of atoms, quantum mechanics, symbol and structure of an electron of ion and molecule, chemical thermodynamics, nature of solid, change of state and liquid, properties of solution, chemical equilibrium, solution and acid-base, equilibrium of aqueous solution, electrochemistry, chemical reaction speed, molecule spectroscopy, hydrogen, oxygen and water, metallic atom; 1A, IIA, IIIA, carbon and atom IVA, nonmetal atom and an inert gas, transition metals, lanthanons, and actinoids, nuclear properties and radioactivity, biochemistry and environment chemistry.

  20. General relativity

    International Nuclear Information System (INIS)

    Gourgoulhon, Eric

    2013-01-01

    The author proposes a course on general relativity. He first presents a geometrical framework by addressing, presenting and discussion the following notions: the relativistic space-time, the metric tensor, Universe lines, observers, principle of equivalence and geodesics. In the next part, he addresses gravitational fields with spherical symmetry: presentation of the Schwarzschild metrics, radial light geodesics, gravitational spectral shift (Einstein effect), orbitals of material objects, photon trajectories. The next parts address the Einstein equation, black holes, gravitational waves, and cosmological solutions. Appendices propose a discussion of the relationship between relativity and GPS, some problems and their solutions, and Sage codes

  1. Metáforas para profesor y estudiante de pedagogía en un grupo de estudiantes de pedagogía chilenos

    Directory of Open Access Journals (Sweden)

    Paola Alarcón

    2014-05-01

    Full Text Available En este artículo se presentan los resultados de una investigación de tipo cualitativo, cuyo objetivo general es identificar los conceptos metafóricos los estudiantes de pedagogía acerca de cómo ellos creen que el profesor es representado por la sociedad, y como representan ellos a sí mismos. El marco de referencia lo constituyen la cognición docente y la metáfora conceptual. Para la elicitación de metáforas se aplicó un cuestionario a un grupo de 70 estudiantes de Pedagogía de la Universidad de Concepción, Chile. Se realizó un análisis de contenido que abarcó las siguientes etapas: etiquetado, clasificación, categorización y juicio de externos. Para las metáforas sobre cómo es representado el profesor por la sociedad, a través del análisis, se identificaron las siguientes categorías: Metáforas centradas en el profesor, Metáforas centradas en el estudiante, Metáforas centradas en la valoración social. Para las metáforas sobre cómo es representado el estudiante de pedagogía se identificaron las siguientes categorías: Metáforas centradas en el proceso de formación profesional, Metáforas centradas en el proceso de enseñanza aprendizaje, Metáforas centradas en la valoración social. Finalmente, se comentan los alcances y proyecciones del estudio, y se discute la pertinencia de algunas categorías en el contexto de la formación de profesores. This article provides the results of a qualitative study, whose main objective is to identify the metaphorical concepts through which teacher candidates believe how teachers are represented by society, and how they represent themselves. The referential framework of this study is given by teacher cognition and conceptual metaphor. A questionnaire was applied to elicit metaphors from 70 teacher candidates at the University of Concepción, Chile. Content analysis was used, following these stages: coding, classification, categorization and scholar review. For the metaphors on how

  2. Collegiate Schemas: The Influence of Institutional Met Expectations on Tenure-Track Faculty Job Satisfaction

    Science.gov (United States)

    Pontius, Jason Lewis

    2012-01-01

    "Met expectations" research into job satisfaction (Locke, 1976; Porter & Steers, 1973) has shown that the expectations employees bring to their jobs influence their overall job satisfaction. At colleges and universities, faculty job satisfaction is important because it can provide a measure of overall institutional effectiveness…

  3. Dorstige glastuinbouw moet op elke druppel water letten (interview met Wim Voogt)

    NARCIS (Netherlands)

    Bezemer, J.; Voogt, W.

    2010-01-01

    Hoge kwaliteit water wordt schaarser. Dat dwingt de glastuinbouw zorgvuldig met de teeltfactor water om te gaan en minder afhankelijk van oppervlaktewater te worden. Hemelwater blijft de belangrijkste bron maar 100% dekking is te duur. Omgekeerde osmose blijft de meest aantrekkelijke techniek om

  4. De eerste 'European Day Without A Road Death' : maak kennis met EDWARD.

    NARCIS (Netherlands)

    Preusting, G.

    2016-01-01

    Op 21 september 2016 vond de eerste European Day Without A Road Death plaats. Het project - naar goed Europees gebruik met een acronym 'EDWARD' gedoopt - is een initiatief van TISPOL, het European Traffic Police Network. TISPOL, waarbij dertig landen zijn aangesloten, vraagt nu aan elke Europese

  5. Kwaliteitsdocument inzake de bepaling van Cadmium in kunststoffen met behulp van Rontgenflurescentie

    NARCIS (Netherlands)

    Hoogerbrugge R; van de Wiel HJ; van de Beek ACW; Kliest JJG; IEM

    1999-01-01

    Bij de handhaving van het besluit Cadmium in Kunststoffen is gebleken, dat de analyse met behulp van Rvntgenfluorescentie (XRF) een snel en goedkoop alternatief zou kunnen zijn voor de op dit moment wettelijk voorgeschreven methoden. In opdracht van de Inspecteur Milieuhygikne is daarom door het

  6. Een kennisintensief proces van waarnemen, beslissen en actie ondernemen. Met nieuwe detectietechnieken minder middelen spuiten

    NARCIS (Netherlands)

    Os, van E.A.; Hemming, J.; Zande, van de J.C.; Snel, J.F.H.

    2007-01-01

    In het verleden werd op een vast moment in de week een cocktail van middelen gespoten om het gewas gezond te houden. Dit veranderde toen duidelijk werd dat chemische middelen ook nadelen hadden. Later kwam daar ook het milieu bij met als gevolg dat de emissie naar de lucht en het oppervlaktewater

  7. Televisual Satire in the Age of Glocalization: The Case of ‘Zondag met Lubach’

    NARCIS (Netherlands)

    Nieuwenhuis, Ivo

    2018-01-01

    textabstractThis article analyses the highly popular Dutch satirical TV-show Zondag met Lubach (ZML) from the perspective of ‘glocalization.’ This places the show both within the global tradition of late-night satire, originating in the United States, and in the local Dutch tradition of satirical

  8. To bee or not to bee (interview met T. Blacquière & J. Calis)

    NARCIS (Netherlands)

    Thoenes, E.; Blacquiere, T.; Calis, J.

    2009-01-01

    Het gaat slecht met de honingbij. Zowel in Europa als in Amerika zien imkers in toenemende mate hun bijenvolken ten prooi vallen aan de ‘verdwijnziekte’. Het symptoom, een lege kast zonder bijen – levend noch dood –, stelt wetenschappers voor een raadsel. Wageningse onderzoekers proberen de oorzaken

  9. Patients' family satisfaction with needs met at the medical intensive care unit.

    Science.gov (United States)

    Khalaila, Rabia

    2013-05-01

    The current study investigated the perceived importance and the perceived met needs of family members in the medical intensive care unit and assessed family members' satisfaction with needs met. Studies conducted throughout the world over the past 30 years indicate that family needs are still neglected. Unmet needs of family members of patients in the intensive care unit lead to dissatisfaction with care. A cross-sectional study. A total of 70 family members of critically ill patients were included in this study conducted in a medical intensive care unit in Israel between October 2007-September 2008, using a structured interview. Three outcomes measured by the Family Satisfaction in the Intensive Care Unit Inventory were regressed separately for baseline variables and family needs met subscales as measured by the Critical Care Family Needs Inventory. Multivariate linear regression analysis was used to detect factors that could have predicted each outcome. The results showed differences between the perceived importance and the perceived met needs of family members. Satisfaction with care was positively related to meeting all needs domains except the information need. However, satisfaction with information and decision-making was related only to meeting information and emotional support needs. Continued unmet needs of family members of intensive care unit patients have a negative impact on family satisfaction. Only sweeping changes in clinical practice will succeed in meeting the unmet needs of patients' families. © 2012 Blackwell Publishing Ltd.

  10. When Allport Met Freud: Using Anecdotes in the Teaching of Psychology.

    Science.gov (United States)

    Kaufman, James C.; Bristol, Adam S.

    2001-01-01

    Proposes using anecdotes in introductory psychology courses to teach key points, principles, and people. Offers theoretical and empirical support for anecdotes as teaching tools. Believes that anecdotes, such as when Gordon Allport met Sigmund Freud, provide an enjoyable experience and enable students to better remember information. (CMK)

  11. Vergelijking van vangsten van een 12 m pulskor met een conventionele wekkerboomkor

    NARCIS (Netherlands)

    Marlen, van B.; Ybema, M.S.; Kraayenoord, A.; Vries, de M.; Rink, G.J.

    2005-01-01

    In het kader van de ontwikkeling van een pulskor als alternatief voor de conventionele boomkor met wekkerkettingen werd in nov-dec 2004 en jan 2005 onderzoek uitgevoerd op het visserij-onderzoekingsvaartuig “Tridens” naar de vangstverschillen van beide visserijtechnieken en de overleving van door

  12. ECO-driving met behulp van serious gaming en social media (fase 1)

    NARCIS (Netherlands)

    Kuiper, H.; Boonekamp, R.C.; Bijlsma, T.; Jansen, S.T.H.; Obdeijn, C.; Stuiver, A.; Spronkmans, S.; Bijnen, D.; Versteegh, T.

    2013-01-01

    Dit rapport beschrijft fase 1 van een EL&I cofinancieringstraject waarin onderzoek wordt gedaan naar gedragsbeïnvloeding bij automobilisten om CO2-reductie te bereiken met behulp van Serious gaming en Social Media. Het onderzoek sluit goed aan bij het overheidswerkprogramma “Schoon en Zuinig”

  13. BDNF val(66)met affects hippocampal volume and emotion-related hippocampal memory activity

    NARCIS (Netherlands)

    Molendijk, M. L.; van Tol, M-J; Penninx, B. W. J. H.; van der Wee, N. J. A.; Aleman, A.; Veltman, D. J.; Spinhoven, P.; Elzinga, B. M.

    2012-01-01

    The val(66)met polymorphism on the BDNF gene has been reported to explain individual differences in hippocampal volume and memory-related activity. These findings, however, have not been replicated consistently and no studies to date controlled for the potentially confounding impact of early life

  14. Gender effects of the COMT Val 158 Met genotype on verbal fluency in healthy adults.

    Science.gov (United States)

    Soeiro-De-Souza, Marcio Gerhardt; Bio, Danielle Soares; David, Denise Petresco; Missio, Giovani; Lima, Bruno; Fernandes, Fernando; Machado-Vieira, Rodrigo; Moreno, Ricardo Alberto

    2013-09-01

    Cognitive performance in healthy individuals is associated with gender differences in specific tests; a female advantage has been demonstrated in language tests, whereas a male advantage has been demonstrated in spatial relation examinations. The prefrontal cortex (PFC) mediates important cognitive domains and is influenced by dopamine (DA) activity. The single nucleotide polymorphism (SNP) rs4680 in the catechol‑O‑methyltransferase (COMT) gene results in an amino acid substitution from valine (Val) to methionine (Met). The Met allele has been demonstrated to decrease COMT enzyme activity and improve PFC cognitive function. COMT regulates DA activity in the PFC and exhibits gender effects. The aim of the present study was to investigate the gender‑specific effects of the COMT genotype on cognition in healthy young adults. Seventy‑six healthy subjects were genotyped for COMT rs4680 and submitted to an extensive range of neuropsychological tests assessing aspects of PFC function. The COMT Met allele influenced the performance of executive function. The results revealed gender effects of the COMT rs4680 Met allele on verbal fluency, with positive effects in males and negative effects in females. This suggested that DA activity affects cognitive function in different ways, according to gender.

  15. Plastic raakt zoek in de oceaan (interview met Jan Andries van Franeker)

    NARCIS (Netherlands)

    Kleis, R.; Franeker, van J.A.

    2015-01-01

    De plastic eilanden op de oceanen verliezen in hoog tempo .....plastic. Jan Andries van Franeker toont dat aan door plastic vangsten in die eilanden te vergelijken met de maaginhoud van Noordse stormvogels op de Noordzee. Waar al dat plastic blijft, is vooralsnog een raadsel.

  16. MET-2-Dependent H3K9 Methylation Suppresses Transgenerational Small RNA Inheritance.

    Science.gov (United States)

    Lev, Itamar; Seroussi, Uri; Gingold, Hila; Bril, Roberta; Anava, Sarit; Rechavi, Oded

    2017-04-24

    In C. elegans, alterations to chromatin produce transgenerational effects, such as inherited increase in lifespan and gradual loss of fertility. Inheritance of histone modifications can be induced by double-stranded RNA-derived heritable small RNAs. Here, we show that the mortal germline phenotype, which is typical of met-2 mutants, defective in H3K9 methylation, depends on HRDE-1, an argonaute that carries small RNAs across generations, and is accompanied by accumulated transgenerational misexpression of heritable small RNAs. We discovered that MET-2 inhibits small RNA inheritance, and, as a consequence, induction of RNAi in met-2 mutants leads to permanent RNAi responses that do not terminate even after more than 30 generations. We found that potentiation of heritable RNAi in met-2 animals results from global hyperactivation of the small RNA inheritance machinery. Thus, changes in histone modifications can give rise to drastic transgenerational epigenetic effects, by controlling the overall potency of small RNA inheritance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Hoe goed weten oudere fietsers wat ze kunnen? : een veldexperiment met gewone en elektrische fietsen.

    NARCIS (Netherlands)

    Groot-Mesken, J. de & Commandeur, J.J.F.

    2015-01-01

    Met de populariteit van de elektrische fiets groeit ook het aantal ouderen dat hiervan gebruikmaakt. Belangrijke vragen zijn of deze ouderen de speciale eigenschappen van de elektrische fiets goed inschatten, of deze het fietsen moeilijker maken en zo ja, of ouderen hun gedrag daarop in voldoende

  18. The East Asian Atmospheric Water Cycle and Monsoon Circulation in the Met Office Unified Model

    Science.gov (United States)

    Rodríguez, José M.; Milton, Sean F.; Marzin, Charline

    2017-10-01

    In this study the low-level monsoon circulation and observed sources of moisture responsible for the maintenance and seasonal evolution of the East Asian monsoon are examined, studying the detailed water budget components. These observational estimates are contrasted with the Met Office Unified Model (MetUM) climate simulation performance in capturing the circulation and water cycle at a variety of model horizontal resolutions and in fully coupled ocean-atmosphere simulations. We study the role of large-scale circulation in determining the hydrological cycle by analyzing key systematic errors in the model simulations. MetUM climate simulations exhibit robust circulation errors, including a weakening of the summer west Pacific Subtropical High, which leads to an underestimation of the southwesterly monsoon flow over the region. Precipitation and implied diabatic heating biases in the South Asian monsoon and Maritime Continent region are shown, via nudging sensitivity experiments, to have an impact on the East Asian monsoon circulation. By inference, the improvement of these tropical biases with increased model horizontal resolution is hypothesized to be a factor in improvements seen over East Asia with increased resolution. Results from the annual cycle of the hydrological budget components in five domains show a good agreement between MetUM simulations and ERA-Interim reanalysis in northern and Tibetan domains. In simulations, the contribution from moisture convergence is larger than in reanalysis, and they display less precipitation recycling over land. The errors are closely linked to monsoon circulation biases.

  19. Circles within circles: crosstalk between protein Ser/Thr/Tyr-phosphorylation and Met oxidation

    Science.gov (United States)

    Background: Reversible posttranslational protein modifications such as phosphorylation of Ser/Thr/Tyr and Met oxidation are critical for both metabolic regulation and cellular signalling. Although these modifications are typically studied individually, herein we describe the potential for cross-talk...

  20. Association Between Smoking, Nicotine Dependence, and BDNF Val(66)Met Polymorphism with BDNF Concentrations in Serum

    NARCIS (Netherlands)

    Jamal, Mumtaz; Van der Does, Willem; Elzinga, Bernet M.; Molendijk, Marc L.; Penninx, Brenda W. J. H.

    Introduction: Nicotine use is associated with the upregulation of brain-derived neurotrophic factor (BDNF) in serum. An association between smoking and the BDNF Val(66)Met polymorphism has also been found. The aim of this study is to examine the levels of serum BDNF in never-smokers, former smokers,

  1. The association of XRCC3 Thr241Met genetic variant with risk of ...

    African Journals Online (AJOL)

    Background: Previous studies suggest that the X-ray repair cross-complementing group 3 gene (XRCC3) Thr241Met genetic variant could be potentially associated with the risk of prostate cancer. However, results from these published studies were conflicting rather than conclusive. Objectives:This meta-analysis aimed to ...

  2. Allemaal digitaal : Een overzicht van digitale spelvormen voor mensen met een licht verstandelijke beperking

    NARCIS (Netherlands)

    Alyssa de Kruif; Carly Kuijper; Josje Louisse

    Voor u ligt een overzicht van vrij toegankelijke digitale spelvormen ter bevordering van de zelfredzaamheid van mensen met een licht verstandelijke beperking. In dit overzicht vindt u digitale spelvormen die beschikbaar zijn als website en/of als applicatie voor op de smartphone of tablet. Voor de

  3. De interactie van SiC met Fe, Ni en hun legeringen

    NARCIS (Netherlands)

    Schiepers, R.C.J.

    1991-01-01

    De interactie tussen SiC en metalen gebaseerd op Fe en Ni is bestudeerd in het temperatuurtraject 700-1035°C door middel van vaste-stof-diffusiekoppels. In de koppels van SiC met Fe, Ni en hun legeringen treden hevige reakties op, die de vorming van een goede verbinding verhinderen. Door het grate

  4. Over Rattus rattus roquei Sody met beschrijving van een nieuw ras van Rattus rattus van Soemba

    NARCIS (Netherlands)

    Sody, H.J.V.

    1930-01-01

    Geen der op Java voorkomende soorten heeft wellicht den werkers in Javaansche ratten zooveel determinatie-zorgen gekost als de voor kort door mij 1) met roquei benoemde Javaansche „boomrat" 2). Door enkele auteurs 3) werd de vorm oorspronkelijk slechts aangeduid als Mus sp. of Rattus sp., ter

  5. Die era van Suid-Afrika se militere hoogbloei met die ...

    African Journals Online (AJOL)

    4 Jun 1976 ... Die Toyota 1200 bakkie is geadverteer met die woorde 'Hier kom die pantserbakkie', teen die agtergrond van 'n olifant tenk.32. Daar is ook 'n betrekking deur Thorold en van Wyk geadverteer waar militere opleiding 'n voorvereiste was.33. Daar was ook films wat weermag en polisie gebasseer is wat in die ...

  6. Worstelen met Risk Appetite : Hoe de inkleuring van de risicomatrix de risicohouding verraadt

    NARCIS (Netherlands)

    dr. A.F. de Wild; V. Versluis

    2016-01-01

    Een risico-averse houding bij het prioriteren van risico’s is aan te bevelen volgens de besliskundige inzichten van Daniël Kahneman. Maar wat bedoelt de besliskunde eigenlijk met risicoaversie? En hoe kan het koppelen van het begrip risicohouding aan de risicomatrix helpen bij de onderbouwing van de

  7. 21 CFR 111.73 - What is your responsibility for determining whether established specifications are met?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What is your responsibility for determining whether established specifications are met? 111.73 Section 111.73 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD...

  8. 21 CFR 111.77 - What must you do if established specifications are not met?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What must you do if established specifications are not met? 111.77 Section 111.77 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  9. Huiskatten in natuurgebieden : kan TNR hybridisatie met de Wilde kat voorkomen?

    NARCIS (Netherlands)

    Lammertsma, D.R.; Janssen, R.; Hout, van der J.; Jansman, H.A.H.

    2011-01-01

    De Wilde kat keert weer terug in Nederland. Een bedreiging daarbij is hybridisatie met verwilderde huiskatten. De provincie Limburg heeft Alterra verzocht om te onderzoeken in hoeverre het TNR-programma van de Dierenbescherming (TNR: trap-neuter-return, vangen-steriliseren-terugplaatsen) een

  10. Met lure&kill-systeem vliegen motten vanzelf naar het insecticide

    NARCIS (Netherlands)

    Kierkels, T.; Griepink, F.C.

    2008-01-01

    Insecten worden zo sterk aangetrokken door feromonen - seksstoffen - dat je daar bij de bestrijding gebruik van kunt maken. Als het insect naar het insecticide toekomt, hoef je niet areaaldekkend te spuiten. Dat heeft veel voordelen. Plant Research International is al ver met de ontwikkeling van

  11. 42 CFR 59.5 - What requirements must be met by a family planning project?

    Science.gov (United States)

    2010-10-01

    ... requirements must be met by a family planning project? (a) Each project supported under this part must: (1... (iii) Promote continued participation in the project by persons to whom family planning services may be... services purchased for project participants will be authorized by the project director or his designee on...

  12. Financiële verslaggeving door het Rijk vergeleken met IPSAS

    NARCIS (Netherlands)

    van Schaik, F.

    2014-01-01

    De Europese Commissie bereidt plannen voor om de financiële verslaggeving door de overheden van de lidstaten te harmoniseren met als doel een verbetering van transparantie en vergelijkbaarheid. De Europese schuldencrisis heeft duidelijk gemaakt dat de jaarrekeningen van de overheden van de lidstaten

  13. Catechol-O-methyltransferase Val(158)Met association with parahippocampal physiology during memory encoding in schizophrenia.

    Science.gov (United States)

    Di Giorgio, A; Caforio, G; Blasi, G; Taurisano, P; Fazio, L; Romano, R; Ursini, G; Gelao, B; Bianco, L Lo; Papazacharias, A; Sinibaldi, L; Popolizio, T; Bellomo, A; Bertolino, A

    2011-08-01

    Catechol-O-methyltransferase (COMT) Val158Met has been associated with activity of the mesial temporal lobe during episodic memory and it may weakly increase risk for schizophrenia. However, how this variant affects parahippocampal and hippocampal physiology when dopamine transmission is perturbed is unclear. The aim of the present study was to compare the effects of the COMT Val158Met genotype on parahippocampal and hippocampal physiology during encoding of recognition memory in patients with schizophrenia and in healthy subjects. Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we studied 28 patients with schizophrenia and 33 healthy subjects matched for a series of sociodemographic and genetic variables while they performed a recognition memory task. We found that healthy subjects had greater parahippocampal and hippocampal activity during memory encoding compared to patients with schizophrenia. We also found different activity of the parahippocampal region between healthy subjects and patients with schizophrenia as a function of the COMT genotype, in that the predicted COMT Met allele dose effect had an opposite direction in controls and patients. Our results demonstrate a COMT Val158Met genotype by diagnosis interaction in parahippocampal activity during memory encoding and may suggest that modulation of dopamine signaling interacts with other disease-related processes in determining the phenotype of parahippocampal physiology in schizophrenia. © Cambridge University Press 2010

  14. Ammoniakemissie uit een vleesvarkensstal met opvang en verwijdering van mest via spoelgoten

    NARCIS (Netherlands)

    Huis in ‘t Veld, J.H.W.; Satter, I.H.G.

    1998-01-01

    Onderzoek werd verricht naar de ammoniakemissie uit een vleesvarkensstal met een zogenaamd spoelgotensysteem. Bij dit systeem bevonden zich onder de roosters, horizontaal gelegen, in V-vorm uitgevoerde goten van 26 cm diep. De mest van de varkens kwam in deze goten terecht en werd tweemaal daags uit

  15. Op zoek naar de identiteit van Asperen : veertien gesprekken met oud-militairen, bewoners en bestuurders

    NARCIS (Netherlands)

    Weijschedé, T.J.; Mulder, J.R.

    2007-01-01

    Binnen het Interreg project Cultured wisselen veertien Europese partners met elkaar uit hoe het cultureel erfgoed een rol kan spelen bij regionale ontwikkeling. Alterra bracht als voorbeeld het Lingekwartier in. Voor het gebied rond Asperen is via gesprekken gebiedskennis vergaard, omdat

  16. The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment

    DEFF Research Database (Denmark)

    Schofield, J.T.; Barnes, J.R.; Crisp, D.

    1997-01-01

    The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment measured the vertical density, pressure, and temperature structure of the martian atmosphere from the surface to 160 km, and monitored surface meteorology and climate for 83 sols (1 sol = 1 martian day = 24...

  17. Radioimmunoassay of met-enkephalin in microdissected areas of paraformaldehyde-fixed rat brain

    International Nuclear Information System (INIS)

    Correa, F.M.A.; Saavedra, J.M.

    1984-01-01

    The effects were studied of various sample preparation procedures on rat brain met-enkephalin content, measured by radioimmunoassay. Whole brain met-enkephalin content of rats killed by decapitation followed by immediate tissue freezing was similar to that of rats killed by microwave irradiation and to those of rats anesthetized with pentobarbital or halothane before killing, whether previously perfused with paraformaldehyde or not. In contrast, a decrease (up to 80%) in met-enkephalin concentrations was observed when brain samples were frozen and thawed to mimic the procedure utilized in the ''punch'' technique for analysis of discrete brain nuclei. This decrease was totally prevented by paraformaldehyde perfusion of the brain prior to sacrifice. Brain perfusion did not alter the amount of immunoassayable met-enkephalin extracted from tissue or its profile after Sephadex chromatography. Paraformaldehyde perfusion results in better morphological tissue preservation and facilitates the ''punch'' dissecting technique. Paraformaldehyde perfusion may be the procedure of choice for the measurement of neuropeptides in specific brain nuclei dissected by the ''punch'' technique

  18. Beheersing intrinsieke kwaliteit potplanten met als pilot Ficus en Anthurium : deelproject 3

    NARCIS (Netherlands)

    Boer, P.; Verberkt, H.; Snel, J.F.H.

    2008-01-01

    Ontwikkelen van een meettechniek waarmee de intrinsieke kwaliteit van potplanten tijdens de teelt gemeten kan worden. Uit deelproject 2 blijkt dat symptomen van lichtstress in een vroeg stadium met MIPS gemeten kunnen worden bij zowel Ficus als Anthurium. Van belang is om na te gaan of al voordat

  19. Metáfora multimodal: representación mediática del despojo

    Directory of Open Access Journals (Sweden)

    Neyla Graciela Pardo Abril

    2012-01-01

    Full Text Available La interacción comunicativa ocurre con frecuencia cuando se acude a sistemas de signos múltiples que se soportan, de manera significativa, en tecnologías y pretende interlocutores impredecibles. Desde esta perspectiva, la lengua es apenas un sistema sígnico y sus modos de significación se han amplificado. En este trabajo, de acuerdo con las teorías cognitivas, se entiende que la metáfora, como recurso semiótico, supera el uso de la lengua, se estructura en diversos sistemas de signos y formula saberes, pensamiento y acción social. Se estudia la metáfora producida y comprendida en diversos modos semióticos y se aplica a un proceso de investigación en curso, en el que se analizan cuatro caricaturas del periódico digital eltiempo.com y tres de elespectador.com, que forman parte de un corpus más amplio compilado en medios virtuales. Se proponen algunas reflexiones sobre la metáfora multimodal, su relación con la metáfora verbal y los procesos de amplificación de los significados que se derivan de una posible interpretación. Finalmente, se presentan algunas conclusiones sobre la representación mediática del despojo.

  20. Fluorescentievingerafdruk van Aardappel, Melganzenvoet en Mais : Eerste resultaten van plantonderscheid met behulp van fluorescentie

    NARCIS (Netherlands)

    Groot, T.T.; Nieuwenhuizen, A.T.

    2012-01-01

    Als het spectrum van één “soort” (gewas) vergeleken wordt met de rest (onkruid) neemt het onderscheid van het “gewas” af tot 70%. Het lijkt dus nodig ook de spectra van alle soorten onkruid in het veld te kennen om een goed onderscheid mogelijk te maken. De doelstelling voor deze metingen is een

  1. TFG-MET fusion in an infantile spindle cell sarcoma with neural features.

    Science.gov (United States)

    Flucke, Uta; van Noesel, Max M; Wijnen, Marc; Zhang, Lei; Chen, Chun-Liang; Sung, Yun-Shao; Antonescu, Cristina R

    2017-09-01

    An increasing number of congenital and infantile sarcomas displaying a primitive, monomorphic spindle cell phenotype have been characterized to harbor recurrent gene fusions, including infantile fibrosarcoma and congenital spindle cell rhabdomyosarcoma. Here, we report an unusual spindle cell sarcoma presenting as a large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The tumor resembled the morphology of an infantile fibrosarcoma with both fascicular and patternless growth, however, it expressed strong S100 protein immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression. Although this immunoprofile suggested partial neural/neuroectodermal differentiation, overall features were unusual and did not fit into any known tumor types (cellular schwannoma, MPNST), raising the possibility of a novel pathologic entity. The TFG-MET gene fusion expands the genetic spectrum implicated in the pathogenesis of congenital spindle cell sarcomas, with yet another example of kinase oncogenic activation through chromosomal translocation. The discovery of this new fusion is significant since the resulting MET activation can potentially be inhibited by targeted therapy, as MET inhibitors are presently available in clinical trials. © 2017 Wiley Periodicals, Inc.

  2. MET receptor tyrosine kinase controls dendritic complexity, spine morphogenesis, and glutamatergic synapse maturation in the hippocampus.

    Science.gov (United States)

    Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

    2014-12-03

    The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. Copyright © 2014 the authors 0270-6474/14/3416166-14$15.00/0.

  3. COMT Val(108/158)Met polymorphism effects on emotional brain function and negativity bias.

    Science.gov (United States)

    Williams, Leanne M; Gatt, Justine M; Grieve, Stuart M; Dobson-Stone, Carol; Paul, Robert H; Gordon, Evian; Schofield, Peter R

    2010-11-15

    Biases toward processing negative versus positive information vary as a function of level of awareness, and are modulated by monoamines. Excessive biases are associated with individual differences in mood and emotional stability, and emotional disorder. Here, we examined the impact of the catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism, involved in dopamine and norepinephrine catabolism, on both emotional brain function and self-reported negativity bias. COMT genotyping and self-reported level of negativity bias were completed for 46 healthy participants taking part in the Brain Resource International Database. Functional MRI was undertaken during perception of facial expressions of fear and happiness presented under unmasked (consciously identified) and masked (to prevent conscious detection) conditions. Structural MR images were also acquired. A greater number of COMT Met alleles predicted increased activation in brainstem, amygdala, basal ganglia and medial prefrontal regions for conscious fear, but decreased activation for conscious happiness. This pattern was also apparent for brainstem activation for the masked condition. Effects were most apparent for females. These differences could not be explained by gray matter variations. The Met-related profile of activation, particularly prefrontally, predicted greater negativity bias associated with risk for emotional disorder. The findings suggest that the COMT Met allele modulates neural substrates of negative versus positive emotion processing. This effect may contribute to negativity biases, which confer susceptibility for emotional disorders. Copyright 2010 Elsevier Inc. All rights reserved.

  4. COMT val108/158 met genotype affects neural but not cognitive processing in healthy individuals.

    Science.gov (United States)

    Dennis, Nancy A; Need, Anna C; LaBar, Kevin S; Waters-Metenier, Sheena; Cirulli, Elizabeth T; Kragel, James; Goldstein, David B; Cabeza, Roberto

    2010-03-01

    The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496-1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output.

  5. Ervaringen met een solid phase enzyme immunoassay voor het aantonen van gonorroe bij promiscue vrouwen

    NARCIS (Netherlands)

    Ulsen; J.van*; Michel; M.F.*; Strik; R.van*; Joost; T.H.van*; Stolz; E.*; Eijk; R.V.W.van

    1985-01-01

    De Gonozyme test (Abbott Laboratories), een nieuwe enzyme immunoassay (EIA) voor het aantonen van Neisseria gonorrhoeae werd geevalueerd in een grote groep promiscue vrouwen. Als de EIA werd uitgevoerd met materiaal afkomstig van de cervix, bedroeg de prevalentie van gonorroe 8,2%. Vergeleken

  6. Reconstruction of 3D structures of MET antibodies from electron microscopy 2D class averages.

    Directory of Open Access Journals (Sweden)

    Qi Chen

    Full Text Available Dynamics of three MET antibody constructs (IgG1, IgG2, and IgG4 and the IgG4-MET antigen complex was investigated by creating their atomic models with an integrative experimental and computational approach. In particular, we used two-dimensional (2D Electron Microscopy (EM images, image class averaging, homology modeling, Rapidly exploring Random Tree (RRT structure sampling, and fitting of models to images, to find the relative orientations of antibody domains that are consistent with the EM images. We revealed that the conformational preferences of the constructs depend on the extent of the hinge flexibility. We also quantified how the MET antigen impacts on the conformational dynamics of IgG4. These observations allow to create testable hypothesis to investigate MET biology. Our protocol may also help describe structural diversity of other antigen systems at approximately 5 Å precision, as quantified by Root-Mean-Square Deviation (RMSD among good-scoring models.

  7. Self-perceived met and unmet care needs of frail older adults in primary care

    NARCIS (Netherlands)

    Hoogendijk, Emiel O; Muntinga, Maaike E; van Leeuwen, Karen M; van der Horst, Henriëtte E; Deeg, Dorly J H; Frijters, Dinnus H M; Hermsen, Lotte A H; Jansen, Aaltje P D; Nijpels, Giel; van Hout, Hein P J

    2013-01-01

    In order to provide adequate care for frail older adults in primary care it is essential to have insight into their care needs. Our aim was to describe the met and unmet care needs as perceived by frail older adults using a multi-dimensional needs assessment, and to explore their associations with

  8. Simple and effective procedure for conformational search of macromolecules. Application to Met- and Leu-Enkephalin

    Energy Technology Data Exchange (ETDEWEB)

    Meirovitch, H.; Meirovitch, E. (Florida State Univ., Tallahassee, FL (United States)); Michel, A.G. (Institut de Recherches Serrier, Suresnes (France)); Vasquez, M. (Protein Design Lab., Mountain View, CA (United States))

    1994-06-23

    A simple and efficient method for searching the conformational space of macromolecules is presented. With this method an initial set of relatively low-energy structures is generated, and their energies are further minimized with a procedure that enables escaping from local energy minima. Illustrative calculations are described for Met- and Leu-enkephalin. 37 refs., 1 tab.

  9. 75 FR 44289 - MET Laboratories, Inc.; Application for Expansion of Recognition

    Science.gov (United States)

    2010-07-28

    ... connection with this request, NRTL Program staff did not perform an on-site review of MET's recognized sites...-Finishing Machines UL 1230 Amateur Movie Lights UL 1278 Movable and Wall or Ceiling Hung Electric Room... acceptable request for expansion of its recognition as an NRTL. OSHA's review of the application file and...

  10. Ei van Columbus of paard van Troje : Inoculeren met zwakke pepinostam

    NARCIS (Netherlands)

    Boonekamp, G.; Vlugt, van der R.A.A.

    2010-01-01

    Pepino mozaïekvirus lijkt een onvermijdelijk probleem in de tomatenteelt. De vrij milde virusstammen uit de beginperiode zijn bijna volledig verdrongen door agressieve vormen. Veel stemmen gaan op voor inenten met een zwakke virusstam, maar is dat wel zo slim?

  11. A user's guide to the MultiMet Sensor Management and Calibration Facility

    OpenAIRE

    Pascal, R.W.; Williams, A.; Ahmed, R.

    1991-01-01

    The report describes the operating instructions and procedures for the MultiMet Sensor Management and Calibration Facility. This includes a description of the Meteological database ME'IDB, and the Sensor Management database which organises the large number of sensors required by the Multimet System. Calibration procedures and policies are also described for the various types of sensors used.

  12. Instructional Coding System for Mathematics Program of Studies. MET, A Title IV-C Project.

    Science.gov (United States)

    Fairfax County Public Schools, VA. Dept. of Instructional Services.

    This document is part of the Management for Effective Teaching (MET) support kit, a pilot project designed by the Fairfax County (Virginia) Public Schools to assist elementary school teachers in planning, managing, and implementing the county's Program of Studies (POS). This document provides an alpha-numeric coding system to be used in…

  13. Robots niet langer Science Fiction: scenario's voor de samenwerking met robots

    NARCIS (Netherlands)

    Popma, J.

    2015-01-01

    Hoewel industriële robots al jaren bestaan, lijkt hun opmars nu toch echt begonnen. Diverse scenario's buitelen over elkaar: hoeveel banen gaat dit kosten? Maar zeker zo interessant is wat de robotisering betekent voor de werknemers die wél hun baan houden. Hoe gaan die samenwerken met robots? En

  14. Intracardiale chirurgie met behulp van een cirrestor : een experimentele en klinische studie

    NARCIS (Netherlands)

    Homan van der Heide, Jan Nico

    1960-01-01

    SAMENVATTING De intracardiale chirurgie is op grote schaal mogelijk geworden dank zij het feit, dat afwijkingen in bloedvrije hartholten met direct zicht hersteld kunnen worden. Voordat de operatieve correctie plaats vindt, moet de patient in een bepaalde, voor de operatie geschikte conditie

  15. A meteorological distribution system for high-resolution terrestrial modeling (MicroMet)

    Science.gov (United States)

    Glen E. Liston; Kelly Elder

    2006-01-01

    An intermediate-complexity, quasi-physically based, meteorological model (MicroMet) has been developed to produce high-resolution (e.g., 30-m to 1-km horizontal grid increment) atmospheric forcings required to run spatially distributed terrestrial models over a wide variety of landscapes. The following eight variables, required to run most terrestrial models, are...

  16. Validation Engine for Observational Protocols. Measures of Effective Teaching (MET) Project

    Science.gov (United States)

    Bill & Melinda Gates Foundation, 2010

    2010-01-01

    In the fall of 2009, the Bill and Melinda Gates Foundation launched the two-year Measures of Effective Teaching (MET) project to rigorously develop and test multiple measures of teacher effectiveness. As part of the project, partners from more than a dozen reputable academic, non-profit and for-profit organizations collected and analyzed data from…

  17. Operationalisering van de flow-injectietechniek in combinatie met ICP-MS

    NARCIS (Netherlands)

    Velde-Koerts T van der; Boer JLM de; LAC

    1994-01-01

    In dit onderzoek werd de flow-injectietechniek gecombineerd met ICP-MS. Hoewel de onderste analysegrenzen iets hoger waren dan bij continue verstuiving, heeft de flow-injectietechniek een aantal belangrijke voordelen: ten eerste het kleine monstervolume dat nodig is voor de analyse (0,7 ml,

  18. Prestatiekenmerken van een TotalQuant-elementanalyse met ICP-MS

    NARCIS (Netherlands)

    Velde-Koerts T van der; LAC

    1998-01-01

    TotalQuant-analyse met ICP-MS is een geschikte methode om snel oplossingen van diverse materialen te scannen op alle elementen van het periodieke systeem, behalve H, N, O, F, edelgassen en kortlevende (radio-actieve) elementen. Bij een TotalQuant-analyse wordt gebruik gemaakt van een standaard

  19. Operational assimilation of ASCAT surface soil wetness at the Met Office

    Directory of Open Access Journals (Sweden)

    I. Dharssi

    2011-08-01

    Full Text Available Currently, no extensive, near real time, global soil moisture observation network exists. Therefore, the Met Office global soil moisture analysis scheme has instead used observations of screen temperature and humidity. A number of new space-borne remote sensing systems, operating at microwave frequencies, have been developed that provide a more direct retrieval of surface soil moisture. These systems are attractive since they provide global data coverage and the horizontal resolution is similar to weather forecasting models. Several studies show that measurements of normalised backscatter (surface soil wetness from the Advanced Scatterometer (ASCAT on the meteorological operational (MetOp satellite contain good quality information about surface soil moisture. This study describes methods to convert ASCAT surface soil wetness measurements to volumetric surface soil moisture together with bias correction and quality control. A computationally efficient nudging scheme is used to assimilate the ASCAT volumetric surface soil moisture data into the Met Office global soil moisture analysis. This ASCAT nudging scheme works alongside a soil moisture nudging scheme that uses observations of screen temperature and humidity. Trials, using the Met Office global Unified Model, of the ASCAT nudging scheme show a positive impact on forecasts of screen temperature and humidity for the tropics, North America and Australia. A comparison with in-situ soil moisture measurements from the US also indicates that assimilation of ASCAT surface soil wetness improves the soil moisture analysis. Assimilation of ASCAT surface soil wetness measurements became operational during July 2010.

  20. Tracking and orbit determination performance of the GRAS instrument on MetOp-A

    NARCIS (Netherlands)

    Montenbruck, O.; Andres, Y.; Bock, H.; Van Helleputte, T.; Van den IJssel, J.; Loiselet, M.; Marquardt, M.; Silvestrin, P.; Visser, P.; Yoon, Y.

    2008-01-01

    The global navigation satellite system receiver for atmospheric sounding (GRAS) on MetOp-A is the first European GPS receiver providing dual-frequency navigation and occultation measurements from a spaceborne platform on a routine basis. The receiver is based on ESA’s AGGA-2 correlator chip, which

  1. Schermgebruik en blauw licht : Omvang van blootstelling en relatie met slaap

    NARCIS (Netherlands)

    van Kerkhof LWM; Vlaanderen JJ; Berkhout AJC; Dollé MET; Vermeulen RCH; van Steeg H; EVG; V&Z

    2017-01-01

    Veel volwassenen (58 procent) gebruiken in het laatste uur voordat ze gaan slapen een tablet, smartphone of computer. Ze doen dit meerdere keren per week of dagelijks. Het gebruik van deze apparaten kort voor het slapen gaat gepaard met minder en slechter slapen. Of het blauwe licht van deze

  2. Patterns of learning organisation in Estonian companies / Tõnis Mets, Made Torokoff

    Index Scriptorium Estoniae

    Mets, Tõnis, 1952-

    2007-01-01

    Uuringu eesmärgiks on määratleda õppiva organisatsiooni põhiomadused ja hinnata organisatsioonilise õppimise olukorda Eesti tootmisettevõtetes. Empiirilise uuringu põhimudelid tulenevad Senge viiest distsipliinist ja Mets'ia kolmedimensioonilisest õppimise raamistikust. Tabelid

  3. The Association between Symptoms of Dry Eye Syndrome and Metabolic Outcome in a General Population in Korea.

    Science.gov (United States)

    Park, Hye Won; Park, Jong Woon

    2016-07-01

    Dry eye syndrome (DES) is recognized as a public health concern. One of the pathophysiologies in the development of DES is inflammation, and metabolic syndrome (MetS), which is highly prevalent in the general population, is a well-known chronic and systemic inflammatory condition. Despite the increasing interest regarding a relationship between DES and MetS, information is lacking on the association between DES and MetS and its individual components. We investigated the association between DES symptoms and MetS and its components among adults aged ≥ 19 years using population-based data from the Korea National Health and Nutrition Examination Survey V. A sample group of 15,294 adults (42.67% men and 57.33% women) completed household interviews in which they provided blood (for high-density lipoprotein cholesterol, triglyceride, and glucose) and anthropometric measurements (including waist circumference, weight, and height) to define MetS. We also collected information regarding sociodemographic and behavioral risk factors. The survey results showed that 11.50% of men and 22.35% of women experienced DES and 5.30% of patients had both DES and diagnosis of MetS, including 204 men and 606 women. Thus, no significant difference was observed between DES and the diagnosis of MetS according to sex (P = 0.4008 in men; P = 0.0804 in women); however, a significant association was observed between DES and hypertriglyceridemia in women (OR, 1.13; 95% CI, 1.01-1.29). Therefore, hypertriglyceridemia might be an important factor in the association between DES and MetS. Further longitudinal research is needed to evaluate this relationship.

  4. Improvement with insight. Healthier indoor climate and lower energy consumption with wireless Sensor networks; Verbeteren met inzicht. Gezonder binnenklimaat en lager energiegebruik met draadloze Sensor netwerken

    Energy Technology Data Exchange (ETDEWEB)

    Peekstok, E.J. [MakeMoreSense, Sommelsdijk (Netherlands)

    2010-11-15

    Wireless Sensor Networks connected to the internet will dramatically influence the future of Indoor Climate and Energy use. Munisense, a Dutch company, has developed a real-time and web-based monitoring tool called InSightNow. With Insight it is possible to improve the environment, often with very simple measures. The majority of things going wrong are caused by human interventions. For example engineers when programming installations and users adjusting settings. Giving people insight in their behaviour via a 'dashboard for buildings', creates awareness and makes it possible to improve. Installers are able to limit failure cost, improve quality of service and contribute to the customers success by limiting sick-leave, improve work performance, reduce energy cost and unused floor space. [Dutch] Het is noodzakelijk om in schoolgebouwen een blijvend gezond binnenklimaat te creeren, want binnenklimaat, ziekteverzuim en leerprestaties hebben volgens wetenschappelijk onderzoek een direct verband met elkaar. Netwerken met draadloze sensors kunnen daar een rol bij spelen.

  5. Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism.

    Science.gov (United States)

    Asthana, Manish Kumar; Brunhuber, Bettina; Mühlberger, Andreas; Reif, Andreas; Schneider, Simone; Herrmann, Martin J

    2016-06-01

    Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans. An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265. The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation. Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  6. Oxidative stress inactivates cobalamin-independent methionine synthase (MetE in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Elise R Hondorp

    2004-11-01

    Full Text Available In nature, Escherichia coli are exposed to harsh and non-ideal growth environments-nutrients may be limiting, and cells are often challenged by oxidative stress. For E. coli cells confronting these realities, there appears to be a link between oxidative stress, methionine availability, and the enzyme that catalyzes the final step of methionine biosynthesis, cobalamin-independent methionine synthase (MetE. We found that E. coli cells subjected to transient oxidative stress during growth in minimal medium develop a methionine auxotrophy, which can be traced to an effect on MetE. Further experiments demonstrated that the purified enzyme is inactivated by oxidized glutathione (GSSG at a rate that correlates with protein oxidation. The unique site of oxidation was identified by selectively cleaving N-terminally to each reduced cysteine and analyzing the results by liquid chromatography mass spectrometry. Stoichiometric glutathionylation of MetE by GSSG occurs at cysteine 645, which is strategically located at the entrance to the active site. Direct evidence of MetE oxidation in vivo was obtained from thiol-trapping experiments in two different E. coli strains that contain highly oxidizing cytoplasmic environments. Moreover, MetE is completely oxidized in wild-type E. coli treated with the thiol-oxidizing agent diamide; reduced enzyme reappears just prior to the cells resuming normal growth. We argue that for E. coli experiencing oxidizing conditions in minimal medium, MetE is readily inactivated, resulting in cellular methionine limitation. Glutathionylation of the protein provides a strategy to modulate in vivo activity of the enzyme while protecting the active site from further damage, in an easily reversible manner. While glutathionylation of proteins is a fairly common mode of redox regulation in eukaryotes, very few proteins in E. coli are known to be modified in this manner. Our results are complementary to the independent findings of Leichert

  7. Pasarela metálica excéntrica suspendida y apoyada en un arco metálico en Orense, España

    Directory of Open Access Journals (Sweden)

    Besiga Díaz-Blanco, Julio

    2007-12-01

    Full Text Available The article explains the design and project of a steel footbridge, suspended and supported by an eccentric arc, situated in Orense. The footbridge, known as “Bellour”, has a main span of 20 meters, with a leaned steel eccentric arc that supports the deck. The deck was designed with a uniform slope of 8%, due the difference of level between each end. It is suspended from the arc in the Orense side and supported in the other boarder, because of the headway limitations. The deck is 2,80 meters wide. The cross section is composed of a steel eccentric tube with steel cantilever beams, of variable depth, and is joined at the other edge to a small steel tube. The pedestrian zone is narrower than the board, leaving individual empty spaces at both sides, and is constituted by a structural concrete slab of 7 centimeters thick and 2 meters wide, linked to the deck top sheet, with a steel profiles. The board was designed with a structural skeleton, spine shaped, suspended or supported from the arc, and it´s joined to the skin, a rough concrete surface that avoids frost and slides due to the rain.En este artículo se expone el diseño de una pasarela metálica excéntrica suspendida y apoyada en un arco metálico situada en la ciudad de Orense. La pasarela, conocida por «Bellour», tiene un único vano de 20 metros de luz, soportado excéntricamente por un arco metálico inclinado. Las cotas de inicio y fin de la pasarela obligaron a diseñar un tablero inclinado que está suspendido del arco en el lado Orense y apoyado en el otro extremo al permitirlo el gálibo de la carretera. La sección transversal del tablero está formada por un tubo excéntrico del que parten unas ménsulas metálicas de canto variable, unidas en su otro extremo por otro tubo más pequeño. El pavimento de la pasarela, que es más estrecho que el propio tablero, dejando sendos espacios vacíos a ambos lados, está formado por una losa de hormigón armado conectada a

  8. Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

    Science.gov (United States)

    Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

    2006-07-01

    Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

  9. Correlation among genetic variations of c-MET in Chinese patients with non-small cell lung cancer.

    Science.gov (United States)

    Duan, Jianchun; Yang, Xiaodan; Zhao, Jun; Zhuo, Minglei; Wang, Zhijie; An, Tongtong; Bai, Hua; Wang, Jie

    2018-01-05

    The purpose of our research was to determine the correlation of amplification, protein expression and somatic mutation of c-MET in IIIb-IV stage NSCLC (Non-small cell lung cancer). We also explored correlation of c-MET variation with clinical outcome. c-MET expression was observed in 28.6% (56/196) cases, and among those 13.8% (27/196) were shown to be FISH positive. Only 2.67% patients in this study carried the c-MET mutation. Cases with c-MET FISH positive were all IHC positive ,but in IHC positive cases, only half were FISH positive. Among patients with IHC 2+ staining, 35.5% was FISH positive, while cases with IHC 3+ staining,64% was FISH positive. Both protein expression and copy number of c-MET did not significantly correlate with clinical prognosis in these patients treated with EGFR-TKIs. IHC could be used as a preliminary screening method for c-MET copy number amplification and should be confirmed by FISH only in IHC positive case which facilitate selection of ALK or MET inhibitor therapy. c-MET gene copy number, protein expression and somatic mutation for exon 14 were detected by fluorescent- In-Situ -Hybridization (FISH), Immunohistochemistry (IHC), and Denaturing-High-Performance-Liquid-Chromatography (DHPLC), respectively, in 196 NSCLC patients. The relationship between c-MET abnormalities and clinical outcome of targeted therapy was analyzed by McNemar's test.

  10. Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress

    Directory of Open Access Journals (Sweden)

    Tsuru J

    2014-11-01

    Full Text Available Jusen Tsuru,1 Yoshihiro Tanaka,1 Yoshinobu Ishitobi,1 Yoshihiro Maruyama,1 Ayako Inoue,1 Aimi Kawano,1 Rie Ikeda,1 Tomoko Ando,1 Harumi Oshita,2 Saeko Aizawa,1 Koji Masuda,1 Haruka Higuma,1 Masayuki Kanehisa,1 Taiga Ninomiya,1 Jotaro Akiyoshi1 1Department of Neuropsychiatry, 2Department of Applied Linguistics, Faculty of Medicine, Oita University, Oita, Japan Background: Decreased expression of brain-derived neurotrophic factor (BDNF is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder.Methods: To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men using a social stress procedure (Trier Social Stress Test [TSST] and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A.Results: A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; P<0.05 was demonstrated that revealed different salivary cortisol responses in the TSST but not in electrical stimulation. Met/Met women had stronger cortisol responses than Val/Met and Val/Val individuals in the TSST. Met/Met men exhibited stronger salivary cortisol responses than Val/Met and Val/Val individuals in the TSST.Conclusion: These results indicate that a common, functionally significant polymorphism in BDNF had different effects on hypothalamic–pituitary–adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests. Keywords: stress, brain-derived neurotrophic factor, cortisol, saliva

  11. Generalizing quasinormality

    Directory of Open Access Journals (Sweden)

    John Cossey

    2015-03-01

    Full Text Available Quasinormal subgroups have been studied for nearly 80 years. In finite groups, questions concerning them invariably reduce to p-groups, and here they have the added interest of being invariant under projectivities, unlike normal subgroups. However, it has been shown recently that certain groups, constructed by Berger and Gross in 1982, of an important universal nature with regard to the existence of core-free quasinormal subgroups gener- ally, have remarkably few such subgroups. Therefore in order to overcome this misfortune, a generalization of the concept of quasi- normality will be defined. It could be the beginning of a lengthy undertaking. But some of the initial findings are encouraging, in particular the fact that this larger class of subgroups also remains invariant under projectivities of finite p-groups, thus connecting group and subgroup lattice structures.

  12. The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress.

    Science.gov (United States)

    Alexander, Nina; Osinsky, Roman; Schmitz, Anja; Mueller, Eva; Kuepper, Yvonne; Hennig, Juergen

    2010-07-01

    Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date. Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity. Healthy male adults (N=100) were genotyped and exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol and self-reported mood levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Furthermore, heart rate reactivity as an indicator of sympathetic activation was monitored continuously during the experimental procedure. We report a small, but significant effect of the BDNF Val66Met polymorphism on stress reactivity. More precisely, carriers of the met-allele showed a significantly attenuated HPA-axis and cardiovascular reactivity to the psychosocial stressor compared to subjects with the val/val genotype. Furthermore, the diminished physiological response in met-allele carriers was also attended by significantly lower self-reported ratings of perceived stress and nervousness. Our findings of a diminished endocrine and cardiovascular stress response in healthy male adults is consistent with a previously published study and adds further evidence for a crucial role of the BDNF Val66Met polymorphism in the modulation of stress reactivity. Copyright 2010. Published by Elsevier Ltd.

  13. Association of BDNF Val66Met Polymorphism and Brain BDNF levels with Major Depression and Suicide.

    Science.gov (United States)

    Youssef, Mariam M; Underwood, Mark D; Huang, Yung-Yu; Hsiung, Shu-Chi; Liu, Yan; Simpson, Norman R; Bakalian, Mihran J; Rosoklija, Gorazd B; Dwork, Andrew J; Arango, Victoria; Mann, J John

    2018-02-08

    Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depressive disorder (MDD) and suicide. Both are partly caused by early life adversity (ELA) and ELA reduces BDNF protein levels. This study examines the association of BDNF Val66Met polymorphism and brain BDNF levels with depression and suicide. We hypothesized that both MDD and ELA would be associated with the Met allele and lower brain BDNF levels. Such an association would be consistent with low BDNF mediating the effect of ELA on adulthood suicide and MDD. BDNF Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 non-suicides. Additionally, BDNF protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9; BA9), anterior cingulate cortex (ACC, BA24), caudal brainstem and rostral brainstem. The relationships between these measures and MDD, death by suicide and reported ELA were examined. Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower BDNF levels in ACC and caudal brainstem compared with non-depressed subjects. No effect of history of suicide death or ELA was observed with genotype, but lower BDNF levels in ACC were found in subjects who had been exposed to ELA and/or died by suicide compared to non-suicide decedents and no reported ELA. This study provides further evidence implicating low brain BDNF and the BDNF Met allele in major depression risk. Future studies should seek to determine how altered BDNF expression contributes to depression and suicide. © The Author(s) 2018. Published by Oxford University Press on behalf of CINP.

  14. General report

    International Nuclear Information System (INIS)

    Nicklisch, F.

    1984-01-01

    Growing complexity of technical matter has meant that technical expertise is called upon in more and more legal proceedings. The technical expert is, in general terms, the mediator between technology and the law, he is also entrusted with the task of pointing up the differences in approach and in the nature of authority in these two areas and thus paving the way for mutual understanding. The evaluation of the technical expert's opinion is one of the cardinal problems bound up with the role of the expert in legal procedure. After the presentation of the expert's opinion, the judge is supposed to possess so much specialised knowledge that he can assess the opinion itself in scientific and technical respects and put his finger on any errors the expert may have made. This problem can only be solved via an assessment opinion. First of all, the opinion can be assessed indirectly via evaluation of the credentials and the neutrality and independence of the expert. In direct terms, the opinion can be subjected to a certain - albeit restricted - scrutiny, whether it is generally convincing, as far as the layman is competent to judge. This interpretation alone makes it possible to classify and integrate legally the technical standards and regulations represent expert statements on the scientific and technical theorems based on the knowledge and experience gained in a given area. They are designed to reflect prevailing opinion among leading representatives of the profession and can thus themselves be regarded as expert opinions. As a rule, these opinions will have such weight that - other than in exceptional cases - they will not be invalidated in procedure by deviating opinions from individual experts. (orig./HSCH) [de

  15. Discovery of imidazopyridine derivatives as novel c-Met kinase inhibitors: Synthesis, SAR study, and biological activity.

    Science.gov (United States)

    Yang, Yifei; Zhang, Yuan; Yang, LingYun; Zhao, Leilei; Si, Lianghui; Zhang, Huibin; Liu, Qingsong; Zhou, Jinpei

    2017-02-01

    Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar potency against c-Met in both biochemical enzymatic screens and cellular pharmacology studies. Especially, compound 7g exhibited the most inhibitory activity against c-Met with IC 50 of 53.4nM and 253nM in enzymatic and cellular level, respectively. Following that, the compound 7g was docked into the protein of c-Met and the structure-activity relationship was analyzed in detail. These findings indicated that the novel imidazopyridine derivative compound 7g was a potential c-Met inhibitor deserving further investigation for cancer treatment. Copyright © 2016. Published by Elsevier Inc.

  16. Cathecol-O-methyl transferase Val158Met genotype is not a risk factor for conversion disorder.

    Science.gov (United States)

    Armagan, E; Almacıoglu, M L; Yakut, T; Köse, A; Karkucak, M; Köksal, O; Görükmez, O

    2013-03-19

    Alterations in catechol-O-methyltransferase (COMT) activity are involved in various types of neurological disorders. We examined a possible association between the COMT Val158Met polymorphism and conversion disorder in a study of 48 patients with conversion disorder and 48 control patients. In the conversion disorder group, 31 patients were Val/Met heterozygotes, 15 patients were Val/Val homozygotes and 2 patients were Met/Met homozygotes. In the control group, 32 patients were Val/Met heterozygotes and 16 patients were Val/Val homozygotes. There was no significant difference between the groups. We conclude that the COMT Val158Met genotype is quite common in Turkey and that it is not a risk factor for conversion disorder in the Turkish population.

  17. COMT Val158 Met moderates the link between rank and aggression in a non-human primate.

    Science.gov (United States)

    Gutleb, D R; Roos, C; Noll, A; Ostner, J; Schülke, O

    2018-04-01

    The COMT Val 158 Met polymorphism is one of the most widely studied genetic polymorphisms in humans implicated in aggression and the moderation of stressful life event effects. We screened a wild primate population for polymorphisms at the COMT Val 158 Met site and phenotyped them for aggression to test whether the human polymorphism exists and is associated with variation in aggressive behavior. Subjects were all adults from 4 study groups (37 males, 40 females) of Assamese macaques (Macaca assamensis) in their natural habitat (Phu Khieo Wildlife Sanctuary, Thailand). We collected focal animal behavioral data (27 males, 36 females, 5964 focal hours) and fecal samples for non-invasive DNA analysis. We identified the human COMT Val 158 Met polymorphism (14 Met/Met, 41 Val/Met and 22 Val/Val). Preliminary results suggest that COMT genotype and dominance rank interact to influence aggression rates. Aggression rates increased with rank in Val/Val, but decreased in Met/Met and Val/Met individuals, with no significant main effect of COMT genotype on aggression. Further support for the interaction effect comes from time series analyses revealing that when changing from lower to higher rank position Val/Val individuals decreased, whereas Met/Met individuals increased their aggression rate. Contradicting the interpretation of earlier studies, we show that the widely studied Val 158 Met polymorphism in COMT is not unique to humans and yields similar behavioral phenotypes in a non-human primate. This study represents an important step towards understanding individual variation in aggression in a wild primate population and may inform human behavioral geneticists about the evolutionary roots of inter-individual variation in aggression. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  18. Brain-derived neurotrophic factor Val66Met polymorphism and hippocampal activation during episodic encoding and retrieval tasks

    OpenAIRE

    Dennis, Nancy A.; Cabeza, Roberto; Need, Anna C.; Waters-Metenier, Sheena; Goldstein, David B.; LaBar, Kevin S.

    2010-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin which has been shown to regulate cell survival and proliferation, as well as synaptic growth and hippocampal long-term potentiation. A naturally occurring single nucleotide polymorphism in the human BDNF gene (val66met) has been associated with altered intercellular trafficking and regulated secretion of BDNF in met compared to val carriers. Additionally, previous studies have found a relationship between the BDNF val66met genotype an...

  19. Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis

    OpenAIRE

    Maida Rakanović-Todić; Lejla Burnazović-Ristić; Slavka Ibrulj; Nedžad Mulabegović

    2014-01-01

    Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of t...

  20. Transition of NOAA's GPS-Met Data Acquisition and Processing System to the Commercial Sector

    Science.gov (United States)

    Jackson, M. E.; Holub, K.; Callahan, W.; Blatt, S.

    2014-12-01

    In April of 2014, NOAA/OAR/ESRL Global Systems Division (GSD) and Trimble, in collaboration with Earth Networks, Inc. (ENI) signed a Cooperative Research and Development Agreement (CRADA) to transfer the existing NOAA GPS-Met Data Acquisition and Processing System (GPS-Met DAPS) technology to a commercial Trimble/ENI partnership. NOAA's GPS-Met DAPS is currently operated in a pseudo-operational mode but has proven highly reliable and running at over 95% uptime. The DAPS uses the GAMIT software to ingest dual frequency carrier phase GPS/GNSS observations and ancillary information such as real-time satellite orbits to estimate the zenith-scaled tropospheric (ZTD) signal delays and, where surface MET data are available, retrieve integrated precipitable water vapor (PWV). The NOAA data and products are made available to end users in near real-time. The Trimble/ENI partnership will use the Trimble Pivot™ software with the Atmosphere App to calculate zenith tropospheric (ZTD), tropospheric slant delay, and integrated precipitable water vapor (PWV). Evaluation of the Trimble software is underway starting with a comparison of ZTD and PWV values determined from GPS stations located near NOAA Radiosonde Observation (Upper-Air Observation) launch sites. A success metric was established that requires Trimble's PWV estimates to match ESRL/GSD's to within 1.5 mm 95% of the time, which corresponds to a ZTD uncertainty of less than 10 mm 95% of the time. Initial results indicate that Trimble/ENI data meet and exceed the ZTD metric, but for some stations PWV estimates are out of specification. These discrepancies are primarily due to how offsets between MET and GPS stations are handled and are easily resolved. Additional test networks are proposed that include low terrain/high moisture variability stations, high terrain/low moisture variability stations, as well as high terrain/high moisture variability stations. We will present results from further testing along with a timeline

  1. Sex- and age-specific associations between major depressive disorder and metabolic syndrome in two general population samples in Germany.

    Science.gov (United States)

    Block, Andrea; Schipf, Sabine; Van der Auwera, Sandra; Hannemann, Anke; Nauck, Matthias; John, Ulrich; Völzke, Henry; Freyberger, Harald Jürgen; Dörr, Marcus; Felix, Stephan; Zygmunt, Marek; Wallaschofski, Henri; Grabe, Hans Jörgen

    2016-11-01

    Major depressive disorder (MDD) has been associated with the Metabolic Syndrome (MetS). As previous data strongly suggested sex and age effects on this association, this study aimed to analyse the association between MDD and MetS in two general population samples under explicit consideration of sex and age. This study analysed cross-sectional data based on two independent general population samples: SHIP-0 (n = 4083; 20-81 years; 49.4% male) and SHIP-TREND-0 (n = 3957; 20-83 years; 49.0% male) that were part of the Study of Health in Pomerania. MDD (SHIP-0: 12.6%; SHIP-TREND-0: 27.2%) was assessed using the Composite International Diagnostic-Screener (CID-S) in both samples. Interview assessment of MDD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria was performed in SHIP-TREND-0 (18.1% MDD). MetS was defined by abdominal obesity, elevated blood pressure, elevated glucose, elevated triglycerides and reduced high-density lipoprotein cholesterol according to established criteria. Data analysis was performed sex- and age-stratified. Prevalence of MetS was high in both samples: 19.4% of females and 30.2% of males in SHIP-0 and 22.1% and 33.2% in SHIP-TREND-0, respectively. Effect modifications were observed by sex and age on the association between MDD and MetS. Particularly, younger females (20-49 years) with MDD were more often affected by MetS than younger females without MDD: OR = 2.21 (95% CI = 1.39-3.50). This association vanished in elderly participants (50-82 years). The data suggest that especially younger (presumably pre-menopausal) females with MDD are more likely to have MetS than those without major depressive disorders, and that age extenuates this association.

  2. Expression of the c-Met oncogene by tumor cells predicts a favorable outcome in classical Hodgkin's lymphoma.

    Science.gov (United States)

    Xu, Chuanhui; Plattel, Wouter; van den Berg, Anke; Rüther, Nele; Huang, Xin; Wang, Miao; de Jong, Debora; Vos, Hans; van Imhoff, Gustaaf; Viardot, Andreas; Möller, Peter; Poppema, Sibrand; Diepstra, Arjan; Visser, Lydia

    2012-04-01

    The c-Met signaling pathway regulates a variety of biological processes, including proliferation, survival and migration. Deregulated c-Met activation has been implicated in the pathogenesis and prognosis of many human malignancies. We studied the function and prognostic significance of c-Met and hepatocyte growth factor protein expression in patients with classical Hodgkin's lymphoma. Expression of c-Met and its ligand, hepatocyte growth factor, were determined by immunohistochemistry. Prognostic values were defined in cohorts of German and Dutch patients with classical Hodgkin's lymphoma. Functional studies were performed on Hodgkin's lymphoma cell lines. Expression of c-Met was detected in the tumor cells of 52% (80/153) of the patients and expression of its ligand, hepatocyte growth factor, in 8% (10/121) of the patients. c-Met expression correlated with a 5-year freedom from tumor progression of 94%, whereas lack of expression correlated with a 5-year freedom from tumor progression of 73% (Pfreedom from tumor progression. In functional studies activation with hepatocyte growth factor did not affect cell growth, while the c-Met inhibitor SU11274 suppressed cell growth by inducing G2/M cell cycle arrest. Although functional studies showed an oncogenic role of the hepatocyte growth factor/c-Met signaling pathway in cell cycle progression, expression of c-Met in tumor cells from patients with classical Hodgkin's lymphoma strongly correlated with a favorable prognosis in two independent cohorts.

  3. MET18 Deficiency Increases the Sensitivity of Yeast to Oxidative Stress and Shortens Replicative Lifespan by Inhibiting Catalase Activity.

    Science.gov (United States)

    Chen, Ya-Qin; Liu, Xin-Guang; Zhao, Wei; Cui, Hongjing; Ruan, Jie; Yuan, Yuan; Tu, Zhiguang

    2017-01-01

    Yeast MET18 , a subunit of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery which is responsible for the maturation of Fe/S proteins, has been reported to participate in the oxidative stress response. However, the underlying molecular mechanisms remain unclear. In this study, we constructed a MET18/met18Δ heterozygous mutant yeast strain and found that MET18 deficiency in yeast cells impaired oxidative stress resistance as evidenced by increased sensitivity to hydrogen peroxide (H 2 O 2 ) and cumene hydroperoxide (CHP). Mechanistically, the mRNA levels of catalase A (CTA1) and catalase T (CTT1) as well as the total catalase activity were significantly reduced in MET18 -deficient cells. In contrast, overexpression of CTT1 or CTA1 in MET18 -deficient cells significantly increased the intracellular catalase activity and enhanced the resistance ability against H 2 O 2 and CHP. In addition, MET18 deficiency diminished the replicative capacity of yeast cells as evidenced by the shortened replicative lifespan, which can be restored by CTT1 overexpression, but not by CTA1 , in the MET18 -deficient cells. These results suggest that MET18 , in a catalase-dependent manner, plays an essential role in enhancing the resistance of yeast cells to oxidative stress and increasing the replicative capacity of yeast cells.

  4. The resolution sensitivity of the Asian summer monsoon and its inter-model comparison between MRI-AGCM and MetUM

    Science.gov (United States)

    Ogata, Tomomichi; Johnson, Stephanie J.; Schiemann, Reinhard; Demory, Marie-Estelle; Mizuta, Ryo; Yoshida, Kohei; Osamu Arakawa

    2017-11-01

    In this study, we compare the resolution sensitivity of the Asian Summer Monsoon (ASM) in two Atmospheric General Circulation Models (AGCMs): the MRI-AGCM and the MetUM. We analyze the MetUM at three different resolutions, N96 (approximately 200-km mesh on the equator), N216 (90-km mesh) and N512 (40-km mesh), and the MRI-AGCM at TL95 (approximately 180-km mesh on the equator), TL319 (60-km mesh), and TL959 (20-km mesh). The MRI-AGCM and the MetUM both show decreasing precipitation over the western Pacific with increasing resolution, but their precipitation responses differ over the Indian Ocean. In MRI-AGCM, a large precipitation increase appears off the equator (5-20°N). In MetUM, this off-equatorial precipitation increase is less significant and precipitation decreases over the equator. Moisture budget analysis demonstrates that a changing in moisture flux convergence at higher resolution is related to the precipitation response. Orographic effects, intra-seasonal variability and the representation of the meridional thermal gradient are explored as possible causes of the resolution sensitivity. Both high-resolution AGCMs (TL959 and N512) can represent steep topography, which anchors the rainfall pattern over south Asia and the Maritime Continent. In MRI-AGCM, representation of low pressure systems in TL959 also contributes to the rainfall pattern. Furthermore, the seasonal evolution of the meridional thermal gradient appears to be more accurate at higher resolution, particularly in the MRI-AGCM. These findings emphasize that the impact of resolution is only robust across the two AGCMs for some features of the ASM, and highlights the importance of multi-model studies of GCM resolution sensitivity.

  5. Una metáfora Cervantina: el norte de la Caballería andante

    Directory of Open Access Journals (Sweden)

    Mitja Skubic

    1993-12-01

    Full Text Available El punto de partida es la concepción tradicional de la metáfora, magistralmente presentada en las obras de Stephen Ullmann; aceptamos también su clasificación en metaforas antropomórficas, animates y sinestésicas, a las que el lingüista húngaro añade una cuarta metáfora donde las experiencias abstractas se expresan por medio de términos concretos. Querríamos tomar en consideración unas metafóras El Quijote donde un término concreto sustituye a otro: tertium comparationis es una cualidad del mundo material, luminosidad, y el término sustitutivo, metafórico, que cbntiene el sema /luminosidad/, sustituye al nombre de persona que es muy a menudo -aunque no exclusivamente -el héroe de la novela.    

  6. Semi-implicit semi-Lagrangian modelling of the atmosphere: a Met Office perspective

    Directory of Open Access Journals (Sweden)

    Benacchio Tommaso

    2016-09-01

    Full Text Available The semi-Lagrangian numerical method, in conjunction with semi-implicit time integration, provides numerical weather prediction models with numerical stability for large time steps, accurate modes of interest, and good representation of hydrostatic and geostrophic balance. Drawing on the legacy of dynamical cores at the Met Office, the use of the semi-implicit semi-Lagrangian method in an operational numerical weather prediction context is surveyed, together with details of the solution approach and associated issues and challenges. The numerical properties and performance of the current operational version of the Met Office’s numerical model are then investigated in a simplified setting along with the impact of different modelling choices.

  7. Comportamento experimental de diferentes tipos de conectores metálicos

    OpenAIRE

    Valente, Isabel B.

    2016-01-01

    A realização de estruturas mistas de aço e betão requer o funcionamento conjunto destes dois materiais. A ligação entre eles é conseguida com a utilização de conectores metálicos. Neste âmbito, tem sido realizada uma considerável quantidade de estudos que abordam o comportamento de diversos tipos de conectores metálicos. O desejo de obter um comportamento óptimo com custos mínimos motivou o desenvolvimento de várias soluções. Neste artigo, procura-se descrever o comportamento de diferente...

  8. Characterization of the Met326Ile variant of phosphatidylinositol 3-kinase p85alpha

    DEFF Research Database (Denmark)

    Almind, Katrine; Delahaye, Laurent; Hansen, Torben

    2002-01-01

    . When the four human p85alpha proteins were expressed in yeast, a 27% decrease occurred in the level of protein expression of p85alpha(Ile/Asp) (P = 0.03) and a 43% decrease in p85alpha(Ile/Asn) (P = 0.08) as compared with p85alpha(Met/Asp). Both p85alpha(Ile/Asp) and p85alpha(Ile/Asn) also exhibited...... increased binding to phospho-insulin receptor substrate-1 by 41% and 83%, respectively (P substrate-1 slightly increased in brown preadipocytes derived from p85alpha...... knockout mice. Both p85alpha(Met) and p85alpha(Ile) had similar effects on AKT activity and were able to reconstitute differentiation of the preadipocytes, although the triglyceride concentration in fully differentiated adipocytes and insulin-stimulated 2-deoxyglucose uptake were slightly lower than...

  9. Forecast of winter performances of dry coolers with fin tubes; Voorspelling winterprestaties droge koelers met ribbenbuizen

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Bing [Shanghai DFYH Tech Services Co. Ltd, Shanghai (China); Wang, Xichun [Arup, Shanghai (China); Luscuere, P.G. [Faculteit Bouwkunde, Technische Universiteit Delft, Delft (Netherlands)

    2011-01-15

    A mathematical model is presented to predict the behaviors of dry coolers by considering the condensing and frosting. It employs one-dimensional transient finite differential formulation with variation of the frost density and thickness. The model is validated by experiments and predicts the heat transfer performance with an accuracy within 2.19%. It is helpful for the operation of dry coolers in winter. [Dutch] In dit artikel wordt een wiskundig model gepresenteerd, waarmee voortschrijdende condens- en ijsvorming op warmteoverdrachtsoppervlakken kunnen worden voorspeld aan de hand van de gevormde condens- en ijslagen. Het model maakt gebruik van eendimensionale transiente formuleringen op basis van een techniek voor lokale uitmiddeling. Hierbij wordt rekening gehouden met de varierende dichtheid en dikte van de ijslaag. Validatie van het model heeft plaatsgevonden door de resultaten te vergelijken met proefgegevens van de fabrikant van de droge koeler.

  10. Metástases extracranianas de tumores meningencefálicos

    Directory of Open Access Journals (Sweden)

    O. Ricciardi-Cruz

    1965-12-01

    Full Text Available Os autores apresentam 3 casos de tumores intracranianos com metástases extracranianas; no primeiro caso o quadro clínico e a documentação histopatológica permitem sua inclusão dentre os casos provávelmente válidos. Os outros dois casos são admitidos como questionàvelmente válidos.

  11. Eindhoven trendsetter with Smart Light Grid; Eindhoven voorloper met Slim Light-Grid

    Energy Technology Data Exchange (ETDEWEB)

    Van Lieshout, M.

    2013-07-15

    The municipality of Eindhoven in the Netherlands asked the Intelligent Lighting Institute of the Technical University of Eindhoven to develop a vision and a roadmap for urban lighting for 2030 in cooperation with private partners [Dutch] De gemeente Eindhoven heeft het Intelligent Lighting Institute van de Technische Universiteit Eindhoven gevraagd een visie en een roadmap te ontwikkelen voor stedelijke verlichting voor 2030. Samen met private partners moet dit worden uitgevoerd.

  12. Both COMT Val158Met single nucleotide polymorphism and sex-dependent differences influence response inhibition

    Directory of Open Access Journals (Sweden)

    Valentina eMione

    2015-05-01

    Full Text Available Reactive and proactive control of actions are cognitive abilities that allow to deal with a continuously changing environment by adjusting already programmed actions. They also set forthcoming acts by evaluating the outcome of the previous ones. Earlier studies highlighted sex related differences in the strategies and in the pattern of brain activation during cognitive tasks involving reactive and proactive control. To further identify sex-dependent characteristics in the cognitive control of actions, in this study we have assessed whether/how differences in reactive and proactive control were modulated by the COMT Val158Met single nucleotide polymorphism, a genetic factor known to influence the functionality of the dopaminergic system, in particular at the level of prefrontal cortex. Two groups of male and female participants were further sorted according to their genotype (Val/Met, Val/Val and Met/Met and tested in a stop signal task, a consolidated tool to measure reactive and proactive control in experimental and clinical settings. In each group of participants we estimated both a measure of the capacity to react to unexpected events and the ability of monitoring their performance. The between groups comparison of these measures indicated a poorer ability of male individuals carrying the Val/Val genotype in error-monitoring, suggesting that differences between sexes could be influenced by the efficiency of COMT and that other sex-specific factors have to be considered. The comprehension of inter-groups behavioral and physiological correlates of cognitive control will provide more accurate diagnostic tools for predicting the incidence and the development of pathologies like ADHD or deviant behaviors as drug or alcohol abuse.

  13. Interaction Between 5-HTTLPR and BDNF Val66Met Polymorphisms on HPA Axis Reactivity in Preschoolers

    OpenAIRE

    Dougherty, Lea R.; Klein, Daniel N.; Congdon, Eliza; Canli, Turhan; Hayden, Elizabeth P.

    2009-01-01

    This study examined whether the interaction between the serotonin transporter promoter region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms was associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. A community sample of 144 preschool-aged children was genotyped and exposed to stress-inducing laboratory tasks. Salivary cortisol was obtained at four time points during a standardized laboratory assessment before and after stressors invol...

  14. Simultaneous extraction of. beta. -endorphin and leu- and met-enkephalins from human and rat plasma

    Energy Technology Data Exchange (ETDEWEB)

    Bhathena, S.J.; Smith, P.M.; Kennedy, B.W. (Dept. of Agriculture, Beltsville, MD (USA)); Voyles, N.R.; Recant, L. (Diabetes Research Laboratory, Washington, DC (USA))

    1989-01-01

    A simple, rapid and reliable procedure is described to simultaneously concentrated and purify {beta}-endorphin, leu-and met-enkephalins from small volumes of human and rat plasma before radioimmunoassay is performed. It uses C{sub 18} Sep-Pak reverse phase cartridges. The effectiveness of different protease inhibitors in preventing degradation of opiates by plasma and different solvent systems for eluting opiates is also evaluated.

  15. ADAM10/17-Dependent Release of Soluble c-Met Correlates with Hepatocellular Damage

    Czech Academy of Sciences Publication Activity Database

    Chalupský, Karel; Kanchev, Ivan; Žbodáková, Olga; Buryová, Halka; Jiroušková, Markéta; Kořínek, Vladimír; Gregor, Martin; Sedláček, Radislav

    2013-01-01

    Roč. 59, č. 2 (2013), s. 76-78 ISSN 0015-5500 R&D Projects: GA ČR GAP305/10/2143; GA ČR GAP303/10/2044; GA AV ČR IAA500520812 Institutional support: RVO:68378050 Keywords : c-Met * HGF * shedding * ADAM metalloproteinase * liver Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.778, year: 2013

  16. Vrijwillige inzet bij sociaal geïsoleerden met multiproblematiek: mogelijkheden, voorwaarden en rollen

    Directory of Open Access Journals (Sweden)

    Anja Machielse

    2013-12-01

    Full Text Available Volunteering to social isolated people with multiple problems: possibilities, conditions and rolesThe Social Support Act (Wmo presumes that citizens should be able to solve their problems themselves, eventually with help from their own network. In this context, social professionals are expected to mobilize informal support and create conditions for the use of volunteers; also in the outreach to very vulnerable people, such as social isolated with multiple problems. However, professionals are very cautious with the use of volunteers for this target group. This article offers insight into the obstacles that professionals encounter and shows the conditions under which they want to engage with volunteers for this group. The article is based on a survey conducted among professionals from 16 organizations for welfare and social services. The main conclusion is that the professionals set high demands on volunteers for this target group and that the volunteers commitment is mainly considered as a supplement to their professional endeavors.Vrijwillige inzet bij sociaal geïsoleerden met multiproblematiek: mogelijkheden, voorwaarden en rollenUitgangspunt van de Wmo is dat burgers hun problemen zoveel mogelijk zelf oplossen, al dan niet met behulp van hun eigen netwerk. In deze context wordt van sociale professionals verwacht dat ze informele vormen van ondersteuning mobiliseren en voorwaarden scheppen voor de inzet van vrijwilligers; ook bij de hulpverlening aan zeer kwetsbare burgers, zoals sociaal geïsoleerden met multiproblematiek. Professionals zijn echter zeer terughoudend met het inzetten van vrijwilligers voor deze doelgroep. Dit artikel biedt inzicht in de belemmeringen die beroepskrachten hierbij ervaren en in de voorwaarden waaronder ze vrijwilligers bij deze  doelgroep willen inzetten. Het artikel is gebaseerd op een onderzoek onder professionals van 16 organisaties voor welzijn en maatschappelijke dienstverlening. De belangrijkste conclusie

  17. Aardverwarming en Klimaatsverandering met spesi- fieke verwysing na Suid-Afrika: Enkele perspektiewe

    Directory of Open Access Journals (Sweden)

    Gawie de Villiers

    2008-09-01

    Full Text Available Nagaan van die geologiese geskiedenis van die aarde toon dat klimaatsverandering ’n integrale deel is van omgewingsveranderinge wat met verloop van tyd plaasvind. Voldoende bewyse kom voor dat tydperke van natter en droër en kouer en warmer toestande mekaar met verloop van tyd, as gevolg van natuurlike gebeure, opgevolg het. Sedert die industriële revolusie het menslike aktiwiteite toenemend lugbesoedeling veroorsaak, soveel so dat dit tans algemeen aanvaar word dat toename in aardverwarming die afgelope dekades direk aan menslike aktiwiteite, wat groot volumes koolsuur en ander gasse aan die atmosfeer vrystel, gekoppel kan word. Waarneembare tekens van mens geïnduseerde klimaatsverandering sluit in styging in gemiddelde temperature op baie plekke, smelting van ysbedekking in poolgebiede, verhoging van seevlakke op globale skaal en kuslyn versteurings en skades as gevolg van hewige see-aanslag op kusgebiede in verskeie lande, ook in Suid-Afrika. Konsensus uit ’n aantal algemene hidrologiese-weerkundige sirkulasie modelle, toon vir Suid-Afrika dat die gemiddelde jaarlikse temperatuur met ongeveer 1.5 tot 3.0 grade Celsius in beide die somer en winter oor die volgende paar dekades gaan verhoog en dat daar ’n sterk moontlikheid van ’n toename in reënval in die oostelike dele en afname in reënval in die westelike dele bestaan.

  18. La metáfora del pasado en la narrativa de Vincenzo Consolo

    Directory of Open Access Journals (Sweden)

    Carolina Martín López

    2015-06-01

    Full Text Available El artículo plantea una lectura de la narrativa de Vincenzo Consolo a través de la dialéctica que la metáfora del pasado histórico, literario y lingüístico entabla en el tejido intertextual de su escritura. Los periodos históricos que Consolo elige como fondo y escenario por el que transcurren las vicisitudes y experiencias de sus personajes han sido de crucial importancia en la historia nacional italiana y, precisamente por ello, son altamente recurrentes como representación del presente al que alude el autor. Para expresar la concepción del mundo en que vivimos y su posible actuación en él es asimismo imprescindible para Consolo la exigencia de la metáfora topográfica, de la metáfora del nostos (de la cita constante del viaje de regreso narrado en la Odisea y la recuperación de términos lingüísticos del pasado capaces de contrarrestar la vacuidad terminológica de los medios de comunicación de masas.

  19. Suicide attempt, clinical correlates, and BDNF Val66Met polymorphism in chronic patients with schizophrenia.

    Science.gov (United States)

    Xia, Haisen; Zhang, Guangya; Du, Xiangdong; Zhang, Yingyang; Yin, Guangzhong; Dai, Jing; He, Man-Xi; Soares, Jair C; Li, Xiaosi; Zhang, Xiang Yang

    2018-02-01

    Recent evidence suggests the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidal behavior. Because schizophrenia patients usually have high suicide rates and numerous studies have suggested that BDNF may contribute to the psychopathology of schizophrenia, we hypothesized that the functional polymorphism of BDNF (Val66Met) was associated with suicide attempts in patients with schizophrenia in a Chinese Han population. This polymorphism was genotyped in 825 chronic schizophrenia patients with (n = 123) and without (n = 702) suicide attempts and 445 healthy controls without a history of suicide attempts using a case-control design. The schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale. There were no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls. However, we found the Val allele (p = .023) and the Val/Val genotypes (p = .058) to be associated with a history of suicide attempts. Moreover, some clinical characteristics, including age and cigarettes smoked each day, interacted with the BDNF gene variant and appeared to play an important role in suicide attempts among schizophrenia patients. The BDNF Val66Met polymorphism itself and its interaction with some clinical variables may influence suicide attempts among schizophrenia patients. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  20. Wittgenstein, the body, its metaphors Wittgenstein, o corpo, suas metáforas

    Directory of Open Access Journals (Sweden)

    Helena Martins

    2010-01-01

    Full Text Available Contemporary theories of metaphor often give the body a foundational status, by claiming that it provides the universal ground upon which imagination engenders figurative thought. This paper goes against this idea, discussing the relationship between the body and metaphor from a non foundationalist point of view. Taking a Wittgensteinean stance on metaphor and on the body, it aims to provide elements to rethink the issue, exploring in particular the path open by the Austrian philosopher in his critique of traditional mental/ physical, inner/outer dichotomies.Teorias contemporâneas da metáfora amiúde incluem o corpo entre seus fundamentos últimos, sustentando que nossa experiência corpórea constitui o solo universal de onde a imaginação faz brotar o pensamento figurativo. Contrapondo-se a essa tese, este trabalho busca discutir a relação entre corpo e metáfora de uma perspectiva não fundacionalista. A partir de um ponto de vista wittgensteiniano quanto aos estatutos do corpo e da metáfora, busca fornecer elementos para repensar a questão, explorando em particular o caminho aberto pelo filósofo austríaco em sua crítica às dicotomias físico/mental, exterior/interior.

  1. Post-traumatic stress disorder risk and brain-derived neurotrophic factor Val66Met

    Science.gov (United States)

    Zhang, Lei; Li, Xiao-Xia; Hu, Xian-Zhang

    2016-01-01

    Brain-derived neurotrophic factor (BDNF), which regulates neuronal survival, growth differentiation, and synapse formation, is known to be associated with depression and post-traumatic stress disorder (PTSD). However, the molecular mechanism for those mental disorders remains unknown. Studies have shown that BDNF is associated with PTSD risk and exaggerated startle reaction (a major arousal manifestation of PTSD) in United States military service members who were deployed during the wars in Iraq and Afghanistan. The frequency of the Met/Met in BDNF gene was greater among those with PTSD than those without PTSD. Among individuals who experienced fewer lifetime stressful events, the Met carriers have significantly higher total and startle scores on the PTSD Checklist than the Val/Val carriers. In addition, subjects with PTSD showed higher levels of BDNF in their peripheral blood plasma than the non-probable-PTSD controls. Increased BDNF levels and startle response were observed in both blood plasma and brain hippocampus by inescapable tail shock in rats. In this paper, we reviewed these data to discuss BDNF as a potential biomarker for PTSD risk and its possible roles in the onset of PTSD. PMID:27014593

  2. Onderskeiding tussen beroepsrealistiese en -onrealistiese adolessente met behulp van die waardeskaal

    Directory of Open Access Journals (Sweden)

    R. E. Zeier

    1995-06-01

    Full Text Available Differentiation between vocational realistic and unrealistic adolescents by means of a value scale. The usefulness of the Value Scale for distinguishing between adolescents with realistic or unrealistic approaches towards vocational choice was studied. A group of std. 10 pupils from a specific secondary school in the Cape Peninsula participated in the study. An evaluation with regard to the degree of realism of vocational decisions was made by three counselling psychologists. Classification of subjects was based on the agreement between their vocational choice, interest profiles, academic performance, intelligence test scores and course prerequisites. A number of variables were identified by discriminant analysis which distinguished significantly between realistic and unrealistic approaches. Value-preferences for realistic adolescents were more homogeneous and were globally interpreted as an intrinsic value pattern while subjects with unrealistic approaches showed a more differentiated pattern. Opsomming Die bruikbaarheid van die Waardeskaal vir die onderskeiding tussen beroepsrealistiese en beroepsonrealistiese adolessente is ondersoek deur 'n groep st. 10-leerlinge uit 'n spesifieke hoerskool in die Kaapse Skiereiland by die ondersoek te betrek. 'n Evaluering met betrekking tot realisme van verklaarde loopbaankeuse is deur drie voorligtingsielkundiges gemaak op grond van ooreenstemming tussen verklaarde beroepskeuse, belangstellings, akademiese prestasie, verstandstoetstellings en kursusvoorvereistes. Beduidende verskille met betrekking tot werkwaardes is tussen die groepe met behulp van diskriminant-analise gei'dentifiseer. Die waardevoorkeure van die beroepsrealistiese groep was meer homogeen van aard en kon globaal as intrinsieke waardevoorkeure beskryf word, terwyl die beroepsonrealistiese groep meer gedifferensieerde waardevoorkeurpatrone geopenbaar het.

  3. The Leu72Met polymorphism of the ghrelin gene is significantly associated with binge eating disorder.

    Science.gov (United States)

    Monteleone, Palmiero; Tortorella, Alfonso; Castaldo, Eloisa; Di Filippo, Carmela; Maj, Mario

    2007-02-01

    The pathophysiological mechanisms underlying binge eating disorder are poorly understood. Evidence exists for the fact that abnormalities in peptides involved in the regulation of appetite, including ghrelin, may play a role in binge eating behavior. Genes involved in the ghrelin physiology may therefore contribute to the biological vulnerability to binge eating disorder. We examined whether two polymorphisms of the ghrelin gene, the G152A (Arg51Gln) and C214A (Leu72Met), were associated with binge eating disorder. Ninety obese or nonobese women with binge eating disorder and 119 normal weight women were genotyped at the ghrelin gene. Statistical analyses showed that the Leu72Met ghrelin gene variant was significantly more frequent in binge eating disorder patients (chi2=5.940; d.f.=1, P=0.01) and was associated with a moderate, but significant risk to develop binge eating disorder (odds ratio=2.725, 95% confidence interval: 1.168-6.350). Although these data should be regarded as preliminary because of the small sample size, they suggest that the Leu72Met ghrelin gene variant may contribute to the genetic susceptibility to binge eating disorder.

  4. A metáfora na ensaística de Borges

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    Gustavo Ponciano Cunha de Oliveira

    2014-12-01

    Full Text Available http://dx.doi.org/10.5007/2176-8552.2014n17p115 A metáfora é uma recorrência temática na ensaística de Jorge Luis Borges. Porém, o tratamento dado pelo autor portenho ao objeto ensaiado não foi sempre o mesmo. Do jovem poeta e ensaísta ultraísta ao maduro palestrante, as concepções foram profundamente alteradas. Neste ensaio, pretendemos passar por estas diversificadas concepções para nos concentrarmos em uma delas: a metáfora entendida como possibilidade de convergência de conceitos diversos, mesmo contraditórios. Mais do que tema, defendemos a tese de que esta metáfora é própria ao funcionamento ensaístico de Borges. Para promover o debate, nos apoiamos em textos de Paul Ricoeur, Jaime Alazraki, Joseph Hillis Miller, Joaquina Navarro, Álvaro Salvador, entre outros.

  5. The effect of the COMT val(158)met polymorphism on neural correlates of semantic verbal fluency.

    Science.gov (United States)

    Krug, Axel; Markov, Valentin; Sheldrick, Abigail; Krach, Sören; Jansen, Andreas; Zerres, Klaus; Eggermann, Thomas; Stöcker, Tony; Shah, N Jon; Kircher, Tilo

    2009-12-01

    Variation in the val(158)met polymorphism of the COMT gene has been found to be associated with cognitive performance. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal areas. Given the complex modulation and functional heterogeneity of frontal lobe systems, further specification of COMT gene-related phenotypes differing in prefrontally mediated cognitive performance are of major interest. Eighty healthy individuals (54 men, 26 women; mean age 23.3 years) performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (fMRI). COMT val(158)met genotype was determined and correlated with brain activation measured with fMRI during the task. Although there were no differences in performance, brain activation in the left inferior frontal gyrus [Brodmann area 10] was positively correlated with the number of val alleles in the COMT gene. COMT val(158)met status modulates brain activation during the language production on a semantic level in an area related to executive functions.

  6. Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders

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    Shih-Jen Tsai

    2018-05-01

    Full Text Available Neurotrophins have been implicated in the pathophysiology of many neuropsychiatric diseases. Brain-derived neurotrophic factor (BDNF is the most abundant and widely distributed neurotrophin in the brain. Its Val66Met polymorphism (refSNP Cluster Report: rs6265 is a common and functional single-nucleotide polymorphism (SNP affecting the activity-dependent release of BDNF. BDNF Val66Met transgenic mice have been generated, which may provide further insight into the functional impact of this polymorphism in the brain. Considering the important role of BDNF in brain function, more than 1,100 genetic studies have investigated this polymorphism in the past 15 years. Although these studies have reported some encouraging positive findings initially, most of the findings cannot be replicated in following studies. These inconsistencies in BDNF Val66Met genetic studies may be attributed to many factors such as age, sex, environmental factors, ethnicity, genetic model used for analysis, and gene–gene interaction, which are discussed in this review. We also discuss the results of recent studies that have reported the novel functions of this polymorphism. Because many BDNF polymorphisms and non-genetic factors have been implicated in the complex traits of neuropsychiatric diseases, the conventional genetic association-based method is limited to address these complex interactions. Future studies should apply data mining and machine learning techniques to determine the genetic role of BDNF in neuropsychiatric diseases.

  7. Enfocando la metáfora visual: ópticas cognitivas I

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    Oquitzin Aguilar Leyva

    2012-01-01

    Full Text Available La reflexión en torno a la metáfora ha acompañado el devenir del pensamiento occidental desde sus orígenes. Desde las tentativas iniciales de su elucidación, acuñadas en la Retórica y Poética aristotélicas, hasta las modernas teorías de la interacción emergidas ya bien entrado el siglo veinte, se ha acumulado un gran número de acercamientos cuyo censo y comentario constituyen materia prima de no pocas monografías, como las de Hawkes (1972 y Ricoeur (1980, por citar algunas destacadas. Lejos de buscar prolongar dichos esfuerzos, nuestra aportación se inspira en el creciente auge de iconos en la comunicación mediática contemporánea para desarrollar una reflexión, tanto sobre la plausible existencia de la metáfora visual y/o audiovisual, como de los términos teórico-metodológicos con los que su análisis podría ser encarado. De corte teórico, la pesquisa que aquí avanzamos busca acercarnos a un encuadramiento para explorar la metáfora visual en tanto instrumento de comunicación, describriendo los procesos fundamentalmente cognitivos que su actualización en todo momento presupone…

  8. Development and Initial Validation of a Client-Rated MET-CBT Adherence Measure

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    Wendy R. Ulaszek

    2012-01-01

    Full Text Available Traditional mechanisms for rating adherence or fidelity are labor-intensive. We developed and validated a tool to rate adherence to Motivational Enhancement Therapy–-Cognitive Behavioral Treatment (MET-CBT through anonymous client surveys. The instrument was used to survey clients in 3 methadone programs over 2 waves. Explanatory and Confirmatory Factor Analyses were used to establish construct validity for both MET and CBT. Internal consistency based on Cronbach's alpha was within adequate range (α > 0.70 for all but 2 of the subscales in one of the samples. Consensus between clients’ ratings (r wg(j scores were in the range of 0.6 and higher, indicating a moderate to strong degree of agreement among clients’ ratings of the same counselor. These results suggest that client surveys could be used to measure adherence to MET-CBT for quality monitoring that is more objective than counselor self-report and less resource-intensive than supervisor review of taped sessions. However, additional work is needed to develop this scale.

  9. Medical Emergency Team: How do we play when we stay? Characterization of MET actions at the scene.

    Science.gov (United States)

    Silva, Raquel; Saraiva, Manuel; Cardoso, Teresa; Aragão, Irene C

    2016-03-22

    The creation, implementation and effectiveness of a medical emergency team (MET) in every hospital is encourage and supported by international bodies of quality certification. Issues such as what is the best composition of the team or the interventions performed by the MET at the scene and the immediate outcomes of the patients after MET intervention have not yet been sufficiently explored. The purpose of the study is to characterize MET actions at the scene and the immediate patient outcome. Retrospective cohort study, at a tertiary care, university-affiliated, 600-bed hospital, in the north of Portugal, over two years. There were 511 MET activations: 389 (76%) were for inpatients. MET activation rate was 8.6/1,000 inpatients. The main criteria for activation were airway threatening in 143 (36.8%), concern of medical staff in 121 (31.1%) and decrease in GCS > 2 in 98 (25.2%) patients; MET calls for cardiac arrest occurred in 68 patients (17.5%). The median (IQR) time the team stayed at the scene was 35 (20-50) minutes. At the scene, the most frequent actions were related to airway and ventilation, namely oxygen administration in 145 (37.3%); in circulation, fluid were administered in 158 (40.6%); overall medication was administered in 185 (47.5%) patients. End-of-life decisions were part of the MET actions in 94 (24.1%) patients. At the end of MET intervention, 73 (18.7%) patients died at the scene, 190 (60.7%) stayed on the ward and the remaining 123 patients were transferred to an increased level of care. Crude hospital mortality rate was 4.1% in the 3 years previously to MET implementation and 3.6% in the following 3 years (p residence. The team stayed on site for half an hour and during that time most of the actions were simple and nurse-driven, but in one third of all activations medical actions were taken, and in a forth (24%) end-of-life decisions made, reinforcing the inclusion of a doctor in the MET. A significant decrease in overall hospital

  10. Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice.

    Science.gov (United States)

    Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L; Lee, Francis S; Blendy, Julie A

    2015-12-01

    Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine withdrawal. Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For

  11. BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity.

    Science.gov (United States)

    Notaras, Michael J; Hill, Rachel A; Gogos, Joseph A; van den Buuse, Maarten

    2017-05-01

    Reduced expression of Brain-Derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of schizophrenia. The BDNF Val66Met polymorphism, which results in deficient activity-dependent secretion of BDNF, is associated with clinical features of schizophrenia. We investigated the effect of this polymorphism on Prepulse Inhibition (PPI), a translational model of sensorimotor gating which is disrupted in schizophrenia. We utilized humanized BDNFVal66Met (hBDNFVal66Met) mice which have been modified to carry the Val66Met polymorphism, as well as express humanized BDNF in vivo. We also studied the long-term effect of chronic corticosterone (CORT) exposure in these animals as a model of history of stress. PPI was assessed at 30ms and 100ms interstimulus intervals (ISI). Analysis of PPI at the commonly used 100ms ISI identified that, irrespective of CORT treatment, the hBDNFVal/Met genotype was associated with significantly reduced PPI. In contrast, PPI was not different between hBDNFMet/Met and hBDNFVal/Val genotype mice. At the 30ms ISI, CORT treatment selectively disrupted sensorimotor gating of hBDNFVal/Met heterozygote mice but not hBDNFVal/Val or hBDNFMet/Met mice. Analysis of startle reactivity revealed that chronic CORT reduced startle reactivity of hBDNFVal/Val male mice by 51%. However, this was independent of the effect of CORT on PPI. In summary, we provide evidence of a distinct BDNFVal66Met heterozygote-specific phenotype using the sensorimotor gating endophenotype of schizophrenia. These data have important implications for clinical studies where, if possible, the BDNFVal/Met heterozygote genotype should be distinguished from the BDNFMet/Met genotype. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. The Hepatocyte Growth Factor (HGF/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

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    Marjorie Boissinot

    2014-08-01

    Full Text Available Met is the receptor of hepatocyte growth factor (HGF, a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML, and myeloproliferative neoplasms (MPNs. The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs.

  13. BDNF Val66Met polymorphism as a moderator of exercise enhancement of smoking cessation treatment in anxiety vulnerable adults

    NARCIS (Netherlands)

    Smits, J.A.J.; Powers, M.B.; Rosenfield, D.; Zvolensky, M.J.; Jacquart, J.; Davis, M.L.; Beevers, C.G.; Marcus, B.H.; Church, T.S.; Otto, M.W.

    2016-01-01

    Background: Exercise interventions facilitate the odds of quit success among high-anxiety sensitive adults smokers. We examined the dependency of these benefits on the genetic BDNF Val66Met (rs6265) polymorphism; individuals who are Met carriers have lower BDNF responses and reduced associated

  14. Expression and prognostic relevance of MET and phospho-BAD in non-small cell lung cancer.

    Science.gov (United States)

    Sun, Wenze; Ai, Ting; Gao, Ying; Zhang, Yingbing; Cui, Jie; Song, Liping

    2013-01-01

    MET is involved in the progression of several types of human cancers, while phospho-BAD(Ser-136) is a key molecule in apoptosis and might be regulated by MET. The aim of this study was to investigate the correlation between altered expression of MET and phospho-BAD in non-small cell lung cancer (NSCLC) and their association with clinicopathologic parameters and overall survival. MET and phospho-BAD(Ser-136) proteins were evaluated by immunohistochemical analysis in 183 paraffin-embedded specimens and were also assessed by Western blotting analysis in 12 frozen tumor tissue samples, which were representative examples of immunohistochemical staining. Positive expression of MET and phospho-BAD(Ser-136) occurred in 67.2% and 49.2% of the 183 cases of NSCLC, respectively. However, neither MET expression nor phospho-BAD(Ser-136) expression was associated with any clinicopathologic parameter. A significant correlation was found between MET and phospho-BAD(Ser-136) expression levels evaluated by immunohistochemistry (r = 0.268, P BAD(Ser-136)+ phenotype had a poorer prognosis than others (P BAD(Ser-136) expression, and may be an adverse predictor for NSCLC. Activation of the MET/phospho-BAD(Ser-136) signaling pathway might play a role in the development and progression of NSCLC.

  15. The BDNF Val66Met polymorphism: relation to familiar risk of affective disorder, BDNF levels and salivary cortisol.

    Science.gov (United States)

    Vinberg, Maj; Trajkovska, Viktorija; Bennike, Bente; Knorr, Ulla; Knudsen, Gitte M; Kessing, Lars V

    2009-10-01

    Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are considered to play an important role in the pathophysiology of affective disorders. The aim of the present study was to investigate whether the BDNF Val66Met polymorphism is associated with a familiar risk of affective disorder and whether these genotypes affect whole blood BDNF level and salivary cortisol. In a high-risk study, healthy monozygotic and dizygotic twins with and without a co-twin (high- and low-risk twins, respectively) history of affective disorder were identified through nationwide registers. Familiar predisposition to unipolar and bipolar disorder was not associated with any specific genotype pattern of the BDNF Val66Met polymorphism, not in this sample of 124 val/val, 58 val/met and 8 met/met individuals. However, the combination of having a high familiar risk of affective disorder and the met allele was associated with a higher whole blood BDNF (p=0.02) and a higher evening cortisol level (p=0.01), but not with awakening cortisol. Individuals at high risk of affective disorders and who are carriers of the met allele of the Val66Met polymorphism may present with an enhanced stress response. The presence of a specific genotype alone may not enhance the risk of developing an affective episode. Rather, the altered stress response may be expressed only in combination with other risk variants through interactions with the environment.

  16. Betere vochtbeheersing maakt intensiever schermen mogelijk: aanzuigen van buitenlucht verlaagt RV (interview met o.a. Peter van Weel)

    NARCIS (Netherlands)

    Staalduinen, van J.; Weel, van P.A.

    2008-01-01

    Intensief schermen om energie te besparen, staat vooral in grondteelten op gespannen voet met het handhaven van een goed klimaat. Hoge vochtgehaltes dwingen telers tot het werken met een minimum buistemperatuur, onvolledig schermen (kieren) en vroegtijdig luchten om overtollige warmte en vocht af te

  17. In vivo detection of c-MET expression in a rat hepatocarcinogenesis model using molecularly targeted magnetic resonance imaging.

    Science.gov (United States)

    Towner, Rheal A; Smith, Nataliya; Tesiram, Yasvir A; Abbott, Andrew; Saunders, Debbie; Blindauer, Rebecca; Herlea, Oana; Silasi-Mansat, Robert; Lupu, Florea

    2007-01-01

    The multifunctional growth factor scatter factor/hepatocyte growth factor and its tyrosine kinase receptor, c-MET, have been implicated in the genesis and malignant progression of numerous human malignancies, including hepatocellular carcinomas. The incidence of hepatocellular carcinomas in the United States has increased noticeably over the past two decades and is listed as the fifth major cancer in men worldwide. In this study, we used a choline-deficient l-amino acid (CDAA)-defined rat hepatocarcinogenesis model to visualize increased in vivo expression of the c-MET antigen in neoplastic lesion formation with the use of a super paramagnetic iron oxide (SPIO)-anti-c-MET molecularly targeted magnetic resonance imaging (MRI) contrast agent. SPIO-anti-c-MET was used for the first time to detect overexpression of c-MET in neoplastic nodules and tumors within the livers of CDAA-treated rats, as determined by a decrease in MRI signal intensity and a decrease in regional T(2) values. Specificity for the binding of the molecularly targeted anti-c-MET contrast agent was determined using rat hepatoma (H4-II-E-C3) cell cultures and immunofluorescence microscopic imaging of the targeting agents within neoplastic liver tissue 1 to 2 hours following intravenous administration of SPIO-anti-c-MET and MRI investigation. This method has the ability to visualize in vivo the overexpression of c-MET at early developmental stages of tumor formation.

  18. In Vivo Detection of c-MET Expression in a Rat Hepatocarcinogenesis Model Using Molecularly Targeted Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Rheal A. Towner

    2007-01-01

    Full Text Available The multifunctional growth factor scatter factor/hepatocyte growth factor and its tyrosine kinase receptor, c-MET, have been implicated in the genesis and malignant progression of numerous human malignancies, including hepatocellular carcinomas. The incidence of hepatocellular carcinomas in the United States has increased noticeably over the past two decades and is listed as the fifth major cancer in men worldwide. In this study, we used a choline-deficient l-amino acid (CDAA-defined rat hepatocarcinogenesis model to visualize increased in vivo expression of the c-MET antigen in neoplastic lesion formation with the use of a super paramagnetic iron oxide (SPIO–anti-c-MET molecularly targeted magnetic resonance imaging (MRI contrast agent. SPIO–anti-c-MET was used for the first time to detect overexpression of c-MET in neoplastic nodules and tumors within the livers of CDAA-treated rats, as determined by a decrease in MRI signal intensity and a decrease in regional T2 values. Specificity for the binding of the molecularly targeted anti-c-MET contrast agent was determined using rat hepatoma (H4-II-E-C3 cell cultures and immunofluorescence microscopic imaging of the targeting agents within neoplastic liver tissue 1 to 2 hours following intravenous administration of SPIO–anti-c-MET and MRI investigation. This method has the ability to visualize in vivo the overexpression of c-MET at early developmental stages of tumor formation.

  19. Expression of hepatocyte growth factor and the proto-oncogenic receptor c-Met in canine osteosarcoma

    NARCIS (Netherlands)

    Fieten, H; Spee, B; Ijzer, J; Kik, M J; Penning, L C; Kirpensteijn, J

    Hepatocyte growth factor (HGF) and the proto-oncogenic receptor c-Met are implicated in growth, invasion, and metastasis in human cancer. Little information is available on the expression and role of both gene products in canine osteosarcoma. We hypothesized that the expression of c-Met is

  20. Case note: Gerechtshof 's-Hertogenbosch (ABP partnerpensioen ene partner wordt verminderd met aan andere partner toekomend ABP bijzonder partnerpensioen)

    NARCIS (Netherlands)

    Reinhartz, B.E.

    2009-01-01

    De man is gehuwd geweest met mevrouw X tussen 1962 en 1976. Tussentijds heeft de man van 1986 tot 1990 samengewoond met mevrouw Z. In 1988 is er een samenlevingsovereenkomst gesloten tussen de man en vrouw Z. Tussen 1991 en 1995 hebben de man en mevrouw Z weer samengewoond. In 1994 heeft de man het