WorldWideScience

Sample records for unique studies met

  1. Genomics of a Metamorphic Timing QTL: met1 Maps to a Unique Genomic Position and Regulates Morph and Species-Specific Patterns of Brain Transcription

    Science.gov (United States)

    Page, Robert B.; Boley, Meredith A.; Kump, David K.; Voss, Stephen R.

    2013-01-01

    Very little is known about genetic factors that regulate life history transitions during ontogeny. Closely related tiger salamanders (Ambystoma species complex) show extreme variation in metamorphic timing, with some species foregoing metamorphosis altogether, an adaptive trait called paedomorphosis. Previous studies identified a major effect quantitative trait locus (met1) for metamorphic timing and expression of paedomorphosis in hybrid crosses between the biphasic Eastern tiger salamander (Ambystoma tigrinum tigrinum) and the paedomorphic Mexican axolotl (Ambystoma mexicanum). We used existing hybrid mapping panels and a newly created hybrid cross to map the met1 genomic region and determine the effect of met1 on larval growth, metamorphic timing, and gene expression in the brain. We show that met1 maps to the position of a urodele-specific chromosome rearrangement on linkage group 2 that uniquely brought functionally associated genes into linkage. Furthermore, we found that more than 200 genes were differentially expressed during larval development as a function of met1 genotype. This list of differentially expressed genes is enriched for proteins that function in the mitochondria, providing evidence of a link between met1, thyroid hormone signaling, and mitochondrial energetics associated with metamorphosis. Finally, we found that met1 significantly affected metamorphic timing in hybrids, but not early larval growth rate. Collectively, our results show that met1 regulates species and morph-specific patterns of brain transcription and life history variation. PMID:23946331

  2. Extraboard performance : TriMet case study.

    Science.gov (United States)

    2012-02-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    Orhan, Dr Ö Emre; Ahmet, Gökhan

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-12-01

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

  9. [Uniqueness seeking behavior as a self-verification: an alternative approach to the study of uniqueness].

    Science.gov (United States)

    Yamaoka, S

    1995-06-01

    Uniqueness theory explains that extremely high perceived similarity between self and others evokes negative emotional reactions and causes uniqueness seeking behavior. However, the theory conceptualizes similarity so ambiguously that it appears to suffer from low predictive validity. The purpose of the current article is to propose an alternative explanation of uniqueness seeking behavior. It posits that perceived uniqueness deprivation is a threat to self-concepts, and therefore causes self-verification behavior. Two levels of self verification are conceived: one based on personal categorization and the other on social categorization. The present approach regards uniqueness seeking behavior as the personal-level self verification. To test these propositions, a 2 (very high or moderate similarity information) x 2 (with or without outgroup information) x 2 (high or low need for uniqueness) between-subject factorial-design experiment was conducted with 95 university students. Results supported the self-verification approach, and were discussed in terms of effects of uniqueness deprivation, levels of self-categorization, and individual differences in need for uniqueness.

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

    OpenAIRE

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Science.gov (United States)

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

    2010-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Márcio Gerhardt Soeiro-de-Souza

    2014-03-01

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

  14. Instructional Coding System for Mathematics Program of Studies. MET, A Title IV-C Project.

    Science.gov (United States)

    Fairfax County Public Schools, VA. Dept. of Instructional Services.

    This document is part of the Management for Effective Teaching (MET) support kit, a pilot project designed by the Fairfax County (Virginia) Public Schools to assist elementary school teachers in planning, managing, and implementing the county's Program of Studies (POS). This document provides an alpha-numeric coding system to be used in…

  15. IDGenerator: unique identifier generator for epidemiologic or clinical studies

    Directory of Open Access Journals (Sweden)

    Matthias Olden

    2016-09-01

    Full Text Available Abstract Background Creating study identifiers and assigning them to study participants is an important feature in epidemiologic studies, ensuring the consistency and privacy of the study data. The numbering system for identifiers needs to be random within certain number constraints, to carry extensions coding for organizational information, or to contain multiple layers of numbers per participant to diversify data access. Available software can generate globally-unique identifiers, but identifier-creating tools meeting the special needs of epidemiological studies are lacking. We have thus set out to develop a software program to generate IDs for epidemiological or clinical studies. Results Our software IDGenerator creates unique identifiers that not only carry a random identifier for a study participant, but also support the creation of structured IDs, where organizational information is coded into the ID directly. This may include study center (for multicenter-studies, study track (for studies with diversified study programs, or study visit (baseline, follow-up, regularly repeated visits. Our software can be used to add a check digit to the ID to minimize data entry errors. It facilitates the generation of IDs in batches and the creation of layered IDs (personal data ID, study data ID, temporary ID, external data ID to ensure a high standard of data privacy. The software is supported by a user-friendly graphic interface that enables the generation of IDs in both standard text and barcode 128B format. Conclusion Our software IDGenerator can create identifiers meeting the specific needs for epidemiologic or clinical studies to facilitate study organization and data privacy. IDGenerator is freeware under the GNU General Public License version 3; a Windows port and the source code can be downloaded at the Open Science Framework website: https://osf.io/urs2g/ .

  16. Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Shih-Jen Tsai

    2018-05-01

    Full Text Available Neurotrophins have been implicated in the pathophysiology of many neuropsychiatric diseases. Brain-derived neurotrophic factor (BDNF is the most abundant and widely distributed neurotrophin in the brain. Its Val66Met polymorphism (refSNP Cluster Report: rs6265 is a common and functional single-nucleotide polymorphism (SNP affecting the activity-dependent release of BDNF. BDNF Val66Met transgenic mice have been generated, which may provide further insight into the functional impact of this polymorphism in the brain. Considering the important role of BDNF in brain function, more than 1,100 genetic studies have investigated this polymorphism in the past 15 years. Although these studies have reported some encouraging positive findings initially, most of the findings cannot be replicated in following studies. These inconsistencies in BDNF Val66Met genetic studies may be attributed to many factors such as age, sex, environmental factors, ethnicity, genetic model used for analysis, and gene–gene interaction, which are discussed in this review. We also discuss the results of recent studies that have reported the novel functions of this polymorphism. Because many BDNF polymorphisms and non-genetic factors have been implicated in the complex traits of neuropsychiatric diseases, the conventional genetic association-based method is limited to address these complex interactions. Future studies should apply data mining and machine learning techniques to determine the genetic role of BDNF in neuropsychiatric diseases.

  17. Discovery of imidazopyridine derivatives as novel c-Met kinase inhibitors: Synthesis, SAR study, and biological activity.

    Science.gov (United States)

    Yang, Yifei; Zhang, Yuan; Yang, LingYun; Zhao, Leilei; Si, Lianghui; Zhang, Huibin; Liu, Qingsong; Zhou, Jinpei

    2017-02-01

    Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar potency against c-Met in both biochemical enzymatic screens and cellular pharmacology studies. Especially, compound 7g exhibited the most inhibitory activity against c-Met with IC 50 of 53.4nM and 253nM in enzymatic and cellular level, respectively. Following that, the compound 7g was docked into the protein of c-Met and the structure-activity relationship was analyzed in detail. These findings indicated that the novel imidazopyridine derivative compound 7g was a potential c-Met inhibitor deserving further investigation for cancer treatment. Copyright © 2016. Published by Elsevier Inc.

  18. The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays.

    Science.gov (United States)

    Sotoudeh, Kambiz; Hashemi, Forough; Madjd, Zahra; Sadeghipour, Alireza; Molanaei, Saadat; Kalantary, Elham

    2012-05-28

    c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008-2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044). The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were observed. c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429.

  19. Unique Opportunities: Influence of Study Abroad on Black Students

    Science.gov (United States)

    Lee, Jasmine; Green, Qiana

    2016-01-01

    This research adds to the dearth of literature examining the experiences of Black students who study abroad. Additionally, this project extends the literature on the influence of diasporic travel on US Black undergraduate students. Because study abroad has positive benefits for student learning and development (Brux & Fry, 2010), targeted…

  20. Climate-sensitive urban design through Envi-Met simulation: case study in Kemayoran, Jakarta

    Science.gov (United States)

    Kusumastuty, K. D.; Poerbo, H. W.; Koerniawan, M. D.

    2018-03-01

    Indonesia as a tropical country which the character of its climate are hot and humid, the outdoor activity applications are often disrupted due to discomfort in thermal conditions. Massive construction of skyscrapers in urban areas are caused by the increase of human population leads to reduced green and infiltration areas that impact to environmental imbalances and triggering microclimate changes with rising air temperatures on the surface. The area that significantly experiences the rise of temperature in the Central Business District (CBD), which has need an analysis to create thermal comfort conditions to improve the ease of outdoor activities by an approach. This study aims to design the Kemayoran CBD through Climate Sensitive Urban Design especially in hot and humid tropical climate area and analyze thermal comfort level and optimal air conditioning in the outdoor area. This research used a quantitative method by generating the design using Climate Sensitive Urban Design principle through Envi-met 4.1 simulation program to find out the value of PMV, air temperature, wind speed and relative humidity conditions. The design area considers the configuration of buildings such as the distance between buildings, the average height, the orientation of the building, and the width of the road.

  1. Considering dance practices as unique cases in interdisciplinary research studies

    DEFF Research Database (Denmark)

    Ravn, Susanne

    ” (Flyvbjerg, 2011) in the domain of qualitative research. Such designs are of specific relevance for research projects exploring body, movement and sensing in general. Thereafter I present the results of some of my resent studies. These studies are based in a critical constructive interdisciplinary......The aim of this paper is to present interdisciplinary considerations of relevance to strengthen dance research in relation to – and in cooperation with - other academic disciplines. I firstly describe how dance practices can be handled as “extreme cases” and cases with “maximal variations...

  2. Lipschitz Continuity The study of existence and uniqueness

    Indian Academy of Sciences (India)

    Department of Applied. Mathematics. University ... ential equation (DE) allows us to study all kinds of evolutionary processes with the ... This is a well known example of a non linear ODE. 492 ..... linear DEs is still a very active area of research.

  3. The unique experience of adults with multimorbidity: a qualitative study

    Directory of Open Access Journals (Sweden)

    Cynthia Duguay

    2014-05-01

    Full Text Available Background: Findings from several countries indicate that the prevalence of multimorbidity is very high among clients of primary healthcare. A deeper understanding of patients’ experiences from their own perspective can greatly enrich any intervention to help them live as well as possible with multimorbidity. Objective: To describe the fundamental structure of adults’ experience with multimorbidity. Design: A phenomenological study was undertaken to describe the experiences of 11 adults with multimorbidity. These adults participated in two semi-structured interviews, the content of which was rigorously analyzed. Results: At the core of the study participants’ multimorbidity experience are the impression of aging prematurely, difficulties with self-care management, and issues with access to the healthcare system, which contribute to the problem’s complexity. Despite these issues, participants with multimorbidity report attempting to take control of their situation and adjusting to daily living. Conclusions: The description of this experience, through the systemic vision of participants, provides a better understanding of the realities experienced by people with multimorbidity.

  4. Identification of Phytochemicals Targeting c-Met Kinase Domain using Consensus Docking and Molecular Dynamics Simulation Studies.

    Science.gov (United States)

    Aliebrahimi, Shima; Montasser Kouhsari, Shideh; Ostad, Seyed Nasser; Arab, Seyed Shahriar; Karami, Leila

    2018-06-01

    c-Met receptor tyrosine kinase is a proto-oncogene whose aberrant activation is attributed to a lower rate of survival in most cancers. Natural product-derived inhibitors known as "fourth generation inhibitors" constitute more than 60% of anticancer drugs. Furthermore, consensus docking approach has recently been introduced to augment docking accuracy and reduce false positives during a virtual screening. In order to obtain novel small-molecule Met inhibitors, consensus docking approach was performed using Autodock Vina and Autodock 4.2 to virtual screen Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database against active and inactive conformation of c-Met kinase domain structure. Two hit molecules that were in line with drug-likeness criteria, desired docking score, and binding pose were subjected to molecular dynamics simulations to elucidate intermolecular contacts in protein-ligand complexes. Analysis of molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area studies showed that ZINC08234189 is a plausible inhibitor for the active state of c-Met, whereas ZINC03871891 may be more effective toward active c-Met kinase domain compared to the inactive form due to higher binding energy. Our analysis showed that both the hit molecules formed hydrogen bonds with key residues of the hinge region (P1158, M1160) in the active form, which is a hallmark of kinase domain inhibitors. Considering the pivotal role of HGF/c-Met signaling in carcinogenesis, our results propose ZINC08234189 and ZINC03871891 as the therapeutic options to surmount Met-dependent cancers.

  5. Intracardiale chirurgie met behulp van een cirrestor : een experimentele en klinische studie

    NARCIS (Netherlands)

    Homan van der Heide, Jan Nico

    1960-01-01

    SAMENVATTING De intracardiale chirurgie is op grote schaal mogelijk geworden dank zij het feit, dat afwijkingen in bloedvrije hartholten met direct zicht hersteld kunnen worden. Voordat de operatieve correctie plaats vindt, moet de patient in een bepaalde, voor de operatie geschikte conditie

  6. BDNF-Val66Met-Polymorphism Impact on Cortical Plasticity in Schizophrenia Patients: A Proof-of-Concept Study

    Science.gov (United States)

    Nitsche, Michael A.; Wobrock, Thomas; Bunse, Tilmann; Rein, Bettina; Herrmann, Maximiliane; Schmitt, Andrea; Nieratschker, Vanessa; Witt, Stephanie H.; Rietschel, Marcella; Falkai, Peter; Hasan, Alkomiet

    2015-01-01

    Background: Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients. Methods: Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied. Results: Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS. Conclusions: These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory

  7. The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

    Directory of Open Access Journals (Sweden)

    Sotoudeh Kambiz

    2012-05-01

    Full Text Available Abstract Background c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. Methods In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008–2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. Results Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124 of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04, deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014, neural invasion (P = 0.002 and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044. The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065 and vascular invasion (P = 0.078 were observed. Conclusions c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429

  8. The Study of Thermal Comfort in Transforming Residential Area in Bandung using ENVI-met Software. Case Study: Progo Street

    Science.gov (United States)

    Aziz Soelaiman, Tubagus M.; Soedarsono, Woerjantari K.; Donny Koerniawan, M.

    2018-05-01

    Bandung has a high potential in attracting tourists. This potential impact on building function near tourist attraction that can transform residential uses into commercial uses. Progo Street and its surrounding area used as the case study, which is close to Gedung Sate and Riau Street as tourist destinations in Bandung. Moreover, this transformation is also reinforced by the spatial planning policies in Bandung, known as RTRW and RDTR, said that this area will be fully non-residential area. This condition in some cases could affect thermal comfort. This paper provides the changes of thermal comfort phenomenon that occurs using EnviMet software. The study compares Predicted Mean Voted (PMV) as thermal comfort indicator between existing and Bandung detailed spatial plan (RDTR) condition. The result shows that the PMV value of current condition is higher than future planning, nonetheless the planned area will be changed into higher non-residential buildings and less greeneries. Some environmental factors that are used to calculate PMV such as air temperature, mean radiant temperature, humidity, and wind speed are also examined to find out what makes the plan more comfortable than the existing. Simulations using ENVI-met software could be considered in making more objective planning policy in the future.

  9. Gender-specific differences in the incidence of microalbuminuria in metabolic syndrome patients after treatment with fimasartan: The K-MetS study.

    Science.gov (United States)

    Park, Jeong Bae; Kim, Su-A; Sung, Ki-Chul; Kim, Jang Young

    2017-01-01

    The effect of resolving metabolic syndrome on target organ damage in hypertensive patients is not well described. We evaluated whether treating metabolic syndrome (MetS) with an angiotensin receptor blocker subsequently reduced microalbuminuria in the K-MetS cohort. Among 10,601 total metabolic syndrome patients, 3,250 (52.2% male, 56.2±10.0 years) with sufficient data on five specific metabolic components were included in this study. Patients were divided into four groups based on MetS status at baseline and 3 months. All patients received an angiotensin receptor blocker, fimasartan, for these 3 months; thereafter, treatment was modified at the discretion of each patient's physician. Microalbuminuria and the albumin/creatine ratio were evaluated as a proxy of organ damage. Blood pressure and waist circumference decreased from baseline to 3 months and 1 year. The average albumin/creatinine ratio significantly improved during the first three months of the study from 36.0±147.4 to 21.0±74.9 mg/g (pTreatment of hypertensive patients for one year with the angiotensin receptor blocker fimasartan significantly reduced the albumin/creatine ratio, irrespective of whether the patient had MetS; however, the albumin/creatinine ratio was significantly higher in patents with persistent or newly developed MetS compared to patients without MetS. Additionally, these findings were more prominent in women than in men.

  10. Catechol-O-methyltransferase Val 108/158 Met polymorphism and breast cancer risk: a case control study in Syria.

    Science.gov (United States)

    Lajin, Bassam; Hamzeh, Abdul Rezzak; Ghabreau, Lina; Mohamed, Ali; Al Moustafa, Ala-Eddin; Alachkar, Amal

    2013-01-01

    Catechol-O-methyltransferase (COMT) inactivates catechol estrogens by methylation and thus may play a protective role against mutations induced by estrogen metabolites. In this study we investigated the relationship between the Vall58Met polymorphism in the COMT gene and breast cancer risk in a population-based case control study in Syria. We examined 135 breast cancer patients and 107 healthy controls in North Syria to determine the association between the functional genetic Val158Met polymorphism in the COMT gene and female breast cancer risk. There was no significant overall association between the COMT genotype and individual susceptibility to breast cancer. Our data suggest that there may be no overall association between the COMT genotype and breast cancer.

  11. Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study.

    Science.gov (United States)

    Deuschl, Cornelius; Moenninghoff, Christoph; Goericke, Sophia; Kirchner, Julian; Köppen, Susanne; Binse, Ina; Poeppel, Thorsten D; Quick, Harald H; Forsting, Michael; Umutlu, Lale; Herrmann, Ken; Hense, Joerg; Schlamann, Marc

    2017-08-01

    The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM.

  12. Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Deuschl, Cornelius [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Duisburg (Germany); Moenninghoff, Christoph; Goericke, Sophia; Forsting, Michael; Umutlu, Lale [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Kirchner, Julian [University Hospital Duesseldorf, Institute of Diagnostic and Interventional Radiology, Duesseldorf (Germany); Koeppen, Susanne [University Hospital Essen, Department of Neurology, Essen (Germany); Binse, Ina; Poeppel, Thorsten D.; Herrmann, Ken [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Quick, Harald H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Duisburg (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); Hense, Joerg [University Hospital Essen, Department of Medical Oncology, West German Cancer Center, Essen (Germany); Schlamann, Marc [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Hospital Giessen, Department of Neuroradiology, Essen (Germany)

    2017-08-15

    The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM. (orig.)

  13. X-ray diffraction studies of 145MeV proton-irradiated AlBeMet 162

    Directory of Open Access Journals (Sweden)

    Mohamed Elbakhshwan

    2016-08-01

    Full Text Available AlBeMet 162 (Materion Co., formerly Brush Wellman has been irradiated with 145MeV protons up to 1.2×1020cm−2 fluence, with irradiation temperatures in the range of 100–220°C. Macroscopic post-irradiation evaluation on the evolution of mechanical and thermal properties was integrated with a comprehensive X-ray- diffraction study using high-energy monochromatic and polychromatic X-ray beams, which offered a microscopic view of the irradiation damage effects on AlBeMet. The study confirmed the stability of the metal–matrix composite, its resistance to proton damage, and the continuing separation of the two distinct phases, fcc aluminum and hcp beryllium, following irradiation. Furthermore, based on the absence of inter-planar distance change during proton irradiation, it was confirmed that the stacking faults and clusters on the Al (111 planes are stable, and thus can migrate from the cascade region and be absorbed at various sinks. XRD analysis of the unirradiated AlBeMet 162 showed clear change in the texture of the fcc phase with orientation especially in the Al (111 reflection which exhibits a “non-perfect” six-fold symmetry, implying lack of isotropy in the composite.

  14. COMT Val158Met, but not BDNF Val66Met, is associated with white matter abnormalities of the temporal lobe in patients with first-episode, treatment-naïve major depressive disorder: a diffusion tensor imaging study

    Directory of Open Access Journals (Sweden)

    Hayashi K

    2014-06-01

    Full Text Available Kenji Hayashi,1 Reiji Yoshimura,1 Shingo Kakeda,2 Taro Kishi,3 Osamu Abe,4 Wakako Umene-Nakano,1 Asuka Katsuki,1 Hikaru Hori,1 Atsuko Ikenouchi-Sugita,1 Keita Watanabe,2 Satoru Ide,2 Issei Ueda,2 Junji Moriya,2 Nakao Iwata,3 Yukunori Korogi,2 Marek Kubicki,5 Jun Nakamura1 1Department of Psychiatry, 2Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Psychiatry, Fujita Health University, Toyoake, Japan; 4Department of Radiology, Nihon University School of Medicine, Tokyo, Japan; 5Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Abstract: We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF gene, and white matter changes in patients with major depressive disorder (MDD and healthy subjects using diffusion tensor imaging (DTI. We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years. Using DTI analysis with a tract-based spatial statistics (TBSS approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects. In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P<0.05. No correlations in fractional anisotropy, axial diffusivity, or radial diffusivity were observed between the MDD patients and the controls, either among those with the BDNF Val/Val genotype or among the BDNF Met-carriers. These results suggest an association

  15. Survey of English Teaching and Learning Process in Maritme Education and Training in Indonesia: A Case Study in Private MET in Indonesia

    Science.gov (United States)

    Dirgayasa, I Wy.

    2014-01-01

    This paper intends to evaluate the process of teaching and learning of Maritime English in private Maritime Education and Training (MET) in Indonesia. This study was conducted in three private MET such as Maritime Academy Indonesia Medan (AMI-Medan), Maritime Academy Belawan (AMB-Belawan,), and Maritime Academy Sapta Samudra Padang (AMSSP-Padang).…

  16. Social marketing's unique contribution to mental health stigma reduction and HIV testing: two case studies.

    Science.gov (United States)

    Thackeray, Rosemary; Keller, Heidi; Heilbronner, Jennifer Messenger; Dellinger, Laura K Lee

    2011-03-01

    Since its inception in 2005, articles in Health Promotion Practice's social marketing department have focused on describing social marketing's unique contributions and the application of each to the practice of health promotion. This article provides a brief review of six unique features (marketing mix, consumer orientation, segmentation, exchange, competition, and continuous monitoring) and then presents two case studies-one on reducing stigma related to mental health and the other a large-scale campaign focused on increasing HIV testing among African American youth. The two successful case studies show that social marketing principles can be applied to a wide variety of topics among various population groups.

  17. COMT Val158Met genotype is associated with reward learning: A replication study and meta-analysis

    Science.gov (United States)

    Corral-Frías, Nadia S.; Pizzagalli, Diego A.; Carré, Justin; Michalski, Lindsay J; Nikolova, Yuliya S.; Perlis, Roy H.; Fagerness, Jesen; Lee, Mary R.; Conley, Emily Drabant; Lancaster, Thomas M.; Haddad, Stephen; Wolf, Aaron; Smoller, Jordan W.; Hariri, Ahmad R.; Bogdan, Ryan

    2016-01-01

    Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val158Met) has been linked to reward learning where homozygosity for the Met allele (associated with heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across 3 separate samples that were combined for analyses (age: 21.80 ± 3.95; n=392; 268 female; European-American, n=208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European-American participants (β=0.20, t= 2.75, p< 0.01; ΔR2= 0.04). Moreover, a meta-analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI −0.11 to −0.03; z=3.2; p<0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction. PMID:27138112

  18. Executive control in schizophrenia: a preliminary study on the moderating role of COMT Val158Met for comorbid alcohol and substance use disorders.

    Science.gov (United States)

    Carrà, Giuseppe; Nicolini, Gabriella; Crocamo, Cristina; Lax, Annamaria; Amidani, Francesca; Bartoli, Francesco; Castellano, Filippo; Chiorazzi, Alessia; Gamba, Giulia; Papagno, Costanza; Clerici, Massimo

    2017-07-01

    A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val158Met) appears to influence cognition in people with alcohol/substance use disorders (AUD/SUD) and in those with psychosis. To explore the potential moderating effect of these factors, a cross-sectional study was conducted, randomly recruiting subjects with DSM-IV diagnosis of schizophrenia. AUD/SUD was rigorously assessed, as well as COMT Val158Met polymorphism. Executive control functioning was measured using the Intra-Extra Dimensional Set Shift (IED). The effect of a possible interaction between comorbid AUD/SUD and COMT Val158Met polymorphism on IED scores was explored. Subjects with schizophrenia, comorbid AUD/SUD, and MetMet carriers for SNP rs4680 of the COMT gene showed worse performance on IED completed stages scores, as compared with individuals with ValVal genotype. However, among subjects without AUD/SUD, those with the MetMet variant performed better than people carrying ValVal genotype. This study is the first to date examining the impact of COMT on cognition in a highly representative sample of people with schizophrenia and comorbid AUD/SUD. Differential moderating effects of COMT Val/Met genotype variations may similarly influence executive functions in people with schizophrenia and comorbid AUD/SUD.

  19. Logic without unique readability - a study of semantic and syntactic ambiguity

    DEFF Research Database (Denmark)

    Bentzen, Martin Mose

    One of the main reasons for introducing a formal language is to remove ambiguity, the possibility of assigning several meanings to a linguistic expression. Typically, this is achieved through ensuring unique readability of formulas by using brackets (or another convention, such as Polish notation...... not hold true universally. Whereas e.g. scope ambiguities in natural languages have been studied extensively, ambiguous formal languages have not been the focus of in depth research. Here, we lift the assumption of unique readability by omitting the brackets from propositional logic, making it possible...... to formally distinguish between syntactic and semantic ambiguity. A valuation then amounts to a semantic disambiguation, and rather than a unique valuation (truth value), there is a set of valuations corresponding to ways a formula could have been constructed. We show what happens to familiar concepts...

  20. Phase II and Biomarker Study of the Dual MET/VEGFR2 Inhibitor Foretinib in Patients With Papillary Renal Cell Carcinoma

    Science.gov (United States)

    Choueiri, Toni K.; Vaishampayan, Ulka; Rosenberg, Jonathan E.; Logan, Theodore F.; Harzstark, Andrea L.; Bukowski, Ronald M.; Rini, Brian I.; Srinivas, Sandy; Stein, Mark N.; Adams, Laurel M.; Ottesen, Lone H.; Laubscher, Kevin H.; Sherman, Laurie; McDermott, David F.; Haas, Naomi B.; Flaherty, Keith T.; Ross, Robert; Eisenberg, Peter; Meltzer, Paul S.; Merino, Maria J.; Bottaro, Donald P.; Linehan, W. Marston; Srinivasan, Ramaprasad

    2013-01-01

    Purpose Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors. Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). We aimed to evaluate the efficacy and safety of foretinib in patients with PRCC. Patients and Methods Patients were enrolled onto the study in two cohorts with different dosing schedules of foretinib: cohort A, 240 mg once per day on days 1 through 5 every 14 days (intermittent arm); cohort B, 80 mg daily (daily dosing arm). Patients were stratified on the basis of MET pathway activation (germline or somatic MET mutation, MET [7q31] amplification, or gain of chromosome 7). The primary end point was overall response rate (ORR). Results Overall, 74 patients were enrolled, with 37 in each dosing cohort. ORR by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was 13.5%, median progression-free survival was 9.3 months, and median overall survival was not reached. The presence of a germline MET mutation was highly predictive of a response (five of 10 v five of 57 patients with and without germline MET mutations, respectively). The most frequent adverse events of any grade associated with foretinib were fatigue, hypertension, gastrointestinal toxicities, and nonfatal pulmonary emboli. Conclusion Foretinib demonstrated activity in patients with advanced PRCC with a manageable toxicity profile and a high response rate in patients with germline MET mutations. PMID:23213094

  1. The Munich MIDY Pig Biobank – A unique resource for studying organ crosstalk in diabetes

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    Andreas Blutke

    2017-08-01

    Conclusions: The broad spectrum of well-defined biosamples in the Munich MIDY Pig Biobank that will be available to the scientific community provides a unique resource for systematic studies of organ crosstalk in diabetes in a multi-organ, multi-omics dimension.

  2. Unique associations among emotion dysregulation dimensions and aggressive tendencies : A multi-site study

    NARCIS (Netherlands)

    Velotti, Patrizia; Casselman, Robert B.; Garofalo, C.; McKenzie, Melissa D.

    2017-01-01

    While problems with emotion regulation (ER) have long been associated with internalizing symptoms, only recently has an ER framework been applied to the study of aggression. Therefore, little is known about the unique and independent associations between specific domains of the ER construct and

  3. COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of 'switching on' hallucinations in the flow of daily life.

    Science.gov (United States)

    Henquet, C; Rosa, A; Delespaul, P; Papiol, S; Fananás, L; van Os, J; Myin-Germeys, I

    2009-02-01

    A functional polymorphism in the catechol-o-methyltransferase gene (COMT Val(158)Met) may moderate the psychosis-inducing effects of cannabis. In order to extend this finding to dynamic effects in the flow of daily life, a momentary assessment study of psychotic symptoms in response to cannabis use was conducted. The experience sampling technique was used to collect data on cannabis use and occurrence of symptoms in daily life in patients with a psychotic disorder (n = 31) and healthy controls (n = 25). Carriers of the COMT Val(158)Met Val allele, but not subjects with the Met/Met genotype, showed an increase in hallucinations after cannabis exposure, conditional on prior evidence of psychometric psychosis liability. The findings confirm that in people with psychometric evidence of psychosis liability, COMT Val(158)Met genotype moderates the association between cannabis and psychotic phenomena in the flow of daily life.

  4. Lip prints- A study of its uniqueness among students of MediCiti Medical College.

    Science.gov (United States)

    Alzapur, Archana; Nagothu, Rajani S; Nalluri, Hima B

    2017-01-01

    "Cheiloscopy" is a technique that deals with lip prints. The pattern of fine creases on the lips are unique to the individual. They are similar to finger prints and useful in crime investigation. To study the uniqueness, prevalence, and gender significance of lip print patterns in human subjects. The study was conducted on 100 randomly selected male and female undergraduate medical students. The lip print of each subject was obtained and its pattern was analyzed according to Suzuki and Tsuchihashi classification. The study showed that Type I lip pattern was the commonest. Our study has added to confirmation of the distinctiveness of cheiloscopy, which can be used as an additional tool for identification. Studies on lip prints being very scanty, our findings add significantly to the meager literature on this subject. Further in-depth studies to establish prevalence of patterns in lip prints will certainly help as useful evidence in forensic investigations.

  5. Met expectations and the wellbeing of diaspora immigrants: a longitudinal study.

    Science.gov (United States)

    Mähönen, Tuuli Anna; Leinonen, Elina; Jasinskaja-Lahti, Inga

    2013-01-01

    Previous research has pointed to the importance of expectations for the adaptation of immigrants. However, most studies have been methodologically retrospective with only limited possibilities to show the optimal relationship between migrants' expectations and actual acculturation experiences for their wellbeing and other aspects of psychological adaptation. Moreover, previous research has been conducted mostly among sojourners and students. This longitudinal study focused on the relationship between premigration expectations and postmigration experiences of diaspora immigrants from Russia to Finland (N = 153). We examined how the fulfillment of premigration expectations in social (i.e., family relations, friendships, and free time) and economic (i.e., occupational position, working conditions, and economic and career situation) domains affects immigrants' wellbeing (i.e., satisfaction with life and general mood) after migration. Three alternative models of expectation confirmation (i.e., disconfirmation model, ideal point model, and the importance of experiences only) derived from previous organizational psychological research were tested with polynomial regression and response surface analysis. In the economic domain, immigrants' expectations, experiences, and their interrelationship did not affect wellbeing in the postmigration stage. However, in the social domain, the more expectations were exceeded by actual experiences, the better were life satisfaction and the general mood of immigrants. The results underline the importance of social relationships and the context-dependent nature of immigrants' wellbeing. Interventions in the preacculturation stage should create positive but realistic expectations for diaspora immigrants and other groups of voluntary (re)migrants. Furthermore, policies concerning the postmigration stage should facilitate the fulfillment of these expectations and support the social adaptation of immigrants.

  6. YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study.

    Science.gov (United States)

    Senetta, Rebecca; Duregon, Eleonora; Sonetto, Cristina; Spadi, Rossella; Mistrangelo, Massimiliano; Racca, Patrizia; Chiusa, Luigi; Munoz, Fernando H; Ricardi, Umberto; Arezzo, Alberto; Cassenti, Adele; Castellano, Isabella; Papotti, Mauro; Morino, Mario; Risio, Mauro; Cassoni, Paola

    2015-01-01

    Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, prectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

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

    Directory of Open Access Journals (Sweden)

    Skorpen Frank

    2007-06-01

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

  8. Gratitude uniquely predicts lower depression in chronic illness populations: A longitudinal study of inflammatory bowel disease and arthritis.

    Science.gov (United States)

    Sirois, Fuschia M; Wood, Alex M

    2017-02-01

    Although gratitude has been identified as a key clinically relevant trait for improving well-being, it is understudied within medical populations. The current study addressed this gap and extended previous and limited cross-sectional research by examining the longitudinal associations of gratitude to depression in 2 chronic illness samples, arthritis and inflammatory bowel disease (IBD). Two chronic illness samples, arthritis (N = 423) and IBD (N = 427), completed online surveys at Time 1 (T1). One hundred sixty-three people with arthritis and 144 people with IBD completed the 6-month follow-up survey (T2). Depression, gratitude, illness cognitions, perceived stress, social support, and disease-related variables were assessed at T1 and T2. At T2, 57.2% of the arthritis sample and 53.4% of the IBD sample met the cut off scores for significant depression. T1 gratitude was negatively associated with depressive symptoms at T1 and T2 in both samples (rs from -.43 to -.50). Regression analyses revealed that T1 gratitude remained a significant and unique predictor of lower T2 depression after controlling for T1 depression, relevant demographic variables, illness cognitions, changes in illness-relevant variables, and another positive psychological construct, thriving, in both samples. As the first investigation of the longitudinal associations of gratitude to psychological well-being in the context of chronic illness, the current study provides important evidence for the relevance of gratitude for health-related clinical populations. Further intervention-based research is warranted to more fully understand the potential benefits of gratitude for adjustment to chronic illness. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  9. Metallurgical Laboratory (MetLab) Treatability Study: An Analysis of Passive Soil Vapor Extraction Wells (PSVE) FY1999 Update; ANNUAL

    International Nuclear Information System (INIS)

    Riha, B.D.

    1999-01-01

    The results to date on the treatability study of the PSVE system at the MetLab of the Savannah River Site (SRS) indicate the technology is performing well. Well concentrations are decreasing and contour maps of the vadose zone soil gas plume show a decrease in the extent of the plume. In the 18 months of operation approximately 200 pounds of chlorinated organic contaminants have been removed by natural barometric pumping of wells fitted with BaroBall valves (low pressure check valves). The mass removal estimates are approximate since the flow rates are estimated, the concentration data is based on exponential fits of a limited data set, and the concentration data is normalized to the average CO2.The concentration values presented in this report should be taken as the general trend or order of magnitude of concentration until longer-term data is collected. These trends are of exponentially decreasing concentration showing the same characteristics as the concentration trends at the SRS Miscellaneous Chemical Basin after three years of PSVE (Riha et. al., 1999)

  10. Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

    Science.gov (United States)

    Hu, Peizhen; Chung, Leland W K; Berel, Dror; Frierson, Henry F; Yang, Hua; Liu, Chunyan; Wang, Ruoxiang; Li, Qinlong; Rogatko, Andre; Zhau, Haiyen E

    2013-01-01

    We reported (PLoS One 6 (12):e28670, 2011) that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC) tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE) tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1) expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

  11. Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

    Directory of Open Access Journals (Sweden)

    Peizhen Hu

    Full Text Available We reported (PLoS One 6 (12:e28670, 2011 that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1 expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

  12. Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and post-stroke dementia: a hospital-based study from northern Iran.

    Science.gov (United States)

    Rezaei, Sajjad; Asgari Mobarake, Karim; Saberi, Alia; Keshavarz, Parvaneh; Leili, Ehsan Kazemnejad

    2016-06-01

    Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with functional and cognitive outcomes of stroke and plays a key role in preventing neuronal death. This study aimed to answer the following question: does BDNF Val66Met polymorphism prognosticate survival status and risk of post-stroke dementia (PSD)? In a retrospective cohort study, 206 patients with ischemic stroke (IS) entered the study. They were consecutively being admitted to the neurology clinic in Poursina Hospital (northern Iran) from 2012 to 2014. The diagnosis of PSD was based on DSM-5 criteria. The current and the premorbid cognitive statuses of the patients were respectively assessed through the third edition of Addenbrooke's Cognitive Examination and the Informant Questionnaire on Cognitive Decline in the Elderly. BDNF Val66Met gene polymorphism was determined by PCR-RFLP. On average, 48 patients (23.3 %) developed PSD 6 months after IS. Log-rank test showed that the survival rate of at least one Val-allele carriers was significantly lower than that of Met/Met homozygotes (P = 0.0005), and the former developed PSD sooner than the latter (375, 492 days, respectively). Cox model showed that heterozygous carriers of Val/Met were at greater risk of PSD over time (HR 2.280, 95 % CI 1.566-4.106, P = 0.006). However, the risk ratio of patients with PSD among different BDNF genotypes decreased after adjusting demographic, clinical, and vascular risk factors, and was no longer statistically significant (AHR 2.434, 95 % CI 0.597-9.926, P = 0.215). Val-allele carriers or Val/Met genotypes were more quickly diagnosed as having dementia after IS. However, this genetic vulnerability became more destructive when it was added to demographic, clinical, and vascular risk factors.

  13. Plutonium uniqueness

    International Nuclear Information System (INIS)

    Silver, G.L.

    1984-01-01

    A standard is suggested against which the putative uniqueness of plutonium may be tested. It is common folklore that plutonium is unique among the chemical elements because its four common oxidation states can coexist in the same solution. Whether this putative uniqueness appears only during transit to equilibrium, or only at equilibrium, or all of the time, is not generally made clear. But while the folklore may contain some truth, it cannot be put to test until some measure of 'uniqueness' is agreed upon so that quantitative comparisons are possible. One way of measuring uniqueness is as the magnitude of the product of the mole fractions of the element at equilibrium. A 'coexistence index' is defined and discussed. (author)

  14. Sereniteit met een dip

    NARCIS (Netherlands)

    dr Ed de Jonge

    2015-01-01

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

  15. Unique characteristics of regulatory approval and pivotal studies of orphan anticancer drugs in Japan.

    Science.gov (United States)

    Nakayama, Hiroki; Tsukamoto, Katsura

    2018-04-17

    The approval of orphan anticancer drugs has increased, with the number exceeding that of non-orphan drugs in Japan in recent years. Although orphan anticancer drugs may have unique characteristics due to their rarity, these have not been fully characterized. We investigated anticancer drugs approved in Japan between April 2004 and November 2017 to reveal the characteristics of regulatory approval and pivotal studies on orphan anticancer drugs compared to non-orphan drugs. The median regulatory review time and number of patients in pivotal studies on orphan anticancer drugs (281.0 days [interquartile range, 263.3-336.0]; 222.5 patients [66.0-454.3]) were significantly lower than those on non-orphan drugs (353.0 days [277.0-535.5]; 521.0 patients [303.5-814.5], respectively) (P < 0.001). Phase II, non-randomized and non-controlled designs were more frequently used in pivotal studies on orphan anticancer drugs (45.9%, 41.9% and 43.2%) than non-orphan drugs (17.2%, 14.1% and 14.1%, respectively). Response rate was more commonly used as a primary endpoint in pivotal studies on orphan anticancer drugs (48.6%) than non-orphan drugs (17.2%). Indications limited by molecular features, second or later treatment line, and accelerated approval in the United States were associated with the use of response rate in orphan anticancer drug studies. In conclusion, we demonstrated that orphan anticancer drugs in Japan have unique characteristics compared to non-orphan drugs: shorter regulatory review and pivotal studies frequently using phase II, non-randomized, or non-controlled designs and response rate as a primary endpoint, with fewer patients.

  16. The zenithal 4-m International Liquid Mirror Telescope: a unique facility for supernova studies

    Science.gov (United States)

    Kumar, Brajesh; Pandey, Kanhaiya L.; Pandey, S. B.; Hickson, P.; Borra, E. F.; Anupama, G. C.; Surdej, J.

    2018-05-01

    The 4-m International Liquid Mirror Telescope (ILMT) will soon become operational at the newly developed Devasthal observatory near Nainital (Uttarakhand, India). Coupled with a 4k × 4k pixels CCD detector and TDI optical corrector, it will reach approximately 22.8, 22.3, and 21.4 mag in the g΄, r΄, and i΄ spectral bands, respectively, in a single scan. The limiting magnitudes can be further improved by co-adding the consecutive night images in particular filters. The uniqueness to observe the same sky region by looking towards the zenith direction every night makes the ILMT a unique instrument to detect new supernovae (SNe) by applying the image subtraction technique. High cadence (˜24 h) observations will help to construct dense sampling multi-band SNe light curves. We discuss the importance of the ILMT facility in the context of SNe studies. Considering the various plausible cosmological parameters and observational constraints, we perform detailed calculations of the expected SNe rate that can be detected with the ILMT in different spectral bands.

  17. The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: a fMRI study.

    Science.gov (United States)

    Kempton, Matthew J; Haldane, Morgan; Jogia, Jigar; Christodoulou, Tessa; Powell, John; Collier, David; Williams, Steven C R; Frangou, Sophia

    2009-04-01

    The functional catechol-O-methyltransferase (COMT Val108/158Met) polymorphism has been shown to have an impact on tasks of executive function, memory and attention and recently, tasks with an affective component. As oestrogen reduces COMT activity, we focused on the interaction between gender and COMT genotype on brain activations during an affective processing task. We used functional MRI (fMRI) to record brain activations from 74 healthy subjects who engaged in a facial affect recognition task; subjects viewed and identified fearful compared to neutral faces. There was no main effect of the COMT polymorphism, gender or genotypexgender interaction on task performance. We found a significant effect of gender on brain activations in the left amygdala and right temporal pole, where females demonstrated increased activations over males. Within these regions, Val/Val carriers showed greater signal magnitude compared to Met/Met carriers, particularly in females. The COMT Val108/158Met polymorphism impacts on gender-related patterns of activation in limbic and paralimbic regions but the functional significance of any oestrogen-related COMT inhibition appears modest.

  18. The L3+C detector, a unique tool-set to study cosmic rays

    International Nuclear Information System (INIS)

    Adriani, O.; Akker, M. van den; Banerjee, S.; Baehr, J.; Betev, B.; Bourilkov, D.; Bottai, S.; Bobbink, G.; Cartacci, A.; Chemarin, M.; Chen, G.; Chen, H.S.; Chiarusi, T.; Dai, C.J.; Ding, L.K.; Duran, I.; Faber, G.; Fay, J.; Grabosch, H.J.; Groenstege, H.; Guo, Y.N.; Gupta, S.; Haller, Ch.; Hayashi, Y.; He, Z.X.; Hebbeker, T.; Hofer, H.; Hoferjun, H.; Huo, A.X.; Ito, N.; Jing, C.L.; Jones, L.; Kantserov, V.; Kawakami, S.; Kittel, W.; Koenig, A.C.; Kok, E.; Korn, A.; Kuang, H.H.; Kuijpers, J.; Ladron de Guevara, P.; Le Coultre, P.; Lei, Y.; Leich, H.; Leiste, R.; Li, D.; Li, L.; Li, Z.C.; Liu, Z.A.; Liu, H.T.; Lohmann, W.; Lu, Y.S.; Ma, X.H.; Ma, Y.Q.; Mil, A. van; Monteleoni, B.; Nahnhauer, R.; Pauss, F.; Parriaud, J.-F.; Petersen, B.; Pohl, M.; Qing, C.R.; Ramelli, R.; Ravindran, K.C.; Rewiersma, P.; Rojkov, A.; Saidi, R.; Schmitt, V.; Schoeneich, B.; Schotanus, D.J.; Shen, C.Q.; Sulanke, H.; Tang, X.W.; Timmermans, C.; Tonwar, S.; Trowitzsch, G.; Unger, M.; Verkooijen, H.; Wang, X.L.; Wang, X.W.; Wang, Z.M.; Wijk, R. van; Wijnen, Th.A.M.; Wilkens, H.; Xu, Y.P.; Xu, Z.Z.; Yang, C.G.; Yang, X.F.; Yao, Z.G.; Yu, Z.Q.; Zhang, S.; Zhu, G.Y.; Zhu, Q.Q.; Zhuang, H.L.; Zwart, A.N.M.

    2002-01-01

    The L3 detector at the CERN electron-positron collider, LEP, has been employed for the study of cosmic ray muons. The muon spectrometer of L3 consists of a set of high-precision drift chambers installed inside a magnet with a volume of about 1000 m 3 and a field of 0.5 T. Muon momenta are measured with a resolution of a few percent at 50 GeV. The detector is located under 30 m of overburden. A scintillator air shower array of 54 m by 30 m is installed on the roof of the surface hall above L3 in order to estimate the energy and the core position of the shower associated with a sample of detected muons. Thanks to the unique properties of the L3+C detector, muon research topics relevant to various current problems in cosmic ray and particle astrophysics can be studied

  19. The L3+C detector, a unique tool-set to study cosmic rays

    CERN Document Server

    Adriani, O; Banerjee, S; Bähr, J; Betev, B L; Bourilkov, D; Bottai, S; Bobbink, Gerjan J; Cartacci, A M; Chemarin, M; Chen, G; Chen He Sheng; Chiarusi, T; Dai Chang Jiang; Ding, L K

    2002-01-01

    The L3 detector at the CERN electron-positron collider, LEP, has been employed for the study of cosmic ray muons. The muon spectrometer of L3 consists of a set of high-precision drift chambers installed inside a magnet with a volume of about 1000 m**3 and a field of 0.5 T. Muon momenta are measured with a resolution of a few percent at 50 GeV. The detector is located under 30 m of overburden. A scintillator air shower array of 54 m by 30 m is installed on the roof of the surface hall above L3 in order to estimate the energy and the core position of the shower associated with a sample of detected muons. Thanks to the unique properties of the L3+C detector, muon research topics relevant to various current problems in cosmic ray and particle astrophysics can be studied.

  20. Age-related olfactory decline is associated with the BDNF val66met polymorphism: evidence from a population-based study

    Directory of Open Access Journals (Sweden)

    Margareta Hedner

    2010-06-01

    Full Text Available The present study investigates the effect of the brain-derived neurotrophic factor (BDNF val66met polymorphism on change in olfactory function in a large scale, longitudinal population-based sample (n=836. The subjects were tested on a 13 item force-choice odor identification test on two test occasions over a 5-year-interval. Sex, education, health-related factors, and semantic ability were controlled for in the statistical analyses. Results showed an interaction effect of age and BDNF val66met on olfactory change, such that the magnitude of olfactory decline in the older age cohort (70-90 years old at baseline was larger for the val homozygote carriers than for the met carriers. The older met carriers did not display larger age-related decline in olfactory function compared to the younger group. The BDNF val66met polymorphism did not affect the rate of decline in the younger age cohort (45-65 years. The findings are discussed in the light of the proposed roles of BDNF in neural development and maintenance.

  1. Ervaringen met beeldverwerking.

    NARCIS (Netherlands)

    Meuleman, J.

    1989-01-01

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

  2. Nisine geholpen met hordentechnologie

    NARCIS (Netherlands)

    Jong, de L.S.

    2001-01-01

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

  3. Autorijden met ADHD

    NARCIS (Netherlands)

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

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

  4. When Historiography Met Epistemology

    Directory of Open Access Journals (Sweden)

    Jean-François Stoffel

    2017-06-01

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

  5. Eye Movement Desensitization and Reprocessing (EMDR) bij verkeersslachtoffers met chronische whiplash-klachten: een exploratieve studie naar het verzachten van traumasymptomen.

    NARCIS (Netherlands)

    Renssen, M.; Winkel, F.W.

    1999-01-01

    Dit onderzoek bij verkeersslachtoffers met whiplash-klachten maakte deel uit van een omvangrijker studie naar de kwaliteit van hulpverlening aan slachtoffers van verkeersongevallen, in het kader van het Achmea-project ‘Kwaliteit Slachtofferhulp’. Gerapporteerd wordt een viertal gevalsbeschrijvingen

  6. Unveiling the 'unique bone': a study of the distribution of focal clavicular lesions

    International Nuclear Information System (INIS)

    Suresh, S.; Saifuddin, A.

    2008-01-01

    Clavicle is a unique bone for many reasons. There is no study discussing the differential diagnosis of clavicular lesions based on the site of occurrence or age at presentation. This study aims to determine whether the distribution of lesions affecting the clavicle and age at presentation aid in the differential diagnosis of focal clavicular lesions. Clinical notes, imaging and histopathological reports of the clavicular lesions between Jan 1999 and Jan 2006 were reviewed. Virtually, all patients had been referred as suspected neoplasm. Fifty-nine patients were identified. Patients 50 years (n=18) had predominantly malignant lesions. The lesions most commonly affected the medial third (n=35) and were predominantly non-neoplastic or benign. The middle third was affected in 15 patients and showed both benign and malignant lesions. The lateral third was least affected with predominance of malignant lesions. The clavicle is not a primary common site for any particular tumour; hence, diagnosis of the lesions can be challenging. Our study has suggested that few factors like age and site of the lesions may be helpful in diagnosis. (orig.)

  7. Open versus laparoscopic liver resection for colorectal liver metastases (the Oslo-CoMet Study): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Fretland, Åsmund Avdem; Kazaryan, Airazat M; Bjørnbeth, Bjørn Atle; Flatmark, Kjersti; Andersen, Marit Helen; Tønnessen, Tor Inge; Bjørnelv, Gudrun Maria Waaler; Fagerland, Morten Wang; Kristiansen, Ronny; Øyri, Karl; Edwin, Bjørn

    2015-03-04

    Laparoscopic liver resection is used in specialized centers all over the world. However, laparoscopic liver resection has never been compared with open liver resection in a prospective, randomized trial. The Oslo-CoMet Study is a randomized trial into laparoscopic versus open liver resection for the surgical management of hepatic colorectal metastases. The primary outcome is 30-day perioperative morbidity. Secondary outcomes include 5-year survival (overall, disease-free and recurrence-free), resection margins, recurrence pattern, postoperative pain, health-related quality of life, and evaluation of the inflammatory response. A cost-utility analysis of replacing open surgery with laparoscopic surgery will also be performed. The study includes all resections for colorectal liver metastases, except formal hemihepatectomies, resections where reconstruction of vessels/bile ducts is necessary and resections that need to be combined with ablation. All patients will participate in an enhanced recovery after surgery program. A biobank of liver and tumor tissue will be established and molecular analysis will be performed. After 35 months of recruitment, 200 patients have been included in the trial. Molecular and immunology data are being analyzed. Results for primary and secondary outcome measures will be presented following the conclusion of the study (late 2015). The Oslo-CoMet Study will provide the first level 1 evidence on the benefits of laparoscopic liver resection for colorectal liver metastases. The trial was registered in ClinicalTrals.gov (NCT01516710) on 19 January 2012.

  8. Gallium a unique anti-resorptive agent in bone: Preclinical studies on its mechanisms of action

    International Nuclear Information System (INIS)

    Bockman, R.; Adelman, R.; Donnelly, R.; Brody, L.; Warrell, R.; Jones, K.W.

    1990-01-01

    The discovery of gallium as a new and unique agent for the treatment of metabolic bone disorders was in part fortuitous. Gallium is an exciting new therapeutic agent for the treatment of pathologic states characterized by accelerated bone resorption. Compared to other therapeutic metal compounds containing platinum or germanium, gallium affects its antiresorptive action without any evidence of a cytotoxic effect on bone cells. Gallium is unique amongst all therapeutically available antiresorptive agents in that it favors bone formation. 18 refs., 1 fig

  9. Facial emotion recognition in schizophrenia: An exploratory study on the role of comorbid alcohol and substance use disorders and COMT Val158Met.

    Science.gov (United States)

    Carrà, Giuseppe; Nicolini, Gabriella; Lax, Annamaria; Bartoli, Francesco; Castellano, Filippo; Chiorazzi, Alessia; Gamba, Giulia; Bava, Mattia; Crocamo, Cristina; Papagno, Costanza

    2017-11-01

    To explore whether facial emotion recognition (FER), impaired in both schizophrenia and alcohol and substance use disorders (AUDs/SUDs), is additionally compromised among comorbid subjects, also considering the role of catechol-O-methyltransferase (COMT) Val158Met. We conducted a cross-sectional study, randomly recruiting 67 subjects with a DSM-IV-TR diagnosis of schizophrenia, and rigorously assessing AUDs/SUDs and COMT Val158Met polymorphism. FER was assessed using the Ekman 60 Faces Test- EK-60F. As a whole, the sample scored significantly lower than normative data on EK-60F. However, subjects with comorbid AUDs/SUDs did not perform worse on EK-60F than those without, who had a better performance on EK-60F if they carried the COMT Val/Met variant. This study is the first to date examining the impact of AUDs/SUDs and COMT variants on FER in an epidemiologically representative sample of subjects with schizophrenia. Our findings do not suggest an additional impairment from comorbid AUDs/SUDs on FER among subjects with schizophrenia, whilst COMT Val158Met, though based on a limited sample, might have a role just among those without AUDs/SUDs. Based on our results, additional research is needed also exploring differential roles of various substances. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Dynamical contibution of Mean Potential Vorticity pseudo-observations derived from MetOp/GOME2 Ozone data into weather forecast, a Mediterranean High Precipitation Event study.

    Science.gov (United States)

    Sbii, Siham; Zazoui, Mimoun; Semane, Noureddine

    2015-04-01

    In the absence of observations covering the upper troposphere - lower stratophere, headquarters of several disturbances, and knowing that satellites are uniquely capable of providing uniform data coverage globally, a methodology is followed [1] to convert Total Column Ozone, observed by MetOp/GOME2, into pseudo-observations of Mean Potential Vorticity (MPV). The aim is to study the dynamical impact of Ozone data in the prediction of a Mediterranean Heavy Precipitation Event observed during 28-29 September 2012 in the context of HYMEX1. This study builds on a previously described methodology [2] that generates numerical weather prediction model initial conditions from ozone data. Indeed, the assimilation of MPV in a 3D-var framework is based on a linear regression between observed Ozone and vertical integrated Ertel PV. The latter is calculated using dynamical fields from the moroccan operational limited area model ALADIN-MAROC according to [3]: δθ fp p0 -R δU δV P V = - gξaδp- g-R-(p )Cp [(δp-)2 + (δp-)2] (1) Where ξa is the vertical component of the absolute vorticity, U and V the horizontal wind components, θ the potential temperature, R gas constant, Cp specific heat at constant pressure, p the pressure, p0 a reference pressure, g the gravity and f is the Coriolis parameter. The MPV is estimated using the following expression: --1--∫ P2 M PV = P1 - P2 P P V.δp 1 (2) With P1 = 500hPa and P2 = 100hPa In the present study, the linear regression is performed over September 2012 with a correlation coefficient of 0.8265 and is described as follows: M P V = 5.314610- 2 *O3 - 13.445 (3) where O3 and MPV are given in Dobson Unit (DU) and PVU (1 PV U = 10-6 m2 K kg-1 s-1), respectively. It is found that the ozone-influenced upper-level initializing fields affect the precipitation forecast, as diagnosed by a comparison with the ECMWF model. References [1] S. Sbii, N. Semane, Y. Michel, P. Arbogast and M. Zazoui (2012). Using METOP/GOME-2 data and MSG ozone

  11. Detection of Met-enkephalin: Development of a RIA and of an extraction method for studies on hypophyseal and brain tissues

    International Nuclear Information System (INIS)

    Holl, R.

    1982-01-01

    The thesis describes the development of a method of detecting Met-enkephalin, and the verification of the method's suitability to measurements in extracted tissue. The tissue extraction method reported has been the first step towards the goal of establishing the method for determining Met-enkephalin in cell and tissue extracts, in culture media, plasma and liquor samples. The difficulties involved in the development of the RIA for Met-enkephalin specifically arose from the following peculiarities of the substance: a) Due to the low molecular weight, (574), ME itself does not act as an antigen, antibodies can only be obtained by means of fixation to carrier molecules. b) Enkephalin very rapidly is decomposed by endogenic proteinases. c) The fact that normal physiological processes will produce peptides very similar in sequence requires the RIA to be extremely specific. The method has first been applied to screening measurements of Met-enkephalin concentrations in various brain sectors. The radioimmunological studies have been intended to supplement and verify the immunocytochemical results obtained, with the latter experiments having been made using the same antiserum, in order to improve the basis of comparison between the immunocytochemical results and the findings on antibody specifity obtained from the RIA. (orig./MG) [de

  12. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer

    OpenAIRE

    Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

    2017-01-01

    SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260–570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety...

  13. Unique properties associated with normal martensitic transition and strain glass transition – A simulation study

    International Nuclear Information System (INIS)

    Wang, Dong; Ni, Yan; Gao, Jinghui; Zhang, Zhen; Ren, Xiaobing; Wang, Yunzhi

    2013-01-01

    Highlights: ► We model the unique properties of strain glass which is different from that of normal martensite. ► We describe the importance of point defects in the formation of strain glass and related properties. ► The role of point defect can be attributed to global transition temperature effect (GTTE) and local field effect (LFE). -- Abstract: The transition behavior and unique properties associated with normal martensitic transition and strain glass transition are investigated by computer simulations using the phase field method. The simulations are based on a physical model that assumes that point defects alter the thermodynamic stability of martensite and create local lattice distortion. The simulation results show that strain glass transition exhibits different properties from those found in normal martensitic transformations. These unique properties include diffuse scattering pattern, “smear” elastic modulus peak, disappearance of heat flow peak and non-ergodicity. These simulation predictions agree well with the experimental observations

  14. C-MET overexpression and amplification in gliomas.

    Science.gov (United States)

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

    2015-01-01

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

  15. Lewenskwaliteit te midde van ‘n erge stressor: ‘n studie van bejaardes met alzheimer se siekte of rumatoïede artritis

    Directory of Open Access Journals (Sweden)

    Pieter M Heyns

    2004-11-01

    Full Text Available This study addresses the role of psychofortigenic factors in maintaining quality of life in elderly people diagnosed with either rheumatoid arthritis or Alzheimer's disease. Opsomming Hierdie studie handel oor die rol wat psigofortigene faktore speel in die handhawing van lewenskwaliteit deur bejaardes wat gediagnoseer is met rumatoïede artritis of Alzheimer se siekte. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.

  16. Jeugd met beperkingen

    NARCIS (Netherlands)

    Sjoerd Kooiker

    2006-01-01

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

  17. Studeren met Hans Rosenberg

    NARCIS (Netherlands)

    Rutten, R.J.

    2001-01-01

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

  18. SPSS met syntax

    NARCIS (Netherlands)

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

    2007-01-01

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

  19. Photo-Elicitation and Visual Semiotics: A Unique Methodology for Studying Inclusion for Children with Disabilities

    Science.gov (United States)

    Stockall, Nancy

    2013-01-01

    The methodology in this paper discusses the use of photographs as an elicitation strategy that can reveal the thinking processes of participants in a qualitatively rich manner. Photo-elicitation techniques combined with a Piercian semiotic perspective offer a unique method for creating a frame of action for later participant analysis. Illustrative…

  20. A Case-Control Study and Meta-Analysis Reveal BDNF Val66Met Is a Possible Risk Factor for PTSD

    Directory of Open Access Journals (Sweden)

    Dagmar Bruenig

    2016-01-01

    Full Text Available Posttraumatic stress disorder (PTSD is a debilitating condition that develops in some people after exposure to a traumatic event. Brain-derived neurotrophic factor (BDNF is highly expressed in the mammalian brain and is thought to be involved in learning and memory processes. A nonsynonymous polymorphism in the BDNF gene, rs6265 (Val66Met, has been hypothesised to be associated with PTSD. Association studies examining the Val66Met polymorphism and PTSD have been inconclusive, likely due to the variability in type of trauma exposure analysed. Vietnam veterans (n=257 screened for PTSD and controlled for trauma exposure were genotyped for BDNF Val66Met. The association was not significant so we incorporated our data into a meta-analysis to obtain greater statistical power. A comprehensive search of more than 1237 articles revealed eight additional studies suitable for meta-analysis (n=3625. A random-effects meta-analysis observed a potential protective factor of the Val/Val genotype. After removing two studies with violation of Hardy-Weinberg equilibrium, findings for the Val/Val genotype reached significance. Subgroup analyses confirmed a trend for this finding. Limitations of some studies that inform this meta-analysis include poorly screened controls and a lack of examination of population stratification. Effectively designed studies should inform this line of research in the future.

  1. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer.

    Science.gov (United States)

    Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

    2017-10-03

    SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m 2 ) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort ( N = 19; unselected population, including three patients with MET -amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m 2 . Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose-dependent. Grade ≥ 3 AEs were observed in 39.5% of patients and considered drug-related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m 2 in the dose-expansion cohort, comprising patients with MET -amplified tumors ( N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m 2 has acceptable tolerability and modest

  2. BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms: a prospective study.

    Science.gov (United States)

    Buchmann, Arlette F; Hellweg, Rainer; Rietschel, Marcella; Treutlein, Jens; Witt, Stephanie H; Zimmermann, Ulrich S; Schmidt, Martin H; Esser, Günter; Banaschewski, Tobias; Laucht, Manfred; Deuschle, Michael

    2013-08-01

    Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val⁶⁶Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val⁶⁶Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val⁶⁶Met and 5-HTTLPR genotype. Copyright © 2013. Published by Elsevier B.V.

  3. Um estudo experimental do processamento de metáforas do português brasileiro / An experimental study on Brazilian Portuguese metaphor processing

    Directory of Open Access Journals (Sweden)

    Antonio João Carvalho Ribeiro

    2017-06-01

    Full Text Available Um estudo experimental do processamento psicolinguístico de metáforas nominais do português brasileiro (X é um Y, p. ex., “Irene é um furacão”, foi realizado com o objetivo de evidenciar, a partir de tempos de leitura (RTs, a compreensão de expressões familiares, high-apt (“bem construídas” e cujo veículo se acha convencionalizado. Na primeira fase da pesquisa, realizaram-se dois norming studies (“estudos normativos” com vistas ao ranqueamento de metáforas nominais (p. ex. “Algumas mulheres são furacões” em relação a familiaridade, aptness (“adequação” e convencionalidade. Na segunda fase da pesquisa, um experimento de leitura automonitorada (self-paced, non-cumulative, moving-window reading foi conduzido, recorrendo, para a composição dos estímulos, às metáforas, p. ex., “Irene é um furacão”, que alcançaram, nos estudos normativos da primeira fase, ratings (ou “classificações” de “muito familiares”, “very high-apt’’ e “altamente convencionalizadas”. Evidências do português brasileiro em favor do processamento direto de metáforas foram obtidas, conforme preconiza o modelo de Class-inclusion, de Glucksberg e Keysar (1990, pois não se revelaram diferenças significativas entre os RTs médios nas três condições: “metáfora”, “literal” e “declaração literal de inclusão em classe”, em contraposição aos achados de Janus e Bever (1985, que observaram tempos de leitura de metáforas novas significativamente maiores do que os de expressões literais, conforme as predições do Modelo Pragmático Padrão de processamento indireto.

  4. New opportunities for the study of Mediterranean storms: the unique capabilities of the Global Hawk aircraft

    Science.gov (United States)

    Cairo, F.; Curry, R. E.; Carli, B.

    2009-09-01

    Airborne measurements have often played a pivotal role in unravelling critical processess and improving our understanding of the genesis and development of atmospheric disturbances. The availability of innovative aerial platforms now opens new perspectives for the scientific research. One of these platforms is the high altitude long endurance unmanned aircraft Global Hawk (GH), which has unique capabilities in terms of altitude, range of operation, diurnal coverage and flexibility. The GH has an endurance of 31 hrs, a service ceiling of 20000 m and can host a payload of 680 kg. Since it can operate at altitudes close to the boundary conditions of radiative processes, can follow the diurnal variation of aerosol and clouds, can rapidly deploy new instruments with space-time coverage comparable to space-borne ones, it is a platform which is at the same time complementary and competitive with satellites. In fact it combines the short time deployment of aircraft instruments with the global coverage of satellite instruments, while its flight altitude allows better spatial resolution than a satellite and its endurance provides a sufficiently broad overview at a scale relevant for sinoptic meteorology studies. NASA has recently acquired two of such unmanned high altitude aircraft to address a variety of Earth Science objectives, and Italy has a decade long experience of stratospheric in-situ and remote sensing science missions using the Russian M-55 "Geophysica" high altitude piloted aircraft. There is a common interest in a bilateral cooperative program in climate change science using the GH. The collaboration between NASA and Italian scientific institutions may offer the opportunity of deploying the GH over the Mediterranean Basin. The Mediterranean area is of particular interest under many respects. As instance, it would be of great interest to measure, when possible, the 3-dimensional structure and evolution of the aerosol content over the Mediterranean, with

  5. Saving wild tigers: a case study in biodiversity loss and challenges to be met for recovery beyond 2010.

    Science.gov (United States)

    Seidensticker, John

    2010-12-01

    Wild tigers are being annihilated. Tiger range countries and their partners met at the 1st Asian Ministerial Conference on Tiger Conservation in January 2010 to mandate the creation of the Global Tiger Recovery Program to double the number of tigers by 2022. Only 3200-3600 wild adult tigers remain, approximately half of the population estimated a decade ago. Tigers now live in only 13 countries, all of which are experiencing severe environmental challenges and degradation from the effects of human population growth, brisk economic expansion, rapid urbanization, massive infrastructure development and climate change. The overarching challenge of tiger conservation, and the conservation of biodiversity generally, is that there is insufficient demand for the survival of wild tigers living in natural landscapes. This allows the criminal activities of poaching wild tigers and their prey and trafficking in tiger derivatives to flourish and tiger landscapes to be diminished. The Global Tiger Recovery Program will support scaling up of practices already proven effective in one or more tiger range countries that need wider policy support, usually resources, and new transnational actions that enhance the effectiveness of individual country actions. The program is built on robust National Tiger Recovery Priorities that are grouped into themes: (i) strengthening policies that protect tigers; (ii) protecting tiger conservation landscapes; (iii) scientific management and monitoring; (iv) engaging communities; (v) cooperative management of international tiger landscapes; (vi) eliminating transnational illegal wildlife trade; (vii) persuading people to stop consuming tiger; (viii) enhancing professional capacity of policy-makers and practitioners; and (ix) developing sustainable, long-term financing mechanisms for tiger and biodiversity conservation. © 2010 ISZS, Blackwell Publishing and IOZ/CAS.

  6. Unique Path Partitions

    DEFF Research Database (Denmark)

    Bessenrodt, Christine; Olsson, Jørn Børling; Sellers, James A.

    2013-01-01

    We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions.......We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions....

  7. Simulation study on exchange interaction and unique magnetization near ferromagnetic morphotropic phase boundary.

    Science.gov (United States)

    Wei, Songrui; Liao, Xiaoqi; Gao, Yipeng; Yang, Sen; Wang, Dong; Song, Xiaoping

    2017-11-08

    Extensive efforts have been made in searching enhanced functionalities near the so-called morphotropic phase boundaries (MPBs) in both ferroelectric and ferromagnetic materials. Due to the exchange anti-symmetry of the wave function of fermions, it is widely recognized that the exchange interaction plays a critical role in ferromagnetism. As a quantum effect, the exchange interaction is magnitudes larger than electric interaction, leading to a fundamental difference between ferroelectricity and ferromagnetism. In this paper, we establish an energetic model capturing the interplay among the anisotropy energy, magnetostatic energy and the exchange energy to investigate systematically the effects of the exchange energy on the behavior of the ferromagnetic MPB. For the first time, it is found that the exchange energy can narrow the width of MPB region in the composition temperature phase diagram for ferromagnetic MPB systems. As temperature increases, MPB region becomes wider because of the weakening of the exchange interaction. Our simulation results suggest that the exchange energy play a critical role on the unique behavior of ferromagnetic MPB, which is in contrast different from that of ferroelectric MPB.

  8. Study of unique trajectories in SU(2) and SU(3) lattice Gauge theories

    International Nuclear Information System (INIS)

    Nerses, Hudaverdian

    1985-01-01

    As is well known, in the context of quantum field theories describing different types of interactions in the domain of particle physics, there are rampant ultraviolet infinite which are subtly taken care of by adequate renormalization procedures. The most conventional perturbative regularization schemes are based on the Feynman expansion, so successfully used in quantum electrodynamics. But the unique feature of confinement in strong interactions has forced physicists to search for a non-perturbative cut-off, and this has been provided by the introduction of discrete spacetime lattices over which the field theories have been formulated. the lattice represents a mathematical trick, a more scaffolding, an intermediate step, used to analyze a difficult non-linear system, of an infinite number of degree of freedom. Herein lies the main virtue of the lattice, which directly eliminates all wavelengths less than twice the lattice spacing.Consequently, regarding the lattice merely as an ultraviolet cut-off, physicists should remove this regulator and expect observable quantities to approach their physical values. However as the removal of the regulator is discussed, the question of renormalization emerges, and it is here that the Migdal-Kadanoff recursion relations, representing a simple approximate method for comparing theories with different lattice spacings bring in their virtue by providing a simple method for obtaining an approximate renormalization group function. It is hoped, and currently extensively investigated whether the Migdal renormalization group approach, combined with some other methods, can really provide useful information on the phase structures of lattice gauge theories

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

    African Journals Online (AJOL)

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

  10. The Svalbard study 1988-89: a unique setting for validation of self-reported alcohol consumption.

    Science.gov (United States)

    Høyer, G; Nilssen, O; Brenn, T; Schirmer, H

    1995-04-01

    The Norwegian island of Spitzbergen, Svalbard offers a unique setting for validation studies on self-reported alcohol consumption. No counterfeit production or illegal import exists, thus making complete registration of all sources of alcohol possible. In this study we recorded sales from all agencies selling alcohol on Svalbard over a 2-month period in 1988. During the same period all adults living permanently on Svalbard were invited to take part in a health screening. As part of the screening a self-administered questionnaire on alcohol consumption was introduced to the participants. We found that the self-reported volume accounted for approximately 40 percent of the sales volume. Because of the unique situation applying to Svalbard, the estimate made in this study is believed to be more reliable compared to other studies using sales volume to validate self-reports.

  11. Case Studies of Leading Edge Small Urban High Schools. Personalization Strategic Designs: 9. MetWest High School

    Science.gov (United States)

    Shields, Regis Anne; Ireland, Nicole; City, Elizabeth; Derderian, Julie; Miles, Karen Hawley

    2008-01-01

    This report is one of nine detailed case studies of small urban high schools that served as the foundation for the Education Resource Strategies (ERS) report "Strategic Designs: Lessons from Leading Edge Small Urban High Schools." These nine schools were dubbed "Leading Edge Schools" because they stand apart from other high…

  12. De kans op infectie en ziekte na het eten van schelpdieren, besmet met Campylobacter lari - een orienterende studie

    NARCIS (Netherlands)

    Teunis PFM; Havelaar AH; Vliegenthart JS; Roessink GL; MGB

    1996-01-01

    In order to assess health risks caused by consumption of raw shellfish contaminated with Campylobacter lari, quantitative information on the dose and the dose response relation is required. In this study, numbers of C. lari, present in raw oysters or mussels, are estimated from a single dilution,

  13. Study of problems met in muon pattern recognition for a deep inelastic scattering experiment at the S.P.S

    International Nuclear Information System (INIS)

    Besson, C.

    1976-01-01

    The problems of the muon pattern recognition are studied for a muon-proton deep inelastic scattering experiment at the S.P.S. The pattern recognition program is described together with the problems caused by some characteristics of the apparatus of the European muon collaboration. Several reconstruction technics are compared, and a way of handling big drift chamber problems is found. Some results on Monte-Carlo tracks are given [fr

  14. COMT Val158 Met moderates the link between rank and aggression in a non-human primate.

    Science.gov (United States)

    Gutleb, D R; Roos, C; Noll, A; Ostner, J; Schülke, O

    2018-04-01

    The COMT Val 158 Met polymorphism is one of the most widely studied genetic polymorphisms in humans implicated in aggression and the moderation of stressful life event effects. We screened a wild primate population for polymorphisms at the COMT Val 158 Met site and phenotyped them for aggression to test whether the human polymorphism exists and is associated with variation in aggressive behavior. Subjects were all adults from 4 study groups (37 males, 40 females) of Assamese macaques (Macaca assamensis) in their natural habitat (Phu Khieo Wildlife Sanctuary, Thailand). We collected focal animal behavioral data (27 males, 36 females, 5964 focal hours) and fecal samples for non-invasive DNA analysis. We identified the human COMT Val 158 Met polymorphism (14 Met/Met, 41 Val/Met and 22 Val/Val). Preliminary results suggest that COMT genotype and dominance rank interact to influence aggression rates. Aggression rates increased with rank in Val/Val, but decreased in Met/Met and Val/Met individuals, with no significant main effect of COMT genotype on aggression. Further support for the interaction effect comes from time series analyses revealing that when changing from lower to higher rank position Val/Val individuals decreased, whereas Met/Met individuals increased their aggression rate. Contradicting the interpretation of earlier studies, we show that the widely studied Val 158 Met polymorphism in COMT is not unique to humans and yields similar behavioral phenotypes in a non-human primate. This study represents an important step towards understanding individual variation in aggression in a wild primate population and may inform human behavioral geneticists about the evolutionary roots of inter-individual variation in aggression. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  15. Association of car ownership and physical activity across the spectrum of human development: Modeling the Epidemiologic Transition Study (METS).

    Science.gov (United States)

    Shoham, David A; Dugas, Lara R; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Plange-Rhule, Jacob; Schoeller, Dale A; Brage, Soren; Ekelund, Ulf; Durazo-Arvizu, Ramon A; Cooper, Richard S; Luke, Amy

    2015-02-21

    Variations in physical activity (PA) across nations may be driven by socioeconomic position. As national incomes increase, car ownership becomes within reach of more individuals. This report characterizes associations between car ownership and PA in African-origin populations across 5 sites at different levels of economic development and with different transportation infrastructures: US, Seychelles, Jamaica, South Africa, and Ghana. Twenty-five hundred adults, ages 25-45, were enrolled in the study. A total of 2,101 subjects had valid accelerometer-based PA measures (reported as average daily duration of moderate to vigorous PA, MVPA) and complete socioeconomic information. Our primary exposure of interest was whether the household owned a car. We adjusted for socioeconomic position using household income and ownership of common goods. Overall, PA levels did not vary largely between sites, with highest levels in South Africa, lowest in the US. Across all sites, greater PA was consistently associated with male gender, fewer years of education, manual occupations, lower income, and owning fewer material goods. We found heterogeneity across sites in car ownership: after adjustment for confounders, car owners in the US had 24.3 fewer minutes of MVPA compared to non-car owners in the US (20.7 vs. 45.1 minutes/day of MVPA); in the non-US sites, car-owners had an average of 9.7 fewer minutes of MVPA than non-car owners (24.9 vs. 34.6 minutes/day of MVPA). PA levels are similar across all study sites except Jamaica, despite very different levels of socioeconomic development. Not owning a car in the US is associated with especially high levels of MVPA. As car ownership becomes prevalent in the developing world, strategies to promote alternative forms of active transit may become important.

  16. A Unique Automation Platform for Measuring Low Level Radioactivity in Metabolite Identification Studies

    Science.gov (United States)

    Krauser, Joel; Walles, Markus; Wolf, Thierry; Graf, Daniel; Swart, Piet

    2012-01-01

    Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using 14C or 3H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector. PMID:22723932

  17. A unique automation platform for measuring low level radioactivity in metabolite identification studies.

    Directory of Open Access Journals (Sweden)

    Joel Krauser

    Full Text Available Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using (14C or (3H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector.

  18. EX-MET study: exercise in prevention on of metabolic syndrome - a randomized multicenter trial: rational and design.

    Science.gov (United States)

    Tjønna, Arnt Erik; Ramos, Joyce S; Pressler, Axel; Halle, Martin; Jungbluth, Klaus; Ermacora, Erika; Salvesen, Øyvind; Rodrigues, Jhennyfer; Bueno, Carlos Roberto; Munk, Peter Scott; Coombes, Jeff; Wisløff, Ulrik

    2018-04-02

    Metabolic syndrome substantially increases risk of cardiovascular events. It is therefore imperative to develop or optimize ways to prevent or attenuate this condition. Exercise training has been long recognized as a corner-stone therapy for reducing individual cardiovascular risk factors constituting the metabolic syndrome. However, the optimal exercise dose and its feasibility in a real world setting has yet to be established. The primary objective of this randomized trial is to investigate the effects of different volumes of aerobic interval training (AIT) compared to the current exercise guideline of moderate-intensity continuous training (MICT) on the composite number of cardiovascular disease risk factors constituting the metabolic syndrome after a 16 week, 1-year, and 3-year follow-up. This is a randomized international multi-center trial including men and women aged ≥30 years diagnosed with the metabolic syndrome according to the International Diabetes Federation criteria. Recruitment began in August 2012 and concluded in December 2016. This trial consists of supervised and unsupervised phases to evaluate the efficacy and feasibility of different exercise doses on the metabolic syndrome in a real world setting. This study aims to include and randomize 465 participants to 3 years of one of the following training groups: i) 3 times/week of 4 × 4 min AIT at 85-95% peak heart rate (HRpeak); ii) 3 times/week of 1 × 4 min AIT at 85-95% HRpeak; or iii) 5-7 times/week of ≥30 min MICT at 60-70% HRpeak. Clinical examinations, physical tests and questionnaires are administered to all participants during all testing time points (baseline, 16 weeks and after 1-, and 3-years). This multi-center international trial indeed aims to ease the burden in healthcare/economic cost arising from treating end-stage CVD related conditions such as stroke and myocardial infarction, that could eventually emerge from the metabolic syndrome condition. Clinical

  19. Clinical Study of Bacillus coagulans Unique IS-2 (ATCC PTA-11748) in the Treatment of Patients with Bacterial Vaginosis.

    Science.gov (United States)

    Ratna Sudha, M; Yelikar, Kanan A; Deshpande, Sonali

    2012-09-01

    Bacterial vaginosis (BV) is the most prevalent vaginal infection worldwide and is characterized by reduction of native lactobacilli. Antimicrobial therapy used to cure the disease is often found to be ineffective. We postulate that Bacillus coagulans Unique IS-2 (Unique Biotech Limited, India) might provide an appendage to antimicrobial treatment and improve curing rate. In the present study 40 Indian women diagnosed with BV by the presence of symptoms including white discharge, pH greater than 4.7, burning micturation, itching, soreness and redness at vulva. The subjects were divided in 2 groups probiotic (n = 20) and control (n = 20) based on age (control group, 33 ± 3 years and probiotic group, 32.5 ± 3 years), history of previous vaginosis (control group, 75% or 15/20 and probiotic group, 75% or 15/20) and severity of current vaginosis infection (burning micturation and itching, 35% in each group). Probiotic group subjects were assigned to receive a dose of antibiotic therapy [Ofloxacin-Ornidazole with strength of 200-500 mg per capsule/day for 5 days along with vaginal peccaries (co-kimaxazol) for 3 days] simultaneously with two probiotic capsules (10(9) CFUs of Bacillus coagulans Unique IS-2 per capsule). The control group received only antibiotic therapy. At the end of the treatment the 80% of probiotic group subjects showed significant positive response as revealed by reduction of vaginosis symptoms compared to the control group which exhibited reduction in 45% subjects only. Thus, the results of present study indicate that strain Bacillus coagulans Unique IS-2 can provide benefits to women being treated with antibiotics to cure an infectious condition.

  20. No Need to Wait for Superman: A Case Study of One Unique High School

    Science.gov (United States)

    Ratcliff, N. J.; Jones, C. R.; Costner, R. H.; Knight, C.; Disney, G.; Savage-Davis, E.; Sheehan, H.; Hunt, G. H.

    2012-01-01

    Based on a theoretical model developed by Schlechty, this case study focuses on a small high school, located on a college campus and designed to address the educational needs of gifted 9th- through 12th-grade students. Eight teachers who taught 9th- and 12th-grade classes and their 60 students were observed. Each teacher was observed during six…

  1. Study unique artistic lopburi province for design brass tea set of bantahkrayang community

    Science.gov (United States)

    Pliansiri, V.; Seviset, S.

    2017-07-01

    The objectives of this study were as follows: 1) to study the production process of handcrafted Brass Tea Set; and 2) to design and develop the handcrafted of Brass Tea Set. The process of design was started by mutual analytical processes and conceptual framework for product design, Quality Function Deployment, Theory of Inventive Problem Solving, Principles of Craft Design, and Principle of Reverse Engineering. The experts in field of both Industrial Product Design and Brass Handicraft Product, have evaluated the Brass Tea Set design and created prototype of Brass tea set by the sample of consumers who have ever bought the Brass Tea Set of Bantahkrayang Community on this research. The statistics methods used were percentage, mean ({{{\\overline X}} = }) and standard deviation (S.D.) 3. To assess consumer satisfaction toward of handcrafted Brass tea set was at the high level.

  2. Unique roles of SPET brain imaging in clinical and research studies

    International Nuclear Information System (INIS)

    Seibyl, J.; Jennings, D.; Tabamo, R.; Marek, K.

    2005-01-01

    The increasing availability of PET imaging in Nuclear medicine expands the armamentarium of clinical and research tools for improving diagnosis and treatment of neuropsychiatric disorders. Nonetheless, the role of SPEC imaging remains critical to both research and clinical practice. The development of rational strategies for guiding the selection of imaging modalities flows from primarily the nature of the clinical or research question and the availability of appropriate radiopharmaceuticals. There has been extensive SPECT and PET work in Parkinson's disease (PD) which highlights the value of both these scintigraphic modalities. Three main areas of interest in PD include imaging for improving diagnostic accuracy, for monitoring the progression of disease, and for assessing the therapeutic efficacy of drugs with neoroprotective potential. The demands of the clinical or research question posed to imaging dictates the selection of radiotracer and imaging modality. Diagnosis of PD represents the easiest challenge with many imaging bio markers showing high sensitivity for detecting abnormal reduction of dopaminergic function based on qualitative review of images. On the other hand, using imaging to evaluate treatments which purportedly slow the rate of disease progression, indicated by the reduction of the rate of loss in a quantitative imaging signal in patients studied over time, represents the most rigorous requirement of the imaging measure. In each of these applications presynaptic markers of dopaminergic function using SPECT and PET have been extremely valuable. Review of neuroimaging studies of PD provides a useful example of optimized approaches to clinical and research studies in neuropsychiatric disorders

  3. Interaction studies in Japanese primatology: their scope, uniqueness, and the future.

    Science.gov (United States)

    Nakamura, Michio

    2009-04-01

    This paper aims to review social interaction studies in Japanese primatology, in order to introduce their utility into the current framework of primatology and their potential for understanding primate sociality. In the first part, I introduce some of the achievements in the field of Japanese primatology. It is a well-known fact that Japanese primatology, in its initial phases, strongly focused on society and sociality in nonhuman primates with respect to human society and sociality. Although Jun'ichiro Itani's theory on the evolution of social structure significantly influenced some of the Japanese primatologists, it had a comparatively minor impact on the West. As Itani himself admitted, he only treated the so-called "hardware" of society and did not deal with its "software" comprehensively, although he understood its importance and even provided some insightful ideas. In the latter part of the paper, I introduce some of the studies that directly dealt with the social interactions of primates and that were written mostly in Japanese. As compared to works in standard primatology, many of these papers were descriptive. This is because interaction cannot be decomposed into individual behaviors; thus, we have to focus on interaction itself. Finally, I argue that we need to explore the methodology for describing the lively and dynamic aspects of primate sociality.

  4. Modeling time-series count data: the unique challenges facing political communication studies.

    Science.gov (United States)

    Fogarty, Brian J; Monogan, James E

    2014-05-01

    This paper demonstrates the importance of proper model specification when analyzing time-series count data in political communication studies. It is common for scholars of media and politics to investigate counts of coverage of an issue as it evolves over time. Many scholars rightly consider the issues of time dependence and dynamic causality to be the most important when crafting a model. However, to ignore the count features of the outcome variable overlooks an important feature of the data. This is particularly the case when modeling data with a low number of counts. In this paper, we argue that the Poisson autoregressive model (Brandt and Williams, 2001) accurately meets the needs of many media studies. We replicate the analyses of Flemming et al. (1997), Peake and Eshbaugh-Soha (2008), and Ura (2009) and demonstrate that models missing some of the assumptions of the Poisson autoregressive model often yield invalid inferences. We also demonstrate that the effect of any of these models can be illustrated dynamically with estimates of uncertainty through a simulation procedure. The paper concludes with implications of these findings for the practical researcher. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. The Role of the Catechol-o-methyltransferase (COMT) Gene Val158Met in Aggressive Behavior, A Review of Genetic Studies

    Science.gov (United States)

    Qayyum, Arqam; Zai, Clement C.; Hirata, Yuko; Tiwari, Arun K.; Cheema, Sheraz; Nowrouzi, Behdin; Beitchman, Joseph H.; Kennedy, James L.

    2015-01-01

    Aggressive behaviors have become a major public health problem, and early-onset aggression can lead to outcomes such as substance abuse, antisocial personality disorder among other issues. In recent years, there has been an increase in research in the molecular and genetic underpinnings of aggressive behavior, and one of the candidate genes codes for the catechol-O-methyltransferase (COMT). COMT is involved in catabolizing catecholamines such as dopamine. These neurotransmitters appear to be involved in regulating mood which can contribute to aggression. The most common gene variant studied in the COMT gene is the Valine (Val) to Methionine (Met) substitution at codon 158. We will be reviewing the current literature on this gene variant in aggressive behavior. PMID:26630958

  6. Specific Preschool Executive Functions Predict Unique Aspects of Mathematics Development: A 3-Year Longitudinal Study.

    Science.gov (United States)

    Simanowski, Stefanie; Krajewski, Kristin

    2017-08-10

    This study assessed the extent to which executive functions (EF), according to their factor structure in 5-year-olds (N = 244), influenced early quantity-number competencies, arithmetic fluency, and mathematics school achievement throughout first and second grades. A confirmatory factor analysis resulted in updating as a first, and inhibition and shifting as a combined second factor. In the structural equation model, updating significantly affected knowledge of the number word sequence, suggesting a facilitatory effect on basic encoding processes in numerical materials that can be learnt purely by rote. Shifting and inhibition significantly influenced quantity to number word linkages, indicating that these processes promote developing a profound understanding of numbers. These results show the supportive role of specific EF for specific aspects of a numerical foundation. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  7. Unique electron transport in ultrathin black phosphorene: Ab-initio study

    International Nuclear Information System (INIS)

    Srivastava, Anurag; Khan, Md. Shahzad; Gupta, Sanjeev Kumar; Pandey, Ravindra

    2015-01-01

    Graphical abstract: Charge transfer configuration for NH 3 and NO 2 adsorbed 2D black-phospherene. - Highlights: • Ultrathin black phosphorene has been investigated, in terms of its optical and ballistic quantum transport properties. • The device performance subtaintially increases in armchair direction of black phosphorene. • Maximum reflectivity (43%) is observed at 1.85 eV (670 nm) and the reflective spectrum dispersed in visible range. • At low bias semiconducting and higher bias ohmic nature pointing black phospherene a promising material for high perfomrance device applications. • For NO 2 gas, this quasi 2D-black phosphorene surface shows strong affinity followed with substantial charge tranfer. - Abstract: We present first principle structural, electronic, optical and transport analysis of black phosphorene a 2D layered material. The studied configuration shows semiconducting nature and the states around the Fermi energy are mainly contributed by the p-orbitals of atoms. In optical properties, the reflective spectrum is approximately dispersed in visible range suggesting that this 2D-nanostructure can be considered as shielding for visible region. Due to the anisotropy of the electronic structure of black phosphorene, the device performance is subtaintially preferable in armchair direction. Zero-bias transmission shows no conductance channel near Fermi level but in far region prominent spectra for the same is observed for black-phospherene. The studied configurations show non-linear current–voltage (I–V) characteristics. The sensitivity for NH 3 and NO 2 gas molecule is explored using electronic and current–voltage (I–V) characteristics. Investigations show that the black phosphorene has strong affinity for electron seeking NO 2 molecule, thus providing an opportunity for its sensor application.

  8. Unique electron transport in ultrathin black phosphorene: Ab-initio study

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Anurag, E-mail: profanurag@gmail.com [Advanced Materials Research Group, Computational Nanoscience & Technology Lab, ABV-Indian Institute of Information Technology and Management, Gwalior (M.P.) 474010 India (India); Khan, Md. Shahzad [Advanced Materials Research Group, Computational Nanoscience & Technology Lab, ABV-Indian Institute of Information Technology and Management, Gwalior (M.P.) 474010 India (India); Gupta, Sanjeev Kumar [Department of Physics, St. Xavier' s College, Ahmedabad 380009 (India); Pandey, Ravindra [Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931 (United States)

    2015-11-30

    Graphical abstract: Charge transfer configuration for NH{sub 3} and NO{sub 2} adsorbed 2D black-phospherene. - Highlights: • Ultrathin black phosphorene has been investigated, in terms of its optical and ballistic quantum transport properties. • The device performance subtaintially increases in armchair direction of black phosphorene. • Maximum reflectivity (43%) is observed at 1.85 eV (670 nm) and the reflective spectrum dispersed in visible range. • At low bias semiconducting and higher bias ohmic nature pointing black phospherene a promising material for high perfomrance device applications. • For NO{sub 2} gas, this quasi 2D-black phosphorene surface shows strong affinity followed with substantial charge tranfer. - Abstract: We present first principle structural, electronic, optical and transport analysis of black phosphorene a 2D layered material. The studied configuration shows semiconducting nature and the states around the Fermi energy are mainly contributed by the p-orbitals of atoms. In optical properties, the reflective spectrum is approximately dispersed in visible range suggesting that this 2D-nanostructure can be considered as shielding for visible region. Due to the anisotropy of the electronic structure of black phosphorene, the device performance is subtaintially preferable in armchair direction. Zero-bias transmission shows no conductance channel near Fermi level but in far region prominent spectra for the same is observed for black-phospherene. The studied configurations show non-linear current–voltage (I–V) characteristics. The sensitivity for NH{sub 3} and NO{sub 2} gas molecule is explored using electronic and current–voltage (I–V) characteristics. Investigations show that the black phosphorene has strong affinity for electron seeking NO{sub 2} molecule, thus providing an opportunity for its sensor application.

  9. COMT Val(158)Met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence: results from the Victorian Adolescent Health Cohort Study.

    Science.gov (United States)

    Olsson, C A; Byrnes, G B; Anney, R J L; Collins, V; Hemphill, S A; Williamson, R; Patton, G C

    2007-10-01

    We investigated whether a composite genetic factor, based on the combined actions of catechol-O-methyltransferase (COMT) (Val(158)Met) and serotonin transporter (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight-wave longitudinal study of mental health and well-being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose-response reductions in the odds of reporting persisting generalized (free-floating) anxiety across adolescence were observed for the COMT Met(158) [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76-0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79-0.99, P = 0.033). There was no evidence for a dose-response interaction effect between loci. However, there was a double-recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29-0.70, P anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.

  10. Surmounting the unique challenges in health disparities education: a multi-institution qualitative study.

    Science.gov (United States)

    Carter-Pokras, Olivia; Bereknyei, Sylvia; Lie, Desiree; Braddock, Clarence H

    2010-05-01

    The National Consortium for Multicultural Education for Health Professionals (Consortium) comprises educators representing 18 US medical schools, funded by the National Institutes of Health. Collective lessons learned from curriculum implementation by principal investigators (PIs) have the potential to guide similar educational endeavors. Describe Consortium PI's self-reported challenges with curricular development, solutions and their new curricular products. Information was collected from PIs over 2 months using a 53-question structured three-part questionnaire. The questionnaire addressed PI demographics, curriculum implementation challenges and solutions, and newly created curricular products. Study participants were 18 Consortium PIs. Descriptive analysis was used for quantitative data. Narrative responses were analyzed and interpreted using qualitative thematic coding. Response rate was 100%. Common barriers and challenges identified by PIs were: finding administrative and leadership support, sustaining the momentum, continued funding, finding curricular space, accessing and engaging communities, and lack of education research methodology skills. Solutions identified included engaging stakeholders, project-sharing across schools, advocacy and active participation in committees and community, and seeking sustainable funding. All Consortium PIs reported new curricular products and extensive dissemination efforts outside their own institutions. The Consortium model has added benefits for curricular innovation and dissemination for cultural competence education to address health disparities. Lessons learned may be applicable to other educational innovation efforts.

  11. Living with pulmonary hypertension: unique insights from an international ethnographic study.

    Science.gov (United States)

    Kingman, Martha; Hinzmann, Barbara; Sweet, Oliver; Vachiéry, Jean-Luc

    2014-05-16

    To better understand the patient's perspective of pulmonary hypertension (PH), including the impact of living with PH, disease management and treatment. This qualitative ethnographic study collected observational video footage, supplemented by field notes and patient diaries to assess the impact of PH on the patient's life. Patients were observed and filmed in their home for up to 6 h, capturing the environment, interactions and activities of everyday life. Patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic PH who were receiving PAH-specific medication were recruited through healthcare professionals (HCPs) and patient associations in seven countries across four continents. Sampling was purposive and subgroup analysis was not intended. Overall, 39 patients with PH were enrolled. Many patients had a poor understanding of PH and found their 'invisible' disease difficult to explain to others. An important finding was the secrecy surrounding PH. Feelings of insecurity and isolation were regularly reported, and many patients admitted to hiding their symptoms. The marked improvement in symptoms after therapy initiation made assessment of disease progression more difficult as patients compared their quality of life (QoL) against pretreatment levels. Extensive planning and adherence to daily routines were required in patients' everyday life. Ethnography was used for the first time, in several countries, to evaluate the patient's perception of living with PH. This approach revealed key findings that would not typically be uncovered using other qualitative techniques, including the secrecy surrounding PH, the difficulties in describing the disease and the challenges in assessing disease progression. A more tailored dissemination of information from HCPs and development of a simple and understandable PH definition may be beneficial in alleviating the secrecy reported by patients. A greater appreciation of how patients perceive their disease and Qo

  12. Towards a network of Urban Forest Eddy Covariance stations: a unique case study in Naples

    Science.gov (United States)

    Guidolotti, Gabriele; Pallozzi, Emanuele; Esposito, Raffaela; Mattioni, Michele; Calfapietra, Carlo

    2015-04-01

    Urban forests are by definition integrated in highly human-made areas, and interact with different components of our cities. Thanks to those interactions, urban forests provide to people and to the urban environment a number of ecosystem services, including the absorption of CO2 and air pollutants thus influencing the local air quality. Moreover, in urban areas a relevant role is played by the photochemical pollution which is strongly influenced by the interactions between volatile organic compounds (VOC) and nitrogen oxides (NOx). In several cities, a high percentage of VOC is of biogenic origin mainly emitted from the urban trees. Despite their importance, experimental sites monitoring fluxes of trace gases fluxes in urban forest ecosystems are still scarce. Here we show the preliminary results of an innovative experimental site located in the Royal Park of Capodimonte within the city of Naples (40°51'N-14°15'E, 130 m above sea level). The site is mainly characterised by Quercus ilex with some patches of Pinus pinea and equipped with an eddy-covariance tower measuring the exchange of CO2, H2O, N2O, CH4, O3, PM, VOCs and NOx using state-of-the art instrumentations; it is running since the end of 2014 and it is part of the large infrastructural I-AMICA project. We suggest that the experience gained with research networks such as Fluxnet and ICOS should be duplicated for urban forests. This is crucial for carbon as there is now the ambition to include urban forests in the carbon stocks accounting system. This is even more important to understand the difficult interactions between anthropogenic and biogenic sources that often have negative implications for urban air quality. Urban environment can thus become an extraordinary case study and a network of such kind of stations might represent an important strategy both from the scientific and the applicative point of view.

  13. Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Skiöld, Sara [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Azimzadeh, Omid [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Merl-Pham, Juliane [Research Unit Protein Science, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg (Germany); Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet [Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm (Sweden); Tapio, Soile [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Harms-Ringdahl, Mats [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Haghdoost, Siamak, E-mail: Siamak.Haghdoost@su.se [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden)

    2015-06-15

    Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy.

  14. Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

    International Nuclear Information System (INIS)

    Skiöld, Sara; Azimzadeh, Omid; Merl-Pham, Juliane; Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet; Tapio, Soile; Harms-Ringdahl, Mats; Haghdoost, Siamak

    2015-01-01

    Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy

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

    NARCIS (Netherlands)

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

    1989-01-01

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

  16. Observations from Space: A Unique Vantage Point for the Study of the Environment and Possible Associations with Disease Occurrence

    Science.gov (United States)

    Estes, S.; Haynes, J.; Hamdan, M. Al; Estes, M.; Sprigg, W.

    2009-01-01

    Health providers/researchers need environmental data to study and understand the geographic, environmental, and meteorological differences in disease. Satellite remote sensing of the environment offers a unique vantage point that can fill in the gaps of environmental, spatial, and temporal data for tracking disease. The field of geospatial health remains in its infancy, and this program will demonstrate the need for collaborations between multi-disciplinary research groups to develop the full potential. NASA will discuss the Public Health Projects developed to work with Grantees and the CDC while providing them with information on opportunities for future collaborations with NASA for future research.

  17. Microbewerking met behulp van lasers

    NARCIS (Netherlands)

    Ezendam, M.M.M.

    1994-01-01

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

  18. A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

    Science.gov (United States)

    2018-01-29

    Non-Small Cell Lung Cancer ALK-positive; Non-Small Cell Lung Cancer c-Met Dependent; Non-Small Cell Lung Cancer ROS Marker Positive; Systemic Anaplastic Large-Cell Lymphoma; Advanced Malignancies Except Leukemia

  19. Reactions of Met-Cars

    International Nuclear Information System (INIS)

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

    1993-01-01

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

  20. NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research.

    Science.gov (United States)

    Zhang, Guo-Qiang; Tao, Shiqiang; Xing, Guangming; Mozes, Jeno; Zonjy, Bilal; Lhatoo, Samden D; Cui, Licong

    2015-11-10

    A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. This paper introduces a novel method called "Randomized N-gram Hashing (NHash)," for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f1, f2, ..., fk. The input for each function fi has 3 components: a random number r, an integer n, and input data m. The result, fi(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f1(r1, n1, m1), f2(r2, n2, m2), ..., fk(rk, nk, mk). In the second phase, the intermediate string generated in Phase 1 is encrypted using techniques such as shift cipher. The result

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

    International Nuclear Information System (INIS)

    Wang Bingkui; Jin Ziyu; Zhao Miaozhen; Zhao Yanshen

    1993-01-01

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

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

    NARCIS (Netherlands)

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

    1989-01-01

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

  3. 'Geschiedenis is nu eenmaal altijd politiek.' De studie-Drooglever als symptoom van de moeizame omgang van Nederland met het koloniaal verleden en de complexe relatie met Indonesië. Discussie over Een daad van vrije keuze

    Directory of Open Access Journals (Sweden)

    H. Meijer

    2007-01-01

    Full Text Available ‘History is by definition political’. The Drooglever study as a symptom of the uneasy relationship the Netherlands has with its colonial past and its complex relationship with IndonesiaIn December 1999, the Dutch Minister of Foreign Affairs, J.J. van Aartsen, complied with a request from parliament for an historical study into the referendum held in 1969 among the Papua population in the former Dutch New Guinea. The outcome of this ‘Act of Free Choice’ was manipulated and resulted in the territory becoming a permanent part of Indonesia, which is what Indonesia had coveted all along.  The decision to carry out the study angered the Indonesian government and resulted in a deterioration of the already fragile bilateral relations between both countries. When Drooglever’s findings were published the Balkenende II (2003-2006 cabinet was confronted with a dilemma: how could it do justice to the study carried out by the historian P. J. Drooglever on the one hand, yet try to repair the political damage to its relations with Indonesia on the other. In the context of the complex Dutch-Indonesian relationship in general this article not only deals with Van Aartsen’s motives for accepting this controversial research, but also explains why Indonesia reacted as it did and outlines how the Balkenende government tried to deal with this thorny issue.

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

    Science.gov (United States)

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

    2014-06-01

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

  5. Study of expression of genes cIAP and cMET, in liver tissue with and without neoplasia of Rattus norvegicus

    International Nuclear Information System (INIS)

    Coto Valverde, Daniel Esteban

    2010-01-01

    The expression levels of cIAP genes and cMET were determined in liver tissues with and without neoplasm of the organism Rattus norvegicus, for prevention, diagnosis and treatment of hepatocellular carcinoma. The technique of reaction Polymerase Chain in real time (qPCR), is used to obtain the expression, of both genes cIAP and cMET, and this has decreased in neoplastic samples compared to samples not affected. The expression of these genes has been analyzed in samples with neoplastic formations, but treated with an anti-tumor agent. The expression has presented an increase of the cMET gene, unlike the cIAP gene, which has decreased its expression. Perform statistical analysis has been impossible because the number of samples used has been reduced. The results obtained differ with those expected theoretically. (author) [es

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

    Science.gov (United States)

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

    2018-04-08

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

  7. The social patterning of risk factors for noncommunicable diseases in five countries: evidence from the modeling the epidemiologic transition study (METS

    Directory of Open Access Journals (Sweden)

    Silvia Stringhini

    2016-09-01

    Full Text Available Abstract Background Associations between socioeconomic status (SES and risk factors for noncommunicable diseases (NCD-RFs may differ in populations at different stages of the epidemiological transition. We assessed the social patterning of NCD-RFs in a study including populations with different levels of socioeconomic development. Methods Data on SES, smoking, physical activity, body mass index, blood pressure, cholesterol and glucose were available from the Modeling the Epidemiologic Transition Study (METS, with about 500 participants aged 25–45 in each of five sites (Ghana, South Africa, Jamaica, Seychelles, United States. Results The prevalence of NCD-RFs differed between these populations from five countries (e.g., lower prevalence of smoking, obesity and hypertension in rural Ghana and by sex (e.g., higher prevalence of smoking and physical activity in men and of obesity in women in most populations. Smoking and physical activity were associated with low SES in most populations. The associations of SES with obesity, hypertension, cholesterol and elevated blood glucose differed by population, sex, and SES indicator. For example, the prevalence of elevated blood glucose tended to be associated with low education, but not with wealth, in Seychelles and USA. The association of SES with obesity and cholesterol was direct in some populations but inverse in others. Conclusions In conclusion, the distribution of NCD-RFs was socially patterned in these populations at different stages of the epidemiological transition, but associations between SES and NCD-RFs differed substantially according to risk factor, population, sex, and SES indicator. These findings emphasize the need to assess and integrate the social patterning of NCD-RFs in NCD prevention and control programs in LMICs.

  8. A survival analysis of the liver-first reversed management of advanced simultaneous colorectal liver metastases: a LiverMetSurvey-based study.

    Science.gov (United States)

    Andres, Axel; Toso, Christian; Adam, Rene; Barroso, Eduardo; Hubert, Catherine; Capussotti, Lorenzo; Gerstel, Eric; Roth, Arnaud; Majno, Pietro E; Mentha, Gilles

    2012-11-01

    Liver-first reversed management (RM) for the treatment of patients with simultaneous colorectal liver metastases (CRLM) includes liver-directed chemotherapy, the resection of the CRLM, and the subsequent resection of the primary cancer. Retrospective data have shown that up to 80% of patients can successfully undergo a complete RM, whereas less than 30% of those undergoing classical management (CM) do so. This registry-based study compared the 2 approaches. The study was based on the LiverMetSurvey (January 1, 2000 to December 31, 2010) and included patients with 2 or more metastases. All patients had irinotecan and/or oxaliplatin-based chemotherapy before liver surgery. Patients undergoing simultaneous liver and colorectal surgery were excluded. A total of 787 patients were included: 729 in the CM group and 58 in the RM group. Patients in the 2 groups had similar numbers of metastases (4.20 vs 4.80 for RM and CM, P = 0.231) and Fong scores of 3 or more (79% vs 87%, P = 0.164). Rectal cancer, neoadjuvant rectal radiotherapy, and the use of combined irinotecan/oxaliplatin chemotherapy were more frequent in the RM group (P < 0.001), whereas colorectal lymph node involvement was more frequent in the CM group (P < 0.001). Overall survival and disease-free survival were similar in the RM and CM groups (48% vs 46% at 5 years, P = 0.965 and 30% vs 26%, P = 0.992). Classical and reversed managements of metastatic liver disease in colorectal cancer are associated with similar survival when successfully completed.

  9. The role of brain-derived neurotrophic factor (BDNF) Val66Met genetic polymorphism in bipolar disorder: a case-control study, comorbidities, and meta-analysis of 16,786 subjects.

    Science.gov (United States)

    González-Castro, Thelma Beatriz; Nicolini, Humberto; Lanzagorta, Nuria; López-Narváez, Lilia; Genis, Alma; Pool García, Sherezada; Tovilla-Zárate, Carlos Alfonso

    2015-02-01

    The aim of this study was to evaluate the association of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism with bipolar disorder in (i) a meta-analysis and (ii) a case-control study in a Mexican population. We also investigated the possible association of this polymorphism with clinical features. We performed a keyword search of the PubMed and Web of Science databases. A total of 22 studies that have investigated the association of Val66Met (rs6265) with bipolar disorder were selected for inclusion and combined with random effects meta-analysis, using allelic, additive, dominant, and recessive models. Finally, the single nucleotide polymorphism (rs6265) Val66Met in the BDNF gene was genotyped and compared between 139 patients with bipolar disorder and 141 healthy volunteers in a Mexican population. The pooled results from the meta-analysis (9,349 cases and 7,437 controls) did not show a significant association in any of the models. The same results were obtained in our case-control study when analyzing the distribution of the genotypic frequencies of the Val66Met polymorphism in patients with bipolar disorder. However, when we analyzed the association between rs6265 and lifetime history of suicidal behavior, we found an association between genotype Val-Val and suicide attempt (p = 0.02). Although the present study has some limitations, the results indicate a lack of association between the Val66Met polymorphism and bipolar disorder. However, in our case-control study in a Mexican population, the Val66Met polymorphism was associated with suicidal behavior in patients with bipolar disorder. Nevertheless, it is important to consider potential interactions of the BDNF gene, the environment, and different inheritance patterns, when carrying out future genetic studies with larger samples. © 2014 The Authors. Bipolar Disorders Published by John Wiley & Sons Ltd.

  10. Studentmonitor 2013, constantly connected : Studie 1: een onderzoek naar het social mediagebruik onder NHL-studenten in 2013, vergeleken met 2012

    NARCIS (Netherlands)

    R Rozenberg; M Oldengarm; Klaas Jan Huizing; J Veltman; S Schotanus; GJ van Dam

    2014-01-01

    Facebook, Instagram, Snapchat: de student van nu is de hele dag in de weer met zijn smartphone. Bij Sowijs vroegen we ons af: hoe ontwikkelt het social mediagebruik van studenten zich? Veranderen de motieven om social media te gebruiken? En veranderen de onderwerpen die ze posten?

  11. Complete study of the existence and uniqueness of solutions for semilinear elliptic equations involving measures concentrated on boundary

    KAUST Repository

    Chen, Huyuan

    2017-02-06

    The purpose of this paper is to study the weak solutions of the fractional elliptic problem(Formula presented.) where (Formula presented.), (Formula presented.) or (Formula presented.), (Formula presented.) with (Formula presented.) is the fractional Laplacian defined in the principle value sense, (Formula presented.) is a bounded (Formula presented.) open set in (Formula presented.) with (Formula presented.), (Formula presented.) is a bounded Radon measure supported in (Formula presented.) and (Formula presented.) is defined in the distribution sense, i.e.(Formula presented.) here (Formula presented.) denotes the unit inward normal vector at (Formula presented.). In this paper, we prove that (0.1) with (Formula presented.) admits a unique weak solution when g is a continuous nondecreasing function satisfying(Formula presented.) Our interest then is to analyse the properties of weak solution when (Formula presented.) with (Formula presented.), including the asymptotic behaviour near (Formula presented.) and the limit of weak solutions as (Formula presented.). Furthermore, we show the optimality of the critical value (Formula presented.) in a certain sense, by proving the non-existence of weak solutions when (Formula presented.). The final part of this article is devoted to the study of existence for positive weak solutions to (0.1) when (Formula presented.) and (Formula presented.) is a bounded nonnegative Radon measure supported in (Formula presented.). We employ the Schauder’s fixed point theorem to obtain positive solution under the hypothesis that g is a continuous function satisfying(Formula presented.)-pagination

  12. Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

    Science.gov (United States)

    Mager, U; Lindi, V; Lindström, J; Eriksson, J G; Valle, T T; Hämäläinen, H; Ilanne-Parikka, P; Keinänen-Kiukaanniemi, S; Tuomilehto, J; Laakso, M; Pulkkinen, L; Uusitupa, M

    2006-06-01

    Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.

  13. Base pair mismatches and carcinogen-modified bases in DNA: an NMR study of G x T and G x O4meT pairing in dodecanucleotide duplexes

    International Nuclear Information System (INIS)

    Kalnik, M.W.; Kouchakdjian, M.; Li, B.F.L.; Swann, P.F.; Patel, D.J.

    1988-01-01

    High-resolution two-dimensional NMR studies have been completed on the self-complementary d(C-G-C-G-A-G-C-T-T-G-C-G) duplex (designated G x T 12-mer) and the self-complementary d(C-G-C-G-A-G-C-T-O 4 meT-G-C-G) duplex (designated G x O 4 meT 12-mer) containing G x T and G x O 4 meT pairs at identical positions four base pairs in from either end of the duplex. The exchangeable and nonexchangeable proton resonances have been assigned from an analysis of two-dimensional nuclear Overhauser enhancement (NOESY) spectra for the G x T 12-mer and G x O 4 meT 12-mer duplexes in H 2 O and D 2 O solution. The guanosine and thymidine imino protons in the G x T mismatch resonate at 10.57 and 11.98 ppm, respectively, and exhibit a strong NOE between themselves and to imino protons of flanking base pairs in the G x T 12-mer duplex. The large upfield chemical shift of this proton relative to that of the imino proton resonance of G in the G x T mismatch or in G x C base pairs indicates that hydrogen bonding to O 4 meT is either very weak or absent. This guanosine imino proton has an NOE to the OCH 3 group of O 4 meT across the pair and NOEs to the imino protons of flanking base pairs. Taken together with data from the NMR of nonexchangeable protons, this shows that both G and O 4 meT have anti-glycosidic torsion angles and are stacked into the duplex. Comparison of the intensity of the NOEs between the guanosine imino proton and the OCH 3 of O 4 meT as well as other protons in its vicinity demonstrates that the OCH 3 group of O 4 meT adopts the syn orientation with respect to N3 of the methylated thymidine. The authors propose an alternate base pairing mode stabilized by one short hydrogen bond between the 2-amino group of guanosine and the 2-carbonyl group of O 4 met

  14. Impact of extracorporeal shock waves on the human skin with cellulite: A case study of an unique instance

    Science.gov (United States)

    Kuhn, Christoph; Angehrn, Fiorenzo; Sonnabend, Ortrud; Voss, Axel

    2008-01-01

    In this case study of an unique instance, effects of medium-energy, high-focused extracorporeal generated shock waves (ESW) onto the skin and the underlying fat tissue of a cellulite afflicted, 50-year-old woman were investigated. The treatment consisted of four ESW applications within 21 days. Diagnostic high-resolution ultrasound (Collagenoson) was performed before and after treatment. Directly after the last ESW application, skin samples were taken for histopathological analysis from the treated and from the contra-lateral untreated area of skin with cellulite. No damage to the treated skin tissue, in particular no mechanical destruction to the subcutaneous fat, could be demonstrated by histopathological analysis. However an astounding induction of neocollageno- and neoelastino-genesis within the scaffolding fabric of the dermis and subcutis was observed. The dermis increased in thickness as well as the scaffolding within the subcutaneous fat-tissue. Optimization of critical application parameters may turn ESW into a noninvasive cellulite therapy. PMID:18488890

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

    Science.gov (United States)

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

    2016-01-01

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

  16. The Interacting Effect of the BDNF Val66Met Polymorphism and Stressful Life Events on Adolescent Depression Is Not an Artifact of Gene-Environment Correlation: Evidence from a Longitudinal Twin Study

    Science.gov (United States)

    Chen, Jie; Li, Xinying; McGue, Matt

    2013-01-01

    Background: Confounding introduced by gene-environment correlation (rGE) may prevent one from observing a true gene-environment interaction (G × E) effect on psychopathology. The present study investigated the interacting effect of the BDNF Val66Met polymorphism and stressful life events (SLEs) on adolescent depression while controlling for the…

  17. An Australian Aboriginal birth cohort: a unique resource for a life course study of an Indigenous population. A study protocol

    Directory of Open Access Journals (Sweden)

    Flynn Kathryn

    2003-03-01

    Full Text Available Abstract Background The global rise of Type 2 diabetes and its complications has drawn attention to the burden of non-communicable diseases on populations undergoing epidemiological transition. The life course approach of a birth cohort has the potential to increase our understanding of the development of these chronic diseases. In 1987 we sought to establish an Australian Indigenous birth cohort to be used as a resource for descriptive and analytical studies with particular attention on non-communicable diseases. The focus of this report is the methodology of recruiting and following-up an Aboriginal birth cohort of mobile subjects belonging to diverse cultural and language groups living in a large sparsely populated area in the Top End of the Northern Territory of Australia. Methods A prospective longitudinal study of Aboriginal singletons born at the Royal Darwin Hospital 1987–1990, with second wave cross-sectional follow-up examination of subjects 1998–2001 in over 70 different locations. A multiphase protocol was used to locate and collect data on 686 subjects with different approaches for urban and rural children. Manual chart audits, faxes to remote communities, death registries and a full time subject locator with past experience of Aboriginal communities were all used. Discussion The successful recruitment of 686 Indigenous subjects followed up 14 years later with vital status determined for 95% of subjects and examination of 86% shows an Indigenous birth cohort can be established in an environment with geographic, cultural and climatic challenges. The high rates of recruitment and follow up indicate there were effective strategies of follow-up in a supportive population.

  18. A Validation Study of the Rank-Preserving Structural Failure Time Model: Confidence Intervals and Unique, Multiple, and Erroneous Solutions.

    Science.gov (United States)

    Ouwens, Mario; Hauch, Ole; Franzén, Stefan

    2018-05-01

    The rank-preserving structural failure time model (RPSFTM) is used for health technology assessment submissions to adjust for switching patients from reference to investigational treatment in cancer trials. It uses counterfactual survival (survival when only reference treatment would have been used) and assumes that, at randomization, the counterfactual survival distribution for the investigational and reference arms is identical. Previous validation reports have assumed that patients in the investigational treatment arm stay on therapy throughout the study period. To evaluate the validity of the RPSFTM at various levels of crossover in situations in which patients are taken off the investigational drug in the investigational arm. The RPSFTM was applied to simulated datasets differing in percentage of patients switching, time of switching, underlying acceleration factor, and number of patients, using exponential distributions for the time on investigational and reference treatment. There were multiple scenarios in which two solutions were found: one corresponding to identical counterfactual distributions, and the other to two different crossing counterfactual distributions. The same was found for the hazard ratio (HR). Unique solutions were observed only when switching patients were on investigational treatment for <40% of the time that patients in the investigational arm were on treatment. Distributions other than exponential could have been used for time on treatment. An HR equal to 1 is a necessary but not always sufficient condition to indicate acceleration factors associated with equal counterfactual survival. Further assessment to distinguish crossing counterfactual curves from equal counterfactual curves is especially needed when the time that switchers stay on investigational treatment is relatively long compared to the time direct starters stay on investigational treatment.

  19. La metáfora

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2007-01-01

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

  20. Integration of an In Situ MALDI-Based High-Throughput Screening Process: A Case Study with Receptor Tyrosine Kinase c-MET.

    Science.gov (United States)

    Beeman, Katrin; Baumgärtner, Jens; Laubenheimer, Manuel; Hergesell, Karlheinz; Hoffmann, Martin; Pehl, Ulrich; Fischer, Frank; Pieck, Jan-Carsten

    2017-12-01

    Mass spectrometry (MS) is known for its label-free detection of substrates and products from a variety of enzyme reactions. Recent hardware improvements have increased interest in the use of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS for high-throughput drug discovery. Despite interest in this technology, several challenges remain and must be overcome before MALDI-MS can be integrated as an automated "in-line reader" for high-throughput drug discovery. Two such hurdles include in situ sample processing and deposition, as well as integration of MALDI-MS for enzymatic screening assays that usually contain high levels of MS-incompatible components. Here we adapt our c-MET kinase assay to optimize for MALDI-MS compatibility and test its feasibility for compound screening. The pros and cons of the Echo (Labcyte) as a transfer system for in situ MALDI-MS sample preparation are discussed. We demonstrate that this method generates robust data in a 1536-grid format. We use the MALDI-MS to directly measure the ratio of c-MET substrate and phosphorylated product to acquire IC50 curves and demonstrate that the pharmacology is unaffected. The resulting IC50 values correlate well between the common label-based capillary electrophoresis and the label-free MALDI-MS detection method. We predict that label-free MALDI-MS-based high-throughput screening will become increasingly important and more widely used for drug discovery.

  1. Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment

    DEFF Research Database (Denmark)

    Johnsen, Hanne; Geisler, C; Juvonen, E

    2011-01-01

    methionyl human G-CSF (filgrastim, r-metHuG-CSF) (experimental arm A) or routine chemotherapy plus filgrastim (conventional arm B). The primary objective was to evaluate the side effects and toxicity during priming and mobilization. The secondary objectives were efficacy by the level of blood......-circulating PBPCs, the number of harvest days and the time to three-lineage engraftment after autografting. First, during priming 5 patients had 8 serious events, 4 in each arm. A summary of all adverse events revealed 30 (94%) patients suffering from 132 events of all grading. Second, neutropenia...... and thrombocytopenia was documented in arm B. Third, 9/14 (64%) patients in arm A reached the target of 5 million CD34(+) cells/kg body weight (bw) compared with 13/15 (87%) in arm B. The results represent the first randomized trial of growth factor plus chemotherapy priming and indicate that a formal phase III trial...

  2. A Signal Detection Approach in a Multiple Cohort Study: Different Admission Tools Uniquely Select Different Successful Students

    Directory of Open Access Journals (Sweden)

    Linda van Ooijen-van der Linden

    2018-05-01

    Full Text Available Using multiple admission tools in university admission procedures is common practice. This is particularly useful if different admission tools uniquely select different subgroups of students who will be successful in university programs. A signal-detection approach was used to investigate the accuracy of Secondary School grade point average (SSGPA, an admission test score (ACS, and a non-cognitive score (NCS in uniquely selecting successful students. This was done for three consecutive first year cohorts of a broad psychology program. Each applicant's score on SSGPA, ACS, or NCS alone—and on seven combinations of these scores, all considered separate “admission tools”—was compared at two different (medium and high cut-off scores (criterion levels. Each of the tools selected successful students who were not selected by any of the other tools. Both sensitivity and specificity were enhanced by implementing multiple tools. The signal-detection approach distinctively provided useful information for decisions on admission instruments and cut-off scores.

  3. Targeting MET Amplification as a New Oncogenic Driver

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-22

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

  4. Targeting MET Amplification as a New Oncogenic Driver

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Na Song

    2014-04-01

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

  7. Efficacy of Bacillus coagulans Unique IS2 in treatment of irritable bowel syndrome in children: a double blind, randomised placebo controlled study.

    Science.gov (United States)

    Sudha, M Ratna; Jayanthi, N; Aasin, M; Dhanashri, R D; Anirudh, T

    2018-04-26

    The efficacy of the probiotic strain, Bacillus coagulans Unique IS2 in the treatment of Irritable Bowel Syndrome (IBS) was evaluated in children. A total of 141 children of either sex in the age group 4-12 years, diagnosed with IBS according to the Rome III criteria, participated in the double-blind randomised controlled trial. Children received either B. coagulans Unique IS2 chewable tablets or placebo once daily for eight weeks followed by a two week follow-up period. Reduction in pain intensity as well as other symptoms associated with Irritable Bowel Syndrome like abdominal discomfort, bloating, distension, sense of incomplete evacuation, straining at stool, urgency of bowel movement, passage of gas and mucus, and bowel habit satisfaction were assessed. B. coagulans Unique IS2 treated group showed a greater reduction in pain scores as evaluated by a weekly pain intensity scale. There was a significant reduction (Pcoagulans Unique IS2 treated group as compared to the placebo group. This study demonstrates the efficacy of B. coagulans Unique IS2 in reducing the symptoms of Irritable Bowel Syndrome in children in the age group of 4-12 years.

  8. Unique Capabilities of the Situational Awareness Sensor Suite for the ISS (SASSI) Mission Concept to Study the Equatorial Ionosphere

    Science.gov (United States)

    Habash Krause, L.; Gilchrist, B. E.; Minow, J. I.; Gallagher, D. L.; Hoegy, W. R.; Coffey, V. N.; Willis, E. M.

    2014-12-01

    We present an overview of a mission concept named Situational Awareness Sensor Suite for the ISS (SASSI) with a special focus here on low-latitude ionospheric plasma turbulence measurements relevant to equatorial spread-F. SASSI is a suite of sensors that improves Space Situational Awareness for the ISS local space environment, as well as unique ionospheric measurements and support active plasma experiments on the ISS. As such, the mission concept has both operational and basic research objectives. We will describe two compelling measurement techniques enabled by SASSI's unique mission architecture. That is, SASSI provides new abilities to 1) measure space plasma potentials in low Earth orbit over ~100 m relative to a common potential, and 2) to investigate multi-scale ionospheric plasma turbulence morphology simultaneously of both ~ 1 cm and ~ 10 m scale lengths. The first measurement technique will aid in the distinction of vertical drifts within equatorial plasma bubbles from the vertical motions of the bulk of the layer due to zonal electric fields. The second will aid in understanding ionospheric plasma turbulence cascading in scale sizes that affect over the horizon radar. During many years of ISS operation, we have conducted effective (but not perfect) human and robotic extravehicular activities within the space plasma environment surrounding the ISS structure. However, because of the complexity of the interaction between the ISS and the space environment, there remain important sources of unpredictable environmental situations that affect operations. Examples of affected systems include EVA safety, solar panel efficiency, and scientific instrument integrity. Models and heuristically-derived best practices are well-suited for routine operations, but when it comes to unusual or anomalous events or situations, there is no substitute for real-time monitoring. SASSI is being designed to deploy and operate a suite of low-cost, medium/high-TRL plasma sensors on

  9. Proef met duurzaam watergebruik in de bollenstreek

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  11. Uniqueness in time measurement

    International Nuclear Information System (INIS)

    Lorenzen, P.

    1981-01-01

    According to P. Janich a clock is defined as an apparatus in which a point ( hand ) is moving uniformly on a straight line ( path ). For the definition of uniformly first the scaling (as a constant ratio of velocities) is defined without clocks. Thereafter the uniqueness of the time measurement can be proved using the prove of scaling of all clocks. But the uniqueness can be defined without scaling, as it is pointed out here. (orig.) [de

  12. An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

    Science.gov (United States)

    Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

    2016-12-01

    Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

  13. The liberal illusion of uniqueness.

    Science.gov (United States)

    Stern, Chadly; West, Tessa V; Schmitt, Peter G

    2014-01-01

    In two studies, we demonstrated that liberals underestimate their similarity to other liberals (i.e., display truly false uniqueness), whereas moderates and conservatives overestimate their similarity to other moderates and conservatives (i.e., display truly false consensus; Studies 1 and 2). We further demonstrated that a fundamental difference between liberals and conservatives in the motivation to feel unique explains this ideological distinction in the accuracy of estimating similarity (Study 2). Implications of the accuracy of consensus estimates for mobilizing liberal and conservative political movements are discussed.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chris M Dodds

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

  16. A case of Occupational Methemoglobinemia (MetHb: A Rare Entity and Unique Treatment

    Directory of Open Access Journals (Sweden)

    Suvarna Patil

    2017-11-01

    Full Text Available Methemoglobinemia is acute emergency which have precise and effective treatment if instituted in time. Methemoglobinemia due to chemical exposure is a known entity. But it required a high index of suspicion to look for it in busy casualty. Treatment with methylene blue is safe and truly lifesaving if instituted in time. Here we are presenting a case of Occupational methemoglobinemia who was treated successfully.

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

    OpenAIRE

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

    2013-01-01

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

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

    2018-06-01

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

  20. NASA Satellite Observations: A Unique Asset for the Study of the Environment and Implications for Public Health

    Science.gov (United States)

    Estes Sue M.

    2010-01-01

    This slide presentation highlights how satellite observation systems are assets for studying the environment in relation to public health. It includes information on current and future satellite observation systems, NASA's public health and safety research, surveillance projects, and NASA's public health partners.

  1. The study of polymeric hydro-gels with unique properties obtained by polymerization with gamma radiation processing

    International Nuclear Information System (INIS)

    Dragusin, M.

    1995-01-01

    This thesis presents the work carried out on polymeric hydro-gels obtained by radiation processing using 60 Co gamma rays from the irradiation facility IETI-10.000 (10 k Ci), and on the polymeric hydro-gels obtained by irradiation with the electron beams from a linear accelerator (6 MeV). The aim of the study was to determine the effect of the rate dose and total dose absorbed in the materials. There are presented the preparation methods of homo- and co-polymer hydro-gels (acrylics, namely anionic and neutral monomers (acrylamide, acrylic acid, vinyl acetate) and cationic monomers (di-methyl di-allyl ammonium chloride)) such as floculants, additives, absorbers, etc. Concerning with these we have analysed the preparation methods, the mechanical, thermal, diffusivity, and swelling properties of polymeric hydro-gels in a large variety of gels of type I or II. The technological aspects and end use were studied in connection with the characteristics of the radiation processing of these hydro-gels as a function of chemical composition rate and absorbed dose, swelling degree (low and very high hydro-soluble), mechanical and diffusional properties. (author) 33 figs., 12 tabs., 101 refs

  2. Responding to Trauma at Sea: A Case Study in Psychological First Aid, Unique Occupational Stressors, and Resiliency Self-Care.

    Science.gov (United States)

    Millegan, Jeffrey; Delaney, Eileen M; Klam, Warren

    2016-11-01

    The U.S. Navy deploys Special Psychiatric Rapid Intervention Teams (SPRINT) to sites of military disasters to assist survivors and the command. SPRINT functions primarily as a consultant to help commands effectively respond to the mental health needs of their service members following a traumatic event. Utilizing the principles of psychological first aid, the overall goal of SPRINT is to mitigate long-term mental health dysfunction and facilitate recovery at both the individual and unit level. We present a case study of a SPRINT mission to a deployed U.S. Navy ship in response to a cluster of suicides and subsequent concerns about the well-being of the remaining crew. Throughout this mission, important themes emerged, such as the impact of accumulated operational stressors and the subsequent development of mental health stigma. Also, this case study demonstrates the potential effectiveness of introducing resiliency self-care meditation training to remote environments that lack ready access to mental health resources. From here, SPRINT can provide a model for immediate disaster mental health response that has potential relevancy beyond the military. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  3. The role of catechol-O-methyl transferase Val(108/158Met polymorphism (rs4680 in the effect of green tea on resting energy expenditure and fat oxidation: a pilot study.

    Directory of Open Access Journals (Sweden)

    Rick Hursel

    Full Text Available INTRODUCTION: Green tea(GT is able to increase energy expenditure(EE and fat oxidation(FATox via inhibition of catechol-O-methyl transferase(COMT by catechins. However, this does not always appear unanimously because of large inter-individual variability. This may be explained by different alleles of the functional COMT Val108/158Met polymorphism that are associated with COMT enzyme activity; high-activity enzyme, COMT(H(Val/Val genotype, and low-activity COMT(L(Met/Met genotype. METHODS: Fourteen Caucasian subjects (BMI: 22.2±2.3 kg/m2, age: 21.4±2.2 years of whom 7 with the COMT(H-genotype and 7 with the COMT(L-genotype were included in a randomized, cross-over study in which EE and substrate oxidation were measured with a ventilated-hood system after decaffeinated GT and placebo(PL consumption. RESULTS: At baseline, EE, RQ, FATox and carbohydrate oxidation(CHOox did not differ between groups. Significant interactions were observed between COMT genotypes and treatment for RQ, FATox and CHOox (p<0.05. After GT vs. PL, EE(GT: 62.2 vs. PL: 35.4 kJ.3.5 hrs; p<0.01, RQ(GT: 0.80 vs. PL: 0.83; p<0.01, FATox(GT: 18.3 vs. PL: 15.3 g/d; p<0.001 and CHOox(GT: 18.5 vs. PL: 24.3 g/d; p<0.001 were significantly different for subjects carrying the COMT(H genotype, but not for subjects carrying the COMT(L genotype (EE, GT: 60.3 vs. PL: 51.7 kJ.3.5 hrs; NS, (RQ, GT: 0.81 vs. PL: 0.81; NS, (FATox, GT: 17.3 vs. PL: 17.0 g/d; NS, (CHOox, GT: 22.1 vs. PL: 21.4 g/d; NS. CONCLUSION: Subjects carrying the COMT(H genotype increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs, placebo, whereas COMT(L genotype carriers reacted similarly to GT and PL ingestion. The differences in responses were due to the different responses on PL ingestion, but similar responses to GT ingestion, pointing to different mechanisms. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter

  4. Large-scale studies of the Leu72Met polymorphism of the ghrelin gene in relation to the metabolic syndrome and associated quantitative traits

    DEFF Research Database (Denmark)

    Bing, C; Ambye, L; Fenger, M

    2005-01-01

    Recently, low-frequency polymorphisms in the coding region of the ghrelin gene were suggested to be involved in the aetiology of obesity and to modulate glucose-induced insulin secretion in different ethnic study groups. The objective of the present large study was to investigate whether the Leu7...

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

    Directory of Open Access Journals (Sweden)

    Steven N Steinway

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

  6. Metsämaisema ulkoilijoiden kokemana

    OpenAIRE

    Vuohijoki, Jaana

    2010-01-01

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

  7. The structural chemistry of metallocorroles: combined X-ray crystallography and quantum chemistry studies afford unique insights.

    Science.gov (United States)

    Thomas, Kolle E; Alemayehu, Abraham B; Conradie, Jeanet; Beavers, Christine M; Ghosh, Abhik

    2012-08-21

    Although they share some superficial structural similarities with porphyrins, corroles, trianionic ligands with contracted cores, give rise to fundamentally different transition metal complexes in comparison with the dianionic porphyrins. Many metallocorroles are formally high-valent, although a good fraction of them are also noninnocent, with significant corrole radical character. These electronic-structural characteristics result in a variety of fascinating spectroscopic behavior, including highly characteristic, paramagnetically shifted NMR spectra and textbook cases of charge-transfer spectra. Although our early research on corroles focused on spectroscopy, we soon learned that the geometric structures of metallocorroles provide a fascinating window into their electronic-structural characteristics. Thus, we used X-ray structure determinations and quantum chemical studies, chiefly using DFT, to obtain a comprehensive understanding of metallocorrole geometric and electronic structures. This Account describes our studies of the structural chemistry of metallocorroles. At first blush, the planar or mildly domed structure of metallocorroles might appear somewhat uninteresting particularly when compared to metalloporphyrins. Metalloporphyrins, especially sterically hindered ones, are routinely ruffled or saddled, but the missing meso carbon apparently makes the corrole skeleton much more resistant to nonplanar distortions. Ruffling, where the pyrrole rings are alternately twisted about the M-N bonds, is energetically impossible for metallocorroles. Saddling is also uncommon; thus, a number of sterically hindered, fully substituted metallocorroles exhibit almost perfectly planar macrocycle cores. Against this backdrop, copper corroles stand out as an important exception. As a result of an energetically favorable Cu(d(x2-y2))-corrole(π) orbital interaction, copper corroles, even sterically unhindered ones, are inherently saddled. Sterically hindered substituents

  8. Oxidative stress inactivates cobalamin-independent methionine synthase (MetE in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Elise R Hondorp

    2004-11-01

    Full Text Available In nature, Escherichia coli are exposed to harsh and non-ideal growth environments-nutrients may be limiting, and cells are often challenged by oxidative stress. For E. coli cells confronting these realities, there appears to be a link between oxidative stress, methionine availability, and the enzyme that catalyzes the final step of methionine biosynthesis, cobalamin-independent methionine synthase (MetE. We found that E. coli cells subjected to transient oxidative stress during growth in minimal medium develop a methionine auxotrophy, which can be traced to an effect on MetE. Further experiments demonstrated that the purified enzyme is inactivated by oxidized glutathione (GSSG at a rate that correlates with protein oxidation. The unique site of oxidation was identified by selectively cleaving N-terminally to each reduced cysteine and analyzing the results by liquid chromatography mass spectrometry. Stoichiometric glutathionylation of MetE by GSSG occurs at cysteine 645, which is strategically located at the entrance to the active site. Direct evidence of MetE oxidation in vivo was obtained from thiol-trapping experiments in two different E. coli strains that contain highly oxidizing cytoplasmic environments. Moreover, MetE is completely oxidized in wild-type E. coli treated with the thiol-oxidizing agent diamide; reduced enzyme reappears just prior to the cells resuming normal growth. We argue that for E. coli experiencing oxidizing conditions in minimal medium, MetE is readily inactivated, resulting in cellular methionine limitation. Glutathionylation of the protein provides a strategy to modulate in vivo activity of the enzyme while protecting the active site from further damage, in an easily reversible manner. While glutathionylation of proteins is a fairly common mode of redox regulation in eukaryotes, very few proteins in E. coli are known to be modified in this manner. Our results are complementary to the independent findings of Leichert

  9. Studies toward the unique pederin family member psymberin: full structure elucidation, two alternative total syntheses, and analogs.

    Science.gov (United States)

    Feng, Yu; Jiang, Xin; De Brabander, Jef K

    2012-10-17

    Two synthetic approaches to psymberin have been accomplished. A highly convergent first generation synthesis led to the complete stereochemical assignment and demonstrated that psymberin and irciniastatin A are identical compounds. This synthesis featured a diastereoselective aldol coupling between the aryl fragment and a central tetrahydropyran core and a novel one-pot procedure to convert an amide, via intermediacy of a sensitive methyl imidate, to the N-acyl aminal reminiscent of psymberin. The highlights of the second generation synthesis include an efficient iridium-catalyzed enantioselective bisallylation of neopentyl glycol and a stepwise Sonogashira coupling/cycloisomerization/reduction sequence to construct the dihydroisocoumarin unit. The two synthetic avenues were achieved in 17-18 steps (longest linear sequence, ~14-15 isolations) from 3 fragments prepared in 7-8 (first generation) and 3-8 (second generation) steps each. This convergent approach allowed for the preparation of sufficient amounts of psymberin (~ 0.5 g) for follow-up biological studies. Meanwhile, our highly flexible strategy enabled the design and synthesis of multiple analogs, including a psymberin-pederin hybrid, termed psympederin, that proved crucial to a comprehensive understanding of the chemical biology of psymberin and related compounds that will be described in a subsequent manuscript.

  10. Kinetic and structural studies reveal a unique binding mode of sulfite to the nickel center in urease.

    Science.gov (United States)

    Mazzei, Luca; Cianci, Michele; Benini, Stefano; Bertini, Leonardo; Musiani, Francesco; Ciurli, Stefano

    2016-01-01

    Urease is the most efficient enzyme known to date, and catalyzes the hydrolysis of urea using two Ni(II) ions in the active site. Urease is a virulence factor in several human pathogens, while causing severe environmental and agronomic problems. Sporosarcina pasteurii urease has been used extensively in the structural characterization of the enzyme. Sodium sulfite has been widely used as a preservative in urease solutions to prevent oxygen-induced oxidation, but its role as an inhibitor has also been suggested. In the present study, isothermal titration microcalorimetry was used to establish sulfite as a competitive inhibitor for S. pasteurii urease, with an inhibition constant of 0.19mM at pH7. The structure of the urease-sulfite complex, determined at 1.65Å resolution, shows the inhibitor bound to the dinuclear Ni(II) center of urease in a tridentate mode involving bonds between the two Ni(II) ions in the active site and all three oxygen atoms of the inhibitor, supporting the observed competitive inhibition kinetics. This coordination mode of sulfite has never been observed, either in proteins or in small molecule complexes, and could inspire synthetic coordination chemists as well as biochemists to develop urease inhibitors based on this chemical moiety. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Computational topology and the Unique Games Conjecture

    OpenAIRE

    Grochow, Joshua A.; Tucker-Foltz, Jamie

    2018-01-01

    Covering spaces of graphs have long been useful for studying expanders (as "graph lifts") and unique games (as the "label-extended graph"). In this paper we advocate for the thesis that there is a much deeper relationship between computational topology and the Unique Games Conjecture. Our starting point is Linial's 2005 observation that the only known problems whose inapproximability is equivalent to the Unique Games Conjecture - Unique Games and Max-2Lin - are instances of Maximum Section of...

  12. Highly diverse, poorly studied and uniquely threatened by climate change: an assessment of marine biodiversity on South Georgia's continental shelf.

    Directory of Open Access Journals (Sweden)

    Oliver T Hogg

    Full Text Available We attempt to quantify how significant the polar archipelago of South Georgia is as a source of regional and global marine biodiversity. We evaluate numbers of rare, endemic and range-edge species and how the faunal structure of South Georgia may respond to some of the fastest warming waters on the planet. Biodiversity data was collated from a comprehensive review of reports, papers and databases, collectively representing over 125 years of polar exploration. Classification of each specimen was recorded to species level and fully geo-referenced by depth, latitude and longitude. This information was integrated with physical data layers (e.g. temperature, salinity and flow providing a visualisation of South Georgia's biogeography across spatial, temporal and taxonomic scales, placing it in the wider context of the Southern Hemisphere. This study marks the first attempt to map the biogeography of an archipelago south of the Polar Front. Through it we identify the South Georgian shelf as the most speciose region of the Southern Ocean recorded to date. Marine biodiversity was recorded as rich across taxonomic levels with 17,732 records yielding 1,445 species from 436 families, 51 classes and 22 phyla. Most species recorded were rare, with 35% recorded only once and 86% recorded <10 times. Its marine fauna is marked by the cumulative dominance of endemic and range-edge species, potentially at their thermal tolerance limits. Consequently, our data suggests the ecological implications of environmental change to the South Georgian marine ecosystem could be severe. If sea temperatures continue to rise, we suggest that changes will include depth profile shifts of some fauna towards cooler Antarctic Winter Water (90-150 m, the loss of some range-edge species from regional waters, and the wholesale extinction at a global scale of some of South Georgia's endemic species.

  13. Lattices with unique complements

    CERN Document Server

    Saliĭ, V N

    1988-01-01

    The class of uniquely complemented lattices properly contains all Boolean lattices. However, no explicit example of a non-Boolean lattice of this class has been found. In addition, the question of whether this class contains any complete non-Boolean lattices remains unanswered. This book focuses on these classical problems of lattice theory and the various attempts to solve them. Requiring no specialized knowledge, the book is directed at researchers and students interested in general algebra and mathematical logic.

  14. Blanke vroue-arbeid in die Unie van Suid-Afrika : 'n sosiologiese studie, met spesiale verwysing na die grootstedelike gebiede van die land

    NARCIS (Netherlands)

    Prinsloo, Maria Johanna Magdalena

    1957-01-01

    The purpose of this study is to present a sociological analysis of the phenomenon of European female-labour in the Union of South Africa, with special reference to the industrial areas of the country. The inspiration for this undertaking can be summed up in two main points: (i) That female-labour is

  15. Computerized control of circulation. Optimal storage climate with minimal energy consumption. Pilot study; Computergestuurde Circulatieregelingen. Optimaal bewaarklimaat met minimaal energieverbruik. Praktijkonderzoek

    Energy Technology Data Exchange (ETDEWEB)

    Wildschut, J. [Praktijkonderzoek Plant en Omgeving PPO, Bloembollen, Boomkwekerij en Fruit, Lisse (Netherlands); Janssen, H.H.J.; Gielen, T.G.; Sapounas, A. [WUR Glastuinbouw, Wageningen (Netherlands)

    2011-04-15

    The objective of this study is to develop computerized controls for circulation that are based on sensors, allowing for significant conservation in the electricity use of circulation [Dutch] Doelstelling van dit project is het ontwikkelen van op sensoren gebaseerde computergestuurde regelingen voor de circulatie, waardoor bij een optimaal bewaarklimaat voor alle bolgewassen zeer fors op het elektraverbruik voor circulatie bespaard kan worden.

  16. Glykemische regulatie en behandeling van hypertensie essentieel bij personen met diabetes mellitus type 2; de 'United Kingdom prospective diabetes study' naar diabetische complicaties

    NARCIS (Netherlands)

    Wolffenbuttel, B H; Heine, R J

    1999-01-01

    Patients with type 2 diabetes mellitus often develop micro- and macrovascular complications. In 25% of them, complications are already present at the time of diagnosis. The principal objective of the United Kingdom prospective diabetes study was to determine if good blood glucose control and

  17. Het gezin als sociologisch studie-object : een historisch overzicht van de ontwikkeling van een sub-discipline, speciaal met het oog op de situatie in Nederland

    NARCIS (Netherlands)

    Leeuwen, van L.T.

    1976-01-01

    This thesis has been inspired by the international trend reports of Reuben Hill and John Mogey on the output of family sociology. Originally the author aimed at the answering of the following fourfold problem: the development of the interest in the study of marriage and the family in the

  18. DNA Repair Mechanism Gene, XRCC1A (Arg194Trp) but not XRCC3 (Thr241Met) Polymorphism Increased the Risk of Breast Cancer in Premenopausal Females: A Case–Control Study in Northeastern Region of India

    Science.gov (United States)

    Ahmed, Jishan; Narain, Kanwar; Mukherjee, Kaustab; Majumdar, Gautam; Chenkual, Saia; Zonunmawia, Jason C.

    2017-01-01

    X-ray repair cross complementary group gene is one of the most studied candidate gene involved in different types of cancers. Studies have shown that X-ray repair cross complementary genes are significantly associated with increased risk of breast cancer in females. Moreover, studies have revealed that X-ray repair cross complementary gene polymorphism significantly varies between and within different ethnic groups globally. The present case–control study was aimed to investigate the association of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast cancer in females from northeastern region of India. The present case–control study includes histopathologically confirmed and newly diagnosed 464 cases with breast cancer and 534 apparently healthy neighborhood community controls. Information on sociodemographic factors and putative risk factors were collected from each study participant by conducting face-to-face interviews. Genotyping of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) was carried out by polymerase chain reaction-restriction fragment length polymorphism. For statistical analysis, both univariate and multivariate logistic regression analyses were performed. We also performed stratified analysis to find out the association of X-ray repair cross complementary genes with the risk of breast cancer stratified based on menstrual status. This study revealed that tryptophan allele (R/W-W/W genotype) in X-ray repair cross complementary 1A (Arg194Trp) gene significantly increased the risk of breast cancer (adjusted odds ratio = 1.44, 95% confidence interval = 1.06-1.97, P India which may be beneficial for prognostic purposes. PMID:29332455

  19. A Unique (3+2) Annulation Reaction between Meldrum's Acid and Nitrones: Mechanistic Insight by ESI-IMS-MS and DFT Studies.

    Science.gov (United States)

    Lespes, Nicolas; Pair, Etienne; Maganga, Clisy; Bretier, Marie; Tognetti, Vincent; Joubert, Laurent; Levacher, Vincent; Hubert-Roux, Marie; Afonso, Carlos; Loutelier-Bourhis, Corinne; Brière, Jean-François

    2018-03-15

    The fragile intermediates of the domino process leading to an isoxazolidin-5-one, triggered by unique reactivity between Meldrum's acid and an N-benzyl nitrone in the presence of a Brønsted base, were determined thanks to the softness and accuracy of electrospray ionization mass spectrometry coupled to ion mobility spectrometry (ESI-IMS-MS). The combined DFT study shed light on the overall organocatalytic sequence that starts with a stepwise (3+2) annulation reaction that is followed by a decarboxylative protonation sequence encompassing a stereoselective pathway issue. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Is neurofeedback effectief bij kinderen met ADHD?

    NARCIS (Netherlands)

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

    2008-01-01

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

  1. GAVE multi-actor process. A exemplified study with recommendations for a follow-up traject; GAVE multi-actor proces. Een voorbeeldstudie met aanbevelingen voor het vervolgtraject

    Energy Technology Data Exchange (ETDEWEB)

    Diepenmaat, H.B. [Actors Procesmanagement, Zeist (Netherlands)

    2000-02-01

    The focus is on GAVE as an integral multi-actor process, as a collaboration process in which the parties have to find each other. The reason for this multi-actor approach is that the parties themselves have to realise the importance of sustainable energy. A multi-actor approach uses this crucial fact as the starting point. By means of the use of specific multi-actor methods and insights, it is possible during the collaboration process to develop a clear idea of the content of the joint path and the intended collaborative future, while paying specific attention to the individual roles of the players. Based on this, a well- considered and promising realisation path can be followed. The objective of this study is to illustrate - on the basis of two GAVE options - how the multi-actor approach can support the GAVE programme. In doing this, emphasis is placed on examples, the demonstration of added value of such an approach, and making recommendations for the future. Two experiments have been carried out on the basis of the Trinity approach. The Trinity approach is a set of methods specifically developed for supporting change processes which involve many parties (i.e. multi-actor processes). Trinity helps those involved to obtain a clear picture of both the route to be followed and the future situation to be aimed at. The term 'picture' must be understood literally: an important aspect of Trinity is the collaboration and communication with multi-actor models (also referred to as actorprints). By means of a diagram technique (figures and arrows) these models demonstrate the cohesion between the roles and activities of the various parties involved. The modelling process is instrumental in this; the actual result is that the image that is developed is formed and backed up by the participants in the process. Within these experiments, we have, so far, worked mainly in the shadow of the current GAVE process. A forceful participative use of the actor approach is

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

    Science.gov (United States)

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

    2015-06-03

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    ramin saravani

    2017-10-01

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

  5. Is Life Unique?

    Science.gov (United States)

    Abel, David L.

    2011-01-01

    Is life physicochemically unique? No. Is life unique? Yes. Life manifests innumerable formalisms that cannot be generated or explained by physicodynamics alone. Life pursues thousands of biofunctional goals, not the least of which is staying alive. Neither physicodynamics, nor evolution, pursue goals. Life is largely directed by linear digital programming and by the Prescriptive Information (PI) instantiated particularly into physicodynamically indeterminate nucleotide sequencing. Epigenomic controls only compound the sophistication of these formalisms. Life employs representationalism through the use of symbol systems. Life manifests autonomy, homeostasis far from equilibrium in the harshest of environments, positive and negative feedback mechanisms, prevention and correction of its own errors, and organization of its components into Sustained Functional Systems (SFS). Chance and necessity—heat agitation and the cause-and-effect determinism of nature’s orderliness—cannot spawn formalisms such as mathematics, language, symbol systems, coding, decoding, logic, organization (not to be confused with mere self-ordering), integration of circuits, computational success, and the pursuit of functionality. All of these characteristics of life are formal, not physical. PMID:25382119

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

    NARCIS (Netherlands)

    Tom Langhorst

    2010-01-01

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

  7. Geoengineering by stratospheric SO2 injection: results from the Met Office HadGEM2 climate model and comparison with the Goddard Institute for Space Studies ModelE

    Directory of Open Access Journals (Sweden)

    B. Kravitz

    2010-07-01

    Full Text Available We examine the response of the Met Office Hadley Centre's HadGEM2-AO climate model to simulated geoengineering by continuous injection of SO2 into the lower stratosphere, and compare the results with those from the Goddard Institute for Space Studies ModelE. Despite the differences between the models, we find a broadly similar geographic distribution of the response to geoengineering in both models in terms of near-surface air temperature and mean June–August precipitation. The simulations also suggest that significant changes in regional climate would be experienced even if geoengineering was successful in maintaining global-mean temperature near current values, and both models indicate rapid warming if geoengineering is not sustained.

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

    NARCIS (Netherlands)

    Pater, Mathieu; van Yperen, Tom

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

  9. Leren vermenigvuldigen met meercijferige getallen

    NARCIS (Netherlands)

    Buijs, C.

    2008-01-01

    The reason for this study lies in the fact that efforts to create a learning trajectory for the domain of multidigit multiplication based on the realistic approach of mathematics education and building on children’s own informal strategies with the aim of transforming these strategies into efficient

  10. Met1-linked Ubiquitination in Immune Signalling

    DEFF Research Database (Denmark)

    Fiil, Berthe Katrine; Gyrd-Hansen, Mads

    2014-01-01

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

  11. Mars MetNet Mission Payload Overview

    Science.gov (United States)

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

    2012-09-01

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

  12. Wind flow around met masts

    Energy Technology Data Exchange (ETDEWEB)

    Heraud, P.; Masson, C.; Tusch, M. [Garrad Hassan Canada Inc., Ottawa, ON (Canada)

    2010-07-01

    This PowerPoint presentation discussed the impacts of meteorological masts on the measurement of wind resources. Two types of meteorological masts are used in wind power applications, namely lattice, and tubular masts. Anemometer accuracy can be impacted by the logger as well as by the instrumentation layout. The International Electrochemical Commission (IEC) recommends that anemometers are placed at a 45 degree angle from pre-dominant winds. However, the impact of turbulent flow around meteorological masts is poorly understood. The numerical model developed in the study included mass and momentum conservation models for tubular and lattice towers. Distortion level recommendations were presented. The study showed that distortion depends on the layout, and that IEC recommendations for instrumentation layouts need to be revised. tabs., figs.

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

    Science.gov (United States)

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

    2008-01-01

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

  14. Application of next-generation sequencing technology to study genetic diversity and identify unique SNP markers in bread wheat from Kazakhstan.

    Science.gov (United States)

    Shavrukov, Yuri; Suchecki, Radoslaw; Eliby, Serik; Abugalieva, Aigul; Kenebayev, Serik; Langridge, Peter

    2014-09-28

    New SNP marker platforms offer the opportunity to investigate the relationships between wheat cultivars from different regions and assess the mechanism and processes that have led to adaptation to particular production environments. Wheat breeding has a long history in Kazakhstan and the aim of this study was to explore the relationship between key varieties from Kazakhstan and germplasm from breeding programs for other regions. The study revealed 5,898 polymorphic markers amongst ten cultivars, of which 2,730 were mapped in the consensus genetic map. Mapped SNP markers were distributed almost equally across the A and B genomes, with between 279 and 484 markers assigned to each chromosome. Marker coverage was approximately 10-fold lower in the D genome. There were 863 SNP markers identified as unique to specific cultivars, and clusters of these markers (regions containing more than three closely mapped unique SNPs) showed specific patterns on the consensus genetic map for each cultivar. Significant intra-varietal genetic polymorphism was identified in three cultivars (Tzelinnaya 3C, Kazakhstanskaya rannespelaya and Kazakhstanskaya 15). Phylogenetic analysis based on inter-varietal polymorphism showed that the very old cultivar Erythrospermum 841 was the most genetically distinct from the other nine cultivars from Kazakhstan, falling in a clade together with the American cultivar Sonora and genotypes from Central and South Asia. The modern cultivar Kazakhstanskaya 19 also fell into a separate clade, together with the American cultivar Thatcher. The remaining eight cultivars shared a single sub-clade but were categorised into four clusters. The accumulated data for SNP marker polymorphisms amongst bread wheat genotypes from Kazakhstan may be used for studying genetic diversity in bread wheat, with potential application for marker-assisted selection and the preparation of a set of genotype-specific markers.

  15. Teen camp: a unique approach to recruit future nurses.

    Science.gov (United States)

    Redding, Donna A; Riech, Sandy; Prater, Marsha A

    2004-01-01

    A collaborative and unique approach to interest high school students in nursing. To inform educators and nursing departments about an innovative approach to recruit future nurses. Professional literature and authors' experience. All students related positive experiences. The initial camp evaluation produced innovative input from the students, and each camp met its goal of creating career interest in the nursing profession.

  16. Gesloten kringloop met omgekeerde osmose of membraandestilatie

    NARCIS (Netherlands)

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

    2011-01-01

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

  17. Mars MetNet Mission Status

    Science.gov (United States)

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

    2015-10-01

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

  18. Mars MetNet Precursor Mission Status

    Science.gov (United States)

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

    2013-09-01

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

  19. Bio-composiet : Thermoplastische kunsstof met natuurvezels

    NARCIS (Netherlands)

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

    2013-01-01

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

  20. Intern transport beter te plannen met computer

    NARCIS (Netherlands)

    Annevelink, E.

    1999-01-01

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

  1. Fosfaatwerking ogranische meststoffen vergelijkbaar met kunstmest

    NARCIS (Netherlands)

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

    2000-01-01

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

  2. Technisch lego met een Duplo-interface

    NARCIS (Netherlands)

    Pimentel, A.; Schipper, D.

    2008-01-01

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

  3. Uniqueness theorems in linear elasticity

    CERN Document Server

    Knops, Robin John

    1971-01-01

    The classical result for uniqueness in elasticity theory is due to Kirchhoff. It states that the standard mixed boundary value problem for a homogeneous isotropic linear elastic material in equilibrium and occupying a bounded three-dimensional region of space possesses at most one solution in the classical sense, provided the Lame and shear moduli, A and J1 respectively, obey the inequalities (3 A + 2 J1) > 0 and J1>O. In linear elastodynamics the analogous result, due to Neumann, is that the initial-mixed boundary value problem possesses at most one solution provided the elastic moduli satisfy the same set of inequalities as in Kirchhoffs theorem. Most standard textbooks on the linear theory of elasticity mention only these two classical criteria for uniqueness and neglect altogether the abundant literature which has appeared since the original publications of Kirchhoff. To remedy this deficiency it seems appropriate to attempt a coherent description ofthe various contributions made to the study of uniquenes...

  4. MMPM - Mars MetNet Precursor Mission

    Science.gov (United States)

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

    2008-09-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2009/2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Detailed characterization of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatology cycles, require simultaneous in-situ measurements by a network of observation posts on the Martian surface. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe technologies have been developed and the critical subsystems have been qualified to meet the Martian environmental and functional conditions. Prototyping of the payload instrumentation with final dimensions was carried out in 2003-2006.This huge development effort has been fulfilled in collaboration between the Finnish Meteorological Institute (FMI), the Russian Lavoschkin Association (LA) and the Russian Space Research Institute (IKI) since August 2001. Currently the INTA (Instituto Nacional de Técnica Aeroespacial) from Spain is also participating in the MetNet payload development. To understand the behavior and dynamics of the Martian atmosphere, a wealth of simultaneous in situ observations are needed on varying types of Martian orography, terrain and altitude spanning all latitudes and longitudes. This will be performed by the Mars MetNet Mission. In addition to the science aspects the

  5. Mars MetNet Mission Status

    Science.gov (United States)

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

    2015-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Luis J. Herrera

    2005-01-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  8. MetReS, an Efficient Database for Genomic Applications.

    Science.gov (United States)

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

    2018-02-01

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  10. Erlotinib e metástases cerebrais

    Directory of Open Access Journals (Sweden)

    Fernando Barata

    2008-10-01

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

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

    Science.gov (United States)

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

    2011-10-01

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

  12. Abordagem de redes no estudo de movimentos sociais: entre o modelo e a metáfora Network approaches in the study of social movements: between model and metaphor

    Directory of Open Access Journals (Sweden)

    Maria Ceci Misoczky

    2009-10-01

    Full Text Available Este artigo faz parte de um conjunto de reflexões sobre as consequências do uso de abordagens fortemente influenciadas pela lógica empresarial como lentes para compreender movimentos orientados pela oposição a essa lógica. Neste artigo a preocupação é retomada, aprofundando a abordagem de redes. O ponto de partida foi uma apropriação crítica de autores e formulações representativos dessa abordagem. Foi impossível deixar de lado a hibridização entre a(s teoria(s do capital social e a abordagem de redes sociais. Parte deste artigo redundou em retirar as formulações de Pierre Bourdieu da vala comum, em que leituras equivocadas as têm jogado, ao classificálo como um teórico do capital social e da análise de redes. Também é revisada a expressão predominante da abordagem de redes nos estudos sobre movimentos sociais. Finalmente é abordada a distinção entre metáfora e modelo. A partir daí se pode afirmar que a retomada da estratégia discursiva da metáfora poderia abrir espaço para reconhecer o novo, o que está em construção, e o que ainda não é. Além disso, possibilitariam a coerência com a razão de ser do objeto a ser estudado. Nesse sentido são apresentadas três metáforas - fluidos, teias e rizomas - de modo a ilustrar as potencialidades contidas no uso desse recurso no estudo de movimentos sociais.This article is part of a reflexive effort directed to discuss the consequences of the use of approaches strongly influenced by entrepreneurial logics as lenses to understand social movements oriented by the opposition to such logic. In this text this preoccupation is directed to the network approach. The point of departure is a critical appropriation of representative authors and formulations of such approach. In this review it was impossible to avoid the hybridization between social capital and social network. A relevant part of this review was the separation of Pierre Bourdieu's formulations from the common

  13. Assessing met and unmet needs in the oldest-old and psychometric properties of the German version of the Camberwell assessment of need for the elderly (CANE)--a pilot study.

    Science.gov (United States)

    Stein, Janine; Luppa, Melanie; König, Hans-Helmut; Riedel-Heller, Steffi G

    2014-02-01

    The current demographic and social developments in our society will lead to a significant increase in treatment and healthcare needs in the future, particularly in the elderly population. The Camberwell Assessment of Need for the Elderly (CANE) was developed in the United Kingdom to measure physical-, psychological-, and environment-related treatment as well as healthcare needs of older people in order to identify their unmet needs. So far, the German version of the CANE has not been established in health services research. Major reasons for this are a lack of publications of CANE's German version and the missing validation of the instrument. The aims of the present study were to evaluate the currently available German version of the CANE in a sample of older primary care patients. Descriptive statistics and inference-statistical analyses were calculated. Patients reported unmet needs mostly in CANE's following sections: mobility/falls, physical health, continence, company, and intimate relationships. Agreement level between patients' and relatives' ratings in CANE was moderate to low. Evidence for the construct validity of CANE was found in terms of significant associations between CANE and other instruments or scores. The study results provide an important basis for studies aiming at the assessment of met and unmet needs in the elderly population. Using the German version of the CANE may substantially contribute to an effective and good-quality health and social care as well as an appropriate allocation of healthcare resources in the elderly population.

  14. Rocket experiment METS - Microwave Energy Transmission in Space

    Science.gov (United States)

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

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

  15. Rocket experiment METS Microwave Energy Transmission in Space

    Science.gov (United States)

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

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

  16. Cancer: Unique to Older Adults

    Science.gov (United States)

    ... A to Z › Cancer › Unique to Older Adults Font size A A A Print Share Glossary Unique ... group with other older people with the same type of cancer. Researchers have found that support groups ...

  17. MetBaro - Pressure Device for Mars MetNet Lander

    Science.gov (United States)

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

    2010-05-01

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

  18. MetHumi - Humidity Device for Mars MetNet Lander

    Science.gov (United States)

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

    2010-05-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

    Granito, Alessandro; Guidetti, Elena; Gramantieri, Laura

    2015-01-01

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

  1. Unique Distribution of Aromatase in the Human Brain: In Vivo Studies With PET and (N-Methyl-11C)Vorozole

    International Nuclear Information System (INIS)

    Biegon, A.; Kim, S.W.; Alexoff, D.; Millard, J.; Carter, P.; Hubbard, B.; King, P.; Logan, J.; Muench, L.; Pareto, D.; Schlyer, D.; Shea, C.; Telang, F.; Wang, G.-J.; Xu, Y.; Fowler, J.

    2010-01-01

    Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor (N-methyl- 11 C)vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V T ) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region-dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.

  2. Unique Distribution of Aromatase in the Human Brain: In Vivo Studies With PET and [N-Methyl-11C]Vorozole

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Biegon, A.; Kim, S.W.; Alexoff, D.; Millard, J.; Carter, P.; Hubbard, B.; King, P.; Logan, J.; Muench, L.; Pareto, D.; Schlyer, D.; Shea, C.; Telang, F.; Wang, G.-J.; Xu, Y.; Fowler, J.

    2010-10-01

    Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-{sup 11}C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V{sub T}) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region-dependent, ranging from {approx}70% blocking in thalamus andpreoptic area to {approx}10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.

  3. How a Training Program Is Transforming the Role of Traditional Birth Attendants from Cultural Practitioners to Unique Health-care Providers: A Community Case Study in Rural Guatemala

    Directory of Open Access Journals (Sweden)

    Sasha Hernandez

    2017-05-01

    Full Text Available In low- and middle-income countries (LMICs, where the rates of maternal mortality continue to be inappropriately high, there has been recognition of the importance of training traditional birth attendants (TBAs to help improve outcomes during pregnancy and childbirth. In Guatemala, there is no national comprehensive training program in place despite the fact that the majority of women rely on TBAs during pregnancy and childbirth. This community case study presents a unique education program led by TBAs for TBAs in rural Guatemala. Discussion of this training program focuses on programming implementation, curriculum development, sustainable methodology, and how an educational partnership with the current national health-care system can increase access to health care for women in LMICs. Recent modifications to this training model are also discussed including how a change in the clinical curriculum is further integrating TBAs into the national health infrastructure. The training program has demonstrated that Guatemalan TBAs are able to improve their basic obstetrical knowledge, are capable of identifying and referring early complications of pregnancy and labor, and can deliver basic prenatal care that would otherwise not be provided. This training model is helping transform the role of the TBA from a sole cultural practitioner to a validated health-care provider within the health-care infrastructure of Guatemala and has the potential to do the same in other LMICs.

  4. How a Training Program Is Transforming the Role of Traditional Birth Attendants from Cultural Practitioners to Unique Health-care Providers: A Community Case Study in Rural Guatemala.

    Science.gov (United States)

    Hernandez, Sasha; Oliveira, Jessica Bastos; Shirazian, Taraneh

    2017-01-01

    In low- and middle-income countries (LMICs), where the rates of maternal mortality continue to be inappropriately high, there has been recognition of the importance of training traditional birth attendants (TBAs) to help improve outcomes during pregnancy and childbirth. In Guatemala, there is no national comprehensive training program in place despite the fact that the majority of women rely on TBAs during pregnancy and childbirth. This community case study presents a unique education program led by TBAs for TBAs in rural Guatemala. Discussion of this training program focuses on programming implementation, curriculum development, sustainable methodology, and how an educational partnership with the current national health-care system can increase access to health care for women in LMICs. Recent modifications to this training model are also discussed including how a change in the clinical curriculum is further integrating TBAs into the national health infrastructure. The training program has demonstrated that Guatemalan TBAs are able to improve their basic obstetrical knowledge, are capable of identifying and referring early complications of pregnancy and labor, and can deliver basic prenatal care that would otherwise not be provided. This training model is helping transform the role of the TBA from a sole cultural practitioner to a validated health-care provider within the health-care infrastructure of Guatemala and has the potential to do the same in other LMICs.

  5. Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole.

    Science.gov (United States)

    Biegon, Anat; Kim, Sung Won; Alexoff, David L; Jayne, Millard; Carter, Pauline; Hubbard, Barbara; King, Payton; Logan, Jean; Muench, Lisa; Pareto, Deborah; Schlyer, David; Shea, Colleen; Telang, Frank; Wang, Gene-Jack; Xu, Youwen; Fowler, Joanna S

    2010-11-01

    Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-(11)C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V(T)) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced V(T) in all regions, though the size of the reduction was region-dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.

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

    Science.gov (United States)

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

    2016-03-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  8. MetBaro - Pressure Instrument for Mars MetNet Lander

    Science.gov (United States)

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

    2009-04-01

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

  9. Inhaken met sociale media in 60 minuten

    NARCIS (Netherlands)

    Thijs Waardenburg; Komala Mazerant

    2018-01-01

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

  10. Varroabestrijding met bijenbroed als mijtenval (2)

    NARCIS (Netherlands)

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

    1994-01-01

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

  11. Beeldverwerking met de Micron Automatic Processor

    OpenAIRE

    Goyens, Frank

    2017-01-01

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

  12. Groen proceswater: zuivering brouwerijprocesafvalwater met microalgen

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    African Journals Online (AJOL)

    Test

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

  14. Risicoanalyse voor buisleidingen met brandbare vloeistoffen

    NARCIS (Netherlands)

    van Vliet AAC; Laheij GMH; Wolting AG; CEV

    2006-01-01

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

  15. A brief report on mets system

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, W.A.

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

  16. Progress in switching technology for METS systems

    International Nuclear Information System (INIS)

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

    1977-01-01

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

  17. RNase MRP cleaves pre-tRNASer-Met in the tRNA maturation pathway.

    Science.gov (United States)

    Saito, Yuichiro; Takeda, Jun; Adachi, Kousuke; Nobe, Yuko; Kobayashi, Junya; Hirota, Kouji; Oliveira, Douglas V; Taoka, Masato; Isobe, Toshiaki

    2014-01-01

    Ribonuclease mitochondrial RNA processing (RNase MRP) is a multifunctional ribonucleoprotein (RNP) complex that is involved in the maturation of various types of RNA including ribosomal RNA. RNase MRP consists of a potential catalytic RNA and several protein components, all of which are required for cell viability. We show here that the temperature-sensitive mutant of rmp1, the gene for a unique protein component of RNase MRP, accumulates the dimeric tRNA precursor, pre-tRNA(Ser-Met). To examine whether RNase MRP mediates tRNA maturation, we purified the RNase MRP holoenzyme from the fission yeast Schizosaccharomyces pombe and found that the enzyme directly and selectively cleaves pre-tRNA(Ser-Met), suggesting that RNase MRP participates in the maturation of specific tRNA in vivo. In addition, mass spectrometry-based ribonucleoproteomic analysis demonstrated that this RNase MRP consists of one RNA molecule and 11 protein components, including a previously unknown component Rpl701. Notably, limited nucleolysis of RNase MRP generated an active catalytic core consisting of partial mrp1 RNA fragments, which constitute "Domain 1" in the secondary structure of RNase MRP, and 8 proteins. Thus, the present study provides new insight into the structure and function of RNase MRP.

  18. EUV microexposures at the ALS using the 0.3-NA MET projection optics

    International Nuclear Information System (INIS)

    Naulleau, Patrick; Goldberg, Kenneth A.; Anderson, Erik; Cain, Jason P.; Denham, Paul; Hoef, Brian; Jackson, Keith; Morlens, Anne-Sophie; Rekawa, Seno; Dean, Kim

    2005-01-01

    The recent development of high numerical aperture (NA) EUV optics such as the 0.3-NA Micro Exposure Tool (MET) optic has given rise to a new class of ultra-high resolution microexposure stations. Once such printing station has been developed and implemented at Lawrence Berkeley National Laboratory's Advanced Light Source. This flexible printing station utilizes a programmable coherence illuminator providing real-time pupil-fill control for advanced EUV resist and mask development. The Berkeley exposure system programmable illuminator enables several unique capabilities. Using dipole illumination out to σ=1, the Berkeley tool supports equal-line-space printing down to 12 nm, well beyond the capabilities of similar tools. Using small-sigma illumination combined with the central obscuration of the MET optic enables the system to print feature sizes that are twice as small as those coded on the mask. In this configuration, the effective 10x-demagnification for equal lines and spaces reduces the mask fabrication burden for ultra-high-resolution printing. The illuminator facilitates coherence studies such as the impact of coherence on line-edge roughness (LER) and flare. Finally the illuminator enables novel print-based aberration monitoring techniques as described elsewhere in these proceedings. Here we describe the capabilities of the new MET printing station and present system characterization results. Moreover, we present the latest printing results obtained in experimental resists. Limited by the availability of high-resolution photoresists, equal line-space printing down to 25 nm has been demonstrated as well as isolated line printing down to 29 nm with an LER of approaching 3 nm

  19. Milnacipran: a unique antidepressant?

    Directory of Open Access Journals (Sweden)

    Siegfried Kasper

    2010-08-01

    Full Text Available Siegfried Kasper, Gerald PailDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, AustriaAbstract: Tricyclic antidepressants (TCAs are among the most effective antidepressants available, although their poor tolerance at usual recommended doses and toxicity in ­overdose make them difficult to use. While selective serotonin reuptake inhibitors (SSRIs are ­better tolerated than TCAs, they have their own specific problems, such as the aggravation of sexual dysfunction, interaction with coadministered drugs, and for many, a discontinuation syndrome. In addition, some of them appear to be less effective than TCAs in more severely depressed patients. Increasing evidence of the importance of norepinephrine in the etiology of depression has led to the development of a new generation of antidepressants, the serotonin and ­norepinephrine reuptake inhibitors (SNRIs. Milnacipran, one of the pioneer SNRIs, was designed from theoretic considerations to be more effective than SSRIs and better tolerated than TCAs, and with a simple pharmacokinetic profile. Milnacipran has the most balanced potency ratio for reuptake inhibition of the two neurotransmitters compared with other SNRIs (1:1.6 for milnacipran, 1:10 for duloxetine, and 1:30 for venlafaxine, and in some studies milnacipran has been shown to inhibit norepinephrine uptake with greater potency than serotonin (2.2:1. Clinical studies have shown that milnacipran has efficacy comparable with the TCAs and is superior to SSRIs in severe depression. In addition, milnacipran is well tolerated, with a low potential for pharmacokinetic drug–drug interactions. Milnacipran is a first-line therapy suitable for most depressed patients. It is frequently successful when other treatments fail for reasons of efficacy or tolerability.Keywords: milnacipran, SNRI, antidepressant efficacy, tolerability

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

  2. De Doop met de Heilige Geest

    Directory of Open Access Journals (Sweden)

    S. C.W. Duvenage.

    1965-03-01

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

  3. MET and Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Gelsomino

    2014-10-01

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

  4. MetAssimulo:Simulation of Realistic NMR Metabolic Profiles

    Directory of Open Access Journals (Sweden)

    De Iorio Maria

    2010-10-01

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

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

    NARCIS (Netherlands)

    Voogd, Joanna Bernarda

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

  6. Metáfora y estructura conceptual

    Directory of Open Access Journals (Sweden)

    Emilia Castaño

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Eisen Judith S

    2008-07-01

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

  8. Uniquely Strongly Clean Group Rings

    Institute of Scientific and Technical Information of China (English)

    WANG XIU-LAN

    2012-01-01

    A ring R is called clean if every element is the sum of an idempotent and a unit,and R is called uniquely strongly clean (USC for short) if every element is uniquely the sum of an idempotent and a unit that commute.In this article,some conditions on a ring R and a group G such that RG is clean are given.It is also shown that if G is a locally finite group,then the group ring RG is USC if and only if R is USC,and G is a 2-group.The left uniquely exchange group ring,as a middle ring of the uniquely clean ring and the USC ring,does not possess this property,and so does the uniquely exchange group ring.

  9. Are endometrial nerve fibres unique to endometriosis? A prospective case-control study of endometrial biopsy as a diagnostic test for endometriosis in women with pelvic pain.

    Science.gov (United States)

    Ellett, Lenore; Readman, Emma; Newman, Marsali; McIlwaine, Kate; Villegas, Rocio; Jagasia, Nisha; Maher, Peter

    2015-12-01

    Can the presence of endometrial nerve fibres be used as a diagnostic test for endometriosis in women with pelvic pain? Endometrial fine nerve fibres were seen in the endometrium of women both with and without endometriosis, making their detection a poor diagnostic tool for endometriosis. Laparoscopy and biopsy are currently the gold standard for making a diagnosis of endometriosis. It has been reported that small density nerve fibres in the functional layer of the endometrium are unique to women with endometriosis and hence nerve fibre detection could function as a less invasive diagnostic test of endometriosis. However, it may be that other painful conditions of the pelvis are also associated with these nerve fibres. We therefore focused this prospective study on women with pelvic pain to examine the efficacy of endometrial nerve fibre detection as a diagnostic test for endometriosis. This prospective case-control study conducted between July 2009 and July 2013 included 44 women with pelvic pain undergoing laparoscopic examination for the diagnosis of endometriosis. Immunohistochemical nerve fibre detection in endometrial curettings and biopsies using anti-protein gene product 9.5 was compared with surgical diagnosis. Paired endometrial biopsies and curettings were taken from patients with (n = 22, study group) and without (n = 22, control group) endometriosis. Tissue was analysed by immunohistochemistry and nerve fibres were counted whenever they were present in the functional layer of the endometrium. Fine nerve fibres were present in the eutopic endometrium of patients both with and without endometriosis. The presence of nerve fibres in curettings was not effective for either diagnosing or excluding endometriosis; sensitivity and specificity were 31.8 and 45.5% respectively, positive predictive value was 36.8% and negative predictive value was 40.0%. Few endometrial biopsy specimens were found to have nerve fibres present; sensitivity and specificity for

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2006-03-01

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

  12. Inversion, error analysis, and validation of GPS/MET occultation data

    Directory of Open Access Journals (Sweden)

    A. K. Steiner

    Full Text Available The global positioning system meteorology (GPS/MET experiment was the first practical demonstration of global navigation satellite system (GNSS-based active limb sounding employing the radio occultation technique. This method measures, as principal observable and with millimetric accuracy, the excess phase path (relative to propagation in vacuum of GNSS-transmitted radio waves caused by refraction during passage through the Earth's neutral atmosphere and ionosphere in limb geometry. It shows great potential utility for weather and climate system studies in providing an unique combination of global coverage, high vertical resolution and accuracy, long-term stability, and all-weather capability. We first describe our GPS/MET data processing scheme from excess phases via bending angles to the neutral atmospheric parameters refractivity, density, pressure and temperature. Special emphasis is given to ionospheric correction methodology and the inversion of bending angles to refractivities, where we introduce a matrix inversion technique (instead of the usual integral inversion. The matrix technique is shown to lead to identical results as integral inversion but is more directly extendable to inversion by optimal estimation. The quality of GPS/MET-derived profiles is analyzed with an error estimation analysis employing a Monte Carlo technique. We consider statistical errors together with systematic errors due to upper-boundary initialization of the retrieval by a priori bending angles. Perfect initialization and properly smoothed statistical errors allow for better than 1 K temperature retrieval accuracy up to the stratopause. No initialization and statistical errors yield better than 1 K accuracy up to 30 km but less than 3 K accuracy above 40 km. Given imperfect initialization, biases >2 K propagate down to below 30 km height in unfavorable realistic cases. Furthermore, results of a statistical validation of GPS/MET profiles through comparison

  13. Activating mutation in MET oncogene in familial colorectal cancer

    Directory of Open Access Journals (Sweden)

    Schildkraut Joellen M

    2011-10-01

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

  14. Central nervous system metastases from breast carcinoma: a clinical and laboratorial study in 47 patients Metástases do sistema nervoso central por câncer de mama: estudo clínico-laboratorial em 47 pacientes

    Directory of Open Access Journals (Sweden)

    ALUÍZIO B.B. MACHADO

    1998-06-01

    Full Text Available In this retrospective study, 47 patients with clinical diagnosis of central nervous system metastases of breast cancer were evaluated by computerized tomography (CT, magnetic resonance imaging (MRI and cerebrospinal fluid (CSF examination. The patients were divided in 2 groups: 1, without leptomeningeal neoplasm and 2, with leptomeningeal neoplasm. In the group 2, the time interval between the primary disease and the central nervous system metastasis as well as the survival time were shorter than in group 1 (40 and 4.3 months in group 2 versus 57 and 10 months respectively, in group 1. In both groups the most common neurological symptoms and signs were intracranial hypertension and motor deficits. The most sensitive diagnostic methods were CT and MRI in group 1, and the CSF examination in group 2. The use of the tumor markers CEA and CA-15.3 in the routine examination of CSF showed promising results, mainly in leptomeningeal forms.Neste estudo retrospectivo, 47 pacientes com diagnóstico clínico de metástases do sistema nervoso por câncer de mama foram avaliados por tomografia computadorizada (TC, ressonância nuclear magnética (RNM e por exames do líquido cefalorraqueano (LCR. Os pacientes foram divididos em 2 grupos: 1, sem neoplasia leptomeníngea e 2, com neoplasia leptomeníngea. No grupo 2 o intervalo de tempo entre a doença primária e o comprometimento do sistema nervoso e o tempo de sobrevida foram menores do que no grupo 1 (40 e 4,3 meses no grupo 2 versus 57 e 10 meses respectivamente, no grupo 1. Os sinais e sintomas neurológicos mais frequentes foram hipertensão intracraniana e déficits motores. Os exames mais sensíveis para o diagnóstico foram a TC e RNM no grupo 1 e o exame do LCR no grupo 2. O uso dos marcadores CEA e CA-15.3 na rotina do LCR mostrou resultados promissores, particularmente nas formas leptomeníngeas.

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Granito A

    2015-04-01

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

  17. Tattoos and piercings: bodily expressions of uniqueness?

    Science.gov (United States)

    Tiggemann, Marika; Hopkins, Louise A

    2011-06-01

    The study aimed to investigate the motivations underlying the body modification practices of tattooing and piercing. There were 80 participants recruited from an Australian music store, who provided descriptions of their tattoos and piercings and completed measures of need for uniqueness, appearance investment and distinctive appearance investment. It was found that tattooed individuals scored significantly higher on need for uniqueness than non-tattooed individuals. Further, individuals with conventional ear piercings scored significantly lower on need for uniqueness than individuals with no piercings or with facial and body piercings. Neither appearance investment nor distinctive appearance investment differed significantly among tattoo or piercing status groups. Strength of identification with music was significantly correlated with number of tattoos, but not number of piercings. It was concluded that tattooing, but not body piercing, represents a bodily expression of uniqueness. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Metáfora y conceptos abstractos

    OpenAIRE

    Danesi, Marcel

    2006-01-01

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

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

    Science.gov (United States)

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

    2017-02-07

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-25

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

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Peyda Korhan

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

  4. Diabetes: Unique to Older Adults

    Science.gov (United States)

    ... Stroke Urinary Incontinence Related Documents PDF Choosing Wisely: Diabetes Tests and Treatments Download Related Video Join our e-newsletter! Aging & Health A to Z Diabetes Unique to Older Adults This section provides information ...

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  6. Modularity, comparative cognition and human uniqueness.

    Science.gov (United States)

    Shettleworth, Sara J

    2012-10-05

    Darwin's claim 'that the difference in mind between man and the higher animals … is certainly one of degree and not of kind' is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference in cognitive capabilities and/or mechanisms between adult humans and other animals. Dual-process theories for some cognitive domains propose that adult human cognition shares simple basic processes with that of other animals while additionally including slower-developing and more explicit uniquely human processes. These theories are consistent with a modular account of cognition and the 'core knowledge' account of children's cognitive development. A complementary proposal is that human infants have unique social and/or cognitive adaptations for uniquely human learning. A view of human cognitive architecture as a mosaic of unique and species-general modular and domain-general processes together with a focus on uniquely human developmental mechanisms is consistent with modern evolutionary-developmental biology and suggests new questions for comparative research.

  7. Studies on transfer ribonucleic acids and related compounds. XXXII. Synthesis of ribonucleotides corresponding to residues 1-5 and 6-10 of tRNAfMet from E. coli and their base conversion analogs.

    Science.gov (United States)

    Ohtsuka, E; Tanaka, T; Ikehara, M

    1979-01-01

    E. Coli tRNAfMet fragments, C-G-C-G-Gp (bases 1-5), U-G-C-G-Gp (base 1 transition, analog) pG-G-C-G-Gp (base 1 transversion analog) and pG-G-s4U-G-Gp (bases 6-10) were synthesized by triester methods using 2'-O-(o-nitrobenzyl) nucleotides including a 3',5'-bisphosphorylated guanosine derivative. The s4U containing pentanucleotide was derived from the pG-G-C-G-Gp by treatment with liquid hydrogen sulfide. Images PMID:390499

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

    Science.gov (United States)

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

    2010-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

  10. Highly active antiretroviral therapy including protease inhibitors does not confer a unique CD4 cell benefit. The AVANTI and INCAS Study Groups.

    Science.gov (United States)

    2000-07-07

    To determine if triple combination therapy, particularly including HIV protease inhibitors (PI), confers an unique immunological benefit that is independent of reductions of plasma viral load (pVL). The correlation between changes from baseline in CD4 cell count and pVL was examined at all time points up to 52 weeks in three randomized clinical trials (AVANTI-2, AVANTI-3 and INCAS) that compared dual nucleoside therapy with triple combination therapy. Individual pVL and CD4 cell counts changes from baseline were entered into multivariate linear regression models for patients receiving double therapy and for those receiving triple therapy including a PI and/or a non-nucleoside reverse transcriptase inhibitor (NNRTI), and the null hypothesis was tested. After 52 weeks of therapy, the relationship between changes from baseline CD4 cell count and pVL was independent of whether patients were assigned double or triple therapy (P = 0.23 and 0.69 for intercept and slope, respectively), or whether patients were assigned triple therapy including a PI or triple therapy including an NNRTI (P = 0.92 and 0.95, respectively). Less than 5% of patients ever had 'discordant' increases in both CD4 cell count and pVL compared with baseline, and this proportion was unrelated to the class of therapy used. 'Discordant' decreases from baseline in both parameters were observed in up to 35% of individuals. The correlation between pVL and CD4 cell count changes from baseline improved over time on therapy, regardless of the therapeutic regimen involved. The data provide no evidence for a CD4 cell count benefit of highly active antiretroviral therapy (HAART) unique to triple therapy or PI-containing regimens.

  11. Using a Theoretical Framework to Investigate Whether the HIV/AIDS Information Needs of the AfroAIDSinfo Web Portal Members Are Met: A South African eHealth Study

    Directory of Open Access Journals (Sweden)

    Hendra Van Zyl

    2014-03-01

    Full Text Available eHealth has been identified as a useful approach to disseminate HIV/AIDS information. Together with Consumer Health Informatics (CHI, the Web-to-Public Knowledge Transfer Model (WPKTM has been applied as a theoretical framework to identify consumer needs for AfroAIDSinfo, a South African Web portal. As part of the CHI practice, regular eSurveys are conducted to determine whether these needs are changing and are continually being met. eSurveys show high rates of satisfaction with the content as well as the modes of delivery. The nature of information is thought of as reliable to reuse; both for education and for referencing of information. Using CHI and the WPKTM as a theoretical framework, it ensures that needs of consumers are being met and that they find the tailored methods of presenting the information agreeable. Combining ICTs and theories in eHealth interventions, this approach can be expanded to deliver information in other sectors of public health.

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

    Science.gov (United States)

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

    2015-01-01

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

  13. MET Standards for Electro-Technical Officers

    Directory of Open Access Journals (Sweden)

    Janusz Mindykowski

    2014-12-01

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

  14. Tidal analysis of Met rocket wind data

    Science.gov (United States)

    Bedinger, J. F.; Constantinides, E.

    1976-01-01

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

  15. Metástasis hipofisaria Hypophyseal metastasis

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Yanes Quesada

    2009-04-01

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

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

    NARCIS (Netherlands)

    Boois, de I.J.

    2013-01-01

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

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

    NARCIS (Netherlands)

    Pastoors, M.A.

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  19. MetNet Network Mission for Martian Atmospheric Investigations

    Science.gov (United States)

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

    2014-07-01

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

  20. Dimensionering van de Uniqfill chemischer wasser met lamellen

    NARCIS (Netherlands)

    Starmans, D.A.J.

    2006-01-01

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

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

    NARCIS (Netherlands)

    Bennink, P.; Kopinga, J.

    2010-01-01

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

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

    Science.gov (United States)

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

    2010-08-06

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

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

    Science.gov (United States)

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

    2017-10-01

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

  4. Unique bar-like sulfur-doped C3N4/TiO2 nanocomposite: Excellent visible light driven photocatalytic activity and mechanism study

    Science.gov (United States)

    Zhao, Yu; Xu, Shiping; Sun, Xiang; Xu, Xing; Gao, Baoyu

    2018-04-01

    In this work, a nanocomposite of TiO2 nanoparticles coupled with sulfur-doped C3N4 (S-C3N4) laminated layer was successfully fabricated using a facile impregnation method and the nanocomposite exhibited superior photocatalytic activity in pollutant removal under visible light irradiation, compared to bare TiO2, g-C3N4 and binary C3N4-TiO2 nanocomposite. The enhanced photocatalytic activity was benefited from the efficient migration and transformation of electron-hole (e--h+) pairs, improved visible light absorption capability, and relatively large specific surface area induce by sulfur doping. Interestingly, the introduction of sulfur changes regulated the morphology of g-C3N4 leading to the formation of ultrathin g-C3N4 layer nanosheet assemblies and unique bar-like g-C3N4/TiO2 nanocomposite, which is beneficial for the outstanding performance of the product. In addition, trapping experiment was carried out to identify the main active species in the photocatalytic reaction over the S-C3N4/TiO2 photocatalyst, and functional mechanism of the composite was proposed. This work may provide new ideas for the fabrication and utilization of highly efficient photocatalyst with excellent visible light response in environmental purification applications.

  5. Study of the 'Clay of Boom' with regard to the storage of nuclear waste. Appendices; Onderzoek Klei van Boom in verband met eventuele opslag kernafval. Bijlagen

    Energy Technology Data Exchange (ETDEWEB)

    Brugge, J.V.M.; Vrouwe, B.J. [T and A Survey, Amsterdam (Netherlands)

    2011-01-15

    The Dutch government aims to store nuclear waste in the Dutch soil. Geological research organization T and A Survey mapped the areas that match with the demands of the Dutch government regarding underground storage of nuclear waste. These are areas in which the Clay layer of Boom has a minimal thickness of 100 meters and the depth of the top of the clay formation is at least 500 meters. This report contains the appendices with (geological) maps and data. [Dutch] De Nederlandse overheid wil kernafval ondergronds opslaan in de Nederlandse bodem. Geologisch onderzoeksbureau T and A Survey brengt de gebieden in kaart, die voldoen aan de door de overheid gestelde eisen voor mogelijke ondergrondse opslag van kernafval. Het gaat om gebieden waar de Boomse kleilaag een minimale dikte van 100 meter heeft en de diepte van de top van de kleiformatie minimaal 500 meter bedraagt. Dit rapport bevat de bijlagen met (geologische) kaarten en gegevens.

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

    NARCIS (Netherlands)

    Werkhoven, P.J.

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2018-03-02

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

  9. Brain penetration of telmisartan, a unique centrally acting angiotensin II type 1 receptor blocker, studied by PET in conscious rhesus macaques

    International Nuclear Information System (INIS)

    Noda, Akihiro; Fushiki, Hiroshi; Murakami, Yoshihiro; Sasaki, Hiroshi; Miyoshi, Sosuke; Kakuta, Hirotoshi; Nishimura, Shintaro

    2012-01-01

    Introduction: Telmisartan is a widely used, long-acting antihypertensive agent. Known to be a selective angiotensin II type 1 (AT 1 ) receptor (AT 1 R) blocker (ARB), telmisartan acts as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and inhibits centrally mediated effects of angiotensin II in rats following peripheral administration, although the brain penetration of telmisartan remains unclear. We investigated the brain concentration and localization of telmisartan using 11 C-labeled telmisartan and positron emission tomography (PET) in conscious rhesus macaques. Methods: Three male rhesus macaques were bolus intravenously administered [ 11 C]telmisartan either alone or as a mixture with unlabeled telmisartan (1 mg/kg). Dynamic PET images were acquired for 95 min following administration. Blood samples were collected for the analysis of plasma concentration and metabolites, and brain and plasma concentrations were calculated from detected radioactivity using the specific activity of the administered drug preparation, in which whole blood radioactivity was used for the correction of intravascular blood radioactivity in brain. Results: Telmisartan penetrated into the brain little but enough to block AT 1 R and showed a consistently increasing brain/plasma ratio within the PET scanning period, suggesting slow clearance of the compound from the brain compared to the plasma clearance. Brain/plasma ratios at 30, 60, and 90 min were 0.06, 0.13, and 0.18, respectively. No marked localization according to the AT 1 R distribution was noted over the entire brain, even on tracer alone dosing. Conclusions: Telmisartan penetrated into the brain enough to block AT 1 R and showed a slow clearance from the brain in conscious rhesus macaques, supporting the long-acting and central responses of telmisartan as a unique property among ARBs.

  10. Chemical-modification studies of a unique sialic acid-binding lectin from the snail Achatina fulica. Involvement of tryptophan and histidine residues in biological activity.

    Science.gov (United States)

    Basu, S; Mandal, C; Allen, A K

    1988-01-01

    A unique sialic acid-binding lectin, achatininH (ATNH) was purified in single step from the haemolymph of the snail Achatina fulica by affinity chromatography on sheep submaxillary-gland mucin coupled to Sepharose 4B. The homogeneity was checked by alkaline gel electrophoresis, immunodiffusion and immunoelectrophoresis. Amino acid analysis showed that the lectin has a fairly high content of acidic amino acid residues (22% of the total). About 1.3% of the residues are half-cystine. The glycoprotein contains 21% carbohydrate. The unusually high content of xylose (6%) and fucose (2.7%) in this snail lectin is quite interesting. The protein was subjected to various chemical modifications in order to detect the amino acid residues and carbohydrate residues present in its binding sites. Modification of tyrosine and arginine residues did not affect the binding activity of ATNH; however, modification of tryptophan and histidine residues led to a complete loss of its biological activity. A marked decrease in the fluorescence emission was found as the tryptophan residues of ATNH were modified. The c.d. data showed the presence of an identical type of conformation in the native and modified agglutinin. The modification of lysine and carboxy residues partially diminished the biological activity. The activity was completely lost after a beta-elimination reaction, indicating that the sugars are O-glycosidically linked to the glycoprotein's protein moiety. This result confirms that the carbohydrate moiety also plays an important role in the agglutination property of this lectin. Images Fig. 3. PMID:3140796

  11. Betel quid chewing leads to the development of unique de novo malignancies in liver transplant recipients, a retrospective single center study in Taiwan.

    Science.gov (United States)

    Chen, Yi-Chan; Cheng, Chih-Hsien; Wang, Yu-Chao; Wu, Ting-Jun; Chou, Hong-Shiue; Chan, Kun-Ming; Lee, Wei-Chen; Lee, Chen-Fang; Soong, Ruey Shyang

    2016-09-01

    Orthotopic liver transplantation (OLT) is the choice of treatment not only for end-stage liver disease and acute liver failure but also for hepatocellular carcinoma (HCC). The development of de novo malignancies after liver transplantation plays an important role in late mortality; the incidence of late mortality has increased owing to improved survival. The incidence of de novo malignancies is 2.3% to 25%, which is 2 to 3 times that of malignancies in the general population. The most commonly reported de novo malignancies in solid organs are skin cancer, Karposi sarcoma, and colon cancer according to the frequency of exposure to a specific carcinogen. We hypothesized that exposure to different carcinogens would change the distribution of de novo malignancies among patients after OLT. In Taiwan, 10% of the population is exposed to a unique carcinogen, the betel quid, which is associated with a high incidence of head and neck cancer (HNC) among the Taiwanese population.From 2004 to 2014, we retrospectively reviewed 484 cases post-OLT at our institution and 16 patients with 17 de novo malignancies were identified. Most of the patients had HNC, which is in contrast to previous literature reports.Univariate and multivariate analyses identified betel quid chewing as the main leading factor for HNC in the Taiwanese population.Routine screening of the oral mucosa in patients with the habit of betel quid chewing is recommended in Taiwan for the early detection of HNC. Routine screening with aggressive treatment after diagnosis of HNC in patients with the habit of chewing betel quid, who underwent OLT, resulted in good patient prognosis.

  12. 3D RoboMET Characterization

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-01

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

  13. Coriocarcinoma con metástasis pulmonar

    Directory of Open Access Journals (Sweden)

    Vicia Sánchez Abalos

    2014-05-01

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

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

    Science.gov (United States)

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

    2016-09-20

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

  15. Esperanto: A Unique Model for General Linguistics.

    Science.gov (United States)

    Dulichenko, Aleksandr D.

    1988-01-01

    Esperanto presents a unique model for linguistic research by allowing the study of language development from project to fully functioning language. Esperanto provides insight into the growth of polysemy and redundancy, as well as into language universals and the phenomenon of social control. (Author/CB)

  16. The end of the unique myocardial band

    DEFF Research Database (Denmark)

    MacIver, David H; Partridge, John B; Agger, Peter

    2018-01-01

    Two of the leading concepts of mural ventricular architecture are the unique myocardial band and the myocardial mesh model. We have described, in an accompanying article published in this journal, how the anatomical, histological and high-resolution computed tomographic studies strongly favour th...

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

    Science.gov (United States)

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

    2018-07-02

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

  18. Association of Catechol-O-methyltransferase polymorphism Val158Met and mammographic density: A meta-analysis.

    Science.gov (United States)

    Kallionpää, Roope A; Uusitalo, Elina; Peltonen, Juha

    2017-08-15

    The Val158Met polymorphism in catechol-O-methyltransferase (COMT) enzyme reduces the methylation of catechol estrogens, which may affect mammographic density. High mammographic density is a known risk factor of breast cancer. Our aim was to perform meta-analysis of the effect of COMT Val158Met polymorphism on mammographic density. Original studies reporting data on mammographic density, stratified by the presence of COMT Val158Met polymorphism, were identified and combined using genetic models Met/Val vs. Val/Val, Met/Met vs. Val/Val, Val/Met+Met/Met vs. Val/Val (dominant model) and Met/Met vs. Val/Met+Val/Val (recessive model). Subgroup analyses by breast cancer status, menopausal status and use of hormone replacement therapy (HRT) were also performed. Eight studies were included in the meta-analysis. The overall effect in percent mammographic density was -1.41 (CI -2.86 to 0.05; P=0.06) in the recessive model. Exclusion of breast cancer patients increased the effect size to -1.93 (CI -3.49 to -0.37; P=0.02). The results suggested opposite effect of COMT Val158Met for postmenopausal users of HRT versus premenopausal women or postmenopausal non-users of HRT. COMT Val158Met polymorphism may be associated with mammographic density at least in healthy women. Menopausal status and HRT should be taken into account in future studies to avoid masking of the underlying effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Kosovo case: A unique arbitrariness

    Directory of Open Access Journals (Sweden)

    Nakarada Radmila

    2007-01-01

    Full Text Available The end of Cold war, contrary to expectations has brought new conflicts and forms of violence, new divisions and new relativizations of the international legal order. Taking as an example the endeavors to resolve the Kosovo conflict, the author attempts to indicate the broader implications of the international efforts to constitute an independent state on part of the territory of an existing sovereign state. The arguments used to justify the redefinition of the borders of the Serbian state without its consent, the moral, democratic, peace arguments, are reviewed. Particular attention is paid to the argument that Kosovo is a unique case and therefore unique rules should be applied. The author seeks to understand the deeper significance of these efforts, concluding that dismantling the present international legal order is not only a potential danger but a possible aim.

  20. Advanced CerMet ceramic composites for medical applications.

    Science.gov (United States)

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

    2017-11-01

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

  1. When cosmology and particle physics met

    International Nuclear Information System (INIS)

    Kaiser, D.

    2007-01-01

    Primordial cosmology describes the first moments of the universe when the interactions of elementary particles with one another determined its evolution. The mutual ignorance between the community of cosmologists with that of elementary physicists is well illustrated by the fact that both communities conceived distinct concepts of mass that 10 years later were found similar: Brans-Dicke gravitation and Higgs field. Now the collaboration between cosmology and particle physics appears necessary since the great unification theory that imposes the 3 basic forces: weak interaction, electromagnetic interaction and strong interaction to merge in a unique force at an energy scale of 10 24 eV, is supposed to have occurred just after the big-bang when the universe was dense and hot. (A.C.)

  2. Complete or partial reduction of the Met receptor tyrosine kinase in distinct circuits differentially impacts mouse behavior.

    Science.gov (United States)

    Thompson, Barbara L; Levitt, Pat

    2015-01-01

    Our laboratory discovered that the gene encoding the receptor tyrosine kinase, MET, contributes to autism risk. Expression of MET is reduced in human postmortem temporal lobe in autism and Rett Syndrome. Subsequent studies revealed a role for MET in human and mouse functional and structural cortical connectivity. To further understand the contribution of Met to brain development and its impact on behavior, we generated two conditional mouse lines in which Met is deleted from select populations of central nervous system neurons. Mice were then tested to determine the consequences of disrupting Met expression. Mating of Emx1 (cre) and Met (fx/fx) mice eliminates receptor signaling from all cells arising from the dorsal pallium. Met (fx/fx) and Nestin (cre) crosses result in receptor signaling elimination from all neural cells. Behavioral tests were performed to assess cognitive, emotional, and social impairments that are observed in multiple neurodevelopmental disorders and that are in part subserved by circuits that express Met. Met (fx/fx) /Emx1 (cre) null mice displayed significant hypoactivity in the activity chamber and in the T-maze despite superior performance on the rotarod. Additionally, these animals showed a deficit in spontaneous alternation. Surprisingly, Met (fx/fx; fx/+) /Nestin (cre) null and heterozygous mice exhibited deficits in contextual fear conditioning, and Met (fx/+) /Nestin (cre) heterozygous mice spent less time in the closed arms of the elevated plus maze. These data suggest a complex contribution of Met in the development of circuits mediating social, emotional, and cognitive behavior. The impact of disrupting developmental Met expression is dependent upon circuit-specific deletion patterns and levels of receptor activity.

  3. ethnomedicinal study o inhabitants of kano met omedicinal study

    African Journals Online (AJOL)

    userpc

    changing pattern of food choice and urbani therefore the need ... coloring or preserving food. These spices playe an integral role in enhancing the taste of food beverages ..... and platelet reactivity by garlic oil in ... In: Essential Human. Nutrition ...

  4. The Uniqueness of Milton Friedman

    OpenAIRE

    J. Daniel Hammond

    2013-01-01

    That there is no Milton Friedman today is not a mystery; the mystery is how Milton Friedman could have been. The facts of Friedman’s biography make him unique among twentieth-century public figures. He had extensive knowledge and expertise in mathematics and statistics. Yet he became a critic of ‘formal’ theory, exemplified by mathematical economics, that failed to engage with real-world facts and data, and of econometric modeling that presumed more knowledge of economic structure than Friedm...

  5. Unique Features of Halophilic Proteins.

    Science.gov (United States)

    Arakawa, Tsutomu; Yamaguchi, Rui; Tokunaga, Hiroko; Tokunaga, Masao

    2017-01-01

    Proteins from moderate and extreme halophiles have unique characteristics. They are highly acidic and hydrophilic, similar to intrinsically disordered proteins. These characteristics make the halophilic proteins soluble in water and fold reversibly. In addition to reversible folding, the rate of refolding of halophilic proteins from denatured structure is generally slow, often taking several days, for example, for extremely halophilic proteins. This slow folding rate makes the halophilic proteins a novel model system for folding mechanism analysis. High solubility and reversible folding also make the halophilic proteins excellent fusion partners for soluble expression of recombinant proteins.

  6. A unique gesture of sharing

    International Nuclear Information System (INIS)

    Mustafa, T.

    1985-01-01

    The Atoms for Peace program was a unique gesture of sharing on the part of the leading industrialized nation, and has very few parallels in modern history. The author says one of the major advantages of the program for developing nations was the much needed stimulation of their indigenous science and technology efforts and the awakening of their governments to the multifaceted benefits of atomic energy. The author discusses how the program benefited Pakistan in the production of electrical energy and in the application of nuclear techniques in the fields of agriculture and medicine, which help to alleviate hunger and combat disease

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Science.gov (United States)

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

    2011-03-31

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

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

    Directory of Open Access Journals (Sweden)

    Kathryn T Hall

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

  10. Harsh Parenting and Serotonin Transporter and BDNF Val66Met Polymorphisms as Predictors of Adolescent Depressive Symptoms.

    Science.gov (United States)

    Koss, Kalsea J; Cummings, E Mark; Davies, Patrick T; Hetzel, Susan; Cicchetti, Dante

    2016-10-13

    Depressive symptoms are prevalent and rise during adolescence. The present study is a prospective investigation of environmental and genetic factors that contribute to the growth in depressive symptoms and the frequency of heightened symptoms during adolescence. Participants included 206 mother-father-adolescent triads (M age at Time 1 = 13.06 years, SD = .51, 52% female). Harsh parenting was observationally assessed during a family conflict paradigm. DNA was extracted from saliva samples and genotyped for the 5-HTTLPR and BDNF Val66Met polymorphisms. Adolescents provide self-reports of depressive symptoms annually across early adolescence. The results reveal Gene × Environment interactions as predictors of adolescent depressive symptom trajectories in the context of harsh parenting as an environmental risk factor. A BDNF Val66Met × Harsh Parenting interaction predicted the rise in depressive symptoms across a 3-year period, whereas a 5-HTTLPR × Harsh Parenting interaction predicted greater frequency in elevated depressive symptoms. The findings highlight the importance of unique genetic and environmental influences in the development and course of heightened depressive symptoms during adolescence.

  11. Metaphor and Corpus Linguistics Metáfora e linguística de corpus

    Directory of Open Access Journals (Sweden)

    Tony Berber Sardinha

    2011-01-01

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

  12. Research progress in c-Met and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    WANG Changqing

    2015-06-01

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

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

    Science.gov (United States)

    1992-01-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

  15. Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

    Science.gov (United States)

    Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

    2006-07-01

    Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

  16. Correlation among genetic variations of c-MET in Chinese patients with non-small cell lung cancer.

    Science.gov (United States)

    Duan, Jianchun; Yang, Xiaodan; Zhao, Jun; Zhuo, Minglei; Wang, Zhijie; An, Tongtong; Bai, Hua; Wang, Jie

    2018-01-05

    The purpose of our research was to determine the correlation of amplification, protein expression and somatic mutation of c-MET in IIIb-IV stage NSCLC (Non-small cell lung cancer). We also explored correlation of c-MET variation with clinical outcome. c-MET expression was observed in 28.6% (56/196) cases, and among those 13.8% (27/196) were shown to be FISH positive. Only 2.67% patients in this study carried the c-MET mutation. Cases with c-MET FISH positive were all IHC positive ,but in IHC positive cases, only half were FISH positive. Among patients with IHC 2+ staining, 35.5% was FISH positive, while cases with IHC 3+ staining,64% was FISH positive. Both protein expression and copy number of c-MET did not significantly correlate with clinical prognosis in these patients treated with EGFR-TKIs. IHC could be used as a preliminary screening method for c-MET copy number amplification and should be confirmed by FISH only in IHC positive case which facilitate selection of ALK or MET inhibitor therapy. c-MET gene copy number, protein expression and somatic mutation for exon 14 were detected by fluorescent- In-Situ -Hybridization (FISH), Immunohistochemistry (IHC), and Denaturing-High-Performance-Liquid-Chromatography (DHPLC), respectively, in 196 NSCLC patients. The relationship between c-MET abnormalities and clinical outcome of targeted therapy was analyzed by McNemar's test.

  17. Preproghrelin Leu72Met polymorphism in obese Korean children.

    Science.gov (United States)

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

    2005-11-01

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

  18. Mars MetNet Mission Pressure and Humidity Devices

    Science.gov (United States)

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

    2012-09-01

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

  19. Unique Features of Mobile Commerce

    Institute of Scientific and Technical Information of China (English)

    DING Xiaojun; IIJIMA Junichi; HO Sho

    2004-01-01

    While the market potentials and impacts of web-based e-commerce are still in the ascendant, the advances in wireless technologies and mobile networks have brought about a new business opportunity and research attention, what is termed mobile commerce. Commonly, mobile commerce is considered to be another new application of existing web-based e-commerce onto wireless networks, but as an independent business area, mobile commerce has its own advantages and challenges as opposed to traditional e-commerce applications. This paper focuses on exploring the unique features of mobile commerce as. Compared with traditional e-commerce. Also, there are still some limitations arisen in m-commerce in contrast to web-based e-commerce. Finally, current state of mobile commerce in Japan is presented in brief, with an introduction of several cases involving mobile commerce applications in today 's marketplace.

  20. Unique features of space reactors

    International Nuclear Information System (INIS)

    Buden, D.

    1990-01-01

    This paper reports on space reactors that are designed to meet a unique set of requirements; they must be sufficiently compact to be launched in a rocket to their operational location, operate for many years without maintenance and servicing, operate in extreme environments, and reject heat by radiation to space. To meet these restrictions, operating temperatures are much greater than in terrestrial power plants, and the reactors tend to have a fast neutron spectrum. Currently, a new generation of space reactor power plants is being developed. The major effort is in the SP-100 program, where the power plant is being designed for seven years of full power, and no maintenance operation at a reactor outlet operating temperature of 1350 K

  1. The Uniqueness of Islamic Culture

    Directory of Open Access Journals (Sweden)

    Sinan YILMAZ

    2014-12-01

    Full Text Available Abstract This paper examines the main reasons behind why Islamic culture is different than other cultures. In the introduction part of the paper, the usage area of the words culture and civilization were tackled. In the first part of the paper, an evaluation of the uniqueness of Islamic culture was made and examples about this were given. In the second part of the paper, evaluations about how Islamic culture has struggled with modernization and secularization and how it has shaped itself as a result of this were made. In the third part of the paper, the situation in which Islamic civilization has regressed against the Western civilization causing emerging arguments and the current situation in Islamic civilization have been addressed by making evaluations on culture and civilization. In the final part, evaluations on thesis this paper has used were made.

  2. A combined study of gas geochemistry, petrology, and lava effusion at Bagana, a unique persistently active lava cone in Papua New Guinea

    Science.gov (United States)

    McCormick, B. T.; Salem, L. C.; Edmonds, M.; D'Aleo, R. N. M.; Aiuppa, A.; Arellano, S. R.; Wallius, J.; Galle, B.; Barry, P. H.; Ballentine, C. J.; Mulina, K.; Sindang, M.; Itikarai, I.; Wadge, G.; Lopez, T. M.; Fischer, T. P.

    2016-12-01

    Bagana volcano (Bougainville Island, Papua New Guinea) has exhibited nearly continuous extrusion of andesitic lava for over a century, but has largely been studied by satellite remote sensing. Satellite UV spectroscopy has revealed Bagana to be among the largest volcanic sources of sulfur dioxide worldwide. Satellite radar measurements of lava extrusion rate suggest that the entire edifice could have been built in only a few centuries. Bagana is dominantly constructed from lava flows, but also exhibits violent PDC-forming explosive eruptions, which threaten local populations.We present new multi-parameter data from fieldwork on Bagana in September 2016. UV spectrometers were deployed to ground-truth satellite observations of SO2 emissions, and track sub-daily variations in gas output. In situ measurements and sampling of emissions provide the first gas composition data for this volcano. Aerial imagery filmed by UAV was obtained to generate a high resolution DEM of the edifice for use in calibrating ongoing satellite radar studies of deformation and extrusion rate. Lava and tephra samples were gathered, with the aim of comparing melt composition and volatile content between eruptions of different style. The combination of gas geochemistry, geophysical monitoring from space, and petrology will be used to build a model framework to understand the pulsatory nature of Bagana's lava extrusion, and transitions to explosive activity.A campaign to a continuously active but poorly-studied volcano affords many opportunities for education and outreach. The campaign participants included early career scientists from five countries, who planned and carried out the fieldwork and exchanged expertise in a range of techniques. All work was undertaken in close collaboration with Rabaul Volcano Observatory, and was informed by their strategic monitoring goals, a valuable experience for the field team of synergising research activities with more operational concerns. Footage obtained

  3. Characterization of a unique tomaymycin-d(CICGAATTCICG)2 adduct containing two drug molecules per duplex by NMR, fluorescence, and molecular modeling studies

    International Nuclear Information System (INIS)

    Boyd, F.L.; Stewart, D.; Hurley, L.H.; Remers, W.A.; Barkley, M.D.

    1990-01-01

    Tomaymycin is a member of the pyrrolo[1,4]benzodiazepine [P(1,4)B] antitumor antibiotic group. This antibiotic is proposed to react with the exocyclic 2-amino group (N2) of guanine to form a covalent adduct that lies snugly within the minor groove of DNA. While DNA-footprinting experiments using methidiumpropyl-EDTA have revealed the favored bonding sequences for tomaymycin and related drugs on DNA, the stereochemistry at the covalent bonding site (C-11) and orientation in the minor groove were not established by these experiments. In previous studies using a combined fluorescence, high-field NMR, and molecular modeling approach, the authors have shown that for tomaymycin there are two diastereomeric species (11R and 11S) on both calf thymus DNA and d(ATGCAT) 2 . Although they were able to infer the identify of the two species on d(ATGCAT) 2 , definitive experimental evidence was lacking. They have designed and synthesized a self-complementary 12-mer [d(CICGAATTCICG) 2 ] based on the Dickerson dodecamer [d(CGCGAATTCGCG) 2 ] that bonds identically two tomaymycin molecules, each having a defined orientation and stereochemistry. The results presented in this study together with previous investigations show that the orientation of the drug molecule in the minor groove, and stereochemistry at the covalent linkage site, is dependent upon both the flanking sequence and drug structure. This conclusion mandates caution be used in rationalizing the biochemical and and biological effects of P(1,4)B bonding to DNA until precise structural information is established

  4. Modularity, comparative cognition and human uniqueness

    OpenAIRE

    Shettleworth, Sara J.

    2012-01-01

    Darwin's claim ‘that the difference in mind between man and the higher animals … is certainly one of degree and not of kind’ is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference ...

  5. Early estimation of pandemic influenza Antiviral and Vaccine Effectiveness (EAVE): use of a unique community and laboratory national data-linked cohort study.

    Science.gov (United States)

    Simpson, Colin R; Lone, Nazir; McMenamin, Jim; Gunson, Rory; Robertson, Chris; Ritchie, Lewis D; Sheikh, Aziz

    2015-10-01

    After the introduction of any new pandemic influenza, population-level surveillance and rapid assessment of the effectiveness of a new vaccination will be required to ensure that it is targeted to those at increased risk of serious illness or death from influenza. We aimed to build a pandemic influenza reporting platform that will determine, once a new pandemic is under way: the uptake and effectiveness of any new pandemic vaccine or any protective effect conferred by antiviral drugs once available; the clinical attack rate of pandemic influenza; and the existence of protection provided by previous exposure to, and vaccination from, A/H1N1 pandemic or seasonal influenza/identification of susceptible groups. An observational cohort and test-negative study design will be used (post pandemic). A national linkage of patient-level general practice data from 41 Practice Team Information general practices, hospitalisation and death certification, virological swab and serology-linked data. We will study a nationally representative sample of the Scottish population comprising 300,000 patients. Confirmation of influenza using reverse transcription polymerase chain reaction and, in a subset of the population, serology. Future available pandemic influenza vaccination and antivirals will be evaluated. To build a reporting platform tailored towards the evaluation of pandemic influenza vaccination. This system will rapidly measure vaccine effectiveness (VE), adjusting for confounders, estimated by determining laboratory-confirmed influenza; influenza-related morbidity and mortality, including general practice influenza-like illnesses (ILIs); and hospitalisation and death from influenza and pneumonia. Once a validated haemagglutination inhibition assay has been developed (and prior to the introduction of any vaccination), cross-reactivity with previous exposure to A/H1N1 or A/H1N1 vaccination, other pandemic influenza or other seasonal influenza vaccination or exposure will be

  6. In vivo and in vitro studies of Cry5B and nicotinic acetylcholine receptor agonist anthelmintics reveal a powerful and unique combination therapy against intestinal nematode parasites.

    Directory of Open Access Journals (Sweden)

    Yan Hu

    2018-05-01

    Full Text Available The soil-transmitted nematodes (STNs or helminths (hookworms, whipworms, large roundworms infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define the characteristics of these combinations in vivo.Working with the hookworm Ancylostoma ceylanicum-hamster infection system, we establish a laboratory paradigm for studying anti-nematode combinations in vivo using Cry5B and the nicotinic acetylcholine receptor (nAChR agonists tribendimidine and pyrantel pamoate. We demonstrate that Cry5B strongly synergizes in vivo with both tribendimidine and pyrantel at specific dose ratios against hookworm infections. For example, whereas 1 mg/kg Cry5B and 1 mg/kg tribendimidine individually resulted in only a 0%-6% reduction in hookworm burdens, the combination of the two resulted in a 41% reduction (P = 0.020. Furthermore, when mixed at synergistic ratios, these combinations eradicate hookworm infections at doses where the individual doses do not. Using cyathostomin nematode parasites of horses, we find based on inhibitory concentration 50% values that a strongylid parasite population doubly resistant to nAChR agonists and benzimidazoles is more susceptible or "hypersusceptible" to Cry5B than a cyathostomin population not resistant to nAChR agonists, consistent with previous Caenhorhabditis elegans results.Our study provides a powerful means by which anthelmintic combination therapies can be examined in vivo

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

    Science.gov (United States)

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

    2016-01-01

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

  8. A unique mountainous vertical distribution patterns and related environmental interpretation-a case study on the northern slope of the ili river valley

    International Nuclear Information System (INIS)

    Tian, Z.P.; Wang, X.L.; Zhuang, L.

    2016-01-01

    Patterns of plant diversity and soil factors along the altitude gradient on the northern slope of Ili River Valley were examined. Plant and environment characteristics were surveyed from 1000-2200 m. There were a total of 155 vascular plant, 133 herbage, 18 shrub, and 7 tree species in 44 sampled plots. The plant richness of vegetation types generally showed a special pattern along altitude, with a bimodal change of plant species number at 100m intervals of altitude samples. The two belts of higher plant richness were in transient areas between vegetation types, the first in areas from low-mountain desert to forest, and the other from dry grass to coniferous forest. Matching the change of richness of plant species to environmental factors along altitude by GAM model and relation analysis revealed that the environmental factors controlling species richness and their patterns were the combined effects of soil salt and nutrition. Water was more important at lower altitude, and temperature at higher altitude, the role of the inversion layer at high altitude coniferous forest species diversity appearing to rise. Soil nutrition and salt also showed a similar distribution pattern of diversity. Especially, diversity index and soil salinity showed a strong correlation. This study provides insights into plant diversity conservation of ili River Valley in Tianshan Mountain. (author)

  9. Evaluation of international case studies within 'Live.Learn.Laugh.': a unique global public-private partnership to promote oral health.

    Science.gov (United States)

    Dugdill, Lindsey; Pine, Cynthia M

    2011-08-01

    The partnership between the Féderation Dentaire International (FDI), and Unilever Oral Care, aims to raise awareness of oral health globally; to enable FDI member associations to promote oral health; and to increase the visibility of the FDI and authority of Unilever oral care brands worldwide. Country Projects between National Dental Associations (NDAs), the member associations of FDI, and Unilever Oral Care local companies have been established as a key strand of the partnership. This paper reports on the evaluation of an in-depth sample of Country Projects (n=5) to determine their potential to impact on oral health. Five country sites were selected as being indicative of different programme delivery types. Each site received a two-day visit during Spring-Summer 2009, which enabled the evaluators to audit what was delivered in practice compared with the original written project briefs and to undertake interviews of study site staff. 39 projects in 36 countries have been initiated. In those examined by site visits, clear evidence was found of capacity building to deliver oral health. In some countries, widespread population reach had been prioritised. Effectiveness of partnership working varied depending on the strength of the relationship between the NDA and local Unilever Oral Care representatives and alignment with national marketing strategy. The quality of internal evaluation varied considerably. Over a million people had been reached directly by Country Projects and this public-private partnership has made a successful start. To move towards improving oral health rather than only awareness raising; future Country Projects would benefit from being limited to certain evidence-based intervention designs, and using an agreed core indicator set in order to allow cross-country comparison of intervention outcomes. © 2011 FDI World Dental Federation.

  10. Brain-derived neurotrophic factor Val66Met polymorphism and hippocampal activation during episodic encoding and retrieval tasks

    OpenAIRE

    Dennis, Nancy A.; Cabeza, Roberto; Need, Anna C.; Waters-Metenier, Sheena; Goldstein, David B.; LaBar, Kevin S.

    2010-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin which has been shown to regulate cell survival and proliferation, as well as synaptic growth and hippocampal long-term potentiation. A naturally occurring single nucleotide polymorphism in the human BDNF gene (val66met) has been associated with altered intercellular trafficking and regulated secretion of BDNF in met compared to val carriers. Additionally, previous studies have found a relationship between the BDNF val66met genotype an...

  11. Expression of the c-Met oncogene by tumor cells predicts a favorable outcome in classical Hodgkin's lymphoma.

    Science.gov (United States)

    Xu, Chuanhui; Plattel, Wouter; van den Berg, Anke; Rüther, Nele; Huang, Xin; Wang, Miao; de Jong, Debora; Vos, Hans; van Imhoff, Gustaaf; Viardot, Andreas; Möller, Peter; Poppema, Sibrand; Diepstra, Arjan; Visser, Lydia

    2012-04-01

    The c-Met signaling pathway regulates a variety of biological processes, including proliferation, survival and migration. Deregulated c-Met activation has been implicated in the pathogenesis and prognosis of many human malignancies. We studied the function and prognostic significance of c-Met and hepatocyte growth factor protein expression in patients with classical Hodgkin's lymphoma. Expression of c-Met and its ligand, hepatocyte growth factor, were determined by immunohistochemistry. Prognostic values were defined in cohorts of German and Dutch patients with classical Hodgkin's lymphoma. Functional studies were performed on Hodgkin's lymphoma cell lines. Expression of c-Met was detected in the tumor cells of 52% (80/153) of the patients and expression of its ligand, hepatocyte growth factor, in 8% (10/121) of the patients. c-Met expression correlated with a 5-year freedom from tumor progression of 94%, whereas lack of expression correlated with a 5-year freedom from tumor progression of 73% (Pfreedom from tumor progression. In functional studies activation with hepatocyte growth factor did not affect cell growth, while the c-Met inhibitor SU11274 suppressed cell growth by inducing G2/M cell cycle arrest. Although functional studies showed an oncogenic role of the hepatocyte growth factor/c-Met signaling pathway in cell cycle progression, expression of c-Met in tumor cells from patients with classical Hodgkin's lymphoma strongly correlated with a favorable prognosis in two independent cohorts.

  12. Novel organic NLO material bis(N-phenylbiguanidium(1+)) oxalate - A combined X-ray diffraction, DSC and vibrational spectroscopic study of its unique polymorphism

    Science.gov (United States)

    Matulková, Irena; Císařová, Ivana; Vaněk, Přemysl; Němec, Petr; Němec, Ivan

    2017-01-01

    Three polymorphic modifications of bis(N-phenylbiguanidium(1+)) oxalate are reported, and their characterization is discussed in this paper. The non-centrosymmetric bis(N-phenylbiguanidium(1+)) oxalate (I), which was obtained from an aqueous solution at 313 K, belongs to the monoclinic space group Cc (a = 6.2560(2) Å, b = 18.6920(3) Å, c = 18.2980(5) Å, β = 96.249(1)°, V = 2127.0(1) Å3, Z = 4, R = 0.0314 for 4738 observed reflections). The centrosymmetric bis(N-phenylbiguanidium(1+)) oxalate (II) was obtained from an aqueous solution at 298 K and belongs to the monoclinic space group P21/n (a = 6.1335(3) Å, b = 11.7862(6) Å, c = 14.5962(8) Å, β = 95.728(2)°, V = 1049.90(9) Å3, Z = 4, R = 0.0420 for 2396 observed reflections). The cooling of the centrosymmetric phase (II) leads to the formation of bis(N-phenylbiguanidium(1+)) oxalate (III) (a = 6.1083(2) Å, b = 11.3178(5) Å, c = 14.9947(5) Å, β = 93.151(2)°, V = 1035.05(8) Å3, Z = 4, R = 0.0345 for 2367 observed reflections and a temperature of 110 K), which also belongs to the monoclinic space group P21/n. The crystal structures of the three characterized phases are generally based on layers of isolated N-phenylbiguanidium(1 +) cations separated by oxalate anions and interconnected with them by several types of N-H...O hydrogen bonds. The observed phases generally differ not only in their crystal packing but also in the lengths and characteristics of their hydrogen bonds. The thermal behaviour of the prepared compounds was studied using the DSC method in the temperature range from 90 K up to a temperature near the melting point of each crystal. The bis(N-phenylbiguanidium(1+)) oxalate (II) crystals exhibit weak reversible thermal effects on the DSC curve at 147 K (heating run). Further investigation of this effect, which was assigned to the isostructural phase transformation, was performed using FTIR, Raman spectroscopy and X-ray diffraction analysis in a wide temperature range.

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

    Directory of Open Access Journals (Sweden)

    Brian Shuch

    2015-01-01

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

  14. Cathecol-O-methyl transferase Val158Met genotype is not a risk factor for conversion disorder.

    Science.gov (United States)

    Armagan, E; Almacıoglu, M L; Yakut, T; Köse, A; Karkucak, M; Köksal, O; Görükmez, O

    2013-03-19

    Alterations in catechol-O-methyltransferase (COMT) activity are involved in various types of neurological disorders. We examined a possible association between the COMT Val158Met polymorphism and conversion disorder in a study of 48 patients with conversion disorder and 48 control patients. In the conversion disorder group, 31 patients were Val/Met heterozygotes, 15 patients were Val/Val homozygotes and 2 patients were Met/Met homozygotes. In the control group, 32 patients were Val/Met heterozygotes and 16 patients were Val/Val homozygotes. There was no significant difference between the groups. We conclude that the COMT Val158Met genotype is quite common in Turkey and that it is not a risk factor for conversion disorder in the Turkish population.

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

    Directory of Open Access Journals (Sweden)

    Erkol İnal E

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Birgit Piater

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

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

    Science.gov (United States)

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

  18. Invloed krachtvoerniveau op vleesproduktiekenmerken van Piemontese met zwartbont kruislingstieren

    NARCIS (Netherlands)

    Hanekamp, W.J.A.

    1989-01-01

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

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

    NARCIS (Netherlands)

    van Diepen, A.; Huisman, C.

    2008-01-01

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

  20. Mindfulness voor volwassenen met een licht verstandelijke beperking

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    African Journals Online (AJOL)

    Test

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

  2. Human uniqueness-self-interest and social cooperation.

    Science.gov (United States)

    Okada, Daijiro; Bingham, Paul M

    2008-07-21

    Humans are unique among all species of terrestrial history in both ecological dominance and individual properties. Many, or perhaps all, of the unique elements of this nonpareil status can be plausibly interpreted as evolutionary and strategic elements and consequences of the unprecedented intensity and scale of our social cooperation. Convincing explanation of this unique human social adaptation remains a central, unmet challenge to the scientific enterprise. We develop a hypothesis for the ancestral origin of expanded cooperative social behavior. Specifically, we present a game theoretic analysis demonstrating that a specific pattern of expanded social cooperation between conspecific individuals with conflicts of interest (including non-kin) can be strategically viable, but only in animals that possess a highly unusual capacity for conspecific violence (credible threat) having very specific properties that dramatically reduce the costs of coercive violence. The resulting reduced costs allow preemptive or compensated coercion to be an instantaneously self-interested behavior under diverse circumstances rather than in rare, idiosyncratic circumstances as in actors (animals) who do not have access to inexpensive coercive threat. Humans are apparently unique among terrestrial organisms in having evolved conspecific coercive capabilities that fulfill these stringent requirements. Thus, our results support the proposal that access to a novel capacity for projection of coercive threat might represent the essential initiating event for the evolution of a human-like pattern of social cooperation and the subsequent evolution of the diverse features of human uniqueness. Empirical evidence indicates that these constraints were, in fact, met only in our evolutionary lineage. The logic for the emergence of uniquely human cooperation suggested by our analysis apparently accounts simply for the human fossil record.

  3. Study of Wind Effects on Unique Buildings

    Science.gov (United States)

    Olenkov, V.; Puzyrev, P.

    2017-11-01

    The article deals with a numerical simulation of wind effects on the building of the Church of the Intercession of the Holy Virgin in the village Bulzi of the Chelyabinsk region. We presented a calculation algorithm and obtained pressure fields, velocity fields and the fields of kinetic energy of a wind stream, as well as streamlines. Computational fluid dynamic (CFD) evolved three decades ago at the interfaces of calculus mathematics and theoretical hydromechanics and has become a separate branch of science the subject of which is a numerical simulation of different fluid and gas flows as well as the solution of arising problems with the help of methods that involve computer systems. This scientific field which is of a great practical value is intensively developing. The increase in CFD-calculations is caused by the improvement of computer technologies, creation of multipurpose easy-to-use CFD-packagers that are available to a wide group of researchers and cope with various tasks. Such programs are not only competitive in comparison with physical experiments but sometimes they provide the only opportunity to answer the research questions. The following advantages of computer simulation can be pointed out: a) Reduction in time spent on design and development of a model in comparison with a real experiment (variation of boundary conditions). b) Numerical experiment allows for the simulation of conditions that are not reproducible with environmental tests (use of ideal gas as environment). c) Use of computational gas dynamics methods provides a researcher with a complete and ample information that is necessary to fully describe different processes of the experiment. d) Economic efficiency of computer calculations is more attractive than an experiment. e) Possibility to modify a computational model which ensures efficient timing (change of the sizes of wall layer cells in accordance with the chosen turbulence model).

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

    Directory of Open Access Journals (Sweden)

    Chang-hyun Park

    2017-08-01

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

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

    Science.gov (United States)

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

    2012-08-10

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

  6. Het consumentengedrag met betrekking tot melk

    NARCIS (Netherlands)

    Termorshuizen, J.G.

    1982-01-01

    In this study, consumer behaviour with respect to fluid milk in the Netherlands is examined. The objectives of the study are
    - to gain insight into the factors that influence buying and consumption be haviour with respect to milk, and
    - to gain insight into the usefulness of a so called

  7. The MeteoMet2 project—highlights and results

    Science.gov (United States)

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

    2018-02-01

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

  8. 11C-MET PET/MRI for detection of recurrent glioma.

    Science.gov (United States)

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

    2018-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2018-04-15

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

  10. MET18 Deficiency Increases the Sensitivity of Yeast to Oxidative Stress and Shortens Replicative Lifespan by Inhibiting Catalase Activity.

    Science.gov (United States)

    Chen, Ya-Qin; Liu, Xin-Guang; Zhao, Wei; Cui, Hongjing; Ruan, Jie; Yuan, Yuan; Tu, Zhiguang

    2017-01-01

    Yeast MET18 , a subunit of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery which is responsible for the maturation of Fe/S proteins, has been reported to participate in the oxidative stress response. However, the underlying molecular mechanisms remain unclear. In this study, we constructed a MET18/met18Δ heterozygous mutant yeast strain and found that MET18 deficiency in yeast cells impaired oxidative stress resistance as evidenced by increased sensitivity to hydrogen peroxide (H 2 O 2 ) and cumene hydroperoxide (CHP). Mechanistically, the mRNA levels of catalase A (CTA1) and catalase T (CTT1) as well as the total catalase activity were significantly reduced in MET18 -deficient cells. In contrast, overexpression of CTT1 or CTA1 in MET18 -deficient cells significantly increased the intracellular catalase activity and enhanced the resistance ability against H 2 O 2 and CHP. In addition, MET18 deficiency diminished the replicative capacity of yeast cells as evidenced by the shortened replicative lifespan, which can be restored by CTT1 overexpression, but not by CTA1 , in the MET18 -deficient cells. These results suggest that MET18 , in a catalase-dependent manner, plays an essential role in enhancing the resistance of yeast cells to oxidative stress and increasing the replicative capacity of yeast cells.

  11. Het consumentengedrag met betrekking tot melk

    OpenAIRE

    Termorshuizen, J.G.

    1982-01-01

    In this study, consumer behaviour with respect to fluid milk in the Netherlands is examined. The objectives of the study are- to gain insight into the factors that influence buying and consumption be haviour with respect to milk, and- to gain insight into the usefulness of a so called integreated model of consumer behaviour.Chapter 2 presents an analysis of the pattern of milk consumption by Dutch households and the changes that have occurred in it since 1950. First, the trend and seasonal fl...

  12. Interview met professor Joan Wallach Scott

    NARCIS (Netherlands)

    Bijl, Greetje; Tijhoff, Esmeralda

    2012-01-01

    Joan Scott, professor at the School of Social Science in the Institute for Avanced Study in Princeton, New Jersey (USA), was the keynote speaker at the conference 'Uitsluitend emancipatie' in de Beurs van Berlage in Amsterdam in October 2012. An interview on gender, history, feminism and her book

  13. HIV is Now a Manageable Long-Term Condition, But What Makes it Unique? A Qualitative Study Exploring Views About Distinguishing Features from Multi-Professional HIV Specialists in North West England.

    Science.gov (United States)

    Jelliman, Pauline; Porcellato, Lorna

    HIV is evolving from a life-threatening infection to a long-term, manageable condition because of medical advances, radical changes in health and social care policy, and the impact of an aging population. However, HIV remains complex, presenting unique characteristics distinguishing it from other long-term conditions (LTCs). Our aim in this qualitative descriptive study was to identify and explore these features in the context of LTCs. A focus group (FG) method was used to gather the views and experiences of multi-professional HIV specialists who worked in North West England. Twenty-four staff participated in FGs (n = 3), which were audio recorded, manually transcribed, and thematically analyzed. We found four main themes: (a) stigma, (b) challenges faced by HIV specialists, (c) lack HIV-related knowledge, and (d) unique features, termed "stand alone." We concluded that these distinguishing features hindered full recognition and acceptance of HIV as an LTC. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  14. Heart Failure: Unique to Older Adults

    Science.gov (United States)

    ... to Z › Heart Failure › Unique to Older Adults Font size A A A Print Share Glossary Unique ... will suffer from depression at some point. This type of severe depression is more serious than the ...

  15. Medical Emergency Team: How do we play when we stay? Characterization of MET actions at the scene.

    Science.gov (United States)

    Silva, Raquel; Saraiva, Manuel; Cardoso, Teresa; Aragão, Irene C

    2016-03-22

    The creation, implementation and effectiveness of a medical emergency team (MET) in every hospital is encourage and supported by international bodies of quality certification. Issues such as what is the best composition of the team or the interventions performed by the MET at the scene and the immediate outcomes of the patients after MET intervention have not yet been sufficiently explored. The purpose of the study is to characterize MET actions at the scene and the immediate patient outcome. Retrospective cohort study, at a tertiary care, university-affiliated, 600-bed hospital, in the north of Portugal, over two years. There were 511 MET activations: 389 (76%) were for inpatients. MET activation rate was 8.6/1,000 inpatients. The main criteria for activation were airway threatening in 143 (36.8%), concern of medical staff in 121 (31.1%) and decrease in GCS > 2 in 98 (25.2%) patients; MET calls for cardiac arrest occurred in 68 patients (17.5%). The median (IQR) time the team stayed at the scene was 35 (20-50) minutes. At the scene, the most frequent actions were related to airway and ventilation, namely oxygen administration in 145 (37.3%); in circulation, fluid were administered in 158 (40.6%); overall medication was administered in 185 (47.5%) patients. End-of-life decisions were part of the MET actions in 94 (24.1%) patients. At the end of MET intervention, 73 (18.7%) patients died at the scene, 190 (60.7%) stayed on the ward and the remaining 123 patients were transferred to an increased level of care. Crude hospital mortality rate was 4.1% in the 3 years previously to MET implementation and 3.6% in the following 3 years (p residence. The team stayed on site for half an hour and during that time most of the actions were simple and nurse-driven, but in one third of all activations medical actions were taken, and in a forth (24%) end-of-life decisions made, reinforcing the inclusion of a doctor in the MET. A significant decrease in overall hospital

  16. Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice.

    Science.gov (United States)

    Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L; Lee, Francis S; Blendy, Julie A

    2015-12-01

    Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine withdrawal. Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For

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

    Science.gov (United States)

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

    2009-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Nils Freundlieb

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

  19. Evolutionary theory, human uniqueness and the image of God

    Directory of Open Access Journals (Sweden)

    Gijsbert van den Brink

    2012-10-01

    Full Text Available In this article, I examined what might be called the evolutionary argument against human uniqueness and human dignity. After having rehearsed briefly the roots of the classical Judeo- Christian view on human uniqueness and human dignity in the first chapters of Genesis, I went on to explore and delineate the nature of the evolutionary argument against this view. Next, I examined whether Christian theology might widen the concept of imago Dei so as to include other beings as well as humans, thus giving up the idea of human uniqueness. I concluded, however, that this move is deeply problematic. Therefore, I turned to a discussion of some recent attempts to define both human uniqueness and the image of God in theological rather than empirical terms. One of these, which is based on the concept of incarnation, is found wanting, but another one is construed in such a way that it enables us to reconcile the idea of human uniqueness as encapsulated in the doctrine of the imago Dei with contemporary evolutionary theory. Thus, this article can be seen as an exercise in bringing classical Christian theology to terms with evolution, further highlighting this theology’s ongoing vitality. Evolusieteorie, menslike uniekheid and die beeld van God. In hierdie artikel ondersoek ek die sogenaamde evolusionêre argument teen menslike uniekheid en menswaardigheid. Na ‘n kort oorsig oor die oorsprong van die klassieke Joods-Christelike siening van menslike uniekheid en menswaardigheid soos uit die eerste vyf hoofstukke van Genesis blyk, ondersoek en beeld ek die aard van die evolusionêre argument hierteenoor uit. Vervolgens word die vraag ondersoek of die Christelike teologie die konsep van imago Dei sodanig kan verbreed dat dit ook ander wesens behalwe mense kan insluit, waardeur die idee van menslike uniekheid dus prysgegee word. Ek kom egter tot die slotsom dat hierdie skuif hoogs problematies is. Daarom wend ek my tot ’n bespreking van onlangse pogings om

  20. ‘Schamoteren met de grote woorden’

    Directory of Open Access Journals (Sweden)

    Wendy Lemmens

    2016-02-01

    Full Text Available ‘Juggling with big words’: Register variation in Hugo Claus’s De verwondering (1962 The prose of Hugo Claus has been the subject of broad scholarly interest, regarding – amongst other things – intertextuality and allegories. The presence of various, contrasting language registers has been briefly touched upon, but has – mainly because of the lack of an appropriate research method – never been studied in greater detail. This preliminary article analyses some excerpts of De verwondering (1962, the first novel in which Claus experiments with register variation, based on the stylistic methodology developed by Leech and Short (2007. The analyses demonstrate that this methodology is highly applicable to analyse not just ‘the style’ of a text, but also to ‘zoom in’ on various registers. In doing so, numerous aspects that help constitute (but at the same time undermine a certain interpretation come more profoundly to the fore, showing that the study of register variation is promising, especially regarding novels in which different varieties of the same language appear.

  1. BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity.

    Science.gov (United States)

    Notaras, Michael J; Hill, Rachel A; Gogos, Joseph A; van den Buuse, Maarten

    2017-05-01

    Reduced expression of Brain-Derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of schizophrenia. The BDNF Val66Met polymorphism, which results in deficient activity-dependent secretion of BDNF, is associated with clinical features of schizophrenia. We investigated the effect of this polymorphism on Prepulse Inhibition (PPI), a translational model of sensorimotor gating which is disrupted in schizophrenia. We utilized humanized BDNFVal66Met (hBDNFVal66Met) mice which have been modified to carry the Val66Met polymorphism, as well as express humanized BDNF in vivo. We also studied the long-term effect of chronic corticosterone (CORT) exposure in these animals as a model of history of stress. PPI was assessed at 30ms and 100ms interstimulus intervals (ISI). Analysis of PPI at the commonly used 100ms ISI identified that, irrespective of CORT treatment, the hBDNFVal/Met genotype was associated with significantly reduced PPI. In contrast, PPI was not different between hBDNFMet/Met and hBDNFVal/Val genotype mice. At the 30ms ISI, CORT treatment selectively disrupted sensorimotor gating of hBDNFVal/Met heterozygote mice but not hBDNFVal/Val or hBDNFMet/Met mice. Analysis of startle reactivity revealed that chronic CORT reduced startle reactivity of hBDNFVal/Val male mice by 51%. However, this was independent of the effect of CORT on PPI. In summary, we provide evidence of a distinct BDNFVal66Met heterozygote-specific phenotype using the sensorimotor gating endophenotype of schizophrenia. These data have important implications for clinical studies where, if possible, the BDNFVal/Met heterozygote genotype should be distinguished from the BDNFMet/Met genotype. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. A comparison of students who chose a traditional or a problem-based learning curriculum after failing year 2 in the traditional curriculum: a unique case study at the Nelson R. Mandela School of Medicine.

    Science.gov (United States)

    McLean, Michelle

    2004-01-01

    To canvas perceptions and experiences of students who had failed Year 2 of a traditional medical program and who chose to remain in the conventional program (n = 6) or had swapped to Curriculum 2001 (C2001), a problem-based learning (PBL) curriculum (n = 14). A year after their decision regarding curriculum choice, students were canvassed (largely open-ended survey) about this decision and about their perceptions of their curricular experiences. C2001 students were positive about their PBL experiences. Overwhelmingly, their decision to swap streams had been a good one. They identified PBL features as supporting their learning. Repeating traditional curriculum students were, however, more circumspect in their opinions. C2001 students had clearly embraced PBL. They were now medical students, largely because of PBL activities underpinned by a sound educational philosophy. This unique case study has provided additional evidence that PBL students are generally more content with their studies than their conventional curriculum counterparts.

  3. Customization: Ideal Varieties, Product Uniqueness and Price Competition

    OpenAIRE

    Oksana Loginova; X. Henry Wang

    2009-01-01

    We study customization in the Hotelling model with two firms. In addition to providing ideal varieties, the perceived uniqueness of a customized product contributes independently to consumer utility. We show that only when consumer preferences for uniqueness are high customization occurs in equilibrium.

  4. Role of Met Axis in Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-26

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

  5. Met flora meer fauna de stad in trekken

    NARCIS (Netherlands)

    Hoffman, M.H.A.

    2010-01-01

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

  6. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Science.gov (United States)

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

    2017-09-01

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

  7. Leven met de varroamijt in de 21ste eeuw

    NARCIS (Netherlands)

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

    2002-01-01

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

  8. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Science.gov (United States)

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

    2017-04-01

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

  9. Association between COMT Polymorphism Val158Met and Opioid Consumption in Patients with Postoperative Pain: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Bo Hu

    2018-01-01

    Full Text Available Background/Aims: Several factors influencing postoperative pain and the effect of opioid analgesics have been investigated on an individual level. The aim of this study was to clarify the impact of catecholamine-O-methyltransferase (COMT gene Val158Met on opioid consumption in postoperative patients. Methods: A systematic review and meta-analysis of the literature up to September 30, 2017, were performed by using PubMed, Cochrane Library, ISI Web of Science, and Chinese National Knowledge Infrastructure (CNKI database. The meta-analysis examined all studies involving the association between genetic polymorphisms of COMT Val158Met and opioid consumption during the acute postoperative period. Results: Of the 153 identified studies, 23 studies were retrieved for systematic review and 10 studies were retrieved for meta-analysis. However, it was impossible to conduct meta-analysis on the association between COMT Val158Met polymorphism and postoperative pain because of heterogeneity of the data. Overall, meta-analysis showed that COMT Val/Met carriers consumed less opioid for analgesia within the first 24 hours after surgery (SMD = 0.14, 95% CI = [0.03, 0.25], P = 0.01 but not within 48 hours (SMD = 0.14, 95% CI = [0.08, 0.36], P = 0.21. There was no significant difference in opioid consumption between Val/ Val and Met/Met patients. Conclusion: Patients with Val/Met but not Met/Met allele variant consumed less opioid, though larger and better-designed studies are required to obtain an exclusive conclusion about the correlation between postoperative pain and COMT Val158Met polymorphism.

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

    Science.gov (United States)

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

    2002-10-01

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

  11. The BDNF Val66Met polymorphism: relation to familiar risk of affective disorder, BDNF levels and salivary cortisol

    DEFF Research Database (Denmark)

    Vinberg, Maj; Trajkovska, Viktorija; Bennike, Bente

    2009-01-01

    BACKGROUND: Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are considered to play an important role in the pathophysiology of affective disorders. The aim of the present study was to investigate whether the BDNF Val66Met polymorphism is associated...... with a familiar risk of affective disorder and whether these genotypes affect whole blood BDNF level and salivary cortisol. METHOD: In a high-risk study, healthy monozygotic and dizygotic twins with and without a co-twin (high- and low-risk twins, respectively) history of affective disorder were identified...... through nationwide registers. RESULTS: Familiar predisposition to unipolar and bipolar disorder was not associated with any specific genotype pattern of the BDNF Val66Met polymorphism, not in this sample of 124 val/val, 58 val/met and 8 met/met individuals. However, the combination of having a high...

  12. Study of a unique 16th century Antwerp majolica floor in the Rameyenhof castle's chapel by means of X-ray fluorescence and portable Raman analytical instrumentation

    Energy Technology Data Exchange (ETDEWEB)

    Van de Voorde, Lien, E-mail: lien.vandevoorde@ugent.be [Ghent University, Department of Analytical Chemistry, X-Ray Microspectroscopy and Imaging Research Group, Krijgslaan 281 S12, B-9000 Ghent (Belgium); Vandevijvere, Melissa [Ghent University, Department of Analytical Chemistry, X-Ray Microspectroscopy and Imaging Research Group, Krijgslaan 281 S12, B-9000 Ghent (Belgium); University of Antwerp, Faculty of Architecture and Design, Conservation Studies, Centre for Conservation Research (CCR), Blindestraat 9, 2000 Antwerp (Belgium); University of Antwerp, Department of Chemistry, X-ray and Instrumentation Lab (AXI2L), Groenenborgerlaan 171, 2020 Antwerp (Belgium); Vekemans, Bart [Ghent University, Department of Analytical Chemistry, X-Ray Microspectroscopy and Imaging Research Group, Krijgslaan 281 S12, B-9000 Ghent (Belgium); Van Pevenage, Jolien [Ghent University, Department of Analytical Chemistry, Raman Spectroscopy Research Group, Krijgslaan 281 S12, B-9000 Ghent (Belgium); Caen, Joost [University of Antwerp, Faculty of Architecture and Design, Conservation Studies, Centre for Conservation Research (CCR), Blindestraat 9, 2000 Antwerp (Belgium); Vandenabeele, Peter [Ghent University, Department of Archaeology, Archaeometry Research Group, Sint-Pietersnieuwstraat 35, B-9000 Ghent (Belgium); Van Espen, Piet [University of Antwerp, Department of Chemistry, X-ray and Instrumentation Lab (AXI2L), Groenenborgerlaan 171, 2020 Antwerp (Belgium); Vincze, Laszlo [Ghent University, Department of Analytical Chemistry, X-Ray Microspectroscopy and Imaging Research Group, Krijgslaan 281 S12, B-9000 Ghent (Belgium)

    2014-12-01

    The most unique and only known 16th century Antwerp majolica tile floor in Belgium is situated in a tower of the Rameyenhof castle (Gestel, Belgium). This exceptional work of art has recently been investigated in situ by using X-ray fluorescence (XRF) and Raman spectroscopy in order to study the material characteristics. This study reports on the result of the analyses based on the novel combination of non-destructive and portable instrumentation, including a handheld XRF spectrometer for obtaining elemental information and a mobile Raman spectrometer for retrieving structural and molecular information on the floor tiles in the Rameyenhof castle and on a second, similar medallion, which is stored in the Rubens House museum in Antwerp (Belgium). The investigated material, majolica, is a type of ceramic, which fascinated many people and potters throughout history by its beauty and colourful appearance. In this study the characteristic major/minor and trace element signature of 16th century Antwerp majolica is determined and the pigments used for the colourful paintings present on the floor are identified. Furthermore, based on the elemental fingerprint of the white glaze, and in particular on the presence of zinc in the tiles – an element that was not used for making 16th century majolica – valuable information about the originality of the chapel floor and the two central medallions is acquired. - Highlights: • In situ, non-destructive investigation of a unique Antwerp majolica floor • Multi-methodological approach: make use of a mobile Raman and X-ray spectrometer • Obtaining information about layered structure of Antwerp majolica • The used pigments in the majolica floor in Rameyenhof castle are characterized. • The verification of the authenticity of the floor and two central medallions are performed.

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

    Science.gov (United States)

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

    2017-04-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  15. The BDNF Val66Met polymorphism: relation to familiar risk of affective disorder, BDNF levels and salivary cortisol.

    Science.gov (United States)

    Vinberg, Maj; Trajkovska, Viktorija; Bennike, Bente; Knorr, Ulla; Knudsen, Gitte M; Kessing, Lars V

    2009-10-01

    Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are considered to play an important role in the pathophysiology of affective disorders. The aim of the present study was to investigate whether the BDNF Val66Met polymorphism is associated with a familiar risk of affective disorder and whether these genotypes affect whole blood BDNF level and salivary cortisol. In a high-risk study, healthy monozygotic and dizygotic twins with and without a co-twin (high- and low-risk twins, respectively) history of affective disorder were identified through nationwide registers. Familiar predisposition to unipolar and bipolar disorder was not associated with any specific genotype pattern of the BDNF Val66Met polymorphism, not in this sample of 124 val/val, 58 val/met and 8 met/met individuals. However, the combination of having a high familiar risk of affective disorder and the met allele was associated with a higher whole blood BDNF (p=0.02) and a higher evening cortisol level (p=0.01), but not with awakening cortisol. Individuals at high risk of affective disorders and who are carriers of the met allele of the Val66Met polymorphism may present with an enhanced stress response. The presence of a specific genotype alone may not enhance the risk of developing an affective episode. Rather, the altered stress response may be expressed only in combination with other risk variants through interactions with the environment.

  16. TEM and EELS study of deuterated carbon: application to the fuel retention in tokamaks; Etude couplee MET-EELS du carbone deutere: application a la retention du combustible dans les tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Bernier, N

    2007-12-15

    We developed a methodology, based on the combination of TEM and EELS techniques, for a structural and chemical characterization, at a high spatial resolution, of a wide range of carbon materials. We i) optimized, in the framework of theoretical models, the sp2 fraction quantification from pure carbons by EELS ii) transferred this quantification to deuterated amorphous carbon layers iii) showed, from graphitized carbons, how the TEM-EELS combination allows to detect low concentrations of implanted D. Due to the accomplishment of these developments, we applied our approach to the study of D retention in composites C/C, which are the plasma-facing materials in TS. We showed that specific localized retention sites correspond to relatively large ({approx} 3 mm.) cracks between fibres and matrix; such cracks offer a simple and direct path for deuterated amorphous carbon. The particle balance performed in TS is discussed in the light of this trapping mechanism. (author)

  17. Straightening: existence, uniqueness and stability

    Science.gov (United States)

    Destrade, M.; Ogden, R. W.; Sgura, I.; Vergori, L.

    2014-01-01

    One of the least studied universal deformations of incompressible nonlinear elasticity, namely the straightening of a sector of a circular cylinder into a rectangular block, is revisited here and, in particular, issues of existence and stability are addressed. Particular attention is paid to the system of forces required to sustain the large static deformation, including by the application of end couples. The influence of geometric parameters and constitutive models on the appearance of wrinkles on the compressed face of the block is also studied. Different numerical methods for solving the incremental stability problem are compared and it is found that the impedance matrix method, based on the resolution of a matrix Riccati differential equation, is the more precise. PMID:24711723

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

    Science.gov (United States)

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

    2015-11-01

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

  19. The Hepatocyte Growth Factor (HGF/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

    Directory of Open Access Journals (Sweden)

    Marjorie Boissinot

    2014-08-01

    Full Text Available Met is the receptor of hepatocyte growth factor (HGF, a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML, and myeloproliferative neoplasms (MPNs. The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs.

  20. Expression and prognostic relevance of MET and phospho-BAD in non-small cell lung cancer.

    Science.gov (United States)

    Sun, Wenze; Ai, Ting; Gao, Ying; Zhang, Yingbing; Cui, Jie; Song, Liping

    2013-01-01

    MET is involved in the progression of several types of human cancers, while phospho-BAD(Ser-136) is a key molecule in apoptosis and might be regulated by MET. The aim of this study was to investigate the correlation between altered expression of MET and phospho-BAD in non-small cell lung cancer (NSCLC) and their association with clinicopathologic parameters and overall survival. MET and phospho-BAD(Ser-136) proteins were evaluated by immunohistochemical analysis in 183 paraffin-embedded specimens and were also assessed by Western blotting analysis in 12 frozen tumor tissue samples, which were representative examples of immunohistochemical staining. Positive expression of MET and phospho-BAD(Ser-136) occurred in 67.2% and 49.2% of the 183 cases of NSCLC, respectively. However, neither MET expression nor phospho-BAD(Ser-136) expression was associated with any clinicopathologic parameter. A significant correlation was found between MET and phospho-BAD(Ser-136) expression levels evaluated by immunohistochemistry (r = 0.268, P BAD(Ser-136)+ phenotype had a poorer prognosis than others (P BAD(Ser-136) expression, and may be an adverse predictor for NSCLC. Activation of the MET/phospho-BAD(Ser-136) signaling pathway might play a role in the development and progression of NSCLC.

  1. In vivo detection of c-MET expression in a rat hepatocarcinogenesis model using molecularly targeted magnetic resonance imaging.

    Science.gov (United States)

    Towner, Rheal A; Smith, Nataliya; Tesiram, Yasvir A; Abbott, Andrew; Saunders, Debbie; Blindauer, Rebecca; Herlea, Oana; Silasi-Mansat, Robert; Lupu, Florea

    2007-01-01

    The multifunctional growth factor scatter factor/hepatocyte growth factor and its tyrosine kinase receptor, c-MET, have been implicated in the genesis and malignant progression of numerous human malignancies, including hepatocellular carcinomas. The incidence of hepatocellular carcinomas in the United States has increased noticeably over the past two decades and is listed as the fifth major cancer in men worldwide. In this study, we used a choline-deficient l-amino acid (CDAA)-defined rat hepatocarcinogenesis model to visualize increased in vivo expression of the c-MET antigen in neoplastic lesion formation with the use of a super paramagnetic iron oxide (SPIO)-anti-c-MET molecularly targeted magnetic resonance imaging (MRI) contrast agent. SPIO-anti-c-MET was used for the first time to detect overexpression of c-MET in neoplastic nodules and tumors within the livers of CDAA-treated rats, as determined by a decrease in MRI signal intensity and a decrease in regional T(2) values. Specificity for the binding of the molecularly targeted anti-c-MET contrast agent was determined using rat hepatoma (H4-II-E-C3) cell cultures and immunofluorescence microscopic imaging of the targeting agents within neoplastic liver tissue 1 to 2 hours following intravenous administration of SPIO-anti-c-MET and MRI investigation. This method has the ability to visualize in vivo the overexpression of c-MET at early developmental stages of tumor formation.

  2. In Vivo Detection of c-MET Expression in a Rat Hepatocarcinogenesis Model Using Molecularly Targeted Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Rheal A. Towner

    2007-01-01

    Full Text Available The multifunctional growth factor scatter factor/hepatocyte growth factor and its tyrosine kinase receptor, c-MET, have been implicated in the genesis and malignant progression of numerous human malignancies, including hepatocellular carcinomas. The incidence of hepatocellular carcinomas in the United States has increased noticeably over the past two decades and is listed as the fifth major cancer in men worldwide. In this study, we used a choline-deficient l-amino acid (CDAA-defined rat hepatocarcinogenesis model to visualize increased in vivo expression of the c-MET antigen in neoplastic lesion formation with the use of a super paramagnetic iron oxide (SPIO–anti-c-MET molecularly targeted magnetic resonance imaging (MRI contrast agent. SPIO–anti-c-MET was used for the first time to detect overexpression of c-MET in neoplastic nodules and tumors within the livers of CDAA-treated rats, as determined by a decrease in MRI signal intensity and a decrease in regional T2 values. Specificity for the binding of the molecularly targeted anti-c-MET contrast agent was determined using rat hepatoma (H4-II-E-C3 cell cultures and immunofluorescence microscopic imaging of the targeting agents within neoplastic liver tissue 1 to 2 hours following intravenous administration of SPIO–anti-c-MET and MRI investigation. This method has the ability to visualize in vivo the overexpression of c-MET at early developmental stages of tumor formation.

  3. The Hepatocyte Growth Factor (HGF)/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

    Energy Technology Data Exchange (ETDEWEB)

    Boissinot, Marjorie [Translational Neuro-Oncology Group, Leeds Institute of Cancer and Pathology, University of Leeds, Level 5 Wellcome Trust Brenner Building, St James’s Hospital, Leeds LS9 7TF (United Kingdom); Vilaine, Mathias [Institute of Research on Cancer and Aging (IRCAN), CNRS-Inserm-UNS UMR 7284, U 1081, Centre A. Lacassagne, 33 Avenue Valombrose, Nice 06189 (France); Hermouet, Sylvie, E-mail: sylvie.hermouet@univ-nantes.fr [Centre Hospitalier Universitaire (CHU), Place Alexis Ricordeau, Nantes 44093 (France); Inserm UMR892, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 8 quai Moncousu, Nantes cedex 44007 (France)

    2014-08-12

    Met is the receptor of hepatocyte growth factor (HGF), a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML), and myeloproliferative neoplasms (MPNs). The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs)

  4. Event segmentation ability uniquely predicts event memory.

    Science.gov (United States)

    Sargent, Jesse Q; Zacks, Jeffrey M; Hambrick, David Z; Zacks, Rose T; Kurby, Christopher A; Bailey, Heather R; Eisenberg, Michelle L; Beck, Taylor M

    2013-11-01

    Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. The association of XRCC3 Thr241Met genetic variant with risk of ...

    African Journals Online (AJOL)

    Background: Previous studies suggest that the X-ray repair cross-complementing group 3 gene (XRCC3) Thr241Met genetic variant could be potentially associated with the risk of prostate cancer. However, results from these published studies were conflicting rather than conclusive. Objectives:This meta-analysis aimed to ...

  6. A unique collaboration in Chile.

    Science.gov (United States)

    1989-01-01

    The Chilean Red Cross Society and the family planning association--APROFA, International Planned Parenthood Federation's affiliate, are joining forces to help prevent the spread of the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection. APROFA established a working group to study the knowledge, attitudes, and sexual behavior of students at the National Training Institute, INACAP. 7000 students were sampled in 11 Chilean cities. The study found that 36% of the females, and 77% of males were sexually active before the age of 20. Nearly 1/2 of the women and 1/5 of the men did not know that condoms could protect them against sexually transmitted diseases (STDs) and pregnancy. APROFA designed a program to increase students knowledge of AIDS, reduce promiscuity and increase knowledge of and use of condoms. In October, 1988 an educational package distributed, consisting of a training manual, slides, educational booklets, a poster, and a video of 3 films. It has proved so successful that APROFA has adapted it for community groups, educational institutions, and its youth program. APROFA/Red Cross nurses and Red Cross volunteers have participated in workshops and training with the package. The Red Cross has organized AIDS-related activities in Chile since 1986, including education campaigns, information for blood donors, and a telephone hotline to provide AIDS counseling. Goals are to target more poor areas and groups outside of society's mainstream in the next year for sex education and information on STDs.

  7. The roles of the RIIβ linker and N-terminal cyclic nucleotide-binding domain in determining the unique structures of the type IIβ protein kinase A: a small angle x-ray and neutron scattering study.

    Science.gov (United States)

    Blumenthal, Donald K; Copps, Jeffrey; Smith-Nguyen, Eric V; Zhang, Ping; Heller, William T; Taylor, Susan S

    2014-10-10

    Protein kinase A (PKA) is ubiquitously expressed and is responsible for regulating many important cellular functions in response to changes in intracellular cAMP concentrations. The PKA holoenzyme is a tetramer (R2:C2), with a regulatory subunit homodimer (R2) that binds and inhibits two catalytic (C) subunits; binding of cAMP to the regulatory subunit homodimer causes activation of the catalytic subunits. Four different R subunit isoforms exist in mammalian cells, and these confer different structural features, subcellular localization, and biochemical properties upon the PKA holoenzymes they form. The holoenzyme containing RIIβ is structurally unique in that the type IIβ holoenzyme is much more compact than the free RIIβ homodimer. We have used small angle x-ray scattering and small angle neutron scattering to study the solution structure and subunit organization of a holoenzyme containing an RIIβ C-terminal deletion mutant (RIIβ(1-280)), which is missing the C-terminal cAMP-binding domain to better understand the structural organization of the type IIβ holoenzyme and the RIIβ domains that contribute to stabilizing the holoenzyme conformation. Our results demonstrate that compaction of the type IIβ holoenzyme does not require the C-terminal cAMP-binding domain but rather involves large structural rearrangements within the linker and N-terminal cyclic nucleotide-binding domain of the RIIβ homodimer. The structural rearrangements are significantly greater than seen previously with RIIα and are likely to be important in mediating short range and long range interdomain and intersubunit interactions that uniquely regulate the activity of the type IIβ isoform of PKA. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Why Pandemic Response is Unique

    DEFF Research Database (Denmark)

    Bækkeskov, Erik; Rubin, Olivier

    2014-01-01

    , the case studies of media coverage in the USA and Denmark demonstrate that the response was bureaucratized in the public health agencies (CDC and DMHA, respectively). Hence, while natural disaster responses appear to follow a political logic, the response to pandemics appears to be more strongly instituted......Purpose – The purpose of this paper is to show that 2009 H1N1 “swine” influenza pandemic vaccination policies deviated from predictions established in the theory of political survival, and to propose that pandemic response deviated because it was ruled by bureaucratized experts rather than...... by elected politicians. Design/methodology/approach – Focussing on the 2009 H1N1 pandemic, the paper employs descriptive statistical analysis of vaccination policies in nine western democracies. To probe the plausibility of the novel explanation, it uses quantitative and qualitative content analyses of media...

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

    Directory of Open Access Journals (Sweden)

    Maaike Hermsen

    2017-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-08-01

    5.3±0.9, P=0.06. HGF was widely expressed in both primary and metastatic lesions while Met expression of metastatic lesions was higher than that of primary lesions (primary lesions: 24.7%; liver metastases: 40%; lung metastases: 29%; lymph node metastases: 29%, P<0.05, and overall survival of NPC patients with higher expression of Met was shorter (P=0.13.Conclusion: Our results demonstrated that HGF/Met signaling promoted NPC growth, further resulting in metastasis and poor prognosis. Met TKI, PF-2341066, showed potent antitumor activity in vivo and in vitro which was enhanced by combination with cisplatin. Our study implied that HGF/Met signaling was the potential therapeutic target in NPC, and blockage of the signaling could prevent growth and metastasis of NPC and derive clinical benefit. Keywords: HGF/Met pathway, proliferation, invasion

  11. PWR.2 - the unique transportation

    International Nuclear Information System (INIS)

    Howell, G.E.; Wills, L.I.

    1987-01-01

    Design studies of the prototype machinery and installation of same to be used for test and evaluation of a new design of nuclear power plant for submarines, showed that there were advantages if large units could be fitted out entirely at the manufacturer's base in Barrow-in-Furness. However, they had then to be shipped to the customer at the Vulcan Naval Reactor Test Establishment in Caithness, Scotland. The transportation of the loads involved is described. The main loads were the primary unit which weighed 1300 tonnes and the secondary unit which was transported as five separate assemblies, the largest two of which weighed 151 and 43 tonnes. Five basic transportation methods were used: skidding on PTFE pads, sea passage with barge on submersible barge, rolling on airbags, skating on water skates and lifting and rolling on multi-wheeled trailers. By careful planning the primary unit was moved in 16 days and the secondary unit in 19 days. The route and methods used are described and illustrated. (U.K.)

  12. Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome.

    Science.gov (United States)

    Plummer, J T; Evgrafov, O V; Bergman, M Y; Friez, M; Haiman, C A; Levitt, P; Aldinger, K A

    2013-10-22

    Single nucleotide variants (SNV) in the gene encoding the MET receptor tyrosine kinase have been associated with an increased risk for autism spectrum disorders (ASD). The MET promoter SNV rs1858830 C 'low activity' allele is enriched in ASD, associated with reduced protein expression, and impacts functional and structural circuit connectivity in humans. To gain insight into the transcriptional regulation of MET on ASD-risk etiology, we examined an interaction between the methyl CpG-binding protein 2 (MeCP2) and the MET 5' promoter region. Mutations in MeCP2 cause Rett syndrome (RTT), a predominantly female neurodevelopmental disorder sharing some ASD clinical symptoms. MeCP2 binds to a region of the MET promoter containing the ASD-risk SNV, and displays rs1858830 genotype-specific binding in human neural progenitor cells derived from the olfactory neuroepithelium. MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2. In the postmortem temporal cortex, a region normally enriched in MET, gene expression is reduced dramatically in females with RTT, although not due to enrichment of the rs1858830 C 'low activity' allele. We newly identified a sex-based reduction in MET expression, with male ASD cases, but not female ASD cases compared with sex-matched controls. The experimental data reveal a prominent allele-specific regulation of MET transcription by MeCP2. The mechanisms underlying the pronounced reduction of MET in ASD and RTT temporal cortex are distinct and likely related to factors unique to each disorder, including a noted sex bias.

  13. Requirements to be met by the operation manual

    International Nuclear Information System (INIS)

    1981-03-01

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

  14. Hydrogen storage capacity of titanium met-cars

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  16. Unique Physician Identification Number (UPIN) Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Unique Physician Identification Number (UPIN) Directory contains selected information on physicians, doctors of Osteopathy, limited licensed practitioners and...

  17. Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice

    Science.gov (United States)

    Ieraci, Alessandro; Madaio, Alessandro I; Mallei, Alessandra; Lee, Francis S; Popoli, Maurizio

    2016-01-01

    Several studies have shown that exercise improves cognitive functions and emotional behaviors. Positive effects of exercise have been associated with enhanced brain plasticity, adult hippocampal neurogenesis, and increased levels of brain-derived neurotrophic factor (BDNF). However, a substantial variability of individual response to exercise has been described, which may be accounted for by individual genetic variants. Here, we have assessed whether and how the common human BDNF Val66Met polymorphism influences the neurobiological effects modulated by exercise in BDNF Val66Met knock-in male mice. Wild-type (BDNFVal/Val) and homozygous BDNF Val66Met (BDNFMet/Met) male mice were housed in cages equipped with or without running wheels for 4 weeks. Changes in behavioral phenotype, hippocampal adult neurogenesis, and gene expression were evaluated in exercised and sedentary control mice. We found that exercise reduced the latency to feed in the novelty suppressed feeding and the immobility time in the forced swimming test in BDNFVal/Val but not in BDNFMet/Met mice. Hippocampal neurogenesis was reduced in BDNFMet/Met mice compared with BDNFVal/Val mice. BDNFMet/Met mice had lower basal BDNF protein levels in the hippocampus, which was not recovered following exercise. Moreover, exercise-induced expression of total BDNF, BDNF splice variants 1, 2, 4, 6 and fibronectin type III domain-containing protein 5 (FNDC5) mRNA levels were absent or reduced in the dentate gyrus of BDNFMet/Met mice. Exercise failed to enhance PGC-1α and FNDC5 mRNA levels in the BDNFMet/Met muscle. Overall these results indicate that, in adult male mice, the BDNF Val66Met polymorphism impairs the beneficial behavioral and neuroplasticity effects induced by physical exercise. PMID:27388329

  18. Energy expenditure during common sitting and standing tasks: examining the 1.5 MET definition of sedentary behaviour.

    Science.gov (United States)

    Mansoubi, Maedeh; Pearson, Natalie; Clemes, Stacy A; Biddle, Stuart Jh; Bodicoat, Danielle H; Tolfrey, Keith; Edwardson, Charlotte L; Yates, Thomas

    2015-05-29

    Sedentary behavior is defined as any waking behavior characterized by an energy expenditure of 1.5 METS or less while in a sitting or reclining posture. This study examines this definition by assessing the energy cost (METs) of common sitting, standing and walking tasks. Fifty one adults spent 10 min during each activity in a variety of sitting tasks (watching TV, Playing on the Wii, Playing on the PlayStation Portable (PSP) and typing) and non-sedentary tasks (standing still, walking at 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, and 1.6 mph). Activities were completed on the same day in a random order following an assessment of resting metabolic rate (RMR). A portable gas analyzer was used to measure oxygen uptake, and data were converted to units of energy expenditure (METs). Average of standardized MET values for screen-based sitting tasks were: 1.33 (SD: 0.24) METS (TV), 1.41 (SD: 0.28) (PSP), and 1.45 (SD: 0.32) (Typing). The more active, yet still seated, games on the Wii yielded an average of 2.06 (SD: 0.5) METS. Standing still yielded an average of 1.59 (SD: 0.37) METs. Walking MET values increased incrementally with speed from 2.17 to 2.99 (SD: 0.5 - 0.69) METs. The suggested 1.5 MET threshold for sedentary behaviors seems reasonable however some sitting based activities may be classified as non-sedentary. The effect of this on the definition of sedentary behavior and associations with metabolic health needs further investigation.

  19. El acertijo de la metáfora visual

    OpenAIRE

    De la Rosa Alzate, Adriana; Universidad Autónoma de Occidente

    2016-01-01

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

  20. Met Ed gets reprieve: banks lend tax money

    International Nuclear Information System (INIS)

    Utroska, D.

    1981-01-01

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

  1. Detecting beer intake by unique metabolite patterns

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian

    2016-01-01

    Evaluation of health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern...... representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were...... assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum...

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

    Science.gov (United States)

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

    2015-07-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

  4. Remembering the early days of the Met Lab

    International Nuclear Information System (INIS)

    Katz, J.J.

    1990-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-03-15

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

  6. Physiological Signaling and Structure of the HGF Receptor MET

    Directory of Open Access Journals (Sweden)

    Gianluca Baldanzi

    2014-12-01

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

  7. Patients' family satisfaction with needs met at the medical intensive care unit.

    Science.gov (United States)

    Khalaila, Rabia

    2013-05-01

    The current study investigated the perceived importance and the perceived met needs of family members in the medical intensive care unit and assessed family members' satisfaction with needs met. Studies conducted throughout the world over the past 30 years indicate that family needs are still neglected. Unmet needs of family members of patients in the intensive care unit lead to dissatisfaction with care. A cross-sectional study. A total of 70 family members of critically ill patients were included in this study conducted in a medical intensive care unit in Israel between October 2007-September 2008, using a structured interview. Three outcomes measured by the Family Satisfaction in the Intensive Care Unit Inventory were regressed separately for baseline variables and family needs met subscales as measured by the Critical Care Family Needs Inventory. Multivariate linear regression analysis was used to detect factors that could have predicted each outcome. The results showed differences between the perceived importance and the perceived met needs of family members. Satisfaction with care was positively related to meeting all needs domains except the information need. However, satisfaction with information and decision-making was related only to meeting information and emotional support needs. Continued unmet needs of family members of intensive care unit patients have a negative impact on family satisfaction. Only sweeping changes in clinical practice will succeed in meeting the unmet needs of patients' families. © 2012 Blackwell Publishing Ltd.

  8. BDNF val(66)met affects hippocampal volume and emotion-related hippocampal memory activity

    NARCIS (Netherlands)

    Molendijk, M. L.; van Tol, M-J; Penninx, B. W. J. H.; van der Wee, N. J. A.; Aleman, A.; Veltman, D. J.; Spinhoven, P.; Elzinga, B. M.

    2012-01-01

    The val(66)met polymorphism on the BDNF gene has been reported to explain individual differences in hippocampal volume and memory-related activity. These findings, however, have not been replicated consistently and no studies to date controlled for the potentially confounding impact of early life

  9. Circles within circles: crosstalk between protein Ser/Thr/Tyr-phosphorylation and Met oxidation

    Science.gov (United States)

    Background: Reversible posttranslational protein modifications such as phosphorylation of Ser/Thr/Tyr and Met oxidation are critical for both metabolic regulation and cellular signalling. Although these modifications are typically studied individually, herein we describe the potential for cross-talk...

  10. Association Between Smoking, Nicotine Dependence, and BDNF Val(66)Met Polymorphism with BDNF Concentrations in Serum

    NARCIS (Netherlands)

    Jamal, Mumtaz; Van der Does, Willem; Elzinga, Bernet M.; Molendijk, Marc L.; Penninx, Brenda W. J. H.

    Introduction: Nicotine use is associated with the upregulation of brain-derived neurotrophic factor (BDNF) in serum. An association between smoking and the BDNF Val(66)Met polymorphism has also been found. The aim of this study is to examine the levels of serum BDNF in never-smokers, former smokers,

  11. A study of Huntington disease-like syndromes in black South African patients reveals a single SCA2 mutation and a unique distribution of normal alleles across five repeat loci.

    Science.gov (United States)

    Baine, Fiona K; Peerbhai, Nabeelah; Krause, Amanda

    2018-07-15

    Huntington disease (HD) is a progressive neurodegenerative disease, characterised by a triad of movement disorder, emotional and behavioural disturbances and cognitive impairment. The underlying cause is an expanded CAG repeat in the huntingtin gene. For a small proportion of patients presenting with HD-like symptoms, the mutation in this gene is not identified and they are said to have a HD "phenocopy". South Africa has the highest number of recorded cases of an African-specific phenocopy, Huntington disease-like 2 (HDL2), caused by a repeat expansion in the junctophilin-3 gene. However, a significant proportion of black patients with clinical symptoms suggestive of HD still test negative for HD and HDL2. This study thus aimed to investigate five other loci associated with HD phenocopy syndromes - ATN1, ATXN2, ATXN7, TBP and C9orf72. In a sample of patients in whom HD and HDL2 had been excluded, a single expansion was identified in the ATXN2 gene, confirming a diagnosis of Spinocerebellar ataxia 2. The results indicate that common repeat expansion disorders do not contribute significantly to the HD-like phenotype in black South African patients. Importantly, allele sizing reveals unique distributions of normal repeat lengths across the associated loci in the African population studied. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Uniqueness of time-independent electromagnetic fields

    DEFF Research Database (Denmark)

    Karlsson, Per W.

    1974-01-01

    As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics......As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics...

  13. Unique specification of Yang-Mills solutions

    International Nuclear Information System (INIS)

    Campbell, W.B.; Joseph, D.W.; Morgan, T.A.

    1980-01-01

    Screened time-independent cylindrically-symmetric solutions of Yang-Mills equations are given which show that the source does not uniquely determine the field. However, these particular solutions suggest a natural way of uniquely specifying solutions in terms of a physical realization of a symmetry group. (orig.)

  14. Constructing Dense Graphs with Unique Hamiltonian Cycles

    Science.gov (United States)

    Lynch, Mark A. M.

    2012-01-01

    It is not difficult to construct dense graphs containing Hamiltonian cycles, but it is difficult to generate dense graphs that are guaranteed to contain a unique Hamiltonian cycle. This article presents an algorithm for generating arbitrarily large simple graphs containing "unique" Hamiltonian cycles. These graphs can be turned into dense graphs…

  15. The East Asian Atmospheric Water Cycle and Monsoon Circulation in the Met Office Unified Model

    Science.gov (United States)

    Rodríguez, José M.; Milton, Sean F.; Marzin, Charline

    2017-10-01

    In this study the low-level monsoon circulation and observed sources of moisture responsible for the maintenance and seasonal evolution of the East Asian monsoon are examined, studying the detailed water budget components. These observational estimates are contrasted with the Met Office Unified Model (MetUM) climate simulation performance in capturing the circulation and water cycle at a variety of model horizontal resolutions and in fully coupled ocean-atmosphere simulations. We study the role of large-scale circulation in determining the hydrological cycle by analyzing key systematic errors in the model simulations. MetUM climate simulations exhibit robust circulation errors, including a weakening of the summer west Pacific Subtropical High, which leads to an underestimation of the southwesterly monsoon flow over the region. Precipitation and implied diabatic heating biases in the South Asian monsoon and Maritime Continent region are shown, via nudging sensitivity experiments, to have an impact on the East Asian monsoon circulation. By inference, the improvement of these tropical biases with increased model horizontal resolution is hypothesized to be a factor in improvements seen over East Asia with increased resolution. Results from the annual cycle of the hydrological budget components in five domains show a good agreement between MetUM simulations and ERA-Interim reanalysis in northern and Tibetan domains. In simulations, the contribution from moisture convergence is larger than in reanalysis, and they display less precipitation recycling over land. The errors are closely linked to monsoon circulation biases.

  16. Unique Fock quantization of scalar cosmological perturbations

    Science.gov (United States)

    Fernández-Méndez, Mikel; Mena Marugán, Guillermo A.; Olmedo, Javier; Velhinho, José M.

    2012-05-01

    We investigate the ambiguities in the Fock quantization of the scalar perturbations of a Friedmann-Lemaître-Robertson-Walker model with a massive scalar field as matter content. We consider the case of compact spatial sections (thus avoiding infrared divergences), with the topology of a three-sphere. After expanding the perturbations in series of eigenfunctions of the Laplace-Beltrami operator, the Hamiltonian of the system is written up to quadratic order in them. We fix the gauge of the local degrees of freedom in two different ways, reaching in both cases the same qualitative results. A canonical transformation, which includes the scaling of the matter-field perturbations by the scale factor of the geometry, is performed in order to arrive at a convenient formulation of the system. We then study the quantization of these perturbations in the classical background determined by the homogeneous variables. Based on previous work, we introduce a Fock representation for the perturbations in which: (a) the complex structure is invariant under the isometries of the spatial sections and (b) the field dynamics is implemented as a unitary operator. These two properties select not only a unique unitary equivalence class of representations, but also a preferred field description, picking up a canonical pair of field variables among all those that can be obtained by means of a time-dependent scaling of the matter field (completed into a linear canonical transformation). Finally, we present an equivalent quantization constructed in terms of gauge-invariant quantities. We prove that this quantization can be attained by a mode-by-mode time-dependent linear canonical transformation which admits a unitary implementation, so that it is also uniquely determined.

  17. MiR-181a-5p is downregulated in hepatocellular carcinoma and suppresses motility, invasion and branching-morphogenesis by directly targeting c-Met.

    Science.gov (United States)

    Korhan, Peyda; Erdal, Esra; Atabey, Neşe

    2014-08-08

    c-Met receptor tyrosine kinase has been regarded as a promising therapeutic target for hepatocellular carcinoma (HCC). Recently, microRNAs (miRNAs) have been shown as a novel mechanism to control c-Met expression in cancer. In this study, we investigate the potential contribution of miR-181a-5p dysregulation to the biology of c-Met overexpression in HCC. Herein, we found an inverse expression pattern between miR-181a-5p and c-Met expression in normal, cirrhotic and HCC liver tissues. Luciferase assay confirmed that miR-181a-5p binding to the 3'-UTR of c-Met downregulated the expression of c-Met in HCC cells. Overexpression of miR-181a-5p suppressed both HGF-independent and -dependent activation of c-Met and consequently diminished branching-morphogenesis and invasion. Combined treatment with miR-181a-5p and c-Met inhibitor led to a further inhibition of c-Met-driven cellular activities. Knockdown of miR-181a-5p promoted HGF-independent/-dependent signaling of c-Met and accelerated migration, invasion and branching-morphogenesis. In conclusion, our results demonstrated for the first time that c-Met is a functional target gene of miR-181a-5p and the loss of miR-181a-5p expression led to the activation of c-Met-mediated oncogenic signaling in hepatocarcinogenesis. These findings display a novel molecular mechanism of c-Met regulation in HCC and strategies to increase miR-181a5p level might be an alternative approach for the enhancement of the inhibitory effects of c-Met inhibitors. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

    Stelma, Juurd Hari

    1938-01-01

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

  20. Constant Cremer, voetballer in Tilburg met Afrikaanse wortels

    NARCIS (Netherlands)

    Drs. Thijs Kemmeren

    2012-01-01

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

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

    NARCIS (Netherlands)

    Gijselaers, Jérôme; De Groot, Renate

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  4. Ervaringen met ICT-onderzoek in het HBO.

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

    Nijland, R.; Kik, C.

    2011-01-01

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

  7. Slim in het verkeer met open data : adviesrapport

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    1985-01-01

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

  9. Subtiel verleiden met nudging : Verhogen van enquêterespons

    NARCIS (Netherlands)

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

    2015-01-01

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

  10. Aan de slag met honors : praktijklessen uit Europa

    NARCIS (Netherlands)

    Wolfensberger, Marca; Hogenstijn, Maarten

    2015-01-01

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

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

    Science.gov (United States)

    Principal Leadership, 2010

    2010-01-01

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

  12. Randvoorwaarden ontwerp happy games voor ouderen met dementie

    NARCIS (Netherlands)

    Dr. A.L. Cordia

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  16. Praktijkervaringen met de Venlow energy kas 2010-2012

    NARCIS (Netherlands)

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

    2013-01-01

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

  17. MET-RODOS: A comprehensive atmospheric dispersion module

    DEFF Research Database (Denmark)

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

    1997-01-01

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

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

    African Journals Online (AJOL)

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

  19. Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism interacts with gender to influence cortisol responses to mental stress.

    Science.gov (United States)

    Jiang, Rong; Babyak, Michael A; Brummett, Beverly H; Siegler, Ilene C; Kuhn, Cynthia M; Williams, Redford B

    2017-05-01

    Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with cortisol responses to stress with gender differences reported, although the findings are not entirely consistent. To evaluate the role of Val66Met genotype and gender on cortisol responses to stress, we conducted a 45-min mental stress protocol including four tasks and four rest periods. Blood cortisol was collected for assay immediately before and after each task and rest period. A significant two-way interaction of Val66Met genotype×gender (P=0.022) was observed on the total area under the curve (AUC), a total cortisol response over time, such that the Val/Val genotype was associated with a larger cortisol response to stress as compared to the Met group in women but not in men. Further contrast analyses between the Val/Val and Met group for each stress task showed a similar increased cortisol pattern among women Val/Val genotype but not among men. The present findings indicate the gender differences in the effect of Val66Met genotype on the cortisol responses to stress protocol, and extend the evidence for the importance of gender and the role of Val66Met in the modulation of stress reactivity and subsequent depression prevalence. Further studies and the underlying mechanism need to be investigated, which may provide an insight for prevention, intervention, and treatment strategies that target those at high risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Catechol-O-methyltransferase Val(158)Met association with parahippocampal physiology during memory encoding in schizophrenia.

    Science.gov (United States)

    Di Giorgio, A; Caforio, G; Blasi, G; Taurisano, P; Fazio, L; Romano, R; Ursini, G; Gelao, B; Bianco, L Lo; Papazacharias, A; Sinibaldi, L; Popolizio, T; Bellomo, A; Bertolino, A

    2011-08-01

    Catechol-O-methyltransferase (COMT) Val158Met has been associated with activity of the mesial temporal lobe during episodic memory and it may weakly increase risk for schizophrenia. However, how this variant affects parahippocampal and hippocampal physiology when dopamine transmission is perturbed is unclear. The aim of the present study was to compare the effects of the COMT Val158Met genotype on parahippocampal and hippocampal physiology during encoding of recognition memory in patients with schizophrenia and in healthy subjects. Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we studied 28 patients with schizophrenia and 33 healthy subjects matched for a series of sociodemographic and genetic variables while they performed a recognition memory task. We found that healthy subjects had greater parahippocampal and hippocampal activity during memory encoding compared to patients with schizophrenia. We also found different activity of the parahippocampal region between healthy subjects and patients with schizophrenia as a function of the COMT genotype, in that the predicted COMT Met allele dose effect had an opposite direction in controls and patients. Our results demonstrate a COMT Val158Met genotype by diagnosis interaction in parahippocampal activity during memory encoding and may suggest that modulation of dopamine signaling interacts with other disease-related processes in determining the phenotype of parahippocampal physiology in schizophrenia. © Cambridge University Press 2010

  1. Operational assimilation of ASCAT surface soil wetness at the Met Office

    Directory of Open Access Journals (Sweden)

    I. Dharssi

    2011-08-01

    Full Text Available Currently, no extensive, near real time, global soil moisture observation network exists. Therefore, the Met Office global soil moisture analysis scheme has instead used observations of screen temperature and humidity. A number of new space-borne remote sensing systems, operating at microwave frequencies, have been developed that provide a more direct retrieval of surface soil moisture. These systems are attractive since they provide global data coverage and the horizontal resolution is similar to weather forecasting models. Several studies show that measurements of normalised backscatter (surface soil wetness from the Advanced Scatterometer (ASCAT on the meteorological operational (MetOp satellite contain good quality information about surface soil moisture. This study describes methods to convert ASCAT surface soil wetness measurements to volumetric surface soil moisture together with bias correction and quality control. A computationally efficient nudging scheme is used to assimilate the ASCAT volumetric surface soil moisture data into the Met Office global soil moisture analysis. This ASCAT nudging scheme works alongside a soil moisture nudging scheme that uses observations of screen temperature and humidity. Trials, using the Met Office global Unified Model, of the ASCAT nudging scheme show a positive impact on forecasts of screen temperature and humidity for the tropics, North America and Australia. A comparison with in-situ soil moisture measurements from the US also indicates that assimilation of ASCAT surface soil wetness improves the soil moisture analysis. Assimilation of ASCAT surface soil wetness measurements became operational during July 2010.

  2. Metástasis cervical contralateral en el carcinoma epidermoide de la cavidad oral: Estudio clínico analítico retrospectivo en 315 pacientes primariamente tratados con cirugía Contralateral neck metastasis in squamous cell carcinoma of the oral cavity: An analytical retrospective clinical study of 315 patients primarily treated with surgery

    Directory of Open Access Journals (Sweden)

    R. González-García

    2008-06-01

    carcinoma epidermoide de lengua. El tiempo de supervivencia medio libre de enfermedad fue 147± 6 meses. Veintinueve (9,1% pacientes desarrollaron recurrencia cervical ipsilateral, mientras que 18 (5,69% mostraron recurrencia cervical contralateral. Para los pacientes con carcinoma epidermoide de lengua, y considerando los porcentajes en relación a los 203 pacientes con esta entidad, estas cifras fueron de 20 (9,8% y 9 (4,4%, respectivamente. El tiempo medio de aparición de las metástasis cervicales desde la cirugía fue de 12,52 meses (rango: 3-49, algo menor para el subgrupo de pacientes con carcinoma epidermoide de lengua (11,4 meses, rango: 3-27. Dieciocho de los 29 pacientes con recurrencia cervical ipsilateral murieron finalmente de la enfermedad. Siete de 18 pacientes con metástasis contralateral murieron igualmente de la enfermedad. En el subgrupo de pacientes con carcinoma epidermoide de lengua, estas cifras fueron: catorce de 20 pacientes con metástasis cervical ipsilateral y ocho de 9 pacientes con metástasis cervical contralateral. Varios factores clínicopatológicos mostraron asociación estadísticamente significativa (pObjectives. There are numerous studies in the literature on the prognostic factors involved in the appearance of ipsilateral neck metastasis in squamous cell carcinoma of the oral cavity. However, there are no extensive clinical studies on the association of clinicopathological factors and the appearance of contralateral neck metastasis after the surgical resection of the primary tumor. The object of this study is to analyze the factors implied in the appearance of contralateral neck metastasis in patients with squamous cell carcinoma of the oral cavity treated primarily with surgery. Patients and methods. A series of 315 consecutive patients with squamous cell carcinoma of the oral cavity, who had not been treated previously, were analyzed. A complementary study of a subgroup of 203 patients with squamous cell carcinoma of the lateral

  3. Uniqueness conditions for finitely dependent random fields

    International Nuclear Information System (INIS)

    Dobrushin, R.L.; Pecherski, E.A.

    1981-01-01

    The authors consider a random field for which uniqueness and some additional conditions guaranteeing that the correlations between the variables of the field decrease rapidly enough with the distance between the values of the parameter occur. The main result of the paper states that in such a case uniqueness is true for any other field with transition probabilities sufficiently close to those of the original field. Then they apply this result to some ''degenerate'' classes of random fields for which one can check this condition of correlation to decay, and thus obtain some new conditions of uniqueness. (Auth.)

  4. Association of BDNF Val66Met Polymorphism and Brain BDNF levels with Major Depression and Suicide.

    Science.gov (United States)

    Youssef, Mariam M; Underwood, Mark D; Huang, Yung-Yu; Hsiung, Shu-Chi; Liu, Yan; Simpson, Norman R; Bakalian, Mihran J; Rosoklija, Gorazd B; Dwork, Andrew J; Arango, Victoria; Mann, J John

    2018-02-08

    Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depressive disorder (MDD) and suicide. Both are partly caused by early life adversity (ELA) and ELA reduces BDNF protein levels. This study examines the association of BDNF Val66Met polymorphism and brain BDNF levels with depression and suicide. We hypothesized that both MDD and ELA would be associated with the Met allele and lower brain BDNF levels. Such an association would be consistent with low BDNF mediating the effect of ELA on adulthood suicide and MDD. BDNF Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 non-suicides. Additionally, BDNF protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9; BA9), anterior cingulate cortex (ACC, BA24), caudal brainstem and rostral brainstem. The relationships between these measures and MDD, death by suicide and reported ELA were examined. Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower BDNF levels in ACC and caudal brainstem compared with non-depressed subjects. No effect of history of suicide death or ELA was observed with genotype, but lower BDNF levels in ACC were found in subjects who had been exposed to ELA and/or died by suicide compared to non-suicide decedents and no reported ELA. This study provides further evidence implicating low brain BDNF and the BDNF Met allele in major depression risk. Future studies should seek to determine how altered BDNF expression contributes to depression and suicide. © The Author(s) 2018. Published by Oxford University Press on behalf of CINP.

  5. Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and induces cholestatic liver damage by aggravating oxidative stress

    International Nuclear Information System (INIS)

    Gomez-Quiroz, Luis E.; Seo, Daekwan; Lee, Yun-Han; Kitade, Mitsuteru; Gaiser, Timo; Gillen, Matthew; Lee, Seung-Bum; Gutierrez-Ruiz, Ma Concepcion; Conner, Elizabeth A.; Factor, Valentina M; Thorgeirsson, Snorri S.; Marquardt, Jens U.

    2016-01-01

    Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting. Loss of c-Met signaling amplified the extent of liver injury in MetKO mice fed with high-cholesterol diet for 30 days as evidenced by upregulation of liver enzymes and increased synthesis of total bile acids, aggravated inflammatory response and enhanced intrahepatic lipid deposition. Global transcriptomic changes confirmed the enrichment of networks involved in steatosis and cholestasis. In addition, signaling pathways related to glutathione and lipid metabolism, oxidative stress and mitochondria dysfunction were significantly affected by the loss of c-Met function. Mechanistically, exacerbation of oxidative stress in MetKO livers was corroborated by increased lipid and protein oxidation. Western blot analysis further revealed suppression of Erk, NF-kB and Nrf2 survival pathways and downstream target genes (e.g. cyclin D1, SOD1, gamma-GCS), as well as up-regulation of proapoptotic signaling (e.g. p53, caspase 3). Consistent with the observed steatotic and cholestatic phenotype, nuclear receptors RAR, RXR showed increased activation while expression levels of CAR, FXR and PPAR-alpha were decreased in MetKO. Collectively, our data provide evidence for the critical involvement of c-Met signaling in cholesterol and bile acids toxicity.

  6. Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain.

    Science.gov (United States)

    Judson, Matthew C; Bergman, Mica Y; Campbell, Daniel B; Eagleson, Kathie L; Levitt, Pat

    2009-04-10

    The establishment of appropriate neural circuitry depends on the coordination of multiple developmental events across space and time. These events include proliferation, migration, differentiation, and survival-all of which can be mediated by hepatocyte growth factor (HGF) signaling through the Met receptor tyrosine kinase. We previously found a functional promoter variant of the MET gene to be associated with autism spectrum disorder, suggesting that forebrain circuits governing social and emotional function may be especially vulnerable to developmental disruptions in HGF/Met signaling. However, little is known about the spatiotemporal distribution of Met expression in the forebrain during the development of such circuits. To advance our understanding of the neurodevelopmental influences of Met activation, we employed complementary Western blotting, in situ hybridization, and immunohistochemistry to comprehensively map Met transcript and protein expression throughout perinatal and postnatal development of the mouse forebrain. Our studies reveal complex and dynamic spatiotemporal patterns of expression during this period. Spatially, Met transcript is localized primarily to specific populations of projection neurons within the neocortex and in structures of the limbic system, including the amygdala, hippocampus, and septum. Met protein appears to be principally located in axon tracts. Temporally, peak expression of transcript and protein occurs during the second postnatal week. This period is characterized by extensive neurite outgrowth and synaptogenesis, supporting a role for the receptor in these processes. Collectively, these data suggest that Met signaling may be necessary for the appropriate wiring of forebrain circuits, with particular relevance to the social and emotional dimensions of behavior. (c) 2009 Wiley-Liss, Inc.

  7. Differential impact of Met receptor gene interaction with early-life stress on neuronal morphology and behavior in mice.

    Science.gov (United States)

    Heun-Johnson, Hanke; Levitt, Pat

    2018-02-01

    Early adversity in childhood increases the risk of anxiety, mood, and post-traumatic stress disorders in adulthood, and specific gene-by-environment interactions may increase risk further. A common functional variant in the promoter region of the gene encoding the human MET receptor tyrosine kinase (rs1858830 ' C' allele) reduces expression of MET and is associated with altered cortical circuit function and structural connectivity. Mice with reduced Met expression exhibit changes in anxiety-like and conditioned fear behavior, precocious synaptic maturation in the hippocampus, and reduced neuronal arbor complexity and synaptogenesis. These phenotypes also can be produced independently by early adversity in wild-type mice. The present study addresses the outcome of combining early-life stress and genetic influences that alter timing of maturation on enduring functional and structural phenotypes. Using a model of reduced Met expression ( Met +/- ) and early-life stress from postnatal day 2-9, social, anxiety-like, and contextual fear behaviors in later life were measured. Mice that experienced early-life stress exhibited impairments in social interaction, whereas alterations in anxiety-like behavior and fear learning were driven by Met haploinsufficiency, independent of rearing condition. Early-life stress or reduced Met expression decreased arbor complexity of ventral hippocampal CA1 pyramidal neurons projecting to basolateral amygdala. Paradoxically, arbor complexity in Met +/- mice was increased following early-life stress, and thus not different from arbors in wild-type mice raised in control conditions. The changes in dendritic morphology are consistent with the hypothesis that the physiological state of maturation of CA1 neurons in Met +/- mice influences their responsiveness to early-life stress. The dissociation of behavioral and structural changes suggests that there may be phenotype-specific sensitivities to early-life stress.

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

    Science.gov (United States)

    2010-01-07

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

  9. Successful 1:1 proportion ventilation with a unique device for independent lung ventilation using a double-lumen tube without complications in the supine and lateral decubitus positions. A pilot study.

    Directory of Open Access Journals (Sweden)

    Michał Kowalczyk

    Full Text Available Adequate blood oxygenation and ventilation/perfusion matching should be main goal of anaesthetic and intensive care management. At present, one of the methods of improving gas exchange restricted by ventilation/perfusion mismatching is independent ventilation with two ventilators. Recently, however, a unique device has been developed, enabling ventilation of independent lungs in 1:1, 2:1, 3:1, and 5:1 proportions. The main goal of the study was to evaluate the device's utility, precision and impact on pulmonary mechanics. Secondly- to measure the gas distribution in supine and lateral decubitus position.69 patients who underwent elective thoracic surgery were eligible for the study. During general anaesthesia, after double lumen tube intubation, the aforementioned control system was placed between the anaesthetic machine and the patient. In the supine and lateral decubitus (left/right positions, measurements of conventional and independent (1:1 proportion ventilation were performed separately for each lung, including the following: tidal volume, peak pressure and dynamic compliance.Our results show that conventional ventilation using Robertshaw tube in the supine position directs 47% of the tidal volume to the left lung and 53% to the right lung. Furthermore, in the left lateral position, 44% is directed to the dependent lung and 56% to the non-dependent lung. In the right lateral position, 49% is directed to the dependent lung and 51% to the non-dependent lung. The control system positively affected non-dependent and dependent lung ventilation by delivering equal tidal volumes into both lungs with no adverse effects, regardless of patient's position.We report that gas distribution is uneven during conventional ventilation using Robertshaw tube in the supine and lateral decubitus positions. However, this recently released control system enables precise and safe independent ventilation in the supine and the left and right lateral decubitus

  10. Gender effects of the COMT Val 158 Met genotype on verbal fluency in healthy adults.

    Science.gov (United States)

    Soeiro-De-Souza, Marcio Gerhardt; Bio, Danielle Soares; David, Denise Petresco; Missio, Giovani; Lima, Bruno; Fernandes, Fernando; Machado-Vieira, Rodrigo; Moreno, Ricardo Alberto

    2013-09-01

    Cognitive performance in healthy individuals is associated with gender differences in specific tests; a female advantage has been demonstrated in language tests, whereas a male advantage has been demonstrated in spatial relation examinations. The prefrontal cortex (PFC) mediates important cognitive domains and is influenced by dopamine (DA) activity. The single nucleotide polymorphism (SNP) rs4680 in the catechol‑O‑methyltransferase (COMT) gene results in an amino acid substitution from valine (Val) to methionine (Met). The Met allele has been demonstrated to decrease COMT enzyme activity and improve PFC cognitive function. COMT regulates DA activity in the PFC and exhibits gender effects. The aim of the present study was to investigate the gender‑specific effects of the COMT genotype on cognition in healthy young adults. Seventy‑six healthy subjects were genotyped for COMT rs4680 and submitted to an extensive range of neuropsychological tests assessing aspects of PFC function. The COMT Met allele influenced the performance of executive function. The results revealed gender effects of the COMT rs4680 Met allele on verbal fluency, with positive effects in males and negative effects in females. This suggested that DA activity affects cognitive function in different ways, according to gender.

  11. Radioimmunoassay of met-enkephalin in microdissected areas of paraformaldehyde-fixed rat brain

    International Nuclear Information System (INIS)

    Correa, F.M.A.; Saavedra, J.M.

    1984-01-01

    The effects were studied of various sample preparation procedures on rat brain met-enkephalin content, measured by radioimmunoassay. Whole brain met-enkephalin content of rats killed by decapitation followed by immediate tissue freezing was similar to that of rats killed by microwave irradiation and to those of rats anesthetized with pentobarbital or halothane before killing, whether previously perfused with paraformaldehyde or not. In contrast, a decrease (up to 80%) in met-enkephalin concentrations was observed when brain samples were frozen and thawed to mimic the procedure utilized in the ''punch'' technique for analysis of discrete brain nuclei. This decrease was totally prevented by paraformaldehyde perfusion of the brain prior to sacrifice. Brain perfusion did not alter the amount of immunoassayable met-enkephalin extracted from tissue or its profile after Sephadex chromatography. Paraformaldehyde perfusion results in better morphological tissue preservation and facilitates the ''punch'' dissecting technique. Paraformaldehyde perfusion may be the procedure of choice for the measurement of neuropeptides in specific brain nuclei dissected by the ''punch'' technique

  12. MET receptor tyrosine kinase controls dendritic complexity, spine morphogenesis, and glutamatergic synapse maturation in the hippocampus.

    Science.gov (United States)

    Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

    2014-12-03

    The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. Copyright © 2014 the authors 0270-6474/14/3416166-14$15.00/0.

  13. COMT val108/158 met genotype affects neural but not cognitive processing in healthy individuals.

    Science.gov (United States)

    Dennis, Nancy A; Need, Anna C; LaBar, Kevin S; Waters-Metenier, Sheena; Cirulli, Elizabeth T; Kragel, James; Goldstein, David B; Cabeza, Roberto

    2010-03-01

    The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496-1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output.

  14. MetRxn: a knowledgebase of metabolites and reactions spanning metabolic models and databases

    Directory of Open Access Journals (Sweden)

    Kumar Akhil

    2012-01-01

    Full Text Available Abstract Background Increasingly, metabolite and reaction information is organized in the form of genome-scale metabolic reconstructions that describe the reaction stoichiometry, directionality, and gene to protein to reaction associations. A key bottleneck in the pace of reconstruction of new, high-quality metabolic models is the inability to directly make use of metabolite/reaction information from biological databases or other models due to incompatibilities in content representation (i.e., metabolites with multiple names across databases and models, stoichiometric errors such as elemental or charge imbalances, and incomplete atomistic detail (e.g., use of generic R-group or non-explicit specification of stereo-specificity. Description MetRxn is a knowledgebase that includes standardized metabolite and reaction descriptions by integrating information from BRENDA, KEGG, MetaCyc, Reactome.org and 44 metabolic models into a single unified data set. All metabolite entries have matched synonyms, resolved protonation states, and are linked to unique structures. All reaction entries are elementally and charge balanced. This is accomplished through the use of a workflow of lexicographic, phonetic, and structural comparison algorithms. MetRxn allows for the download of standardized versions of existing genome-scale metabolic models and the use of metabolic information for the rapid reconstruction of new ones. Conclusions The standardization in description allows for the direct comparison of the metabolite and reaction content between metabolic models and databases and the exhaustive prospecting of pathways for biotechnological production. This ever-growing dataset currently consists of over 76,000 metabolites participating in more than 72,000 reactions (including unresolved entries. MetRxn is hosted on a web-based platform that uses relational database models (MySQL.

  15. Teaching weather and climate science in primary schools - a pilot project from the UK Met Office

    Science.gov (United States)

    Orrell, Richard; Liggins, Felicity; Challenger, Lesley; Lethem, Dom; Campbell, Katy

    2017-04-01

    Wow Schools is a pilot project from the Met Office with an aim to inspire and educate the next generation of scientists and, uniquely, use the data collected by schools to improve weather forecasts and warnings across the UK. Wow Schools was launched in late 2015 with a competition open to primary schools across the UK. 74 schools entered the draw, all hoping to be picked as one of the ten lucky schools taking part in the pilot scheme. Each winning school received a fully automatic weather station (AWS), enabling them to transmit real-time local weather observations to the Met Office's Weather Observation Website (WOW - wow.metoffice.gov.uk), an award winning web portal for uploading and sharing a range of environmental observations. They were also given a package of materials designed to get students out of the classroom to observe the weather, get hands-on with the science underpinning weather forecasting, and analyse the data they are collecting. The curriculum-relevant materials were designed with the age group 7 to 11 in mind, but could be extended to support other age groups. Each school was offered a visit by a Wow Schools Ambassador (a Met Office employee) to bring the students' learning to life, and access to a dedicated forecast for its location generated by our new supercomputer. These forecasts are improved by the school's onsite AWS reinforcing the link between observations and forecast production. The Wow Schools pilot ran throughout 2016. Here, we present the initial findings of the project, examining the potential benefits and challenges of working with schools across the UK to: enrich students' understanding of the science of weather forecasting; to source an ongoing supply of weather observations and discover how these might be used in the forecasting process; and explore what materials and business model(s) would be most useful and affordable if a wider roll-out of the initiative was undertaken.

  16. High Blood Pressure: Unique to Older Adults

    Science.gov (United States)

    ... our e-newsletter! Aging & Health A to Z High Blood Pressure Hypertension Unique to Older Adults This section provides ... Pressure Targets are Different for Very Old Adults High blood pressure (also called hypertension) increases your chance of having ...

  17. Evaluation of unique identifiers used as keys to match identical publications in Pure and SciVal – a case study from health science [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Heidi Holst Madsen

    2016-09-01

    Full Text Available Unique identifiers (UID are seen as an effective key to match identical publications across databases or identify duplicates in a database. The objective of the present study is to investigate how well UIDs work as match keys in the integration between Pure and SciVal, based on a case with publications from the health sciences. We evaluate the matching process based on information about coverage, precision, and characteristics of publications matched versus not matched with UIDs as the match keys. We analyze this information to detect errors, if any, in the matching process. As an example we also briefly discuss how publication sets formed by using UIDs as the match keys may affect the bibliometric indicators number of publications, number of citations, and the average number of citations per publication.  The objective is addressed in a literature review and a case study. The literature review shows that only a few studies evaluate how well UIDs work as a match key. From the literature we identify four error types: Duplicate digital object identifiers (DOI, incorrect DOIs in reference lists and databases, DOIs not registered by the database where a bibliometric analysis is performed, and erroneous optical or special character recognition. The case study explores the use of UIDs in the integration between the databases Pure and SciVal. Specifically journal publications in English are matched between the two databases. We find all error types except erroneous optical or special character recognition in our publication sets. In particular the duplicate DOIs constitute a problem for the calculation of bibliometric indicators as both keeping the duplicates to improve the reliability of citation counts and deleting them to improve the reliability of publication counts will distort the calculation of average number of citations per publication. The use of UIDs as a match key in citation linking is implemented in many settings, and the availability of

  18. Remote Sensing of Volcanic ASH at the Met Office

    Directory of Open Access Journals (Sweden)

    Marenco F.

    2016-01-01

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

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

    Science.gov (United States)

    Wright, Bruce

    2010-05-01

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

  20. Estimation of METs by Accelerometers while Walking and Running

    Science.gov (United States)

    Kurihara, Yosuke; Watanabe, Kajiro; Yoneyama, Mitsuru

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

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

    International Nuclear Information System (INIS)

    Lu, Xiaochuan; Terada, Takahiro

    2016-05-01

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

  2. BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction.

    Science.gov (United States)

    Zhao, Mingzhe; Chen, Lu; Yang, Jiarun; Han, Dong; Fang, Deyu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Ma, Jingsong; Wang, Lin; Jiang, Shixiang; Song, Xuejia; Zhou, Jiawei; Zhang, Jian; Chen, Mingqi; Qi, Dong; Yang, Yanjie; Pan, Hui

    2018-02-01

    Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Detecting Beer Intake by Unique Metabolite Patterns.

    Science.gov (United States)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian; Bech, Lene; Lund, Erik; Dragsted, Lars Ove

    2016-12-02

    Evaluation of the health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1), 18 participants were given, one at a time, four different test beverages: strong, regular, and nonalcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort, and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e., N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

  4. MetWAMer: eukaryotic translation initiation site prediction

    Directory of Open Access Journals (Sweden)

    Brendel Volker

    2008-09-01

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

  5. The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress.

    Science.gov (United States)

    Alexander, Nina; Osinsky, Roman; Schmitz, Anja; Mueller, Eva; Kuepper, Yvonne; Hennig, Juergen

    2010-07-01

    Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date. Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity. Healthy male adults (N=100) were genotyped and exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol and self-reported mood levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Furthermore, heart rate reactivity as an indicator of sympathetic activation was monitored continuously during the experimental procedure. We report a small, but significant effect of the BDNF Val66Met polymorphism on stress reactivity. More precisely, carriers of the met-allele showed a significantly attenuated HPA-axis and cardiovascular reactivity to the psychosocial stressor compared to subjects with the val/val genotype. Furthermore, the diminished physiological response in met-allele carriers was also attended by significantly lower self-reported ratings of perceived stress and nervousness. Our findings of a diminished endocrine and cardiovascular stress response in healthy male adults is consistent with a previously published study and adds further evidence for a crucial role of the BDNF Val66Met polymorphism in the modulation of stress reactivity. Copyright 2010. Published by Elsevier Ltd.

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

    Science.gov (United States)

    Liston, G. E.; Elder, K.

    2004-12-01

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

  7. a solution through Praxis? reflections about the Ivory Tower metaphor and the indissociability between theory and practice in organizational studies / Uma saída pela Práxis ? reflexões sobre a metáfora da Torre de Marfim e a indissociabilidade entre a teoria e a prática nos estudos organizacionais

    Directory of Open Access Journals (Sweden)

    Valderí de Castro Alcântara

    2016-10-01

    Full Text Available Purpose: The aim of the current study is to use the Ivory Tower metaphor to discuss and question the false dichotomy between theory and practice, as well as the insufficient pragmatic and performative solution towards the market logic, and to problematize the concept of praxis as a possibility through critical approaches. Originality/gap/relevance/implications: 1. the Ivory Tower demonstrates the existence of a gap in the relation between theory and practice; 2. the essay is conducted according to critical approaches; 3. the Critical Theory has the potential to deconstruct the assigned and socially constructed meanings of the Ivory Tower. Key methodological aspects: This is a theoretical essay that dialectically explores the Ivory Tower metaphor. Summary of key results: 1. the organizational science linked to the instrumental logic makes no place for praxis; 2. the Traditional Theory does not allow thinking about the relation between theory and practice through praxis, because it polarizes such categories and gives primacy to practice by demanding performance and productivity from theory; 3. based on the Ivory Tower metaphor, it is necessary to make criticisms for the sake of praxis and not for the sake of the practice understood just as technical and instrumental utility. Key considerations/conclusions: We pursuit solutions to remove the dichotomies that take the dialectical nature away from reality; it is necessary (reconstructing new ways to get in and out of the tower on behalf of emancipation, in the permanent and inseparable relation between theory and practice. Objetivo: Por meio da metáfora da Torre de Marfim buscamos discutir e questionar a falsa dicotomia entre a teoria e a prática, além da insuficiente saída pragmática e performática na direção da lógica do mercado para no fim problematizar o conceito de práxis como possibilidade mediante abordagens críticas. Originalidade/Lacuna/Relevância/Implicações: (a A Torre de

  8. El sexo de las metáforas

    Directory of Open Access Journals (Sweden)

    Pérez Sedeño, Eulalia

    2011-02-01

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

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

  9. MET Signaling Mediates Intestinal Crypt-Villus Development, Regeneration, and Adenoma Formation and Is Promoted by Stem Cell CD44 Isoforms.

    Science.gov (United States)

    Joosten, Sander P J; Zeilstra, Jurrit; van Andel, Harmen; Mijnals, R Clinton; Zaunbrecher, Joost; Duivenvoorden, Annet A M; van de Wetering, Marc; Clevers, Hans; Spaargaren, Marcel; Pals, Steven T

    2017-10-01

    Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor (EGF) receptor signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET coreceptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice. We established organoid cultures from ISCs stimulated with HGF or EGF and assessed intestinal differentiation by immunohistochemistry. Mice with total epithelial disruption of MET (Ah Cre /Met fl/fl /LacZ) or ISC-specific disruption of MET (Lgr5 Creert2 /Met fl/fl /LacZ) and control mice (Ah Cre /Met +/+ /LacZ, Lgr5 Creert2 /Met +/+ /LacZ) were exposed to 10 Gy total body irradiation; intestinal tissues were collected, and homeostasis and regeneration were assessed by immunohistochemistry. We investigated adenoma organoid expansion stimulated by HGF or EGF using adenomas derived from Lgr5 Creert2 /Met fl/fl /Apc fl/fl and Lgr5 Creert2 /Met +/+ /Apc fl/fl mice. The same mice were evaluated for adenoma prevalence and size. We also quantified adenomas in Ah Cre /Met fl/fl /Apc fl/+ mice compared with Ah Cre /Met +/+ /Apc fl/+ control mice. We studied expansion of organoids generated from crypts and adenomas, stimulated by HGF or EGF, that were derived from mice expressing different CD44 splice variants (Cd44 +/+ , Cd44 -/- , Cd44 s/s , or Cd44 v4-10/v4-10 mice). Crypts incubated with EGF or HGF expanded into self-organizing mini-guts with similar levels of efficacy and contained all differentiated cell lineages. MET-deficient mice did not have defects in intestinal homeostasis. Total body irradiation reduced numbers of proliferating crypts in Ah Cre

  10. Het instellen op insuline van patiënten met diabetes mellitus type 2: In een transmurale organisatievorm minstens even effectief als poliklinisch; een retrospectief onderzoek met 4 jaar follow-up [Initiating insulin therapy in patients with diabetes mellitus type 2: In a transmural form of care at least as effective as an outpatients form; a retrospective study with a 4-year follow-up

    NARCIS (Netherlands)

    Rosendal, H.; Vondeling, H.; Witte, L.P. de; Hutubessy, R.C.W.; Beekum, W.T. van; Heine, R.J.

    2002-01-01

    Objective. Assessing whether the initiation of insulin therapy in patients with diabetes mellitus type 2 can be delivered as effectively in a structured transmural care model as in the more usual outpatients structure. Design. Retrospective comparative cohort study. Method. In 1997 data were

  11. Increasing Need for Uniqueness in Contemporary China: Empirical Evidence

    Directory of Open Access Journals (Sweden)

    Huajian Cai

    2018-05-01

    Full Text Available Past research has documented various cultural and psychological changes in contemporary China. In two studies, we examine how Chinese people’s need for uniqueness (NFU also has changed. In Study 1, we found a significant cross-generational increase in Chinese participants’ self-reported NFU. In Study 2, we sampled the names of Chinese newborn babies over the last five decades and found that parents have been increasingly likely to use unique characters to name their children. These findings suggest that the NFU has been rising in China, a historically collectivistic-oriented society. Theoretical and practical implications of our findings were discussed.

  12. CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling

    Directory of Open Access Journals (Sweden)

    Matous Hrdinka

    2016-03-01

    Full Text Available Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub is assembled by the linear ubiquitin assembly complex (LUBAC, and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation.

  13. XRCC3 Thr241Met Polymorphism is not Associated with Lung Cancer Risk in a Romanian Population.

    Science.gov (United States)

    Catana, Andreea; Pop, Monica; Marginean, Dragos Horea; Blaga, Ioana Cristina; Porojan, Mihai Dumitru; Popp, Radu Anghel; Pop, Ioan Victor

    2016-01-01

    Deoxyribonucleic Acid (DNA) repair mechanisms play a critical role in protecting the cellular genome against carcinogens. X-ray cross-complementing gene 3 (XRCC3) is involved in DNA repair and therefore certain genetic polymorphisms that occur in DNA repair genes may affect the ability to repair DNA defects and may represent a risk factor in carcinogenesis. The purpose of our study was to investigate the association between XRCC3 gene substitution of Threonine with Methionine in codon 241 of XRCC3 gene (Thr241Met) polymorphism and the risk of lung cancer, in a Romanian population. We recruited 93 healthy controls and 85 patients with lung cancer, all smokers. Thr241Met, XRCC3 gene genotyping was determined by multiplex Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Statistical analysis (OR, recessive model), did not revealed an increased risk for lung cancer, for the variant 241Met allele and Thr241Met genotypes (p=0.138, OR=0.634, CI=0.348-1.157; p=0.023, OR=0.257, CI=0.085-6.824). Also, there were no positive statistical associations between Thr241Met polymorphism of XRCC3 gene, gender, tobacco and various histopathological tumor type of lung cancer. In conclusion, the results of the study suggest that the XRCC3 gene Thr241Met polymorphism is not associated with an increased risk for the development of lung cancer in this Romanian group.

  14. BDNF Val66Met polymorphism is associated with higher anticipatory cortisol stress response, anxiety, and alcohol consumption in healthy adults.

    Science.gov (United States)

    Colzato, Lorenza S; Van der Does, A J Willem; Kouwenhoven, Coen; Elzinga, Bernet M; Hommel, Bernhard

    2011-11-01

    The brain-derived neurotrophic factor (BDNF) is a key protein in maintaining neuronal integrity. The BDNF gene is thought to play an important role in the pathophysiology of mood and anxiety disorders. The aim of this study was to investigate, for the first time in a single study, the association between BDNF Val(66)Met polymorphism, anxiety, alcohol consumption, and cortisol stress response. 98 healthy university students (54 females and 44 males), genotyped for the Val(66)Met polymorphism, participated in a physical-stress procedure (cold pressure test, CPT) after having been informed that they would undergo a painful experience. Indices of anxiety and of stress were collected from repeated measurement of salivary cortisol, blood pressure, and heart rate. BDNF Met carriers, were more anxious during the CPT (pBDNF Val(66)Met polymorphism with HPA axis reactivity to stress was not modulated by gender. These results suggest that Met carriers are particularly sensitive in anticipating stressful events, which extends previous findings on the moderating role of the BDNF Val(66)Met polymorphism in the face of stressful life events. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  16. The BDNF Val66Met polymorphism moderates the relationship between Posttraumatic Stress Disorder and fear extinction learning.

    Science.gov (United States)

    Felmingham, Kim L; Zuj, Daniel V; Hsu, Ken Chia Ming; Nicholson, Emma; Palmer, Matthew A; Stuart, Kimberley; Vickers, James C; Malhi, Gin S; Bryant, Richard A

    2018-05-01

    The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism. Moderation analyses using PROCESS examined whether BDNF genotype (Val-Val vs Met carriers) moderated the relationship between PTSD symptom severity (and diagnostic status) and skin conductance response (SCR) amplitude during fear extinction. The PTSD group displayed significantly slower fear extinction learning compared to TC and NTC in the early extinction phase. The BDNF Val66Met polymorphism moderated the relationship between PTSD and fear extinction learning, such that poorer fear extinction learning was associated with greater PTSD symptom severity (and PTSD diagnostic status) in individuals with the low-expression Met allele, but no relationship was demonstrated in individuals with the Val-Val allele. This study reveals that impaired fear extinction learning is particularly evident in individuals with PTSD who carry the low-expression BDNF Met allele and importantly not in those with the Val-Val allele. This provides novel evidence of a link between BDNF and impaired fear extinction learning in PTSD, which may contribute to poorer response to exposure therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-12-01

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

  18. Impaired cognitive flexibility during sleep deprivation among carriers of the Brain Derived Neurotrophic Factor (BDNF) Val66Met allele.

    Science.gov (United States)

    Grant, Leilah K; Cain, Sean W; Chang, Anne-Marie; Saxena, Richa; Czeisler, Charles A; Anderson, Clare

    2018-02-15

    Accumulating evidence points to a genetic contribution to explain inter-individual vulnerability to sleep deprivation. A functional polymorphism in the BDNF gene, which causes a valine (Val) to methionine (Met) amino acid substitution at Codon 66, has been associated with cognitive impairment, particularly in populations with impaired frontal functioning. We hypothesised that sleep deprivation, which affects frontal function, may lead to cognitive dysfunction in Met allele carriers. To examine this, we investigated, in different BDNF genotypes, the effects of sleep deprivation on cognitive flexibility, as measured by response inhibition using the Stroop Color Naming Task. Thirty healthy, adults of European ancestry, including 12 heterozygous Met allele carriers and 18 Val/Val homozygotes, underwent 30-h of extended wakefulness under constant routine conditions. A computerised Stroop task was administered every 2h. Error rate and reaction times increased with time awake for all individuals. Participants with the Val/Met genotype made more errors on incongruent trials after 20h awake. While Val/Met participants also took significantly longer to respond when inhibiting a prepotent response irrespective of time awake, this was particularly evident during the biological night. Our study shows that carriers of the BDNF Met allele are more vulnerable to the impact of prolonged wakefulness and the biological night on a critical component of executive function, as measured by response inhibition on the Stroop task. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Why Is Family Firms' Internationalization Unique? : A Meta-Analysis

    NARCIS (Netherlands)

    Arregle, Jean-Luc; Duran, Patricio; Hitt, Michael A.; van Essen, M.

    Despite its importance, there is no clear understanding of the uniqueness of family firms' internationalization. This article sheds new light on this issue with a meta-analysis of 76 studies covering 41 countries. We show that the considerable study and cross-country differences in the relationship

  20. Interaction Between 5-HTTLPR and BDNF Val66Met Polymorphisms on HPA Axis Reactivity in Preschoolers

    OpenAIRE

    Dougherty, Lea R.; Klein, Daniel N.; Congdon, Eliza; Canli, Turhan; Hayden, Elizabeth P.

    2009-01-01

    This study examined whether the interaction between the serotonin transporter promoter region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms was associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. A community sample of 144 preschool-aged children was genotyped and exposed to stress-inducing laboratory tasks. Salivary cortisol was obtained at four time points during a standardized laboratory assessment before and after stressors invol...

  1. Peatlands as a unique climatic hotspots

    Science.gov (United States)

    Slowinska, S.; Marcisz, K.; Slowinski, M. M.; Blazejczyk, K.; Lamentowicz, M.

    2017-12-01

    Peatlands are unique environments, often acting as microrefugia of various taxa. High groundwater table, organic soils, specific vegetation and topography are important determinants of their local climatic conditions. However, relations between those determinants are not stable. For example, seasonal changes in weather patterns, hydrological dynamics, and local vegetation may alter microclimate. Additionally, long-term changes are important factor, as for example overgrowing due to significant change of microclimate conditions, what in turn changes geochemical and biological processes in the peat layer. We have been investigating interactions between abiotic and biotic factors of a small Sphagnum mire (ca. 6.0 ha) for over ten years now. The mire is located in Poland in transitional temperate climate and is the only place in polish lowlands where glacial relict Betula nana occurs. Identification of local climate of the mire, its microclimatic differentiation and its influence on surroundings were objectives of the study. We recorded water level fluctuations, photosynthetically active radiation (PAR), air temperature and humidity, and peat temperature at five monitoring plots at the mire and observed significant differences between them. We also investigated Sphagnum mosses growth and testate amoeba diversity and community structure to understand biological response of those differences. We observed that local climate of the mire was significantly different from open area reference place, it was much colder especially during nights. The average minimal temperature at the height 30 cm for growing seasons 2010-2012 was 3.7oC lower there and ground frosts occurred even in the summer. The climate of the mire affected the forest directly adjacent to it, and depending on weather conditions the strength and the distance of this interaction was different. Our results show that micro-environmental changes affects on biological processes and should be taken into consideration

  2. Evolution of a Unique Systems Engineering Capability

    Energy Technology Data Exchange (ETDEWEB)

    Robert M. Caliva; James A. Murphy; Kyle B. Oswald

    2011-06-01

    The Idaho National Laboratory (INL) is a science-based, applied engineering laboratory dedicated to supporting U.S. Department of Energy missions in nuclear and energy research, science, and national security. The INL’s Systems Engineering organization supports all of the various programs under this wide array of missions. As with any multifaceted organization, strategic planning is essential to establishing a consistent culture and a value discipline throughout all levels of the enterprise. While an organization can pursue operational excellence, product leadership or customer intimacy, it is extremely difficult to excel or achieve best-in-class at all three. In fact, trying to do so has resulted in the demise of a number of organizations given the very intricate balancing act that is necessary. The INL’s Systems Engineering Department has chosen to focus on customer intimacy where the customer’s needs are first and foremost and a more total solution is the goal. Frequently a total solution requires the employment of specialized tools to manage system complexity. However, it is only after understanding customer needs that tool selection and use would be pursued. This results in using both commercial-off-the-shelf (COTS) tools and, in some cases, requires internal development of specialized tools. This paper describes how a unique systems engineering capability, through the development of customized tools, evolved as a result of this customer-focused culture. It also addresses the need for a common information model or analysis framework and presents an overview of the tools developed to manage and display relationships between entities, support trade studies through the application of utility theory, and facilitate the development of a technology roadmap to manage system risk and uncertainty.

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

    OpenAIRE

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

    2008-01-01

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

  4. The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Zhuang, Langen; Li, Ming; Yu, Changhua; Li, Can; Zhao, Mingming; Lu, Ming; Zheng, Taishan; Zhang, Rong; Zhao, Weijing; Bao, Yuqian; Xiang, Kunsan; Jia, Weiping; Wang, Niansong; Liu, Limei

    2014-02-01

    The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case-control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.

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

    Science.gov (United States)

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

    2017-04-01

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

  6. Marketing the Uniqueness of Small Towns. Revised.

    Science.gov (United States)

    Dunn, Douglas; Hogg, David H.

    The key to marketing a town is determining and promoting the town's "differential advantage" or uniqueness that would make people want to visit or live there. Exercises to help communities gain important insights into the town's competitive edge include a brainstorming session with knowledgeable community members, a visitor…

  7. On uniqueness in evolution quasivariational inequalities

    Czech Academy of Sciences Publication Activity Database

    Brokate, M.; Krejčí, Pavel; Schnabel, H.

    2004-01-01

    Roč. 11, č. 1 (2004), s. 111-130 ISSN 0944-6532 Institutional research plan: CEZ:AV0Z1019905 Keywords : evolution quasivariational inequality * uniqueness * sweeping process Subject RIV: BA - General Mathematics Impact factor: 0.425, year: 2004 http://www.heldermann-verlag.de/jca/jca11/jca0386.pdf

  8. Weeping dragon, a unique ornamenal citrus

    Science.gov (United States)

    ‘Weeping Dragon’ is a new ornamental citrus cultivar developed by intercrossing of two unusual and unique citrus types, Poncirus trifoliata cultivated variety (cv.) Flying Dragon, and Citrus sinensis cv. ‘Cipo’. This new hybrid cultivar combines strongly contorted and weeping growth traits in a smal...

  9. Using Quantum Confinement to Uniquely Identify Devices

    Science.gov (United States)

    Roberts, J.; Bagci, I. E.; Zawawi, M. A. M.; Sexton, J.; Hulbert, N.; Noori, Y. J.; Young, M. P.; Woodhead, C. S.; Missous, M.; Migliorato, M. A.; Roedig, U.; Young, R. J.

    2015-11-01

    Modern technology unintentionally provides resources that enable the trust of everyday interactions to be undermined. Some authentication schemes address this issue using devices that give a unique output in response to a challenge. These signatures are generated by hard-to-predict physical responses derived from structural characteristics, which lend themselves to two different architectures, known as unique objects (UNOs) and physically unclonable functions (PUFs). The classical design of UNOs and PUFs limits their size and, in some cases, their security. Here we show that quantum confinement lends itself to the provision of unique identities at the nanoscale, by using fluctuations in tunnelling measurements through quantum wells in resonant tunnelling diodes (RTDs). This provides an uncomplicated measurement of identity without conventional resource limitations whilst providing robust security. The confined energy levels are highly sensitive to the specific nanostructure within each RTD, resulting in a distinct tunnelling spectrum for every device, as they contain a unique and unpredictable structure that is presently impossible to clone. This new class of authentication device operates with minimal resources in simple electronic structures above room temperature.

  10. The effect of COMT Val158 Met genotype on decision-making and preliminary findings on its interaction with the 5-HTTLPR in healthy females.

    Science.gov (United States)

    van den Bos, Ruud; Homberg, Judith; Gijsbers, Ellen; den Heijer, Esther; Cuppen, Edwin

    2009-02-01

    Poor decision-making is inherent to several psychiatric conditions for which a genetic basis may exist. We previously showed that healthy female volunteers homozygous for the short allele (s/s) of the serotonin transporter length polymorphic region (5-HTTLPR) chose more often cards from disadvantageous decks in the Iowa Gambling Task (IGT), which measures decision-making, than long (l) allele carriers. The 5-HTTLPR and catechol-O-methyltransferase (COMT) Val(158) Met polymorphism affect the same set of neuronal structures. Therefore, we explored the effect of the (COMT) Val(158) Met polymorphism on IGT performance and its interaction with the 5-HTTLPR in the same subjects in this study. We observed that subjects homozygous for methionine (Met/Met) chose more disadvantageously than subjects homozygous for valine (Val/Val). s/s-Met/Met-subjects appeared to show the poorest IGT performance of all possible combinations of 5-HTTLPR and COMT allelic variants. Using the Expectancy-Valence model, no differences were found for the three different 5-HTTLPR or COMT genotypes regarding (i) attention to wins versus losses, (ii) updating rate, or (iii) response consistency. However, subjects with at least one Met-allele were paying more attention to wins than subjects with no Met-alleles. We discuss whether a common neuronal mechanism relates to s- and Met-allele-related deficits in updating and/or processing of choice outcome to guide subsequent choices in this gamble-based test.

  11. BDNF VAL66MET Polymorphism Elevates the Risk of Bladder Cancer via MiRNA-146b in Micro-Vehicles

    Directory of Open Access Journals (Sweden)

    Cong Li

    2018-01-01

    Full Text Available Background/Aims: Emerging studies on brain-derived neurotrophic factor (BDNF have shown that might be novel biomarkers and therapeutic targets for cancer. We explore the role of BDNF in the tumorigenesis of bladder cancer and the underlying molecular mechanism. Methods: 368 patients with diagnosed bladder cancer and 352 healthy controls were enrolled to evaluate the association of BDNF and the miR-146b. Bioinformatics algorithm analysis and luciferase assay were performed to identify the target genes of miR-146b. Real-time PCR and western-blot were carried out to validate the relationship between miR-146b and CRK. MTT assay and FACS were used to evaluated the proliferation and apoptosis of cancer cells. MVs were isolated and transfect into the culture cells to confirm the above observation. Results: The clinical study shows that BDNF Met/Met was significantly associated with the risk of bladder cancer. In addition, comparing with Val/Val and Val/Met, Met/Met has lower miR-146b level. Luciferase assay shows that BDNF Val/Val is apparently enhanced miR-146b promoter-luciferase, but not BDNF Met/Met. Based on luciferase assay, CRK is a direct target gene of miR-146b. MiR-146b mimics significantly inhibited the expression of CRK and activation of AKT level. The expression of CRK and the activation of AKT (p-AKT were significantly inhibited by MV-BDNF Val/Val-miR-146b or MV-BDNF Val/Met-miR-146b, but not MV-BDNF Met/Met-miR-146b. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b obviously inhibited cell proliferation, which eliminated by CRK. Meanwhile, with MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not affect the proliferation. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b enhanced cell apoptosis, which could be eliminated by CRK. Meanwhile, MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not promote apoptosis. Conclusion: BDNF VAL66MET polymorphism is associated with miR-146b and its target gene CRK. MiR-146b and CRK mediated BDNF VAL66

  12. Executive Functions Contribute Uniquely to Reading Competence in Minority Youth

    Science.gov (United States)

    Jacobson, Lisa A.; Koriakin, Taylor; Lipkin, Paul; Boada, Richard; Frijters, Jan; Lovett, Maureen; Hill, Dina; Willcutt, Erik; Gottwald, Stephanie; Wolf, Maryanne; Bosson-Heenan, Joan; Gruen, Jeffrey R.; Mahone, E. Mark

    2018-01-01

    Competent reading requires various skills beyond those for basic word reading (i.e., core language skills, rapid naming, phonological processing). Contributing “higher-level” or domain-general processes include information processing speed and executive functions (working memory, strategic problem solving, attentional switching). Research in this area has relied on largely Caucasian samples, with limited representation of children from racial or ethnic minority groups. This study examined contributions of executive skills to reading competence in 761 children of minority backgrounds. Hierarchical linear regressions examined unique contributions of executive functions (EF) to word reading, fluency, and comprehension. EF contributed uniquely to reading performance, over and above reading-related language skills; working memory contributed uniquely to all components of reading; while attentional switching, but not problem solving, contributed to isolated and contextual word reading and reading fluency. Problem solving uniquely predicted comprehension, suggesting that this skill may be especially important for reading comprehension in minority youth. Attentional switching may play a unique role in development of reading fluency in minority youth, perhaps as a result of the increased demand for switching between spoken versus written dialects. Findings have implications for educational and clinical practice with regard to reading instruction, remedial reading intervention, and assessment of individuals with reading difficulty. PMID:26755569

  13. Onderskeiding tussen beroepsrealistiese en -onrealistiese adolessente met behulp van die waardeskaal

    Directory of Open Access Journals (Sweden)

    R. E. Zeier

    1995-06-01

    Full Text Available Differentiation between vocational realistic and unrealistic adolescents by means of a value scale. The usefulness of the Value Scale for distinguishing between adolescents with realistic or unrealistic approaches towards vocational choice was studied. A group of std. 10 pupils from a specific secondary school in the Cape Peninsula participated in the study. An evaluation with regard to the degree of realism of vocational decisions was made by three counselling psychologists. Classification of subjects was based on the agreement between their vocational choice, interest profiles, academic performance, intelligence test scores and course prerequisites. A number of variables were identified by discriminant analysis which distinguished significantly between realistic and unrealistic approaches. Value-preferences for realistic adolescents were more homogeneous and were globally interpreted as an intrinsic value pattern while subjects with unrealistic approaches showed a more differentiated pattern. Opsomming Die bruikbaarheid van die Waardeskaal vir die onderskeiding tussen beroepsrealistiese en beroepsonrealistiese adolessente is ondersoek deur 'n groep st. 10-leerlinge uit 'n spesifieke hoerskool in die Kaapse Skiereiland by die ondersoek te betrek. 'n Evaluering met betrekking tot realisme van verklaarde loopbaankeuse is deur drie voorligtingsielkundiges gemaak op grond van ooreenstemming tussen verklaarde beroepskeuse, belangstellings, akademiese prestasie, verstandstoetstellings en kursusvoorvereistes. Beduidende verskille met betrekking tot werkwaardes is tussen die groepe met behulp van diskriminant-analise gei'dentifiseer. Die waardevoorkeure van die beroepsrealistiese groep was meer homogeen van aard en kon globaal as intrinsieke waardevoorkeure beskryf word, terwyl die beroepsonrealistiese groep meer gedifferensieerde waardevoorkeurpatrone geopenbaar het.

  14. Both COMT Val158Met single nucleotide polymorphism and sex-dependent differences influence response inhibition

    Directory of Open Access Journals (Sweden)

    Valentina eMione

    2015-05-01

    Full Text Available Reactive and proactive control of actions are cognitive abilities that allow to deal with a continuously changing environment by adjusting already programmed actions. They also set forthcoming acts by evaluating the outcome of the previous ones. Earlier studies highlighted sex related differences in the strategies and in the pattern of brain activation during cognitive tasks involving reactive and proactive control. To further identify sex-dependent characteristics in the cognitive control of actions, in this study we have assessed whether/how differences in reactive and proactive control were modulated by the COMT Val158Met single nucleotide polymorphism, a genetic factor known to influence the functionality of the dopaminergic system, in particular at the level of prefrontal cortex. Two groups of male and female participants were further sorted according to their genotype (Val/Met, Val/Val and Met/Met and tested in a stop signal task, a consolidated tool to measure reactive and proactive control in experimental and clinical settings. In each group of participants we estimated both a measure of the capacity to react to unexpected events and the ability of monitoring their performance. The between groups comparison of these measures indicated a poorer ability of male individuals carrying the Val/Val genotype in error-monitoring, suggesting that differences between sexes could be influenced by the efficiency of COMT and that other sex-specific factors have to be considered. The comprehension of inter-groups behavioral and physiological correlates of cognitive control will provide more accurate diagnostic tools for predicting the incidence and the development of pathologies like ADHD or deviant behaviors as drug or alcohol abuse.

  15. Word from the CSO - CERN’s unique scientific breadth

    CERN Multimedia

    2008-01-01

    Whilst we are all clearly focused on completion of the LHC and the detectors around it and look forward to a successful start of operations later this year, we should not forget that CERN has yet more to offer in addition to this highest priority programme ‘at the energy frontier’. Indeed, CERN also attracts a large scientific community seizing the opportunities offered by its other facilities. Sometimes I wonder whether we are not too modest and should not emphasize more CERN’s unique scientific breadth. ISOLDE, at the PS Booster, relies on innovative techniques to produce results at the forefront of nuclear physics very cost-effectively. nTOF has provided unique measurements of interest to nuclear technology, nuclear astrophysics and basic nuclear physics, and still has an ambitious programme ahead of it after refurbishment of the target. Another unique facility is the Antiproton Decelerator, at which the study of antimatter is being pursued with ingenious experiment...

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Gabriel Gerard Rooney

    2013-12-01

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

  18. La metáfora como proceso cognitivo

    Directory of Open Access Journals (Sweden)

    Luz Amparo Fajardo Uribe

    2006-01-01

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

  19. Information and Communication Technology for French and English Speaking Postsecondary Students with Disabilities: What Are Their Needs and How Well Are These Being Met?

    Science.gov (United States)

    Fichten, Catherine S.; Nguyen, Mai N.; Asuncion, Jennison V.; Barile, Maria; Budd, Jillian; Amsel, Rhonda; Libman, Eva

    2010-01-01

    This study evaluates how well information and communication technology (ICT) related needs of students with various disabilities are met at school, at home, and in e-learning contexts. Results are based on the POSITIVES Scale, a 26 item objective measure of how well the ICT related needs of these students are met. The sample consists of 131…

  20. Peripheral blood progenitor cell transplantation mobilised by r-metHuG-CSF (filgrastim); a less costly alternative to autologous bone marrow transplantation

    NARCIS (Netherlands)

    C.A. Uyl-de Groot (Carin); D.J. Richel (Dirk); F.F.H. Rutten (Frans)

    1994-01-01

    textabstractIn a retrospective study, we calculated the treatment costs of 63 patients who received either autologous bone marrow transplantation (ABMT) with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) (filgrastim) (n=13) or without r-metHuG-CSF (n=22) or altenatively,