Persistent psychogenic d?j? vu: a case report

OpenAIRE

Wells, Christine E; Moulin, Chris JA; Ethridge, Paige; Illman, Nathan A; Davies, Emma; Zeman, Adam

2014-01-01

Introduction: Déjà vu is typically a transient mental state in which a novel experience feels highly familiar. Although extensively studied in relation to temporal lobe epilepsy as part of simple partial seizures, déjà vu has been less studied in other clinical populations. A recent review of temporal lobe epilepsy suggested a possible link between clinical levels of anxiety and debilitating déjà vu, indicating further research is required. Here, for the first time in the literature, we prese...

New Measurements of Methyl Ethyl Ketone (MEK) Photolysis Rates and Their Relevance to Global Oxidative Capacity

Science.gov (United States)

Brewer, J.; Ravishankara, A. R.; Mellouki, A.; Fischer, E. V.; Kukui, A.; Véronique, D.; Ait-helal, W.; Leglise, J.; Ren, Y.

2017-12-01

Methyl ethyl ketone (MEK) is one of the most abundant ketones in the atmosphere. MEK can be emitted directly into the atmosphere from both anthropogenic and natural sources, and it is also formed during the gas-phase oxidation of volatile organic compounds (VOCs). MEK is lost via reaction with OH, photolysis and deposition to the surface. Similar to the other atmospheric ketones, the photolysis of MEK may represent a source of HOx (OH + HO2) radicals in the upper troposphere. The degradation of MEK also leads to the atmospheric formation of acetaldehyde and formaldehyde. This work presents a new analysis of the temperature dependence of MEK photolysis cross-sections and a quantification of MEK photolysis rates under surface pressures using the CNRS HELIOS outdoor atmospheric chamber (Chambre de simulation atmosphérique à irradiation naturelle d'Orléans; http://www.era-orleans.org/ERA-TOOLS/helios-project.html). Additionally, we use the GEOS-Chem 3-D CTM (version 10-01, www.geos-chem.org) to investigate the impact of these newly measured rates and cross-sections on the global distribution and seasonality of MEK, as well as its importance to the tropospheric oxidative capacity.

miR-322 stabilizes MEK1 expression to inhibit RAF/MEK/ERK pathway activation in cartilage.

Science.gov (United States)

Bluhm, Björn; Ehlen, Harald W A; Holzer, Tatjana; Georgieva, Veronika S; Heilig, Juliane; Pitzler, Lena; Etich, Julia; Bortecen, Toman; Frie, Christian; Probst, Kristina; Niehoff, Anja; Belluoccio, Daniele; Van den Bergen, Jocelyn; Brachvogel, Bent

2017-10-01

Cartilage originates from mesenchymal cell condensations that differentiate into chondrocytes of transient growth plate cartilage or permanent cartilage of the articular joint surface and trachea. MicroRNAs fine-tune the activation of entire signaling networks and thereby modulate complex cellular responses, but so far only limited data are available on miRNAs that regulate cartilage development. Here, we characterize a miRNA that promotes the biosynthesis of a key component in the RAF/MEK/ERK pathway in cartilage. Specifically, by transcriptome profiling we identified miR-322 to be upregulated during chondrocyte differentiation. Among the various miR-322 target genes in the RAF/MEK/ERK pathway, only Mek1 was identified as a regulated target in chondrocytes. Surprisingly, an increased concentration of miR-322 stabilizes Mek1 mRNA to raise protein levels and dampen ERK1/2 phosphorylation, while cartilage-specific inactivation of miR322 in mice linked the loss of miR-322 to decreased MEK1 levels and to increased RAF/MEK/ERK pathway activation. Such mice died perinatally due to tracheal growth restriction and respiratory failure. Hence, a single miRNA can stimulate the production of an inhibitory component of a central signaling pathway to impair cartilage development. © 2017. Published by The Company of Biologists Ltd.

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_FM1+FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2003-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_FM1+FM4_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_FM1+FM3_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_FM1+FM2_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2002-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_FM1+FM4_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

Expressão diferencial dos genes VuUCP1a e VuUCP1b em caupi sob estresse salino Differential expression of VuUCP1a and VuUCP1b in caupi under salt stress

Directory of Open Access Journals (Sweden)

Francisco Edson Alves Garantizado

2011-06-01

Full Text Available O estresse salino afeta o crescimento e o desenvolvimento das plantas, induzindo respostas bioquímicas e fisiológicas como mecanismo de adaptação para sua sobrevivência. As proteínas desacopladoras de planta (pUCPs dissipam o gradiente eletroquímico mitocondrial de prótons como calor e são codificadas por famílias multigênicas. Elas atuam como sistema de defesa evitando a formação de espécies reativas de oxigênio geradas em resposta a estresses ambientais. O objetivo do trabalho foi estudar a expressão de genes das pUCPs (VuUCP1a e VuUCP1b em raízes e folhas de plântulas de Vigna unguiculata submetidas ao estresse salino (NaCl 100 mM. Sementes foram germinadas no escuro e após 3 dias, as plântulas foram transferidas para solução de Hoagland, permanecendo 3 dias antes da aplicação do estresse. As raízes e folhas foram coletadas com 0; 6; 12 e 24 horas, após adição de NaCl, para avaliar o perfil de expressão dos genes da pUCP por RT- PCR. A análise de transcritos mostrou que VuUCP1a é expresso em raízes e folhas revelando um perfil constitutivo enquanto que VuUCP1b é dependente do tecido, isto é, expresso nas folhas, sem alteração em resposta ao estresse e induzido pelo estresse salino nas raízes. A peculiaridade da duplicação gênica de pUCP1 em caupi com perfil diferencial de expressão, sugere tanto um papel dessa enzima nos mecanismos de ajustamento ao estresse salino quanto promove essa espécie como um modelo atrativo para compreensão do papel da família multigênica da pUCP em plantas.Salt stress affects growth and development of plants, inducing a variety of physiological and biochemical responses as an adaptation mechanism for survival. The plant uncoupling mitochondrial proteins (pUCPs are able to dissipate the proton electrochemical gradient as heat and are encoded by a multigene family. They works as defence systems avoiding the formation of reactive oxygen species promoted by environmental

MANY FACES OF DÉJÀ VU: A NARRATIVE REVIEW

OpenAIRE

Bošnjak Pašić, Marija; Horvat Velić, Emina; Fotak, Luka; Pašić, Hanna; Srkalović Imširagić, Azijada; Milat, Davorka; Šarac, Helena; Bjedov, Sarah; Petelin Gadže, Željka

2018-01-01

French expression standing for the phrase “already seen” is a déjà vu. It is thought that as much as 97% of the population have experienced déjà vu at least once in their lifetime and 67% experience it regularly. The explanations of this phenomenon in novels and poems include reincarnation, dreams, organic factors, and unconscious memories. In this narrative review connection between déjà vu and various other conditions has been mentioned: false memories, temporal lobe epilepsy and other neur...

Deja vu: The Unified Command Plan of the Future Revisited

Science.gov (United States)

2011-05-19

Approved for Public Release; Distribution is Unlimited Déjà vu : The Unified Command Plan of the Future Revisited A Monograph by Lieutenant...DD-MM-YYYY) 19-05-2011 2. REPORT TYPE Monograph 3. DATES COVERED (From - To) JUL 2010 – MAY 2011 4. TITLE AND SUBTITLE Déjà vu : The Unified...i SCHOOL OF ADVANCED MILITARY STUDIES MONOGRAPH APPROVAL Lieutenant Colonel Edward Francis Martignetti Title of Monograph: Déjà vu : The Unified

47 CFR 74.1290 - FM translator and booster station information available on the Internet.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false FM translator and booster station information... DISTRIBUTIONAL SERVICES FM Broadcast Translator Stations and FM Broadcast Booster Stations § 74.1290 FM translator and booster station information available on the Internet. The Media Bureau's Audio Division...

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Terra-FM2_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2006-10-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

VALUE OF THE PHENOMENON OF DEJA VU IN HEALTHY EXAMINEES

Directory of Open Access Journals (Sweden)

Pavel Nikolaevich Vlasov

2009-01-01

Full Text Available The purpose of the investigation was to study the clinical value of the deja vu phenomenon in healthy examinees as it may occur in healthy individuals, on the one hand, and is a symptom of a number of psychoneurological diseases, on the other. One hundred and twenty-nine subjects, mean age 25,2±4,4 years, were examined. All the examinees were questioned by the original questionnaire developed by the authors, which was to reveal the characteristics of the phenomenon, and the Cambridge depersonalization questionnaire; standard electroencephalography was also performed. The deja vu phenomenon was detected in 97% of the respondents. In healthy individuals, the phenomenon was most common at the age of 21-25 years; 52,2% experienced deja vu several times a year; 64,5% of the respondents reported the 10-sec state; 85% did not associate the occurrence of the phenomenon with any provoking factor; 66% perceived deja vu with a positive emotional tinge, and only 4% of the respondents were afraid of the onset of this phenomenon. These criteria may be used to rule out pathological deja vu

The clinical and neurophysiological characteristics of the deja vu phenomenon in epilepsy

Directory of Open Access Journals (Sweden)

P. N. Vlasov

2012-01-01

Full Text Available Objective: to study the clinical and neurophysiological characteristics of the deja vu phenomenon in epilepsy. Patients and methods. The manifestations of the dВjЕ vu phenomenon were compared in 154 examinees in two groups: 1 139 healthy individuals and 2 25 patients with epilepsy (mean age 25.17±9.19 years; women, 63.2% The characteristics of the phenomenon were determined, by questioning the examinees; 12—16-hour ambulatory electroencephalogram (EEG monitoring was made. Results. The deja vu phenomenon occurred with cryptogenic and symptomatic focal epilepsy with equal frequency; however, the phenomenon was also seen in the idiopathic generalized form of the latter and could be concurrent virtually with any types of seizures and observed as an individual seizure and in the structure of a partial and secondarily generalized seizure. In epileptic patients, the main clinical characteristics of the deja vu vu phenomenon are its frequency, fear before its onset, and emotional coloring. The most important criterion is a change in the characteristics of deja vu vu: prolongation, more frequencies, and the emergence of negative emotions. On EEG, the phenomenon was characterized by the onset of polyspike activity in the right temporal leads and, in some cases, ended with slow-wave, theta-delta activity in the right hemisphere.

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF ( CER_ES9_Aqua-FM3_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2006-10-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF ( CER_ES9_Terra-FM1_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2006-09-30] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

MEK inhibition in non-small cell lung cancer.

Science.gov (United States)

Stinchcombe, Thomas E; Johnson, Gary L

2014-11-01

KRAS mutations are the most common mutations in non-small cell lung cancer (NSCLC) with adenocarcinoma histology. KRAS mutations result in the activation of the RAF-MEK-ERK pathway, and agents that target RAF-MEK-ERK pathways have been investigated in KRAS mutant NSCLC. The two agents furthest in development are selumetinib and trametinib. Trametinib has greater binding for the MEK1/2 allosteric site, and generally has superior pharmacokinetics. A randomized phase II trial of docetaxel with and without selumetinib revealed that the combination resulted numerically superior overall survival, and a statistically significant improvement in progression-free survival and objective response rate. However, a concerning rate of hospital admission, grade 3 or 4 neutropenia, and febrile neutropenia was observed with the combination. Trials have investigated MEK inhibitors as single agents and in combination with erlotinib, and the data do not support the further development. The activity of MEK inhibitors appears to be similar in patients with KRAS mutant and wild-type NSCLC suggesting KRAS mutation status is not a reliable biomarker for efficacy. It is possible that mutations of genes in addition to KRAS mutations impact the activity of MEK inhibitors, or specific subsets of KRAS mutations may be resistant or susceptible to MEK inhibition. Other potential explanations are gene amplifications, alternative RNA splicing of genes resulting in activation of their protein products, and deregulation of noncoding RNAs and consequent altered protein expression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The significance of FM associations for women with FM.

Science.gov (United States)

Juuso, Päivi; Söderberg, Siv; Olsson, Malin; Skär, Lisa

2014-01-01

Living with fibromyalgia (FM) means living with a long-term pain syndrome that is invisible to others. Support and understanding from others seem to be important to managing the affected daily life. The aim of this study was to describe the significance of FM associations for women with FM. Data collection was carried out through focus group discussions with seventeen women with FM. Data were analyzed through thematic content analysis. The findings show that women experienced associations for people with FM as important as they gave access to contacts with others with similar experiences. Their need of togetherness was fulfilled at the association and they described being strengthened by the support received. Because of the lack of information and knowledge about FM, the association was described as an important venue for getting and mediating information about the illness. At the association the women seem to be empowered, which increases their ability to manage their daily lives despite the limitations imposed by FM. Healthcare personnel could not satisfy the women's needs and to manage to support women with FM. There is a need for communication based on a shared understanding between the women and healthcare personnel. This study highlighted the need for communication based on a shared understanding between people with chronic illness and healthcare personnel to support and strengthen women with FM in their daily lives. The FM associations meet the needs for togetherness, confirmation, and information that the women with FM in this study described and healthcare personnel could not satisfy. Healthcare personnel can learn from FM associations how to empower women with FM in their everyday lives.

Tippdisain Hank Vu'lt Urbana teostuses

Index Scriptorium Estoniae

1999-01-01

Vietnamis sündinud, Ameerika Ühendriikides Kalifornias töötav arhitektiharidusega mööblidisainer Hank Vu teeb lihtsat, funktsionaalset, abstraktselt orgaanilise vormiga mööblit. 6 illustratsiooni

15 CFR 200.106 - Publications.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Publications. 200.106 Section 200.106... FEES § 200.106 Publications. Publications provide the primary means of communicating the results of the... issues some fifteen categories of publications including three periodicals, ten non-periodicals series...

7 CFR 1924.106 - Location.

Science.gov (United States)

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Location. 1924.106 Section 1924.106 Agriculture... CONSTRUCTION AND REPAIR Planning and Performing Site Development Work § 1924.106 Location. (a) General. It is... will not finance development on locations that adversely affect properties which are listed or are...

Telemetry Standards, RCC Standard 106-17. Chapter 3. Frequency Division Multiplexing Telemetry Standards

Science.gov (United States)

2017-07-01

Standard 106-17 Chapter 3, July 2017 3-5 Table 3-4. Constant-Bandwidth FM Subcarrier Channels Frequency Criteria\\Channels: A B C D E F G H Deviation ...Telemetry Standards , RCC Standard 106-17 Chapter 3, July 2017 3-i CHAPTER 3 Frequency Division Multiplexing Telemetry Standards Acronyms...Frequency Division Multiplexing Telemetry Standards ................................ 3-1 3.1 General

7 CFR 1150.106 - United States.

Science.gov (United States)

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true United States. 1150.106 Section 1150.106 Agriculture... Order Definitions § 1150.106 United States. United States means the 48 contiguous States in the continental United States. ...

CERES Single Scanner Satellite Footprint, TOA, Surface Fluxes and Clouds (SSF) data in HDF (CER_SSF_Terra-FM2-MODIS_Edition2B)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The Single Scanner Footprint TOA/Surface Fluxes and Clouds (SSF) product contains one hour of instantaneous Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The SSF combines instantaneous CERES data with scene information from a higher-resolution imager such as Visible/Infrared Scanner (VIRS) on TRMM or Moderate-Resolution Imaging Spectroradiometer (MODIS) on Terra and Aqua. Scene identification and cloud properties are defined at the higher imager resolution and these data are averaged over the larger CERES footprint. For each CERES footprint, the SSF contains the number of cloud layers and for each layer the cloud amount, height, temperature, pressure, optical depth, emissivity, ice and liquid water path, and water particle size. The SSF also contains the CERES filtered radiances for the total, shortwave (SW), and window (WN) channels and the unfiltered SW, longwave (LW), and WN radiances. The SW, LW, and WN radiances at spacecraft altitude are converted to Top-of-the-Atmosphere (TOA) fluxes based on the imager defined scene. These TOA fluxes are used to estimate surface fluxes. Only footprints with adequate imager coverage are included on CER_SSF_TRMM-PFM-VIRS_Subset_Edition1the SSF which is much less than the full set of footprints on the CERES ES-8 product. The following CERES SSF data sets are currently available: CER_SSF_TRMM-PFM-VIRS_Edition1 CER_SSF_TRMM-PFM-VIRS_Subset_Edition1 CER_SSF_TRMM-PFM-VIRS_Edition2A CER_SSF_TRMM-SIM-VIRS_Edition2_VIRSonly CER_SSF_TRMM-PFM-VIRS_Edition2A-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition2A CER_SSF_Terra-FM2-MODIS_Edition2A CER_SSF_Terra-FM1-MODIS_Edition2B CER_SSF_Terra-FM2-MODIS_Edition2B CER_SSF_Aqua-FM4-MODIS_Beta1 CER_SSF_Aqua-FM3-MODIS_Beta2 CER_SSF_Aqua-FM4-MODIS_Beta2. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop

48 CFR 3028.106 - Administration.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Administration. 3028.106 Section 3028.106 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY... 3028.106 Administration. ...

48 CFR 2828.106 - Administration.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Administration. 2828.106 Section 2828.106 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE General Contracting Requirements BONDS AND INSURANCE Bonds 2828.106 Administration. ...

Mek1Y130C mice recapitulate aspects of human cardio-facio-cutaneous syndrome

Science.gov (United States)

Aoidi, Rifdat; Houde, Nicolas; Landry-Truchon, Kim; Holter, Michael; Jacquet, Kevin; Charron, Louis; Yu, Benjamin D.; Rauen, Katherine A.; Bisson, Nicolas; Newbern, Jason

2018-01-01

ABSTRACT The RAS/MAPK signaling pathway is one of the most investigated pathways, owing to its established role in numerous cellular processes and implication in cancer. Germline mutations in genes encoding members of the RAS/MAPK pathway also cause severe developmental syndromes collectively known as RASopathies. These syndromes share overlapping characteristics, including craniofacial dysmorphology, cardiac malformations, cutaneous abnormalities and developmental delay. Cardio-facio-cutaneous syndrome (CFC) is a rare RASopathy associated with mutations in BRAF, KRAS, MEK1 (MAP2K1) and MEK2 (MAP2K2). MEK1 and MEK2 mutations are found in ∼25% of the CFC patients and the MEK1Y130C substitution is the most common one. However, little is known about the origins and mechanisms responsible for the development of CFC. To our knowledge, no mouse model carrying RASopathy-linked Mek1 or Mek2 gene mutations has been reported. To investigate the molecular and developmental consequences of the Mek1Y130C mutation, we generated a mouse line carrying this mutation. Analysis of mice from a Mek1 allelic series revealed that the Mek1Y130C allele expresses both wild-type and Y130C mutant forms of MEK1. However, despite reduced levels of MEK1 protein and the lower abundance of MEK1 Y130C protein than wild type, Mek1Y130C mutants showed increased ERK (MAPK) protein activation in response to growth factors, supporting a role for MEK1 Y130C in hyperactivation of the RAS/MAPK pathway, leading to CFC. Mek1Y130C mutant mice exhibited pulmonary artery stenosis, cranial dysmorphia and neurological anomalies, including increased numbers of GFAP+ astrocytes and Olig2+ oligodendrocytes in regions of the cerebral cortex. These data indicate that the Mek1Y130C mutation recapitulates major aspects of CFC, providing a new animal model to investigate the physiopathology of this RASopathy. This article has an associated First Person interview with the first author of the paper. PMID:29590634

Bioloģisko aktīvu uzskaite SIA "Lielvircava Agro"

OpenAIRE

Laščenko, Jeļena

2010-01-01

Latvijā bioloģisko aktīvu uzskaites problemātika ir neizpētīts jautājums, gan no zinātnisko pētījumu, gan no regulējuma aspekta. Darba mērķis ir izpētīt SIA „Lielvircava AGRO” piederošo bioloģisko aktīvu uzskaites īpatnības un izstrādāt priekšlikumus bioloģisko aktīvu uzskaites pilnveidošanai. Darba mērķi un uzdevumi tiek atspoguļoti darba divās loģiski saistītās nodaļās, secinājumos un priekšlikumos, literatūras sarakstā, kā arī pielikumos. Darba pirmā nodaļā tiek skaidrots bioloģis...

48 CFR 1028.106 - Administration.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Administration. 1028.106 Section 1028.106 Federal Acquisition Regulations System DEPARTMENT OF THE TREASURY GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds 1028.106 Administration. ...

CERES Single Satellite Footprint, TOA and Surface Fluxes, Clouds (SSF) data in HDF (CER_SSF_Aqua-FM4-MODIS_Ed2A-NoSW)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The Single Scanner Footprint TOA/Surface Fluxes and Clouds (SSF) product contains one hour of instantaneous Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The SSF combines instantaneous CERES data with scene information from a higher-resolution imager such as Visible/Infrared Scanner (VIRS) on TRMM or Moderate-Resolution Imaging Spectroradiometer (MODIS) on Terra and Aqua. Scene identification and cloud properties are defined at the higher imager resolution and these data are averaged over the larger CERES footprint. For each CERES footprint, the SSF contains the number of cloud layers and for each layer the cloud amount, height, temperature, pressure, optical depth, emissivity, ice and liquid water path, and water particle size. The SSF also contains the CERES filtered radiances for the total, shortwave (SW), and window (WN) channels and the unfiltered SW, longwave (LW), and WN radiances. The SW, LW, and WN radiances at spacecraft altitude are converted to Top-of-the-Atmosphere (TOA) fluxes based on the imager defined scene. These TOA fluxes are used to estimate surface fluxes. Only footprints with adequate imager coverage are included on CER_SSF_TRMM-PFM-VIRS_Subset_Edition1the SSF which is much less than the full set of footprints on the CERES ES-8 product. The following CERES SSF data sets are currently available: CER_SSF_TRMM-PFM-VIRS_Edition1 CER_SSF_TRMM-PFM-VIRS_Subset_Edition1 CER_SSF_TRMM-PFM-VIRS_Edition2A CER_SSF_TRMM-SIM-VIRS_Edition2_VIRSonly CER_SSF_TRMM-PFM-VIRS_Edition2A-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition2A CER_SSF_Terra-FM2-MODIS_Edition2A CER_SSF_Terra-FM1-MODIS_Edition2B CER_SSF_Terra-FM2-MODIS_Edition2B CER_SSF_Aqua-FM4-MODIS_Beta1 CER_SSF_Aqua-FM3-MODIS_Beta2 CER_SSF_Aqua-FM4-MODIS_Beta2. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop

47 CFR 73.7002 - Fair distribution of service on reserved band FM channels.

Science.gov (United States)

2010-10-01

...-Reserved Channels § 73.7002 Fair distribution of service on reserved band FM channels. (a) If timely filed... 47 Telecommunication 4 2010-10-01 2010-10-01 false Fair distribution of service on reserved band FM channels. 73.7002 Section 73.7002 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED...

Unveiling the mystery of déjà vu: The structural anatomy of déjà vu

Czech Academy of Sciences Publication Activity Database

Brázdil, M.; Mareček, R.; Urbánek, Tomáš; Kašpárek, T.; Mikl, M.; Rektor, I.; Zeman, A.

2012-01-01

Roč. 48, č. 9 (2012), s. 1240-1243 ISSN 0010-9452 Institutional support: RVO:68081740 Keywords : déjà vu * temporal lobe epilepsy * neuroanatomy Subject RIV: FH - Neurology Impact factor: 6.161, year: 2012

5 CFR 960.106 - OPM leadership.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false OPM leadership. 960.106 Section 960.106 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EXECUTIVE BOARDS § 960.106 OPM leadership. (a) Role of the Director. The Director is responsible to the...

48 CFR 228.106 - Administration.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Administration. 228.106 Section 228.106 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds 228.106 Administration. ...

48 CFR 1228.106 - Administration.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Administration. 1228.106 Section 1228.106 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 1228.106 Administration. ...

48 CFR 828.106 - Administration.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Administration. 828.106 Section 828.106 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 828.106 Administration. ...

48 CFR 428.106 - Administration.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Administration. 428.106 Section 428.106 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 428.106 Administration. ...

48 CFR 1328.106 - Administration.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Administration. 1328.106 Section 1328.106 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 1328.106 Administration. ...

7 CFR 3550.106 - Dwelling requirements.

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Dwelling requirements. 3550.106 Section 3550.106... Waste Disposal Grants § 3550.106 Dwelling requirements. (a) Modest dwelling. The property must be one... § 3550.63. (b) Post-repair condition. Dwellings repaired with section 504 funds need not be brought to...

RAF Suppression Synergizes with MEK Inhibition in KRAS Mutant Cancer Cells

Directory of Open Access Journals (Sweden)

Simona Lamba

2014-09-01

Full Text Available KRAS is the most frequently mutated oncogene in human cancer, yet no therapies are available to treat KRAS mutant cancers. We used two independent reverse genetic approaches to identify components of the RAS-signaling pathways required for growth of KRAS mutant tumors. Small interfering RNA (siRNA screening of 37 KRAS mutant colorectal cancer cell lines showed that RAF1 suppression was synthetic lethal with MEK inhibition. An unbiased kinome short hairpin RNA (shRNA-based screen confirmed this synthetic lethal interaction in colorectal as well as in lung cancer cells bearing KRAS mutations. Compounds targeting RAF kinases can reverse resistance to the MEK inhibitor selumetinib. MEK inhibition induces RAS activation and BRAF-RAF1 dimerization and sustains MEK-ERK signaling, which is responsible for intrinsic resistance to selumetinib. Prolonged dual blockade of RAF and MEK leads to persistent ERK suppression and efficiently induces apoptosis. Our data underlie the relevance of developing combinatorial regimens of drugs targeting the RAF-MEK pathway in KRAS mutant tumors.

9 CFR 3.106 - Water quality.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Water quality. 3.106 Section 3.106... Mammals Animal Health and Husbandry Standards § 3.106 Water quality. (a) General. The primary enclosure... additives (e.g. chlorine and copper) that are added to the water to maintain water quality standards...

12 CFR 347.106 - Going concerns.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Going concerns. 347.106 Section 347.106 Banks... INTERNATIONAL BANKING § 347.106 Going concerns. Going concerns. If a bank acquires an equity interest in a foreign organization that is a going concern, no more than 5 percent of either the consolidated assets or...

34 CFR 106.23 - Recruitment.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Recruitment. 106.23 Section 106.23 Education... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 106.23 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which this subpart applies shall not discriminate on the basis of sex...

42 CFR 401.106 - Publication.

Science.gov (United States)

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Publication. 401.106 Section 401.106 Public Health... GENERAL ADMINISTRATIVE REQUIREMENTS Confidentiality and Disclosure § 401.106 Publication. (a) Methods of publication. Materials required to be published under the provisions of The Freedom of Information Act, 5 U.S...

29 CFR 4.106 - [Reserved

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true [Reserved] 4.106 Section 4.106 Labor Office of the Secretary of Labor LABOR STANDARDS FOR FEDERAL SERVICE CONTRACTS Application of the McNamara-O'Hara Service Contract Act Introductory § 4.106 [Reserved] Agencies Whose Contracts May Be Covered ...

13 CFR 106.101 - Definitions.

Science.gov (United States)

2010-01-01

... legal consideration. (i) Non-Fee Based SBA-Sponsored Activity Record (Non-Fee Based Record) means a... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Definitions. 106.101 Section 106.101 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION COSPONSORSHIPS, FEE AND NON-FEE BASED...

21 CFR 106.90 - Coding.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Coding. 106.90 Section 106.90 Food and Drugs FOOD... of Infant Formulas § 106.90 Coding. The manufacturer shall code all infant formulas in conformity with the coding requirements that are applicable to thermally processed low-acid foods packaged in...

34 CFR 106.32 - Housing.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Housing. 106.32 Section 106.32 Education Regulations of... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 106.32 Housing. (a) Generally... fees or requirements, or offer different services or benefits related to housing, except as provided in...

34 CFR 106.51 - Employment.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Employment. 106.51 Section 106.51 Education Regulations... Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 106.51 Employment. (a) General. (1) No person shall, on the basis of sex, be excluded from participation in, be...

48 CFR 45.106 - Transferring accountability.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Transferring accountability. 45.106 Section 45.106 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT GOVERNMENT PROPERTY General 45.106 Transferring accountability. Government property...

Deja vu: a database of highly similar citations in the scientific literature.

Science.gov (United States)

Errami, Mounir; Sun, Zhaohui; Long, Tara C; George, Angela C; Garner, Harold R

2009-01-01

In the scientific research community, plagiarism and covert multiple publications of the same data are considered unacceptable because they undermine the public confidence in the scientific integrity. Yet, little has been done to help authors and editors to identify highly similar citations, which sometimes may represent cases of unethical duplication. For this reason, we have made available Déjà vu, a publicly available database of highly similar Medline citations identified by the text similarity search engine eTBLAST. Following manual verification, highly similar citation pairs are classified into various categories ranging from duplicates with different authors to sanctioned duplicates. Déjà vu records also contain user-provided commentary and supporting information to substantiate each document's categorization. Déjà vu and eTBLAST are available to authors, editors, reviewers, ethicists and sociologists to study, intercept, annotate and deter questionable publication practices. These tools are part of a sustained effort to enhance the quality of Medline as 'the' biomedical corpus. The Déjà vu database is freely accessible at http://spore.swmed.edu/dejavu. The tool eTBLAST is also freely available at http://etblast.org.

48 CFR 570.106 - Publicizing/Advertising.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Publicizing/Advertising. 570.106 Section 570.106 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CONTRACTING PROGRAMS ACQUIRING LEASEHOLD INTERESTS IN REAL PROPERTY General 570.106 Publicizing/Advertising...

7 CFR 4280.106 - Conflict of interest.

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Conflict of interest. 4280.106 Section 4280.106... Efficiency Improvements Program § 4280.106 Conflict of interest. No conflict of interest or appearance of conflict of interest will be allowed. For purposes of this subpart, conflict of interest includes, but is...

28 CFR 301.106 - Repetitious accidents.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Repetitious accidents. 301.106 Section 301.106 Judicial Administration FEDERAL PRISON INDUSTRIES, INC., DEPARTMENT OF JUSTICE INMATE ACCIDENT COMPENSATION General § 301.106 Repetitious accidents. If an inmate worker is involved in successive accidents...

48 CFR 745.106 - Contract clauses.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clauses. 745.106 Section 745.106 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT CONTRACT MANAGEMENT GOVERNMENT PROPERTY General 745.106 Contract clauses. (a) The contracting officer shall insert the...

41 CFR 105-1.106 - Applicability.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Applicability. 105-1.106 Section 105-1.106 Public Contracts and Property Management Federal Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION 1-INTRODUCTION 1.1-Regulations System § 105-1.106 Applicability...

47 CFR 73.1570 - Modulation levels: AM, FM, TV and Class A TV aural.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Modulation levels: AM, FM, TV and Class A TV... levels: AM, FM, TV and Class A TV aural. (a) The percentage of modulation is to be maintained at as high a level as is consistent with good quality of transmission and good broadcast service, with maximum...

CERES BiDirectional Scans (BDS) data in HDF (CER_BDS_Terra-FM1_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

Each BiDirectional Scans (BDS) data product contains twenty-four hours of Level-1b data for each CERES scanner instrument mounted on each spacecraft. The BDS includes samples taken in normal and short Earth scan elevation profiles in both fixed and rotating azimuth scan modes (including space, internal calibration, and solar calibration views). The BDS contains Level-0 raw (unconverted) science and instrument data as well as the geolocated converted science and instrument data. The BDS contains additional data not found in the Level-0 input file, including converted satellite position and velocity data, celestial data, converted digital status data, and parameters used in the radiance count conversion equations. The following CERES BDS data sets are currently available: CER_BDS_TRMM-PFM_Edition1 CER_BDS_Terra-FM1_Edition1 CER_BDS_Terra-FM2_Edition1 CER_BDS_Terra-FM1_Edition2 CER_BDS_Terra-FM2_Edition2 CER_BDS_Aqua-FM3_Edition1 CER_BDS_Aqua-FM4_Edition1 CER_BDS_Aqua-FM3_Edition2 CER_BDS_Aqua-FM4_Edition2 CER_BDS_Aqua-FM3_Edition1-CV CER_BDS_Aqua-FM4_Edition1-CV CER_BDS_Terra-FM1_Edition1-CV CER_BDS_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2006-11-02] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

A rat osteogenic cell line (UMR 106-01) synthesizes a highly sulfated form of bone sialoprotein

International Nuclear Information System (INIS)

Midura, R.J.; McQuillan, D.J.; Benham, K.J.; Fisher, L.W.; Hascall, V.C.

1990-01-01

The rat osteosarcoma cell line (UMR 106-01) synthesizes and secretes relatively large amounts of a sulfated glycoprotein into its culture medium (approximately 240 ng/10(6) cells/day). This glycoprotein was purified, and amino-terminal sequence analysis identified it as bone sialoprotein (BSP). [35S]Sulfate, [3H]glucosamine, and [3H]tyrosine were used as metabolic precursors to label the BSP. Sulfate esters were found on N- and O-linked oligosaccharides and on tyrosine residues, with about half of the total tyrosines in the BSP being sulfated. The proportion of 35S activity in tyrosine-O-sulfate (approximately 70%) was greater than that in N-linked (approximately 20%) and O-linked (approximately 10%) oligosaccharides. From the deduced amino acid sequence for rat BSP, the results indicate that on average approximately 12 tyrosine residues, approximately 3 N-linked, and approximately 2 O-linked oligosaccharides are sulfated/molecule. The carboxyl-terminal quarter of the BSP probably contains most, if not all, of the sulfated tyrosine residues because this region of the polypeptide contains the necessary requirements for tyrosine sulfation. Oligosaccharide analyses indicated that for every N-linked oligosaccharide on the BSP, there are also approximately 2 hexa-, approximately 5 tetra-, and approximately 2 trisaccharides O-linked to serine and threonine residues. On average, the BSP synthesized by UMR 106-01 cells would contain a total of approximately 3 N-linked and approximately 25 of the above O-linked oligosaccharides. This large number of oligosaccharides is in agreement with the known carbohydrate content (approximately 50%) of the BSP.A

Anatomy of Deja Vu in Temporal Lobe Epilepsy

OpenAIRE

J Gordon Millichap

1994-01-01

Sixteen patients, ages 16 to 32 years, implanted with depth electrodes at Hopital Saint-Anne, Paris, France, had experienced a dreamy state (deja-vu - deja vecu, memories of complete scenes, or vague reminiscence) during sterotactic EEG (SEEG).

29 CFR 1614.106 - Individual complaints.

Science.gov (United States)

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Individual complaints. 1614.106 Section 1614.106 Labor... EMPLOYMENT OPPORTUNITY Agency Program To Promote Equal Employment Opportunity § 1614.106 Individual... individual and the agency and to describe generally the action(s) or practice(s) that form the basis of the...

34 CFR 106.33 - Comparable facilities.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Comparable facilities. 106.33 Section 106.33 Education... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 106.33 Comparable facilities. A recipient may provide separate toilet, locker room, and shower facilities on the basis of sex, but...

20 CFR 718.106 - Autopsy; biopsy.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Autopsy; biopsy. 718.106 Section 718.106... PNEUMOCONIOSIS Criteria for the Development of Medical Evidence § 718.106 Autopsy; biopsy. (a) A report of an autopsy or biopsy submitted in connection with a claim shall include a detailed gross macroscopic and...

19 CFR 152.106 - Computed value.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Computed value. 152.106 Section 152.106 Customs... (CONTINUED) CLASSIFICATION AND APPRAISEMENT OF MERCHANDISE Valuation of Merchandise § 152.106 Computed value. (a) Elements. The computed value of imported merchandise is the sum of: (1) The cost or value of the...

01 MutulaFM.fm

African Journals Online (AJOL)

Prof. Dennis Ocholla

in English, is carried over into the LFE, as illustrated below. i. Sipho he .... Zambianisms in Bayreth African Studies Series No.15, Germany. ... Cambridge: Mass: MIT Press. ... Language and Social History: Studies South African Sociolinguistics.

01 MutulaFM.fm

African Journals Online (AJOL)

Prof. Dennis Ocholla

The few that have, offer them at second or third language level – just 'isiZulu .... English mother-tongue teachers from Bantu Education, thereby denying Black children ... that the use of foreign languages negatively impacts the acquisition of.

01 Shamase FM.fm

African Journals Online (AJOL)

Maxwell Zakhele Shamase

conscious citizen of the cosmic order (in southeast Africa). ... normal social setting for a birth), in 1787 in the eLangeni territory at the Nguga homestead of Nandi's uncle. According to ..... each and every girl and to lose it was to lose self-esteem.

01 MutulaFM.fm

African Journals Online (AJOL)

Prof. Dennis Ocholla

the emotional pain experienced by bereaved children may at times be ... Forty children who attended primary school in the KwaZulu-Natal province participated in the study. ..... Elementary School Guidance and Counselling, 29 (2), 129-137.

Familial mesial temporal lobe epilepsy and the borderland of déjà vu.

Science.gov (United States)

Perucca, Piero; Crompton, Douglas E; Bellows, Susannah T; McIntosh, Anne M; Kalincik, Tomas; Newton, Mark R; Vajda, Frank J E; Scheffer, Ingrid E; Kwan, Patrick; O'Brien, Terence J; Tan, K Meng; Berkovic, Samuel F

2017-08-01

The cause of mesial temporal lobe epilepsy (MTLE) is often unknown. We ascertained to what extent newly diagnosed nonlesional MTLE actually represents familial MTLE (FMTLE). We identified all consecutive patients presenting to the Austin Health First Seizure Clinic with MTLE and normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis over a 10-year period. Patients' first-degree relatives and pairwise age- and sex-matched controls underwent a comprehensive epilepsy interview. Each interview transcript was reviewed independently by 2 epileptologists, blinded to relative or control status. Reviewers classified each subject as follows: epilepsy, specifying if MTLE; manifestations suspicious for epilepsy; or unaffected. Physiological déjà vu was noted. Forty-four patients were included. At the Clinic, MTLE had been recognized to be familial in 2 patients only. Among 242 subjects interviewed, MTLE was diagnosed in 9 of 121 relatives versus 0 of 121 controls (p = 0.008). All affected relatives had seizures with intense déjà vu and accompanying features; 6 relatives had not been previously diagnosed. Déjà vu experiences that were suspicious, but not diagnostic, of MTLE occurred in 6 additional relatives versus none of the controls (p = 0.04). Physiological déjà vu was common, and did not differ significantly between relatives and controls. After completing the relatives' interviews, FMTLE was diagnosed in 8 of 44 patients (18.2%). FMTLE accounts for almost one-fifth of newly diagnosed nonlesional MTLE, and it is largely unrecognized without direct questioning of relatives. Relatives of patients with MTLE may experience déjà vu phenomena that clinically lie in the "borderland" between epileptic seizures and physiological déjà vu. Ann Neurol 2017;82:166-176. © 2017 American Neurological Association.

Déjà vu experiences and reduplicative paramnesia

NARCIS (Netherlands)

Sno, H. N.; Linszen, D. H.; de Jonghe, F.

1992-01-01

A schizophrenic patient with different forms of experiences of inappropriate familiarity is described. The authors discuss traumatic experiences as aetiological factors in déjà vu experiences and reduplicative paramnesia. Finally, the differential diagnostic problem in psychotic and dissociative

Telemetry Standards, RCC Standard 106-17, Annex A.1, Pulse Amplitude Modulation Standards

Science.gov (United States)

2017-07-01

Standard 106-17 Annex A.1, July 2017 A.1-iii Acronyms dB decibel FM frequency modulation IF intermediate frequency PAM pulse amplitude...premodulation filter when employed. b. One-fifth of the intermediate frequency (IF) bandwidth (3 dB points) selected from the IF bandwidths listed in

34 CFR 106.59 - Advertising.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Advertising. 106.59 Section 106.59 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION... Advertising. A recipient shall not in any advertising related to employment indicate preference, limitation...

Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression

International Nuclear Information System (INIS)

Woodfield, Sarah E.; Zhang, Linna; Scorsone, Kathleen A.; Liu, Yin; Zage, Peter E.

2016-01-01

Novel therapies are needed for children with high-risk and relapsed neuroblastoma. We hypothesized that MAPK/ERK kinase (MEK) inhibition with the novel MEK1/2 inhibitor binimetinib would be effective in neuroblastoma preclinical models. Levels of total and phosphorylated MEK and extracellular signal-regulated kinase (ERK) were examined in primary neuroblastoma tumor samples and in neuroblastoma cell lines by Western blot. A panel of established neuroblastoma tumor cell lines was treated with increasing concentrations of binimetinib, and their viability was determined using MTT assays. Western blot analyses were performed to examine changes in total and phosphorylated MEK and ERK and to measure apoptosis in neuroblastoma tumor cells after binimetinib treatment. NF1 protein levels in neuroblastoma cell lines were determined using Western blot assays. Gene expression of NF1 and MEK1 was examined in relationship to neuroblastoma patient outcomes. Both primary neuroblastoma tumor samples and cell lines showed detectable levels of total and phosphorylated MEK and ERK. IC 50 values for cells sensitive to binimetinib ranged from 8 nM to 1.16 μM, while resistant cells did not demonstrate any significant reduction in cell viability with doses exceeding 15 μM. Sensitive cells showed higher endogenous expression of phosphorylated MEK and ERK. Gene expression of NF1, but not MEK1, correlated with patient outcomes in neuroblastoma, and NF1 protein expression also correlated with responses to binimetinib. Neuroblastoma tumor cells show a range of sensitivities to the novel MEK inhibitor binimetinib. In response to binimetinib, sensitive cells demonstrated complete loss of phosphorylated ERK, while resistant cells demonstrated either incomplete loss of ERK phosphorylation or minimal effects on MEK phosphorylation, suggesting alternative mechanisms of resistance. NF1 protein expression correlated with responses to binimetinib, supporting the use of NF1 as a biomarker to identify

Developing and validating of predictive model for radiofrequency radiation emission within the vicinity of fm stations in Ghana

International Nuclear Information System (INIS)

Ahenkora-Duodu, Kingsley

2016-07-01

The rapid growing number of FM stations with their corresponding antennas have led to an increase in the concern of the potential health risks that may arise as a result of exposure to RF radiations. The main objective of this research was to develop and validate a predictive model with real time measured data for FM antennas in Ghana. Theoretical and experimental assessment of radiofrequency emission due to FM antennas has been analysed. The maximum and minimum electric field spatial average recorded was 7.17E-01 ± 6.97E-01V/m at Kasapa FM and 6.39E-02 ± 5.39E-02V/m at Asempa FM respectively. At a transmission frequency range of 88 -108 MHz, the average power density of the real time measured data ranged between 3.92E-05W/m"2 and 1.37E-03W/m"2 whiles that of the FM model varied from 9.72E-03W/m"2 to 5.35E-01W/m"2 respectively. Results obtained showed a variation between measured power density levels and the FM model. The FM model overestimates the power density levels as compared to that of the measured data. The impact predictions were based on the maximum values estimated by the FM model, hence these results validates the credibility of the impact analysis for the FM stations. The general public exposure quotient ranged between 9.00E-03 and 2.68E-01 whilst that of the occupational exposure quotient varied from 9.72E-04 to 5.35E-02. The results obtained were found to be in compliance with the International Commission on Non-Ionizing Radiation Protection (ICNIRP) RF exposure limit. (au)

47 CFR 73.827 - Interference to the input signals of FM translator or FM booster stations.

Science.gov (United States)

2010-10-01

... translator or FM booster stations. 73.827 Section 73.827 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... Interference to the input signals of FM translator or FM booster stations. (a) An authorized LPFM station will not be permitted to continue to operate if an FM translator or FM booster station demonstrates that...

A rat osteogenic cell line (UMR 106-01) synthesizes a highly sulfated form of bone sialoprotein.

Science.gov (United States)

Midura, R J; McQuillan, D J; Benham, K J; Fisher, L W; Hascall, V C

1990-03-25

The rat osteosarcoma cell line (UMR 106-01) synthesizes and secretes relatively large amounts of a sulfated glycoprotein into its culture medium (approximately 240 ng/10(6) cells/day). This glycoprotein was purified, and amino-terminal sequence analysis identified it as bone sialoprotein (BSP). [35S]Sulfate, [3H]glucosamine, and [3H]tyrosine were used as metabolic precursors to label the BSP. Sulfate esters were found on N- and O-linked oligosaccharides and on tyrosine residues, with about half of the total tyrosines in the BSP being sulfated. The proportion of 35S activity in tyrosine-O-sulfate (approximately 70%) was greater than that in N-linked (approximately 20%) and O-linked (approximately 10%) oligosaccharides. From the deduced amino acid sequence for rat BSP (Oldberg, A., Franzén, A., and Heinegård, D. (1988) J. Biol. Chem. 263, 19430-19432), the results indicate that on average approximately 12 tyrosine residues, approximately 3 N-linked, and approximately 2 O-linked oligosaccharides are sulfated/molecule. The carboxyl-terminal quarter of the BSP probably contains most, if not all, of the sulfated tyrosine residues because this region of the polypeptide contains the necessary requirements for tyrosine sulfation. Oligosaccharide analyses indicated that for every N-linked oligosaccharide on the BSP, there are also approximately 2 hexa-, approximately 5 tetra-, and approximately 2 trisaccharides O-linked to serine and threonine residues. On average, the BSP synthesized by UMR 106-01 cells would contain a total of approximately 3 N-linked and approximately 25 of the above O-linked oligosaccharides. This large number of oligosaccharides is in agreement with the known carbohydrate content (approximately 50%) of the BSP.

The clinical and neurophysiological characteristics of the deja vu phenomenon in epilepsy

OpenAIRE

P. N. Vlasov; A. V. Chervyakov; G. R. Drozhzhina; М. V. Antonyuk; N. V. Orekhova; V. V. Gnezditsky; T. Yu. Noskova; P. A. Fedin

2012-01-01

Objective: to study the clinical and neurophysiological characteristics of the deja vu phenomenon in epilepsy. Patients and methods. The manifestations of the dВjЕ vu phenomenon were compared in 154 examinees in two groups: 1) 139 healthy individuals and 2) 25 patients with epilepsy (mean age 25.17±9.19 years; women, 63.2%) The characteristics of the phenomenon were determined, by questioning the examinees; 12—16-hour ambulatory electroencephalogram (EEG) monitoring was made. Results. The dej...

Biogas Production from Water Hyacinth (Eichhornia Crassipes): The Effect of F/M Ratio

Science.gov (United States)

Nugraha, W. D.; Syafrudin; Pradita, L. L.; Matin, H. H. A.; Budiyono

2018-05-01

Distribution of water hyacinth (Eichhornia crassipes), generally considered as a water weed, that has been a problem which can harm the environment, irrigation system, and agriculture. However water hyacinth can be used in biogas production because it has large enough amount of hemicellulose contents. The purpose of this study was to know the effect of F/M ratio to biogas production from water hyacinth waste with Liquid Anaerobic Digestion (LAD) method. A series of laboratory experiments using biodigester were performed in batch anaerobic operation at room temperature. F/M ratio that used in each reactor was 39.76, 20.03, 13.32, and 10.01. Degradation process was done in 60 days. The result showed that F/M ratio effects to the biogas production. The best performance of biogas production from this research will be obtained if F/M ratio is in the range of 10.01-20.03 (correspond to 25%-50% of rumen fluid) with water hyacinth as the main substrate.

34 CFR 106.53 - Recruitment.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Recruitment. 106.53 Section 106.53 Education... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

Continual low-level MEK inhibition ameliorates cardio-facio-cutaneous phenotypes in zebrafish

Directory of Open Access Journals (Sweden)

Corina Anastasaki

2012-07-01

Cardio-facio-cutaneous (CFC syndrome is caused by germline mutations in KRAS, BRAF and MEK1/2. The highly selective and potent MEK inhibitors that have been developed as anti-cancer agents hold potential as therapeutics for CFC syndrome. We have previously shown that the effects of CFC mutations on zebrafish gastrulation can be prevented by a 1-hour treatment with MEK inhibitors within a specific developmental time-window. However, MEK activity is essential for normal development and PD0325901 treatment outside this treatment window leads to additional developmental defects in MEK-dependent tissues. We now test ten different doses of PD0325901 at six developmental time points and assess the effects on body axis length, heart development and craniofacial structures in zebrafish embryos. Notably, we find that a continuous low-level dose of PD0325901 that has only minor inhibition of MEK activity can prevent the action of both the common CFC BRAFQ257R kinase-active allele and the BRAFG596V kinase-impaired mutant allele through the first 5 days of development. These results provide a detailed study of the effects of PD0325901 in development and show that, unlike in cancer, which requires robust inhibition of MAPK signalling, a partial reduction in phospho-ERK1/2 activity is sufficient to moderate the developmental effects of BRAFCFC mutations.

Expression and clinical significance of MMP-2, MVD, MEK-2 in endometriosis

Directory of Open Access Journals (Sweden)

Wei Zhang

2016-03-01

Full Text Available Objective: To investigate the expression and clinical significance of MMP-2, MVD, MEK-2in the endometriosis. Methods: A total of 42 endometrial endometriosis patients with surgery were selected in our hospital obstetrics and gynecology from September 1, 2008 to December 18, 2014. Endometriosis were removed during surgery and served as ectopic group. A total of 42 examples of the above-described patients with endometriosis eutopic were taken out as the eutopic group. Another 34 patients with uterine fibroids were selected in our hospital obstetrics and gynecology during the same period. Normal endometrium were taken as the normal endometrium group. Clinical expression of MMP-2, MVD, MEK-2 of three groups were analyzed. Results: MVD in ectopic endometrium group were significantly higher than those in eutopic and normal endometrium (P<0.05. MEK-2 expression in normal endometrial tissue mainly was negative and weakly positive. The expression was positive in ectopic endometrium and eutopic. The expression of ectopic endometrium MEK-2and MMP-2 were the highest, followed by the reign of endometrium, and the expression of normal endometrium were the lowest. Conclusions: MMP-2, MVD, MEK-2 in ectopic endometrium show high expression, detection of MMP-2, MVD, MEK-2-clinical expression in endometriosis can help in pathogenesis, clinical diagnosis and treatment.

Profiling value added position in FM

DEFF Research Database (Denmark)

Katchamart, Akarapong

. It is argued that being strategic is not the pre-requisite condition to add value to the core business and stakeholders but rather matching what does FM organization offer - so called FM product - with how does it being offered - so called FM process? By matching FM products with the right FM process, FM...... organizations can best add value. Based on comprehensive literature studies and 7 case studies of private and public organisations from Denmark, Holland, Hong Kong and Thailand, the dissertation analyses, how FM organizations can best create added value. From the analyses the following four value added...... positions have emerged: 1. Support - FM organizations create benefit to its host organization from economies of scope and scale 2. Enable - FM organizations increase the one-off organizational capacity and capability 3. Ensure - FM organizations contribute the business continuity and reliability 4. Enhance...

R7 VU Born-Assessed Demo Plan

Energy Technology Data Exchange (ETDEWEB)

Robert Nourgaliev

2010-02-01

This is an initial draft of a born-assessed VU plan for the RELAP7 (R7) code development effort. The plan will continue to evolve based on the growth of code capability. This growth will be reflected as additional testing is identified and done. Later versions of this document will reflect that growth.

Ionizing radiation-induced MEK and Erk activation does not enhance survival of irradiated human squamous carcinoma cells

International Nuclear Information System (INIS)

Bonner, James A.; Vroman, Benjamin T.; Christianson, Teresa J.H.; Karnitz, Larry M.

1998-01-01

Purpose: Ionizing radiation (IR) triggers several intracellular signaling cascades that have commonly been regarded as mitogenic, including the Raf-MEK-Erk kinase cascade. In addition to promoting proliferation, activated MEK and Erk may also prevent cell death induced by cytotoxic stimuli. Because Raf, MEK, and Erk are activated by IR in some tumor cell lines, this suggests that IR-induced activation of the kinase cascade may enhance the survival of irradiated cells. Methods and Materials: IR-induced activation of MEK and Erk was assessed in irradiated UM-SCC-6 cells, a human squamous carcinoma cell line. Activation of MEK and Erk was blocked with the pharmacological inhibitor of MEK activation, PD098059. Clonogenic survival was assessed in irradiated UM-SCC-6 cells that were pretreated with nothing or with the MEK inhibitor. Results: In UM-SCC-6 cells, IR doses as low as 2 Gy rapidly activated MEK and Erk. Pretreatment of the cells with the pharmacological inhibitor of MEK activation, PD098059, effectively blocked IR-induced activation of MEK and Erk. However, inhibition of the kinase cascade did not affect the clonogenic survival of irradiated cells in either early or delayed-plating experiments. Conclusion: Taken together, these results suggest that although MEK and Erk are rapidly activated by IR treatment, these protein kinases do not affect the clonogenic survival of irradiated UM-SCC6 cells

42 CFR 66.106 - Awards.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Awards. 66.106 Section 66.106 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL... program leading to the degrees of doctor of medicine and doctor of philosophy. [48 FR 24880, June 3, 1983...

47 CFR 1.573 - Processing FM broadcast and translator station applications.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Processing FM broadcast and translator station applications. 1.573 Section 1.573 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND... and translator station applications. See § 73.3573. ...

49 CFR 230.106 - Steam locomotive frame.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotive frame. 230.106 Section 230.106... Tenders Trucks, Frames and Equalizing System § 230.106 Steam locomotive frame. (a) Maintenance and inspection. Frames, decks, plates, tailpieces, pedestals, and braces shall be maintained in a safe and...

18 CFR 284.103-284.106 - [Reserved

Science.gov (United States)

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false [Reserved] 284.103-284.106 Section 284.103-284.106 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... RELATED AUTHORITIES Certain Transportation by Interstate Pipelines §§ 284.103-284.106 [Reserved] ...

7 CFR 900.106 - Assignment of mediator.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Assignment of mediator. 900.106 Section 900.106 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Assignment of mediator. The Director of the Division shall assign a mediator, from the group designated by...

Effects of simulated weightlessness on the kinase activity of MEK1 induced by bone morphogenetic protein-2 in rat osteosarcoma cells

Science.gov (United States)

Zhang, S.; Wang, B.; Cao, X. S.; Yang, Z.

Objective The mRNA expression of alpha 1 chain of type I collagen COL-I alpha 1 in rat osteosarcoma ROS17 2 8 cells induced by bone morphogenetic protein-2 BMP-2 was reduced under simulated microgravity The protein kinase MEK1 of MAPK signal pathway plays an important role in the expression of COL-I alpha 1 mRNA The purpose of this study is to investigate the effects of simulated weightlessness on the activity of MEK1 induced by BMP-2 in ROS17 2 8 cells Methods ROS17 2 8 cells were cultured in 1G control and rotating clinostat simulated weightlessness for 24 h 48 h and 72 h BMP-2 500 ng ml was added into the medium 1 h before the culture ended There was a control group in which ROS17 2 8 cells were cultured in 1G condition without BMP-2 Then the total protein of cells was extracted and the expression of phosphated-ERK1 2 p-ERK1 2 protein was detected by means of Western Blotting to show the kinase activity of MEK1 Results There were no significant differences in the expression of total ERK1 2 among all groups The expression of p-ERK1 2 was unconspicuous in the control group without BMP-2 but increased significantly when BMP-2 was added P 0 01 The level of p-ERK1 2 in simulated weightlessness group was much more lower than that in 1G group in every time point P 0 01 The expression of p-ERK1 2 gradually decreased along with the time of weightlessness simulation P 0 01 Conclusions The kinase activity of MEK1 induced by BMP-2 in rat osteosarcoma cells was reduced under simulated weightlessness

33 CFR 106.415 - Amendment and audit.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Amendment and audit. 106.415 Section 106.415 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARINE SECURITY: OUTER CONTINENTAL SHELF (OCS) FACILITIES Outer Continental Shelf (OCS) Facility Security Plan (FSP) § 106.415 Amendment and...

Electrochemical incineration of indigo textile dye in filter-press-type FM01-LC electrochemical cell using BDD electrodes

International Nuclear Information System (INIS)

Butron, Edgar; Juarez, Manuel E.; Solis, Myrna; Teutli, Margarita; Gonzalez, Ignacio; Nava, Jose L.

2007-01-01

This work shows results obtained in the incineration of 1 mM indigo textile dye (536 ppm COD) in 0.05 M NaCl aqueous media (which resembles a denim laundry industrial wastewater). Microelectrolysis and macroelectrolysis studies indicated that oxidation of indigo dye was carried out via hydroxyl radicals (OH·) formed by water oxidation on the BDD surface, instead of active chlorine as usually occurs by using DSA. Electrolyses in a FM01-LC reactor was performed at Reynolds between 1600 -2 . The experimental set-up achieved 100% efficiency in color removal, indigo mineralization and current efficiency. Estimated energy consumption, at Re = 12892 and J = 5.3 mA cm -2 , was 9 kWh m -3 . Experimental data revealed that hydrodynamic conditions do not influence either the indigo degradation rate or the current efficiencies; therefore indigo degradation must involve a complex mechanism

9 CFR 113.106 - Clostridium Chauvoei Bacterin.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Clostridium Chauvoei Bacterin. 113.106 Section 113.106 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... Animal and Plant Health Inspection Service, shall be used for challenge 14 to 15 days following the last...

42 CFR 460.106 - Plan of care.

Science.gov (United States)

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Plan of care. 460.106 Section 460.106 Public Health... ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PACE Services § 460.106 Plan of care. (a) Basic requirement. The interdisciplinary team must promptly develop a...

9 CFR 354.106 - Travel expenses and other charges.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Travel expenses and other charges. 354.106 Section 354.106 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... § 354.106 Travel expenses and other charges. Charges are to be made to cover the cost of travel and...

The Structure of the MAP2K MEK6 Reveals an Autoinhibitory Dimer

Energy Technology Data Exchange (ETDEWEB)

Min, Xiaoshan; Akella, Radha; He, Haixia; Humphreys, John M.; Tsutakawa, Susan E.; Lee, Seung-Jae; Tainer, John A.; Cobb, Melanie H.; Goldsmith, Elizabeth J.

2009-07-13

MAP2Ks are dual-specificity protein kinases functioning at the center of three-tiered MAP kinase modules. The structure of the kinase domain of the MAP2K MEK6 with phosphorylation site mimetic aspartic acid mutations (MEK6/{Delta}N/DD) has been solved at 2.3 {angstrom} resolution. The structure reveals an autoinhibited elongated ellipsoidal dimer. The enzyme adopts an inactive conformation, based upon structural queues, despite the phosphomimetic mutations. Gel filtration and small-angle X-ray scattering analysis confirm that the crystallographically observed ellipsoidal dimer is a feature of MEK6/{Delta}N/DD and full-length unphosphorylated wild-type MEK6 in solution. The interface includes the phosphate binding ribbon of each subunit, part of the activation loop, and a rare 'arginine stack' between symmetry-related arginine residues in the N-terminal lobe. The autoinhibited structure likely confers specificity on active MAP2Ks. The dimer may also serve the function in unphosphorylated MEK6 of preventing activation loop phosphorylation by inappropriate kinases.

Combined MEK and ERK inhibition overcomes therapy-mediated pathway reactivation in RAS mutant tumors.

Directory of Open Access Journals (Sweden)

Mark Merchant

Full Text Available Mitogen-activated protein kinase (MAPK pathway dysregulation is implicated in >30% of all cancers, rationalizing the development of RAF, MEK and ERK inhibitors. While BRAF and MEK inhibitors improve BRAF mutant melanoma patient outcomes, these inhibitors had limited success in other MAPK dysregulated tumors, with insufficient pathway suppression and likely pathway reactivation. In this study we show that inhibition of either MEK or ERK alone only transiently inhibits the MAPK pathway due to feedback reactivation. Simultaneous targeting of both MEK and ERK nodes results in deeper and more durable suppression of MAPK signaling that is not achievable with any dose of single agent, in tumors where feedback reactivation occurs. Strikingly, combined MEK and ERK inhibition is synergistic in RAS mutant models but only additive in BRAF mutant models where the RAF complex is dissociated from RAS and thus feedback productivity is disabled. We discovered that pathway reactivation in RAS mutant models occurs at the level of CRAF with combination treatment resulting in a markedly more active pool of CRAF. However, distinct from single node targeting, combining MEK and ERK inhibitor treatment effectively blocks the downstream signaling as assessed by transcriptional signatures and phospho-p90RSK. Importantly, these data reveal that MAPK pathway inhibitors whose activity is attenuated due to feedback reactivation can be rescued with sufficient inhibition by using a combination of MEK and ERK inhibitors. The MEK and ERK combination significantly suppresses MAPK pathway output and tumor growth in vivo to a greater extent than the maximum tolerated doses of single agents, and results in improved anti-tumor activity in multiple xenografts as well as in two Kras mutant genetically engineered mouse (GEM models. Collectively, these data demonstrate that combined MEK and ERK inhibition is functionally unique, yielding greater than additive anti-tumor effects and

48 CFR 9.106-4 - Reports.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Reports. 9.106-4 Section 9... CONTRACTOR QUALIFICATIONS Responsible Prospective Contractors 9.106-4 Reports. (a) The surveying activity... performance. The narrative shall report any persistent pattern of need for costly and burdensome Government...

A study on super-sulfated cement using Dinh Vu phosphogypsum

Science.gov (United States)

Lam, Nguyen Ngoc

2018-04-01

Super-sulfated cement (SSC) is a newly developed unburnt cementitious material. It is a kind of environmental-friendly cementitious material due to its energy-saving, carbon emission reducing, and waste-utilization. It mainly composes of phosphogysum (PG) and ground granulated blast furnace slag (GFS), with a small amount of cement. In Vietnam, the Diammonium Phosphate DAP – Dinh Vu fertilizer plant in Dinh Vu industrial zone in the northern port city of Hai Phong – has discharged millions of tons of solid waste containing gypsum after 9 years of operation. The waste has changed the color of the water, eroded metal and destroyed fauna and floral systems in the surrounding area. Notably, according to the environmental impact assessment, the gypsum landfill area is supposed to be 13 hectares and the storage time reaches up to five years. This paper presents the experimental results on SSC using a high amount of Dinh Vu phosphogypsum and GFS in comparison with those of ordinary Portland cement (PC). The results show that the setting time of SSC is much longer than that of Portland cement but the compressive strength of SSC can be obtained 45-50 MPa at the age of 28 days, similar to that of the control sample using 100% PC40, and 69MPa at the age of 90 days. This value even exceeds the compressive strength of the PC40 cement.

20 CFR 726.106 - Type of security.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Type of security. 726.106 Section 726.106... Authorization of Self-Insurers § 726.106 Type of security. (a) The Office shall determine the type or types of... which the surety on any such bond is a surety company, such company must be one approved by the U.S...

Déjà Vu Experiences in Healthy Czech Adults

Czech Academy of Sciences Publication Activity Database

Lacinová, L.; Neužilová Michalčáková, R.; Širůček, J.; Ježek, S.; Chromec, J.; Masopustová, Z.; Urbánek, Tomáš; Brázdil, M.

2016-01-01

Roč. 204, č. 12 (2016), s. 925-930 ISSN 0022-3018 Institutional support: RVO:68081740 Keywords : déjà vu * attachment * neuroticism * depression * irritability in the limbic system * perceived stress Subject RIV: AN - Psychology Impact factor: 1.860, year: 2016

MEK-ERK inhibition potentiates WAY-600-induced anti-cancer efficiency in preclinical hepatocellular carcinoma (HCC) models

Energy Technology Data Exchange (ETDEWEB)

Wang, Kaifeng, E-mail: kaifeng_wangdr@sina.com [Cancer center, the Affiliated Hospital of Hangzhou Normal University, Hangzhou (China); Fan, Yaohua [Oncology Department, No. 1 Hospital of Jiaxing, Zhejiang Province, Jiaxing (China); Chen, Gongying [Oncology Department, The Affiliated Hospital Hangzhou Normal University, Hangzhou (China); Wang, Zhengrong [Taizhou Hospital, Zhejiang Province, Taizhou (China); Kong, Dexin; Zhang, Peng [Oncology Department, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou (China)

2016-05-27

The search for novel anti-hepatocellular carcinoma (HCC) agents is important. Mammalian target of rapamycin (mTOR) hyper-activation plays a pivotal role in promoting HCC tumorigenesis and chemoresistance. The current preclinical study evaluated the potential anti-HCC activity by a potent mTOR kinase inhibitor, WAY-600. We showed that WAY-600 inhibited survival and proliferation of HCC cell lines (HepG2 and Huh7) and primary human HCC cells. Caspase-dependent apoptosis was activated by WAY-600 in above HCC cells. Reversely, caspase inhibitors largely attenuated WAY-600's lethality against HCC cells. At the signaling level, WAY-600 blocked mTOR complex 1/2 (mTORC1/2) assemble and activation, yet activated MEK-ERK pathway in HCC cells. MEK-ERK inhibitors, PD-98059 and MEK-162, or MEK1/2 shRNA significantly potentiated WAY-600's cytotoxicity in HCC cells. Further studies showed that WAY-600 intraperitoneal (i.p.) administration in nude mice inhibited p-AKT Ser-473 and displayed significant anti-cancer activity against HepG2 xenografts. Remarkably, co-administration of MEK-162 further potentiated WAY-600's anti-HCC activity in vivo. These preclinical results demonstrate the potent anti-HCC activity by WAY-600, either alone or with MEK-ERK inhibitors. -- Highlights: •WAY-600 inhibits HCC cell survival and proliferation in vitro. •WAY-600 activates caspase-dependent apoptosis in HCC cells. •WAY-600 blocks mTORC1/2 activation, but activates MEK-ERK in HCC cells. •MEK-ERK inhibitors or MEK1/2 shRNA enhances WAY-600's cytotoxicity against HCC cells. •MEK-162 co-administration potentiates WAY-600-induced the anti-HepG2 tumor efficacy.

34 CFR 106.56 - Fringe benefits.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Fringe benefits. 106.56 Section 106.56 Education... benefits. (a) Fringe benefits defined. For purposes of this part, fringe benefits means: Any medical, hospital, accident, life insurance or retirement benefit, service, policy or plan, any profit-sharing or...

5 CFR 9901.106 - Relationship to other provisions.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Relationship to other provisions. 9901.106 Section 9901.106 Administrative Personnel DEPARTMENT OF DEFENSE HUMAN RESOURCES MANAGEMENT AND....S.C. 5545b; and (iii) Recruitment, relocation, and retention payments under 5 U.S.C. 5753 through...

VU0477573: Partial Negative Allosteric Modulator of the Subtype 5 Metabotropic Glutamate Receptor with In Vivo Efficacy.

Science.gov (United States)

Nickols, Hilary Highfield; Yuh, Joannes P; Gregory, Karen J; Morrison, Ryan D; Bates, Brittney S; Stauffer, Shaun R; Emmitte, Kyle A; Bubser, Michael; Peng, Weimin; Nedelcovych, Michael T; Thompson, Analisa; Lv, Xiaohui; Xiang, Zixiu; Daniels, J Scott; Niswender, Colleen M; Lindsley, Craig W; Jones, Carrie K; Conn, P Jeffrey

2016-01-01

Negative allosteric modulators (NAMs) of metabotropic glutamate receptor subtype 5 (mGlu5) have potential applications in the treatment of fragile X syndrome, levodopa-induced dyskinesia in Parkinson disease, Alzheimer disease, addiction, and anxiety; however, clinical and preclinical studies raise concerns that complete blockade of mGlu5 and inverse agonist activity of current mGlu5 NAMs contribute to adverse effects that limit the therapeutic use of these compounds. We report the discovery and characterization of a novel mGlu5 NAM, N,N-diethyl-5-((3-fluorophenyl)ethynyl)picolinamide (VU0477573) that binds to the same allosteric site as the prototypical mGlu5 NAM MPEP but displays weak negative cooperativity. Because of this weak cooperativity, VU0477573 acts as a "partial NAM" so that full occupancy of the MPEP site does not completely inhibit maximal effects of mGlu5 agonists on intracellular calcium mobilization, inositol phosphate (IP) accumulation, or inhibition of synaptic transmission at the hippocampal Schaffer collateral-CA1 synapse. Unlike previous mGlu5 NAMs, VU0477573 displays no inverse agonist activity assessed using measures of effects on basal [(3)H]inositol phosphate (IP) accumulation. VU0477573 acts as a full NAM when measuring effects on mGlu5-mediated extracellular signal-related kinases 1/2 phosphorylation, which may indicate functional bias. VU0477573 exhibits an excellent pharmacokinetic profile and good brain penetration in rodents and provides dose-dependent full mGlu5 occupancy in the central nervous system (CNS) with systemic administration. Interestingly, VU0477573 shows robust efficacy, comparable to the mGlu5 NAM MTEP, in models of anxiolytic activity at doses that provide full CNS occupancy of mGlu5 and demonstrate an excellent CNS occupancy-efficacy relationship. VU0477573 provides an exciting new tool to investigate the efficacy of partial NAMs in animal models. Copyright © 2015 by The American Society for Pharmacology and

Characterization of VuMATE1 expression in response to iron nutrition and aluminum stress reveals adaptation of rice bean (Vigna umbellata to acid soils through cis regulation

Directory of Open Access Journals (Sweden)

Meiya eLiu

2016-04-01

Full Text Available Rice bean (Vigna umbellata VuMATE1 appears to be constitutively expressed at vascular system but root apex, and Al stress extends its expression to root apex. Whether VuMATE1 participates in both Al tolerance and Fe nutrition, and how VuMATE1 expression is regulated is of great interest. In this study, the role of VuMATE1 in Fe nutrition was characterized through in planta complementation assays. The transcriptional regulation of VuMATE1 was investigated through promoter analysis and promoter-GUS reporter assays. The results showed that the expression of VuMATE1 was regulated by Al stress but not Fe status. Complementation of frd3-1 with VuMATE1 under VuMATE1 promoter could not restore phenotype, but restored with 35SCaMV promoter. Immunostaining of VuMATE1 revealed abnormal localization of VuMATE1 in vasculature. In planta GUS reporter assay identified Al-responsive cis-acting elements resided between -1228 and -574 bp. Promoter analysis revealed several cis-acting elements, but transcription is not simply regulated by one of these elements. We demonstrated that cis regulation of VuMATE1 expression is involved in Al tolerance mechanism, while not involved in Fe nutrition. These results reveal the evolution of VuMATE1 expression for better adaptation of rice bean to acidic soils where Al stress imposed but Fe deficiency pressure released.

Déjà vu experiences in healthy subjects are unrelated to laboratory tests of recollection and familiarity for word stimuli

Directory of Open Access Journals (Sweden)

Akira Robert O'Connor

2013-11-01

Full Text Available Recent neuropsychological and neuroscientific research suggests that people who experience more déjà vu display characteristic patterns in normal recognition memory. We conducted a large individual differences study (n = 206 to test these predictions using recollection and familiarity parameters recovered from a standard memory task. Participants reported déjà vu frequency and a number of its correlates, and completed a recognition memory task analogous to a Remember-Know procedure. The individual difference measures replicated an established correlation between déjà vu frequency and frequency of travel, and recognition performance showed well-established word frequency and accuracy effects. Contrary to predictions, no relationships were found between déjà vu frequency and recollection or familiarity memory parameters from the recognition test. We suggest that déjà vu in the healthy population reflects a mismatch between errant memory signalling and memory monitoring processes not easily characterised by standard recognition memory task performance.

The Persistence of Erroneous Familiarity in an Epileptic Male: Challenging Perceptual Theories of Deja Vu Activation

Science.gov (United States)

O'Connor, Akira R.; Moulin, Christopher J. A.

2008-01-01

We report the case of a 39-year-old, temporal lobe epileptic male, MH. Prior to complex partial seizure, experienced up to three times a day, MH often experiences an aura experienced as a persistent sensation of deja vu. Data-driven theories of deja vu formation suggest that partial familiarity for the perceived stimulus is responsible for the…

Dual Inhibition of MEK and PI3K/Akt Rescues Cancer Cachexia through Both Tumor Extrinsic and Intrinsic Activities

Science.gov (United States)

Mace, Thomas A.; Farren, Matthew R.; Farris, Alton B.; Young, Gregory S.; Elnaggar, Omar; Che, Zheng; Timmers, Cynthia D.; Rajasekera, Priyani; Maskarinec, Jennifer M.; Bloomston, Mark; Bekaii-Saab, Tanios; Guttridge, Denis C.; Lesinski, Gregory B.

2016-01-01

Involuntary weight loss, a part of the cachexia syndrome, is a debilitating co-morbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses, but surprisingly gained weight and increased their skeletal muscle mass. This implied that MEK inhibition might be anti-cachectic. To test this potential effect of MEK inhibition, we utilized the established Colon-26 model of cancer cachexia and the MEK1/2 inhibitor MEK162. Results showed that MEK inhibition effectively prevented muscle wasting. Importantly, MEK162 retained its ability to spare muscle loss even in mice bearing a Colon-26 clone resistant to the MEK inhibitor, demonstrating that the effects of blocking MEK is at least in part independent of the tumor. Because single agent MEK inhibitors have been limited as a front-line targeted therapy due to compensatory activation of other oncogenic signaling pathways, we combined MEK162 with the PI3K/Akt inhibitor buparlisib. Results showed that this combinatorial treatment significantly reduced tumor growth due to a direct activity on Colon-26 tumor cells in vitro and in vivo, while also preserving skeletal muscle mass. Together, our results suggest that as a monotherapy MEK inhibition preserves muscle mass, but when combined with a PI3K/Akt inhibitor exhibits potent anti-tumor activity. Thus, combinatorial therapy might serve as a new approach for the treatment of cancer cachexia. PMID:27811010

The persistence of erroneous familiarity in an epileptic male : Challenging perceptual theories of déjà vu activation

OpenAIRE

O'Connor, Akira Robert; Moulin, Christopher J. A.

2008-01-01

We report the case of a 39-year-old, temporal lobe epileptic male, MH. Prior to complex partial seizure, experienced up to three times a day, MH often experiences an aura experienced as a persistent sensation of deja vu. Data-driven theories of deja vu formation suggest that partial familiarity for the perceived stimulus is responsible for the sensation. Consequently, diverting attention away from this stimulus should cause the sensation to dissipate. MH, whose sensations of deja vu persist l...

49 CFR 106.10 - Process for issuing rules.

Science.gov (United States)

2010-10-01

... filing written comments or making oral presentations). (4) Whom to call if you have questions about the... 49 Transportation 2 2010-10-01 2010-10-01 false Process for issuing rules. 106.10 Section 106.10... PHMSA Rulemaking Documents § 106.10 Process for issuing rules. (a) PHMSA (“we”) uses informal rulemaking...

7 CFR 1955.12 - Acquisition of property which served as security for a loan guarantee by FmHA or its successor...

Science.gov (United States)

2010-01-01

... Chattel Property § 1955.12 Acquisition of property which served as security for a loan guarantee by FmHA... 7 Agriculture 14 2010-01-01 2009-01-01 true Acquisition of property which served as security for a loan guarantee by FmHA or its successor agency under Public Law 103-354 or at sale by another...

FM Research for Practice in Denmark

DEFF Research Database (Denmark)

Jensen, Per Anker

handover of data from building projects to FM and Building Information Modelling also became an important field of development. Research in FM started at DTU in 2003 and got a major boost by the establishing of CFM in 2008. In recent years sustainability has emerged as a new important research area in FM...... on national level, which have had importance to constitute and form a professional basis for FM. Approach (Theory/Methodology): The paper provides a chronological overview of research and development activities related to FM over the last 30 years in Denmark, including CFM’s ongoing research projects. Results......: In the 1980’s the research activities related to FM mostly concerned indoor climate and there was also some research on briefing and development projects concerning building operation. In the 1990’s the research related to FM was broadened to a wider environmental focus including energy and the external...

FM research for practice in Denmark

DEFF Research Database (Denmark)

Jensen, Per Anker

2012-01-01

handover of data from building projects to FM and Building Information Modelling also became an important field of development. Research in FM started at DTU in 2003 and got a major boost by the establishing of CFM in 2008. In recent years sustainability has emerged as a new important research area in FM...... on national level, which have had importance to constitute and form a professional basis for FM. Approach (Theory/Methodology): The paper provides a chronological overview of research and development activities related to FM over the last 30 years in Denmark, including CFM’s ongoing research projects. Results......: In the 1980’s the research activities related to FM mostly concerned indoor climate and there was also some research on briefing and development projects concerning building operation. In the 1990’s the research related to FM was broadened to a wider environmental focus including energy and the external...

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM4_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Terra-FM1_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM4_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_PFM+FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM3_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-10-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_PFM+FM1_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Terra-FM1_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-10-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Terra-FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-10-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM3_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

34 CFR 106.55 - Job classification and structure.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Job classification and structure. 106.55 Section 106.55 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF... Prohibited § 106.55 Job classification and structure. A recipient shall not: (a) Classify a job as being for...

Electrochemical incineration of indigo textile dye in filter-press-type FM01-LC electrochemical cell using BDD electrodes

Energy Technology Data Exchange (ETDEWEB)

Butron, Edgar [Universidad Nacional Autonoma de Mexico, Facultad de Estudios Superiores-Zaragoza, Mexico, D.F. (Mexico); Juarez, Manuel E.; Solis, Myrna [Instituto Politecnico Nacional, Centro de investigacion en Biotecnologia Avanzada, Tlaxcala (Mexico); Teutli, Margarita [Benemerita Universidad Autonoma de Puebla, Facultad de Ingenieria, Edificio 123, Cd. Universitaria, Puebla, Pue. (Mexico); Gonzalez, Ignacio; Nava, Jose L. [Universidad Autonoma Metropolitana-Iztapalapa, Departamento de Quimica, Mexico, D.F. (Mexico)

2007-08-01

This work shows results obtained in the incineration of 1 mM indigo textile dye (536 ppm COD) in 0.05 M NaCl aqueous media (which resembles a denim laundry industrial wastewater). Microelectrolysis and macroelectrolysis studies indicated that oxidation of indigo dye was carried out via hydroxyl radicals (OH.) formed by water oxidation on the BDD surface, instead of active chlorine as usually occurs by using DSA. Electrolyses in a FM01-LC reactor was performed at Reynolds between 1600 < Re < 18300, and a fixed current density of 5.3 and 15 mA cm{sup -2}. The experimental set-up achieved 100% efficiency in color removal, indigo mineralization and current efficiency. Estimated energy consumption, at Re = 12892 and J = 5.3 mA cm{sup -2}, was 9 kWh m{sup -3}. Experimental data revealed that hydrodynamic conditions do not influence either the indigo degradation rate or the current efficiencies; therefore indigo degradation must involve a complex mechanism. (author)

Dual Inhibition of MEK and PI3K/Akt Rescues Cancer Cachexia through both Tumor-Extrinsic and -Intrinsic Activities.

Science.gov (United States)

Talbert, Erin E; Yang, Jennifer; Mace, Thomas A; Farren, Matthew R; Farris, Alton B; Young, Gregory S; Elnaggar, Omar; Che, Zheng; Timmers, Cynthia D; Rajasekera, Priyani; Maskarinec, Jennifer M; Bloomston, Mark; Bekaii-Saab, Tanios; Guttridge, Denis C; Lesinski, Gregory B

2017-02-01

Involuntary weight loss, a part of the cachexia syndrome, is a debilitating comorbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses but surprisingly gained weight and increased their skeletal muscle mass. This implied that MEK inhibition might be anticachectic. To test this potential effect of MEK inhibition, we utilized the established Colon-26 model of cancer cachexia and the MEK1/2 inhibitor MEK162. Results showed that MEK inhibition effectively prevented muscle wasting. Importantly, MEK162 retained its ability to spare muscle loss even in mice bearing a Colon-26 clone resistant to the MEK inhibitor, demonstrating that the effects of blocking MEK are at least in part independent of the tumor. Because single-agent MEK inhibitors have been limited as a first-line targeted therapy due to compensatory activation of other oncogenic signaling pathways, we combined MEK162 with the PI3K/Akt inhibitor buparlisib. Results showed that this combinatorial treatment significantly reduced tumor growth due to a direct activity on Colon-26 tumor cells in vitro and in vivo, while also preserving skeletal muscle mass. Together, our results suggest that as a monotherapy, MEK inhibition preserves muscle mass, but when combined with a PI3K/Akt inhibitor exhibits potent antitumor activity. Thus, combinatorial therapy might serve as a new approach for the treatment of cancer cachexia. Mol Cancer Ther; 16(2); 344-56. ©2016 AACRSee related article by Kobayashi et al., p. 357. ©2016 American Association for Cancer Research.

5 CFR 3601.106 - Limitation on solicited sales.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Limitation on solicited sales. 3601.106... FOR EMPLOYEES OF THE DEPARTMENT OF DEFENSE § 3601.106 Limitation on solicited sales. A DoD employee shall not knowingly solicit or make solicited sales to DoD personnel who are junior in rank, grade or...

Obama vu de ma banlieue.

Directory of Open Access Journals (Sweden)

Olga Stanislawska

2008-12-01

Full Text Available Une petite brocante est organisée tous les jeudis sur une place proche de la Basilique de Saint-Denis. On y vend des livres, des bibelots, des bijoux fantaisies et des masques africains. L’un des vendeurs a visiblement décidé de bénéficier de l’effet Obama. J’ai pris la photo de ma fenêtre, située au dessus de ce marché. J’ai adoré ce stand, mais ce n’est qu’une fois sur l’écran de mon ordinateur que j’ai vu les petites images Banania... ! Si j’avais su, je serais ...

27 CFR 21.106 - Diethyl phthalate.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Diethyl phthalate. 21.106....106 Diethyl phthalate. (a) Refractive index at 25 °C. 1.497 to 1.502. (b) Color. Colorless. (c) Odor... °/25 °C. 1.115 to 1.118. (f) Ester content (as diethyl phthalate). Not less than 99 percent by weight...

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_Aqua-FM3_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-10-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_Terra-FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-10-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_PFM+FM1_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_Aqua-FM4_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_PFM+FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_Aqua-FM4_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_Terra-FM1_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-10-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

Het presteren van FM

NARCIS (Netherlands)

van der Voordt, D.J.M.

2008-01-01

Prestatieafspraken. Prestatiespecificaties. Prestatiecontracten. Het woord prestatie duikt steeds vaker op in de wereld van FM. Maar wat bedoelen we er nu precies mee? En kunnen we de prestaties van FM wel op een betrouwbare en valide manier meten? Een beschouwing vanuit de wereld van een

PENGARUH REGENERASI KOLOM ALUMINA ASAM TERHADAP RECOVERY DAN KUALITAS 99mTc HASIL EKSTRAKSI PELARUT MEK DARI 99Mo HASIL AKTIVASI NEUTRON

Directory of Open Access Journals (Sweden)

Adang H G

2017-01-01

Full Text Available ABSTRAK PENGARUH REGENERASI KOLOM ALUMINA ASAM TERHADAP RECOVERY DAN KUALITAS 99mTc HASIL EKSTRAKSI PELARUT MEK DARI 99Mo HASIL AKTIVASI NEUTRON. Melalui kerjasama antara PTRR-BATAN, Chiyoda dan JAEA Jepang telah dilakukan pemurnian 99mTc dari 99Mo hasil aktivasi neutron dengan menggunakan metode kromatografi kolom alumina asam terhadap hasil ekstraksi MEK (Metil Etil Keton. Pemurnian 99mTc dengan metode kolom alumina asam hanya dapat digunakan satu kali dan pemurnian berikutnya harus diganti dengan kolom baru. Hal ini dinilai kurang praktis dan juga memerlukan biaya yang mahal. Dalam penelitian ini dicoba penggunaan kolom alumina asam untuk pemurnian 99mTc lebih dari satu kali dengan melakukan proses regenerasi dengan cara melewatkan larutan HNO3 0,1N setiap kali proses pemurnian selesai. Penelitian ini bertujuan untuk mendapatkan larutan 99mTc yang dapat digunakan untuk penandaan kit radiofarmaka. Parameter yang diamati dalam penelitian ini adalah recovery, profil elusi, pH, kemurnian radiokimia dan kemurnian radionuklida (lolosan 99Mo. Hasil penelitian yang dilakukan selama 5 hari telah diperoleh pH ~5, recovery > 60 %, kemurnian radiokimia > 95 % dan lolosan 99Mo tidak terdeteksi. Dari hasil perlakuan terhadap kolom alumina asam dengan larutan HNO3 0,1 N disimpulkan bahwa kolom alumina asam tidak perlu diganti setiap hari. Kata kunci: 99mTc, 99Mo, MEK, kolom alumina asam, kemurnian radiokimia. ABSTRACT Purification of 99mTc from 99Mo activation using acidic alumina column chromatography system from MEK (Methyl Ethyl Keton extraction has been carried out through cooperation between PTRR - BATAN, Chiyoda and JAEA Japan. This method has a limitation that acidic alumina column for purification of 99mTc can be used only once, for the next purification acidic alumina column should be replaced with new column, so it is less practical and also requires high cost. This study aims to obtain a 99mTc solution can be use for labelling of a

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Terra-FM1_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2006-09-30] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM4_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

40 CFR 90.106 - Certificate of conformity.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Certificate of conformity. 90.106... Standards and Certification Provisions § 90.106 Certificate of conformity. (a)(1) Except as provided in § 90... certificate of conformity covering such engines; however, engines manufactured during an annual production...

40 CFR 91.106 - Certificate of conformity.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Certificate of conformity. 91.106... Provisions § 91.106 Certificate of conformity. (a) Every manufacturer of a new marine SI engine produced... obtain a certificate of conformity covering each engine family. The certificate of conformity must be...

Transformation Deja Vu? A Comparison of Military Improvements of Israel (1967-1973) and the United States (1990-2002)

Science.gov (United States)

2002-09-06

Transformation Déjà Vu ? A Comparison of Military Improvements of Israel (1967-1973) and the United States (1990-2002) Major William A. Forkner, USAF...Transformation Déjà Vu ? A Comparison of Military Improvements of Israel (1967-1973) and the United States (1990-2002) 5a. CONTRACT NUMBER 5b. GRANT NUMBER

47 CFR 68.106 - Notification to provider of wireline telecommunications.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Notification to provider of wireline telecommunications. 68.106 Section 68.106 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... of Terminal Equipment § 68.106 Notification to provider of wireline telecommunications. (a) General...

14 CFR 1221.106 - Establishment of the NASA Flag.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Establishment of the NASA Flag. 1221.106 Section 1221.106 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION THE NASA SEAL AND OTHER DEVICES, AND THE CONGRESSIONAL SPACE MEDAL OF HONOR NASA Seal, NASA Insignia, NASA Logotype, NASA...

Comparison of responses of human melanoma cell lines to MEK and BRAF inhibitors

Directory of Open Access Journals (Sweden)

Clare Judith Stones

2013-05-01

Full Text Available The NRAS and BRAF genes are frequently mutated in melanoma, suggesting that the NRAS-BRAF-MEK-ERK signalling pathway is an important target for therapy. Two classes of drugs, one targeting activated BRAF and one targeting MEK, are currently undergoing clinical evaluation. We have analysed the NRAS and BRAF mutational status of a series of 44 early passage lines developed from New Zealand patients with metastatic melanoma. 41% of the lines analysed had BRAF mutations, 23% had NRAS mutations and 36% had neither. We then determined IC50 values (drug concentrations for 50% growth inhibition for CI-1040, a commonly used inhibitor of MEK kinase; trametinib, a clinical agent targeting MEK kinase; and vemurafenib, an inhibitor of mutant BRAF kinase. Cell lines with activating BRAF mutations were significantly more sensitive to vemurafenib than lines with NRAS mutations or lines lacking either mutation (p < 0.001. IC50 values for CI-1040 and trametinib were strongly correlated (r = 0.98 with trametinib showing ~100-fold greater potency. Cell lines sensitive to vemurafenib were also sensitive to CI-1040 and trametinib, but there was no relationship between IC50 values and NRAS mutation status. A small number of lines lacking a BRAF mutation were sensitive to CI-1040 but resistant to vemurafenib. We used western blotting to investigate the effect on ERK phosphorylation of CI-1040 in four lines, of vemurafenib in two lines and of trametinib in two lines. The results support the view that MEK inhibitors might be combined with BRAF inhibitors in the treatment melanomas of with activated BRAF. The high sensitivity to trametinib of some lines with wild-type BRAF status also suggests that MEK inhibitors could have a therapeutic effect against some melanomas as single agents.

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CERES:CER_ES9_PFM+FM1_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF ( CER_ES9_Aqua-FM4_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

47 CFR 73.1210 - TV/FM dual-language broadcasting in Puerto Rico.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false TV/FM dual-language broadcasting in Puerto Rico...-language broadcasting in Puerto Rico. (a) For the purpose of this section, dual-language broadcasting shall... a different language. (b) Television and Class A television licensees in Puerto Rico may enter into...

14 CFR 1203b.106 - Use of deadly force.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Use of deadly force. 1203b.106 Section... AUTHORITY AND USE OF FORCE BY NASA SECURITY FORCE PERSONNEL § 1203b.106 Use of deadly force. Deadly force shall be used only in those circumstances where the security force officer reasonably believes that...

Parachuting from fixed objects: descriptive study of 106 fatal events in BASE jumping 1981-2006.

Science.gov (United States)

Westman, A; Rosén, M; Berggren, P; Björnstig, U

2008-06-01

To analyse the characteristics of fatal incidents in fixed object sport parachuting (building, antenna, span, earth (BASE) jumping) and create a basis for prevention. Descriptive epidemiological study. Data on reported fatal injury events (n = 106) worldwide in 1981-2006 retrieved from the BASE fatality list. Human, equipment and environmental factors. Identification of typical fatal incident and injury mechanisms for each of the four fixed object types of BASE jumping (building, antenna, span, earth). Human factors included parachutist free fall instability (loss of body control before parachute deployment), free fall acrobatics and deployment failure by the parachutist. Equipment factors included pilot chute malfunction and parachute malfunction. In cliff jumping (BASE object type E), parachute opening towards the object jumped was the most frequent equipment factor. Environmental factors included poor visibility, strong or turbulent winds, cold and water. The overall annual fatality risk for all object types during the year 2002 was estimated at about one fatality per 60 participants. Participants in BASE jumping should target risk factors with training and technical interventions. The mechanisms described in this study should be used by rescue units to improve the management of incidents.

13 CFR 106.500 - What is SBA's Gift authority?

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What is SBA's Gift authority? 106... AND NON-FEE BASED SBA-SPONSORED ACTIVITIES AND GIFTS Gifts § 106.500 What is SBA's Gift authority? This section covers SBA's Gift acceptance authority under sections 4(g), 8(b)(1)(G), 5(b)(9) and 7(k)(2...

40 CFR Table 34 to Subpart G of... - Fraction Measured (Fm) and Fraction Emitted (Fe) For HAP Compounds in Wastewater Streams

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Fraction Measured (Fm) and Fraction... Vessels, Transfer Operations, and Wastewater Pt. 63, Subpt. G, Table 34 Table 34 to Subpart G of Part 63—Fraction Measured (Fm) and Fraction Emitted (Fe) For HAP Compounds in Wastewater Streams Chemical name CAS...

41 CFR 115-1.106 - Applicability of FPMR.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Applicability of FPMR. 115-1.106 Section 115-1.106 Public Contracts and Property Management Federal Property Management Regulations System (Continued) ENVIRONMENTAL PROTECTION AGENCY 1-INTRODUCTION 1.1-Regulation System § 115-1...

41 CFR 101-1.106 - Applicability of FPMR.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Applicability of FPMR. 101-1.106 Section 101-1.106 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS GENERAL 1-INTRODUCTION 1.1-Regulation System § 101...

Remote Metrology, Mapping, and Motion Sensing of Plasma Facing Components Using FM Coherent Laser Radar

International Nuclear Information System (INIS)

Menon, M.M.; Barry, R.E.; Slotwinsky, A.; Kugel, H.W.; Skinner, C.H.

2000-01-01

Metrology inside a D/T burning fusion reactor must necessarily be conducted remotely since the in-vessel environment would be highly radioactive due to neutron activation of the torus walls. A technique based on frequency modulated coherent laser radar (FM CLR) for such remote metrology is described. Since the FM CLR relies on frequency shift to measure distances, the results are largely insensitive to surface reflectance characteristics. Results of measurements in TFTR and NSTX fusion devices using a prototype FM CLR unit, capable of remotely measuring distances (range) up to 22 m with better than 0.1-mm precision, are provided. These results illustrate that the FM CLR can be used for precision remote metrology as well as viewing. It is also shown that by conducting Doppler corrected range measurements using the CLR, the motion of objects can be tracked. Thus, the FM CLR has the potential to remotely measure the motion of plasma facing components (PFCs) during plasma disruptions

Deja Vu in Unilateral Temporal-Lobe Epilepsy Is Associated with Selective Familiarity Impairments on Experimental Tasks of Recognition Memory

Science.gov (United States)

Martin, Chris B.; Mirsattari, Seyed M.; Pruessner, Jens C.; Pietrantonio, Sandra; Burneo, Jorge G.; Hayman-Abello, Brent; Kohler, Stefan

2012-01-01

In deja vu, a phenomenological impression of familiarity for the current visual environment is experienced with a sense that it should in fact not feel familiar. The fleeting nature of this phenomenon in daily life, and the difficulty in developing experimental paradigms to elicit it, has hindered progress in understanding deja vu. Some…

29 CFR 1952.106 - Where the plan may be inspected.

Science.gov (United States)

2010-07-01

... and copied during normal business hours at the following locations: Office of State Programs... 29 Labor 9 2010-07-01 2010-07-01 false Where the plan may be inspected. 1952.106 Section 1952.106..., DEPARTMENT OF LABOR (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Oregon § 1952.106...

Déjà Vu: tradução assistida ao pormenor.

Directory of Open Access Journals (Sweden)

Leonel Morgado

2004-01-01

Full Text Available No campo da tradução assistida por computador, apresenta-se aqui o programa Déjà Vu. Entre outras características interessantes, este programa possui uma funcionalidade fundamental e pioneira, que contribui significativamente para a melhoria do desempenho, da coerência e da rapidez do trabalho de tradução: o reaproveitamento automático de partes de expressões, não apenas de expressões inteiras. O tradutor pode, rapidamente, enviar para a memória de tradução pares linguísticos tão simples como uma simples palavra e a respectiva tradução, não apenas frases inteiras. À medida que o programa Déjà Vu recebe os pares, passa a utilizá-los para traduzir pedaços das frases e expressões que vão surgindo, não apenas frases inteiras (se o tradutor preferir, o Déjà Vu pode apenas sugerir as traduções, em vez de as aplicar. Desta forma, o tradutor é apoiado automaticamente, mas não apenas na terminologia e nos casos de repetição de frases, como é mais habitual. Pode passar a ter apoio relativamente às formas que utiliza para expressões ou combinações de palavras que se revelem frequentes num projecto específico, ainda que não sejam suficientemente relevante para integrar glossários ou outras bases de dados terminológicas.

20 CFR 653.106 - JS day-haul responsibilities.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false JS day-haul responsibilities. 653.106 Section... THE EMPLOYMENT SERVICE SYSTEM Services for Migrant and Seasonal Farmworkers (MSFWs) § 653.106 JS day... Regional Administrator is obtained. (b) No JS applicants shall be referred to non-JS operated day-haul...

34 CFR 300.106 - Extended school year services.

Science.gov (United States)

2010-07-01

... services means special education and related services that— (1) Are provided to a child with a disability... 34 Education 2 2010-07-01 2010-07-01 false Extended school year services. 300.106 Section 300.106 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION...

Mod bæredygtig FM i Danmark

DEFF Research Database (Denmark)

Holm, Camilla Bøje; Pietras, Carsten; Maslesa, Esmir

2013-01-01

Klodens begrænsede ressourcer og klimaforandringer kalder på innovation og pionerer indenfor FM faget. Der er brug for nytænkning og gode eksempler på, hvordan FM opgaver forenes med et bæredygtigt samfundsperspektiv. I Danmark synes der, at være store udviklingspotentialer i FM verdenen på dette...... område, og pt. er der ingen endelige svar på, hvad bæredygtig FM egentlig er....

MEK inhibition potentiates the activity of Hsp90 inhibitor 17-AAG against pancreatic cancer cells.

Science.gov (United States)

Zhang, Tao; Li, Yanyan; Zhu, Zhenkun; Gu, Mancang; Newman, Bryan; Sun, Duxin

2010-10-04

The Ras/Raf/MEK/ERK signaling has been implicated in uncontrolled cell proliferation and tumor progression in pancreatic cancer. The purpose of this study is to evaluate the antitumor activity of MEK inhibitor U0126 in combination with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in pancreatic cancer cells. Western blotting showed that 17-AAG caused a 2- to 3-fold transient activation of MEK/ERK signaling in pancreatic cancer cells. The activation sustained for 6 h before phospho-ERK (p-ERK) destabilization. The selective MEK inhibitor U0126 completely abolished 17-AAG induced ERK1/2 activation and resulted in more than 80% of phospho-ERK degradation after only 15 min treatment. Moreover, U0126 had complementary effect on 17-AAG regulated oncogenic and cell cycle related proteins. Although 17-AAG downregulated cyclin D1, cyclin E, CDK4 and CDK6, it led to cyclin A and CDK2 accumulation, which was reversed by the addition of U0126. Antiproliferation assay showed that combination of U0126 and 17-AAG resulted in synergistic cytotoxic effect. More importantly, 17-AAG alone only exhibited moderate inhibition of cell migration in vitro, while addition of U0126 dramatically enhanced the inhibitory effect by 2- to 5-fold. Taken together, these data demonstrate that MEK inhibitor U0126 potentiates the activity of Hsp90 inhibitor 17-AAG against pancreatic cancer cells. The combination of Hsp90 and MEK inhibition could provide a promising avenue for the treatment of pancreatic cancer.

Mek1/Mre4 is a master regulator of meiotic recombination in budding yeast

Directory of Open Access Journals (Sweden)

Nancy M. Hollingsworth

2016-02-01

Full Text Available Sexually reproducing organisms create gametes with half the somatic cell chromosome number so that fusion of gametes at fertilization does not change the ploidy of the cell. This reduction in chromosome number occurs by the specialized cell division of meiosis in which two rounds of chromosome segregation follow a single round of chromosome duplication. Meiotic crossovers formed between the non-sister chromatids of homologous chromosomes, combined with sister chromatid cohesion, physically connect homologs, thereby allowing proper segregation at the first meiotic division. Meiotic recombination is initiated by programmed double strand breaks (DSBs whose repair is highly regulated such that (1 there is a bias for recombination with homologs rather than sister chromatids, (2 crossovers are distributed throughout the genome by a process called interference, (3 crossover homeostasis regulates the balance between crossover and non-crossover repair to maintain a critical number of crossovers and (4 each pair of homologs receives at least one crossover. It was previously known that the imposition of interhomolog bias in budding yeast requires meiosis-specific modifications to the DNA damage response and the local activation of the meiosis-specific Mek1/Mre4 (hereafter Mek1 kinase at DSBs. However, because inactivation of Mek1 results in intersister, rather than interhomolog DSB repair, whether Mek1 had a role in interhomolog pathway choice was unknown. A recent study by Chen et al. (2015 reveals that Mek1 indirectly regulates the crossover/non-crossover decision between homologs as well as genetic interference. It does this by enabling phosphorylation of Zip1, the meiosis-specific transverse filament protein of the synaptonemal complex (SC, by the conserved cell cycle kinase, Cdc7-Dbf4 (DDK. These results suggest that Mek1 is a “master regulator” of meiotic recombination in budding yeast.

The déjà vu experience: remembrance of things past?

NARCIS (Netherlands)

Sno, H. N.; Linszen, D. H.

1990-01-01

The déjà vu experience is a common phenomenon, occurring in pathological as well as nonpathological conditions. It has been defined as any subjectively inappropriate impression of familiarity of a present experience with an undefined past. The authors discuss the epidemiologic data, clinical

34 CFR 106.42 - Textbooks and curricular material.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Textbooks and curricular material. 106.42 Section 106.42 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on...

Disruption of MEK/ERK/c-Myc signaling radiosensitizes prostate cancer cells in vitro and in vivo.

Science.gov (United States)

Ciccarelli, Carmela; Di Rocco, Agnese; Gravina, Giovanni Luca; Mauro, Annunziata; Festuccia, Claudio; Del Fattore, Andrea; Berardinelli, Paolo; De Felice, Francesca; Musio, Daniela; Bouché, Marina; Tombolini, Vincenzo; Zani, Bianca Maria; Marampon, Francesco

2018-06-29

Prostate cancer (PCa) cell radioresistance causes the failure of radiation therapy (RT) in localized or locally advanced disease. The aberrant accumulation of c-Myc oncoprotein, known to promote PCa onset and progression, may be due to the control of gene transcription and/or MEK/ERK-regulated protein stabilization. Here, we investigated the role of MEK/ERK signaling in PCa. LnCAP, 22Rv1, DU145, and PC3 PCa cell lines were used in in vitro and in vivo experiments. U0126, trametinib MEK/ERK inhibitors, and c-Myc shRNAs were used. Radiation was delivered using an x-6 MV photon linear accelerator. U0126 in vivo activity alone or in combination with irradiation was determined in murine xenografts. Inhibition of MEK/ERK signaling down-regulated c-Myc protein in PCa cell lines to varying extents by affecting expression of RNA and protein, which in turn determined radiosensitization in in vitro and in vivo xenograft models of PCa cells. The crucial role played by c-Myc in the MEK/ERK pathways was demonstrated in 22Rv1 cells by the silencing of c-Myc by means of short hairpin mRNA, which yielded effects resembling the targeting of MEK/ERK signaling. The clinically approved compound trametinib used in vitro yielded the same effects as U0126 on growth and C-Myc expression. Notably, U0126 and trametinib induced a drastic down-regulation of BMX, which is known to prevent apoptosis in cancer cells. The results of our study suggest that signal transduction-based therapy can, by disrupting the MEK/ERK/c-Myc axis, reduce human PCa radioresistance caused by increased c-Myc expression in vivo and in vitro and restores apoptosis signals.

MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish

DEFF Research Database (Denmark)

Lundegaard, Pia R.; Anastasaki, Corina; Grant, Nicola J.

2015-01-01

Altered phosphodiesterase (PDE)-cyclic AMP (cAMP) activity is frequently associated with anxiety disorders, but current therapies act by reducing neuronal excitability rather than targeting PDE-cAMP-mediated signaling pathways. Here, we report the novel repositioning of anti-cancer MEK inhibitors...... as anxiolytics in a zebrafish model of anxiety-like behaviors. PDE inhibitors or activators of adenylate cyclase cause behaviors consistent with anxiety in larvae and adult zebrafish. Small-molecule screening identifies MEK inhibitors as potent suppressors of cAMP anxiety behaviors in both larvae and adult...... zebrafish, while causing no anxiolytic behavioral effects on their own. The mechanism underlying cAMP-induced anxiety is via crosstalk to activation of the RAS-MAPK signaling pathway. We propose that targeting crosstalk signaling pathways can be an effective strategy for mental health disorders, and advance...

48 CFR 18.106 - Acquisitions from Federal Prison Industries, Inc. (FPI).

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Acquisitions from Federal Prison Industries, Inc. (FPI). 18.106 Section 18.106 Federal Acquisition Regulations System FEDERAL... Flexibilities 18.106 Acquisitions from Federal Prison Industries, Inc. (FPI). Purchase from FPI is not mandatory...

Pore Polarity and Charge Determine Differential Block of Kir1.1 and Kir7.1 Potassium Channels by Small-Molecule Inhibitor VU590.

Science.gov (United States)

Kharade, Sujay V; Sheehan, Jonathan H; Figueroa, Eric E; Meiler, Jens; Denton, Jerod S

2017-09-01

VU590 was the first publicly disclosed, submicromolar-affinity (IC 50 = 0.2 μ M), small-molecule inhibitor of the inward rectifier potassium (Kir) channel and diuretic target, Kir1.1. VU590 also inhibits Kir7.1 (IC 50 ∼ 8 μ M), and has been used to reveal new roles for Kir7.1 in regulation of myometrial contractility and melanocortin signaling. Here, we employed molecular modeling, mutagenesis, and patch clamp electrophysiology to elucidate the molecular mechanisms underlying VU590 inhibition of Kir1.1 and Kir7.1. Block of both channels is voltage- and K + -dependent, suggesting the VU590 binding site is located within the pore. Mutagenesis analysis in Kir1.1 revealed that asparagine 171 (N171) is the only pore-lining residue required for high-affinity block, and that substituting negatively charged residues (N171D, N171E) at this position dramatically weakens block. In contrast, substituting a negatively charged residue at the equivalent position in Kir7.1 enhances block by VU590, suggesting the VU590 binding mode is different. Interestingly, mutations of threonine 153 (T153) in Kir7.1 that reduce constrained polarity at this site (T153C, T153V, T153S) make wild-type and binding-site mutants (E149Q, A150S) more sensitive to block by VU590. The Kir7.1-T153C mutation enhances block by the structurally unrelated inhibitor VU714 but not by a higher-affinity analog ML418, suggesting that the polar side chain of T153 creates a barrier to low-affinity ligands that interact with E149 and A150. Reverse mutations in Kir1.1 suggest that this mechanism is conserved in other Kir channels. This study reveals a previously unappreciated role of membrane pore polarity in determination of Kir channel inhibitor pharmacology. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Studies on sup(99m)Tc-pertechnetate from the MEK solvent extraction generator

International Nuclear Information System (INIS)

Mohammad, R.; Moore, D.E.; Maddalena, D.J.; Boyd, R.E.

1984-12-01

Analysis by gas chromatography-mass spectrometry and high performance liquid chromatography has revealed organic residues in sup(99m)Tc-pertechnetate obtained from 99 Mo-molybdate by extraction, using the organic solvent methylethylketone (MEK). The organic residues have been identified as either (i) low molecular weight carbonyl compounds such as formaldehyde, acetaldehyde and acetone, presumably caused by the effects of γ-radiation on MEK, or (ii) condensation products resulting from the action of strong alkali on MEK during the extraction process. The quantities of organic residues varied from batch to batch of extracted pertechnetate; up to 40 μ mL -1 was found. When these compounds were tested, in rats, by addition to a pyrophosphate bone-seeking radiopharmaceutical, the tissue distribution was not significantly different from that in the control, which contained no added compound. Assay for 99 Tc in MEK-derived pertechnetate indicated up to 10 μg mL -1 of 99 Tc carrier. An assessment of the biological effect of 99 Tc carrier was obtained by (i) red blood cell labelling, where 6 ng mL -1 of 99 Tc was sufficient to reduce labelling efficiency; and (ii) pyrophosphate tissue distribution, where a significant effect was obtained in the presence of 10 μ mL -1 of 99 Tc carrier

Electrochemical oxidation of bio-refractory dye in a simulated textile industry effluent using DSA electrodes in a filter-press type FM01-LC reactor.

Science.gov (United States)

Rodríguez, Francisca A; Mateo, María N; Aceves, Juan M; Rivero, Eligio P; González, Ignacio

2013-01-01

This work presents a study on degradation of indigo carmine dye in a filter-press type FM01-LC reactor using Sb2O5-doped Ti/IrO2-SnO2 dimensionally stable anode (DSA) electrodes. Micro- and macroelectrolysis studies were carried out using solutions of 0.8 mM indigo carmine in 0.05 M NaCl, which resemble blue denim laundry industrial wastewater. Microelectrolysis results show the behaviour of DSA electrodes in comparison with the behaviour of boron-doped diamond (BDD) electrodes. In general, dye degradation reactions are carried out indirectly through active chlorine generated on DSA, whereas in the case of BDD electrodes more oxidizing species are formed, mainly OH radicals, on the electrode surface. The well-characterized geometry, flow pattern and mass transport of the FM01-LC reactor used in macroelectrolysis experiments allowed the evaluation of the effect of hydrodynamic conditions on the chlorine-mediated degradation rate. Four values of Reynolds number (Re) (93, 371, 464 and 557) at four current densities (50, 100, 150 and 200 A/m2) were tested. The results show that the degradation rate is independent of Re at low current density (50 A/m2) but becomes dependent on the Re at high current density (200 A/m2). This behaviour shows the central role of mass transport and the reactor parameters and design. The low energy consumption (2.02 and 9.04 kWh/m3 for complete discolouration and chemical oxygen demand elimination at 50 A/m2, respectively) and the low cost of DSA electrodes compared to BDD make DSA electrodes promising for practical application in treating industrial textile effluents. In the present study, chlorinated organic compounds were not detected.

The small molecule Mek1/2 inhibitor U0126 disrupts the chordamesoderm to notochord transition in zebrafish

Directory of Open Access Journals (Sweden)

Szabó Gábor

2008-04-01

Full Text Available Abstract Background Key molecules involved in notochord differentiation and function have been identified through genetic analysis in zebrafish and mice, but MEK1 and 2 have so far not been implicated in this process due to early lethality (Mek1-/- and functional redundancy (Mek2-/- in the knockout animals. Results Here, we reveal a potential role for Mek1/2 during notochord development by using the small molecule Mek1/2 inhibitor U0126 which blocks phosphorylation of the Mek1/2 target gene Erk1/2 in vivo. Applying the inhibitor from early gastrulation until the 18-somite stage produces a specific and consistent phenotype with lack of dark pigmentation, shorter tail and an abnormal, undulated notochord. Using morphological analysis, in situ hybridization, immunhistochemistry, TUNEL staining and electron microscopy, we demonstrate that in treated embryos the chordamesoderm to notochord transition is disrupted and identify disorganization in the medial layer of the perinotochordal basement mebrane as the probable cause of the undulations and bulges in the notochord. We also examined and excluded FGF as the upstream signal during this process. Conclusion Using the small chemical U0126, we have established a novel link between MAPK-signaling and notochord differentiation. Our phenotypic analysis suggests a potential connection between the MAPK-pathway, the COPI-mediated intracellular transport and/or the copper-dependent posttranslational regulatory processes during notochord differentiation.

Ocular Toxicity Profile of ST-162 and ST-168 as Novel Bifunctional MEK/PI3K Inhibitors.

Science.gov (United States)

Smith, Andrew; Pawar, Mercy; Van Dort, Marcian E; Galbán, Stefanie; Welton, Amanda R; Thurber, Greg M; Ross, Brian D; Besirli, Cagri G

2018-04-30

ST-162 and ST-168 are small-molecule bifunctional inhibitors of MEK and PI3K signaling pathways that are being developed as novel antitumor agents. Previous small-molecule and biologic MEK inhibitors demonstrated ocular toxicity events that were dose limiting in clinical studies. We evaluated in vitro and in vivo ocular toxicity profiles of ST-162 and ST-168. Photoreceptor cell line 661W and adult retinal pigment epithelium cell line ARPE-19 were treated with increasing concentrations of bifunctional inhibitors. Western blots, cell viability, and caspase activity assays were performed to evaluate MEK and PI3K inhibition and dose-dependent in vitro toxicity, and compared with monotherapy. In vivo toxicity profile was assessed by intravitreal injection of ST-162 and ST-168 in Dutch-Belted rabbits, followed by ocular examination and histological analysis of enucleated eyes. Retinal cell lines treated with ST-162 or ST-168 exhibited dose-dependent inhibition of MEK and PI3K signaling. Compared with inhibition by monotherapies and their combinations, bifunctional inhibitors demonstrated reduced cell death and caspase activity. In vivo, both bifunctional inhibitors exhibited a more favorable toxicity profile when compared with MEK inhibitor PD0325901. Novel MEK and PI3K bifunctional inhibitors ST-162 and ST-168 demonstrate favorable in vitro and in vivo ocular toxicity profiles, supporting their further development as potential therapeutic agents targeting multiple aggressive tumors.

Activation of MEK 1/2 and p42/44 MAPK by Angiotensin II in Hepatocyte Nucleus and their Potentiation by Ethanol

Science.gov (United States)

Aroor, Annayya R.; Lee, Youn Ju; Shukla, Shivendra D.

2009-01-01

Hepato-subcellular effect of Ang II and ethanol on the p42/44 MAP Kinase and MEK1/2 were investigated in the nucleus of rat hepatocytes. Hepatocytes were treated with ethanol (100 mM) for 24 hr and stimulated with angiotensin II (Ang II, 100 nM, 5 min). The levels of p42/44 MAPK and MEK1/2 were monitored in the nuclear fraction using antibodies. Ang II itself caused significant accumulation of phospho-p42/44 MAPK in the nucleus without any significant translocation of p42/44 MAPK protein there by suggesting activation of p42/44 MAPK in the nucleus. Ang II caused marked accumulation of phospho-MEK 1/2 in the nucleus without any significant accumulation of MEK1/2 protein. Ratio of phospho-MEK 1/2 to MEK 1/2 protein in the nucleus after Ang II treatment was 2.4 times greater than control suggesting phosphorylation of MEK 1/2 inside the nucleus. Ethanol had no effect on the protein level or the activation of p42/44 MAPK in the nucleus. Ethanol treatment potentiated nuclear activation of p42/44 MPAK by Ang II but not translocation of p42/44 MAPK protein. This was accompanied by potentiation of Ang II stimulated accumulation of phospho-MEK 1/2 in the nucleus by ethanol. MEK 1/2 inhibitor, U-0126 inhibited Ang II response or its potentiation by ethanol. These results suggest that Ang II mediated accumulation of phospho-p42/44 MAPK in the hepatocyte nucleus involves MEK 1/2 dependent activation and this effect is potentiated by ethanol. PMID:19560630

MEK inhibition induces apoptosis in osteosarcoma cells with constitutive ERK1/2 phosphorylation

OpenAIRE

Baranski, Zuzanna; Booij, Tijmen H.; Kuijjer, Marieke L.; de Jong, Yvonne; Cleton-Jansen, Anne-Marie; Price, Leo S.; van de Water, Bob; Bovée, Judith V. M. G.; Hogendoorn, Pancras C.W.; Danen, Erik H.J.

2015-01-01

Conventional high-grade osteosarcoma is the most common primary bone cancer with relatively high incidence in young people. Recurrent and metastatic tumors are difficult to treat. We performed a kinase inhibitor screen in two osteosarcoma cell lines, which identified MEK1/2 inhibitors. These inhibitors were further validated in a panel of six osteosarcoma cell lines. Western blot analysis was performed to assess ERK activity and efficacy of MEK inhibition. A 3D culture system was used to vali...

Insights into significance of combined inhibition of MEK and m-TOR signalling output in KRAS mutant non-small-cell lung cancer.

Science.gov (United States)

Broutin, Sophie; Stewart, Adam; Thavasu, Parames; Paci, Angelo; Bidart, Jean-Michel; Banerji, Udai

2016-08-23

We aimed to understand the dependence of MEK and m-TOR inhibition in EGFR(WT)/ALK(non-rearranged) NSCLC cell lines. In a panel of KRAS(M) and KRAS(WT) NSCLC cell lines, we determined growth inhibition (GI) following maximal reduction in p-ERK and p-S6RP caused by trametinib (MEK inhibitor) and AZD2014 (m-TOR inhibitor), respectively. GI caused by maximal m-TOR inhibition was significantly greater than GI caused by maximal MEK inhibition in the cell line panel (52% vs 18%, PTOR compared with maximal m-TOR+MEK inhibition. However, GI caused by the combination was significantly greater in the KRAS(M) cell lines (79% vs 61%, P=0.017). m-TOR inhibition was more critical to GI than MEK inhibition in EGFR(WT)/ALK(non-rearranged) NSCLC cells. The combination of MEK and m-TOR inhibition was most effective in KRAS(M) cells.

11 CFR 106.3 - Allocation of expenses between campaign and non-campaign related travel.

Science.gov (United States)

2010-01-01

... 11 Federal Elections 1 2010-01-01 2010-01-01 false Allocation of expenses between campaign and non-campaign related travel. 106.3 Section 106.3 Federal Elections FEDERAL ELECTION COMMISSION GENERAL ALLOCATIONS OF CANDIDATE AND COMMITTEE ACTIVITIES § 106.3 Allocation of expenses between campaign and non...

Art imitates life: Déjà vu experiences in prose and poetry

NARCIS (Netherlands)

Sno, H. N.; Linszen, D. H.; de Jonghe, F.

1992-01-01

the déjà vu experience is a subjective phenomenon that has been described in many novels and poems. Here we review over 20 literary descriptions. These accounts are consistent with the data obtained from psychiatric literature, including various phenomenological, aetiological and psychopathogenetic

Towards sustainable public FM: collective building of capabilities

DEFF Research Database (Denmark)

Ramskov Galamba, Kirsten; Nielsen, Susanne Balslev

2016-01-01

Purpose Public facilities management (FM) is in the unique position of aligning building projects and FM with the policies of sustainable development at societal level. However, sustainable facilities management (SFM) is an emergent profession, and there is a need to build a code of conduct for SFM...... in FM organisations. The purpose is to develop and test a workshop based concept for collective building of capabilities targeting in-house FM organisations, in particular public in-house FM organisations. Design/methodology/approach This research explores the role of public facilities managers...... and examines how an empowerment process can help FM employees develop collective competences for SFM. The methodologies used are literature review, and a 3–year-long action research process in the Danish local authority, Albertslund, which is internationally recognised for its innovative and green profile...

FM Innovation in Science and Practice

DEFF Research Database (Denmark)

Mobach, Mark P.; Nardelli, Giulia; Konkol, Jennifer

2015-01-01

Purpose : To report in FM Innovation. Theory : Innovation theory, service management, space design. Design/methodology/approach : Case studies, workshop. Findings : Barriers, areas of interest, and best practices in FM Innovation. Originality/value : Presents a first exploration of European case...

FM Innovation in Science and Practice

NARCIS (Netherlands)

Mobach, Mark P.; Nardelli, Giulia; Konkol, Jennifer; Kok, Herman B.; Alexander, Keith; Alexander, Keith; Price, Ilfryn

2015-01-01

Purpose: To report in FM Innovation. Theory: Innovation theory, service management, space design. Design/methodology/approach: Case studies, workshop. Findings: Barriers, areas of interest, and best practices in FM Innovation. Originality/value: Presents a first exploration of European case

Centralisering af FM organisationer

DEFF Research Database (Denmark)

Nielsen, Susanne Balslev

2016-01-01

Centralisering af FM organisationer kan let føre til mange frustrerende arbejds- dage for medarbejdere og deres ledere. Denne artikel giver et bud på hvad kom- muner og andre kan gøre for at komme bedre igennem en omorganisering.......Centralisering af FM organisationer kan let føre til mange frustrerende arbejds- dage for medarbejdere og deres ledere. Denne artikel giver et bud på hvad kom- muner og andre kan gøre for at komme bedre igennem en omorganisering....

The making of the FM value map

DEFF Research Database (Denmark)

Jensen, Per Anker

2012-01-01

Purpose: To present the FM Value Map and the background, process and considerations of its development and to reflect on perspectives and limitations. Methodology: The FM Value Map was developed from cases studies as part of the research project Facilities Management Best Practice in the Nordic...... it take the core business strategy as a starting point, and it is a fairly static framework. In spite of these limitations, the FM Value Map is an important element in the ongoing research and development in this area, but it should perhaps more be seen as a starting point rather than an end result...... in specific cases have a special importance for the value creation of FM. Research limitations: The chapter is a retrospective presentation of a research process. Originality/value: The chapter gives a detailed insight in the development process of the conceptual FM Value Map....

Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents

Directory of Open Access Journals (Sweden)

Ping Xu

2013-05-01

Full Text Available In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the ERK pathway in a cellular assay. These compounds also significantly inhibited virus (EV71 replication in HEK293 and RD cells. Several compounds showed potential as agents for the treatment of viral infective diseases, with the most potent compound 18 showing an IC50 value of 54.57 nM in the MEK1 binding assay.

Oncogenic K-Ras Activates p38 to Maintain Colorectal Cancer Cell Proliferation during MEK Inhibition

Directory of Open Access Journals (Sweden)

Winan J. van Houdt

2010-01-01

Full Text Available Background: Colon carcinomas frequently contain activating mutations in the K-ras proto-oncogene. K-ras itself is a poor drug target and drug development efforts have mostly focused on components of the classical Ras-activated MEK/ERK pathway. Here we have studied whether endogenous oncogenic K-ras affects the dependency of colorectal tumor cells on MEK/ERK signaling.

Decay study of {sup 246}Fm at SHIP

Energy Technology Data Exchange (ETDEWEB)

Venhart, M. [Comenius University, Department of Nuclear Physics and Biophysics, Bratislava (Slovakia); Slovak Academy of Sciences, Institute of Physics, Bratislava (Slovakia); Hessberger, F.P.; Ackermann, D.; Heinz, S.; Kindler, B.; Kojouharov, I.; Lommel, B.; Mann, R. [GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, Darmstadt (Germany); Antalic, S.; Saro, S. [Comenius University, Department of Nuclear Physics and Biophysics, Bratislava (Slovakia); Gray-Jones, C.; Herzberg, R.D.; Papadakis, P. [University of Liverpool, Department of Physics, Liverpool (United Kingdom); Greenlees, P.T.; Ketelhut, S.; Leino, M. [University of Jyvaeskylae, Department of Physics, Jyvaeskylae (Finland); Hofmann, S. [GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, Darmstadt (Germany); Goethe-Universitaet, Institut fuer Kernphysik, Frankfurt am Main (Germany); Rostron, D. [Goethe-Universitaet, Institut fuer Kernphysik, Frankfurt am Main (Germany); Rudolph, D. [Lund University, Department of Physics, Lund (Sweden); Sulignano, B. [CEA Saclay, DAPNIA/SPhN, Gif/Yvette Cedex (France)

2011-02-15

The decay chain of {sup 246}Fm has been investigated employing the SHIP separator at GSI Darmstadt. The {sup 246}Fm nuclei were produced via the {sup 40}Ar({sup 208}Pb, 2n){sup 246}Fm fusion-evaporation reaction. Improved values of the half-life, T{sub 1/2} = 1.54(4) s, and of the spontaneous fission branching ratio, b{sub SF} = 0.068(6), of {sup 246}Fm were obtained. The {beta}{sup +} /electron capture branching ratio, b{sub EC} = 0.39(3), of {sup 242}Cf was deduced. Possible structures of high-K states in {sup 246}Fm are discussed within the framework of a model calculation based on the Woods-Saxon potential. (orig.)

EEG characteristics of déjà vu phenomenon

OpenAIRE

Chervyakov, Alexander V.; Gnezditskii, Victor V.; Vlasov, Pavel N.; Kalmykova, Galina V.

2013-01-01

Introduction. Déjà vu (DV, from French “already seen”) is an aberration of psychic activity associated with transitory erroneous perception of novel circumstances, objects, or people as already known. Aim. Investigation of clinical and diagnostic significance of derealization episodes in epilepsy. Materials and methods. The study involved 166 individuals (mean age 25.2 ± 9.2 yrs; 63.2% women). DV episodes were characterized and compared in groups of healthy volunteers (n = 139) and epilepsy...

Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

Science.gov (United States)

2016-09-01

analysis of tumor necrosis factor - alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype...AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor - Associated...Cancer and Impairs Tumor -Associated Angiogenesis 5b. GRANT NUMBER W81XWH-15-1-0296 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

Conjugated linoleic acid induces human adipocyte delipidation: autocrine/paracrine regulation of MEK/ERK signaling by adipocytokines

DEFF Research Database (Denmark)

Brown, J Mark; Boysen, Maria Sandberg; Chung, Soonkyu

2004-01-01

of MEK/ERK could be attenuated by pretreatment with U0126 and pertussis toxin. In parallel, pretreatment with U0126 blocked the ability of trans-10, cis-12 CLA to alter gene expression and attenuate glucose and fatty acid uptake of the cultures. Intriguingly, the induction by CLA of MEK/ERK signaling...

Tīmekļa vietnes ar reaģējošu dizainu izstrāde, izmantojot “Laravel” PHP ietvaru

OpenAIRE

Vergins, Kristaps

2015-01-01

Mūsdienās tīmekļa vietņu pārlūkošanu nodrošina plašs klāsts dažādu ierīču. Cilvēku vidū lielu popularitāti iemantojusi tīmekļa pārlūkošana, izmantojot savus viedtālruņus un planšetdatorus. Protams, lai lietotājs gūtu baudāmu tīmekļa pārlūkošanas pieredzi savā mobilajā ierīcē, ir nepieciešams izstrādāt pielāgotu tīmekļa vietnes versiju. Tieši šim nolūkam arvien vairāk tiek izstrādātas tīmekļa vietnes ar reaģējošu dizainu. Reaģējošs dizains nodrošina iespēju tīmekļa vietni vienlīdz ērti lietot ...

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Terra-FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-11-01] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

MEK inhibitor effective against proliferation in breast cancer cell.

Science.gov (United States)

Zhou, Yan; Hu, Hai-Yan; Meng, Wei; Jiang, Ling; Zhang, Xing; Sha, Jing-Jing; Lu, Zhigang; Yao, Yang

2014-09-01

The targeted small-molecule drug AZD6244 is an allosteric, ATP-noncompetitive inhibitor of MEK1/2 that has shown activity against several malignant tumors. Here, we report that AZD6244 repressed cell growth and induced apoptosis and G1-phase arrest in the breast cancer cell lines MDA-MB-231 and HCC1937. Using microRNA (miRNA) arrays and quantitative RT-PCR, we found that miR-203 was up-regulated after AZD6244 treatment. In accordance with bioinformatics and luciferase activity analyses, CUL1 was found to be the direct target of miR-203. Furthermore, miR-203 inhibition and CUL1 overexpression reversed the cytotoxicity of AZD6244 on the MDA-MB-231 and HCC1937 cells. Collectively, our data indicate that miR-203 mediates the AZD6244-induced cytotoxicity of breast cancer cells and that the MEK/ERK/miR-203/CUL1 signaling pathway may participate in this process.

34 CFR 106.39 - Health and insurance benefits and services.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Health and insurance benefits and services. 106.39... Prohibited § 106.39 Health and insurance benefits and services. In providing a medical, hospital, accident, or life insurance benefit, service, policy, or plan to any of its students, a recipient shall not...

How Can FM Create Value to Organisations? – A critical review of papers from EuroFM Research Symposia 2013-2015

DEFF Research Database (Denmark)

Jensen, Per Anker; van der Voordt, Theo

The main purpose of this report is to provide a state of the art of research and practice in relation to the Added Value of FM. This is done by making a critical review of research papers from FM conferences (chapter 2) and by presenting the concept of Value Adding Management (chapter 3) with res......The main purpose of this report is to provide a state of the art of research and practice in relation to the Added Value of FM. This is done by making a critical review of research papers from FM conferences (chapter 2) and by presenting the concept of Value Adding Management (chapter 3...

The effects of MEK1/2 inhibition on cigarette smoke exposure-induced ET receptor upregulation in rat cerebral arteries

Energy Technology Data Exchange (ETDEWEB)

Cao, Lei [Division of Experimental Vascular Research, Institute of Clinical Sciences in Lund, Lund University (Sweden); Department of Pharmacology, School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an, Shaanxi (China); Ping, Na-Na; Cao, Yong-Xiao [Department of Pharmacology, School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an, Shaanxi (China); Li, Wei, E-mail: 13572512207@163.com [Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Cai, Yan [Department of Pharmacology, School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an, Shaanxi (China); Warfvinge, Karin; Edvinsson, Lars [Division of Experimental Vascular Research, Institute of Clinical Sciences in Lund, Lund University (Sweden)

2016-08-01

Cigarette smoking, a major stroke risk factor, upregulates endothelin receptors in cerebral arteries. The present study examined the effects of MEK1/2 pathway inhibition on cigarette smoke exposure-induced ET receptor upregulation. Rats were exposed to the secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of MEK1/2 inhibitor, U0126 for another 4 weeks. The urine cotinine levels were assessed with high-performance liquid chromatography. Contractile responses of isolated cerebral arteries were recorded by a sensitive wire myograph. The mRNA and protein expression levels of receptor and MEK/ERK1/2 pathway molecules were examined by real-time PCR and Western blotting, respectively. Cerebral artery receptor localization was determined with immunohistochemistry. The results showed the urine cotinine levels from SHS exposure group were significantly higher than those from the fresh group. In addition, the MEK1/2 inhibitor, U0126 significantly reduced SHS exposure-increased ET{sub A} receptor mRNA and protein levels as well as contractile responses mediated by ET{sub A} receptors. The immunoreactivity of increased ET{sub A} receptor expression was primarily cytoplasmic in smooth muscle cells. In contrast, ET{sub B} receptor was noted in endothelial cells. However, the SHS-induced decrease in endothelium-dependent relaxation was unchanged after U0126 treatment. Furthermore, SHS increased the phosphorylation of MEK1/2 and ERK1/2 protein in cerebral arteries. By using U0126 could inhibit the phosphorylated ERK1/2 protein but not MEK1/2. Taken together, our data show that treatment with MEK1/2 pathway inhibitor offsets SHS exposure-induced ET{sub A} receptor upregulation in rat cerebral arteries. - Highlights: • Cigarette smoke exposure induces ET{sub A} receptor upregulation in rat cerebral arteries. • U0126 can alleviate the receptor upregulation. • The mechanism relies on MEK/ERK1/2 pathway activation. • We may provide a new target for the

The effects of MEK1/2 inhibition on cigarette smoke exposure-induced ET receptor upregulation in rat cerebral arteries

International Nuclear Information System (INIS)

Cao, Lei; Ping, Na-Na; Cao, Yong-Xiao; Li, Wei; Cai, Yan; Warfvinge, Karin; Edvinsson, Lars

2016-01-01

Cigarette smoking, a major stroke risk factor, upregulates endothelin receptors in cerebral arteries. The present study examined the effects of MEK1/2 pathway inhibition on cigarette smoke exposure-induced ET receptor upregulation. Rats were exposed to the secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of MEK1/2 inhibitor, U0126 for another 4 weeks. The urine cotinine levels were assessed with high-performance liquid chromatography. Contractile responses of isolated cerebral arteries were recorded by a sensitive wire myograph. The mRNA and protein expression levels of receptor and MEK/ERK1/2 pathway molecules were examined by real-time PCR and Western blotting, respectively. Cerebral artery receptor localization was determined with immunohistochemistry. The results showed the urine cotinine levels from SHS exposure group were significantly higher than those from the fresh group. In addition, the MEK1/2 inhibitor, U0126 significantly reduced SHS exposure-increased ET A receptor mRNA and protein levels as well as contractile responses mediated by ET A receptors. The immunoreactivity of increased ET A receptor expression was primarily cytoplasmic in smooth muscle cells. In contrast, ET B receptor was noted in endothelial cells. However, the SHS-induced decrease in endothelium-dependent relaxation was unchanged after U0126 treatment. Furthermore, SHS increased the phosphorylation of MEK1/2 and ERK1/2 protein in cerebral arteries. By using U0126 could inhibit the phosphorylated ERK1/2 protein but not MEK1/2. Taken together, our data show that treatment with MEK1/2 pathway inhibitor offsets SHS exposure-induced ET A receptor upregulation in rat cerebral arteries. - Highlights: • Cigarette smoke exposure induces ET A receptor upregulation in rat cerebral arteries. • U0126 can alleviate the receptor upregulation. • The mechanism relies on MEK/ERK1/2 pathway activation. • We may provide a new target for the treatment of SHS

Discovery of VU0467485/AZ13713945: An M4 PAM Evaluated as a Preclinical Candidate for the Treatment of Schizophrenia.

Science.gov (United States)

Wood, Michael R; Noetzel, Meredith J; Melancon, Bruce J; Poslusney, Michael S; Nance, Kellie D; Hurtado, Miguel A; Luscombe, Vincent B; Weiner, Rebecca L; Rodriguez, Alice L; Lamsal, Atin; Chang, Sichen; Bubser, Michael; Blobaum, Anna L; Engers, Darren W; Niswender, Colleen M; Jones, Carrie K; Brandon, Nicholas J; Wood, Michael W; Duggan, Mark E; Conn, P Jeffrey; Bridges, Thomas M; Lindsley, Craig W

2017-02-09

Herein, we report the structure-activity relationships within a series of potent, selective, and orally bioavailable muscarinic acetylcholine receptor 4 (M 4 ) positive allosteric modulators (PAMs). Compound 6c (VU0467485) possesses robust in vitro M 4 PAM potency across species and in vivo efficacy in preclinical models of schizophrenia. Coupled with an attractive DMPK profile and suitable predicted human PK, 6c (VU0467485) was evaluated as a preclinical development candidate.

20 CFR 10.6 - What special statutory definitions apply to dependents and survivors?

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false What special statutory definitions apply to dependents and survivors? 10.6 Section 10.6 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS...' COMPENSATION ACT, AS AMENDED General Provisions Definitions and Forms § 10.6 What special statutory definitions...

Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1.

Science.gov (United States)

Callender, Tracy L; Laureau, Raphaelle; Wan, Lihong; Chen, Xiangyu; Sandhu, Rima; Laljee, Saif; Zhou, Sai; Suhandynata, Ray T; Prugar, Evelyn; Gaines, William A; Kwon, YoungHo; Börner, G Valentin; Nicolas, Alain; Neiman, Aaron M; Hollingsworth, Nancy M

2016-08-01

During meiosis, programmed double strand breaks (DSBs) are repaired preferentially between homologs to generate crossovers that promote proper chromosome segregation at Meiosis I. In many organisms, there are two strand exchange proteins, Rad51 and the meiosis-specific Dmc1, required for interhomolog (IH) bias. This bias requires the presence, but not the strand exchange activity of Rad51, while Dmc1 is responsible for the bulk of meiotic recombination. How these activities are regulated is less well established. In dmc1Δ mutants, Rad51 is actively inhibited, thereby resulting in prophase arrest due to unrepaired DSBs triggering the meiotic recombination checkpoint. This inhibition is dependent upon the meiosis-specific kinase Mek1 and occurs through two different mechanisms that prevent complex formation with the Rad51 accessory factor Rad54: (i) phosphorylation of Rad54 by Mek1 and (ii) binding of Rad51 by the meiosis-specific protein Hed1. An open question has been why inhibition of Mek1 affects Hed1 repression of Rad51. This work shows that Hed1 is a direct substrate of Mek1. Phosphorylation of Hed1 at threonine 40 helps suppress Rad51 activity in dmc1Δ mutants by promoting Hed1 protein stability. Rad51-mediated recombination occurring in the absence of Hed1 phosphorylation results in a significant increase in non-exchange chromosomes despite wild-type levels of crossovers, confirming previous results indicating a defect in crossover assurance. We propose that Rad51 function in meiosis is regulated in part by the coordinated phosphorylation of Rad54 and Hed1 by Mek1.

Overcoming IGF1R/IR Resistance Through Inhibition of MEK Signaling in Colorectal Cancer Models

Science.gov (United States)

Flanigan, Sara A.; Pitts, Todd M.; Newton, Timothy P.; Kulikowski, Gillian N.; Tan, Aik Choon; McManus, Martine C.; Spreafico, Anna; Kachaeva, Maria I.; Selby, Heather M.; Tentler, John J.; Eckhardt, S. Gail; Leong, Stephen

2013-01-01

Purpose Results from clinical trials involving resistance to molecularly targeted therapies have revealed the importance of rational single agent and combination treatment strategies. In this study, we tested the efficacy of a type 1 insulin-like growth factor receptor (IGF1R)/insulin receptor (IR) tyrosine kinase inhibitor (TKI), OSI-906, in combination with a MEK 1/2 inhibitor based on evidence that the MAPK pathway was upregulated in colorectal cancer (CRC) cell lines that were resistant to OSI-906. Experimental Design The antiproliferative effects of OSI-906 and the MEK 1/2 inhibitor U0126, were analyzed both as single agents and in combination in 13 CRC cell lines in vitro. Apoptosis, downstream effector proteins, and cell cycle were also assessed. Additionally, the efficacy of OSI-906 combined with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886), was evaluated in vivo using human CRC xenograft models. Results The combination of OSI-906 and U0126 resulted in synergistic effects in 11 out of 13 CRC cell lines tested. This synergy was variably associated with apoptosis or cell cycle arrest in addition to molecular effects on pro-survival pathways. The synergy was also reflected in the in vivo xenograft studies following treatment with the combination of OSI-906 and selumetinib. Conclusions Results from this study demonstrate synergistic antiproliferative effects in response to the combination of OSI-906 with a MEK 1/2 inhibitor in CRC cell line models both in vitro and in vivo, which supports the rational combination of OSI-906 with a MEK inhibitor in patients with CRC. PMID:24045180

Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1.

Directory of Open Access Journals (Sweden)

Tracy L Callender

2016-08-01

Full Text Available During meiosis, programmed double strand breaks (DSBs are repaired preferentially between homologs to generate crossovers that promote proper chromosome segregation at Meiosis I. In many organisms, there are two strand exchange proteins, Rad51 and the meiosis-specific Dmc1, required for interhomolog (IH bias. This bias requires the presence, but not the strand exchange activity of Rad51, while Dmc1 is responsible for the bulk of meiotic recombination. How these activities are regulated is less well established. In dmc1Δ mutants, Rad51 is actively inhibited, thereby resulting in prophase arrest due to unrepaired DSBs triggering the meiotic recombination checkpoint. This inhibition is dependent upon the meiosis-specific kinase Mek1 and occurs through two different mechanisms that prevent complex formation with the Rad51 accessory factor Rad54: (i phosphorylation of Rad54 by Mek1 and (ii binding of Rad51 by the meiosis-specific protein Hed1. An open question has been why inhibition of Mek1 affects Hed1 repression of Rad51. This work shows that Hed1 is a direct substrate of Mek1. Phosphorylation of Hed1 at threonine 40 helps suppress Rad51 activity in dmc1Δ mutants by promoting Hed1 protein stability. Rad51-mediated recombination occurring in the absence of Hed1 phosphorylation results in a significant increase in non-exchange chromosomes despite wild-type levels of crossovers, confirming previous results indicating a defect in crossover assurance. We propose that Rad51 function in meiosis is regulated in part by the coordinated phosphorylation of Rad54 and Hed1 by Mek1.

Genetic Validation of Cell Proliferation via Ras-Independent Activation of the Raf/Mek/Erk Pathway.

Science.gov (United States)

Lechuga, Carmen G; Simón-Carrasco, Lucía; Jacob, Harrys K C; Drosten, Matthias

2017-01-01

Signaling transmitted by the Ras family of small GTPases (H-, N-, and K-Ras) is essential for proliferation of mouse embryonic fibroblasts (MEFs). However, constitutive activation of the downstream Raf/Mek/Erk pathway can bypass the requirement for Ras proteins and allow cells to proliferate in the absence of the three Ras isoforms. Here we describe a protocol for a colony formation assay that permits evaluating the role of candidate proteins that are positive or negative regulators of cell proliferation mediated via Ras-independent Raf/Mek/Erk pathway activation. K-Ras lox (H-Ras -/- , N-Ras -/- , K-Ras lox/lox , RERT ert/ert ) MEFs are infected with retro- or lentiviral vectors expressing wild-type or constitutively activated candidate cDNAs, shRNAs, or sgRNAs in combination with Cas9 to ascertain the possibility of candidate proteins to function either as an activator or inhibitor of Ras-independent Raf/Mek/Erk activation. These cells are then seeded in the absence or presence of 4-Hydroxytamoxifen (4-OHT), which activates the resident CreERT2 alleles resulting in elimination of the conditional K-Ras alleles and ultimately generating Rasless cells. Colony formation in the presence of 4-OHT indicates cell proliferation via Ras-independent Raf/Mek/Erk activation.

Strategic FM Procurement: an issue of aligning services to business needs

DEFF Research Database (Denmark)

Katchamart, Akarapong; Shiem-shin, Danny Then

2014-01-01

Purpose – To illustrate the interdependence between business need and strategic decision on facilities management (FM) procurement model. This interdependence underpins the reason behind strategic decision on FM procurement. It would assist decision makers on FM services procurement that fulfills...... business needs and enriches business outcomes. Design/methodology/approach – By a systematic review of FM-related literature, this research structures and investigates on three aspects of this interdependence between business delivery and FM services: 1. What characteristics of core business impact on FM...... service and provision? 2. What are the interconnections between business support and FM procurement decisions? and 3. What are the available FM services procurement options? Findings – There are four types of core business characteristics that impacts on FM services and provision based on the degree...

01 Inkanyiso Edwards et al.FM.fm

African Journals Online (AJOL)

User

communicate feelings below what the helpee is able to express and, secondly, .... basic electroencephalographic (EEG) data in relation to delta, theta, alpha, beta .... would identify times at work when I would space out and bring me back in ..... The closed circle of empathy: mirror neuron system activation and anterior EEG ...

5 CFR 2606.106 - OGE employee Privacy Act rules of conduct and responsibilities.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false OGE employee Privacy Act rules of conduct and responsibilities. 2606.106 Section 2606.106 Administrative Personnel OFFICE OF GOVERNMENT ETHICS... requirement to inform each individual asked to supply information to be maintained in a system of records the...

48 CFR 1313.106 - Soliciting competition, evaluation of quotations or offers, award and documentation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Soliciting competition, evaluation of quotations or offers, award and documentation. 1313.106 Section 1313.106 Federal Acquisition... PROCEDURES Procedures 1313.106 Soliciting competition, evaluation of quotations or offers, award and...

48 CFR 813.106 - Soliciting competition, evaluation of quotations or offers, award and documentation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Soliciting competition, evaluation of quotations or offers, award and documentation. 813.106 Section 813.106 Federal Acquisition... ACQUISITION PROCEDURES Procedures 813.106 Soliciting competition, evaluation of quotations or offers, award...

26 CFR 521.106 - Control of a domestic enterprise by a Danish enterprise.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 19 2010-04-01 2010-04-01 false Control of a domestic enterprise by a Danish enterprise. 521.106 Section 521.106 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Are Residents of Denmark and of Danish Corporations § 521.106 Control of a domestic enterprise by a...

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

International Nuclear Information System (INIS)

Zhang, Jianhai; Zhang, Yufang; Liang, Chen; Wang, Nasui; Zheng, Heping; Wang, Jundong

2016-01-01

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jianhai [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Zhang, Yufang [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Veterinary Station in Chen Villages of Lin Country, Linxian, Shanxi 033200 (China); Liang, Chen [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Wang, Nasui [Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, VA 22908 (United States); Division of Endocrinology and Metabolism, Department of Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou (China); Zheng, Heping [Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908 (United States); Wang, Jundong, E-mail: wangjd53@outlook.com [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China)

2016-11-01

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.

13 CFR 106.202 - What are the minimum requirements applicable to Cosponsored Activities?

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What are the minimum requirements applicable to Cosponsored Activities? 106.202 Section 106.202 Business Credit and Assistance SMALL BUSINESS... constitute or imply an endorsement by SBA of any Cosponsor or any Cosponsor's products or services; (c) Any...

48 CFR 13.106 - Soliciting competition, evaluation of quotations or offers, award and documentation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Soliciting competition, evaluation of quotations or offers, award and documentation. 13.106 Section 13.106 Federal Acquisition... ACQUISITION PROCEDURES Procedures 13.106 Soliciting competition, evaluation of quotations or offers, award and...

34 CFR 106.3 - Remedial and affirmative action and self-evaluation.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Remedial and affirmative action and self-evaluation. 106.3 Section 106.3 Education Regulations of the Offices of the Department of Education OFFICE FOR.... (c) Self-evaluation. Each recipient education institution shall, within one year of the effective...

The Concept of added value of FM

NARCIS (Netherlands)

Jensen, PA; van der Voordt, Theo; Coenen, C; von Felten, D; Balslev-Nielsen, S; Sarasoja, AL; Riratanaphong, C.; Pfenninger, M; Jensen, PA; van der Voordt, DJM; Coenen, C

2012-01-01

Purpose: This chapter presents research perspectives and theoretical reflections on the concept of added value of FM from a variety of academic fields.
Methodology: A literature review of the most influential journals within the academic fields of Facilities Management (FM), Corporate Real

7 CFR 786.106 - Determination of losses incurred.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Determination of losses incurred. 786.106 Section 786... Determination of losses incurred. (a) Eligible payable losses are calculated on a dairy operation by dairy..., dairy production losses incurred by producers under this part are determined on the established history...

FY05 FM Dial Summary Report

Energy Technology Data Exchange (ETDEWEB)

Harper, Warren W.; Strasburg, Jana D.; Golovich, Elizabeth C.; Thompson, Jason S.; Stewart, Timothy L.; Batdorf, Michael T.

2005-12-01

Pacific Northwest National Laboratory's Infrared Sensors team is focused on developing methods for standoff detection of nuclear proliferation. In FY05, PNNL continued the development of the FM DIAL (frequency-modulated differential absorption LIDAR) experiment. Additional improvements to the FM DIAL trailer provided greater stability during field campaigns which made it easier to explore new locations for field campaigns. In addition to the Hanford Townsite, successful experiments were conducted at the Marine Science Laboratory in Sequim, WA and the Nevada Test Site located outside Las Vegas, NV. The range of chemicals that can be detected by FM DIAL has also increased. Prior to FY05, distributed feedback quantum cascade lasers (DFB-QCL) were used in the FM DIAL experiments. With these lasers, only simple chemicals with narrow (1-2 cm-1) absorption spectra, such as CO2 and N2O, could be detected. Fabry-Perot (FP) QC lasers have much broader spectra (20-40 cm-1) which allows for the detection of larger chemicals and a wider array of chemicals that can be detected. A FP-QCL has been characterized and used during initial studies detecting DMMP (dimethyl methylphosphonate).

25 CFR 39.106 - Who is eligible for special education funding?

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Who is eligible for special education funding? 39.106 Section 39.106 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL... for special education funding? To receive ISEP special education funding, a student must be under 22...

Are school vending machines loaded with calories and fat: an assessment of 106 middle and high schools.

Science.gov (United States)

Pasch, Keryn E; Lytle, Leslie A; Samuelson, Anne C; Farbakhsh, Kian; Kubik, Martha Y; Patnode, Carrie D

2011-04-01

The purpose of this study was to describe the extent to which vending offerings in 106 schools in the St. Paul-Minneapolis, Minnesota metropolitan area, met criteria for types of beverages, fat, and calories based on selected criteria offered by the Institute of Medicine. Schools where youth participants were attending for the 2006-2007 school year were identified and invited to participate in the study (n = 143); 81% of schools (n = 116) agreed to participate. Of the 116 schools, 106 had vending machines. Across schools with vending machines (n = 106), 5085 food and 8442 beverage items were offered. Overall, only 18% of beverage items met criteria for calories and type of beverage; significantly more items in public schools met the criteria as compared to private schools (19% vs 12%; p schools as compared to middle schools (18% vs 22%; p schools (22% vs 18%; p = .01), while high schools (22%) and middle schools (21%) were similar. A very small proportion of foods (schools are doing a slightly better job of providing healthy foods as compared to private schools. © 2011, American School Health Association.

Temperature, salinity and other variables collected from discrete sample and profile observations using CTD, bottle and other instruments from the KNORR in the South Pacific Ocean from 2006-01-30 to 2006-03-14 (NODC Accession 0115593)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0115593 includes chemical, discrete sample, physical and profile data collected from KNORR in the South Pacific Ocean from 2006-01-30 to 2006-03-14...

[Electroencephalographic characteristics of the deja vu phenomenon].

Science.gov (United States)

Vlasov, P N; Cherviakov, A V; Gnezdinsiĭ, V V

2013-01-01

Déjà vu (DV, from French "already seen") is an aberration of psychic activity associated with transitory erroneous perception of novel circumstances, objects, or people as already known. An aim of the study was to investigate EEG characteristics of DV in patients with epilepsy. We studied 166 people (63.2% women, mean age 25.17±9.19 years). The DV phenomenon was studied in patients (27 people) and in a control group (139 healthy people). Patients were interviewed for DV characteristics and underwent a long (12-16 h) ambulatory EEG-monitoring study. In EEG, DV episodes in patients began with polyspike activity in the right temporal lobe and, in some cases, ended with the slow-wave theta-delta activity in the right hemisphere.

48 CFR 828.106-72 - Contract provision.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract provision. 828... GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 828.106-72 Contract provision. Insert 852.228-72, Assisting Service-Disabled Veteran-Owned and Veteran-Owned Small...

Hvad sker der i FM forskningen

DEFF Research Database (Denmark)

Nielsen, Susanne Balslev

2017-01-01

Der er fantastisk meget viden fra forskning i FM, der betyder at du kan skyde genvej, hvis du kender til den. Det tager lang tid, hvis du i stedet skal erfare det hele selv.......Der er fantastisk meget viden fra forskning i FM, der betyder at du kan skyde genvej, hvis du kender til den. Det tager lang tid, hvis du i stedet skal erfare det hele selv....

Risk Management from Corporate and FM Perspectives: Two case studies

DEFF Research Database (Denmark)

Ünver, Kadir; Jensen, Per Anker

2012-01-01

Purpose: To investigate how Risk Management (RM) is perceived and practiced in Facilities Management (FM) and corporate management and to evaluate the potential benefits of an increased application. Theory: RM is a generic management discipline, but apparently it has not achieved the attention...... as most critical in each company. Both companies could benefit from a more integrated application of RM covering both corporate management and FM. Originality/value: This is among the first descriptive studies looking at RM from both corporate and FM perspectives, which is essential to increase...... it deserves in FM. Application of RM in FM could help to increase the strategic importance and awareness of FM among corporate managers. Approach: A preliminary study with expert interviews was initially conducted followed by a main study with an interview survey in two Danish case companies - a real estate...

Msgre. Jan Šrámek a Msgre. Andrej Hlinka

Czech Academy of Sciences Publication Activity Database

Pehr, Michal

2014-2015, [1] (2016), s. 199-211 ISSN 1214-8334 Institutional support: RVO:67985921 Keywords : Šrámek, Jan * Hlinka, Andrej * Czechoslovakia, 1918-1938 Subject RIV: AB - History OBOR OECD: History (history of science and technology to be 6.3, history of specific sciences to be under the respective headings)

The MEK1/2-ERK Pathway Inhibits Type I IFN Production in Plasmacytoid Dendritic Cells

Directory of Open Access Journals (Sweden)

Vaclav Janovec

2018-02-01

Full Text Available Recent studies have reported that the crosslinking of regulatory receptors (RRs, such as blood dendritic cell antigen 2 (BDCA-2 (CD303 or ILT7 (CD85g, of plasmacytoid dendritic cells (pDCs efficiently suppresses the production of type I interferons (IFN-I, α/β/ω and other cytokines in response to toll-like receptor 7 and 9 (TLR7/9 ligands. The exact mechanism of how this B cell receptor (BCR-like signaling blocks TLR7/9-mediated IFN-I production is unknown. Here, we stimulated BCR-like signaling by ligation of RRs with BDCA-2 and ILT7 mAbs, hepatitis C virus particles, or BST2 expressing cells. We compared BCR-like signaling in proliferating pDC cell line GEN2.2 and in primary pDCs from healthy donors, and addressed the question of whether pharmacological targeting of BCR-like signaling can antagonize RR-induced pDC inhibition. To this end, we tested the TLR9-mediated production of IFN-I and proinflammatory cytokines in pDCs exposed to a panel of inhibitors of signaling molecules involved in BCR-like, MAPK, NF-ĸB, and calcium signaling pathways. We found that MEK1/2 inhibitors, PD0325901 and U0126 potentiated TLR9-mediated production of IFN-I in GEN2.2 cells. More importantly, MEK1/2 inhibitors significantly increased the TLR9-mediated IFN-I production blocked in both GEN2.2 cells and primary pDCs upon stimulation of BCR-like or phorbol 12-myristate 13-acetate-induced protein kinase C (PKC signaling. Triggering of BCR-like and PKC signaling in pDCs resulted in an upregulation of the expression and phoshorylation of c-FOS, a downstream gene product of the MEK1/2-ERK pathway. We found that the total level of c-FOS was higher in proliferating GEN2.2 cells than in the resting primary pDCs. The PD0325901-facilitated restoration of the TLR9-mediated IFN-I production correlated with the abrogation of MEK1/2-ERK-c-FOS signaling. These results indicate that the MEK1/2-ERK pathway inhibits TLR9-mediated type I IFN production in pDCs and that

Schizophrenia and the paranormal: more psi belief and superstition, and less déjà vu in medicated schizophrenic patients.

Science.gov (United States)

Shiah, Yung-Jong; Wu, Yi-Zhen; Chen, Yueh-Hua; Chiang, Shih-Kuang

2014-04-01

The present study examined the relation between déjà vu experiences and paranormal beliefs in schizophrenic patients. A total of 522 participants (54.5% female; mean age=33.3, SD=16.02) were recruited, including 422 healthy adults (60.9% female; mean age=29.48, SD=15.07) and 100 medicated adult schizophrenic patients (27.3% female; mean age=48.98, SD=8.57). The Chinese version of the Inventory of Déjà-vu Experiences Assessment was created via back translation. Chinese versions of the Revised Paranormal Belief Scale (CRPB), Beck Anxiety Inventory (CBAI), and Perceived Stress Scale (CPSS) were also used. After controlling for age, gender, education, and anxiety, the results supported the following three hypotheses. Schizophrenic persons have fewer déjà vu experiences than normal persons. These experiences are positively related to paranormal beliefs in healthy adults but not in schizophrenic patients. Schizophrenic patients have higher scores than healthy adults on the psi and superstitious subscales of the CRPB. Copyright © 2014 Elsevier Inc. All rights reserved.

Familial cardiofaciocutaneous syndrome in a father and a son with a novel MEK2 mutation.

Science.gov (United States)

Karaer, Kadri; Lissewski, Christina; Zenker, Martin

2015-02-01

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder belonging to the group of RASopathies. It is typically characterized by congenital heart defects, short stature, dysmorphic craniofacial features, intellectual disability, failure to thrive, and ectodermal abnormalities such as hyperkeratosis and sparse, brittle, curly hair. CFC syndrome is caused by dominant mutations in one of the four genes BRAF, MEK1, MEK2, and KRAS. Only three familial cases of CFC syndrome have been reported to date, whereas the vast majorities are sporadic cases due to de novo mutations. We report on a fourth familial case with transmission of CFC syndrome from father to son due to a novel heterozygous sequence change c.376A>G (p.N126D) in exon 3 of MEK2 gene. This observation further documents the possibility of vertical transmission of CFC syndrome, which appears to be associated with rare mutations and relatively mild intellectual disability in affected individual. The hypomorphic effect of specific mutations particularly regarding neurocognitive issues may be related to the variable fertility of affected individuals. © 2014 Wiley Periodicals, Inc.

Draft genome sequence of Bacillus toyonensis VU-DES13, isolated from Folsomia candida (Collembola: Entomobryidae)

NARCIS (Netherlands)

Janssens, T.K.S.; de Boer, T.E.; Agamennone, V.; Zaagman, N.; van Straalen, N.M.; Roelofs, T.F.M.

2017-01-01

We present here the draft genome of Bacillus toyonensis VU-DES13, which was isolated from the midgut of the soil-living springtail Folsomia candida. Previous research revealed the presence of gene clusters for the biosynthesis of various secondary metabolites, including -lactam antibiotics, in the

Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration.

Science.gov (United States)

Panarese, Joseph D; Cho, Hykeyung P; Adams, Jeffrey J; Nance, Kellie D; Garcia-Barrantes, Pedro M; Chang, Sichen; Morrison, Ryan D; Blobaum, Anna L; Niswender, Colleen M; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

2016-08-01

This Letter describes the continued chemical optimization of the VU0453595 series of M1 positive allosteric modulators (PAMs). By surveying alternative 5,6- and 6,6-heterobicylic cores for the 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one core of VU453595, we found new cores that engendered not only comparable or improved M1 PAM potency, but significantly improved CNS distribution (Kps 0.3-3.1). Moreover, this campaign provided fundamentally distinct M1 PAM chemotypes, greatly expanding the available structural diversity for this valuable CNS target, devoid of hydrogen-bond donors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kent Mobilyalarının Bulundukları Mekânlara Etkileri: Düzce Örneği

Directory of Open Access Journals (Sweden)

Emine ÇOBAN

2014-09-01

Full Text Available Kent mobilyaları kentsel açık alanların vazgeçilmez öğeleridir. Düzce ili önemli ölçüde açık alanlara sahiptir. Bu alanların planlanması, kullanımı, tasarımı konusunda çalışmalar yapılmaktadır. Kentsel mobilyalarda bu tasarım çalışmalarının önemli bir parçasıdır. Kentsel mobilyaların işlevsel, anlamsal, simgesel ve psikolojik etkileri göz önünde bulundurularak çalışmalara yön verilebilir. Bu bağlamda bu çalışmada kent mobilyaları ve yer aldıkları mekânlara etkileri ortaya konulmaya çalışılmıştır. İl genelinde farklı özellikler içeren alanlar (ticari, eğitim, sanayi vb seçilerekbu mekânlarda bulunan aynı kent mobilyalarının farklı etkileri ve farklı kent mobilyalarının aynı etkileri değerlendirilmiş sonuç olarak kent mobilyaları bulundukları mekânların fonksiyonelliklerini arttırdığı, bulundukları mekânları daha fonksiyonel hale getirdiği ve mekânların estetik kalitesini arttırdığı bulgulanmıştır

25 CFR 115.106 - Assets of members of the Agua Caliente Band of Mission Indians.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Assets of members of the Agua Caliente Band of Mission Indians. 115.106 Section 115.106 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES TRUST FUNDS FOR TRIBES AND INDIVIDUAL INDIANS IIM Accounts § 115.106 Assets of members of the Agua...

13 CFR 106.302 - What provisions must be set forth in a Fee Based Record?

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What provisions must be set forth in a Fee Based Record? 106.302 Section 106.302 Business Credit and Assistance SMALL BUSINESS... does not constitute or imply an endorsement by SBA of the Donor or the Donor's products or services. ...

Bazhen Fm matured reservoir evaluation (West Siberia, Russia)

Science.gov (United States)

Parnachev, S.; Skripkin, A.; Baranov, V.; Zakharov, S.

2015-02-01

The depletion of the traditional sources of hydrocarbons leads to the situation when the biggest players of the oil and gas production market turn to unconventional reserves. Commercial shale oil and gas production levels in the USA have largely determined world prospects for oil and gas industry development. Russia takes one of the leading place in the world in terms of shale oil resources. The main source rock of the West Siberia, the biggest oil and gas basin in Russia under development, the Bazhen Fm and its stratigraphic and lithologic analogs, is located in the territory of over 1,000,000 square kilometers. Provided it has similar key properties (organic carbon content, porosity, permeability) with the deposits of the Bakken Fm and Green River Fm, USA, it is still extremely poorly described with laboratory methods. We have performed the laboratory analysis of core samples from a well drilled in Bazhen Fm deposits with matured organic matter (Tmax>435 °C). It was demonstrated the applicability of the improved steady-state gas flow method to evaluate the permeability of nanopermeable rocks. The role of natural fracturing in forming voids was determided that allows regarding potential Bazhen Fm reservoirs as systems with dual porosity and dual permeability.

Bazhen Fm matured reservoir evaluation (West Siberia, Russia)

International Nuclear Information System (INIS)

Parnachev, S; Skripkin, A; Baranov, V; Zakharov, S

2015-01-01

The depletion of the traditional sources of hydrocarbons leads to the situation when the biggest players of the oil and gas production market turn to unconventional reserves. Commercial shale oil and gas production levels in the USA have largely determined world prospects for oil and gas industry development. Russia takes one of the leading place in the world in terms of shale oil resources. The main source rock of the West Siberia, the biggest oil and gas basin in Russia under development, the Bazhen Fm and its stratigraphic and lithologic analogs, is located in the territory of over 1,000,000 square kilometers. Provided it has similar key properties (organic carbon content, porosity, permeability) with the deposits of the Bakken Fm and Green River Fm, USA, it is still extremely poorly described with laboratory methods. We have performed the laboratory analysis of core samples from a well drilled in Bazhen Fm deposits with matured organic matter (T max >435 °C). It was demonstrated the applicability of the improved steady-state gas flow method to evaluate the permeability of nanopermeable rocks. The role of natural fracturing in forming voids was determided that allows regarding potential Bazhen Fm reservoirs as systems with dual porosity and dual permeability

Rac1 is crucial for Ras-dependent skin tumor formation by controlling Pak1-Mek-Erk hyperactivation and hyperproliferation in vivo

DEFF Research Database (Denmark)

Wang, Z; Pedersen, Esben Ditlev Kølle; Basse, A

2010-01-01

that Rac1 is essential for DMBA/TPA-induced skin tumor formation. This corresponded to a decreased keratinocyte hyperproliferation, although apoptosis was not detectably altered. Activated Rac1 promoted Erk-dependent hyperproliferation by Pak1-mediated Mek activation independent of Mek1 phosporylation...

7 CFR Exhibit C to Subpart E of... - FmHA or Its Successor Agency Under Public Law 103-354 Financed Contract

Science.gov (United States)

2010-01-01

... or Its Successor Agency Under Public Law 103-354 Financed Contract To: Area Director, Office of... 7 Agriculture 12 2010-01-01 2010-01-01 false FmHA or Its Successor Agency Under Public Law 103-354 Financed Contract C Exhibit C to Subpart E of Part 1901 Agriculture Regulations of the Department of...

29 CFR 570.106 - “Ship or deliver for shipment in commerce”.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false âShip or deliver for shipment in commerceâ. 570.106 Section 570.106 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION General Statements of Interpretation of the Child Labor Provisions of...

Involvement of Mos-MEK-MAPK pathway in cytostatic factor (CSF) arrest in eggs of the parthenogenetic insect, Athalia rosae.

Science.gov (United States)

Yamamoto, Daisuke S; Tachibana, Kazunori; Sumitani, Megumi; Lee, Jae Min; Hatakeyama, Masatsugu

2008-01-01

Extensive survey of meiotic metaphase II arrest during oocyte maturation in vertebrates revealed that the mitogen-activated protein kinase (MAPK) pathway regulated by the c-mos proto-oncogene product, Mos, has an essential role in cytostatic activity, termed cytostatic factor (CSF). In contrast, little is known in invertebrates in which meiotic arrest occurs in most cases at metaphase I (MI arrest). A parthenogenetic insect, the sawfly Athalia rosae, in which artificial egg activation is practicable, has advantages to investigate the mechanisms of MI arrest. Both the MAPK/extracellular signal-regulated protein kinase kinase (MEK) and MAPK were phosphorylated and maintained active in MI-arrested sawfly eggs, whereas they were dephosphorylated soon after egg activation. Treatment of MI-arrested eggs with U0126, an inhibitor of MEK, resulted in dephosphorylation of MAPK and MI arrest was resumed. The sawfly c-mos gene orthologue encoding a serine/threonine kinase was cloned and analyzed. It was expressed in nurse cells in the ovaries. To examine CSF activity of the sawfly Mos, synthesized glutathione S-transferase (GST)-fusion sawfly Mos protein was injected into MI-resumed eggs in which MEK and MAPK were dephosphorylated. Both MEK and MAPK were phosphorylated again upon injection. In these GST-fusion sawfly Mos-injected eggs subsequent mitotic (syncytial) divisions were blocked and embryonic development was ceased. These results demonstrated that the MEK-MAPK pathway was involved in maintaining CSF arrest in sawfly eggs and Mos functioned as its upstream regulatory molecule.

The inventory for déjà vu experiences assessment. Development, utility, reliability, and validity

NARCIS (Netherlands)

Sno, H. N.; Schalken, H. F.; de Jonghe, F.; Koeter, M. W.

1994-01-01

In this article the development, utility, reliability, and validity of the Inventory for Déjà vu Experiences Assessment (IDEA) are described. The IDEA is a 23-item self-administered questionnaire consisting of a general section of nine questions and qualitative section of 14 questions. The latter

PI3 kinase is important for Ras, MEK and Erk activation of Epo-stimulated human erythroid progenitors

Directory of Open Access Journals (Sweden)

Schmidt Enrico K

2004-05-01

Full Text Available Abstract Background Erythropoietin is a multifunctional cytokine which regulates the number of erythrocytes circulating in mammalian blood. This is crucial in order to maintain an appropriate oxygen supply throughout the body. Stimulation of primary human erythroid progenitors (PEPs with erythropoietin (Epo leads to the activation of the mitogenic kinases (MEKs and Erks. How this is accomplished mechanistically remained unclear. Results Biochemical studies with human cord blood-derived PEPs now show that Ras and the class Ib enzyme of the phosphatidylinositol-3 kinase (PI3K family, PI3K gamma, are activated in response to minimal Epo concentrations. Surprisingly, three structurally different PI3K inhibitors block Ras, MEK and Erk activation in PEPs by Epo. Furthermore, Erk activation in PEPs is insensitive to the inhibition of Raf kinases but suppressed upon PKC inhibition. In contrast, Erk activation induced by stem cell factor, which activates c-Kit in the same cells, is sensitive to Raf inhibition and insensitive to PI3K and PKC inhibitors. Conclusions These unexpected findings contrast with previous results in human primary cells using Epo at supraphysiological concentrations and open new doors to eventually understanding how low Epo concentrations mediate the moderate proliferation of erythroid progenitors under homeostatic blood oxygen levels. They indicate that the basal activation of MEKs and Erks in PEPs by minimal concentrations of Epo does not occur through the classical cascade Shc/Grb2/Sos/Ras/Raf/MEK/Erk. Instead, MEKs and Erks are signal mediators of PI3K, probably the recently described PI3K gamma, through a Raf-independent signaling pathway which requires PKC activity. It is likely that higher concentrations of Epo that are induced by hypoxia, for example, following blood loss, lead to additional mitogenic signals which greatly accelerate erythroid progenitor proliferation.

The Added Value of FM : Different Research Perspectives

NARCIS (Netherlands)

Jensen, P; van der Voordt, Theo; Coenen, C; von Felten, D; Lindholm, A

2010-01-01

Purpose: This paper aims to present and compare research perspectives and theoretical reflections from a variety of academic fields on the concept of Added Value of Facilities Management (FM).
Theory: The starting point is the so-called FM Value Map, which was presented in a paper by Jensen

42 CFR 441.106 - Comprehensive mental health program.

Science.gov (United States)

2010-10-01

... health and public welfare resources; including— (i) Community mental health centers; (ii) Nursing homes... 42 Public Health 4 2010-10-01 2010-10-01 false Comprehensive mental health program. 441.106... Comprehensive mental health program. (a) If the plan includes services in public institutions for mental...

33 CFR 106.140 - Maritime Security (MARSEC) Directive.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Maritime Security (MARSEC... SECURITY MARITIME SECURITY MARINE SECURITY: OUTER CONTINENTAL SHELF (OCS) FACILITIES General § 106.140 Maritime Security (MARSEC) Directive. All OCS facility owners or operators subject to this part must comply...

Reflecting on future research concerning the added value of FM

DEFF Research Database (Denmark)

Jensen, Per Anker; van der Voordt, Theo; Coenen, Christian

2014-01-01

on contributions to the recently published book “The Added Value of Facilities Management” and related future studies, as well as further exploration of five main themes. Findings – Added value is expected to be central in the future development of FM, which is confirmed by recent foresight studies....... There is a need for a better understanding of alignment between FM and core business, performance measurement methods and how models such as the FM Value Map can be of value to the involved stakeholders. Corporate social responsibility (CSR), sustainability and branding have great potential to add value......Purpose – This paper aims to summarize recent research findings and reflections on The Added Value of Facilities Management (FM) and to outline perspectives for future research and development of the added value of FM. Design/methodology/approach – The article is based on reflections...

A novel M1 PAM VU0486846 exerts efficacy in cognition models without displaying agonist activity or cholinergic toxicity.

Science.gov (United States)

Rook, Jerri M; Bertron, Jeanette L; Cho, Hyekyung P; Garcia-Barrantes, Pedro M; Moran, Sean P; Maksymetz, James T; Nance, Kellie D; Dickerson, Jonathan W; Remke, Daniel H; Chang, Sichen; Harp, Joel; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

2018-04-27

Selective activation of the M1 subtype of muscarinic acetylcholine receptor, via positive allosteric modulation (PAM), is an exciting strategy to improve cognition in schizophrenia and Alzheimer's disease patients. However, highly potent M1 ago-PAMs, such as MK-7622, PF-06764427, and PF-06827443, can engender excessive activation of M1, leading to agonist actions in the prefrontal cortex (PFC) that impairs cognitive function, induces behavioral convulsions, and results in other classic cholinergic adverse events (AEs). Here, we report a fundamentally new and highly selective M1 PAM, VU0486846. VU0486846 possesses only weak agonist activity in M1-expressing cell lines with high receptor reserve and is devoid of agonist actions in the PFC, unlike previously reported ago-PAMs MK-7622, PF-06764427 and PF-06827443. Moreover, VU0486846 shows no interaction with antagonist binding at the orthosteric acetylcholine (ACh) site (e.g., neither bitopic nor displaying negative cooperativity with [3H]-NMS binding at theorthosteric site), no seizure liability at high brain exposures, and no cholinergic AEs. However, as opposed to ago-PAMs, VU0486846 produces robust efficacy in the novel object recognition model of cognitive function. Importantly, we show for the first time that an M1 PAM can reverse the cognitive deficits induced by atypical antipsychotics, such as risperidone. These findings further strengthen the argument that compounds with modest in vitro M1 PAM activity (EC50s > 100 nM) and pure-PAM activity in native tissues display robust pro-cognitive efficacy without AEs mediated by excessive activation of M1. Overall, the combination of compound assessment with recombinant in vitro assays (mindful of receptor reserve), native tissue systems (PFC), and phenotypic screens (behavioral convulsions) is essential to fully understand and evaluate lead compounds and enhance success in clinical development.

13 CFR 106.402 - What provisions must be set forth in a Non-Fee Based Record?

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What provisions must be set forth in a Non-Fee Based Record? 106.402 Section 106.402 Business Credit and Assistance SMALL BUSINESS... endorsement by SBA of the Donor, or the Donor's products or services. ...

To procure for better buildings - FM and Public Private Partnerships in Denmark

DEFF Research Database (Denmark)

Kristiansen, Kristian

and a review of literature on issues related to integration of FM considerations in the planning, design and construction of facilities has been made. Some case studies on the influence of elements in partnerships to the integration of FM are being prepared. Results: The results indicate that the effect of PPP......Purpose: The paper is based on a research project investigating whether PPP´s are good for the procurement of FM, i.e. are PPP´s advantageous for the integration of FM considerations into the planning, design and construction of buildings? Background: In Public-Private Partnerships FM services...... process and the relationships between the actors are paramount for the integration of FM. Practical Implications: The results imply that FM practitioners should pay interest to issues related to the sociology of the construction process rather than legal arrangements like PPP....

7 CFR 1421.106 - Warehouse-stored marketing assistance loan collateral.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Warehouse-stored marketing assistance loan collateral... Marketing Assistance Loans § 1421.106 Warehouse-stored marketing assistance loan collateral. (a) A commodity may be pledged as collateral for a warehouse-stored marketing assistance loan in the quantity...

Interleukin-8 stimulates progesterone production via the MEK pathway in ovarian theca cells.

Science.gov (United States)

Shimizu, Takashi; Imamura, Eri; Magata, Fumie; Murayama, Chiaki; Miyamoto, Akio

2013-02-01

Interleukin 8 (IL-8) is a chemoattractant associated with ovulation in the mammalian ovary. This chemokine is also involved in the recruitment and activation of neutrophils. Using bovine tissue, we examined the possible role of IL-8 in steroid production by theca cells of the large ovarian follicles. IL-8 promoted progesterone production and stimulated StAR expression in cultured theca cells. The inhibitor of p38 did not disturb the P4 production and StAR expression in IL-8-treated theca cells. On the other hand, the inhibitor of MEK disturbed the P4 production and expression of StAR in theca cells treated with IL-8. These results suggest that IL-8 is associated with progesterone production in bovine theca cells via the MEK pathway.

A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition.

Science.gov (United States)

Bagheri, Neda; Shiina, Marisa; Lauffenburger, Douglas A; Korn, W Michael

2011-02-01

Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced

Enhanced expressions of microvascular smooth muscle receptors after focal cerebral ischemia occur via the MAPK MEK/ERK pathway

DEFF Research Database (Denmark)

Maddahi, A.; Edvinsson, L.

2008-01-01

), the enhanced vascular receptor expression, and attenuated the cerebral infarct and improved neurology score. CONCLUSION: Our results show that MCAO results in upregulation of cerebrovascular ETB, AT1 and 5-HT1B receptors. Blockade of this event with a MEK1 inhibitor as late as 6 h after the insult reduced...... the role of the MEK/ERK pathway in receptor expression following ischemic brain injury using the specific MEK1 inhibitor U0126. METHODS AND RESULT: Rats were subjected to a 2-h middle cerebral artery occlusion (MCAO) followed by reperfusion for 48-h and the ischemic area was calculated. The expression...... of phosphorylated ERK1/2 and Elk-1, and of endothelin ETA and ETB, angiotensin AT1, and 5-hydroxytryptamine 5-HT1B receptors were analyzed with immunohistochemistry using confocal microscopy in cerebral arteries, microvessels and in brain tissue. The expression of endothelin ETB receptor was analyzed...

E-Learning Readiness in Medicine: Turkish Family Medicine (FM) Physicians Case

Science.gov (United States)

Parlakkiliç, Alaattin

2015-01-01

This research investigates e-learning readiness level of family medicine physicians (FM) in Turkey. The study measures the level of e-learning readiness of Turkish FM physicians by an online e-learning readiness survey. According to results five areas are ready at Turkish FM physicians but need a few improvements:…

The start of a Nordic focus on the added value of FM

DEFF Research Database (Denmark)

Jensen, Per Anker; Malmstrøm, Ole Emil

2012-01-01

. Findings: Different methods to demonstrate the added value of FM are presented and the analysis of the cases shows that a change in responsibility – both between core business and in-house FM and between in-house FM and providers - can be an important element in the possibility for FM to create added value....... On-going collaboration can also be an important leverage for adding value in FM. Practical implications: The findings can provide inspiration and methods for facilities managers to implement adding value initiatives and demonstrate their impact on the core business. Research limitations: The chapter...

26 CFR 509.106 - Control of a United States enterprise by a Swiss enterprise.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 19 2010-04-01 2010-04-01 false Control of a United States enterprise by a Swiss enterprise. 509.106 Section 509.106 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... a United States enterprise by a Swiss enterprise. In effect, Article IV of the convention provides...

CERES Single Satellite Footprint, TOA and Surface Fluxes, Clouds (SSF) data in HDF (CER_SSF_Aqua-FM4-MODIS_Edition2A)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The Single Scanner Footprint TOA/Surface Fluxes and Clouds (SSF) product contains one hour of instantaneous Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The SSF combines instantaneous CERES data with scene information from a higher-resolution imager such as Visible/Infrared Scanner (VIRS) on TRMM or Moderate-Resolution Imaging Spectroradiometer (MODIS) on Terra and Aqua. Scene identification and cloud properties are defined at the higher imager resolution and these data are averaged over the larger CERES footprint. For each CERES footprint, the SSF contains the number of cloud layers and for each layer the cloud amount, height, temperature, pressure, optical depth, emissivity, ice and liquid water path, and water particle size. The SSF also contains the CERES filtered radiances for the total, shortwave (SW), and window (WN) channels and the unfiltered SW, longwave (LW), and WN radiances. The SW, LW, and WN radiances at spacecraft altitude are converted to Top-of-the-Atmosphere (TOA) fluxes based on the imager defined scene. These TOA fluxes are used to estimate surface fluxes. Only footprints with adequate imager coverage are included on CER_SSF_TRMM-PFM-VIRS_Subset_Edition1the SSF which is much less than the full set of footprints on the CERES ES-8 product. The following CERES SSF data sets are currently available: CER_SSF_TRMM-PFM-VIRS_Edition1 CER_SSF_TRMM-PFM-VIRS_Subset_Edition1 CER_SSF_TRMM-PFM-VIRS_Edition2A CER_SSF_TRMM-SIM-VIRS_Edition2_VIRSonly CER_SSF_TRMM-PFM-VIRS_Edition2A-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition2A CER_SSF_Terra-FM2-MODIS_Edition2A CER_SSF_Terra-FM1-MODIS_Edition2B CER_SSF_Terra-FM2-MODIS_Edition2B CER_SSF_Aqua-FM4-MODIS_Beta1 CER_SSF_Aqua-FM3-MODIS_Beta2 CER_SSF_Aqua-FM4-MODIS_Beta2. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop

Cognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M4 PAM VU0467154.

Science.gov (United States)

Gould, Robert W; Grannan, Michael D; Gunter, Barak W; Ball, Jacob; Bubser, Michael; Bridges, Thomas M; Wess, Jurgen; Wood, Michael W; Brandon, Nicholas J; Duggan, Mark E; Niswender, Colleen M; Lindsley, Craig W; Conn, P Jeffrey; Jones, Carrie K

2018-01-01

Although selective activation of the M 1 muscarinic acetylcholine receptor (mAChR) subtype has been shown to improve cognitive function in animal models of neuropsychiatric disorders, recent evidence suggests that enhancing M 4 mAChR function can also improve memory performance. Positive allosteric modulators (PAMs) targeting the M 4 mAChR subtype have shown therapeutic potential for the treatment of multiple symptoms observed in schizophrenia, including positive and cognitive symptoms when assessed in acute preclinical dosing paradigms. Since the cholinergic system has been implicated in multiple stages of learning and memory, we evaluated the effects of repeated dosing with the highly selective M 4 PAM VU0467154 on either acquisition and/or consolidation of learning and memory when dosed alone or after pharmacologic challenge with the N-methyl-d-aspartate subtype of glutamate receptors (NMDAR) antagonist MK-801. MK-801 challenge represents a well-documented preclinical model of NMDAR hypofunction that is thought to underlie some of the positive and cognitive symptoms observed in schizophrenia. In wildtype mice, 10-day, once-daily dosing of VU0467154 either prior to, or immediately after daily testing enhanced the rate of learning in a touchscreen visual pairwise discrimination task; these effects were absent in M 4 mAChR knockout mice. Following a similar 10-day, once-daily dosing regimen of VU0467154, we also observed 1) improved acquisition of memory in a cue-mediated conditioned freezing paradigm, 2) attenuation of MK-801-induced disruptions in the acquisition of memory in a context-mediated conditioned freezing paradigm and 3) reversal of MK-801-induced hyperlocomotion. Comparable efficacy and plasma and brain concentrations of VU0467154 were observed after repeated dosing as those previously reported with an acute, single dose administration of this M 4 PAM. Together, these studies are the first to demonstrate that cognitive enhancing and antipsychotic

Light-Mediated Kinetic Control Reveals the Temporal Effect of the Raf/MEK/ERK Pathway in PC12 Cell Neurite Outgrowth

Science.gov (United States)

Zhang, Kai; Duan, Liting; Ong, Qunxiang; Lin, Ziliang; Varman, Pooja Mahendra; Sung, Kijung; Cui, Bianxiao

2014-01-01

It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network. PMID:24667437

Identification of Putative Mek1 Substrates during Meiosis in Saccharomyces cerevisiae Using Quantitative Phosphoproteomics.

Directory of Open Access Journals (Sweden)

Raymond T Suhandynata

Full Text Available Meiotic recombination plays a key role in sexual reproduction as it generates crossovers that, in combination with sister chromatid cohesion, physically connect homologous chromosomes, thereby promoting their proper segregation at the first meiotic division. Meiotic recombination is initiated by programmed double strand breaks (DSBs catalyzed by the evolutionarily conserved, topoisomerase-like protein Spo11. Repair of these DSBs is highly regulated to create crossovers between homologs that are distributed throughout the genome. This repair requires the presence of the mitotic recombinase, Rad51, as well as the strand exchange activity of the meiosis-specific recombinase, Dmc1. A key regulator of meiotic DSB repair in Saccharomyces cerevisiae is the meiosis-specific kinase Mek1, which promotes interhomolog strand invasion and is required for the meiotic recombination checkpoint and the crossover/noncrossover decision. Understanding how Mek1 regulates meiotic recombination requires the identification of its substrates. Towards that end, an unbiased phosphoproteomic approach utilizing Stable Isotope Labeling by Amino Acids in Cells (SILAC was utilized to generate a list of potential Mek1 substrates, as well as proteins containing consensus phosphorylation sites for cyclin-dependent kinase, the checkpoint kinases, Mec1/Tel1, and the polo-like kinase, Cdc5. These experiments represent the first global phosphoproteomic dataset for proteins in meiotic budding yeast.

27 CFR 26.106 - Marking containers of beer.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Marking containers of beer... Liquors and Articles in Puerto Rico Beer § 26.106 Marking containers of beer. Containers of beer of Puerto... brewer; the serial number, capacity, and size of the container; the kind of beer; and the serial number...

Cytokinetically quiescent (G0/G1) human multiple myeloma cells are susceptible to simultaneous inhibition of Chk1 and MEK1/2.

Science.gov (United States)

Pei, Xin-Yan; Dai, Yun; Youssefian, Leena E; Chen, Shuang; Bodie, Wesley W; Takabatake, Yukie; Felthousen, Jessica; Almenara, Jorge A; Kramer, Lora B; Dent, Paul; Grant, Steven

2011-11-10

Effects of Chk1 and MEK1/2 inhibition were investigated in cytokinetically quiescent multiple myeloma (MM) and primary CD138(+) cells. Coexposure to the Chk1 and MEK1/2 inhibitors AZD7762 and selumetinib (AZD6244) robustly induced apoptosis in various MM cells and CD138(+) primary samples, but spared normal CD138(-) and CD34(+) cells. Furthermore, Chk1/MEK1/2 inhibitor treatment of asynchronized cells induced G(0)/G(1) arrest and increased apoptosis in all cell-cycle phases, including G(0)/G(1). To determine whether this regimen is active against quiescent G(0)/G(1) MM cells, cells were cultured in low-serum medium to enrich the G(0)/G(1) population. G(0)/G(1)-enriched cells exhibited diminished sensitivity to conventional agents (eg, Taxol and VP-16) but significantly increased susceptibility to Chk1 ± MEK1/2 inhibitors or Chk1 shRNA knock-down. These events were associated with increased γH2A.X expression/foci formation and Bim up-regulation, whereas Bim shRNA knock-down markedly attenuated lethality. Immunofluorescent analysis of G(0)/G(1)-enriched or primary MM cells demonstrated colocalization of activated caspase-3 and the quiescent (G(0)) marker statin, a nuclear envelope protein. Finally, Chk1/MEK1/2 inhibition increased cell death in the Hoechst-positive (Hst(+)), low pyronin Y (PY)-staining (2N Hst(+)/PY(-)) G(0) population and in sorted small side-population (SSP) MM cells. These findings provide evidence that cytokinetically quiescent MM cells are highly susceptible to simultaneous Chk1 and MEK1/2 inhibition.

Behandlingen af BRAF-muteret metastatisk melanom med BRAF/MEK-inhibitorer bedre prognosen

DEFF Research Database (Denmark)

Boyles, Tessa Bystrup; Svane, Inge Marie; Bastholt, Lars

2016-01-01

Melanoma is an aggressive form of skin cancer which is the cause of a great number of skin cancer-related deaths worldwide and about 300 deaths in Denmark. After several years of failure of treatment of metastatic melanoma, the development of BRAF- and later MEK inhibitors was considered...

Behandlingen af BRAF-muteret metastatisk melanom med BRAF/MEK-inhibitorer bedrer prognosen

DEFF Research Database (Denmark)

Boyles, Tessa Bystrup; Svane, Inge Marie; Bastholt, Lars

2016-01-01

Melanoma is an aggressive form of skin cancer which is the cause of a great number of skin cancer-related deaths worldwide and about 300 deaths in Denmark. After several years of failure of treatment of metastatic melanoma, the development of BRAF- and later MEK inhibitors was considered...

15 CFR 2006.3 - Determinations regarding petitions.

Science.gov (United States)

2010-01-01

..., including but not limited to a domestic firm or worker, a representative of consumer interests, a United... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Determinations regarding petitions. 2006.3 Section 2006.3 Commerce and Foreign Trade Regulations Relating to Foreign Trade Agreements...

17 CFR 10.106 - Reconsideration; stay pending judicial review.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Reconsideration; stay pending... COMMISSION RULES OF PRACTICE Appeals to the Commission; Settlements § 10.106 Reconsideration; stay pending... operate to stay the effective date of the Commission's order. (b) Stay pending judicial appeal—(1...

33 CFR 106.255 - Security systems and equipment maintenance.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Security systems and equipment... Shelf (OCS) Facility Security Requirements § 106.255 Security systems and equipment maintenance. (a) Security systems and equipment must be in good working order and inspected, tested, calibrated, and...

Academic Training: 2nd Term - 09.01.2006 - 31.03.2006

CERN Multimedia

Françoise Benz

2005-01-01

2005 - 2006 ACADEMIC TRAINING PROGRAMME LECTURE SERIES The world quantum matter by M. Weidemüller, Univ. Freiburg, D 23, 24, 25, 26 January 11:00 -1200 - Auditorium, bldg 500 Deep space telescopes by G. Bignami, CNRS, Toulouse, F 13, 14, 15, 16, 17 February 11:00-12:00 - Auditorium, bldg 500 Bioinformatics: analysing the genome by V. Jongeneel, O. Michielin, S. Antonorakis A. Thomas and P. Descombes 27, 28 February, 1, 2, 3 March11:00-12:00 - Auditorium, bldg 500 LHC luminosity upgrade: detector challengesby A. de Roeck,CERN-PH, D. Bortoletto, Purdue Univ. USA R. Wigmans, Texas Tech. Univ. USA, W. Riegler, CERN-AT, W. Smith, Univ. of Wisconsin, USA 13, 14, 15, 16, March 11:00-12:00 - Auditorium, bldg 500 Supersymmetry and the LHC by M. Drees, Univ. of Bonn, D 20, 21, 22, 23, 24 March 11:00-12:00 - Auditorium, bldg 500 The lectures are open to all those interested, without application. The abstract of the lectures, as well as any change to the above information (title, dates, time, place etc.) will be...

FM contract relationships: from mobilisation to sustainable partnership

OpenAIRE

Ellison, I.; Owen, S.

2010-01-01

Purpose / theory\\ud Outsourcing is a fundamental business model for the Facilities Management (FM) industry. To enable sustained mutual success the parties involved must seek to understand the unique, socially constructed, and often highly complex situational realities of the organisational ecologies they are engaged in. The FM industry can unlock improved performance and strategic credibility through an appreciation of the need for different conversations.\\ud Design / methodology / approach\\...

ETS1 mediates MEK1/2-dependent overexpression of cancerous inhibitor of protein phosphatase 2A (CIP2A in human cancer cells.

Directory of Open Access Journals (Sweden)

Anchit Khanna

2011-03-01

Full Text Available EGFR-MEK-ERK signaling pathway has an established role in promoting malignant growth and disease progression in human cancers. Therefore identification of transcriptional targets mediating the oncogenic effects of the EGFR-MEK-ERK pathway would be highly relevant. Cancerous inhibitor of protein phosphatase 2A (CIP2A is a recently characterized human oncoprotein. CIP2A promotes malignant cell growth and is over expressed at high frequency (40-80% in most of the human cancer types. However, the mechanisms inducing its expression in cancer still remain largely unexplored. Here we present systematic analysis of contribution of potential gene regulatory mechanisms for high CIP2A expression in cancer. Our data shows that evolutionary conserved CpG islands at the proximal CIP2A promoter are not methylated both in normal and cancer cells. Furthermore, sequencing of the active CIP2A promoter region from altogether seven normal and malignant cell types did not reveal any sequence alterations that would increase CIP2A expression specifically in cancer cells. However, treatment of cancer cells with various signaling pathway inhibitors revealed that CIP2A mRNA expression was sensitive to inhibition of EGFR activity as well as inhibition or activation of MEK-ERK pathway. Moreover, MEK1/2-specific siRNAs decreased CIP2A protein expression. Series of CIP2A promoter-luciferase constructs were created to identify proximal -27 to -107 promoter region responsible for MEK-dependent stimulation of CIP2A expression. Additional mutagenesis and chromatin immunoprecipitation experiments revealed ETS1 as the transcription factor mediating stimulation of CIP2A expression through EGFR-MEK pathway. Thus, ETS1 is probably mediating high CIP2A expression in human cancers with increased EGFR-MEK1/2-ERK pathway activity. These results also suggest that in addition to its established role in invasion and angiogenesis, ETS1 may support malignant cellular growth via regulation of

CERES Single Scanner Satellite Footprint, TOA, Surface Fluxes and Clouds (SSF) data in HDF (CER_SSF_Aqua-FM4-MODIS_Edition1B)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The Single Scanner Footprint TOA/Surface Fluxes and Clouds (SSF) product contains one hour of instantaneous Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The SSF combines instantaneous CERES data with scene information from a higher-resolution imager such as Visible/Infrared Scanner (VIRS) on TRMM or Moderate-Resolution Imaging Spectroradiometer (MODIS) on Terra and Aqua. Scene identification and cloud properties are defined at the higher imager resolution and these data are averaged over the larger CERES footprint. For each CERES footprint, the SSF contains the number of cloud layers and for each layer the cloud amount, height, temperature, pressure, optical depth, emissivity, ice and liquid water path, and water particle size. The SSF also contains the CERES filtered radiances for the total, shortwave (SW), and window (WN) channels and the unfiltered SW, longwave (LW), and WN radiances. The SW, LW, and WN radiances at spacecraft altitude are converted to Top-of-the-Atmosphere (TOA) fluxes based on the imager defined scene. These TOA fluxes are used to estimate surface fluxes. Only footprints with adequate imager coverage are included on CER_SSF_TRMM-PFM-VIRS_Subset_Edition1the SSF which is much less than the full set of footprints on the CERES ES-8 product. The following CERES SSF data sets are currently available: CER_SSF_TRMM-PFM-VIRS_Edition1 CER_SSF_TRMM-PFM-VIRS_Subset_Edition1 CER_SSF_TRMM-PFM-VIRS_Edition2A CER_SSF_TRMM-SIM-VIRS_Edition2_VIRSonly CER_SSF_TRMM-PFM-VIRS_Edition2A-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition2A CER_SSF_Terra-FM2-MODIS_Edition2A CER_SSF_Terra-FM1-MODIS_Edition2B CER_SSF_Terra-FM2-MODIS_Edition2B CER_SSF_Aqua-FM4-MODIS_Beta1 CER_SSF_Aqua-FM3-MODIS_Beta2 CER_SSF_Aqua-FM4-MODIS_Beta2. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop

CERES Single Scanner Satellite Footprint, TOA, Surface Fluxes and Clouds (SSF) data in HDF (CER_SSF_Terra-FM2-MODIS_Edition2A)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The Single Scanner Footprint TOA/Surface Fluxes and Clouds (SSF) product contains one hour of instantaneous Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The SSF combines instantaneous CERES data with scene information from a higher-resolution imager such as Visible/Infrared Scanner (VIRS) on TRMM or Moderate-Resolution Imaging Spectroradiometer (MODIS) on Terra and Aqua. Scene identification and cloud properties are defined at the higher imager resolution and these data are averaged over the larger CERES footprint. For each CERES footprint, the SSF contains the number of cloud layers and for each layer the cloud amount, height, temperature, pressure, optical depth, emissivity, ice and liquid water path, and water particle size. The SSF also contains the CERES filtered radiances for the total, shortwave (SW), and window (WN) channels and the unfiltered SW, longwave (LW), and WN radiances. The SW, LW, and WN radiances at spacecraft altitude are converted to Top-of-the-Atmosphere (TOA) fluxes based on the imager defined scene. These TOA fluxes are used to estimate surface fluxes. Only footprints with adequate imager coverage are included on CER_SSF_TRMM-PFM-VIRS_Subset_Edition1the SSF which is much less than the full set of footprints on the CERES ES-8 product. The following CERES SSF data sets are currently available: CER_SSF_TRMM-PFM-VIRS_Edition1 CER_SSF_TRMM-PFM-VIRS_Subset_Edition1 CER_SSF_TRMM-PFM-VIRS_Edition2A CER_SSF_TRMM-SIM-VIRS_Edition2_VIRSonly CER_SSF_TRMM-PFM-VIRS_Edition2A-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition2A CER_SSF_Terra-FM2-MODIS_Edition2A CER_SSF_Terra-FM1-MODIS_Edition2B CER_SSF_Terra-FM2-MODIS_Edition2B CER_SSF_Aqua-FM4-MODIS_Beta1 CER_SSF_Aqua-FM3-MODIS_Beta2 CER_SSF_Aqua-FM4-MODIS_Beta2. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop

CERES Single Scanner Satellite Footprint, TOA, Surface Fluxes and Clouds (SSF) data in HDF (CER_SSF_Terra-FM1-MODIS_Edition2A)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The Single Scanner Footprint TOA/Surface Fluxes and Clouds (SSF) product contains one hour of instantaneous Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The SSF combines instantaneous CERES data with scene information from a higher-resolution imager such as Visible/Infrared Scanner (VIRS) on TRMM or Moderate-Resolution Imaging Spectroradiometer (MODIS) on Terra and Aqua. Scene identification and cloud properties are defined at the higher imager resolution and these data are averaged over the larger CERES footprint. For each CERES footprint, the SSF contains the number of cloud layers and for each layer the cloud amount, height, temperature, pressure, optical depth, emissivity, ice and liquid water path, and water particle size. The SSF also contains the CERES filtered radiances for the total, shortwave (SW), and window (WN) channels and the unfiltered SW, longwave (LW), and WN radiances. The SW, LW, and WN radiances at spacecraft altitude are converted to Top-of-the-Atmosphere (TOA) fluxes based on the imager defined scene. These TOA fluxes are used to estimate surface fluxes. Only footprints with adequate imager coverage are included on CER_SSF_TRMM-PFM-VIRS_Subset_Edition1the SSF which is much less than the full set of footprints on the CERES ES-8 product. The following CERES SSF data sets are currently available: CER_SSF_TRMM-PFM-VIRS_Edition1 CER_SSF_TRMM-PFM-VIRS_Subset_Edition1 CER_SSF_TRMM-PFM-VIRS_Edition2A CER_SSF_TRMM-SIM-VIRS_Edition2_VIRSonly CER_SSF_TRMM-PFM-VIRS_Edition2A-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B-TransOps CER_SSF_TRMM-PFM-VIRS_Edition2B CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition1A CER_SSF_Terra-FM1-MODIS_Edition2A CER_SSF_Terra-FM2-MODIS_Edition2A CER_SSF_Terra-FM1-MODIS_Edition2B CER_SSF_Terra-FM2-MODIS_Edition2B CER_SSF_Aqua-FM4-MODIS_Beta1 CER_SSF_Aqua-FM3-MODIS_Beta2 CER_SSF_Aqua-FM4-MODIS_Beta2. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop

7 CFR 1463.106 - Base quota levels for eligible tobacco producers.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Base quota levels for eligible tobacco producers... TOBACCO TRANSITION PROGRAM Tobacco Transition Payment Program § 1463.106 Base quota levels for eligible... farm's average yield for 2001, 2002, and 2003 to get the 2004 farm base pounds total. 2 Multiply any...

Role of spin polarization in FM/Al/FM trilayer film at low temperature

Science.gov (United States)

Lu, Ning; Webb, Richard

2014-03-01

Measurements of electronic transport in diffusive FM/normal metal/FM trilayer film are performed at temperature ranging from 2K to 300K to determine the behavior of the spin polarized current in normal metal under the influence of quantum phase coherence and spin-orbital interaction. Ten samples of Hall bar with length of 200 micron and width of 20 micron are fabricated through e-beam lithography followed by e-gun evaporation of Ni0.8Fe0.2, aluminum and Ni0.8Fe0.2 with different thickness (5nm to 45nm) in vacuum. At low temperature of 4.2K, coherent backscattering, Rashba spin-orbital interaction and spin flip scattering of conduction electrons contribute to magnetoresistance at low field. Quantitative analysis of magnetoresistance shows transition between weak localization and weak anti-localization for samples with different thickness ratio, which indicates the spin polarization actually affects the phase coherence length and spin-orbital scattering length. However, at temperature between 50K and 300K, only the spin polarization dominates the magnetoresistance.

5 CFR 890.106 - Delegation of authority for resolving certain contract disputes.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Delegation of authority for resolving... (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administration and General Provisions § 890.106 Delegation of authority for resolving certain contract disputes. For...

Antitumor activity in RAS-driven tumors by blocking AKT and MEK.

Science.gov (United States)

Tolcher, Anthony W; Khan, Khurum; Ong, Michael; Banerji, Udai; Papadimitrakopoulou, Vassiliki; Gandara, David R; Patnaik, Amita; Baird, Richard D; Olmos, David; Garrett, Christopher R; Skolnik, Jeffrey M; Rubin, Eric H; Smith, Paul D; Huang, Pearl; Learoyd, Maria; Shannon, Keith A; Morosky, Anne; Tetteh, Ernestina; Jou, Ying-Ming; Papadopoulos, Kyriakos P; Moreno, Victor; Kaiser, Brianne; Yap, Timothy A; Yan, Li; de Bono, Johann S

2015-02-15

KRAS is the most commonly mutated oncogene in human tumors. KRAS-mutant cells may exhibit resistance to the allosteric MEK1/2 inhibitor selumetinib (AZD6244; ARRY-142886) and allosteric AKT inhibitors (such as MK-2206), the combination of which may overcome resistance to both monotherapies. We conducted a dose/schedule-finding study evaluating MK-2206 and selumetinib in patients with advanced treatment-refractory solid tumors. Recommended dosing schedules were defined as MK-2206 at 135 mg weekly and selumetinib at 100 mg once daily. Grade 3 rash was the most common dose-limiting toxicity (DLT); other DLTs included grade 4 lipase increase, grade 3 stomatitis, diarrhea, and fatigue, and grade 3 and grade 2 retinal pigment epithelium detachment. There were no meaningful pharmacokinetic drug-drug interactions. Clinical antitumor activity included RECIST 1.0-confirmed partial responses in non-small cell lung cancer and low-grade ovarian carcinoma. Responses in KRAS-mutant cancers were generally durable. Clinical cotargeting of MEK and AKT signaling may be an important therapeutic strategy in KRAS-driven human malignancies (Trial NCT number NCT01021748). ©2014 American Association for Cancer Research.

Comparisons between PW Doppler system and enhanced FM Doppler system

DEFF Research Database (Denmark)

Wilhjelm, Jens E.; Pedersen, P. C.

1995-01-01

This paper presents a new implementation of an echo-ranging FM Doppler system with improved performance, relative to the FM Doppler system reported previously. The use of long sweeps provides a significant reduction in peak to average power ratio compared to pulsed wave (PW) emission. A PW Doppler...... system exploits the direct relationship between arrival time of the received signal and range from the transducer. In the FM Doppler systems, a similar relationship exists in the spectral domain of the demodulated received signals, so that range is represented by frequency. Thus, a shift in location...... of moving scatterers between consecutive emissions corresponds to a frequency shift in the spectral signature. The improvement relative to the earlier version of the FM Doppler system is attained by utilizing cross-correlation of real spectra rather than of magnitude spectra for assessing flow velocity...

Preparing Students to Take SOA/CAS Exam FM/2

Science.gov (United States)

Marchand, Richard J.

2014-01-01

This paper provides suggestions for preparing students to take the actuarial examination on financial mathematics, SOA/CAS Exam FM/2. It is based on current practices employed at Slippery Rock University, a small public liberal arts university. Detailed descriptions of our Theory of Interest course and subsequent Exam FM/2 prep course are provided…

Principles and Limitations of Ultra-Wideband FM Communications Systems

Directory of Open Access Journals (Sweden)

Kouwenhoven Michiel HL

2005-01-01

Full Text Available This paper presents a novel UWB communications system using double FM: a low-modulation index digital FSK followed by a high-modulation index analog FM to create a constant-envelope UWB signal. FDMA techniques at the subcarrier level are exploited to accommodate multiple users. The system is intended for low (1–10 kbps and medium (100–1000 kbps bit rate, and short-range WPAN systems. A wideband delay-line FM demodulator that is not preceded by any limiting amplifier constitutes the key component of the UWBFM receiver. This unusual approach permits multiple users to share the same RF bandwidth. Multipath, however, may limit the useful subcarrier bandwidth to one octave. This paper addresses the performance with AWGN and multipath, the resistance to narrowband interference, as well as the simultaneous detection of multiple FM signals at the same carrier frequency. SPICE and Matlab simulation results illustrate the principles and limitations of this new technology. A hardware demonstrator has been realized and has allowed the confirmation of theory with practical results.

Enhanced expressions of microvascular smooth muscle receptors after focal cerebral ischemia occur via the MAPK MEK/ERK pathway

Directory of Open Access Journals (Sweden)

Edvinsson Lars

2008-09-01

Full Text Available Abstract Background MEK1/2 is a serine/threonine protein that phosphorylates extracellular signal-regulated kinase (ERK1/2. Cerebral ischemia results in enhanced expression of cerebrovascular contractile receptors in the middle cerebral artery (MCA leading to the ischemic region. Here we explored the role of the MEK/ERK pathway in receptor expression following ischemic brain injury using the specific MEK1 inhibitor U0126. Methods and result Rats were subjected to a 2-h middle cerebral artery occlusion (MCAO followed by reperfusion for 48-h and the ischemic area was calculated. The expression of phosphorylated ERK1/2 and Elk-1, and of endothelin ETA and ETB, angiotensin AT1, and 5-hydroxytryptamine 5-HT1B receptors were analyzed with immunohistochemistry using confocal microscopy in cerebral arteries, microvessels and in brain tissue. The expression of endothelin ETB receptor was analyzed by quantitative Western blot. We demonstrate that there is an increase in the number of contractile smooth muscle receptors in the MCA and in micro- vessels within the ischemic region. The enhanced expression occurs in the smooth muscle cells as verified by co-localization studies. This receptor upregulation is furthermore associated with enhanced expression of pERK1/2 and of transcription factor pElk-1 in the vascular smooth muscle cells. Blockade of transcription with the MEK1 inhibitor U0126, given at the onset of reperfusion or as late as 6 hours after the insult, reduced transcription (pERK1/2 and pElk-1, the enhanced vascular receptor expression, and attenuated the cerebral infarct and improved neurology score. Conclusion Our results show that MCAO results in upregulation of cerebrovascular ETB, AT1 and 5-HT1B receptors. Blockade of this event with a MEK1 inhibitor as late as 6 h after the insult reduced the enhanced vascular receptor expression and the associated cerebral infarction.

Inhibition of MEK5 by BIX02188 induces apoptosis in cells expressing the oncogenic mutant FLT3-ITD

International Nuclear Information System (INIS)

Razumovskaya, Elena; Sun, Jianmin; Roennstrand, Lars

2011-01-01

Highlights: → In this study we have demonstrated that FLT3 activation leads to activation of ERK5. → We have demonstrated that ERK5 is involved in activation of AKT downstream of FLT3. → (BIX02188) blocks activation of ERK5 and induces apoptosis in FLT3 Ba/F3 cells. → (BIX02188) induce apoptosis in the two leukemic cell lines MV4-11 and MOLM-13. -- Abstract: Fms-like tyrosine kinase-3 (FLT3) is a growth factor receptor normally expressed on hematopoietic progenitor cells. Approximately one third of all patients with AML carry an activating mutation in FLT3 that drives proliferation and survival of the leukemic cells. The most common activating mutation is the so-called internal tandem duplication (ITD), which involves an in-frame duplication of a segment of varying length in the region of the FLT3 gene that encodes the juxtamembrane domain. The pathways downstream of FLT3-ITD are partially known but further knowledge regarding the downstream signal transduction molecules is important in order to develop alternative strategies for pharmacological intervention. In this paper we have studied the role of MEK/ERK5 in FLT3-ITD mediated transformation. We have found that both wild-type FLT3 and FLT3-ITD activate MEK5 leading to the activation of ERK5. By use of the selective inhibitor of MEK5, (BIX02188), we have shown that activation of AKT downstream of FLT3 is partially dependent on ERK5. Furthermore, inhibition of MEK5/ERK5 induces apoptosis of both FLT3-ITD transfected Ba/F3 cells as well as the FLT3-ITD carrying leukemic cell lines MV4-11 and MOLM-13. These results suggest that MEK5/ERK5 is important for FLT3-ITD induced hematopoietic transformation and may thus represent an alternative therapeutic target in the treatment of FLT3-ITD positive leukemia.

Bibliotekāru loma bibliotēkas un bibliotekāra tēla veidošanā Tīmekļa 2.0 resursos

OpenAIRE

Moskina, Viktorija

2010-01-01

Tīmeklis 2.0 sniedz lielākas iespējas nekā vienkārši meklēt, lasīt un pārvietoties informācijas telpā. Tas ir interaktīvs: virtuālās sarunas, personalizācija, individuālisms. Uzsvars uz cilvēku mijiedarbību raksturo Tīmekli 2.0 kā izteikti sociālu tīmekli, kurš pirmajā plāna izvirza indivīdu prasmi socializēties. Pētījuma mērķis ir noskaidrot, cik veiksmīgi bibliotekāri tiek galā ar bibliotēkas un bibliotekāru tēla veidošanu Tīmekļa 2.0 resursos un sniegt ieteikumus Latvijas bibliotekārie...

Inhibition of the MEK-1/p42 MAP kinase reduces aryl hydrocarbon receptor-DNA interactions

International Nuclear Information System (INIS)

Yim, Sujin; Oh, Myoungsuk; Choi, Su Mi; Park, Hyunsung

2004-01-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces expression of the cytochrome P450 1A1 gene, cyp1a1, by binding to its receptor, aryl hydrocarbon receptor (AhR). TCDD-bound AhR translocates to the nucleus and forms a heterodimer with its partner protein, AhR nuclear translocator (Arnt). The AhR/Arnt heterodimer then binds to the dioxin-response elements (DREs) in the cyp1a1 enhancer and stimulates transcription of cyp1a1. We tested whether kinase pathways are involved in this process by treating Hepa1c1c7 cells with kinase inhibitors. The MEK-1 inhibitor PD98059 reduced TCDD-induced transcription of cyp1a1. TCDD treatment results in phosphorylation of p44/p42 mitogen-activated protein kinase (MAPK), a substrate of MEK-1. Overexpression of dominant negative form of p42 MAPK suppressed TCDD-dependent transcription of a reporter gene controlled by dioxin-response elements (DREs), and pretreatment with PD98059 also blocked this transcription. PD98059 pretreatment also inhibited TCDD-induced DRE binding of the AhR/Arnt heterodimer. Together these results indicate that TCDD activates the MEK-1/p44/p42 MAPK pathway, which in turn activates AhR and so facilitates binding of AhR to the cyp1a1 DRE

prediction of path loss estimate for a frequency modulation (fm)

African Journals Online (AJOL)

Orinya

Nigeria, FM station, Makurdi which is normally a major component in the ... and can be used to estimate path losses of FM signals in Benue State of ... limited in equipment to measure all the .... path loss while MATLAB R2007b software was.

Numerical Simulation on Natural Convection Cooling of a FM Target

Energy Technology Data Exchange (ETDEWEB)

Park, Jong Pil; Park, Su Ki [KAERI, Daejeon (Korea, Republic of)

2016-05-15

The irradiated FM(Fission-Molly) target is unloaded from the irradiation hole during normal operation, and then cooled down in the reactor pool for a certain period of time. Therefore, it is necessary to identify the minimum decay time needed to cool down FM target sufficiently by natural convection. In the present work, numerical simulations are performed to predict cooling capability of a FM target cooled by natural convection using commercial computational fluid dynamics (CFD) code, CFX. The present study is carried out using CFD code to investigate cooling capability of a FM target cooled by natural convection. The steady state simulation as well as transient simulation is performed in the present work. Based on the transient simulation (T1), the minimum decay time that the maximum fuel temperature does not reach the design limit temperature (TONB-3 .deg. C) is around 15.60 seconds.

The concept of added value of FM

DEFF Research Database (Denmark)

Jensen, Per Anker; van der Voordt, Theo; Coenen, Christian

2012-01-01

Management (CREM) and Business to Business Marketing (B2B Marketing). Findings: The research shows different definitions and focus points, dependent on the academic field and the area of application. The different research perspectives explored a holistic view on the added value of FM by the integration...... of an external market based view (with a focus on the aimed output) and the internal resource based view (with a focus on the input from FM and real estate). Good relationship management and building on trust shows to be equally important as delivering the agreed services. Practical implications: A clear...

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice.

Science.gov (United States)

Zhang, Jianhai; Zhang, Yufang; Liang, Chen; Wang, Nasui; Zheng, Heping; Wang, Jundong

2016-11-01

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150mg/L NaF in drinking water, 5.75g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemistry gains a new element: Z=106

International Nuclear Information System (INIS)

Gaeggeler, H.W.; Eichler, B.; Tuerler, A.

1997-01-01

Even though 112 chemical elements are presently known, for elements with atomic numbers above 105 only nuclear decay properties have been investigated so far. Such data allow to proof the existence of a given nuclide, but they do not yield any information with respect to the position of a chemical element in the Periodic Table. We have performed ever first chemical investigations of element 106. According to the Periodic Table element 106 should be a member of group 6, having similar chemical properties as W, Mo and Cr. Two different techniques were applied to separate and identify element 106: a liquid chromatography system (ARCA = Automated Rapid Chemistry Apparatus) and a continuous isothermal chromatography device (OLGA = On-Line Gaschemistry Apparatus). With ARCA about 5'000 separations on small cation exchange columns (Aminex A6) with a 0.1 M HNO 3 /5.10 -4 M Hf solution were performed and with OLGA the gas adsorption behaviour of oxychlorides on quartz columns using Cl 2 /SOCl 2 /O 2 as reactive gas were studied. On the basis of only ten detected atoms, it was possible to proof that element 106 forms complexes which are eluted at positions similar to those of Mo and W. In addition, in the gas phase element 106 forms oxychlorides of lower volatility compared to those of Mo and W. (author) 1 ref

Hydrological and Agricultural Impacts of Climate Change in the Vu Gia-Thu Bon River Basin in Central Vietnam

NARCIS (Netherlands)

Laux, Patrick; Fink, Manfred; Waongo, Moussa; Pedroso, Rui; Salvini, G.; Hoa Tran, Dang; Quang Thinh, Dang; Cullmann, Johannes; Flügel, Wolfgang-Alvert; Kunstmann, H.

2017-01-01

This paper summarizes some of the climate (change) impact modeling activities conducted in the Land useandClimate Changeinteractionsin Central Vietnam (LUCCi)project. The study area is the Vu Gia-Thu Bon (VGTB) river basin in Central Vietnam, which is characterized by recurrent floods during

29 CFR 780.106 - Employment in “primary” agriculture is farming regardless of why or where work is performed.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Employment in âprimaryâ agriculture is farming regardless of why or where work is performed. 780.106 Section 780.106 Labor Regulations Relating to Labor... for âprimaryâ Agriculture Generally § 780.106 Employment in “primary” agriculture is farming...

Isolation and identification of Paenibacillus sp. FM-6, involved in the biotransformation of albendazole.

Science.gov (United States)

Jin, Lei; Zhang, Xiaojun; Sun, Xiumei; Shi, Hui; Li, Tiejun

2014-10-01

A strain, designated as FM-6, was isolated from fish. Based on the results of phenotypic, physiological characteristics, genotypic and phylogenetic analysis, strain FM-6 was finally identified as Paenibacillus sp. When albendazole was provided as the sole carbon source, strain FM-6 could grow and transform albendazole. About 82.7 % albendazole (50 mg/L) was transformed by strain FM-6 after 5 days incubation at 30 °C, 160 rpm. With HPLC-MS method, the transforming product of albendazole was researched. Based on the molecular weight and the retention time, product was identified as albendazole sulfoxide and the transforming pathway of albendazole by strain FM-6 was proposed finally. The optimum temperature and pH for the bacterium growth and albendazole transformation by strain FM-6 were both 30 °C and 7.0. Moreover, the optimum concentration of albendazole for the bacterium growth was 50 mg/L. Coupled with practical production, 50 mg/L was the optimum concentration of albendazole transformation for strain FM-6. This study highlights an important potential use of strain FM-6 for producing albendazole sulfoxide.

10 CFR 1703.106 - Requests for waiver or reduction of fees.

Science.gov (United States)

2010-01-01

... provided free of charge or provided for an access or publication fee; and (8) Describe any commercial or... 10 Energy 4 2010-01-01 2010-01-01 false Requests for waiver or reduction of fees. 1703.106 Section... Requests for waiver or reduction of fees. (a) The Board shall collect fees for record requests made under...

Pathologies of Hyperfamiliarity in Dreams, Delusions and Déjà Vu

Directory of Open Access Journals (Sweden)

Philip eGerrans

2014-02-01

Full Text Available The ability to challenge and revise thoughts prompted by anomalous experiences depends on activity in right dorsolateral prefrontal circuitry. When activity in those circuits is absent or compromised subjects are less likely to make this kind of correction. This appears to be the cause of some delusions of misidentification consequent on experiences of hyperfamiliarity for faces. Comparing the way the mind responds to the experience of hyperfamiliarity in different conditions such as delusions, dreams, pathological and non pathological déjà vu, provides a way to understand claims that delusions and dreams are both states characterized by deficient reality testing.

The Use of Polysymptomatic Distress Categories in the Evaluation of Fibromyalgia (FM) and FM Severity

NARCIS (Netherlands)

Wolfe, Frederick; Walitt, Brian T.; Rasker, Johannes J.; Katz, Robert S.; Häuser, Winfried

2015-01-01

Objective The polysymptomatic distress (PSD) scale is derived from variables used in the 2010 American College of Rheumatology (ACR) fibromyalgia (FM) criteria modified for survey and clinical research. The scale is useful in measuring the effect of PSD over the full range of pain-related clinical

CERES BiDirectional Scans (BDS) data in HDF (CER_BDS_Terra-FM1_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

Each BiDirectional Scans (BDS) data product contains twenty-four hours of Level-1b data for each CERES scanner instrument mounted on each spacecraft. The BDS includes samples taken in normal and short Earth scan elevation profiles in both fixed and rotating azimuth scan modes (including space, internal calibration, and solar calibration views). The BDS contains Level-0 raw (unconverted) science and instrument data as well as the geolocated converted science and instrument data. The BDS contains additional data not found in the Level-0 input file, including converted satellite position and velocity data, celestial data, converted digital status data, and parameters used in the radiance count conversion equations. The following CERES BDS data sets are currently available: CER_BDS_TRMM-PFM_Edition1 CER_BDS_Terra-FM1_Edition1 CER_BDS_Terra-FM2_Edition1 CER_BDS_Terra-FM1_Edition2 CER_BDS_Terra-FM2_Edition2 CER_BDS_Aqua-FM3_Edition1 CER_BDS_Aqua-FM4_Edition1 CER_BDS_Aqua-FM3_Edition2 CER_BDS_Aqua-FM4_Edition2 CER_BDS_Aqua-FM3_Edition1-CV CER_BDS_Aqua-FM4_Edition1-CV CER_BDS_Terra-FM1_Edition1-CV CER_BDS_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-11-02] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

CERES BiDirectional Scans (BDS) data in HDF (CER_BDS_Aqua-FM3_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

Each BiDirectional Scans (BDS) data product contains twenty-four hours of Level-1b data for each CERES scanner instrument mounted on each spacecraft. The BDS includes samples taken in normal and short Earth scan elevation profiles in both fixed and rotating azimuth scan modes (including space, internal calibration, and solar calibration views). The BDS contains Level-0 raw (unconverted) science and instrument data as well as the geolocated converted science and instrument data. The BDS contains additional data not found in the Level-0 input file, including converted satellite position and velocity data, celestial data, converted digital status data, and parameters used in the radiance count conversion equations. The following CERES BDS data sets are currently available: CER_BDS_TRMM-PFM_Edition1 CER_BDS_Terra-FM1_Edition1 CER_BDS_Terra-FM2_Edition1 CER_BDS_Terra-FM1_Edition2 CER_BDS_Terra-FM2_Edition2 CER_BDS_Aqua-FM3_Edition1 CER_BDS_Aqua-FM4_Edition1 CER_BDS_Aqua-FM3_Edition2 CER_BDS_Aqua-FM4_Edition2 CER_BDS_Aqua-FM3_Edition1-CV CER_BDS_Aqua-FM4_Edition1-CV CER_BDS_Terra-FM1_Edition1-CV CER_BDS_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-11-02] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

CERES BiDirectional Scans (BDS) data in HDF (CER_BDS_Aqua-FM4_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

Each BiDirectional Scans (BDS) data product contains twenty-four hours of Level-1b data for each CERES scanner instrument mounted on each spacecraft. The BDS includes samples taken in normal and short Earth scan elevation profiles in both fixed and rotating azimuth scan modes (including space, internal calibration, and solar calibration views). The BDS contains Level-0 raw (unconverted) science and instrument data as well as the geolocated converted science and instrument data. The BDS contains additional data not found in the Level-0 input file, including converted satellite position and velocity data, celestial data, converted digital status data, and parameters used in the radiance count conversion equations. The following CERES BDS data sets are currently available: CER_BDS_TRMM-PFM_Edition1 CER_BDS_Terra-FM1_Edition1 CER_BDS_Terra-FM2_Edition1 CER_BDS_Terra-FM1_Edition2 CER_BDS_Terra-FM2_Edition2 CER_BDS_Aqua-FM3_Edition1 CER_BDS_Aqua-FM4_Edition1 CER_BDS_Aqua-FM3_Edition2 CER_BDS_Aqua-FM4_Edition2 CER_BDS_Aqua-FM3_Edition1-CV CER_BDS_Aqua-FM4_Edition1-CV CER_BDS_Terra-FM1_Edition1-CV CER_BDS_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-04-02] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

CERES BiDirectional Scans (BDS) data in HDF (CER_BDS_Aqua-FM4_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

Each BiDirectional Scans (BDS) data product contains twenty-four hours of Level-1b data for each CERES scanner instrument mounted on each spacecraft. The BDS includes samples taken in normal and short Earth scan elevation profiles in both fixed and rotating azimuth scan modes (including space, internal calibration, and solar calibration views). The BDS contains Level-0 raw (unconverted) science and instrument data as well as the geolocated converted science and instrument data. The BDS contains additional data not found in the Level-0 input file, including converted satellite position and velocity data, celestial data, converted digital status data, and parameters used in the radiance count conversion equations. The following CERES BDS data sets are currently available: CER_BDS_TRMM-PFM_Edition1 CER_BDS_Terra-FM1_Edition1 CER_BDS_Terra-FM2_Edition1 CER_BDS_Terra-FM1_Edition2 CER_BDS_Terra-FM2_Edition2 CER_BDS_Aqua-FM3_Edition1 CER_BDS_Aqua-FM4_Edition1 CER_BDS_Aqua-FM3_Edition2 CER_BDS_Aqua-FM4_Edition2 CER_BDS_Aqua-FM3_Edition1-CV CER_BDS_Aqua-FM4_Edition1-CV CER_BDS_Terra-FM1_Edition1-CV CER_BDS_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

34 CFR 200.6 - Inclusion of all students.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Inclusion of all students. 200.6 Section 200.6... Basic Programs Operated by Local Educational Agencies Standards and Assessments § 200.6 Inclusion of all...— (A) For each student with a disability, as defined under section 602(3) of the IDEA, appropriate...

Loss of MAPK Pathway Activation in Post-Mitotic Retinal Cells as Mechanism in MEK Inhibition-Related Retinopathy in Cancer Patients.

Science.gov (United States)

van Dijk, Elon H C; Duits, Danique E M; Versluis, Mieke; Luyten, Gregrorius P M; Bergen, Arthur A B; Kapiteijn, Ellen W; de Lange, Mark J; Boon, Camiel J F; van der Velden, Pieter A

2016-05-01

Recently, treatment with MEK inhibitors has been shown to be an effective treatment option for metastatic melanoma. Treatment efficacy is dependent on inhibition of MAPK-related melanoma proliferation. However, targeting of MEK can be accompanied by a time-dependent and reversible serous retinopathy of unknown origin.We analyzed the molecular mechanism by which the MEK inhibitor binimetinib may lead to retinopathy, using neuroretina and cell models of retinal pigment epithelium (RPE).Binimetinib inhibited the MAPK pathway while discontinuation of treatment resulted in reactivation. However, cell proliferation was not inhibited correspondingly during binimetinib treatment of ARPE19 cells. Remarkably, post-mitotic neuroretinal tissue displayed a strong MAPK activation that was lost after binimetinib treatment.We propose that binimetinib-associated retinopathy is correlated with inhibition of the MAPK pathway in multiple retinal components. Retinal cells are able to regain the activation after binimetinib treatment, mimicking the reversibility of the retinopathy. As most retinal cells are nonregenerating, other mechanisms than stimulation of proliferation must be involved.

Synergistic effects of concurrent blockade of PI3K and MEK pathways in pancreatic cancer preclinical models.

Directory of Open Access Journals (Sweden)

Hua Zhong

Full Text Available Patients with pancreatic cancer have dismal prognoses, and novel therapies are urgently needed. Mutations of the KRAS oncogene occur frequently in pancreatic cancer and represent an attractive target. Direct targeting of the predominant KRAS pathways have been challenging and research into therapeutic strategies have been now refocused on pathways downstream of KRAS, phosphoinositide 3-kinase (PI3K and mitogen-activated protein kinase (MAPK [MEK]. We hypothesized that concurrent inhibition of the PI3K and MEK pathways would result in synergistic antitumor activity, as it would circumvent the compensatory feedback loop between the two pathways. We investigated the combined effect of the PI3K inhibitor, GDC0941, and the MEK inhibitor, AZD6244, on cell viability, apoptosis and cell signaling in a panel of pancreatic cancer cell lines. An in vivo analysis was conducted on pancreatic cancer xenografts. While BxPC-3 (KRAS wild type and MIA PaCa-2 (KRAS mutated cell lines were sensitive to GDC0941 and AZD6244 as single agents, synergistic inhibition of tumor cell growth and induction of apoptosis were observed in both cell lines when the two drugs were combined. Interestingly, phosphorylation of the cap-dependent translational components, 4E-binding protein (p-4E-BP1 and S6 was found to be closely associated with sensitivity to GDC0941 and AZD6244. In BxPC-3 cell xenografts, survival differences were observed between the control and the AZD6244, GDC0941, and combination groups. Our study provides the rationale for concurrent targeting of the PI3K and MEK pathways, regardless of KRAS status, and suggests that phosphorylation of 4E-BP1and S6 can serve as a predictive biomarker for response to treatment.

KSR1 is a functional protein kinase capable of serine autophosphorylation and direct phosphorylation of MEK1

International Nuclear Information System (INIS)

Goettel, Jeremy A.; Liang, Dongchun; Hilliard, Valda C.; Edelblum, Karen L.; Broadus, Matthew R.; Gould, Kathleen L.; Hanks, Steven K.; Polk, D. Brent

2011-01-01

The extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway is a highly conserved signaling pathway that regulates diverse cellular processes including differentiation, proliferation, and survival. Kinase suppressor of Ras-1 (KSR1) binds each of the three ERK cascade components to facilitate pathway activation. Even though KSR1 contains a C-terminal kinase domain, evidence supporting the catalytic function of KSR1 remains controversial. In this study, we produced recombinant wild-type or kinase-inactive (D683A/D700A) KSR1 proteins in Escherichia coli to test the hypothesis that KSR1 is a functional protein kinase. Recombinant wild-type KSR1, but not recombinant kinase-inactive KSR1, underwent autophosphorylation on serine residue(s), phosphorylated myelin basic protein (MBP) as a generic substrate, and phosphorylated recombinant kinase-inactive MAPK/ERK kinase-1 (MEK1). Furthermore, FLAG immunoprecipitates from KSR1 -/- colon epithelial cells stably expressing FLAG-tagged wild-type KSR1 (+KSR1), but not vector (+vector) or FLAG-tagged kinase-inactive KSR1 (+D683A/D700A), were able to phosphorylate kinase-inactive MEK1. Since TNF activates the ERK pathway in colon epithelial cells, we tested the biological effects of KSR1 in the survival response downstream of TNF. We found that +vector and +D683A/D700A cells underwent apoptosis when treated with TNF, whereas +KSR1 cells were resistant. However, +KSR1 cells were sensitized to TNF-induced cell loss in the absence of MEK kinase activity. These data provide clear evidence that KSR1 is a functional protein kinase, MEK1 is an in vitro substrate of KSR1, and the catalytic activities of both proteins are required for eliciting cell survival responses downstream of TNF.

Pathologies of hyperfamiliarity in dreams, delusions and déjà vu.

Science.gov (United States)

Gerrans, Philip

2014-01-01

The ability to challenge and revise thoughts prompted by anomalous experiences depends on activity in right dorsolateral prefrontal circuitry. When activity in those circuits is absent or compromised subjects are less likely to make this kind of correction. This appears to be the cause of some delusions of misidentification consequent on experiences of hyperfamiliarity for faces. Comparing the way the mind responds to the experience of hyperfamiliarity in different conditions such as delusions, dreams, pathological and non-pathological déjà vu, provides a way to understand claims that delusions and dreams are both states characterized by deficient "reality testing."

Informační systém pro správu rezervací v restauracích

OpenAIRE

Slanař, David

2009-01-01

Tato bakalářská práce pojednává o stávajícím stavu fungování rezervací v restauracích a jeho inovaci pomocí zavedení informačního systému pro vytváření a správu rezervací. Popisuje návrh internetové webové aplikace umožňující on-line vytváření rezervací samotnými uživateli a jejich následnou správu zaměstnanci. Dále popis ekonomického přínosu a jiných výhod plynoucích ze zavedení tohoto systému v reálném světě a v neposlední řadě řešení případných problémů při nasazování systému v praxi. T...

Anti-tumour activity in RAS-driven tumours by blocking AKT and MEK

Science.gov (United States)

Tolcher, Anthony W.; Khan, Khurum; Ong, Michael; Banerji, Udai; Papadimitrakopoulou, Vassiliki; Gandara, David R.; Patnaik, Amita; Baird, Richard D.; Olmos, David; Garrett, Christopher R.; Skolnik, Jeffrey M.; Rubin, Eric H.; Smith, Paul D.; Huang, Pearl; Learoyd, Maria; Shannon, Keith A.; Morosky, Anne; Tetteh, Ernestina; Jou, Ying-Ming; Papadopoulos, Kyriakos P.; Moreno, Victor; Kaiser, Brianne; Yap, Timothy A.; Yan, Li; de Bono, Johann S.

2014-01-01

Purpose KRAS is the most commonly mutated oncogene in human tumours. KRAS-mutant cells may exhibit resistance to the allosteric MEK1/2 inhibitor selumetinib (AZD6244; ARRY-142886) and allosteric AKT inhibitors (such as MK-2206), the combination of which may overcome resistance to both monotherapies. Experimental Design We conducted a dose/schedule-finding study evaluating MK-2206 and selumetinib in patients with advanced treatment-refractory solid tumours. Recommended dosing schedules were defined as MK-2206 135 mg weekly and selumetinib 100 mg once-daily. Results Grade 3 rash was the most common dose-limiting toxicity (DLT); other DLTs included grade 4 lipase increase, grade 3 stomatitis, diarrhoea, and fatigue, and grade 3 and grade 2 retinal pigment epithelium detachment. There were no meaningful pharmacokinetic drug-drug interactions. Clinical anti-tumour activity included RECIST 1.0-confirmed partial responses in non-small cell lung cancer and low-grade ovarian carcinoma. Conclusion Responses in KRAS-mutant cancers were generally durable. Clinical co-targeting of MEK and AKT signalling may be an important therapeutic strategy in KRAS-driven human malignancies (Trial NCT number NCT01021748). PMID:25516890

Challenges in the development of an M4 PAM in vivo tool compound: The discovery of VU0467154 and unexpected DMPK profiles of close analogs.

Science.gov (United States)

Wood, Michael R; Noetzel, Meredith J; Poslusney, Michael S; Melancon, Bruce J; Tarr, James C; Lamsal, Atin; Chang, Sichen; Luscombe, Vincent B; Weiner, Rebecca L; Cho, Hyekyung P; Bubser, Michael; Jones, Carrie K; Niswender, Colleen M; Wood, Michael W; Engers, Darren W; Brandon, Nicholas J; Duggan, Mark E; Conn, P Jeffrey; Bridges, Thomas M; Lindsley, Craig W

2017-01-15

This letter describes the chemical optimization of a novel series of M 4 positive allosteric modulators (PAMs) based on a 5-amino-thieno[2,3-c]pyridazine core, developed via iterative parallel synthesis, and culminating in the highly utilized rodent in vivo tool compound, VU0467154 (5). This is the first report of the optimization campaign (SAR and DMPK profiling) that led to the discovery of VU0467154, and details all of the challenges faced in allosteric modulator programs (steep SAR, species differences in PAM pharmacology and subtle structural changes affecting CNS penetration). Copyright © 2016 Elsevier Ltd. All rights reserved.

Trénink hněvu: Smrtelný hřích v temperamentní profesi Coaching anger: A deadly sin in a lively profession

Directory of Open Access Journals (Sweden)

Jeffrey P. Fry

2006-02-01

Full Text Available Podle křesťanské tradice je hněv jedním ze "sedmi smrtelných hříchů". Ve východním náboženském myšlení je hněv považován za jedovatý a návykový. Tyto pohledy poukazují na problémovou povahu hněvu. Jiní se však domnívají, že hněv může nabývat vhodného výrazu a pozitivní funkce. Vzhledem k tomu, že hněv se ve sportu projevuje často, je důležité vyhodnotit význam hněvu také v této oblasti lidského života. Zvláště často projevují hněv trenéři. S ohledem na tuto skutečnost se v tomto příspěvku zaměřuji na povahu hněvu a jeho roli v profesi trenéra. Je na roli, kterou trenér zastává, něco, co by trenérům poskytovalo zvláštní svobodu ve vyjadřování hněvu? "Trénink hněvu" se nezabývá výhradně projevy hněvu trenérů, ale také praktickými kroky vedoucími k účinnému a přiměřenému ovládání této složité emoce. According to Christian tradition, anger comprises one of the "seven deadly sins". In Eastern religious thought anger is held to be poisonous and addictive. These views point to the problematic nature of anger. Some hold, however, that anger can have an appropriate expression and a positive function. Since anger is often vented in sport, it is important to assess the significance of anger in this area of life. Coaches, in particular, frequently display anger. Given this fact, in this paper I focus on the nature of anger and its role in the coaching profession. Is there something distinctive about the role of the coach such that coaches should be granted special leeway in the expression of anger? "Coaching anger" refers not merely to the manifestation of coaches’ anger, but also to practical steps towards effective and appropriate dealing with this complex emotion.

PREFACE: 12th Russia/CIS/Baltic/Japan Symposium on Ferroelectricity and 9th International Conference on Functional Materials and Nanotechnologies (RCBJSF-2014-FM&NT)

Science.gov (United States)

Sternberg, Andris; Grinberga, Liga; Sarakovskis, Anatolijs; Rutkis, Martins

2015-03-01

The joint International Symposium RCBJSF-2014-FM&NT successfully has united two international events - 12th Russia/CIS/Baltic/Japan Symposium on Ferroelectricity (RCBJSF-12) and 9th International Conference Functional Materials and Nanotechnologies (FM&NT-2014). The RCBJSF symposium is a continuation of series of meetings on ferroelectricity, the first of which took place in Novosibirsk (USSR) in 1976. FM&NT conferences started in 2006 and have been organized by Institute of Solid State Physics, University of Latvia in Riga. In 2012 the International program committee decided to transform this conference into a traveling Baltic State conference and the FM&NT-2013 was organized by the Institute of Physics, University of Tartu, Estonia. In 2014 the joint international symposium RCBJSF-2014-FM&NT was organized by the Institute of Solid State Physics, University of Latvia and was part of Riga - 2014, the European Capital of Culture event. The purpose of the joint Symposium was to bring together scientists, students and high-level experts in solid state physics, materials science, engineering and related disciplines. The number of the registered participants from 26 countries was over 350. During the Symposium 128 high quality scientific talks (5 plenary, 42 invited, 81 oral) and over 215 posters were presented. All presentations were divided into 4 parallel sessions according to 4 main topics of the Symposium: Ferroelectricity, including ferroelectrics and multiferroics, pyroelectrics, piezoelectrics and actuators, integrated ferroelectrics, relaxors, phase transitions and critical phenomena. Multifunctional Materials, including theory, multiscale and multiphenomenal material modeling and simulation, advanced inorganic, organic and hybrid materials. Nanotechnologies, including progressive methods, technologies and design for production, investigation of nano- particles, composites, structures, thin films and coatings. Energy, including perspective materials and

33 CFR 106.235 - Maritime Security (MARSEC) Level coordination and implementation.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Maritime Security (MARSEC) Level..., DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARINE SECURITY: OUTER CONTINENTAL SHELF (OCS) FACILITIES Outer Continental Shelf (OCS) Facility Security Requirements § 106.235 Maritime Security (MARSEC) Level...

Characterization of a molt-related myostatin gene (FmMstn) from the banana shrimp Fenneropenaeus merguiensis.

Science.gov (United States)

Zhuo, Rui Qun; Zhou, Ting Ting; Yang, Shi Ping; Chan, Siuming Francis

2017-07-01

Myostatin is an important member of the transforming growth factor (TGF) family that functions to regulate muscle growth in animals. In this study, the myostatin gene (FmMstn) and two slightly different (short and long forms) cDNAs of the banana shrimp Fenneropenaeus merguiensis were cloned and characterized. Similar to Mstn gene of the scallop, fish and mammal, FmMstn gene consists of 3 exons and 2 introns. The 2kb upstream promoter region of the FmMstn gene consists of putative response elements for myocyte enhancing factor (MEF2) and E-box factors. The longest open reading frame of the short Mstn consists of 1260bp encoding for a protein with 420 amino acid residues. The long FmMstn is almost identical to the short FmMstn with the exception of 8 amino acid insertions. FmMstn is most similar to the Mstn of Litopenaeus vannamei and Penaeus monodon sharing >92-98% amino acid sequence identity. Multiple sequence alignment results revealed high degree of amino acid conservation of the cysteine residues and mature peptide of the FmMstn with Mstn from other animals. FmMstn transcript was detected in the heart, muscle, optic nerve and thoracic ganglion. FmMstn transcript level in muscle is higher in early postmolt, decreases in intermolt and increases again towards ecdysis. Higher expression level of FmMstn is also observed in smaller shrimp of the same age. Knock-down of FmMstn gene by RNAi can cause a significant increase in molt cycle duration and failure of some shrimp to undergo ecdysis. Direct DNA sequencing results revealed that FmMstn gene is highly polymorphic and several potential SNPs have been identified. Some SNPs are associated with the size difference of the shrimp. In summary, the result of this study indicates that shrimp FmMstn gene is molt/growth-related and the presence of SNP suggests that it could be a candidate gene for shrimp genetic improvement research. Copyright © 2017. Published by Elsevier Inc.

Comparison of MEK/ERK pathway inhibitors on the upregulation of vascular G-protein coupled receptors in rat cerebral arteries

DEFF Research Database (Denmark)

Sandhu, Hardip; Ansar, Saema; Edvinsson, Lars

2010-01-01

on translational level and increased respective contractions. The prostanoid TP receptor mediated contraction curve was left-wards shifted by organ culture. Organ culture was associated with elevated pERK1/2 in the vascular smooth muscle cells: the MEK1/2 inhibitor U0126 attenuated the endothelin ET(B) receptor...... mediated contraction at post-translational level or by changing the receptor affinities. The serotonin 5-HT(1B) receptor and prostanoid TP receptor mediated contractions were abolished by U0126. Administration of U0126 6h after start of incubation blocked the receptor upregulation. In conclusion, MEK...

Facilities management and corporate real estate management : FM/CREM or FREM?

NARCIS (Netherlands)

van der Voordt, Theo

2017-01-01

Purpose: This paper aims to explore similarities and dissimilarities between facilities management (FM) and corporate real estate management (CREM) regarding its history and key issues, and whether the similarities may result in a further integration of FM and CREM. Design/methodology/approach:

24 CFR 3280.106 - Exit facilities; egress windows and devices.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Exit facilities; egress windows and... § 3280.106 Exit facilities; egress windows and devices. (a) Every room designed expressly for sleeping purposes, unless it has an exit door (see § 3280.105), shall have at least one outside window or approved...

The Implementation of Performance Measurement System (PMS: Malaysian Facilities Management (FM Industry

Directory of Open Access Journals (Sweden)

Myeda N.E.

2014-01-01

Full Text Available Performance Measurement System (PMS is an effective performance measurement tool and technique that is being widely implemented in the global industries. Literature has suggested the significant contributions of its implementation in enhancing the strategic service delivery and performance. However, there is little study undertaken to explore the PMS implementation in Facilities Management (FM industry, particularly focusing on Malaysia. This study explores the PMS practice among FM practitioners and their knowledge in Performance Measurement (PM generally. Findings from this study also proposed the 20 contributing factors that the FM practitioners believed are the barriers in implementing PMS. This research also suggests the future research opportunities in developing a PMS framework that can be used as guidance for FM service delivery in Malaysia.

VuWiki: An Ontology-Based Semantic Wiki for Vulnerability Assessments

Science.gov (United States)

Khazai, Bijan; Kunz-Plapp, Tina; Büscher, Christian; Wegner, Antje

2014-05-01

The concept of vulnerability, as well as its implementation in vulnerability assessments, is used in various disciplines and contexts ranging from disaster management and reduction to ecology, public health or climate change and adaptation, and a corresponding multitude of ideas about how to conceptualize and measure vulnerability exists. Three decades of research in vulnerability have generated a complex and growing body of knowledge that challenges newcomers, practitioners and even experienced researchers. To provide a structured representation of the knowledge field "vulnerability assessment", we have set up an ontology-based semantic wiki for reviewing and representing vulnerability assessments: VuWiki, www.vuwiki.org. Based on a survey of 55 vulnerability assessment studies, we first developed an ontology as an explicit reference system for describing vulnerability assessments. We developed the ontology in a theoretically controlled manner based on general systems theory and guided by principles for ontology development in the field of earth and environment (Raskin and Pan 2005). Four key questions form the first level "branches" or categories of the developed ontology: (1) Vulnerability of what? (2) Vulnerability to what? (3) What reference framework was used in the vulnerability assessment?, and (4) What methodological approach was used in the vulnerability assessment? These questions correspond to the basic, abstract structure of the knowledge domain of vulnerability assessments and have been deduced from theories and concepts of various disciplines. The ontology was then implemented in a semantic wiki which allows for the classification and annotation of vulnerability assessments. As a semantic wiki, VuWiki does not aim at "synthesizing" a holistic and overarching model of vulnerability. Instead, it provides both scientists and practitioners with a uniform ontology as a reference system and offers easy and structured access to the knowledge field of

Future Research Agenda for FM in the Nordic Countries in Europe

DEFF Research Database (Denmark)

Jensen, Per Anker; Andersen, Per Dannemand; Rasmussen, Birgitte

2014-01-01

The study is based on theory from innovation systems and strategic foresight. First, a review of literature was carried out and an innovation systems model of the FM sector was developed. Secondly, four national workshops were held involving FM practitioners and researchers from Denmark, Norway......, Sweden and Finland. Third, the results of the workshops were presented and discussed at a Nordic FM conference in August 2011. Finally, an adapted Delphi survey was carried out as a final data collection and validation of the findings. This article has the main focus on the results of the Delphi survey....

The mechanism by which MEK/ERK regulates JNK and p38 activity in polyamine depleted IEC-6 cells during apoptosis

Science.gov (United States)

Bavaria, Mitul N.; Jin, Shi; Ray, Ramesh M.; Johnson, Leonard R.

2014-01-01

Polyamine-depletion inhibited apoptosis by activating ERK1/2, while, preventing JNK1/2 activation. MKP-1 knockdown by SiRNA increased ERK1/2, JNK1/2, and p38 phosphorylation and apoptosis. Therefore, we predicted that polyamines might regulate MKP1 via MEK/ERK and thereby apoptosis. We examined the role of MEK/ERK in the regulation of MKP1 and JNK, and p38 activities and apoptosis. Inhibition of MKP-1 activity with a pharmacological inhibitor, sanguinarine (SA), increased JNK1/2, p38, and ERK1/2 activities without causing apoptosis. However, pre-activation of these kinases by SA significantly increased camptothecin (CPT)-induced apoptosis suggesting different roles for MAPKs during survival and apoptosis. Inhibition of MEK1 activity prevented the expression of MKP-1 protein and augmented CPT-induced apoptosis, which correlated with increased activities of JNK1/2, caspases, and DNA fragmentation. Polyamine depleted cells had higher levels of MKP-1 protein and decreased JNK1/2 activity and apoptosis. Inhibition of MEK1 prevented MKP-1 expression and increased JNK1/2 and apoptosis. Phospho-JNK1/2, phospho-ERK2, MKP-1, and the catalytic subunit of protein phosphatase 2A (PP2Ac) formed a complex in response to TNF/CPT. Inactivation of PP2Ac had no effect on the association of MKP-1 and JNK1. However, inhibition of MKP-1 activity decreased the formation of the MKP-1, PP2Ac and JNK complex. Following inhibition by SA, MKP-1 localized in the cytoplasm, while basal and CPT-induced MKP-1 remained in the nuclear fraction. These results suggest that nuclear MKP-1 translocates to the cytoplasm, binds phosphorylated JNK and p38 resulting in dephosphorylation and decreased activity. Thus, MEK/ERK activity controls the levels of MKP-1 and, thereby, regulates JNK activity in polyamine-depleted cells. PMID:24253595

Tīmekļa lietojumprogrammatūra elektroniskai tirdzniecībai tiešsaistē

OpenAIRE

Folkmanis, Kristaps

2014-01-01

“Tīmekļa lietojumprogrammatūra elektroniskai tirdzniecībai tiešsaistē” ir uz tīmekļa tehnoloģijām balstīta sistēma, kas realizēta kā interneta vietne. Sistēmas lietotājiem ir iespēja apskatīt un iegādāties preces, kas sadalītas pa dažādām kategorijām. Lietotāji var veikt arī citas papildus darbības, piemēram, reģistrēties sistēmā, pievienot precēm komentārus un pārvaldīt savu iepirkumu grozu. Sistēmas administrators var pārvaldīt visu preču klāstu un citus sistēmā esošos datus, izmantojot šim...

CTGF enhances resistance to 5-FU-mediating cell apoptosis through FAK/MEK/ERK signal pathway in colorectal cancer

Directory of Open Access Journals (Sweden)

Yang K

2016-11-01

Full Text Available Kai Yang, Kai Gao, Gui Hu, Yanguang Wen, Changwei Lin, Xiaorong Li Department of General Surgery, The Third Affiliated Hospital of Central South University, Central South University, Changsha, Hunan, People’s Republic of China Abstract: Colorectal cancer (CRC is one of the most commonly diagnosed cancers among both males and females; the chemotherapy drug 5-fluorouracil (5-FU is one of a doctors’ first lines of defense against CRC. However, therapeutic failures are common because of the emergence of drug resistance. Connective tissue growth factor (CTGF is a secreted protein that binds to integrins, and regulates the invasiveness and metastasis of certain carcinoma cells. Here, we found that CTGF was upregulated in drug-resistant phenotype of human CRC cells. Overexpression of CTGF enhanced the resistance to 5-FU-induced cell apoptosis. Moreover, downregulating the expression of CTGF promoted the curative effect of chemotherapy and blocked the cell cycle in the G1 phase. We also found that CTGF facilitated resistance to 5-FU-induced apoptosis by increasing the expression of B-cell lymphoma-extra large (Bcl-xL and survivin. Then we pharmacologically blocked MEK/ERK signal pathway and assessed 5-FU response by MTT assays. Our current results indicate that the expression of phosphorylated forms of MEK/ERK increased in high CTGF expression cells and MEK inhibited increases in 5-FU-mediated apoptosis of resistant CRC cells. Therefore, our data suggest that MEK/ERK signaling contributes to 5-FU resistance through upstream of CTGF, and supports CRC cell growth. Comprehending the molecular mechanism underlying 5-FU resistance may ultimately aid the fight against CRC. Keywords: connective tissue growth factor, 5-fluorouracil, mitogen-activated protein kinase/extracellular regulated protein kinases, phosphatidyl inositol 3-kinase/serine/threonine kinase Akt, colorectal cancer

34 CFR 106.61 - Sex as a bona-fide occupational qualification.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Sex as a bona-fide occupational qualification. 106.61..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or...

Représenter et penser l’affrontement : le magazine Vu face à la Guerre d’Espagne et à la menace d’une deuxième guerre mondiale

Directory of Open Access Journals (Sweden)

Sophie Kurkdjian

2011-04-01

Full Text Available Créé en 1928, Vu est un magazine qui confère à la photographie un nouveau rôle. Celle-ci constitue le propos même du magazine. Homme de gauche, son directeur, Lucien Vogel, est un pacifiste convaincu, dont le regard posé sur la période de l’entre-deux-guerres, plus précisément entre 1928 et 1936, est particulièrement intéressant à étudier. Cet article s’attachera à analyser la manière dont Vu couvre la Guerre d’Espagne et rapporte les tensions des années trente, héritées de la Première Guerre mondiale. Dans un premier temps, par l’intermédiaire de photographies et de mises en page destinées à marquer les esprits, Vu tente de prévenir un nouvel affrontement, la crainte d’une nouvelle guerre étant l’obsession de Lucien Vogel. Dans un second temps, lors de la Guerre d’Espagne, Vu prend, dès le début du conflit, fait et cause pour les Républicains espagnols. L’engagement de Lucien Vogel est tel qu’il est limogé par ses administrateurs qui lui reprochent d’avoir médiatisé l'événement avec un certain parti-pris. Ainsi, dans les deux cas, on se demandera jusqu’à quel point l’idéologie politique du directeur du magazine a un impact sur la représentation de cette période de crise et sur l’élaboration de la figure de l’ennemi. On montrera aussi que les nombreuses possibilités offertes par la photographie influencent la façon dont Lucien Vogel appréhende les événements de cette période.   Vu, created in 1928, is a magazine which endows photography with a new role, in that it became the very contents of the magazine. Its director, Lucien Vogel, is a convinced pacifist with left-wing commitments. His point of view on the period of time, in between the two world wars, is particularly interesting. Our article will study how, between 1928 and 1936, Vu reports the tensions inherited from World War I and covers the Spanish War.  In the first place, by means of photographs and eye

76 FR 79113 - Amendment of Service and Eligibility Rules for FM Broadcast Translator Stations

Science.gov (United States)

2011-12-21

... of Service and Eligibility Rules for FM Broadcast Translator Stations AGENCY: Federal Communications... authorizing the use of FM translators with licenses or permits in effect as of May 1, 2009, to rebroadcast the... and Eligibility Rules for FM Broadcast Translator Stations, published at 74 FR 45126, September 1...

Pathologies of hyperfamiliarity in dreams, delusions and déjà vu

Science.gov (United States)

Gerrans, Philip

2014-01-01

The ability to challenge and revise thoughts prompted by anomalous experiences depends on activity in right dorsolateral prefrontal circuitry. When activity in those circuits is absent or compromised subjects are less likely to make this kind of correction. This appears to be the cause of some delusions of misidentification consequent on experiences of hyperfamiliarity for faces. Comparing the way the mind responds to the experience of hyperfamiliarity in different conditions such as delusions, dreams, pathological and non-pathological déjà vu, provides a way to understand claims that delusions and dreams are both states characterized by deficient “reality testing.” PMID:24600415

Multiple benefits of personal FM system use by children with auditory processing disorder (APD).

Science.gov (United States)

Johnston, Kristin N; John, Andrew B; Kreisman, Nicole V; Hall, James W; Crandell, Carl C

2009-01-01

Children with auditory processing disorders (APD) were fitted with Phonak EduLink FM devices for home and classroom use. Baseline measures of the children with APD, prior to FM use, documented significantly lower speech-perception scores, evidence of decreased academic performance, and psychosocial problems in comparison to an age- and gender-matched control group. Repeated measures during the school year demonstrated speech-perception improvement in noisy classroom environments as well as significant academic and psychosocial benefits. Compared with the control group, the children with APD showed greater speech-perception advantage with FM technology. Notably, after prolonged FM use, even unaided (no FM device) speech-perception performance was improved in the children with APD, suggesting the possibility of fundamentally enhanced auditory system function.

Effect of mitomycin combined with Nd-YAG laser on cell proliferation and invasion as well as MEK/ERK signaling pathway in obstructive lacrimal duct model

Directory of Open Access Journals (Sweden)

Yu Yan

2017-11-01

Full Text Available Objective: To study the effect of mitomycin (MMC combined with Nd-YAG laser on cell proliferation and invasion as well as MEK/ERK signaling pathway in obstructive lacrimal duct model. Methods: New Zealand rabbits were selected as experimental animals and divided into model group, laser group and MMC + laser group; obstructive lacrimal duct model was established, then laser group were given Nd-YAG laser intervention, and MMC + laser group were given Nd-YAG laser combined with mitomycin intervention. 2 months after intervention, the expression of proliferation molecules, invasion molecules and MEK-ERK signaling molecules in lacrimal duct tissue were measured. Results: TGF-β, CTGF, PCNA, Ki-67, Col-I, Col-III, MEK, ERK1/2, MMP2 and MMP9 protein levels in lacrimal duct tissue of laser group were significantly higher than those of model group while TSG-6, Cthrc1 and TIMP1 protein levels were significantly lower than those of model group; TGF-β, CTGF, PCNA, Ki- 67, Col-I, Col-III, MEK, ERK1/2, MMP2 and MMP9 protein levels in lacrimal duct tissue of MMC + laser group were significantly lower than those of laser group while TSG-6, Cthrc1 and TIMP1 protein levels were significantly higher than those of laser group. Conclusion: Mitomycin can inhibit cell proliferation and invasion as well as MEK/ERK signaling pathway activation in obstructive lacrimal duct model after Nd-YAG laser treatment.

Low toxicity binder systems for tape cast Ce0.9Gd0.1O1.95 laminates

DEFF Research Database (Denmark)

Klemensø, Trine; Menon, Mohan; Ramousse, Severine

2010-01-01

Conventional binder systems for tape casting contain toxic phthalate plasticizers and butanone (MEK) as part of the solvent. The effects of exchanging the phthalate with a non-toxic alternative, and butanone with ethanol, were studied on laminates of high-green density CGO (Ce0.9Gd0.1O1.95) tapes....... Samples were prepared with a binder system containing DBP (dibutyl phthalate) plasticizer and MEK solvent, and with a binder system based on a non-toxic non-phthalate plasticizer and ethanol. In both systems, the weight ratio of plasticizer to the PVB (polyvinyl butyral) binder was varied between 0.......4 and 0.7. Substitution to the less toxic binder system had no adverse impacts on the microstructure. In fact, denser packing and improved homogeneity were observed with the non-phthalate-based system at ratio 0.5 indicating improved dispersion in this system. The denser packing also coincided...

Aucun oeil ne l'a vu. Sur une force étrange d'agir pour les choses lointaines d'apres Levinas

Czech Academy of Sciences Publication Activity Database

Bierhanzl, Jan

2015-01-01

Roč. 11, č. 2 (2015) ISSN 1336-6556 R&D Projects: GA ČR(CZ) GAP401/10/1164 Institutional support: RVO:67985955 Keywords : invisibilty * utopia * action * subjectivity Subject RIV: AA - Philosophy ; Religion http://www.ostium.sk/sk/aucun-oeil-ne-la-vu/

Diseño y validación de un radar CW-FM a 94 GHz

OpenAIRE

Varela Agrelo, David

2013-01-01

Diseño y validación de un radar CW-FM a 9g GHz 94 GHz CW-FM radar design and mesurement campaign validation. Desarrollo de un radar CW-FM a 94GHz y verificación de los resultados obtenidos durante la etapa de medidas. Desevolupament d'un radar CW-FM a 94GHz i verificació dels resultat obteinguts durante l'etapa de mesures.

MEK/ERK activation plays a decisive role in yellow fever virus replication: implication as an antiviral therapeutic target.

Science.gov (United States)

Albarnaz, Jonas D; De Oliveira, Leonardo C; Torres, Alice A; Palhares, Rafael M; Casteluber, Marisa C; Rodrigues, Claudiney M; Cardozo, Pablo L; De Souza, Aryádina M R; Pacca, Carolina C; Ferreira, Paulo C P; Kroon, Erna G; Nogueira, Maurício L; Bonjardim, Cláudio A

2014-11-01

Exploiting the inhibition of host signaling pathways aiming for discovery of potential antiflaviviral compounds is clearly a beneficial strategy for the control of life-threatening diseases caused by flaviviruses. Here we describe the antiviral activity of the MEK1/2 inhibitor U0126 against Yellow fever virus 17D vaccine strain (YFV-17D). Infection of VERO cells with YFV-17D stimulates ERK1/2 phosphorylation early during infection. Pharmacological inhibition of MEK1/2 through U0126 treatment of VERO cells blockades not only the YFV-stimulated ERK1/2 phosphorylation, but also inhibits YFV replication by ∼99%. U0126 was also effective against dengue virus (DENV-2 and -3) and Saint-Louis encephalitis virus (SLEV). Levels of NS4AB, as detected by immunofluorescence, are diminished upon treatment with the inhibitor, as well as the characteristic endoplasmic reticulum membrane invagination stimulated during the infection. Though not protective, treatment of YFV-infected, adult BALB/c mice with U0126 resulted in significant reduction of virus titers in brains. Collectively, our data suggest the potential targeting of the MEK1/2 kinase as a therapeutic tool against diseases caused by flaviviruses such as yellow fever, adverse events associated with yellow fever vaccination and dengue. Copyright © 2014 Elsevier B.V. All rights reserved.

Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling

Directory of Open Access Journals (Sweden)

Sarah Filippi

2016-06-01

Full Text Available Cellular signaling processes can exhibit pronounced cell-to-cell variability in genetically identical cells. This affects how individual cells respond differentially to the same environmental stimulus. However, the origins of cell-to-cell variability in cellular signaling systems remain poorly understood. Here, we measure the dynamics of phosphorylated MEK and ERK across cell populations and quantify the levels of population heterogeneity over time using high-throughput image cytometry. We use a statistical modeling framework to show that extrinsic noise, particularly that from upstream MEK, is the dominant factor causing cell-to-cell variability in ERK phosphorylation, rather than stochasticity in the phosphorylation/dephosphorylation of ERK. We furthermore show that without extrinsic noise in the core module, variable (including noisy signals would be faithfully reproduced downstream, but the within-module extrinsic variability distorts these signals and leads to a drastic reduction in the mutual information between incoming signal and ERK activity.

01 Inkanyiso Vol4N2 Towne DanielFM.fm

African Journals Online (AJOL)

sys1

Advancing the capacity of local governments to act effectively and accountably requires democratic local governance, relative autonomy and the political will of the ... when conducted from a central point and far away from the people tend to ... At this point, the essence of local government takes form on the premise that it will ...

Post-modernizm Gelişmek İçin Bir Adım mıdır?

OpenAIRE

Cirhinlioğlu, Zafer

2003-01-01

Günümüzde dünyanın ikiye bölündüğü yaygın kabul görmektedir; gelişmiş ve gelişmemiş, ülkeler. Gelişmemiş ülkeler sadece bir seçenekle karşı karşıyadırlar artık; gelişmek ya da modernleşmek. Bu dönemde, Batı uygarlığı bazı temel değerlere/kavramlara işaret etmektedir; kapitalizm, bireyselcilik, laiklik, insan hakları, tüketim ve bunlardan önemlisi, rasyonalite. Fakat, Batıdaki aydınlar, Batının, rasyonalite ve özellikle pozitif metodolojinin ilkelerine dayanarak kazandığı, göreli imtiyazları v...

NLRB CATS Final C-Case Data in XML - 2006

Data.gov (United States)

National Labor Relations Board — NLRB C-Case (Unfair Labor Practice) data from CATS (Case Activity Tracking System) for the period of 01/01/2006 through 12/31/2006. This dataset represents all data...

FM Radio and Youth: Listeners or Users?

Directory of Open Access Journals (Sweden)

Marina Mučalo

2014-06-01

Full Text Available A survey conducted in the spring of 2013, says that Zagreb’s high school students are not regular listeners to FM radio programs. The dominant media is the Internet, which is used a few hours a day, mostly for Facebook. Despite the expressed need for music, the linear and passive nature of FM radio, does not correspond to the individual requirements of young and networked users. The Internet is the most popular daily source for music, with ability to download, while smartphones are becoming devices for storage and playback. However, this survey has shown that students are interested in web radio sites. Changes in media preferences and habits caused by the Internet show us the importance of information literacy, as a basic skill for participation in a networked society.

34 CFR 106.71 - Procedures.

Science.gov (United States)

2010-07-01

...) Public institutions of undergraduate higher education, 106.15(e) Recruitment, [34, 35]; 106.23 Specific...(d) Pre-Employment Inquiry Recruitment, [83, 90, 91, 95] Sex as a BFOQ, [96]; 106.61 Student... organizations”, 106.31(c) Fraternities/Sororities Social, [53, 27, 28]; 106.14(a) Business/professional, [40, 53...

76 FR 72885 - FM Asymmetric Sideband Operation and Associated Technical Studies

Science.gov (United States)

2011-11-28

... digital facilities with digital effective radiated power (ERP) up to -14 dBc upon notice to the Commission... Bureau of any power increase in their FM digital ERP within 10 days of commencement using the same Form... to non- super-powered FM stations with digital ERP not exceeding -14 dBc and super-powered stations...

Hvad er hot og hvad er not? Forskning i FM - 2016

DEFF Research Database (Denmark)

Nielsen, Susanne Balslev

2016-01-01

I anledning af årsskiftet og DFM netværks nytårskur giver jeg her et bud på, hvad der kendetegner forskning i FM netop nu.......I anledning af årsskiftet og DFM netværks nytårskur giver jeg her et bud på, hvad der kendetegner forskning i FM netop nu....

Kan servicedesign bidrage positivt til FM?

DEFF Research Database (Denmark)

Larsen, Lone Birgitte Ebbeskov

2012-01-01

Professionsbachelorer i Ernæring og sundhed med studieretningen “Ledelse, Fødevarer og Service” tager afsæt i behov for sundhed til mange i form af mad og måltider, hygiejne og fødevaresikkerhed, arbejdsmiljø og medarbejdertrivsel , samt udvikling af FM- og servicekoncepter. Serviceleverandørens...

PREFACE: International Conference on Functional Materials and Nanotechnologies 2013 (FM&NT2013)

Science.gov (United States)

Nõmmiste, Ergo; Kirm, Marco; Plank, Toomas

2013-12-01

The International Conference Functional Materials and Nanotechnologies (FM&NT - 2013) was held in Tartu, 21-24 April 2013 at the Dorpat Conference Centre. The conference was organised by Institute of Physics, University of Tartu. The FM&NT conference series was started in 2006 by scientists from the Institute of Solid State Physics, University of Latvia. It is an annual conference bringing together researchers from the whole world. The warm and open atmosphere of this scientific conference has turned it into event where people from different fields meet under the common name of functional materials and nanotechnology. It is particularly important for early stage scientists who are looking for new knowledge and contact with people from various fields. Our Latvian colleagues with their success in internationalization made us neighbouring Estonians so envious that we could not withstand proposing that we host the conference in every second year in Estonia. Actually this is in a way the continuation of the idea of the famous Baltic seminars which took place over several decades during the last century. Due to political constraints these seminars were only opened to scientist of the former Eastern European countries, but which were extremely popular and attracted attendees from over the whole Soviet Union. Much fruitful cooperation started from the initial personal contacts of scientists at these seminars held twice per year, once in Latvia and the second time in Estonia. At the last FM&NT 2012 conference, the decision was made that Institute of Physics, University of Tartu would organise the event in Tartu in 2013. Along with traditional topics such as multifunctional materials, nanomaterials, materials for sustainable energy applications and theory, this conference focused on studies using synchrotron radiation and other novel light sources. The number of registered participants from 21 countries was nearly 300. During the three days of the conference 14 invited, 45

Case note: CBB (SLAM!FM t. Minister van EZ en Radio 538)

NARCIS (Netherlands)

Hins, W.

2008-01-01

Bij de verdeling van FM-radiofrequenties in 1983 heeft SLAM!FM een frequentiepakket verworven voor recente bijzondere muziek. Haar toezegging om slechts een gering percentage hitmuziek uit te zenden was daarbij doorslaggevend. Later ontstaan problemen over de vraag wat ‘hitmuziek’ eigenlijk is. De

Analog direct-modulation behavior of semiconductor laser transmitters using optical FM demodulation

NARCIS (Netherlands)

Yabre, G.S.

1998-01-01

In this paper, we report a theoretical investigation of the analog modulation performance of a semiconductor laser transmitter which employs the direct optical FM demodulation. This analysis is based on the rate equations in which Langevin noise functions are included. The optical FM response has

Dual Inhibition of PI3K/AKT and MEK/ERK Pathways Induces Synergistic Antitumor Effects in Diffuse Intrinsic Pontine Glioma Cells

Directory of Open Access Journals (Sweden)

Y. Linda Wu

2017-04-01

Full Text Available Diffuse intrinsic pontine glioma (DIPG is a devastating disease with an extremely poor prognosis. Recent studies have shown that platelet-derived growth factor receptor (PDGFR and its downstream effector pathway, PI3K/AKT/mTOR, are frequently amplified in DIPG, and potential therapies targeting this pathway have emerged. However, the addition of targeted single agents has not been found to improve clinical outcomes in DIPG, and targeting this pathway alone has produced insufficient clinical responses in multiple malignancies investigated, including lung, endometrial, and bladder cancers. Acquired resistance also seems inevitable. Activation of the Ras/Raf/MEK/ERK pathway, which shares many nodes of cross talk with the PI3K/AKT pathway, has been implicated in the development of resistance. In the present study, perifosine, a PI3K/AKT pathway inhibitor, and trametinib, a MEK inhibitor, were combined, and their therapeutic efficacy on DIPG cells was assessed. Growth delay assays were performed with each drug individually or in combination. Here, we show that dual inhibition of PI3K/AKT and MEK/ERK pathways synergistically reduced cell viability. We also reveal that trametinib induced AKT phosphorylation in DIPG cells that could not be effectively attenuated by the addition of perifosine, likely due to the activation of other compensatory mechanisms. The synergistic reduction in cell viability was through the pronounced induction of apoptosis, with some effect from cell cycle arrest. We conclude that the concurrent inhibition of the PI3K/AKT and MEK/ERK pathways may be a potential therapeutic strategy for DIPG.

Study of the stability of the ground states and K-isomeric states of 250Fm and 254102 against spontaneous fission

International Nuclear Information System (INIS)

Lazarev, Yu.A.; Lobanov, Yu.V.; Sagajdak, R.N.; Utenkov, V.K.; Kharitonov, Yu.P.; Shirokovskij, I.V.; Tret'yakova, S.P.; Oganessyan, Yu.Ts.

1988-01-01

By employing the 249 Cf( 4 He, 3n) and 208 Pb( 48 Ca,2n) reactions, experiments to study the stability against spontaneous fission of the nuclides 250 Fm and 254 102 as well as of the two-quasi-particle (2 q-p) K isomers 250 Fm (T 1/2 =1,8±0,1 s) and 254 102 (T 1/2 =0,28±0,04 s) have been performed. The groundstate spontaneous fission of the two nuclides has been discovered and the corresponding branching ratios b sf and partial half-lives T sf , respectively, have been determined to be: (6,9±1,0)x10 -5 , 0,83±0,15 yr for 250 Fm; (1,7±0,5)x10 -3 , (3,2±0,9)x10 4 s for 254 102. As a by-product of these studies, new data about cross sections of the 206,208 Pb( 48 Ca,xn) reactions have been obtained. Experiments designed to search for the spontaneous fission of the 2 q-p K-isometric states in 250 Fm and 254 102 have not revealed the effect in question. The lower limits of the ratios of the partial spontaneous fission half-lives for the 2 q-p K-isomeric states to those for the respective ground states, T * sf /T sf , have been established to be≥10 -1 for 250m Fm/ 250 Fm and ≥5x10 -3 for 254m 102/ 254 102. This means that the stability of the 2 q-p K-isomeric states in 250 Fm and 254 102 against spontaneous fission is practically not inferior to that of the ground states of these nuclei. In accord with the experimental findings, the theoretical estimates of T * sf /T sf made in the present paper show that, due to the influence of the specialization and blocking effects on the potential energy and the effective mass associated with fission, spontaneous fission from 2 q-p K-isomeric states cannot be facilitated but, on the contrary, should be essentially hindered compared with ground-state spontaneous fission

New fission valley for 258Fm and nuclei beyond

International Nuclear Information System (INIS)

Moeller, P.; Nix, J.R.; Swiatecki, W.J.

1986-01-01

Experimental results on the fission properties of nuclei close to 264 Fm show sudden and large changes with a change of only one or two neutrons or protons. The nucleus 258 Fm, for instance, undergoes symmetric fission with a half-life of about 0.4 ms and a kinetic energy peaked at about 235 MeV whereas 256 Fm undergoes asymmetric fission with a half-life of about 3 h and a kinetic energy peaked at about 200 MeV. Qualitatively, these sudden changes hve been postulated to be due to the emergence of fragment shells in symmetric fission products close to 132 Sn. A quantitative calculation that shows where high-kinetic-energy symmetric fission occurs and why it is associated with a sudden and large decrease in fission half-lives. The study is based on calculations of potential-energy surfaces in the macroscopic-microscopic model and a semi-empirical model for the nuclear inertia. The implications of the new fission valley on the stability of the heaviest elements is discussed. 33 refs., 12 figs

Ferri-magnetic order in Mn induced spinel Co_3_−_xMn_xO_4 (0.1≤x≤1.0) ceramic compositions

International Nuclear Information System (INIS)

Meena, P.L.; Sreenivas, K.; Singh, M.R.; Kumar, Ashok; Singh, S.P.; Kumar, Ravi

2016-01-01

We report structural and magnetic properties of spinel Co_3_−_xMn_xO_4 (x=0.1–1.0) synthesized by solid state reaction technique. Rietveld refinement analysis of X-ray diffraction (XRD) data, revealed the formation of polycrystalline single phase Co_3_−_xMn_xO_4 without any significant structural change in cubic crystal symmetry with Mn substitution, except change in lattice parameter. Temperature dependent magnetization data show changes in magnetic ordering temperature, indicating formation of antiferromagnetic (AFM) and ferrimagnetic (FM) phase at low Mn concentration (x≤0.3) and well-defined FM phase at high Mn concentration (x≥0.5). The isothermal magnetization records established an AFM/FM mixed phase for composition ranging 0.1 0.5. - Highlights: • Synthesis of single phase polycrystalline Co_3_−_xMn_xO_4 ceramic. • Change in magnetic ordering with varying Mn concentration. • The complex spin distribution is contributing to FM ordering with higher Mn.

The FM Market in the Nordic Countries – Volume, Structure and Trends

DEFF Research Database (Denmark)

Jensen, Per Anker

2012-01-01

The main purpose of this research is to give an overview of the FM market in Denmark, Norway, Sweden and Finland. A detailed study of the Danish FM market was done in 2008-9. This was followed up by a series of workshops facilitated by the author with groups of specialists in each of the countries...... in 2010 and 2011 to collect up-to-date information about all the 4 countries in relation to market volume, degree of outsourcing, structure and trends. The method for data collection was inspired by Delphi method. During the workshop the participants filled in a questionnaire with individual answers after...... about FM Market Data in Europe. In connection with the mentioned workshops another set of workshops were organized – except for Finland on the same day and with the same group of specialist – as part of a research project on FM Futures. The main purpose of this research is to provide input to a common...

BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors.

Science.gov (United States)

Roque, Ashley; Odia, Yazmin

2017-04-01

We present a patient with BRAF-V600E mutant papillary craniopharyngioma successfully treated with combination BRAF (dabrafenib 150 mg twice daily) and MEK (trametinib 2 mg daily) inhibitors after her unresectable tumor proved refractory to radiation. Serial brain MRIs and PET revealed marked tumor reduction with gradual neurological improvement and permanent panhypopituitarism.

Effect of selective attention on recollection and familiarity in recognition memory tasks: differential characteristics in patients with temporal lobe epilepsy with and without a history of déjà vu

OpenAIRE

Santamaría Gago, Paloma

2014-01-01

The most widely accepted contemporary explanation to define the phenomenon of déjà vu revolves around the processes of familiarity and recognition. This theoretical model is based on characteristics that define this experience in healthy subjects and in patients with temporal lobe epilepsy Objective: The main objective of this work is to determine the relationship between phenomenon of familiarity and phenomenon of recall according to the presence or absence of a history of déjà vu in p...

47 CFR 73.310 - FM technical definitions.

Science.gov (United States)

2010-10-01

... sound subcarriers and their associated sidebands. (c) Visual transmissions. Communications or message... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES FM... composite antenna pattern is a relative field horizontal plane pattern for 360 degrees of azimuth, for which...

34 CFR 106.36 - Counseling and use of appraisal and counseling materials.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Counseling and use of appraisal and counseling... Programs or Activities Prohibited § 106.36 Counseling and use of appraisal and counseling materials. (a) Counseling. A recipient shall not discriminate against any person on the basis of sex in the counseling or...

12th Russia/CIS/Baltic/Japan Symposium on Ferroelectricity and 9th International Conference on Functional Materials and Nanotechnologies (RCBJSF–2014–FM and NT)

International Nuclear Information System (INIS)

Sternberg, Andris; Grinberga, Liga; Sarakovskis, Anatolijs; Rutkis, Martins

2015-01-01

The joint International Symposium RCBJSF–2014–FM and NT successfully has united two international events – 12th Russia/CIS/Baltic/Japan Symposium on Ferroelectricity (RCBJSF-12) and 9th International Conference Functional Materials and Nanotechnologies (FM and NT-2014). The RCBJSF symposium is a continuation of series of meetings on ferroelectricity, the first of which took place in Novosibirsk (USSR) in 1976. FM and NT conferences started in 2006 and have been organized by Institute of Solid State Physics, University of Latvia in Riga. In 2012 the International program committee decided to transform this conference into a traveling Baltic State conference and the FM and NT-2013 was organized by the Institute of Physics, University of Tartu, Estonia. In 2014 the joint international symposium RCBJSF–2014–FM and NT was organized by the Institute of Solid State Physics, University of Latvia and was part of Riga – 2014, the European Capital of Culture event. The purpose of the joint Symposium was to bring together scientists, students and high-level experts in solid state physics, materials science, engineering and related disciplines. The number of the registered participants from 26 countries was over 350. During the Symposium 128 high quality scientific talks (5 plenary, 42 invited, 81 oral) and over 215 posters were presented. All presentations were divided into 4 parallel sessions according to 4 main topics of the Symposium: Ferroelectricity, including ferroelectrics and multiferroics, pyroelectrics, piezoelectrics and actuators, integrated ferroelectrics, relaxors, phase transitions and critical phenomena. Multifunctional Materials, including theory, multiscale and multiphenomenal material modeling and simulation, advanced inorganic, organic and hybrid materials. Nanotechnologies, including progressive methods, technologies and design for production, investigation of nano- particles, composites, structures, thin films and coatings. Energy, including

Ferri-magnetic order in Mn induced spinel Co{sub 3−x}Mn{sub x}O{sub 4} (0.1≤x≤1.0) ceramic compositions

Energy Technology Data Exchange (ETDEWEB)

Meena, P.L., E-mail: plmeena@gmail.com [Department of Physics, Deen Dayal Upadhyaya College (University of Delhi), Shivaji Marg, Karampura, New Delhi 110015 (India); Sreenivas, K. [Department of Physics and Astrophysics, University of Delhi, North Campus, Delhi 110007 (India); Singh, M.R. [Technical Physics and Prototype Engineering Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400085 (India); Kumar, Ashok; Singh, S.P. [National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India); Kumar, Ravi [Beant College of Engineering and Technology, Gurdaspur, Punjab 143521 (India)

2016-04-01

We report structural and magnetic properties of spinel Co{sub 3−x}Mn{sub x}O{sub 4} (x=0.1–1.0) synthesized by solid state reaction technique. Rietveld refinement analysis of X-ray diffraction (XRD) data, revealed the formation of polycrystalline single phase Co{sub 3−x}Mn{sub x}O{sub 4} without any significant structural change in cubic crystal symmetry with Mn substitution, except change in lattice parameter. Temperature dependent magnetization data show changes in magnetic ordering temperature, indicating formation of antiferromagnetic (AFM) and ferrimagnetic (FM) phase at low Mn concentration (x≤0.3) and well-defined FM phase at high Mn concentration (x≥0.5). The isothermal magnetization records established an AFM/FM mixed phase for composition ranging 0.1FM phase above x>0.5. - Highlights: • Synthesis of single phase polycrystalline Co{sub 3−x}Mn{sub x}O{sub 4} ceramic. • Change in magnetic ordering with varying Mn concentration. • The complex spin distribution is contributing to FM ordering with higher Mn.

[Effects of electromagnetic radiation on RAF/MEK/ERK signaling pathway in rats hippocampus].

Science.gov (United States)

Zuo, Hong-yan; Wang, De-wen; Peng, Rui-yun; Wang, Shui-ming; Gao, Ya-bing; Xu, Xin-ping; Ma, Jun-Jie

2009-05-01

To study the development of changes for signaling molecules related to Raf/MEK/ERK pathway in hippocampus of rats after electromagnetic radiation, and investigate the mechanisms of radiation injury. Rats were exposed to X-HPM, S-HPM and EMP radiation source respectively, and animal model of electromagnetic radiation was established. Western blot was used to detect the expression of Raf-1, phosphorylated Raf-1 and phospholylated ERK. The expression of Raf-1 down-regulated during 6 h-14 d after radiation, most significantly at 7 d, and recovered at 28 d. There was no significant difference between the radiation groups. The expression of phosphorylated Raf-1 and phosphorylated ERK both up-regulated at 6 h and 7 d after radiation, more significantly at 6 h, and the two microwave groups were more serious for phosphorylated ERK. During 6 h-14 d after S-HPM radiation, the expression of phosphorylated Raf-1 increased continuously, but phosphorylated ERK changed wavily, 6 h and 7 d were expression peak. Raf/MEK/ERK signaling pathway participates in the hippocampus injury induced by electromagnetic radiation. The excessive activation of ERK pathway may result in the apoptosis and death of neurons, which is the important mechanism of recognition disfunction caused by electromagnetic radiation.

Fat Mass Follows a U-Shaped Distribution Based on Estradiol Levels in Postmenopausal Women

Directory of Open Access Journals (Sweden)

Georgia Colleluori

2018-07-01

Full Text Available ObjectiveEstradiol (E2 regulates adipose tissue resulting in increased fat mass (FM with declining E2. However, increased visceral fat and hyperestrogenemia are features of obese individuals. It is possible that adipocytes in obese individuals are less sensitive to E2 resulting in higher FM. Our objective is to identify the range of serum E2 for which postmenopausal women have the lowest FM and best body composition.MethodsCross-sectional data from 252 community-dwelling postmenopausal women, 42–90 years old. Subjects were stratified into categories of E2 (pg/ml: (1 ≤10.5; (2 10.6–13.9; (3 14.0–17.4; and (4 ≥17.5. Body composition by dual-energy X-ray absorptiometry. Serum E2 by radioimmunoassay. Between-group comparisons by analysis of covariance.ResultsE2 linearly increased with increasing body weight and body mass index (r = 0.15 and p = 0.01 for both, but not with total FM (kg or % FM (r = 0.07, p = 0.34 and r = −0.04, p = 0.56, respectively. However, total FM (kg followed a U-shaped distribution and was significantly lower in group 3 (27.6 ± 10.6, compared with groups 1: (34.6 ± 12.5, 2: (34.0 ± 12.4, and 4: (37.0 ± 10.6, p = 0.005. % FM was also lowest in group 3. While fat-free mass (FFM, kg increased with increasing E2 (p < 0.001, % FFM was highest in group 3.ConclusionIn our population of postmenopausal women, FM followed a U-shaped distribution according to E2 levels. E2 between 14.0 and 17.4 pg/ml is associated with the best body composition, i.e., lowest total and % FM and highest % FFM. Given the role of E2 in regulating body fat, high FM at the high end of the E2 spectrum may suggest reduced E2 sensitivity in adipocytes among obese postmenopausal women.Clinical TrialsClinicalTrials.gov identifier: NCT00146107.

Capability challenges of facility management (FM) personnel toward sustainability agenda

Science.gov (United States)

Halim, Ahmad Ilyas Ahmad; Sarpin, Norliana; Kasim, Narimah Binti; Zainal, Rozlin Binti

2017-10-01

The industries business play a significant role to contribute toward economic growth in develop and developing country. However, they always face serious problems such as time overrun, waste generation, and cost overrun during their operation and maintenance. Traditional practice is found unable to control that situation. These challenges accent the need for practitioners to rethink and improve their process management. This show that industries business has major potential when applying sustainable development by focusing on three pillars (economic, environment, and social). By adopting sustainability, it can reduce energy consumption and waste, while increasing productivity, financial return and corporate standing in community. FM personnel are most suitable position to lead organizations toward sustainability implementation. However, lack of skill and capability among FM personnel to achieve sustainable goal had become barrier that need to overcome. This paper focus to identify capability challenges of FM personnel toward sustainability. A multiple researches were conducted and data were gathered through literature review from previous studies.

FM 100-14, Risk Management, 23 April 1998

National Research Council Canada - National Science Library

1998-01-01

.... Risk management is an effective process for preserving resources. FM 100-14 describes the principles, procedures, and responsibilities to successfully apply the risk management process to conserve combat power and resources...

MEK-ERK pathway modulation ameliorates disease phenotypes in a mouse model of Noonan syndrome associated with the Raf1L613V mutation

Science.gov (United States)

Wu, Xue; Simpson, Jeremy; Hong, Jenny H.; Kim, Kyoung-Han; Thavarajah, Nirusha K.; Backx, Peter H.; Neel, Benjamin G.; Araki, Toshiyuki

2011-01-01

Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden death in children and young adults. Abnormalities in several signaling pathways are implicated in the pathogenesis of HCM, but the role of the RAS-RAF-MEK-ERK MAPK pathway has been controversial. Noonan syndrome (NS) is one of several autosomal-dominant conditions known as RASopathies, which are caused by mutations in different components of this pathway. Germline mutations in RAF1 (which encodes the serine-threonine kinase RAF1) account for approximately 3%–5% of cases of NS. Unlike other NS alleles, RAF1 mutations that confer increased kinase activity are highly associated with HCM. To explore the pathogenesis of such mutations, we generated knockin mice expressing the NS-associated Raf1L613V mutation. Like NS patients, mice heterozygous for this mutation (referred to herein as L613V/+ mice) had short stature, craniofacial dysmorphia, and hematologic abnormalities. Valvuloseptal development was normal, but L613V/+ mice exhibited eccentric cardiac hypertrophy and aberrant cardiac fetal gene expression, and decompensated following pressure overload. Agonist-evoked MEK-ERK activation was enhanced in multiple cell types, and postnatal MEK inhibition normalized the growth, facial, and cardiac defects in L613V/+ mice. These data show that different NS genes have intrinsically distinct pathological effects, demonstrate that enhanced MEK-ERK activity is critical for causing HCM and other RAF1-mutant NS phenotypes, and suggest a mutation-specific approach to the treatment of RASopathies. PMID:21339642

42 CFR 1001.2006 - Notice to others regarding exclusion.

Science.gov (United States)

2010-10-01

... Organizations; (4) Hospitals, skilled nursing facilities, home health agencies and health maintenance... 42 Public Health 5 2010-10-01 2010-10-01 false Notice to others regarding exclusion. 1001.2006 Section 1001.2006 Public Health OFFICE OF INSPECTOR GENERAL-HEALTH CARE, DEPARTMENT OF HEALTH AND HUMAN...

FM knowledge – theoretical foundation and application in practice

DEFF Research Database (Denmark)

Jensen, Per Anker

2017-01-01

The idea behind this special issue can be dated back to a whole day workshop that I organised on 7 November 2012 at our Centre for Facilities Management – Realdania Research (CFM), Technical University of Denmark. The title of the workshop was “Added Value and Advancements in FM knowledge......”. The situation was that I since 2009 had chaired a European research group in EuroFM concerning “The Added Value of FM”. In spring 2012 this collaborative research work had culminated in publishing an anthology (Jensen et al., 2012). The purpose of the workshop was to discuss and possibly decide, whether we...

Resarch on the Future of FM in the Nordic Countries

DEFF Research Database (Denmark)

Jensen, Per Anker; Rasmussen, Birgitte; Andersen, Per Dannemand

2012-01-01

input to a common Nordic research agenda. The project was undertaken by Centre for Facilities Management – Realdania Research (CFM) at the Technical University of Denmark (DTU). The project was designed by use of methods from the tradition of strategic foresight. This approach was chosen to ensure...... that the strategy reflects future needs and expectations among Nordic researchers and practitioners within the FM field. The foresight process included four elements: The first element was a preliminary survey of existing studies and foresight projects on the future for FM. In particular the survey included...

MEKS: A program for computation of inclusive jet cross sections at hadron colliders

Science.gov (United States)

Gao, Jun; Liang, Zhihua; Soper, Davison E.; Lai, Hung-Liang; Nadolsky, Pavel M.; Yuan, C.-P.

2013-06-01

EKS is a numerical program that predicts differential cross sections for production of single-inclusive hadronic jets and jet pairs at next-to-leading order (NLO) accuracy in a perturbative QCD calculation. We describe MEKS 1.0, an upgraded EKS program with increased numerical precision, suitable for comparisons to the latest experimental data from the Large Hadron Collider and Tevatron. The program integrates the regularized patron-level matrix elements over the kinematical phase space for production of two and three partons using the VEGAS algorithm. It stores the generated weighted events in finely binned two-dimensional histograms for fast offline analysis. A user interface allows one to customize computation of inclusive jet observables. Results of a benchmark comparison of the MEKS program and the commonly used FastNLO program are also documented. Program SummaryProgram title: MEKS 1.0 Catalogue identifier: AEOX_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEOX_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland. Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 9234 No. of bytes in distributed program, including test data, etc.: 51997 Distribution format: tar.gz Programming language: Fortran (main program), C (CUBA library and analysis program). Computer: All. Operating system: Any UNIX-like system. RAM: ˜300 MB Classification: 11.1. External routines: LHAPDF (https://lhapdf.hepforge.org/) Nature of problem: Computation of differential cross sections for inclusive production of single hadronic jets and jet pairs at next-to-leading order accuracy in perturbative quantum chromodynamics. Solution method: Upon subtraction of infrared singularities, the hard-scattering matrix elements are integrated over available phase space using an optimized VEGAS algorithm. Weighted events are generated and filled

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Aqua-FM3_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways

Science.gov (United States)

Yuen, Hiu-Fung; Chan, Ka-Kui; Grills, Claire; Murray, James T.; Platt-Higgins, Angela; Eldin, Osama Sharaf; O’Byrne, Ken; Janne, Pasi; Fennell, Dean A.; Johnston, Patrick G.; Rudland, Philip S.; El-Tanani, Mohamed

2011-01-01

Purpose Cancer cells have been shown to be more susceptible to Ran knockdown compared to normal cells. We now investigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK and PI3K/Akt/mTORC1 activities. Experimental Design Apoptosis was measured by flow cytometry (PI and Annexin V staining) and MTT assay in cancer cells grown under different conditions after knockdown of Ran.. The correlations between Ran expression and patient survival were examined in breast and lung cancers. Results Cancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. KRas mutated, c-Met amplified and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c-Met or osteopontin expression, or with oncogenic mutations of KRas or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Conclusion Ran is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. PMID:22090358

[Effect of ERK1/2 Signaling Pathway Inhibitor PD98059 on the Expression of Ras, BRaf, MEK, ERK1/2 in Marrow Nucleated Red Blood Cells of CMS Patients].

Science.gov (United States)

Han, Yuan-Fang; Ji, Lin-Hua; Feng, Ting-Ting; Liu, Fang; Cui, Sen; Su, Juan

2017-10-01

To investigate the effect of ERK1 / 2 signaling pathway inhibitor PD98059 on Ras, Raf, MEK, ERK1, ERK2 expression in order to explore a new way for basic research and clinical treatment of the chronic mountain sickness(CMS). Sixteen CMS patients were selected, the bone marrow was collected for isolation of monomuclear cells (MNC), the cells were sorted by using CD71 and CD235a antibody magnetic beads, then positive cells were diveded into 5 groups: blank control, DMSO and PD98059 5, 10 and 20 µmol/L, and were cultured in hypoxid condition for 72 hours. The Ras-GTP levels in supernatant was detected by ELISA, the RT-PCR was used to determine the expression of BRaf, MEK, ERK1, ERK2 mRNA in nucleated red blood cells, and the Western blot method was used to detect expression of BRaf, MEK, ERK1, ERK2 protein. PD98059 had no effect on the level of Ras-GTP in each groups. Compared with the blank control group, the expression levels of BRaf, MEK mRNA in DMSO group were not statistically significant (P values were 0.826, 0.298). Compared with the PD98059 20 mol/L group, the expression level of ERK1/2 mRNA was statistically significant (P=0.001, 0.002). Compared with the blank control group, expression levels of p-BRaf, p-MEK protein in DMSO group were not statistically significant (P=0.370, 0.351). Compared with the PD98059 20 mol/L group, the difference of p-ERK1/2 protein level in other 4 groups were statistically significant (P values were <0.001, 0.007). PD98059 can up-regulate the expressions of ERK1/2 miRNA and p-ERK1/2 protein in bone marrow nucleated red blood cells, the Ras / Raf / MEK / ERK 1/2 pathway is the main signal transduction pathway in regulating bone marrow nucleated red blood cells, suggesting that Ras/Raf /MEK /ERK 1/2 pathway may be involved in the pathogenesis of chronic mountain sickness process.

Combined Arms Maneuver, Wide Area Security, and Dynamic Capabilities

Science.gov (United States)

2012-03-21

Operation (COIN) had its origins in field manuals (FM’s), like FM 31-20, Operations against Guerrilla Forces (1951). The Army revised its doctrinal...work were the publication of a new counterinsurgency doctrinal manual , in December of 2006. Most of the work on this manual did not occur until 2005...October 2, 2007, http://www.washingtonpost.com/wp.dyn/content/article/2007/10/01/ ar2007100101760. htp (accessed January 15, 2012). 53 U.S

Aligning BIM with FM: streamlining the process for future projects

Directory of Open Access Journals (Sweden)

Colleen Kasprzak

2012-12-01

Full Text Available A study performed by the National Institute of Standards and Technology (NIST, USA in 2004 found that owners account for approximately $10.6 billion of the $15.8 billion total inadequate interoperability costs of U.S. capital facility projects in 2002. Because of these inefficiency costs, it becomes vital that information produced during the design and construction phases of a project be transferred into operations with maximum leverage to the end users. However, very few owners have defined these informational needs or developed an integration strategy into existing maintenance management systems. To increase operational efficiency, an organization must first develop an understanding of their operating systems, as well as identify how Building Information Modeling (BIM will add value to their daily tasks. The Pennsylvania State University (PSU has a unique opportunity to diversely implement BIM processes because not only does the University act as an owner, but also as designer and construction manager on the majority of projects. The struggle that PSU faces is one that is unique only to owners with a large, existing, multifaceted building inventory. This paper outlines the current initiative by the Office of Physical Plant (OPP, the asset manager at PSU, to develop an information exchange framework between BIM and FM applications to be used internally. As a result of this research, PSU has been able to define owner operational requirements for future projects and develop a flexible integration framework to support additional BIM tasks and information exchanges.

Deja Vu All over Again: Re-Revisiting the Conceptual Status of Early Word Learning: Comment on Smith and Samuelson (2006)

Science.gov (United States)

Booth, Amy E.; Waxman, Sandra R.

2006-01-01

The authors assert that L. B. Smith and L. Samuelson's (2006; see record EJ750228) most recent critique of A. E. Booth, S. R. Waxman, and Y. T. Huang's (2005; see record EJ684979) work missed its mark, deflecting attention from the important theoretical difference between the two sets of authors' positions and focusing instead on imagined…

Aurora-A overexpression enhances cell-aggregation of Ha-ras transformants through the MEK/ERK signaling pathway

International Nuclear Information System (INIS)

Tseng, Ya-Shih; Lee, Jenq-Chang; Huang, Chi-Ying F; Liu, Hsiao-Sheng

2009-01-01

Overexpression of Aurora-A and mutant Ras (Ras V12 ) together has been detected in human bladder cancer tissue. However, it is not clear whether this phenomenon is a general event or not. Although crosstalk between Aurora-A and Ras signaling pathways has been reported, the role of these two genes acting together in tumorigenesis remains unclear. Real-time PCR and sequence analysis were utilized to identify Ha- and Ki-ras mutation (Gly -> Val). Immunohistochemistry staining was used to measure the level of Aurora-A expression in bladder and colon cancer specimens. To reveal the effect of overexpression of the above two genes on cellular responses, mouse NIH3T3 fibroblast derived cell lines over-expressing either Ras V12 and wild-type Aurora-A (designated WT) or Ras V12 and kinase-inactivated Aurora-A (KD) were established. MTT and focus formation assays were conducted to measure proliferation rate and focus formation capability of the cells. Small interfering RNA, pharmacological inhibitors and dominant negative genes were used to dissect the signaling pathways involved. Overexpression of wild-type Aurora-A and mutation of Ras V12 were detected in human bladder and colon cancer tissues. Wild-type Aurora-A induces focus formation and aggregation of the Ras V12 transformants. Aurora-A activates Ral A and the phosphorylation of AKT as well as enhances the phosphorylation of MEK, ERK of WT cells. Finally, the Ras/MEK/ERK signaling pathway is responsible for Aurora-A induced aggregation of the Ras V12 transformants. Wild-type-Aurora-A enhances focus formation and aggregation of the Ras V12 transformants and the latter occurs through modulating the Ras/MEK/ERK signaling pathway

01 Inkanyiso Natalia and Britz.fm

African Journals Online (AJOL)

Natalie Hazen Burclaff

... libraries are taking advantage of the online social networking boom, ..... Additionally, the words owned, licensed and subscription were each ..... mouth recommendations and commitment, but also through financial support in the future.

Nuclear-physical properties of 105,106m,110mAg

International Nuclear Information System (INIS)

Popov, Yu. S.; Zakharova, L. V.; Sadulin, V. V.; Andreev, O. I.; Pakhomov, A. N.

2005-01-01

The nuclear-physical properties of the nuclides 105,106m,110m Ag, which are concomitant nuclides in reactor production of 103 Pd and 109 Cd used in metrology of ionizing radiations and in nuclear medicine, were studied. The following quantities were determined by semiconductor X-ray and γ-ray spectrometry: the parameter K α /K β of X-ray K radiation accompanying the decay of 110m Ag and the intensities of γ-ray quanta with the energies of 280 and 345 keV ( 105 Ag); 430, 451, and 512 keV ( 106m Ag); 658, 764, 885, 938, and 1384 keV ( 110m Ag). The half-lives determined using the above γ-ray lines are as follows: T 1/2 ( 105 Ag) = 41.2 ± 0.1 days; T 1/2 ( 106m Ag) = 8.30 ± 0.07 days. The errors are given for 95% confidence level [ru

Endocytic trafficking from the small intestinal brush border probed with FM dye

DEFF Research Database (Denmark)

Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte

2009-01-01

-linking galectins/intelectin, but little is known about the dynamic properties of this highly specialized membrane. Here, we probed the endocytic membrane trafficking from the brush border of organ cultured pig intestinal mucosal explants by use of a fixable, lipophilic FM dye. The fluorescent dye readily......, contributes to the overall permeability barrier of the gut. Key words: FM dye, small intestine, brush border, endocytosis....

Exchange bias mechanism in FM/FM/AF spin valve systems in the presence of random unidirectional anisotropy field at the AF interface: The role played by the interface roughness due to randomness

Science.gov (United States)

Yüksel, Yusuf

2018-05-01

We propose an atomistic model and present Monte Carlo simulation results regarding the influence of FM/AF interface structure on the hysteresis mechanism and exchange bias behavior for a spin valve type FM/FM/AF magnetic junction. We simulate perfectly flat and roughened interface structures both with uncompensated interfacial AF moments. In order to simulate rough interface effect, we introduce the concept of random exchange anisotropy field induced at the interface, and acting on the interface AF spins. Our results yield that different types of the random field distributions of anisotropy field may lead to different behavior of exchange bias.

Charge distributions of fission fragments of low- and high-energy fission of Fm, No, and Rf isotopes

Science.gov (United States)

Paşca, H.; Andreev, A. V.; Adamian, G. G.; Antonenko, N. V.

2018-03-01

The charge (mass) distributions of fission fragments resulting from low- and high-energy fission of the even-even nuclei 254 -260 ,264Fm , 258 -264No , and 262 -266Rf are studied with the statistical scission-point model. The calculated results are compared with the available experimental data. In contrast to the experimental data, the calculated mass distribution for 258Fm (s.f.) is strikingly similar to the experimental one for 257Fm (s.f.). The transformation of the shape of charge distribution with increasing isospin and excitation energy occurs gradually and in a similar fashion like that of the mass distribution, but slower. For 254Fm(i.f.), 257Fm(nt h,f), and 260Fm (s.f.), the unexpected difference (symmetric or asymmetric) between the shapes of charge and mass distributions is predicted for the first time. At some critical excitation energy, the saturation of the symmetric component of charge (mass) yields is demonstrated.

Dissolved inorganic carbon, temperature, salinity and other variables collected from discrete sample and profile observations using CTD, Coulometer for DIC measurement and other instruments from the WAKATAKA MARU in the North Pacific Ocean from 2006-03-01 to 2006-03-10 (NODC Accession 0112361)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0112361 includes chemical, discrete sample, physical and profile data collected from WAKATAKA MARU in the North Pacific Ocean from 2006-03-01 to...

Analysis of NRAS gain in 657 patients with melanoma and evaluation of its sensitivity to a MEK inhibitor.

Science.gov (United States)

Yan, Junya; Wu, Xiaowen; Yu, Jiayi; Yu, Huan; Xu, Tianxiao; Brown, Kevin M; Bai, Xue; Dai, Jie; Ma, Meng; Tang, Huan; Si, Lu; Chi, Zhihong; Sheng, Xinan; Cui, Chuanliang; Kong, Yan; Guo, Jun

2018-01-01

Neuroblastoma rat-sarcoma (NRAS) mutations have been described in Chinese patients with melanoma. However, the status and the clinical significance of NRAS gain have not been investigated on a large scale. A total of 657 melanoma samples were included in the study. NRAS copy number was examined using the QuantiGene Plex DNA assay. The sensitivities of cell lines and patient-derived xenograft (PDX) models containing NRAS gain to a MAP/ERK kinase (MEK) inhibitor (binimetinib) were also evaluated. The overall incidence of NRAS gain was 14.0% (92 of 657). Incidence of NRAS gain in acral, mucosal, chronic sun-induced damage (CSD) and non-CSD melanomas was 12.2%, 15.8%, 9.5% and 19.4%, respectively. NRAS gain was mutually exclusive to NRAS mutations (P = 0.036). The median survival time for melanoma patients with NRAS gain was significantly shorter than that for patients with normal NRAS copy number (P = 0.006). For patients containing NRAS gain, the median survival time for higher copy number (>4 copies) was significantly shorter than those with lower copy number (2-4 copies; P = 0.002). The MEK inhibitor (binimetinib) inhibited the proliferation of melanoma cells and the tumour growth of PDX models with NRAS gain. NRAS gain is frequent in patients with melanoma and may predict a poor prognosis of melanoma. The melanoma cells and PDX models containing NRAS gain are sensitive to MEK inhibitor (binimetinib), indicating that NRAS gain might be a new therapeutic target for melanoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations

Directory of Open Access Journals (Sweden)

Ludovica Ciuffreda

2009-08-01

Full Text Available The Raf/MEK/ERK pathway is an importantmediator of tumor cell proliferation and angiogenesis. Here, weinvestigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G1-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27KIP1 and apoptosis (Bcl-2 and survivin regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma.

Friction stir welding of F/M ODS steel plug and F/M steel tube

Energy Technology Data Exchange (ETDEWEB)

Kang, Suk Hoon, E-mail: shkang77@kaeri.re.kr [Nuclear Materials Division, Korea Atomic Energy Research Institute (Korea, Republic of); Vasudevan, M. [Materials Technology Division, Indira Gandhi Centre for Atomic Research, Kalpakkam (India); Noh, Sanghoon; Jin, Hyun Ju; Jang, Jinsung; Kim, Tae Kyu [Nuclear Materials Division, Korea Atomic Energy Research Institute (Korea, Republic of)

2016-11-01

Highlights: • Friction stir welding (FSW) was used for joining of oxide dispersion strengthened (ODS) steel plug and F/M steel tube. • The curvature and smaller thickness of tube was the major limitation for applying FSW method, it was solved using specially designed jig. • Considerable hardening occurs in the joint because the cooling rate was sufficient to reproduce a martensitic microstructure. • The measured hoop strength of the FSWed joint was 70–90 MPa, the value was at around 70% of the tube. - Abstract: Friction stir welding (FSW) was used for joining of oxide dispersion strengthened (ODS) steel plug and F/M steel tube. The dimensions of the tube included outer diameter of 7 mm, wall thickness of 0.5 mm. The objective was to find suitable process variables for gaining enough frictional heat from those thin and curved pieces. A specially designed jig was used for stabilization and slow rotation of tube during FSW. Additionally, the plug was designed to overlap the tube. Inconel 718 was used as FSW tool, the diameter was 3.5 mm. The adequate rotation speed of the tool and jig were 1200 rpm and 1.5 rpm, respectively. The joining was successfully accomplished using above combination, showing a good possibility. The hoop stress tests of joint were conducted by blowing Ar gas into the tube, the flow rate of gas was 10 MPa/min. The measured hoop stress was 70–90 MPa, the value was at around 70% of the tube.

Friction stir welding of F/M ODS steel plug and F/M steel tube

International Nuclear Information System (INIS)

Kang, Suk Hoon; Vasudevan, M.; Noh, Sanghoon; Jin, Hyun Ju; Jang, Jinsung; Kim, Tae Kyu

2016-01-01

Highlights: • Friction stir welding (FSW) was used for joining of oxide dispersion strengthened (ODS) steel plug and F/M steel tube. • The curvature and smaller thickness of tube was the major limitation for applying FSW method, it was solved using specially designed jig. • Considerable hardening occurs in the joint because the cooling rate was sufficient to reproduce a martensitic microstructure. • The measured hoop strength of the FSWed joint was 70–90 MPa, the value was at around 70% of the tube. - Abstract: Friction stir welding (FSW) was used for joining of oxide dispersion strengthened (ODS) steel plug and F/M steel tube. The dimensions of the tube included outer diameter of 7 mm, wall thickness of 0.5 mm. The objective was to find suitable process variables for gaining enough frictional heat from those thin and curved pieces. A specially designed jig was used for stabilization and slow rotation of tube during FSW. Additionally, the plug was designed to overlap the tube. Inconel 718 was used as FSW tool, the diameter was 3.5 mm. The adequate rotation speed of the tool and jig were 1200 rpm and 1.5 rpm, respectively. The joining was successfully accomplished using above combination, showing a good possibility. The hoop stress tests of joint were conducted by blowing Ar gas into the tube, the flow rate of gas was 10 MPa/min. The measured hoop stress was 70–90 MPa, the value was at around 70% of the tube.

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Aqua-FM4_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

Drošas tīmekļa lietotnes izstrāde izmantojot JAVA programmēšanas valodu

OpenAIRE

Ķīvītis, Jānis

2015-01-01

Internetu ar katru dienu izmanto vairāk cilvēku un uzņēmumu. Pieaugošā lietotāju skaita fonā aug arī tīmeklī izvietoto vietņu skaits. Ar katru jaunu vietni kibernoziedzniekiem paliek vairāk mērķu uzbrukumiem. Lai datorlauži nespētu piekļūt datiem, kas glabājas uz servera, kurā izvietota programmatūra, tīmekļa vietni jāaizsargā. Darbā tiks izpētīti bīstamākie tīmekļa programmatūras ievainojumi un iespējas tos novērst. Tiks apskatīti arī daži informācijas tehnoloģiju drošības standarti. Pētī...

Comparison of MEK/ERK pathway inhibitors on the upregulation of vascular G-protein coupled receptors in rat cerebral arteries

DEFF Research Database (Denmark)

Sandhu, Hardip; Ansar, Saema; Edvinsson, Lars

2010-01-01

on translational level and increased respective contractions. The prostanoid TP receptor mediated contraction curve was left-wards shifted by organ culture. Organ culture was associated with elevated pERK1/2 in the vascular smooth muscle cells: the MEK1/2 inhibitor U0126 attenuated the endothelin ET(B) receptor......Organ culture is an in vitro method for investigating cellular mechanisms involved in upregulation of vasocontractile G-protein coupled receptors. We hypothesize that mitogen-activated-protein kinase (MEK) and/or extracellular-signal-regulated kinase (ERK) specific inhibitors will attenuate the G......), prostanoid TP receptor, and angiotensin II receptor type 1 and type 2 were investigated. Results were verified by measurement of mRNA with real time PCR and by protein immunohistochemistry. Organ culture induced transcriptional upregulation of endothelin ET(B) receptor and of serotonin 5-HT(1B) receptor...

Inhibitors of pan PI3K signaling synergize with BRAF or MEK inhibitors to prevent BRAF-mutant melanoma cell growth

Directory of Open Access Journals (Sweden)

Melanie eSweetlove

2015-06-01

Full Text Available BRAF and MEK inhibitors have improved outcomes for patients with BRAF-mutant melanoma, but their efficacy is limited by both intrinsic and acquired resistance. Activation of the PI3K pathway can mediate resistance to these agents, providing a strong rationale for combination therapy in melanoma. Here, a panel of 9 low passage human metastatic melanoma cell lines with BRAF mutations were tested in cell proliferation and protein expression assays for sensitivity to inhibitors of MEK (selumetinib and BRAF (vemurafenib as single agents and in combination with inhibitors of pan-PI3K (ZSTK474, pan-PI3K/mTOR (BEZ235, individual PI3K isoforms (p110α, A66; p110β, TGX-221; p110γ, AS-252424; p110δ, idelalisib, or mTORC1/2 (KU-0063794. Selumetinib and vemurafenib potently inhibited cell proliferation in all cell lines, especially in those that expressed low levels of pAKT. ZSTK474 and BEZ235 also inhibited cell proliferation in all cell lines and enhanced the antitumor activity of selumetinib and vemurafenib in the majority of lines by either interacting synergistically or additively to increase potency or by inducing cytotoxicity by significantly increasing the magnitude of cell growth inhibition. Furthermore, ZSTK474 or BEZ235 combined with selumetinib to produce robust inhibition of pERK, pAKT and pS6 expression and synergistic inhibition of NZM20 tumor growth. The inhibitors of individual PI3K isoforms or mTORC1/2 were less effective at inhibiting cell proliferation either as single agents or in combination with selumetinib or vemurafenib, although KU-0063794 synergistically interacted with vemurafenib and increased the magnitude of cell growth inhibition with selumetinib or vemurafenib in certain cell lines. Overall, these results suggest that the sensitivity of BRAF-mutant melanoma cells to BRAF or MEK inhibitors is at least partly mediated by activation of the PI3K pathway and can be enhanced by combined inhibition of the BRAF/MEK and PI3K

[Antimicrobial effect of a new bio-ceramic material iRoot FM on Porphyromonas endodontalis].

Science.gov (United States)

Bi, Jing; Liu, Yao; Chen, Xu

2017-10-01

To compare the antimicrobial effect of a new bio-ceramic material iRoot FM with traditional intracanal medicaments including calcium hydroxide [Ca(OH) 2 ] and triple antibiotic paste (TAP), on Porphyromonas endodontalis (P. endodontalis), and to evaluate the antimicrobial activity of iRoot FM, providing reference for clinical use of intracanal medicaments. P. endodontalis ATCC 35406 were used in this study. The study was divided into 3 experimental groups including iRoot FM, Ca(OH) 2 and TAP group. Sterile water was used as blank control. Frozen P. endodontalis were seeded and grown overnight in the liquid medium, then P. endodontalis were seeded on BHI-blood agar plates. After the plates were dried, the materials were filled on the plates which were made by a punching machine. Zones of inhibition (mm) were measured after 72 h of anaerobic incubation at 37degrees centigrade. The experimental data were analyzed statistically using SPSS 17.0 software package. The zones of inhibition in the 3 experimental groups: iRoot FM, Ca(OH) 2 and TAP group were (20.74±4.35)mm, (24.89±3.84)mm and (34.51±1.20)mm, respectively. The zones of inhibition of the iRoot FM group and Ca(OH) 2 group were significantly smaller compared with the TAP group (P0.05). There were no zone of inhibition in the control group. As a new bio-ceramic material, iRoot FM shows a good antimicrobial activity against P. endodontalis and may be a promising intracanal material.

Self-ion Irradiation Damage of F/M and ODS steels

International Nuclear Information System (INIS)

Kang, Suk Hoon; Chun, Young-Bum; Noh, Sanghoon; Jang, Jinsung; Kim, Tae Kyu

2014-01-01

Oxide dispersion strengthened (ODS) ferritic steels are potential high-temperature materials that are stabilized by dispersed particles at elevated temperatures. These dispersed particles improve the tensile strength and creep rupture strength, they are expected to increase the operation temperature up to approximately 650 .deg. C and also enhance the energy efficiency of the fusion reactor. Some reports described that the nano-clusters are strongly resistant to coarsening by annealing up to 1000 .deg. C, and nanoclusters do not change after ion irradiation up to 0.7 dpa at 300 .deg. C. ODS steels will be inevitably exposed to neutron irradiation condition; the irradiation damages, creep and swelling are always great concern. The dispersed oxide particles are believed to determine the performance of the steel, even the radiation resistance. In this study, F/M and ODS model alloys of Korea Atomic Energy Research Institute (KAERI) were irradiated by Fe 3+ self-ion to emulate the neutron irradiation effect. In this study, Fe 3+ self-ion irradiation is used as means of introducing radiation damage in F/M steel and ODS steel. The ion accelerator named DuET (in Kyoto University, Japan) was used for irradiation of Fe 3+ ion by 6.4 MeV at 300 .deg. C. The maximum damage rate in F/M and ODS steels were estimated roughly 6 dpa. After radiation, point or line defects were dominantly observed in F/M steel, on the other hands, small circular cavities were typically observed in ODS steel. Nanoindentation is a useful tool to determine the irradiationinduced hardness change in the damage layer of ionirradiated iron base alloys

Von Hippel-Lindau tumor suppressor gene loss in renal cell carcinoma promotes oncogenic epidermal growth factor receptor signaling via Akt-1 and MEK-1.

Science.gov (United States)

Lee, S Justin; Lattouf, Jean-Baptiste; Xanthopoulos, Julie; Linehan, W Marston; Bottaro, Donald P; Vasselli, James R

2008-10-01

Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-alpha (TGF-alpha), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase. To determine the functional impact of EGFR activation on RCC, we suppressed critical components of this pathway: EGFR, Akt-1, and MEK-1. Stable transfection of RCC cells with plasmids bearing shRNA directed against each of these genes was used to individually suppress their expression. Transfectants were characterized for growth and invasiveness in vitro and tumorigenesis in vivo. RCC cell transfectants displayed significantly reduced growth rate and matrix invasion in vitro and RCC tumor xenograft growth rate in vivo. Analysis of tumor cells that emerged after extended periods in each model showed that significant EGFR suppression was sustained, whereas Akt-1 and MEK-1 knock-down cells had escaped shRNA suppression. EGFR, Akt-1, and MEK-1 are individually critical for RCC cell invasiveness in vitro and tumorigenicity in vivo, and even partial suppression of each can have a significant impact on tumor progression. The emergence of transfectants that had escaped Akt-1 and MEK-1 suppression during tumorigenicity experiments suggests that these effectors may each be more critical than EGFR for RCC tumorigenesis, consistent with results from clinical trials of EGFR inhibitors for RCC, where durable clinical responses have not been seen.

Von Hippel-Lindau Tumor Suppressor Gene Loss in Renal Cell Carcinoma Promotes Oncogenic Epidermal Growth Factor Receptor Signaling via Akt-1 and MEK1

Science.gov (United States)

Lee, S. Justin; Lattouf, Jean-Baptiste; Xanthopoulos, Julie; Linehan, W. Marston; Bottaro, Donald P.; Vasselli, James R.

2008-01-01

Objectives Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-α (TGF-α), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase. To determine the functional impact of EGFR activation on RCC, we suppressed critical components of this pathway: EGFR, Akt-1, and MEK-1. Methods Stable transfection of RCC cells with plasmids bearing shRNA directed against each of these genes was used to individually suppress their expression. Transfectants were characterized for growth and invasiveness in vitro and tumorigenesis in vivo. Results RCC cell transfectants displayed significantly reduced growth rate and matrix invasion in vitro and RCC tumor xenograft growth rate in vivo. Analysis of tumor cells that emerged after extended periods in each model showed that significant EGFR suppression was sustained, whereas Akt-1 and MEK-1 knockdown cells had escaped shRNA suppression. Conclusions EGFR, Akt-1, and MEK-1 are individually critical for RCC cell invasiveness in vitro and tumorigenicity in vivo, and even partial suppression of each can have a significant impact on tumor progression. The emergence of transfectants that had escaped Akt-1 and MEK-1 suppression during tumorigenicity experiments suggests that these effectors may each be more critical than EGFR for RCC tumorigenesis, consistent with results from clinical trials of EGFR inhibitors for RCC, where durable clinical responses have not been seen. PMID:18243508

Identifying critical success factors (CSFs) of Facilities Management (FM) in non-low cost high-rise residential buildings

Science.gov (United States)

Dahlan, F. M.; Zainuddin, A.

2018-02-01

Critical success factors (CSFs) are important key areas of activity that must be performed well in any Facilities Management (FM) organisation to achieve its missions, objectives or goals. Before implementing CSFs, an FM organisation must identify the key areas where things must be done properly to enable the business to flourish. Although many performance measurements in FM organisation have been discussed in previous research, not much research has been done on CSFs from the perspective of FM business in non-low cost high-rise residential buildings. The purpose of this study is to develop a methodology in developing the CSFs group and CSFs for FM organisation in non-low cost residential buildings. This research will involve three (3) phases of research strategy to achieve the objective of this research.

A Dual Stage Linear Prediction Approach Towards Wideband FM Demodulation With Multilevel and Partial Response Signaling

Science.gov (United States)

2018-01-19

attributed to the inherent interpolation process in the MFT demodulation approach, which is more error-sensitive to discontinuous waveforms, such as...Multirate Frequency Transformations In the author’s recent work, frequency transformations enacted via multirate signal processing were used for wideband...FM to narrowband FM conversion to enable a wider range of wideband FM signals [9, 11]. The goal of the multirate processing module is to compress the

Metabolism and dosimetry of 106Ru inhaled as 106RuO4 by beagle dogs

International Nuclear Information System (INIS)

Snipes, M.B.

1981-01-01

This report provides metabolism and dosimetry data for inhaled ruthenium developed from studies in Beagle dogs that were exposed by inhalation to 106 RuO 4 . Twenty-six dogs were exposed nose-only to 106 RuO 4 and sacrificed at times from 2 hr to 512 days after inhalation exposure. Ninety-nine percent of the initial body burden was retained with an effective half-time of 1.2 days, 0.7% with a half-time of 14 days and 0.3% with a half-time of 170 days. Initial deposition was primarily in the nasopharyngeal and tracheobronchial regions. Results for deposition and retention of 106 Ru inhaled as 106 RuO 4 in dogs were similar to what has been observed for humans. The data for dogs were used to develop a model to predict potential radiation exposure patterns for humans after inhalation exposure to 106 RuO 4 . The model indicates that for humans the nasopharyngeal region, lower large intestine, and tracheobronchial epithelium would receive approx. 36, 13 and 10 times, respectively, the dose to 500 days after inhalation exposure to 106 RuO 4 that the lung would receive. The nasopharyngeal region should be considered the critical region for inhalation exposures to 106 RuO 4 . (author)

Perspektif Public Relations (KajianTentang Marketing PT. Radio Suara Mandala 96,4 FM Banyuwangi

Directory of Open Access Journals (Sweden)

Abdi Fauji Hadiono

2017-10-01

Full Text Available Public relations adalah keseluruhan upaya yang dilakukan secara terencana dan berkesinambungan dalam rangka menciptakan dan memelihara niat baik (good will dan saling pengertian antara suatu organisasi dengan segenap khalayaknya. Masalah yang diteliti dalam penelitian ini adalah Marketing yang menggunakan public relationspada PT. Radio Suara Mandala 96,4 Fm Banyuwangi. Peneliti menggunakan metode penelitian kualitatif. Dalam melakukan pengumpulan data peneliti memakai metode wawancara, observasi partisipan dan dokumentasi, kemudian data yang dikumpul di olah dan dianalisa dengan menggunakan interactive model Miles dan Huberman, yang terdiri dari tiga rangkaian komponen, yaitu: Reduksi data (data reduction, penyajian data(data display, dan penarikan serta pengujian kesimpulan (drawing and verifying conclusion. Hal yang peneliti lakukan untuk menguji keabsahan data adalah, Trianggulasi Metode dilakukan dengan cara membandingkan informasi atau data  marketing di PT. Radio Suara Mandala 96,4 Fm Banyuwangi menggunakan public relations. Trianggulasi Sumber menggali kebenaran informasi data  marketing di PT. Radio Suara Mandala 96,4 Fm Banyuwangi menggunakan public relations melalui berbagai metode dan sumber perolehan data. Trianggulasi Teori Hasil akhir penelitian kualitatif berupa sebuah rumusan informasi dari data  marketing di PT. Radio Suara Mandala 96,4 FmBanyuwangi menggunakan public relations. Objek dari penelitian ini meliputi Internal PT.  Radio Suara Mandala 96.4 FM, kemudian dari pihak klien yaitu Hotel Santika dan Sisikmelik Batik Banyuwangi. Dari hasil penelitian ini di ketahui bahwa di  PT.  Radio Suara Mandala 96.4 FM, marketing yang menggunakan public relations dengan 3 kriteria, diantaranya Pembuatan Strategi marketing (penelitian, membentuk tujuan pemasaran, Penerapan Strategi marketing (mengimplementasikan rencana public relations dan Evaluasi strategi marketing (mengevaluasikan hasil menggunakan public relation

CREBBP knockdown enhances RAS/RAF/MEK/ERK signaling in Ras pathway mutated acute lymphoblastic leukemia but does not modulate chemotherapeutic response.

Science.gov (United States)

Dixon, Zach A; Nicholson, Lindsay; Zeppetzauer, Martin; Matheson, Elizabeth; Sinclair, Paul; Harrison, Christine J; Irving, Julie A E

2017-04-01

Relapsed acute lymphoblastic leukemia is the most common cause of cancer-related mortality in young people and new therapeutic strategies are needed to improve outcome. Recent studies have shown that heterozygous inactivating mutations in the histone acetyl transferase, CREBBP , are particularly frequent in relapsed childhood acute lymphoblastic leukemia and associated with a hyperdiploid karyotype and KRAS mutations. To study the functional impact of CREBBP haploinsufficiency in acute lymphoblastic leukemia, RNA interference was used to knock down expression of CREBBP in acute lymphoblastic leukemia cell lines and various primagraft acute lymphoblastic leukemia cells. We demonstrate that attenuation of CREBBP results in reduced acetylation of histone 3 lysine 18, but has no significant impact on cAMP-dependent target gene expression. Impaired induction of glucocorticoid receptor targets was only seen in 1 of 4 CREBBP knockdown models, and there was no significant difference in glucocorticoid-induced apoptosis, sensitivity to other acute lymphoblastic leukemia chemotherapeutics or histone deacetylase inhibitors. Importantly, we show that CREBBP directly acetylates KRAS and that CREBBP knockdown enhances signaling of the RAS/RAF/MEK/ERK pathway in Ras pathway mutated acute lymphoblastic leukemia cells, which are still sensitive to MEK inhibitors. Thus, CREBBP mutations might assist in enhancing oncogenic RAS signaling in acute lymphoblastic leukemia but do not alter response to MEK inhibitors. Copyright© Ferrata Storti Foundation.

Detección de movimiento mediante técnicas radar CW-FM en banda W

OpenAIRE

Vargas González, Daniel

2014-01-01

Aplicació de diverses tècniques de detecció i localització per detectar moviments amb un radar C2-FM que opera en banda W. [ANGLÈS] Integration of a SAR adquisition system using a FM-CW 94 GHz radar and test the system by different measurement campaigns with the aim of detecting micrometic displacements using a phase analysis of the recived signal [CASTELLÀ[ Integración de un sistema de adquisición SAR mediante el uso de un radar FM-CW a 94 GHz y probar la validez del mencionado sistema...

Trending Technologies for Indoor FM: Looking for "Geo" in Information

Science.gov (United States)

Gunduz, M.; Isikdag, U.; Basaraner, M.

2016-10-01

Today technological developments in the Architecture Engineering and Construction (AEC) industry provides opportunities to build huge and complex buildings and facilities. In order to operate these facilities and to meet the requirements of the occupants and also to manage energy, waste and to keep all facility services operational, several Facility Management (FM) solutions were developed. This paper starts by presenting a state of art review of research related to Indoor Facility Management Systems. Later, a textual analysis focused to identify the research trends in this field is presented in the paper. The result of the literature review and textual analysis indicates that current research in Indoor FM Systems is underestimating the role of Geoinformation, Geoinformation models and systems.

Tīmekļa vietne videospēļu cienītājiem

OpenAIRE

Freibergs, Raimonds

2012-01-01

„Tīmekļa vietne videospēļu cienītājiem” ir tīmeklī bāzēta sistēma, kura tās lietotājiem dos iespēju iegūt jaunākas ziņas par videospēļu industriju, lasīt spēļu apskatus, dalīties ar saviem personīgajiem iespaidiem un atrast līdzīgi domājošos.

Geniposide activates GSH S-transferase by the induction of GST M1 and GST M2 subunits involving the transcription and phosphorylation of MEK-1 signaling in rat hepatocytes

International Nuclear Information System (INIS)

Kuo, W.-H.; Chou, F.-P.; Young, S.-C.; Chang, Y.-C.; Wang, C.-J.

2005-01-01

Geniposide, an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis, has biological capabilities of detoxication, antioxidation, and anticarcinogenesis. We have recently found that geniposide possesses a potential for detoxication by inducing GST activity and the expression of GST M1 and GST M2 subunits. In this study, the signaling pathway of geniposide leading to the activation of GSH S-transferase (GST) was investigated. Primary cultured rat hepatocytes were treated with geniposide in the presence or absence of mitogen-activated protein kinase (MAPK) inhibitors and examined for GST activity, expression of GST M1 and M2 subunits, and protein levels of MAPK signaling proteins. Western blotting data demonstrated that geniposide induced increased protein levels of GST M1 and GST M2 (∼1.76- and 1.50-fold of control, respectively). The effect of geniposide on the increased protein levels of GST M1 and GST M2 was inhibited by the MEK-1 inhibitor PD98059, but not by other MAPK inhibitors. The GST M1 and GST M2 transcripts as determined by RT-PCR and GST activity were also inhibited concurrently by the MEK-1 inhibitor PD98059. The protein levels of up- and down-stream effectors of the MEK-1, including Ras, Raf, and Erk1/2, and the phosphorylation state of Erk1/2 were found to be induced by geniposide, indicating a two-phase influence of geniposide. The results suggest that geniposide induced GST activity and the expression of GST M1 and GST M2 acting through MEK-1 pathway by activating and increasing expression of Ras/Raf/MEK-1 signaling mediators

Epithelial tissue hyperplasia induced by the RAF inhibitor PF-04880594 is attenuated by a clinically well-tolerated dose of the MEK inhibitor PD-0325901.

Science.gov (United States)

Torti, Vince R; Wojciechowicz, Donald; Hu, Wenyue; John-Baptiste, Annette; Evering, Winston; Troche, Gabriel; Marroquin, Lisa D; Smeal, Tod; Yamazaki, Shinji; Palmer, Cynthia L; Burns-Naas, Leigh Ann; Bagrodia, Shubha

2012-10-01

Clinical trials of selective RAF inhibitors in patients with melanoma tumors harboring activated BRAFV600E have produced very promising results, and a RAF inhibitor has been approved for treatment of advanced melanoma. However, about a third of patients developed resectable skin tumors during the course of trials. This is likely related to observations that RAF inhibitors activate extracellular signal-regulated kinase (ERK) signaling, stimulate proliferation, and induce epithelial hyperplasia in preclinical models. Because these findings raise safety concerns about RAF inhibitor development, we further investigated the underlying mechanisms. We showed that the RAF inhibitor PF-04880594 induces ERK phosphorylation and RAF dimerization in those epithelial tissues that undergo hyperplasia. Hyperplasia and ERK hyperphosphorylation are prevented by treatment with the mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD-0325901 at exposures that extrapolate to clinically well-tolerated doses. To facilitate mechanistic and toxicologic studies, we developed a three-dimensional cell culture model of epithelial layering that recapitulated the RAF inhibitor-induced hyperplasia and reversal by MEK inhibitor in vitro. We also showed that PF-04880594 stimulates production of the inflammatory cytokine interleukin 8 in HL-60 cells, suggesting a possible mechanism for the skin flushing observed in dogs. The complete inhibition of hyperplasia by MEK inhibitor in epithelial tissues does not seem to reduce RAF inhibitor efficacy and, in fact, allows doubling of the PF-04880594 dose without toxicity usually associated with such doses. These findings indicated that combination treatment with MEK inhibitors might greatly increase the safety and therapeutic index of RAF inhibitors for the treatment of melanoma and other cancers. ©2012 AACR.

Transport and divertor studies in the FM-1 spherator

International Nuclear Information System (INIS)

Ando, K.; Ejima, S.; Davis, S.; Hawryluk, R.; Hsuan, H.; Meade, D.; Okabayaski, M.; Sauthoff, N.; Schmidt, J.; Sinnis, J.

1974-10-01

Fundamental problems of toroidal fusion devices have been investigated in the FM-1 Spherator. These subjects include the transport due to drift wave turbulence in the trapped electron regime, poloidal divertor and impurities, and lower hybrid heating. (auth)

Kinetic analysis of DAF-FM activation by NO: toward calibration of a NO-sensitive fluorescent dye.

Science.gov (United States)

Namin, Shabnam M; Nofallah, Sara; Joshi, Mahesh S; Kavallieratos, Konstantinos; Tsoukias, Nikolaos M

2013-01-15

Nitric oxide (NO) research in biomedicine has been hampered by the absence of a method that will allow quantitative measurement of NO in biological tissues with high sensitivity and selectivity, and with adequate spatial and temporal resolution. 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) is a NO sensitive fluorescence probe that has been used widely for qualitative assessment of cellular NO production. However, calibration of the fluorescent signal and quantification of NO concentration in cells and tissues using fluorescent probes, have provided significant challenge. In this study we utilize a combination of mathematical modeling and experimentation to elucidate the kinetics of NO/DAF-FM reaction in solution. Modeling and experiments suggest that the slope of fluorescent intensity (FI) can be related to NO concentration according to the equation: ddtFI=2αk(1)NO(2)O(2)DAF-FMkNO+DAF-FM where α is a proportionality coefficient that relates FI to unit concentration of activated DAF-FM, k(1) is the NO oxidation rate constant, and k was estimated to be 4.3±0.6. The FI slope exhibits saturation kinetics with DAF-FM concentration. Interestingly, the effective half-maximum constant (EC(50)) increases proportionally to NO concentration. This result is not in agreement with the proposition that N(2)O(3) is the NO oxidation byproduct that activates DAF-FM. Kinetic analysis suggests that the reactive intermediate should exhibit NO-dependent consumption and thus NO(2)() is a more likely candidate. The derived rate law can be used for the calibration of DAF-FM fluorescence and the quantification of NO concentration in biological tissues. Copyright © 2012 Elsevier Inc. All rights reserved.

13 CFR 106.503 - Are there types of Gifts which SBA may not solicit and/or accept?

Science.gov (United States)

2010-01-01

... of or for (or use cash Gifts to purchase or engage in) the following: (a) Alcohol products; (b... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Are there types of Gifts which SBA... ADMINISTRATION COSPONSORSHIPS, FEE AND NON-FEE BASED SBA-SPONSORED ACTIVITIES AND GIFTS Gifts § 106.503 Are there...

THE EFFECT OF F/M RATIO TO THE ANAEROBIC DECOMPOSITION OF BIOGAS PRODUCTION FROM FISH OFFAL WASTE

Directory of Open Access Journals (Sweden)

Agus Hadiyarto

2016-01-01

Full Text Available Biogas is a gas produced from the anaerobic decomposition of organic compounds. In the production of biogas from anaerobic digestion, value of F/M ratio shows a ratio between the mass of food available in the waste substrate with a mass of microorganisms that act as decomposers. F/M ratio is too small causing microbes could not metabolize perfectly and vice versa on the value of the ratio F / M overload resulting metabolic imbalance. The purpose of this study was to assess the effect of F/M ratio to optimal production of biogas from fish offal waste. The process of anaerobic digestion is conducted in the biodigester with four-liter volume and batch system operated at ambient temperature for 38 days. As a raw material, fish offal and microbial sludge obtained from the curing of fish and river mud discharges in the region of Bandarharjo, Semarang, Central Java. F/M ratio is set at 0.2, 0.4, and 0.6 are derived from sewage sludge VSS weight ratio of fish offal with sludge containing microbes. The addition of micronutrients supplied with a concentration of 0.4 mg/liter. Yield maximum methane gas obtained was 164,7 l/kg CODMn when the ratio F/M was 0.2. Based on the results of the study, found that the ratio F/M affect the amount of biogas produced. Meanwhile, the retention time (HRT is only influenced by the ratio F/M.

Launch Environmental Test for KITSAT-3 FM

Directory of Open Access Journals (Sweden)

Sang-Hyun Lee

1999-06-01

Full Text Available The satellite experiences the severe launch environment such as vibration, acceleration, shock, and acoustics induced by rocket. Therefore, the satellite should be designed and manufactured to endure such severe launch environments. In this paper, we describe the structure of the KITSAT-3 FM(Flight Model and the processes and results of the launch environmental test to ensure the reliability during launch period.

48 CFR 301.106 - Office of Management and Budget approval under the Paperwork Reduction Act.

Science.gov (United States)

2010-10-01

... Issuance 301.106 Office of Management and Budget approval under the Paperwork Reduction Act. (a) The... approval from the Office of Management and Budget (OMB) before collecting the same information from 10 or... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Office of Management and...

Experiment for buried pipes by stepped FM-CW radar; Step shiki FM-CW radar ni yoru maisetsukan tansa jikken

Energy Technology Data Exchange (ETDEWEB)

Suzuki, K.; Ito, M. [Kawasaki Geological Engineering, Co. Ltd., Tokyo (Japan); Tanabe, K. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

1997-05-27

The underground radar exploration is adopted to surveys of cavity under the road and buried pipes since the result of high resolution is obtained. However, the explorative depth of the radar is shallow, 2-3m in soil basement, and its applicable field has been limited. The continuous wave radar (FM-CW radar) was devised to get deeper explorative depth, but has been used for the geological structure survey such as the fault survey since it is lower in resolution as compared with the pulse radar. Therefore, to make use of characteristics of the continuous wave radar and enhance resolution in the shallow part, an experiment on buried pipes was conducted for the purpose of assessing and improving the FM-CW radar. In this processing, the wave form treatment used in the reflection method seismic survey was adopted for the radar survey. There are some problems, but it is effective to adopt the same algorithm to that used in the seismic survey to the radar exploration. The explorative depth was discussed from the damping rate of electromagnetic waves and dynamic range of facilities of the experimental site, and 7m was obtained. 5 figs., 1 tab.

Experiments for post accident hydrogen dispersion in F.M. vault using helium

International Nuclear Information System (INIS)

Bajaj, S.S.; Bhattacharyya, D.; Mishra, S.

1994-01-01

Under certain postulated accident scenarios involving a Loss of Coolant Accident (LOCA) simultaneous with impairment of Emergency Core Cooling (ECC), generation of hydrogen due to reaction between the zirconium clad and coolant is predicted in the coolant channel. The hydrogen generated in the coolant channels would eventually get released either in Fuelling Machine (FM) vault or in the pump room atmosphere depending on the location of the break. Analytical studies carried out so far to estimate the time dependent hydrogen concentration in the accident FM Vault consider the entire vault as a single volume. Tests were, therefore, planned to assess the mixing within the FM vault atmosphere with and without the availability of cooling fan units by releasing a known quantity of helium (instead of hydrogen) at selected locations and monitoring the relative concentration of helium in air at various locations. Test was conducted by releasing about 360 1 helium over a period of to 4 minutes at preselected locations and by measuring the relative concentration (leak rates indicated by helium leak detectors) at various locations in the FM vault. The results of cases with fans operating indicate repeatable and consistent trends of good mixing in the vault. For other cases (non turbulent, still condition) the results are sensitive to various factors including orientation of release. The former set of cases (turbulent. fans operating) are more relevant for postulated accident conditions. (author). 1 tab., 18 figs

Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma

International Nuclear Information System (INIS)

Shigeoka, Manabu; Urakawa, Naoki; Nishio, Mari; Takase, Nobuhisa; Utsunomiya, Soken; Akiyama, Hiroaki; Kakeji, Yoshihiro; Komori, Takahide; Koma, Yu-ichiro; Yokozaki, Hiroshi

2015-01-01

Tumor-associated macrophages (TAMs) are known to be involved in the progression of various human malignancies. We previously demonstrated that CD204 was a useful marker for TAMs contributing to the angiogenesis, progression, and prognosis of human esophageal squamous cell carcinoma (ESCC). We also showed that conditioned media of ESCC cell lines induced CD204 expression in THP-1 human monocytic leukemia cells. Here, we performed a cDNA microarray analysis between THP-1 cells stimulated with TPA (macrophage [MΦ]-like THP-1 cells) treated with and without conditioned medium of ESCC cell line to clarify the molecular characteristics of TAMs in ESCC. From the microarray data, we discovered that Cyr61 was induced in CD204-positive-differentiated THP-1 cells (TAM-like THP-1 cells). In the ESCC microenvironment, not only cancer cells but also TAMs expressed Cyr61. Interestingly, the expression levels of Cyr61 showed a significant positive correlation with the number of CD204-positive macrophages in ESCCs by immunohistochemistry. Recombinant human Cyr61 (rhCyr61) promoted cell migration and induced the expression of CD204 along with the activation of the MEK/ERK pathway in MΦ-like THP-1 cells. Pretreatment with a MEK1/2 inhibitor significantly inhibited not only the Cyr61-mediated migration but also the CD204 expression in the MΦ-like THP-1 cells. These results suggest that Cyr61 may contribute to the expression of CD204 and the promotion of cell migration via the MEK/ERK pathway in TAMs in the ESCC microenvironment

Performance measurement in the context of CREM and FM

NARCIS (Netherlands)

Riratanaphong, C.; van der Voordt, Theo; Sarasoja, AL; Jensen, PA; van der Voordt, DJM; Coenen, C

2012-01-01

Purpose: To discuss trends in organisational performance measurement, to identify and discuss widely used performance criteria and key performance indicators (KPIs) in general and in the fields of Facility Management (FM) and Corporate Real Estate Management (CREM), and to identify how a more

9-Fluorenylmethyl (Fm) Disulfides: Biomimetic Precursors for Persulfides

Energy Technology Data Exchange (ETDEWEB)

Park, Chung-Min; Johnson, Brett A.; Duan, Jicheng; Park, Jeong-Jin; Day, Jacob J.; Gang, David; Qian, Wei-Jun; Xian, Ming

2016-03-04

Protein S-sulfhydration has been recognized as an important post-translational modification that regulates H2S signals. However, the reactivity and biological implications of the products of S-sulfhydration, i.e. persulfides, are still unclear. This is mainly due to the instability of persulfides and difficulty to access these molecules. Under physiological conditions persulfides mainly exist in anionic forms because of their low pKa values. However, current methods do not allow for the direct generation of persulfide anions under biomimetic and non-H2S conditions. Herein we report the development of a functional disulfide, FmSSPy-A (Fm =9-fluorenylmethyl; Py = pyridinyl). This reagent can effectively convert both small molecule and protein thiols (-SH) to form –S-SFm adducts under mild conditions. It allows for a H2S-free and biomimetic protocol to generate highly reactive persulfides (in their anionic forms). We also demonstrated the high nucleophilicity of persulfides toward a number of thiol-blocking reagents. This method holds promise for further understanding the chemical biology of persulfides and S-sulfhydration.

The awareness of novelty for strangely familiar words: a laboratory analogue of the déjà vu experience

OpenAIRE

Urquhart, Josephine A.; O’Connor, Akira R.

2014-01-01

Akira O’Connor is supported by a SINAPSE (Scottish Imaging Network: A Platform for Scientific Excellence) fellowship. Josephine Urquhart was supported by the University of St Andrews URIP Scheme. Déjà vu is a nebulous memory experience defined by a clash between evaluations of familiarity and novelty for the same stimulus. We sought to generate it in the laboratory by pairing a DRM recognition task, which generates erroneous familiarity for critical words, with a monitoring task by which p...

Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

International Nuclear Information System (INIS)

Huai, Lei; Wang, Cuicui; Zhang, Cuiping; Li, Qihui; Chen, Yirui; Jia, Yujiao; Li, Yan; Xing, Haiyan; Tian, Zheng; Rao, Qing; Wang, Min; Wang, Jianxiang

2012-01-01

Highlights: ► Metformin induces differentiation in NB4 and primary APL cells. ► Metformin induces activation of the MEK/ERK signaling pathway in APL cells. ► Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. ► Metformin induces the relocalization and degradation of the PML-RARα fusion protein. ► The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RARα and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

50 CFR 660.392 - Latitude/longitude coordinates defining the 50 fm (91 m) through 75 fm (137 m) depth contours.

Science.gov (United States)

2010-10-01

... contour between the U.S. border with Canada and the U.S. border with Mexico is defined by straight lines...′ W. long. (b) The 50-fm (91-m) depth contour between the U.S. border with Canada and the Swiftsure Bank is defined by straight lines connecting all of the following points in the order stated: (1) 48°30...

Evaluation of BioFM liquid medium for culture of cerebrospinal fluid in tuberculous meningitis to identify Mycobacterium tuberculosis.

Science.gov (United States)

Kashyap, R S; Ramteke, S S; Gaherwar, H M; Deshpande, P S; Purohit, H J; Taori, G M; Daginawala, H

2010-01-01

The present study was designed to evaluate the sensitivity and specificity of liquid culture medium (BioFM broth) for the diagnosis of tuberculous meningitis (TBM) in cerebrospinal fluid (CSF). CSF samples from 200 patients (TBM group = 150 and non-TBM group = 50) were tested for culture of Mycobacterium tuberculosis in BioFM liquid culture medium. Out of 150 TBM cases, 120 were found to be culture positive, indicating a sensitivity of 80% in BioFM broth within 2-3 weeks of inoculation. Positive cultures were also observed for CSF from 32 (64%) out of 50 non-TBM patients in BioFM liquid culture medium within 4 days of sample inoculation. Therefore, according to our study, BioFM broth system yielded 80% sensitivity [95% confidence interval (CI): 67-93%] and 36% specificity (95% CI: 57-98%) for TBM diagnosis. Our results indicate that although BioFM broth allows the detection of positive cultures within a shorter time, it has a high potential for contamination or for the coexistence of M. tuberculosis and non-tuberculous meningitis (NTM). This coexistence may go undetected or potentially lead to erroneous reporting of results.

Evaluation of BioFM liquid medium for culture of cerebrospinal fluid in tuberculous meningitis to identify Mycobacterium tuberculosis

Directory of Open Access Journals (Sweden)

Kashyap R

2010-01-01

Full Text Available The present study was designed to evaluate the sensitivity and specificity of liquid culture medium (BioFM broth for the diagnosis of tuberculous meningitis (TBM in cerebrospinal fluid (CSF. CSF samples from 200 patients (TBM group = 150 and non-TBM group = 50 were tested for culture of Mycobacterium tuberculosis in BioFM liquid culture medium. Out of 150 TBM cases, 120 were found to be culture positive, indicating a sensitivity of 80% in BioFM broth within 2-3 weeks of inoculation. Positive cultures were also observed for CSF from 32 (64% out of 50 non-TBM patients in BioFM liquid culture medium within 4 days of sample inoculation. Therefore, according to our study, BioFM broth system yielded 80% sensitivity [95% confidence interval (CI: 67-93%] and 36% specificity (95% CI: 57-98% for TBM diagnosis. Our results indicate that although BioFM broth allows the detection of positive cultures within a shorter time, it has a high potential for contamination or for the coexistence of M. tuberculosis and non-tuberculous meningitis (NTM. This coexistence may go undetected or potentially lead to erroneous reporting of results.

Adding Value by FM and CREM in Dutch hospitals

NARCIS (Netherlands)

van der Voordt, D.J.M.; Prevosth, J.; van der Zwart, J.

2012-01-01

Purpose: To explore if and how Dutch hospital managers steer on adding value by well-considered Facility Management (FM) and Corporate Real Estate Management (CREM), which values are leading, and how adding value is being translated into concrete interventions. Methodology: In addition to a review

IRIG 106 Chapter 10 Programmers Handbook

Science.gov (United States)

2016-08-16

szDataItem. Specific parsers are called for specific attribute types, indicated by the first letter of the code name. After all TMATS attributes are...EnI106Status I106_CALL_DECL enI106Ch10Close(int iHandle) { // If handles have been init’ed then bail if

Synthesis, Magnetization, and Electrical Transport Properties of Mn3Zn0.9Cu0.1N

Directory of Open Access Journals (Sweden)

Y. Yin

2013-01-01

Full Text Available We synthesized Mn3Zn0.9Cu0.1N by solid state reaction, and magnetic as well as electrical transport properties were investigated. It is found that Mn3Zn0.9Cu0.1N exhibits a first-order antiferromagnetism (AFM to paramagnetic (PM transition with the Néel temperature TN ~163 K, and substitution of Cu for Zn would favor ferromagnetism (FM state and weaken AFM ground state, leading to a convex curvature character of M(T curve. With high external fields 10 kOe–50 kOe, magnetic transition remains a robust AFM-PM feature while FM phase is completely suppressed. Thermal hysteresis of M(T under 500 Oe is also suppressed when the magnetic field exceeds 10 kOe. Mn3Zn0.9Cu0.1N exhibits a good metallic behavior except for a slope change around TN, which is closely related to AFM-PM magnetic transition. Compared with the first differential of resistivity with respect to temperature for (dρ/dTMn3ZnN in transition temperature range, the absolute value of (dρ/dTMn3Zn0.9Cu0.1N is much lower which is close to zero.

SIARAN RADIO CITRA 99.4 FM SEBAGAI MEDIA PELESTARIAN TEMBANG SUNDA BAGI SISWA SEKOLAH DASAR

Directory of Open Access Journals (Sweden)

Maylan Sofian

2015-01-01

Full Text Available This research inspects about preservation of traditional art through tembang sunda cianjuran on Citra radio 99, 4 FM Sumedang. The problems inspected in this research as follows, First, how does the preservation of tembang sunda cianjuran present on the Citra Radio 99, 4 FM broadcast program? Second, how does the contribution of the electronic media Citra radio broadcast programme for tembang sunda cianjuran and the artist in Sumedang? In order to get the answer to the problems, the qualitative research done, that is the content analysis. Content analysis is one of the research methods to produce objective and systematic description. The result from this research shows that Citra Radio 99, 4 FM Sumedang broadcast program can be a system support to tembang sunda cianjuran. This broadcast can stimulate the listener memory about tembang sunda cianjuran that the listener ever heard or studied when they are still young. The contribution of the radio can be felt by the artist, especially to the popularity of the music player and the singer of Citra radio 99,4 FM. Keywords: tembang, preservation, media.

Alpha-gamma decay studies of 253No and its daughter products 253Md, 249Fm

International Nuclear Information System (INIS)

Hessberger, F.P.; Antalic, S.; Kalaninova, Z.; Saro, S.; Venhart, M.; Ackermann, D.; Heinz, S.; Kindler, B.; Kojouharov, I.; Kuusiniemi, P.; Lommel, B.; Mann, R.; Sulignano, B.; Hofmann, S.; Streicher, B.; Leino, M.; Nishio, K.

2012-01-01

Nuclear structure and decay of the isotope 253 No and its decay products 249 Fm and 253 Md were investigated by means of α - γ spectroscopy. Besides the established strong γ transitions from the 9/2 - [734] Nilsson level in 249 Fm, populated predominantly by the α decay of 253 No, into the ground-state (gs) rotational band, a couple of weaker γ lines (58.3, 129.2, 209.3 and 669.5keV) were observed and placed into the 249 Fm level scheme. The transition from the 7/2 - level in 249 Es, populated by the α decay of 253 Md, into the 9/2 + member of the gs rotational band, so far established for other odd-mass Es isotopes, was observed clearly. GEANT4 simulations were performed to investigate the influence of energy summing between α particles and conversion electrons (CE) on the shape of the α spectra at different implantation energies, leading to evidence for a weak α decay branch of 253 No into the gs of 249 Fm or the ground-state rotational band, respectively. (orig.)

Evaluating the capabilities and uncertainties of droplet measurements for the fog droplet spectrometer (FM-100

Directory of Open Access Journals (Sweden)