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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. 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.

  3. 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%, P<.001). Other MetS component factors (blood pressure, glucose and triglycerides) did not significantly differ between groups. Similar high rates of MetS were observed in Filipino 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.

  4. LCA – Unique and Controversial Case Studies

    Science.gov (United States)

    This session will focus on case studies and applications that have a unique or controversial aspect. Some of the most recent topics that seem to have significant interest include: LCA-based product declarations, LCA-based standards, LCA-based labels, alternative energy, agricul...

  5. MetPetDB: New Directions for Metamorphic Studies

    Science.gov (United States)

    Spear, F. S.; Adali, S.; Szymanski, B. K.; Hallett, B. K.; Waters, A. J.; Linder, Z. J.; Fyffe, M. E.; Goldfarb, D.; Barlett, K.

    2008-12-01

    It is estimated that less than 1% of the data collected on metamorphic rocks is published, and MetPetDB (database for metamorphic geochemistry) is being developed and populated to preserve these data and to foster new and innovative directions for scientific research and education. The data model is based on a sample of metamorphic rock and includes information about location, rock type, mineral assemblage, fabric, plus images of all types and mineral composition data. Mineral analyses are linked to locations on appropriate images so the spatial integrity of the data is preserved. Tools will be available for mineral recalculation, plotting, and thermobarometric applications. Derivative data such as peak P-T conditions, metamorphic P-T path, and cooling rate will also be stored. The database will be searchable based on any number of data fields, permitting rapid location of samples that can be used to test hypotheses and discover new relationships. For example: A student is designing a thesis project and MetPetDB will be a first resource to determine the types of rocks present in a region, the work that has been done on them, and links to the published findings. The Fe/Mg zoning in migmatitic garnets has been used to infer cooling rates. What is the range of cooling rates recorded by migmatitic garnets, and is there a correlation between peak metamorphic temperature and cooling rate? Is it possible that melting triggers rapid thrusting that causes the rapid cooling? A search on: rock type = migmatite plus Fe and Mg X-ray maps of garnet would reveal all samples that could be used in this study. A new geobarometer based on a specific mineral assemblage is proposed that permits pressures to be estimated to within 50 MPa. A search of the database for all samples with this assemblage plus analyses of the necessary minerals would provide a set of samples to which this new barometer can be applied. Recalculating pressures and temperatures for an entire region using new

  6. Twin studies: A unique epidemiological tool

    Directory of Open Access Journals (Sweden)

    Monalisha Sahu

    2016-01-01

    Full Text Available Twin studies are a special type of epidemiological studies designed to measure the contribution of genetics as opposed to the environment, to a given trait. Despite the facts that the classical twin studies are still being guided by assumptions made back in the 1920s and that the inherent limitation lies in the study design itself, the results suggested by earlier twin studies have often been confirmed by molecular genetic studies later. Use of twin registries and various innovative yet complex software packages such as the (SAS and their extensions (e.g., SAS PROC GENMOD and SAS PROC PHREG has increased the potential of this epidemiological tool toward contributing significantly to the field of genetics and other life sciences.

  7. Indazoles as potential c-Met inhibitors: design, synthesis and molecular docking studies.

    Science.gov (United States)

    Ye, Lianbao; Ou, Xiaomin; Tian, Yuanxin; Yu, Bangwei; Luo, Yan; Feng, Binghong; Lin, Hansen; Zhang, Jiajie; Wu, Shuguang

    2013-07-01

    Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of indazoles were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibition on c-Met and compound 4d showed highest activity against c-Met with IC50 value of 0.17 μM in TR-FRET-based assay and IC50 value of 5.45 μM in cell-based assay as compared to other tested compounds. Molecular docking experiments verified the results and explained the molecular mechanism of pretty activities to c-Met.

  8. 'n erge stressor : 'n studie van bejaardes met Alzheimer se siekte of

    African Journals Online (AJOL)

    support

    rumatoïede artritis, een met Alzheimer se siekte en 'n derde groep relatief gesonde bejaardes. ... According to the study a supportive social network and a spiritual belief ...... MROCZEK, D & KOLARZ, C 1998: The effect of age on positive.

  9. A comparative study between met & unmet need groups of contraception in rural area of Maharashtra, India

    Directory of Open Access Journals (Sweden)

    Harsha M Solanki

    2013-03-01

    Full Text Available Objectives To compare met & unmet need groups of contraception with socio-economic, demographic, accessibility & family Planning (FP related factors. Methods Community based cross-sectional, comparative study was conducted among 363 married women of reproductive age groups in rural area selected by stratified simple random technique. After collecting preliminary information, the study population then divided into two groups based on their contraceptive use i.e. MET Group & UNMET NEED Groups. Then the role of socio-economic, demographic, accessibility & family Planning (FP related factors were studies to determine contraceptive use between these groups. Results Mean age of study subjects was 24.12 ± 4.45 years & average number of children per women was 2.02. Males were more literate than females (69.1% Vs 47.2%. 51.8% women were belonging to lower socio-economic status. Early marriages were still prevalent in this study (53.7%. Prevalence of met group of contraception was 59.2% & that of unmet need for contraception was 44.1%. Met groups were mainly from 20-29 years age group (46.6%; most of them (46.8% were literate & were from high socio-economic group (30.9% compared to unmet need groups. On comparison to unmet groups, most of the met group (33.9% got married after 18 years of age, residing within 5km area (26.4%, had visited to FP centre (49.0% & ever visited by FP staff (43.3%. Conclusion Education, income, marriage age, accessibility, FP staff related factors definitely has role among met & unmet need groups in their contraceptive use.

  10. 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.

  11. The Multiwavelength Study of Two Unique Radio Galaxies

    Indian Academy of Sciences (India)

    Nectaria A. B. Gizani; M. A. Garrett; J. P. Leahy

    2002-03-01

    We present the usage of multi-frequency and multi-band radio, VLA, observations as well as X-ray observations in order to study the environment around two powerful radio galaxies, namely Hercules A and 3 C310. We study their environment both in pc- and kpc-scales. We have chosen these two radio galaxies as they present similar and unique characteristics, compared to the ones from our general knowledge about double radio galaxies associated with active galactic nuclei.

  12. Infrared Heterodyne Spectroscopy and its Unique Application to Planetary Studies

    Science.gov (United States)

    Kostiuk, Theodore

    2009-01-01

    Since the early 1970's the infrared heterodyne technique has evolved into a powerful tool for the study of molecular constituents, temperatures, and dynamics in planetary atmospheres. Its extremely high spectral resolution (Lambda/(Delta)Lambda/>10(exp 6)) and highly accurate frequency measurement (to 1 part in 10(exp 8)) enabled the detection of nonthermal/natural lasing phenomena on Mars and Venus; direct measurements of winds on Venus, Mars, and Titan; study of mid-infrared aurorae on Jupiter; direct measurement of species abundances on Mars (ozone, isotopic CO2), hydrocarbons on Jupiter, Saturn., Neptune, and Titan, and stratospheric composition in the Earth's stratosphere (O3, CIO, N2O, CO2 ....). Fully resolved emission and absorption line shapes measured by this method enabled the unambiguous retrieval of molecular abundances and local temperatures and thermal structure in regions not probed by other techniques. The mesosphere of Mars and thermosphere of Venus are uniquely probed by infrared heterodyne spectroscopy. Results of these studies tested and constrained photochemical and dynamical theoretical models describing the phenomena measured. The infrared heterodyne technique will be described. Highlights in its evolution to today's instrumentation and resultant discoveries will be presented, including work at Goddard Space Flight Center and the University of Koln. Resultant work will include studies supporting NASA and ESA space missions and collaborations between instrumental and theoretical groups.

  13. Infrared Heterodyne Spectroscopy and its Unique Application to Planetary Studies

    Science.gov (United States)

    Kostiuk, Theodore

    2009-01-01

    Since the early 1970's the infrared heterodyne technique has evolved into a powerful tool for the study of molecular constituents, temperatures, and dynamics in planetary atmospheres. Its extremely high spectral resolution (Lambda/(Delta)Lambda/>10(exp 6)) and highly accurate frequency measurement (to 1 part in 10(exp 8)) enabled the detection of nonthermal/natural lasing phenomena on Mars and Venus; direct measurements of winds on Venus, Mars, and Titan; study of mid-infrared aurorae on Jupiter; direct measurement of species abundances on Mars (ozone, isotopic CO2), hydrocarbons on Jupiter, Saturn., Neptune, and Titan, and stratospheric composition in the Earth's stratosphere (O3, CIO, N2O, CO2 ....). Fully resolved emission and absorption line shapes measured by this method enabled the unambiguous retrieval of molecular abundances and local temperatures and thermal structure in regions not probed by other techniques. The mesosphere of Mars and thermosphere of Venus are uniquely probed by infrared heterodyne spectroscopy. Results of these studies tested and constrained photochemical and dynamical theoretical models describing the phenomena measured. The infrared heterodyne technique will be described. Highlights in its evolution to today's instrumentation and resultant discoveries will be presented, including work at Goddard Space Flight Center and the University of Koln. Resultant work will include studies supporting NASA and ESA space missions and collaborations between instrumental and theoretical groups.

  14. Met in Urological Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Yasuyoshi, E-mail: int.doc.miya@m3.dion.ne.jp; Asai, Akihiro; Mitsunari, Kensuke; Matsuo, Tomohiro; Ohba, Kojiro; Mochizuki, Yasushi; Sakai, Hideki [Department of Urology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501 (Japan)

    2014-12-16

    Met is a tyrosine kinase receptor that is considered to be a proto-oncogene. The hepatocyte growth factor (HGF)-Met signaling system plays an important role in tumor growth, invasion, and metastasis in many types of malignancies. Furthermore, Met expression has been reported to be a useful predictive biomarker for disease progression and patient survival in these malignancies. Many studies have focused on the clinical significance and prognostic role of Met in urological cancers, including prostate cancer (PCa), renal cell carcinoma (RCC), and urothelial cancer. Several preclinical studies and clinical trials are in progress. In this review, the current understanding of the pathological role of Met in cancer cell lines, its clinical significance in cancer tissues, and its predictive value in patients with urological cancers are summarized. In particular, Met-related malignant behavior in castration-resistant PCa and the different pathological roles Met plays in papillary RCC and other histological types of RCC are the subjects of focus. In addition, the pathological significance of phosphorylated Met in these cancers is shown. In recent years, Met has been recognized as a potential therapeutic target in various types of cancer; therapeutic strategies used by Met-targeted agents in urological cancers are summarized in this review.

  15. MetLab: An In Silico Experimental Design, Simulation and Analysis Tool for Viral Metagenomics Studies.

    Science.gov (United States)

    Norling, Martin; Karlsson-Lindsjö, Oskar E; Gourlé, Hadrien; Bongcam-Rudloff, Erik; Hayer, Juliette

    2016-01-01

    Metagenomics, the sequence characterization of all genomes within a sample, is widely used as a virus discovery tool as well as a tool to study viral diversity of animals. Metagenomics can be considered to have three main steps; sample collection and preparation, sequencing and finally bioinformatics. Bioinformatic analysis of metagenomic datasets is in itself a complex process, involving few standardized methodologies, thereby hampering comparison of metagenomics studies between research groups. In this publication the new bioinformatics framework MetLab is presented, aimed at providing scientists with an integrated tool for experimental design and analysis of viral metagenomes. MetLab provides support in designing the metagenomics experiment by estimating the sequencing depth needed for the complete coverage of a species. This is achieved by applying a methodology to calculate the probability of coverage using an adaptation of Stevens' theorem. It also provides scientists with several pipelines aimed at simplifying the analysis of viral metagenomes, including; quality control, assembly and taxonomic binning. We also implement a tool for simulating metagenomics datasets from several sequencing platforms. The overall aim is to provide virologists with an easy to use tool for designing, simulating and analyzing viral metagenomes. The results presented here include a benchmark towards other existing software, with emphasis on detection of viruses as well as speed of applications. This is packaged, as comprehensive software, readily available for Linux and OSX users at https://github.com/norling/metlab.

  16. A Unique Facility For Metabolic and Thermoregulatory Studies

    Science.gov (United States)

    Williamson, Rebecca C.; Webbon, Bruce W.

    1995-01-01

    A unique exercise facility has been developed and used to perform tipper body ergometry tests for space applications. Originally designed to simulate the muscular, cardiovascular and thermoregulatory responses to working in zero gravity, this facility may be used to conduct basic thermoregulatory investigations applicable to multiple sclerosis patients. An environmental chamber houses the tipper body ergometer and permits control of temperature, air now and humidify. The chamber is a closed system and recirculate-s air after conditioning if. A Cybex Lipper body ergometer has been mounted horizontally on the wall of the environmental chamber. In this configuration, the subject lies underneath the arm crank on a supine seat in order to turn the crank. The supine seat can be removed in order to introduce other equipment into the chamber such as a stool to allow upright arm cranking, or a treadmill to allow walk-run experiments. Physiological and environmental signals are fed into a Strawberry Tree data acquisition system while being monitored and logged using the Workbench software program. Physiological monitoring capabilities include 3-lead EKG using an H-P patient monitor, 5 site skin temperature and core temperature using YSI thermistors, and O2 consumption and CO2 production using AMFTFK Applied Electrochemistry analyzers and sensors. This comprehensive data acquisition set tip allows for calculation of various thermoregulatory indices including heat storage, evaporative heat loss, latent heat loss, and metabolic rate. The current system is capable of adding more data acquisition channels if needed. Some potential studies that could be carried out using the facility include: 1) An investigation into the efficiency of cooling various segments of the body to lower Tc 1-2 F. 2) A series of heat and mass balance studies comparing various LCG configurations.

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

    OpenAIRE

    2014-01-01

    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 ...

  18. Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Yen Ying Lim

    Full Text Available OBJECTIVE: Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF Val66Met and risk of Alzheimer's disease (AD. As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI and high Aβ. METHODS: Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments. RESULTS: In individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020 and hippocampal volume (d = 0.98, p = .035. BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = -0.35, p = .401. CONCLUSIONS: Although preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD.

  19. Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary results.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    Full Text Available The prevalence of the metabolic syndrome (MetS is higher among patients receiving atypical antipsychotics (AAPs treatment, and even among AAPs, treatment with clozapine has been shown to be associated with a higher long-term incidence rate of MetS. Likewise, brain-derived neurotrophic factor (BDNF deficiency has been reported to result in metabolic traits, such as increased food intake, hyperphagia and obesity, etc. In this study, we hypothesized that a functional polymorphism (Val66Met in the BDNF gene may confer susceptibility to clozapine-induced MetS, potentially in a sex-specific manner, since an interaction between Val66Met polymorphism and sex was observed in our previous studies. A total of 199 schizophrenia patients being treated with clozapine were divided into two groups, MetS and non-MetS, based on the diagnostic criteria of the National Cholesterol Education Program's Adult Treatment Panel III. We genotyped the Val66Met polymorphism, and measured the serum levels of fasting glucose (GLU, triglyceride (TG and high density lipoprotein cholesterol (HDL. There was a trend indicating a significant association between the homozygous Met/Met genotype and MetS in male patients (OR = 2.39; 95% CI: 1.05-5.41; p = 0.039; corrected p = 0.078. Among the six risk factors listed in the ATPIII criteria, we found a significant association between fasting GLU levels and Val66Met polymorphism in males (p = 0.005; corrected p = 0.03, but not in females (p = 0.65. Post-hoc analysis in males revealed that the Met/Met carriers had significant higher levels of fasting GLU than those with Val/Val or Val/Met genotypes (p = 0.007; corrected p = 0.042 and p = 0.002; corrected p = 0.012, respectively. In conclusion, we observed a weak association between the Val66Met polymorphism and clozapine-induced MetS in a sex-specific manner. While preliminary, such findings prompt further, large-scale longitudinal studies to

  20. Effect of COMT Val158Met polymorphism on personality traits and educational attainment in a longitudinal population representative study.

    Science.gov (United States)

    Lehto, K; Akkermann, K; Parik, J; Veidebaum, T; Harro, J

    2013-10-01

    The COMT Val158Met polymorphism has been associated with anxiety and affective disorders, but its effect on anxiety-related personality traits varies between studies. Our purpose was to investigate the effect of COMT Val158Met on personality traits from adolescence to young adulthood in a population representative Caucasian birth cohort. Also its association with educational attainment and anxiety and mood disorders by the age 25 were examined. This analysis is based on the older cohort of the Estonian Children Personality Behavior and Health Study (original number of subjects 593). The personality traits were assessed when the participants were 15, 18 and 25 years old. COMT Val158Met had an effect on Neuroticism in females by age 25 (p=0.001, Bonferroni-corrected for five traits), whereas female Val homozygotes scored the highest. In addition, the Conscientiousness scores of subjects with Val/Val genotype were decreasing in time, being the lowest by the age 25 (p=0.006, Bonferroni-corrected for five traits). By the age 25, males with the Val/Met genotype had mainly secondary or vocational education, whereas female heterozygotes mostly had obtained or were obtaining university education. COMT Val158Met was not associated with anxiety or mood disorders in either gender. These results suggest that genes affecting dopamine system are involved in the development of personality traits and contribute to educational attainment.

  1. Studies of the metastable decay of met-cars. The vanadium and niobium systems

    Science.gov (United States)

    Purnell, J.; Wei, S.; Castleman, A. W., Jr.

    1994-10-01

    The decay fractions and metastable decomposition channels were measured for V(m)C(n)(+) and Nb(m)C(n)(+) clusters using a reflectron time-of-flight mass spectrometer. These measurements for the V(m)C(n)(+) clusters reveal stable (8, 12) and (8, 13) met-car species. However, under the present experimental conditions, the Nb(m)C(n)(+) clusters display dominantly cubic structures, but the decay fraction and metastable decomposition measurements also show the presence of a stable (8, 12) species in the parent cluster spectrum. This evidence indicates that cubic structures and met-cars are being formed simultaneously for the niobium system.

  2. Japanese study to organize proper lifestyle modifications for metabolic syndrome (J-STOP-MetS: Design and method

    Directory of Open Access Journals (Sweden)

    Masanori Munakata

    2008-04-01

    Full Text Available Masanori Munakata1, Hiroki Honma2, Mitugu Akasi3, Takaharu Araki4, Takahiko Kawamura5, Masashi Kubota6, Tomoko Yokokawa7, Akira Maruhashi8, Toshihiro Toyonaga9  On behalf of the J-STOP-MetS Study GroupAll authors belong to Preventive Medical Centers of Rosai Hospital Groups in Japan; 1Tohoku Rosai Hospital, Sendai, Japan; 2Iwamizawa Rosai Hospital, Iwamizawa, Japan; 3Kantou Rosai Hospital, Kawasaki, Japan; 4Tokyo Rosai Hospital, Tokyo, Japan; 5Cyubu Rosai Hospital, Nagoya, Japan; 6Oosaka Rosai Hospital, Sakai, Japan; 7Kansai Rosai Hospital, Amagasaki, Japan; 8Chugoku Rosai Hospital, Kure, Japan; 9Kyusyu Rosai Hospital, Kokura, JapanAbstract: Prevalence of the metabolic syndrome is now a very serious health problem in Japan and a public preventive strategy is essential to reduce morbidity. A systematic interventional strategy for the metabolic syndrome remains to be established. In order to address this issue, a multi-center study; Japanese Study to Organize Proper lifestyle modification for the metabolic syndrome (J-STOP-MetS, has been established by nine preventive medical centers among Rosai hospital groups. This study comprises a cross-sectional study (J-STOP-MetS 1 and a prospective randomized control study (J-STOP-MetS 2. J-STOP-MetS 1 examines the causes of the metabolic syndrome by means of a questionnaire in a large cohort of patients with the metabolic syndrome and control subjects matched for age and sex. J-STOP-MetS 2 examines the hypothesis that guidance on lifestyle modifications will help at risk patients to reduce abdominal fat and cardiovascular risk factors. The metabolic syndrome patients are randomly assigned either to a single visit to a guidance group or multiple visits every two months. The individualized guidance is provided by the coordination of physician, trained nurse, dietician and exercise trainer. Several parameters are measured before and six months after the first guidance session, including, body weight, waist

  3. Voorbereiding pilot studie ‘Power for Teens’ voor tieners met overgewicht en angstige en depressieve klachten.

    NARCIS (Netherlands)

    Bouwman, Miranda; Tuinstra, Jolanda; Visser, Marieke; Cox, R.F.A

    2015-01-01

    Abstract Het huidige onderzoek richtte zich op de voorbereidingen die nodig zijn voor het uitvoeren van een pilot studie van de interventie ‘Power for Teens’. Dit is een interventie voor jongeren met overgewicht, angstige en depressieve klachten en een lage self-efficacy. Voordat de pilot studie uit

  4. 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…

  5. No association between chronic musculoskeletal complaints and Val158Met polymorphism in the Catechol-O-methyltransferase gene. The HUNT study

    Directory of Open Access Journals (Sweden)

    Stovner Lars

    2006-05-01

    Full Text Available Abstract Background The Catechol-O-methyltransferase (COMT gene contains a functional polymorphism, Val158Met, that has been found to influence human pain perception. In one study fibromyalgia was less likely among those with Val/Val genotype. Methods In the 1995–97 Nord-Trøndelag Health Study (HUNT, the association between Val/Met polymorphism at the COMT gene and chronic musculoskeletal complaints (MSCs was evaluated in a random sample of 3017 individuals. Results The distribution of the COMT Val158Met genotypes and alleles were similar between controls and the twelve different chronic MSCs groups. Even when the Met/Met and Val/Met genotypes were pooled, the distribution of the Val/Val genotype and other genotypes were similar between controls and the chronic MSCs groups. Conclusion In this population-based study, no significant association was found between Val/Met polymorphism at the COMT gene and chronic MSCs.

  6. Dicentric chromosomes: unique models to study centromere function and inactivation.

    Science.gov (United States)

    Stimpson, Kaitlin M; Matheny, Justyne E; Sullivan, Beth A

    2012-07-01

    Dicentric chromosomes are products of genome rearrangement that place two centromeres on the same chromosome. Depending on the organism, dicentric stability varies after formation. In humans, dicentrics occur naturally in a substantial portion of the population and usually segregate successfully in mitosis and meiosis. Their stability has been attributed to inactivation of one of the two centromeres, creating a functionally monocentric chromosome that can segregate normally during cell division. The molecular basis for centromere inactivation is not well understood, although studies in model organisms and in humans suggest that genomic and epigenetic mechanisms can be involved. Furthermore, constitutional dicentric chromosomes ascertained in patients presumably represent the most stable chromosomes, so the spectrum of dicentric fates, if it exists, is not entirely clear. Studies of engineered or induced dicentrics in budding yeast and plants have provided significant insight into the fate of dicentric chromosomes. And, more recently, studies have shown that dicentrics in humans can also undergo multiple fates after formation. Here, we discuss current experimental evidence from various organisms that has deepened our understanding of dicentric behavior and the intriguingly complex process of centromere inactivation.

  7. Extended metAFLP approach in studies of tissue culture induced variation (TCIV) in triticale.

    Science.gov (United States)

    Machczyńska, Joanna; Orłowska, Renata; Zimny, Janusz; Bednarek, Piotr Tomasz

    2014-01-01

    We present the development of the theoretical background of the metAFLP approach which allows for partition of complex variation into sequence changes, de novo methylation and demethylation of the regenerants derived via in vitro tissue culture methods in the case of triticale. It was demonstrated that, independent of whether andro- or embryogenesis was used for plant regeneration, the level of sequence changes identified between regenerants is about 10 %. Moreover, DNA demethylation prevails over de novo methylation of the regenerants compared to the donor plant. The metAFLP approach allows for the evaluation of numerous quantitative characteristics. For instance, one may quantify the number of sites unaffected by tissue culture approaches, global site DNA methylation etc. It is suggested that the approach could be useful for breeders in order to control plant material uniformity or for the evaluation of modified in vitro tissue culture approaches allowing for control of the (epi)mutation level. The extended metAFLP approach presented here delivers sufficient background for the evaluation of software that could facilitate analyses of the tissue culture induced variation.

  8. A Unique Case of Intraabdominal Polyorchidism: A Case Study

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    Javier Otero

    2016-01-01

    Full Text Available Background. Polyorchidism, alternatively supernumerary testes (SNT, is a condition where an individual is born with more than two testicles. This congenital anomaly is quite rare and the literature has described various presentations. Questions/Purposes. To our knowledge, this presentation of polyorchidism has yet to be described in the literature. The goal of this case study is to add to the pediatric, general, and urologic surgery’s body of knowledge of the subject matter. Case Study. A nine-month-old boy was admitted for an impalpable right testis and phimosis. At the time of surgical exploration, there appeared to be polyorchid testis on the right-hand side, with three masses that potentially appeared to be undescended testes. Discussion. Proponents of a conservative approach argue that infertility is common in patients with polyorchidism and, by preserving a potentially functional SNT, there may be improved spermatogenesis. When performing definitive surgical treatment, meticulous intra-abdominal and intrainguinal exploration must be undertaken. Orchiopexy should be performed to reduce the chances of torsion, malignancy, and infertility. Conclusion. Our case is important to the literature as it is the first known case of polyorchidism with 3 SNT on the right side, located intra-abdominally, and in a patient less than 1 year of age.

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

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    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.

  10. Digging for Treasure - Unique Fate and Transport Study

    Energy Technology Data Exchange (ETDEWEB)

    Larry Zirker; M. K. Adler-Flitton; G. A. Beitel

    2003-02-01

    In 1970, scientists at the National Bureau of Standards (NBS), now called the National Institute of Standards and Testing (NIST), implemented the most ambitious and comprehensive long-term corrosion behavior test for stainless steels in soil environments. This study had historic significance since the NBS 1957 landmark corrosion textbook compiled by Romanoff did not include stainless steels, and this 1970 research set forth to complete the missing body of knowledge. To conduct the test, NIST scientists buried 6,324 coupons from stainless steel types, specialty alloys, composite configurations, multiple material forms, and treatment conditions at six distinctive soil-type sites throughout the country. Between 1971 and 1980, four sets of coupons were removed from the six sites to establish 1-year, 2-year, 4-year, and 8- year corrosion rates data sets for different soil environments. The fifth and last set of coupons (approximately 200 at each site) remains undisturbed after 32-years, providing a virtual buried treasure of material and subsurface scientific data. These buried coupons and the surrounding soils represent an analog to the condition of buried waste and containers. Heretofore, the samples were simply pulled from the soil, measured for mass loss and the corrosion rate determined while the subsurface/fate and transport information was not considered nor gathered. Funded through an Environmental Management Science Program (EMSP) proposal, the Idaho National Engineering and Environmental Laboratory (INEEL) operated for the U.S. Department of Energy by Bechtel-BWXT Idaho, LLC (BBWI), is chartered to restart this corrosion test and concurrently capture the available subsurface/fate and transport information. Since the work of retrieving the buried metal coupons is still in the planning stage, this paper outlines the interdisciplinary team of scientists and engineers and defines the benefits of this research to long-term stewardship, subsurface science, and

  11. Digging for Treasure - Unique Fate and Transport Study

    Energy Technology Data Exchange (ETDEWEB)

    Zirker, L.R.; Adler-Flitton, M.K.; Beitel, G.A.

    2003-02-24

    In 1970, scientists at the National Bureau of Standards (NBS), now called the National Institute of Standards and Testing (NIST), implemented the most ambitious and comprehensive long-term corrosion behavior test for stainless steels in soil environments. This study had historic significance since the NBS 1957 landmark corrosion textbook compiled by Romanoff did not include stainless steels, and this 1970 research set forth to complete the missing body of knowledge. To conduct the test, NIST scientists buried 6,324 coupons from stainless steel types, specialty alloys, composite configurations, multiple material forms, and treatment conditions at six distinctive soil-type sites throughout the country. Between 1971 and 1980, four sets of coupons were removed from six sites to establish 1-year, 2-year, 4-year, and 8-year corrosion rates data sets for different soil environments. The fifth and last set of coupons (approximately 200 at each site) remains undisturbed after 32-years, providing a virtual buried treasure of material and subsurface scientific data. These buried coupons and the surrounding soils represent an analog to the condition of buried waste and containers. Heretofore, the samples were simply pulled from the soil, measured for mass loss and the corrosion rate determined while the subsurface/fate and transport information was not considered nor gathered. Funded through an Environmental Management Science Program (EMSP) proposal, the Idaho National Engineering and Environmental Laboratory (INEEL) operated for the U.S. Department of Energy by Bechtel-BWXT Idaho, LLC (BBWI), is chartered to restart this corrosion test and concurrently capture the available subsurface/fate and transport information. Since the work of retrieving the buried metal coupons is still in the planning stage, this paper outlines the interdisciplinary team of scientists and engineers and defines the benefits of this research to long-term stewardship, subsurface science, and

  12. MetSizeR: selecting the optimal sample size for metabolomic studies using an analysis based approach

    Science.gov (United States)

    2013-01-01

    Background Determining sample sizes for metabolomic experiments is important but due to the complexity of these experiments, there are currently no standard methods for sample size estimation in metabolomics. Since pilot studies are rarely done in metabolomics, currently existing sample size estimation approaches which rely on pilot data can not be applied. Results In this article, an analysis based approach called MetSizeR is developed to estimate sample size for metabolomic experiments even when experimental pilot data are not available. The key motivation for MetSizeR is that it considers the type of analysis the researcher intends to use for data analysis when estimating sample size. MetSizeR uses information about the data analysis technique and prior expert knowledge of the metabolomic experiment to simulate pilot data from a statistical model. Permutation based techniques are then applied to the simulated pilot data to estimate the required sample size. Conclusions The MetSizeR methodology, and a publicly available software package which implements the approach, are illustrated through real metabolomic applications. Sample size estimates, informed by the intended statistical analysis technique, and the associated uncertainty are provided. PMID:24261687

  13. BDNF Val66Met genotype and neuroticism predict life stress: A longitudinal study from childhood to adulthood.

    Science.gov (United States)

    Lehto, Kelli; Mäestu, Jarek; Kiive, Evelyn; Veidebaum, Toomas; Harro, Jaanus

    2016-03-01

    The brain-derived neurotrophic factor gene (BDNF) Val66Met polymorphism and life stress have been associated with negative emotionality (e.g., neuroticism), but relevant evidence is far from unequivocal. Possible confounding factors include the type and timing of stressful events measured, such as childhood adversity vs. recent stressful events, and variable gene × environment interactions. The aim of this study was to longitudinally assess the BDNF Val66Met polymorphism and environment interaction effect on neuroticism in a population representative sample, depending upon the type of stress, gender and family relations. In the original older cohort of the Estonian Children Personality Behavior and Health Study (ECPBHS, n=593), neuroticism was measured at age 15 (parental assessment), 18 and 25 (self-assessments). Childhood stress was reported at age 15, quality of family relations was measured at age 18, and recent stressful life events at age 25. The BDNF Val66Met polymorphism interacted with recent stressful life events, but not with childhood adversities, to impact neuroticism. Interestingly, in female participants, neuroticism at age 18 predicted future stressful life events dependent upon genotype: individuals with Val/Val genotype and high neuroticism experienced higher, but Met-allele carriers with high neuroticism lower stress exposure at age 25. Similar tendencies were observed using parental assessments at age 15. The protective effect of Met-allele in the high stress exposure group could result from better early family environment. In conclusion, we herewith provide further evidence for a role of BDNF gene variance contributing to plasticity in response to environmental demands.

  14. Signal to Noise Ratio Estimations for a Volcanic ASH Detection Lidar. Case Study: The Met Office

    Science.gov (United States)

    Georgoussis, George; Adam, Mariana; Avdikos, George

    2016-06-01

    In this paper we calculate the Signal-to-Noise (SNR) ratio of a 3-channel commercial (Raymetics) volcanic ash detection system, (LR111-D300), already operating under Met Office organization. The methodology for the accurate estimation is presented for day and nighttime conditions. The results show that SNR values are higher than 10 for ranges up to 13 km for both nighttime and daytime conditions. This is a quite good result compared with other values presented in bibliography and proves that such system is able to detect volcanic ash over a range of 20 km.

  15. Signal to Noise Ratio Estimations for a Volcanic ASH Detection Lidar. Case Study: The Met Office

    Directory of Open Access Journals (Sweden)

    Georgoussis George

    2016-01-01

    Full Text Available In this paper we calculate the Signal-to-Noise (SNR ratio of a 3-channel commercial (Raymetics volcanic ash detection system, (LR111-D300, already operating under Met Office organization. The methodology for the accurate estimation is presented for day and nighttime conditions. The results show that SNR values are higher than 10 for ranges up to 13 km for both nighttime and daytime conditions. This is a quite good result compared with other values presented in bibliography and proves that such system is able to detect volcanic ash over a range of 20 km.

  16. 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.

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

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    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.

  18. The effects of catechol-O-methyl-transferase polymorphism Val158Met on functional connectivity in healthy young females: a resting EEG study.

    Science.gov (United States)

    Lee, Tien-Wen; Yu, Younger W-Y; Hong, Chen-Jee; Tsai, Shih-Jen; Wu, Hung-Chi; Chen, Tai-Jui

    2011-03-04

    The catechol-O-methyl-transferase (COMT) gene has been linked to a wide spectrum of human phenotypes, including cognition, affective response, pain sensitivity, anxiety and psychosis. This study examined the modulatory effects of COMT Val158Met on neural interactions, indicated by connectivity strengths. Blood samples and resting state eyes-closed EEG signals were collected in 254 healthy young females. The COMT Val158Met polymorphism was decoded into 3 groups: Val/Val, Val/Met and Met/Met. The values of mutual information of 20 frontal-related channel pairs across delta, theta, alpha and beta frequencies were analyzed based on the time-frequency mutual information method. Our one-way ANOVA analyses revealed that the significant connection-frequency pairs were relatively left lateralized (PF7-T3 and F7-C3 at delta frequency, and F3-F4, F7-T3, F7-C3, F7-P3, F3-C3, F3-F7 and F4-F8 at theta frequency. The F-test at F7-T3 and F7-C3 theta surpassed the statistical threshold of PVal/Met>Met/Met. Our analyses complemented previous literature regarding neural modulation by the COMT Val158Met polymorphism. The implication to the pathogenesis in schizophrenia was also discussed. Further studies are needed to clarify whether there is gender difference on this gene-brain interaction. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Phase II study evaluating 2 dosing schedules of oral foretinib (GSK1363089, cMET/VEGFR2 inhibitor, in patients with metastatic gastric cancer.

    Directory of Open Access Journals (Sweden)

    Manish A Shah

    Full Text Available PURPOSE: The receptors for hepatocyte and vascular endothelial cell growth factors (MET and VEGFR2, respectively are critical oncogenic mediators in gastric adenocarcinoma. The purpose is to examine the safety and efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR2 receptors, for the treatment of metastatic gastric adenocarcinoma. PATIENTS AND METHODS: Foretinib safety and tolerability, and objective response rate (ORR were evaluated in patients using intermittent (240 mg/day, for 5 days every 2 weeks or daily (80 mg/day dosing schedules. Thirty evaluable patients were required to achieve alpha = 0.10 and beta = 0.2 to test the alternative hypothesis that single-agent foretinib would result in an ORR of ≥ 25%. Up to 10 additional patients could be enrolled to ensure at least eight with MET amplification. Correlative studies included tumor MET amplification, MET signaling, pharmacokinetics and plasma biomarkers of foretinib activity. RESULTS: From March 2007 until October 2009, 74 patients were enrolled; 74% male; median age, 61 years (range, 25-88; 93% had received prior therapy. Best response was stable disease (SD in 10 (23% patients receiving intermittent dosing and five (20% receiving daily dosing; SD duration was 1.9-7.2 months (median 3.2 months. Of 67 patients with tumor samples, 3 had MET amplification, one of whom had SD. Treatment-related adverse events occurred in 91% of patients. Rates of hypertension (35% vs. 15% and elevated aspartate aminotransferase (23% vs. 8% were higher with intermittent dosing. In both patients with high baseline tumor phospho-MET (pMET, the pMET:total MET protein ratio decreased with foretinib treatment. CONCLUSION: These results indicate that few gastric carcinomas are driven solely by MET and VEGFR2, and underscore the diverse molecular oncogenesis of this disease. Despite evidence of MET inhibition by foretinib, single-agent foretinib lacked efficacy in

  20. Depression and anxiety in relation to catechol-O-methyltransferase Val158Met genotype in the general population: The Nord-Trøndelag Health Study (HUNT

    Directory of Open Access Journals (Sweden)

    Zwart John-Anker

    2008-06-01

    Full Text Available Abstract Background The catechol-O-methyltransferase (COMT gene contains a functional polymorphism, Val158Met, which has been linked to anxiety and depression, but previous results are not conclusive. The aim of the present study was to examine the relationship between the Val158Met COMT gene polymorphism and anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS in the general adult population. Methods In the Nord-Trøndelag Health Study (HUNT the association between the Val158Met polymorphism and anxiety and depression was evaluated in a random sample of 5531 individuals. Two different cut off scores (≥ 8 and ≥ 11 were used to identify cases with anxiety (HADS-A and depression (HADS-D, whereas controls had HADS-A Results The COMT genotype distribution was similar between controls and individuals in the groups with anxiety and depression using cut-off scores of ≥ 8. When utilizing the alternative cut-off score HADS-D ≥ 11, Met/Met genotype and Met allele were less common among men with depression compared to the controls (genotype: p = 0.017, allele: p = 0.006. In the multivariate analysis, adjusting for age and heart disease, depression (HADS-D ≥ 11 was less likely among men with the Met/Met genotype than among men with the Val/Val genotype (OR = 0.37, 95% CI = 0.18–0.76. Conclusion In this population-based study, no clear association between the Val158Met polymorphism and depression and anxiety was revealed. The Met/Met genotype was less likely among men with depression defined as HADS-D ≥ 11, but this may be an incidental finding.

  1. 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).…

  2. 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

  3. Metformin and its effects on myocardial dimension and left ventricular hypertrophy in normotensive patients with coronary heart disease (the MET-REMODEL study): rationale and design of the MET-REMODEL study.

    Science.gov (United States)

    Mohan, Mohapradeep; McSwiggan, Stephen; Baig, Fatima; Rutherford, Lynn; Lang, Chim C

    2015-02-01

    Left ventricular hypertrophy (LVH) is a common and independent risk factor for cardiovascular events in patients with coronary artery disease (CAD). Controlling blood pressure is the standard approach to the management of LVH, but this is only partially effective as LVH also persists in normotensive patients. Apart from blood pressure (BP), other main risk factors associated with LVH are insulin resistance (IR) and central obesity. The diabetic medication, Metformin, reduces IR and aids weight loss and may therefore regress LVH. The MET REMODEL study will investigate the ability of Metformin to regress LVH in 64 patients with CAD. The MET-REMODEL trial is a single-center, phase IV, double blind, randomized, placebo-controlled trial to investigate the efficacy of Metformin in regression of the independent cardiac risk factor of LVH in patients with CAD who are insulin resistant. A minimum of 64 adults with a history of CAD with LVH and IR will be randomized into two groups to receive, either Metformin XL or placebo. The primary endpoint of this trial is to investigate any change in left ventricular mass index. Secondary endpoints include changes to insulin resistance measured using fasting insulin resistance index (FIRI), obesity, LV size, and function and improvement in endothelial function. A positive result will assist clinicians to identify a new mechanism for LVH regression by administering Metformin XL. This may also lead to investigating the mortality benefit of Metformin in patients with CAD and LVH.

  4. 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

  5. Effectiviteit van leerkrachtgedrag. Een empirische studie naar leerkrachtgedrag en de samenhang met leerwinst

    NARCIS (Netherlands)

    Westerhof, Klaas Jacob

    1989-01-01

    The effects of schools and teachers on the student's learning are of great interest to educational researchers. This thesis reports on two empirical studies on teacher behaviour in primary education (education for children aged 4 to t2). In the first study, which consists of four case studies, the n

  6. 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.

  7. No evidence of association between Catechol-O-Methyltransferase (COMT Val158Met genotype and performance on neuropsychological tasks in children with ADHD: A case-control study

    Directory of Open Access Journals (Sweden)

    O'Donovan Michael C

    2004-06-01

    Full Text Available Abstract Background Several studies have suggested an association between the functional Val158Met polymorphism in the Catechol-O-Methyltransferase (COMT gene and neurocognitive performance. Two studies showed that subjects with the low activity Met allele performed better on the Wisconsin Card Sorting Test (WCST and another study found an effect on processing speed and attention. Methods We set out to examine the association between the Val158Met polymorphism and performance on neurocognitive tasks including those tapping working memory, attention and speed, impulsiveness and response inhibition in a sample of 124 children with ADHD. Task performance for each genotypic group was compared using analysis of variance. Results There was no evidence of association with performance on any of the neurocognitive tasks. Conclusions We conclude that Val158Met COMT genotype is not associated with neurocognitive performance in our sample.

  8. 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.

  9. 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.

  10. 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 diff

  11. Planetary wave coupling processes in the middle atmosphere (30 90 km): A study involving MetO and MFR data

    Science.gov (United States)

    Chshyolkova, T.; Manson, A. H.; Meek, C. E.; Avery, S. K.; Thorsen, D.; MacDougall, J. W.; Hocking, W.; Murayama, Y.; Igarashi, K.

    2006-02-01

    The MetO assimilated data and mesospheric winds provided by five medium frequency radars (MFR) from the Canada US Japan Opportunity (CUJO) network have been used to study coupling processes due to planetary waves (PWs) in the middle atmosphere. It is shown that there is strong vertical coupling between the stratosphere and mesosphere especially during winter months. However, not all observed disturbances in mesospheric winds can be explained by the simple propagation of PWs from below. In addition to the vertical coupling there is also weaker horizontal “inter-hemispheric” coupling during equinoxes. The data used are from December 2000 to December 2002. The time interval was chosen to include austral winters and springs of 2 years: the dynamically unusual year 2002, during which a major stratospheric warming involving a split vortex and wind reversals occurred in the Southern Hemisphere, and a more typical year 2001. The character of PW activity during these 2 years is compared. In contrast to the usually weak PW activity dominated by eastward motions, both strong eastward and westward propagating waves existed during austral winter of 2002. Wavelet spectra of MetO winds show strong peaks near 14 days that match similar signals observed in mesospheric winds at Antarctic stations [Dowdy et al., 2004. The large-scale dynamics of the mesosphere lower thermosphere during the SH stratospheric warming of 2002. Geophysical Research Letters 31, L14102. doi:10.1029/2004GL020282] during the stratospheric warming. It is suggested that this oscillation was generated at low atmospheric heights and propagated upward. The longer duration of the stratospheric mesospheric winter vortex (7 months) compared to that of the summer jet in the Northern Hemisphere provide equinoctial months when eastward winds dominate globally. Results suggest that during equinoxes, with favourable conditions, the PWs with ˜10-, 16- and 25-day periods can penetrate to the opposite hemisphere.

  12. 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.

  13. BDNF Val66Met polymorphism, energy intake and BMI: a follow-up study in schoolchildren at risk of eating disorders

    Directory of Open Access Journals (Sweden)

    Aranda Nuria

    2010-06-01

    Full Text Available Abstract Background Eating disorders (ED have a multifactorial aetiology in which genetics play an important role. Several studies have found an association between the Val66Met (G196A polymorphism of the Brain-Derived Neurotrophic Factor (BDNF and Eating disorders. The aim of this study was to determine the association of the Val66Met (G196A polymorphism of the BDNF gene and its effect on eating disorders (ED, energy intake and BMI in schoolchildren. Methods Two-year cohort study (preadolescence to adolescence. From an initial sample of 1336 Caucasian children (mean age = 11.37 years, a group at risk of ED (n = 141 and a control group (n = 117 were selected using the Children's Eating Attitudes Test. Two years later, they were re-classified into an at-risk group (n = 41 and a control group (n = 159 using the Eating Attitudes Test. The diagnosis of the individuals at risk of ED was confirmed by means of the Diagnostic Interview for Children and Adolescents. BMI, energy intake and the Val66Met (G196A polymorphism of the BDNF gene were analysed in the at-risk and control groups. Results The frequency of genotypes of the Val66Met (G196A polymorphism of the BDNF gene is 28.6% (95% CI: 22.4-34.9 in the heterozygous form (Val/Met and 5% (95% CI: 2.4-9 in the homozygous form (Met/Met. We detected no association between Val66Met genotypes and the severity of ED. Over time, the carriers of the Met66 allele with a persistent risk of ED significantly restricted energy intake (507 Kcal/day; p = 0.033. Conclusion We have not found an association between Val66Met (G196A polymorphism of the BDNF and ED in schoolchildren from general population. The relationship found between this polymorphism and energy intake restriction in adolescents with a persistent risk of ED should be replicated in a larger sample.

  14. Mesostoma ehrenbergii spermatocytes--a unique and advantageous cell for studying meiosis.

    Science.gov (United States)

    Ferraro-Gideon, Jessica; Hoang, Carina; Forer, Arthur

    2013-09-01

    Mesostoma ehrenbergii have a unique male meiosis: their spermatocytes have three large bivalents that oscillate for 1-2 h before entering into anaphase without having formed a metaphase plate, have a precocious ('pre-anaphase') cleavage furrow, and have four univalents that segregate between spindle poles without physical interaction between them, that is via 'distance segregation'. These unique and unconventional features make Mesostoma spermatocytes an ideal organism for studying the force produced by the spindle to move chromosomes, and to study cleavage furrow control and 'distance segregation'. We review the literature on meiosis in Mesostoma spermatocytes and describe our current research with Mesostoma spermatocytes, rearing the animals in the laboratory using methods that described in our companion article [Hoang et al. (2013); Cell Biol Int].

  15. Theoretical study of fMet-tRNA and fAla-tRNA structures by using quantum calculation

    Directory of Open Access Journals (Sweden)

    M. Noei

    2016-11-01

    Full Text Available In the prokaryotes, protein synthesis always starts with N-formylmethionine amino acid. Comparison of this amino acid with other amino acids is attempted and that is why formylmethionine is always the first amino acid to begin protein synthesis, in this paper we added a formyl group to alanine amino acid and then studied it when attached to the tRNA molecule and compared this structure with formylmethionine-tRNA structure. The quantum chemical calculations have performed using Gaussian 03 suite of programs. The fAla-tRNA and fMet-tRNA structures have fully optimized at the HF and B3LYP levels with 3–21G∗ and 6–31G∗ basis sets as well as MP2/3–21G∗ level and theoretically solvent effects on the structures were investigated. Then we studied electronic structures of the compounds using Natural Bond Orbital (NBO analysis and calculated NMR parameters at the gas-phase. Frequency analysis was also calculated at the HF and B3LYP/3-21G∗ levels in the different solvents in 298.15 K, 310.15 K temperatures and 1.00 atmosphere pressure.

  16. 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.

  17. Optimal cut points of waist circumference (WC) and visceral fat area (VFA) predicting for metabolic syndrome (MetS) in elderly population in the Korean Longitudinal Study on Health and Aging (KLoSHA).

    Science.gov (United States)

    Lim, Soo; Kim, Jung Hee; Yoon, Ji Won; Kang, Seon Mee; Choi, Sung Hee; Park, Young Joo; Kim, Ki Woong; Cho, Nam Han; Shin, Hayley; Park, Kyong Soo; Jang, Hak Chul

    2012-01-01

    Optimal cut points of central obesity identifying subjects at risk for MetS were proposed ethnic-specifically, but have not been established yet. Of particular interest are the values for elderly persons, which have not been identified previously. We investigated the appropriate cut points of WC and VFA for elderly in a community-based cohort in Korea. We recruited 294 men and 313 women aged 65 or over who participated in the KLoSHA. A receiver operating characteristic (ROC) curve analysis was used to estimate the optimal cut points of WC and VFA indicative of MetS. The optimal cut points for predicting MetS were 87 cm for WC, 140 cm(2) for VFA in men, and 85 cm for WC, 100 cm(2) for VFA in women with the Youden index. Similar cut points were obtained with the closest-to-(0, 1) criterion except for VFA in men, which was 122 cm(2). When adjusted for age, exercise, smoking, and alcohol consumption, men with ≥122 cm(2) and women with ≥100 cm(2) of VFA had a higher risk of MetS than subjects with lower values. The cut points of VFA and WC at risk for MetS were higher in men than women. In this community-based elderly cohort, the optimal cut points of WC at risk for MetS were lower than the Western criteria. Compared with the cut points in middle-aged Koreans, the cut points for elderly were lower in men and similar in women.

  18. Quantitative study on exact reconstruction sampling condition by verifying solution uniqueness in limited-view CT.

    Science.gov (United States)

    Yan, Bin; Zhang, Wenkun; Li, Lei; Zhang, Hanming; Wang, Linyuan

    2016-10-01

    In limited-view computed tomography reconstruction, iterative image reconstruction with sparsity-exploiting methods, such as total variation (TV) minimization, inspired by compressive sensing, potentially claims large reductions in sampling requirements. However, a quantitative notion of this claim is non-trivial because of the ill-defined reduction in sampling achieved by the sparsity-exploiting method. In this paper, exact reconstruction sampling condition for limited-view problem is studied by verifying the uniqueness of solution in TV minimization model. Uniqueness is tested by solving a convex optimization problem derived from the sufficient and necessary condition of solution uniqueness. Through this method, the sufficient sampling number of exact reconstruction is quantified for any fixed phantom and settled geometrical parameter in the limited-view problem. This paper provides a reference to quantify the sampling condition. Three phantoms are tested to study the sampling condition of limited view exact reconstruction in this paper. The experiment results show the quantified sampling number and indicate that an object would be accurately reconstructed as the scanning range becomes narrower by increasing sampling number. The increased samplings compensate for the deficiency of the projection angle. However, the lower bound of the scanning range corresponding to three different phantoms are presented, in which an exact reconstruction cannot be obtained once the projection angular is narrowed to this extent no matter how to increase sampling.

  19. Met Expectations and Satisfaction with Duration: A Patient-Centered Evaluation of Breastfeeding Outcomes in the Infant Feeding Practices Study II.

    Science.gov (United States)

    Gregory, Emily F; Butz, Arlene M; Ghazarian, Sharon R; Gross, Susan M; Johnson, Sara B

    2015-08-01

    Breastfeeding expectations predict breastfeeding duration. The extent to which expectations for duration are met remains unknown. To evaluate prospective measures of expected breastfeeding duration, changes in expectations over time, and factors associated with meeting expectations. The Infant Feeding Practices Study II followed women from late pregnancy to 1 year postpartum. Expected breastfeeding duration was assessed 5 times. Logistic regression identified factors associated with met prenatal expectations. Subgroup analysis compared met prenatal expectations to satisfaction with breastfeeding duration. One-year postpartum, 34.7% of 1802 participants had met prenatal expected breastfeeding duration, and 23.9% were still breastfeeding. Fifty-eight percent of women met expectations stated at 7 months postpartum. Modifiable risk factors associated with meeting prenatal expectations included early regular breast pump use (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.18-2.07). Return to work was negatively associated with met expectations (return by 6 weeks postpartum: OR, 0.48; 95% CI, 0.33-0.71; later return: OR, 0.73; 95% CI, 0.56-0.95). Among those who reported on satisfaction with duration (n = 1226), 40.4% were satisfied. Satisfaction was associated with meeting expectations (OR, 10.56; 95% CI, 7.67-14.55), but expectation and satisfaction measures were not equivalent. Elevated body mass index and depressive symptoms at 2 months postpartum were negatively associated with both measures. Most participants did not meet prenatal or postnatal expectations for breastfeeding duration and were unsatisfied with duration. However, at 12 months, more participants felt they had met their expectations and were satisfied with their breastfeeding duration than were actually breastfeeding. Therefore, women may perceive greater breastfeeding progress than suggested by Healthy People 2020 benchmarks. © The Author(s) 2015.

  20. Unique features of HLA-mediated HIV evolution in a Mexican cohort: a comparative study

    Directory of Open Access Journals (Sweden)

    Brumme Zabrina L

    2009-08-01

    Full Text Available Abstract Background Mounting evidence indicates that HLA-mediated HIV evolution follows highly stereotypic pathways that result in HLA-associated footprints in HIV at the population level. However, it is not known whether characteristic HLA frequency distributions in different populations have resulted in additional unique footprints. Methods The phylogenetic dependency network model was applied to assess HLA-mediated evolution in datasets of HIV pol sequences from free plasma viruses and peripheral blood mononuclear cell (PBMC-integrated proviruses in an immunogenetically unique cohort of Mexican individuals. Our data were compared with data from the IHAC cohort, a large multi-center cohort of individuals from Canada, Australia and the USA. Results Forty three different HLA-HIV codon associations representing 30 HLA-HIV codon pairs were observed in the Mexican cohort (q Conclusion Our data support universal HLA-mediated HIV evolution at the population level, resulting in detectable HLA-associated footprints in the circulating virus. However, it also strongly suggests that unique genetic backgrounds in different HIV-infected populations may influence HIV evolution in a particular direction as particular HLA-HIV codon associations are determined by specific HLA frequency distributions. Our analysis also suggests a dynamic HLA-associated evolution in HIV with fewer HLA-HIV codon associations observed in the proviral compartment, which is likely enriched in early archived HIV sequences, compared to the plasma virus compartment. These results highlight the importance of comparative HIV evolutionary studies in immunologically different populations worldwide.

  1. Preserving a Unique Archive for Long-Term Solar Variability Studies

    Science.gov (United States)

    Webb, David F.; Hewins, Ian; McFadden, Robert; Emery, Barbara; Gibson, Sarah; Denig, William

    2016-05-01

    In 1964 (solar cycle 20) Patrick McIntosh began creating hand-drawn synoptic maps of solar activity, based on Hydrogen alpha (Hα) imaging measurements. These synoptic maps were unique because they traced the polarity inversion lines (PILs), connecting widely separated filaments, fibril patterns and plage corridors to reveal the large-scale organization of the solar magnetic field. He and his assistants later included coronal hole (CH) boundaries to the maps, usually from ground-based He-I 10830 images. They continued making these maps until 2010 (the start of solar cycle 24), yielding more than 40 years (~ 540 Carrington rotations) or nearly four complete solar cycles (SCs) of synoptic maps. The McIntosh collection of maps forms a unique and consistent set of global solar magnetic field data, and are unique tools for studying the structure and evolution of the large-scale solar fields and polarity boundaries, because: 1) they have excellent spatial resolution for defining polarity boundaries, 2) the organization of the fields into long-lived, coherent features is clear, and 3) the data are relatively homogeneous over four solar cycles. After digitization and archiving, these maps -- along with computer codes permitting efficient searches of the map arrays -- will be made publicly available at NOAA’s National Centers for Environmental Information (NCEI) in their final, searchable form. This poster is a progress report of the project so far and some suggested scientific applications.

  2. 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).

  3. 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.

  4. Molecular modeling studies and synthesis of novel quinoxaline derivatives with potential anticancer activity as inhibitors of c-Met kinase.

    Science.gov (United States)

    Abbas, Hebat-Allah S; Al-Marhabi, Aisha R; Eissa, Sally I; Ammar, Yousry A

    2015-10-15

    In an effort to develop potent anti-cancer agents, we have synthesized some substituted quinoxaline derivatives. Reaction of 6-bromo-3-methylquinoxalin-2(1H)-one 1 with aromatic aldehydes furnished the styryl derivatives 2a-e. Alkylation of 1 with ethyl chloroacetate produced the N-alkyl derivatives 3. Hydrazinolysis of the ester derivative 3 with hydrazine hydrate afforded the hydrazide derivative 4. In addition, chlorination of 1 with phosphorus oxychloride afforded the 2-chloro derivative 5 which was used as a key intermediate for the synthesis of substituted quinoxaline derivatives 6-8, N-pyrazole derivative 9, tetrazolo[1,5-a]quinoxaline derivative 10 and Schiff base derivatives 13, 15 via reaction with several nucleophiles reagents. Docking methodologies were used to predict their binding conformation to explain the differences of their tested biological activities. All the tested compounds were screened in vitro for their cytotoxic effect on three tumor cell lines. Some new quinoxaline derivatives were studied as inhibitors of c-Met kinase, a receptor associated with high tumor grade and poor prognosis in a number of human cancers. Compounds 2e, 4, 7a, 12a, 12b and 13 showed the highest binding affinity with CDOCKER energy score, while showed the lowest IC50 values against three types of cancer cell lines. It is worth to mention that, compounds 2e, 7a, 12b and 13 showed comparable inhibition activity to the reference drug, while compounds 4 and 12a showed a more potent inhibition activity than Doxorubicin.

  5. Study on the Existence and Uniqueness of Solution of Generalized Capillarity Problem

    Directory of Open Access Journals (Sweden)

    Li Wei

    2012-01-01

    Full Text Available By using the perturbation theories on sums of ranges of nonlinear accretive mappings of Calvert and Gupta (1978, the abstract result on the existence and uniqueness of the solution in Lp(Ω of the generalized Capillarity equation with nonlinear Neumann boundary value conditions, where 2N/(N+1studied. The equation discussed in this paper and the methods here are a continuation of and a complement to the previous corresponding results. To obtain the results, some new techniques are used in this paper.

  6. Hanohano: A Deep Ocean Anti-Neutrino Detector for Unique Neutrino Physics and Geophysics Studies

    CERN Document Server

    Learned, John G; Pakvasa, Sandip

    2008-01-01

    The science potential of a 10 kiloton deep-ocean liquid scintillation detector for ~1 MeV energy scale electron anti-neutrinos has been studied. Such an instrument, designed to be portable and function in the deep ocean (3-5 km) can make unique measurements of the anti-neutrinos from radioactive decays in the Earth'.s mantle. Ths information speaks to some of the most fundamental questions in geology about the origin of the Earth, plat e tectonics, the geomagnetic field and even somewhat indirectly to global warming. Measurements in multiple locations will strengthen the potential insights. On the particle physics side, we have identified a unique role in the study of anti-neutrinos from a nuclear power complex, at a range of 55-60 km off shore. Not only can precision measurements be made of most neutrino mixing parameters, including $\\theta_{13}$ (depending on magnitude), but the neutrino mass hierarchy can be determined in a method not heretofore discussed, and one which does not rely upon matter effects. T...

  7. 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

    SCF has been shown to synergize with G-CSF to mobilize CD34(+) PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with malignant lymphoma randomized to receive recombinant methionyl human SCF (ancestim, r-metHuSCF) in combination with recombinant me...

  8. nMET, A New Target in Recurrent Cancer.

    Science.gov (United States)

    Xie, Yingqiu; Istayeva, Sholpan; Chen, Zhanlin; Tokay, Tursonjan; Zhumadilov, Zhaxybay; Wu, Denglong; Hortelano, Gonzalo; Zhang, Jinfu

    2016-01-01

    Membranous Met is classically identified with its role in cancer metastases, while nuclear Met is associated with a more invasive, aggressive and proliferative form of cancer. Full-length Met or N-terminal transmembrane domain cleaved Met can translocate into nucleus in a cell growth and pH dependent but both ligand-dependent (full length Met) and -independent (cleaved Met) manner. nMET may play greater essential roles in cancer recurrence than membranous Met. For example, in prostate cancer, it has been found that androgen receptor (AR) may inhibit the expression of membranous Met so anti-androgen based prostate cancer therapy may promote the expression of nuclear Met (nMET). We recently found a novel nMET/SOX9/ β-Catenin/AR pathway in relapsed prostate cancer which may contribute to the formation of the feedback loop of AR reactivation via MET/nMET. Emerging evidence suggests the possibility of nMET as a prognostic marker in relapsed cancer. This review summarizes recent findings about nMET and its unique role in recurrent cancer.

  9. Determination of the heavy metal binding capacity of aquatic samples using MetPLATE: a preliminary study.

    Science.gov (United States)

    Huang, F; Bitton, G; Kong, I C

    1999-08-30

    MetPLATE, a microbial toxicity test which is specific for heavy metal toxicity, was used to rapidly determine the heavy metal binding capacity (HMBC) of a wide range of surface waters from Florida and Georgia. HMBC determines the impact of physicochemical factors on metal bioavailability and toxicity. The new developed protocol, using MetPLATE as the toxicity assay, showed that HMBC varied from 1.7 to 39.2 for Cd whereas the ranges for Cu and Ag were Hogtown Creek, Gainesville, FL, and from the St John's river in Jacksonville, FL. Both surface waters displayed the highest HMBC during the Fall season. Preliminary examination of the limited data set confirms that HMBC may be influenced by the concentration of dissolved organic carbon (DOC). These preliminary data show that the impact of physical and chemical parameters on the toxicity of metals in aquatic environments can be rapidly assessed using rapid and low-cost microbiotests.

  10. Unique features of HLA-mediated HIV evolution in a Mexican cohort: a comparative study

    Science.gov (United States)

    Avila-Rios, Santiago; Ormsby, Christopher E; Carlson, Jonathan M; Valenzuela-Ponce, Humberto; Blanco-Heredia, Juan; Garrido-Rodriguez, Daniela; Garcia-Morales, Claudia; Heckerman, David; Brumme, Zabrina L; Mallal, Simon; John, Mina; Espinosa, Enrique; Reyes-Teran, Gustavo

    2009-01-01

    Background Mounting evidence indicates that HLA-mediated HIV evolution follows highly stereotypic pathways that result in HLA-associated footprints in HIV at the population level. However, it is not known whether characteristic HLA frequency distributions in different populations have resulted in additional unique footprints. Methods The phylogenetic dependency network model was applied to assess HLA-mediated evolution in datasets of HIV pol sequences from free plasma viruses and peripheral blood mononuclear cell (PBMC)-integrated proviruses in an immunogenetically unique cohort of Mexican individuals. Our data were compared with data from the IHAC cohort, a large multi-center cohort of individuals from Canada, Australia and the USA. Results Forty three different HLA-HIV codon associations representing 30 HLA-HIV codon pairs were observed in the Mexican cohort (q < 0.2). Strikingly, 23 (53%) of these associations differed from those observed in the well-powered IHAC cohort, strongly suggesting the existence of unique characteristics in HLA-mediated HIV evolution in the Mexican cohort. Furthermore, 17 of the 23 novel associations involved HLA alleles whose frequencies were not significantly different from those in IHAC, suggesting that their detection was not due to increased statistical power but to differences in patterns of epitope targeting. Interestingly, the consensus differed in four positions between the two cohorts and three of these positions could be explained by HLA-associated selection. Additionally, different HLA-HIV codon associations were seen when comparing HLA-mediated selection in plasma viruses and PBMC archived proviruses at the population level, with a significantly lower number of associations in the proviral dataset. Conclusion Our data support universal HLA-mediated HIV evolution at the population level, resulting in detectable HLA-associated footprints in the circulating virus. However, it also strongly suggests that unique genetic

  11. 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

  12. Sterren scoren met airbag

    NARCIS (Netherlands)

    Slütter, M.

    2010-01-01

    De praktijktest voor het airbagsysteem voor fietsers begint deze maand in Den Haag en Utrecht. Autofabrikanten hebben nu al interesse getoond. Dat is niet verwonderlijk, want met deze airbag kunnen ze sterren verdienen in de botsproeven van EuroNCAP.

  13. Zuinig met antibiotica

    NARCIS (Netherlands)

    Kuipers, A.; Wemmenhove, H.

    2011-01-01

    Het antibioticagebruik op melkveebedrijven is in beeld gebracht. Hoe benutten we deze gegevens om zuiniger met antibiotica om te gaan en hoe denken dierenartsen hierop in te spelen? Speelt de keuze voor verschillende middelen een rol?

  14. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. E-mail: pierre.le.coultre@cern.ch; 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

    2002-08-01

    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{sup 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.

  16. 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

  17. Experimental study of wind loads on unique buildings and structures in Russia

    Directory of Open Access Journals (Sweden)

    Poddaeva Olga

    2016-01-01

    Full Text Available Design and construction of unique buildings and structures (sports arenas, airport complexes, business centres, etc. from an engineering point of view is a very difficult task as in most cases these facilities have an original architectural form. Therefore, consideration of wind loads is an important part of the design. The paper presents the definition of wind load for two complex of airport. Researches was applied the combined calculation an experimental method. During the experimental study a wind tunnel architectural and construction type NRU MSUCE was used. Numerical simulations were performed using the software package ANSYS. The result of research on each object are integral aerodynamic loads on the object (coefficients Cx, Cy, Cmz and picture of the distribution of aerodynamic pressure coefficient Cp obtained in the numerical simulation. In conclusion, we discuss the possible formation of deposits of snow and recommendations to eliminate them from the roof of researched objects.

  18. NanoSIMS, TEM, and XANES studies of a Unique Presolar Supernova Graphite Grain

    CERN Document Server

    Groopman, Evan; Bernatowicz, Thomas; Zinner, Ernst

    2014-01-01

    We report on isotopic and microstructural investigations of a unique presolar supernova (SN) graphite grain, referred to as G6, isolated from the Orgueil CI chondrite. G6 contains complex heterogeneities in its isotopic composition and in its microstructure. Nano-scale secondary ion mass spectrometer isotope images of ultramicrotome sections reveal heterogeneities in its C, N, and O isotopic compositions, including anomalous shell-like structures. Transmission electron microscope studies reveal a nanocrystalline core surrounded by a turbostratic graphite mantle, the first reported nanocrystalline core from a low-density SN graphite grain. Electron diffraction analysis shows that the nanocrystalline core consists of randomly oriented 2-4 nm graphene particles, similar to those in cores of high-density (HD) presolar graphite grains from asymptotic giant branch stars. G6's core also exhibits evidence for planar stacking of these graphene nano-sheets with a domain size up to 4.5 nm, which was unobserved in the na...

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

    Directory of Open Access Journals (Sweden)

    Dirk C Odendaal

    2004-01-01

    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.

  20. Germline met mutations in mice reveal mutation- and background-associated differences in tumor profiles.

    Directory of Open Access Journals (Sweden)

    Carrie R Graveel

    Full Text Available BACKGROUND: The receptor tyrosine kinase Met is involved in the progression and metastasis of numerous human cancers. Although overexpression and autocrine activation of the Met signaling pathway are commonly found in human cancers, mutational activation of Met has been observed in small cell and non-small cell lung cancers, lung adenocarcinomas, renal carcinomas, and mesotheliomas. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the influence of mutationally activated Met in tumorigenesis, we utilized a novel mouse model. Previously, we observed that various Met mutations developed unique mutation-specific tumor spectra on a C57BL/6 background. Here, we assessed the effect of genetic background on the tumorigenic potential of mutationally activated Met. For this purpose, we created congenic knock-in lines of the Met mutations D1226N, M1248T, and Y1228C on the FVB/N background. Consistent with the mutation-specific tumor spectra, several of the mutations were associated with the same tumor types as observed on C57BL/6 background. However, on the FVB/N background most developed a high incidence of mammary carcinomas with diverse histopathologies. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that on two distinct mouse backgrounds, Met is able to initiate tumorigenesis in multiple cell types, including epithelial, hematopoietic, and endothelial. Furthermore, these observations emphasize that even a modest increase in Met activation can initiate tumorigenesis with both the Met mutational spectra and host background having profound influence on the type of tumor generated. Greater insight into the interaction of genetic modifiers and Met signaling will significantly enhance our ability to tailor combination therapies for Met-driven cancers.

  1. 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.

  2. Unique contributions of ISCOLE to the advancement of accelerometry in large studies.

    Science.gov (United States)

    Tudor-Locke, C; Barreira, T V; Schuna, J M; Katzmarzyk, P T

    2015-12-01

    Accelerometry has become a mainstay approach for objectively monitoring children's physical activity and sedentary time in epidemiological studies. The magnitude of effort underlying successful data collection, management and treatment is prodigious and its complexity has been associated with increasingly diverse methodological choices that, while defensible relative to specific research questions, conspire to undermine the ability to compare results between studies. Although respecting widespread calls for best practices, it is also important to openly share tools and resources supporting potential improvements to research practice and study design, thus allowing others to replicate, further improve, and/or otherwise build on this foundation. The International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) is a large multinational study that included accelerometer-based measures of physical activity, sedentary time and sleep. This review summarizes the unique contributions of ISCOLE to the advancement of accelerometry in large studies of children's behavior, and in particular: (1) open-access publication of the ISCOLE accelerometry Manual of Operations; (2) 24-h waist-worn accelerometry protocol; (3) identification and extraction of nocturnal total sleep episode time (with open access to editable SAS syntax); (4) development of the first interpretive infrastructure for identifying and defining an evolved list of sleep-related variables from 24-h waist-worn accelerometry; (5) provision of a detailed model for reporting accelerometer paradata (administrative data related to accelerometry); and (6) cataloging the most detailed and defensible list of accelerometry-derived physical activity and sedentary time variables to date. The novel tools and resources associated with these innovations are shared openly in an effort to support methodological harmonization and overall advancement of accelerometry in large epidemiological studies.

  3. Association between the COMT Val158Met polymorphism and risk of cancer: evidence from 99 case–control studies

    Directory of Open Access Journals (Sweden)

    Zhou Q

    2015-10-01

    Full Text Available Quan Zhou, Yan Wang, Aihua Chen, Yaling Tao, Huamei Song, Wei Li, Jing Tao, Manzhen ZuoDepartment of Gynecology and Obstetrics, The People’s Hospital of Three Gorges University, The First People’s Hospital of Yichang, Yichang, People’s Republic of ChinaAbstract: Catechol-O-methyltransferase (COMT plays a central role in DNA repair and estrogen-induced carcinogenesis. Many recent epidemiologic studies have investigated the association between the COMT Val158Met polymorphism and cancer risk, but the results are inconclusive. In this study, we performed a meta-analysis to investigate the association between cancer susceptibility and COMT Val158Met in different genetic models. Overall, no significant associations were found between COMT Val158Met polymorphism and cancer risk (homozygote model: odds ratio [OR] =1.05, 95% confidence interval [CI] = [0.98, 1.13]; heterozygote model: OR =1.01, 95% CI = [0.98, 1.04]; dominant model: OR =1.02, 95% CI [0.97, 1.06], and recessive model: OR =1.03, 95% CI [0.97, 1.09]. In the subgroup ­analysis of cancer type, COMT Val158Met was significantly associated with increased risks of ­bladder cancer in recessive model, and esophageal cancer in homozygote model, heterozygote model, and dominant model. Subgroup analyses based on ethnicities, COMT Val158Met was significantly associated with increased risk of cancer in homozygote and recessive model among Asians. In addition, homozygote, recessive, and dominant models were significantly associated with increased cancer risk in the subgroup of allele-specific polymerase chain reaction genotyping. Significant associations were not observed when data were stratified by the source of the controls. In summary, this meta-analysis suggested that COMT Val158Met polymorphism might not be a risk factor for overall cancer risk, but it might be involved in cancer development at least in some ethnic groups (Asian or some specific cancer types (bladder and esophageal cell

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

    Energy Technology Data Exchange (ETDEWEB)

    Bockman, R.; Adelman, R.; Donnelly, R.; Brody, L.; Warrell, R. (Hospital for Special Surgery, New York, NY (USA)); Jones, K.W. (Brookhaven National Lab., Upton, NY (USA))

    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.

  5. High resolution NMR study of T{sub 1} magnetic relaxation dispersion. IV. Proton relaxation in amino acids and Met-enkephalin pentapeptide

    Energy Technology Data Exchange (ETDEWEB)

    Pravdivtsev, Andrey N.; Yurkovskaya, Alexandra V.; Ivanov, Konstantin L., E-mail: ivanov@tomo.nsc.ru [International Tomography Center, Institutskaya 3a, Novosibirsk 630090 (Russian Federation); Department of Physics, Novosibirsk State University, Pirogova 2, Novosibirsk 630090 (Russian Federation); Vieth, Hans-Martin [Institut für Experimentalphysik, Freie Universität Berlin Arnimallee 14, 14195 Berlin (Germany)

    2014-10-21

    Nuclear Magnetic Relaxation Dispersion (NMRD) of protons was studied in the pentapeptide Met-enkephalin and the amino acids, which constitute it. Experiments were run by using high-resolution Nuclear Magnetic Resonance (NMR) in combination with fast field-cycling, thus enabling measuring NMRD curves for all individual protons. As in earlier works, Papers I–III, pronounced effects of intramolecular scalar spin-spin interactions, J-couplings, on spin relaxation were found. Notably, at low fields J-couplings tend to equalize the apparent relaxation rates within networks of coupled protons. In Met-enkephalin, in contrast to the free amino acids, there is a sharp increase in the proton T{sub 1}-relaxation times at high fields due to the changes in the regime of molecular motion. The experimental data are in good agreement with theory. From modelling the relaxation experiments we were able to determine motional correlation times of different residues in Met-enkephalin with atomic resolution. This allows us to draw conclusions about preferential conformation of the pentapeptide in solution, which is also in agreement with data from two-dimensional NMR experiments (rotating frame Overhauser effect spectroscopy). Altogether, our study demonstrates that high-resolution NMR studies of magnetic field-dependent relaxation allow one to probe molecular mobility in biomolecules with atomic resolution.

  6. Rekenen met vercijferde data

    NARCIS (Netherlands)

    Veugen, P.J.M.

    2011-01-01

    Een nieuwe techniek om bestaande en nieuwe toepassingen ‘privacy vriendelijk’ te maken is gebaseerd op het concept ‘rekenen met vercijferde data’. In dit artikel wordt dit mysterieuze idee uit de doeken gedaan en wordt de kracht ervan duidelijk gemaakt.

  7. BacMet

    DEFF Research Database (Denmark)

    Pal, Chandan; Bengtsson-Palme, Johan; Rensing, Christopher Günther T;

    2014-01-01

    -selection. Information on metal and biocide resistance genes, including their sequences and molecular functions, is, however, scattered. Here, we introduce BacMet (http://bacmet.biomedicine.gu.se) - a manually curated database of antibacterial biocide- and metal-resistance genes based on an in-depth review...

  8. Pionieren met informeel overleg

    NARCIS (Netherlands)

    Doornbos, N.

    2012-01-01

    Conflicthanteringspalet’, ‘escalatieladder’, ‘keukentafelgesprek’… Het zogenoemde pioniersproject van het Ministerie van Binnenlandse Zaken en Koninkrijksrelaties ‘Prettig contact met de overheid’ heeft de woordenschat aardig wat aangevuld. Zelfs de term LSD krijgt een nieuwe inhoud: luisteren - sam

  9. Pionieren met informeel overleg

    NARCIS (Netherlands)

    Doornbos, N.

    2012-01-01

    Conflicthanteringspalet’, ‘escalatieladder’, ‘keukentafelgesprek’… Het zogenoemde pioniersproject van het Ministerie van Binnenlandse Zaken en Koninkrijksrelaties ‘Prettig contact met de overheid’ heeft de woordenschat aardig wat aangevuld. Zelfs de term LSD krijgt een nieuwe inhoud: luisteren -

  10. Mechanische onkruidbestrijding met perspectief

    NARCIS (Netherlands)

    Bleeker, P.O.

    2011-01-01

    Intra-rijwieders met schoffels, lichtsensoren en camera’s: deze intelligente machines bestrijden het onkruid in de gewasrij mechanisch. Ze zijn ontwikkeld voor de biologische landbouw. De sensoren en camera’s bepalen de plaats van het gewas, waarna de schoffels per rij het onkruid tussen de planten

  11. Pionieren met informeel overleg

    NARCIS (Netherlands)

    Doornbos, N.

    2012-01-01

    Conflicthanteringspalet’, ‘escalatieladder’, ‘keukentafelgesprek’… Het zogenoemde pioniersproject van het Ministerie van Binnenlandse Zaken en Koninkrijksrelaties ‘Prettig contact met de overheid’ heeft de woordenschat aardig wat aangevuld. Zelfs de term LSD krijgt een nieuwe inhoud: luisteren - sam

  12. 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.

  13. NanoSIMS, TEM, and XANES studies of a unique presolar supernova graphite grain

    Energy Technology Data Exchange (ETDEWEB)

    Groopman, Evan; Bernatowicz, Thomas; Zinner, Ernst [Laboratory for Space Sciences, Physics Department, Washington University, One Brookings Drive, Campus Box 1105, Saint Louis, MO 63130 (United States); Nittler, Larry R., E-mail: eegroopm@physics.wustl.edu [Department of Terrestrial Magnetism, Carnegie Institution of Washington, 5241 Broad Branch Road, NW, Washington, DC 20015 (United States)

    2014-07-20

    We report on isotopic and microstructural investigations of a unique presolar supernova (SN) graphite grain, referred to as G6, isolated from the Orgueil CI chondrite. G6 contains complex heterogeneities in its isotopic composition and in its microstructure. Nano-scale secondary ion mass spectrometer isotope images of ultramicrotome sections reveal heterogeneities in its C, N, and O isotopic compositions, including anomalous shell-like structures. Transmission electron microscope studies reveal a nanocrystalline core surrounded by a turbostratic graphite mantle, the first reported nanocrystalline core from a low-density SN graphite grain. Electron diffraction analysis shows that the nanocrystalline core consists of randomly oriented 2-4 nm graphene particles, similar to those in cores of high-density (HD) presolar graphite grains from asymptotic giant branch stars. G6's core also exhibits evidence for planar stacking of these graphene nano-sheets with a domain size up to 4.5 nm, which was unobserved in the nanocrystalline cores of HD graphite grains. We also report on X-ray absorption near-edge structure measurements of G6. The complex isotopic- and micro-structure of G6 provides evidence for mixing and/or granular transport in SN ejecta.

  14. Comparative study of the human ficolins reveals unique features of Ficolin-3 (Hakata antigen).

    Science.gov (United States)

    Hummelshoj, Tina; Fog, Lea Munthe; Madsen, Hans O; Sim, Robert B; Garred, Peter

    2008-03-01

    The ficolins and mannose-binding lectin (MBL) are collagen-like defence proteins that serve as recognition molecules in lectin complement pathway. Differential features that may indicate diverse functions of these proteins are poorly understood. In this study we compared important biological features of the ficolins and MBL. We investigated the tissue distribution of the FCN1-3 and the MBL2 genes encoding the ficolins and MBL by quantitative PCR. Recombinant proteins were produced and structural and biological characteristics were investigated and compared. Our main findings were that FCN3 mRNA was highly expressed in the liver and lung compared with the other genes revealing the lung as the tissue with the highest FCN3 expression pattern. Ficolin-3 revealed higher complement activating capacity compared with Ficolin-2, MBL and Ficolin-1 and was highly resistant to bacterial collagenase treatment, which is different from the other ficolins and MBL. We discovered several unique properties of Ficolin-3 showing that FCN3 is the most highly expressed gene in liver and lung among the lectin complement pathway initiators. Moreover, Ficolin-3 has a high complement activating potential and is the only collagenase proteolytic resistant molecule among the lectin complement pathway initiators.

  15. Metástases dos ossos gnáticos: estudo retrospectivo de 10 casos Gnathic bone metastasis: a retrospective study of 10 cases

    Directory of Open Access Journals (Sweden)

    Antonio Azoubel Antunes

    2008-08-01

    Full Text Available Metástases em cavidade oral são extremamente raras, representando 1% de todas as neoplasias malignas orais. OBJETIVO: Analisar retrospectivamente a incidência de metástase nos maxilares, traçando seu perfil de comportamento epidemiológico. MATERIAL E MÉTODOS: Através de estudo retrospectivo, foram analisados o sexo, idade, localização topográfica da metástase, sítio do tumor primário e tipo histológico, no período de janeiro de 1980 a janeiro de 2000, de um total de 10 pacientes. RESULTADOS: Observou-se que 5 pacientes eram do sexo masculino (50%, 3 casos ocorreram nas 2ª e 4ª décadas de vida (30 e 30%. Concernente à localização topográfica da metástase, metade dos casos ocorreu na maxila e metade na mandíbula. A tireóide e próstata foram os sítios de tumor primário que mais metastizaram para os ossos gnáticos (3 casos cada e o adenocarcinoma foi o tipo histológico de maior ocorrência de metástase (50%. Conclusões: As metástases nos maxilares acometem igualmente faixa etária, sexo e localização topográfica. A tireóide e próstata parecem ser os sítios mais freqüentes de metástase à distância, e o adenocarcinoma o tipo histológico de maior incidência de metástase.Oral cavity metastases are extremely rare, and comprise 1% of all mouth malignant neoplasms. AIM: to retrospectively analyze the incidence of maxillary metastases, and to trace its epidemiological behavior. MATERIAL AND METHODS: A retrospective study was done of the period between January 1980 and January 2000;the following indicators were reviewed: sex, age, site of the metastasis, site of the primary tumor, and the histological type of tumors in 10 patients. RESULTS: The prevalence was similar in males and females (05 cases - 50%; three cases presented in the 2nd and 4th decades of life (30 - 30%. About half of the cases of metastases occurred in the maxilla and half in the mandible. The thyroid and prostate glands were the most prevalent

  16. 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…

  17. Acetylcholinesterase converts Met5-enkephalin-containing peptides to Met5-enkephalin.

    Science.gov (United States)

    Dowton, M; Boelen, M

    1988-11-22

    Acetylcholinesterase (AChE; E.C. 3.1.1.7) was incubated with a number of enkephalin-containing neuropeptides found in the bovine adrenal medulla. Met5-enkephalin and Leu5-enkephalin were the most stable of the peptides studied, while precursors of Met5-enkephalin were converted to Met5-enkephalin. AChE is therefore capable of limited peptidase activity on Met5-enkephalin precursors. The enzyme hydrolysed the Met5-enkephalin precursor BAM-12P on the C-terminal side of the pair of basic amino acid residues, and cleaved basic amino acids from the carboxy-terminal of Met5-enkephalin-Arg6 and Met5-enkephalin-Arg6-Arg7. These results indicate that AChE, acting alone, is capable of the same pattern of enkephalin processing as that observed in the adrenal medulla.

  18. Metsään.fi-metsäsuunnitelma OTSO Metsäpalveluissa

    OpenAIRE

    Karimo, Jussi

    2016-01-01

    Opinnäytetyön lähtökohtana oli OTSO Metsäpalveluiden halu kehittää Metsään.fi-palvelusta saatavan tiedon perusteella tehtävä metsäsuunnitelmatuote. Metsäsuunnitelmatuotteella tarkoitettiin uudenlaista metsäsuunnitelmaa, joka tehtäisiin Metsään.fi-palvelun tietoa hyödyntäen. Opinnäytetyön tarkoituksena oli kartoittaa OTSOn metsäpalveluhenkilöstön näkemyksiä Metsään.fi-palvelusta, jotta selviäisi, kannattaako heidän mielestään Metsään.fi-palvelua hyödyntää metsäsuunnitelmatyökaluna. Lisäksi hal...

  19. 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

  20. Gastrointestinal malignancies harbor actionable MET exon 14 deletions

    Science.gov (United States)

    Hong, Mineui; Kim, Sun Young; Jang, Jiryeon; Ahn, Soomin; Kang, So Young; Lee, Sujin; Kim, Seung Tae; Kim, Bogyou; Choi, Jaehyun; Kim, Kyung-Ah; Lee, Jiyun; Park, Charny; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Keunchil; Park, Young Suk; Kim, Kyoung-Mee

    2015-01-01

    Recently, MET exon 14 deletion (METex14del) has been postulated to be one potential mechanism for MET protein overexpression. We screened for the presence of METex14del transcript by multiplexed fusion transcript analysis using nCounter assay followed by confirmation with quantitative reverse transcription PCR with correlation to MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH). We extracted RNAs from 230 patients enrolled onto the prospective molecular profiling clinical trial (NEXT-1) (NCT02141152) between November 2013 and August 2014. Thirteen METex14del cases were identified including 3 gastric cancer, 4 colon cancer, 5 non-small cell lung cancer, and one adenocarcinoma of unknown primary. Of these 13 METex14del cases, 11 were MET IHC 3+ and 2 were 2+. Only one out of the 13 METex14del cases was MET amplified (MET/CEP ratio > 2.0). Growths of two (gastric, colon) METex14del+ patient tumor derived cell lines were profoundly inhibited by both MET tyrosine kinase inhibitors and a monoclonal antibody targeting MET. In conclusion, METex14del is a unique molecular aberration present in gastrointestinal (GI) malignancies corresponding with overexpression of MET protein but rarely with MET amplification. Substantial growth inhibition of METex14del+ patient tumor derived cell lines by several MET targeting drugs strongly suggests METex14del is a potential actionable driver mutation in GI malignancies. PMID:26375439

  1. Clinical significance of MET in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Mikito; Inokuchi; Sho; Otsuki; Yoshitaka; Fujimori; Yuya; Sato; Masatoshi; Nakagawa; Kazuyuki; Kojima

    2015-01-01

    Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer(GC),although outcomes remain unfavorable.Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed,and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC.Hepatocyte growth factor and its receptor,c-MET(MET),play key roles in tumor growth through activated signaling pathways from receptor in GC cells.Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC.This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC.Preclinical studies in animal models have shown that MET antibodies or smallmolecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells.These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.

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

    DEFF Research Database (Denmark)

    Bentzen, Martin Mose

    of logic such as definability, satisfiability and validity. Here follows two simple examples illustrating the relation between syntactic and semantic ambiguity. In some cases unique readability can be regained through careful construction of formulas. E.g., although an attempt to define p → q as ¬p ∨ q...... would be syntactically and semantically ambiguous, one may define it as q ∨ ¬p, which can be read only one way (but obviously this construction is not stable under substitution). Syntactic ambiguity does not imply semantic ambiguity, although it is typically the case. For instance, although the formula...

  3. Association of the insulin-receptor variant Met-985 with hyperglycemia and non-insulin-dependent diabetes mellitus in the Netherlands: A population-based study

    Energy Technology Data Exchange (ETDEWEB)

    `t Hart, L.M.; Maassen, J.A. [Leiden Univ. (Netherlands); Does, F.E.E. van der [Free Univ., Amsterdam (Netherlands)] [and others

    1996-11-01

    One of the characteristics of non-insulin-dependent diabetes mellitus (NIDDM) is the presence of insulin. Most NIDDM patients have a normal sequence of the insulin receptor, indicating that, if insulin-receptor mutations contribute to the development of NIDDM, they will be present only in a minor fraction of the NIDDM population. The goal of the present study was to examine whether insulin-receptor mutations contribute to the development of NIDDM. We examined 161 individuals with NIDDM and 538 healthy controls from the population-based Rotterdam study for the presence of mutations in the insulin-receptor gene by SSCP. A heterozygous mutation changing valine-985 into methionine was detected in 5.6% of diabetic subjects and in 1.3% of individuals with normal oral glucose tolerance test. Adjusted for age, gender, and body-mass index, this revealed a relative risk for diabetes of 4.49 (95% confidence interval 1.59-12.25) for Met-985 carriers. When the total study group was analyzed, the prevalence of the mutation increased with increasing serum glucose levels (test for trend P < .005). We conclude that the Met-985 insulin-receptor variant associates with hyperglycemia and represents a risk factor for NIDDM. 30 refs., 3 figs., 1 tab.

  4. 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....

  5. 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......Met polymorphism of the ghrelin gene associates with features of the metabolic syndrome (MS) in the Danish population.......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 Leu72...

  6. The primitive matrix components of the unique carbonaceous chondrite Acfer 094: a TEM study.

    Science.gov (United States)

    Greshake, A

    1997-01-01

    The mineralogical and chemical characteristics of the fine-grained matrix (chondrite Acfer 094 have been investigated in detail by scanning electron microscopy (SEM) and analytical transmission electron microscopy (ATEM). Generally, the fine-grained matrix represents a highly unequilibrated assemblage of an amorphous material, small forsteritic olivines (200-300 nm), low Ca-pyroxenes (300-400 nm), and Fe,Ni-sulfides (100-300 nm). The matrix is basically unaffected by secondary processes. Only minor amounts of serpentine and ferrihydrite, as products of hydrous alteration, are present. Texturally, the amorphous material acts as a groundmass to olivines, pyroxenes, and sulfides, mostly exhibiting rounded or elongated morphologies. Only very few clastic mineral grains have been found. The texture and chemical composition of the amorphous material are consistent with an origin by disequilibrium condensation in either the cooling solar nebula or a circumstellar environment. As such, the amorphous material may be considered as a possible precursor of matrix materials in other types of chondrites. The non-clastic matrix olivines (Fo98-99) and pyroxenes (En97-100) are suggested to have formed either by condensation in the solar nebula under highly oxidizing conditions or by recrystallization from the amorphous material. The formation of these grains by fragmentation of chondrule components is unlikely due to chemical and microstructural reasons. Rapid cooling caused the observed intergrowths of clino/orthoenstatite in the Mg-rich matrix pyroxenes. Although some similarities exist comparing the fine-grained matrix of Acfer 094 with the matrices of the unequilibrated CO3 chondrite ALHA77307 and the unique type 3 chondrite Kakangari, Acfer 094 remains unique. Since it contains the highest measured concentrations of circumstellar SiC and the second highest of diamond (highest is Orgueil), it seems reasonable to suggested that at least parts of the amorphous material in the

  7. La metáfora

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2007-01-01

    La función de la metáfora ha sido revisada desde distintas disciplinas. Desde la hermenéutica, se destaca la naturaleza tensional de la metáfora y el modo en que contribuye a crear significaciones nuevas, que rehacen los órdenes semánticos preexistentes. Desde el cognitivismo, la metáfora...

  8. The role of c-Met in prognosis and clinicopathology of renal cell carcinoma: Results from a single-centre study and systematic review.

    Science.gov (United States)

    Chen, Shouzhen; Zhu, Yaofeng; Cui, Jianfeng; Wang, Yong; Xia, Yangyang; Song, Jing; Cheng, Shanshan; Zhou, Changkuo; Zhang, Dongqing; Zhang, Bing; Shi, Benkang

    2017-08-01

    The c-Met proto-oncogene pathway plays an important role in the progression of various cancers. However, the effect of the c-Met pathway on renal cell carcinoma (RCC) remains controversial. We decided to clarify the role of c-Met in prognosis and clinicopathology of RCC. A total of 10 pairs of tumour and adjacent tissues were obtained from patients with primary RCC between 2013 and 2014 and tissue microarrays to assess c-Met expression in tumour tissues from 90 patients with RCC by Western blot and immunohistochemical staining. We also presented a meta-analysis to explore the correlation between c-Met and pathological grade and stage of RCC. The two-tailed Pearson's χ(2) and Fischer exact tests were used to compare categorical variables. Multivariate analysis was performed using the multivariate Cox proportional hazards model. C-Met protein levels were increased in 8 of 10 RCC tissue samples compared with their adjacent normal tissue and c-Met expression levels were positively associated with a high nuclear grade (P = 0.008) and pT stage (P = 0.002). Multivariate analysis showed that a high expression of c-Met was an independent predictor of disease-specific survival (P = 0.017). A meta-analysis found that increased c-Met expression in RCC tissues was closely correlated with high tumour grade (Pc-Met expression was significantly correlated with disease-specific survival (Pc-Met is strongly associated with pathological grade, stage and disease-specific survival, c-Met levels may have potential to predict patient prognosis and to guide clinical diagnosis and treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Functional COMT Val158Met polymorphism, risk of acute coronary events and serum homocysteine: the Kuopio ischaemic heart disease risk factor study.

    Directory of Open Access Journals (Sweden)

    Sari Voutilainen

    Full Text Available BACKGROUND: The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met in the Catechol-O-methyltransferase (COMT gene. METHODOLOGY AND FINDINGS: Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middle-aged men from eastern Finland. A population-based prospective cohort of 792 men aged 46-64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR of 1.73 (95% confidence interval (CI, 1.07-2.79, and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05-2.77. Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93-2.49, subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50-5.76 as compared with other men. CONCLUSIONS: This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels.

  10. 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

  11. Preliminary study of anxiety symptoms, family dysfunction, and the brain-derived neurotrophic factor (BDNF) Val66Met genotype in offspring of parents with bipolar disorder.

    Science.gov (United States)

    Park, Min-Hyeon; Chang, Kiki D; Hallmayer, Joachim; Howe, Meghan E; Kim, Eunjoo; Hong, Seung Chul; Singh, Manpreet K

    2015-02-01

    Several genetic and environmental factors place youth offspring of parents with bipolar disorder (BD) at high risk for developing mood and anxiety disorders. Recent studies suggest that anxiety symptoms, even at subclinical levels, have been associated with an increased risk for developing BD. The brain-derived neurotrophic factor (BDNF) gene has been implicated in the pathophysiology of both BD and anxiety disorders. We aimed to explore whether anxiety in BD offspring was associated with the BDNF Val66Met polymorphism. 64 BD offspring (mean age: 13.73 (S.D. 3.45) M = 30, F = 34) and 51 HC (mean age: 13.68 (S.D. 2.68) M = 23, F = 28) were compared on presence of the met allele and on scores from the Multidimensional Anxiety Scale for Children (MASC). To assess family function, we used the Family Adaptability and Cohesion Evaluation Scales (FACES-IV). The Baron & Kenny method was the statistical approach used to examine the moderating effects between variables. BD offspring showed higher levels of overall anxiety than did the HC group. BD offspring with the val/val genotype showed higher levels of anxiety than BD offspring with other genotypes. No significant levels of anxiety or its association with BDNF genotype were found in the HC group. BD offspring group showed significantly more family dysfunction when compared with the HC group and the family dysfunction moderated the association between the BDNF genotype and anxiety symptoms. This study demonstrated the potential interplay of three factors: BD offspring, anxiety symptoms and family dysfunction.

  12. c-Met in chromophobe renal cell carcinoma.

    Science.gov (United States)

    Erlmeier, Franziska; Ivanyi, Philipp; Hartmann, Arndt; Autenrieth, Michael; Wiedemann, Max; Weichert, Wilko; Steffens, Sandra

    2017-02-01

    c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for c-Met expression by immunohistochemistry. Expression data were associated with clinicopathological parameters including patient survival. Eighty-one chRCC patients were eligible for analysis. Twenty-four (29.6%) patients showed a high c-Met expression (c-Met(high), staining intensity higher than median). Our results showed an association between c-Met(high) expression and the existence of lymph node metastasis (p = 0.007). No further significant clinicopathological associations with c-Met were identified, also regarding c-Met expression and overall survival. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of c-Met in a considerably large cohort of chRCC. High c-Met expression is associated with the occurrence of lymph node metastasis. This indicates that c-Met might be implicated into metastatic progression in chRCC.

  13. NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies effects of cigarette smoking on risk of elevated levels of serum liver enzyme in male Japanese health check-up examinees: a cross-sectional study

    OpenAIRE

    Kokaze, Akatsuki; Yoshida, Masao; Ishikawa, Mamoru; Matsunaga, Naomi; Karita, Kanae; Ohtsu, Tadahiro; Ochiai, Hirotaka; Shirasawa, Takako; Nanri, Hinako; Baba, Yuta; HOSHINO, Hiromi; Takashima, Yutaka

    2014-01-01

    Background NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism reportedly influences the effects of cigarette smoking on respiratory function, risk of dyslipidemia, serum non-high-density lipoprotein cholesterol levels, hematological parameters and intraocular pressure. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of cigarette smoking on serum liver enzyme levels in male Japanese health check-up examine...

  14. Unique Contributions of Eye-Tracking Research to the Study of Learning with Graphics

    Science.gov (United States)

    Mayer, Richard E.

    2010-01-01

    The author examines the empirical, methodological, theoretical, and practical contributions of the six studies in this special issue on eye tracking as a tool to study and enhance multimedia learning. The design of learning environments involving graphics should be consistent with a research-based theory of how people learn and evidence-based…

  15. Unique contributions of ISCOLE to the advancement of accelerometry in large studies

    OpenAIRE

    Tudor-Locke, C.; Barreira, T V; Schuna, J. M.; Katzmarzyk, P. T.

    2015-01-01

    Accelerometry has become a mainstay approach for objectively monitoring children's physical activity and sedentary time in epidemiological studies. The magnitude of effort underlying successful data collection, management and treatment is prodigious and its complexity has been associated with increasingly diverse methodological choices that, while defensible relative to specific research questions, conspire to undermine the ability to compare results between studies. Although respecting wides...

  16. Unique Contributions of Eye-Tracking Research to the Study of Learning with Graphics

    Science.gov (United States)

    Mayer, Richard E.

    2010-01-01

    The author examines the empirical, methodological, theoretical, and practical contributions of the six studies in this special issue on eye tracking as a tool to study and enhance multimedia learning. The design of learning environments involving graphics should be consistent with a research-based theory of how people learn and evidence-based…

  17. Vroegtijdig Phytophthora opsporen met biosensor

    NARCIS (Netherlands)

    Jansen, R.M.C.

    2003-01-01

    Phytophthora kan vroegtijdig worden opgespoord met biosensoren. Bij de Leerstoelgroep Agrarische Bedrijfstechnologie van Wageningen Universiteit wordt verder gekeken naar praktische toepassingen van deze techniek

  18. Houtcomposities met glas, beton en kunststof. Onderzoeken TNO Bouw

    NARCIS (Netherlands)

    Kuilen, J.W.G. van de; Robson, D.J.

    1999-01-01

    TNO Bouw in Rijswijk probeert hout een meerwaarde te geven door het te combineren met andere materialen. De studies richten zich onder meer op de versterking van balken met vezels en van vloeren met een laag beton. Bovendien kijken de onderzoekers naar moge-lijkheden om afvalhout in kunststof te

  19. 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.

  20. 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

  1. 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 (14)C or (3)H 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.

  2. Copper-Zinc Superoxide Dismutase: A Unique Biological "Ligand" for Bioinorganic Studies.

    Science.gov (United States)

    Valentine, Joan Selverstone; de Freitas, Duarte Mota

    1985-01-01

    Discusses superoxide dismutase (SOD) research and the properties of copper, zinc (Cu, Zn)-SOD. Emphasizes the controversy concerning the role of Cu,Zn-SOD and other SOD enzymes as protective agents in reactions involving dioxygen metabolism, and the properties of Cu, Zn-SOD that make it an interesting biological ligand for physical studies of…

  3. Comparative study of the human ficolins reveals unique features of Ficolin-3 (Hakata antigen)

    DEFF Research Database (Denmark)

    Hummelshoj, Tina; Fog, Lea Munthe; Madsen, Hans O;

    2007-01-01

    The ficolins and mannose-binding lectin (MBL) are collagen-like defence proteins that serve as recognition molecules in lectin complement pathway. Differential features that may indicate diverse functions of these proteins are poorly understood. In this study we compared important biological...

  4. 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…

  5. 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.

  6. Unique roles of SPET brain imaging in clinical and research studies. Lessons from Parkinson's disease research.

    Science.gov (United States)

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

    2005-06-01

    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 SPECT 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 neuroprotective 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 biomarkers 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 in 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.

  7. Enterprising with energy. Behavioral study on the motives of greenhouse owners to save energy; Ondernemen met energie. Gedragsonderzoek naar de drijfveren van glastuinders ten aanzien van energiebesparing

    Energy Technology Data Exchange (ETDEWEB)

    Verstegen, J.; Westerman, E.; Ravensbergen, P.; Bremmer, J.

    2003-05-01

    Based on the results of interviews with representatives in the greenhouse sector in the Netherlands insight is given into constraints and motives for energy conservation and the use of renewable energy in greenhouses. [Dutch] In de AMvB Glastuinbouw zijn individuele energieverbruiknormen voor 2010 vastgesteld. Doelstelling van dit onderzoek was om, met het oog op deze AMvB, duidelijk te krijgen welke belemmeringen en drijfveren er zijn voor verdere energiebesparing en inzet van duurzame energie door ondernemers in de glastuinbouw. Hiertoe zijn aan de hand van een uitgebreide vragenlijst interviews uitgevoerd op 29 glasbloemen-, 34 glasgroente- en 32 potplantenbedrijven. Op basis van variabelen met betrekking tot de perceptie, de houding en het gedrag van ondernemers ten aanzien van energiebesparing, zijn met behulp van clusteranalyse de bedrijven onderverdeeld in vijf clusters. Het rapport besluit met enkele hoofdlijnen uit de resultaten en een beschrijving per cluster van bedrijfssituaties, belemmeringen en drijfveren van ondernemers, in zogenaamde clusterprofielen.

  8. 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

  9. 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.

  10. Structure of AcMet-Gly and Its Interaction with Palladium(II)Tetraaqua Complex Studied by Electrospray Mass Spectrome try and Density Functional Theory

    Institute of Scientific and Technical Information of China (English)

    JIN,Chen(金晨); ZHANG,Lin(张琳); HONG,Jin(洪瑾); YANG,Gao-Sheng(杨高升); ZHU,Long-Gen(朱龙根)

    2004-01-01

    The structure of dipepide AcMet-Gly was determined by X-ray crystallographic analysis. It possesses monoclinic, space group P21 (No. 4), with cell dimensions of a=0.8571(2) nm, b=0.5871(2) nm, c= 1.197(3) nm,β=99.290(10)°, V=0.5944(15) nm3, Z=2, .μ=2.74 cm-1. Mononuclear chelates, described as [Pd(X)(S,N,O-AcMet-Gly)] +, in which Pd(II) is coordinated by thioether, deprotonated amide nitrogen, carbonyl oxygen of methionine and X (AcMetGly or other ligands present in aqueous solution or in mobile phase solution), were detected 5 min after mixing AcMet-Gly with [Pd(H2O)4]2- at room temperature using electrospray ionization mass spectrometry. The geometry of [Pd(H2O)(S,N,O-AcMet-Gly)]+ is optimized at density functional B3LYP/LanL2DZ level. The fused five- and six-membered chelate is responsible for cleavage of Met-Gly bond. This is the first time to provide a direct evidence for Pd(II)-mediated cleavage of dipeptides via external solvent attack.

  11. 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.

  12. The Unique Capabilities of the Global Hawk Aircraft for the Study of Climate Changes

    Science.gov (United States)

    Cairo, F.; Carli, Bruno; Curry, Robert

    2009-01-01

    Due to unprecedented extent and flexibility of the coverage that is now attainable both in space and time, stratospheric unmanned aircraft, such as the Global Hawk (GH), offers new opportunities for the study of climate changes. The capability of performing long flights at altitudes close to the boundary conditions of radiative processes, and of following the diurnal variation of chemical species and clouds, make the GH competitive with LEO and geosynchronous satellites, and even capable of new observations that are not possible from satellites. This paper discusses how the GH can be used to make relevant advancements in most of the issues that are related to climate change studies, such as: Earth Radiation Budget, Water Cycle, Ecosystems and Upper Troposphere-Lower Stratosphere, as well as to the monitoring and control of Greenhouse Gases and Air Quality . Collaboration between NASA and Italian scientific institutions, within the framework of the US.-Italy Cooperation on Climate Change, is providing the opportunity to rapidly deploy new instruments on the GH and to possibly operate the aircraft from an Italian site in the Mediterranean area. From this area, which is considered highly vulnerable to climate change, meridional transects would allow the crossing of Polar and Sub Tropical Jets, as well as a complete crossing of the Inter Tropical Convergence Zone, while latitudinal ones would follow the influx from Asia and North America. Regions otherwise difficult to access, such as Central Africa and the Tibetan Plateau, could be reached and better investigated. An overview of these new opportunities will be given and discussed.

  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. 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.

  15. In vitro study of novel collagenase (XIAFLEX® on Dupuytren's disease fibroblasts displays unique drug related properties.

    Directory of Open Access Journals (Sweden)

    Farhatullah Syed

    Full Text Available Dupuytren's disease (DD is a benign, fibroproliferative disease of the palmar fascia, with excessive extracellular matrix (ECM deposition and over-production of cytokines and growth factors, resulting in digital fixed flexion contractures limiting hand function and patient quality of life. Surgical fasciectomy is the gold standard treatment but is invasive and has associated morbidity without limiting disease recurrence. Injectable Collagenase Clostridium histolyticum (CCH--Xiaflex®--is a novel, nonsurgical option with clinically proven in vivo reduction of DD contractures but with limited in vitro data demonstrating its cellular and molecular effects. The aim of this study was to delineate the effects of CCH on primary fibroblasts isolated from DD and non-DD anatomical sites (using RTCA, LDH, WST-1, FACS, qRT-PCR, ELISA and In-Cell Quantitative Western Blotting to compare the efficacy of varying concentrations of Xiaflex® against a reagent grade Collagenase, Collagenase A. Results demonstrated that DD nodule and cord fibroblasts had greater proliferation than those from fat and skin. Xiaflex® exposure resulted in dose- and time-dependent inhibition of cellular spreading, attachment and proliferation, with cellular recovery after enzyme removal. Unlike Collagenase A, Xiaflex® did not cause apoptosis. Collagen expression patterns were significantly (p<0.05 different in DD fibroblasts across anatomical sites - the highest levels of collagen I and III were detected in DD nodule, with DD cord and fat fibroblasts demonstrating a smaller increase in both collagen expression relative to DD skin. Xiaflex® significantly (p<0.05 down-regulated ECM components, cytokines and growth factors in a dose-dependent manner. An in vitro scratch wound assay model demonstrated that, at low concentrations, Xiaflex® enabled a faster fibroblast reparatory migration into the wound, whereas, at high concentrations, this process was significantly (p<0.05 inhibited

  16. 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 (

  17. '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.

  18. '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.

  19. Marked for life? A prospective study of tattoos on appearance anxiety and dissatisfaction, perceptions of uniqueness, and self-esteem.

    Science.gov (United States)

    Swami, Viren

    2011-06-01

    Previous studies on psychosocial aspects of tattooing have not examined prospective changes in self- and body-related attitudes as a result of obtaining a tattoo. In the present study, 82 British residents obtaining their first tattoo completed measures of state appearance anxiety and dissatisfaction prior to, and immediately after, obtaining a tattoo. They also completed measures of trait body appreciation, distinctive appearance investment, self-ascribed uniqueness, social physique anxiety, and self-esteem before obtaining a tattoo and three weeks later. Results showed that both women and men had significantly lower appearance anxiety and dissatisfaction immediately after obtaining their tattoo, and significantly higher body appreciation, distinctive appearance investment, self-ascribed uniqueness, and self-esteem after three weeks. Women reported greater social physique anxiety after three weeks, whereas men reported lower anxiety. These results are discussed in relation to the positive impacts of obtaining body art and the mainstreaming of tattooing in Western societies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Spectral Study on Coordination Reaction between metMyoglobin and Nitric Oxide%光谱法研究高铁肌红蛋白活性中心与一氧化氮的配位反应

    Institute of Scientific and Technical Information of China (English)

    唐乾; 张越; 曹洪玉; 史珊珊; 郑学仿

    2015-01-01

    As we all known ,the instantaneous reaction between protein and ligands are very important to adjust the normal pla‐ying of biological function .And nitric oxide interactions with iron are the most important biological reactions in which NO partic‐ipates .Unlike carbon monoxide or oxygen ,NO can also bind reversibly to ferric iron .In this paper ,UV‐Vis absorption and CD spectra were used to study coordination reaction process between horse heart metMb and NO ,to demonstrate the coordination reaction mechanism and to explore the influencing factors of metMb with NO .The experimental results showed that metMb could react with NO ,and obtained three new peaks at 420 nm ,534 and 568 nm ,respectively ,which implied metMb and NO have reacted and generated a new complex‐nitrosylmetmyoglobin (metMbNO) .Then as time went on ,NO concentration de‐creased in the solution ,and the Fe‐N bond fractured under the attack of H2O ,then NO leaves slowly from metMbNO ,and met‐Mb was regenerated .In this experiment ,we also found that external conditions such as buffer medium ,ionic strength ,pH , temperature ,etc ,had an important influence on the coordination reaction between metMb and NO .It was favorable for the coor‐dination reaction ,when the 0.01 mol・L -1 phosphate buffer solution is near neutral condition ,the temperature is 280 K ,the co‐ordination reaction could reach equilibrium at a fastest speed .In addition ,the CD date show that NO only reacts with Fe atom in the center of heme and has less effect on the secondary structuers of protein .The research of metMb and NO played an important role to further study the function of NO .Especially the establish of equilibrium reaction mechanism between NO and heme pro‐tein has an important research value on maintaining the balance of NO in vivo and keeping the normal function in the body ’s cells .%蛋白质与配体作用的瞬时性对调节生物功能的正常发挥至关重要。采用紫外‐可见

  1. Cahier Welzijnsgids. Omgaan met beroepsgeheim

    Directory of Open Access Journals (Sweden)

    Hilde Vlaeminck

    2016-03-01

    Full Text Available Bernard Hubeau, Jos Mertens, Johan Put, Rudi Roose, Kris Stas, Freya Vander Laenen (Eds.. Cahier Welzijnsgids. Omgaan met beroepsgeheim. Mechelen: Kluwer, 182 p., €31,60. ISBN 978 90 4655 475 3

  2. Compost voor biggen met diarree

    NARCIS (Netherlands)

    Gommers, T.

    1990-01-01

    Het geven van compost aan biggen met diarree zorgt op het Proefstation voor de Varkenshouderij voor minder medicijngebruik. De biggen krijgen de compost van groente-, fruit- en tuinafval vanaf de tweede dag na de geboorte, zodra de diarreeverschijnselen zichtbaar zijn.

  3. Metallurgical Laboratory (MET-LAB)

    Data.gov (United States)

    Federal Laboratory Consortium — The MET-LAB can perform materials characterization for all types of metallic components and systems to any industry-specific or military standard. Capabilities: The...

  4. Role of gravity wavelike seed perturbations on the triggering of ESF – a case study from unique dayglow observations

    Directory of Open Access Journals (Sweden)

    R. Sridharan

    2009-01-01

    Full Text Available First observational evidence, from the Indian longitudes, for the presence of gravity wavelike perturbations with periods of 20–30 min, acting as probable seeds for Equatorial Spread F (ESF irregularities is described. The study is based on the daytime optical measurements of the mesopause temperature and the intensity of the thermospheric O(1D 630.0 nm dayglow emissions using the unique MultiWavelength Dayglow PhotoMeter from Trivandrum (8.5° N; 77° E; dip lat ~0.5° N, a dip equatorial station. Measurements during the equinoctial months of a solar maximum (2001 and a solar minimum year (2006 have been used in this study. It is shown that under identical background ionospheric conditions within a solar epoch, the power of the gravity waves have a deterministic role in the generation of ESF. The mesopause temperature simultaneously observed, indicate that possible source regions for these perturbations lie in the lower atmosphere.

  5. MMTV-PyMT and Derived Met-1 Mouse Mammary Tumor Cells as Models for Studying the Role of the Androgen Receptor in Triple-Negative Breast Cancer Progression.

    Science.gov (United States)

    Christenson, Jessica L; Butterfield, Kiel T; Spoelstra, Nicole S; Norris, John D; Josan, Jatinder S; Pollock, Julie A; McDonnell, Donald P; Katzenellenbogen, Benita S; Katzenellenbogen, John A; Richer, Jennifer K

    2017-04-01

    Triple-negative breast cancer (TNBC) has a faster rate of metastasis compared to other breast cancer subtypes, and no effective targeted therapies are currently FDA-approved. Recent data indicate that the androgen receptor (AR) promotes tumor survival and may serve as a potential therapeutic target in TNBC. Studies of AR in disease progression and the systemic effects of anti-androgens have been hindered by the lack of an AR-positive (AR+) immunocompetent preclinical model. In this study, we identified the transgenic MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor-antigen) mouse mammary gland carcinoma model of breast cancer and Met-1 cells derived from this model as tools to study the role of AR in breast cancer progression. AR protein expression was examined in late-stage primary tumors and lung metastases from MMTV-PyMT mice as well as in Met-1 cells by immunohistochemistry (IHC). Sensitivity of Met-1 cells to the AR agonist dihydrotestosterone (DHT) and anti-androgen therapy was examined using cell viability, migration/invasion, and anchorage-independent growth assays. Late-stage primary tumors and lung metastases from MMTV-PyMT mice and Met-1 cells expressed abundant nuclear AR protein, while negative for estrogen and progesterone receptors. Met-1 sensitivity to DHT and AR antagonists demonstrated a reliance on AR for survival, and AR antagonists inhibited invasion and anchorage-independent growth. These data suggest that the MMTV-PyMT model and Met-1 cells may serve as valuable tools for mechanistic studies of the role of AR in disease progression and how anti-androgens affect the tumor microenvironment.

  6. Absence of tpr-met and expression of c-met in human gastric mucosa and carcinoma.

    Science.gov (United States)

    Heideman, D A; Snijders, P J; Bloemena, E; Meijer, C J; Offerhaus, G J; Meuwissen, S G; Gerritsen, W R; Craanen, M E

    2001-08-01

    The c-met proto-oncogene, encoding the hepatocyte growth factor receptor, can be activated by various mechanisms. These include, among others, gene amplification with concomitant overexpression and the tpr-met oncogenic rearrangement. In the case of gastric cancer, contradictory results on the presence of the tpr-met oncogenic rearrangement have been published. The current study aimed therefore to assess the prevalence of tpr-met expression in Caucasian gastric adenocarcinomas, to evaluate the importance of this oncogene in their carcinogenesis. In addition, the level of c-met expression was determined, to evaluate the role of this alternative mode of activation of the proto-oncogene. A series of Caucasian gastric adenocarcinomas (n=43) and normal gastric mucosal samples (n=14) was analysed for tpr-met and c-met expression. Expression of tpr-met mRNA in the samples was performed by two reverse transcriptase polymerase chain reaction (RT-PCR) assays, with excellent correlation. The specificity of both methods was confirmed by direct sequencing of the PCR products of the MNNG-HOS cell line, which is known to contain the rearrangement. The level of c-met expression was assessed using semi-quantitative RT-PCR assays and immunohistochemistry (IHC). None of the normal gastric mucosal or gastric adenocarcinoma samples expressed tpr-met mRNA, as determined by both RT-PCR assays. Seventy per cent of the adenocarcinomas showed overexpression of c-met, according to elevated c-met mRNA levels, compared with the expression level of normal gastric mucosa. A significant correlation was found between the level of c-met mRNA and protein expression. In conclusion, these results strongly suggest that tpr-met activation does not play a role in Caucasian gastric carcinogenesis, while overexpression of the c-met gene occurs in the majority of Caucasian gastric adenocarcinomas.

  7. Kwaliteit van leven en klachten na een zelfmanagementtraining bij patiënten met chronische angst en depressie: Een gerandomiseerde studie

    NARCIS (Netherlands)

    Muntingh, A.D.T.; Laheij, M.A.; Sinnema, H.; Zoun, M.H.H.; Balkom, A.J.L.M. van; Schene, A.H.; Spijker, J.

    2016-01-01

    Achtergrond: Er bestaat geen evidence-based rehabilitatieaanbod in de geestelijke gezondheidszorg (ggz) voor patiënten met chronische angst en/of depressie. Doel: Evalueren van het effect van de module 'Rehabilitatie door zelfmanagement' op kwaliteit van leven en klachten na zes maanden bij deze pat

  8. 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 PMID:27242035

  9. 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.

  10. 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…

  11. The Effect of a Unique Pacifier on Anterior Open Bite and Overjet in the Primary Dentition: A Pilot Study.

    Science.gov (United States)

    Nowak, Arthur J; Kim, Amy S; Scott, Jo Anna M; Berg, Joel H

    2016-01-01

    Pacifiers are the most common device used by children to satisfy their sucking needs. Because of their design, reports of anterior open bite and increased overjet are common. The purposes of this pilot study were to measure the effects of a unique pacifier in toddlers who have existing open bites and increased overjets; and secondly to determine the feasibility of recruiting and retaining toddlers for a six-month study. Toddlers with existing open bite and increased overjet currently using a conventional pacifier were recruited from a university pediatric dental clinic. Baseline information was obtained. Visual examination and intraoral measurements were obtained. The study pacifier was introduced to replace the existing pacifier. Follow-up data was collected at three and six months post-intervention. Eight of the 11 toddlers (73 percent) completed the study. Recruitment was challenging because of the inclusion criteria and transportation; retaining participants required numerous reminders to parents. There was a significant difference between initial and final open bite and overjet measurements. It is feasible to recruit and retain toddlers but it required significant staff interventions. There was a significant improvement in reducing existing open bite and overjet with the pacifier after six months.

  12. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Buchanan, Sean G.; Hendle, Jorg; Lee, Patrick S.; Smith, Christopher R.; Bounaud, Pierre-Yves; Jessen, Katti A.; Tang, Crystal M.; Huser, Nanni H.; Felce, Jeremy D.; Froning, Karen J.; Peterman, Marshall C.; Aubol, Brandon E.; Gessert, Steve F.; Sauder, J. Michael; Schwinn, Kenneth D.; Russell, Marijane; Rooney, Isabelle A.; Adams, Jason; Leon, Barbara C.; Do, Tuan H.; Blaney, Jeff M.; Sprengeler, Paul A.; Thompson, Devon A.; Smyth, Lydia; Pelletier, Laura A.; Atwell, Shane; Holme, Kevin; Wasserman, Stephen R.; Emtage, Spencer; Burley, Stephen K.; Reich, Siegfried H.; (Ventana); (SGX); (Genentech); (Amira)

    2010-01-12

    The MET receptor tyrosine kinase has emerged as an important target for the development of novel cancer therapeutics. Activation of MET by mutation or gene amplification has been linked to kidney, gastric, and lung cancers. In other cancers, such as glioblastoma, autocrine activation of MET has been demonstrated. Several classes of ATP-competitive inhibitor have been described, which inhibit MET but also other kinases. Here, we describe SGX523, a novel, ATP-competitive kinase inhibitor remarkable for its exquisite selectivity for MET. SGX523 potently inhibited MET with an IC{sub 50} of 4 nmol/L and is >1,000-fold selective versus the >200-fold selectivity of other protein kinases tested in biochemical assays. Crystallographic study revealed that SGX523 stabilizes MET in a unique inactive conformation that is inaccessible to other protein kinases, suggesting an explanation for the selectivity. SGX523 inhibited MET-mediated signaling, cell proliferation, and cell migration at nanomolar concentrations but had no effect on signaling dependent on other protein kinases, including the closely related RON, even at micromolar concentrations. SGX523 inhibition of MET in vivo was associated with the dose-dependent inhibition of growth of tumor xenografts derived from human glioblastoma and lung and gastric cancers, confirming the dependence of these tumors on MET catalytic activity. Our results show that SGX523 is the most selective inhibitor of MET catalytic activity described to date and is thus a useful tool to investigate the role of MET kinase in cancer without the confounding effects of promiscuous protein kinase inhibition.

  13. 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 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...

  14. Rapportage gewasbescherming 2007 Telen met toekomst - Bloembollen

    NARCIS (Netherlands)

    Haan, de J.J.

    2008-01-01

    Dit is het vierde rapportage gewasbescherming van het praktijknetwerk Telen met toekomst voor de open teelten. Het praktijknetwerk Telen met toekomst organiseert groepen praktijkbedrijven met hun relaties rond de ontwikkeling van meer duurzame productiesystemen (milieutechnisch, ecologisch en

  15. Active index model: a unique approach for regional quantitative morphometry in longitudinal and cross-sectional studies

    Science.gov (United States)

    Saha, P. K.; Zhang, H.; Sonka, M.; Christensen, G. E.; Rajapakse, C. S.

    2007-03-01

    Recent advancements in digital medical imaging have opened avenues for quantitative analyses of different volumetric and morphometric indices in response to a disease or a treatment. However, a major challenge in performing such an analysis is the lack of a technology of building a mean anatomic space (MAS) that allows mapping data of a given subject onto MAS. This approach leads to a tool for point-by-point regional analysis and comparison of quantitative indices for data coming from a longitudinal or transverse study. Toward this goal, we develop a new computation technique, called Active Index Model (AIM), which is a unique tool to solve the stated problem. AIM consists of three building blocks - (1) development of MAS for a particular anatomic site, (2) mapping a specific data onto MAS, (3) regional statistical analysis of data from different populations assessing regional response to a disease or treatment progression. The AIM presented here is built at the training phase from two known populations (e.g., normal and diseased) which will be immediately ready for diagnostic purpose in a subject whose clinical status is unknown. AIM will be useful for both cross sectional and longitudinal studies and for early diagnostic. This technique will be a vital tool for understanding regional response of a disease or treatment at various stages of its progression. This method has been applied for analyzing regional trabecular bone structural distribution in rabbit femur via micro-CT imaging and to localize the affected myocardial regions from cardiac MR data.

  16. 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

  17. Leven met Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Duijvendijk J. van, [No Value

    2004-01-01

    Leven met Inflammatory Bowel Disease Inflammatory bowel disease (IBD) is de verzamelnaam voor Colitis ulcerosa en de ziekte van Crohn. Het zijn chronische darmontstekingen, waarvan de ziekteactiviteit wisselt en zich niet laat voorspellen. Door de lichamelijke klachten en het onvoorspelbare karakter

  18. Water zuiveren met drijvende planten

    NARCIS (Netherlands)

    Keizer-Vlek, H.E.; Verdonschot, P.F.M.; Verdonschot, R.C.M.; Dekkers, T.B.M.

    2013-01-01

    Drijvende moerassystemen met helofyten, ook wel floating treatment wetlands of floatlands genoemd, worden in Nederland uitsluitend toegepast om natuurbeleving te stimuleren en de biodiversiteit van het oppervlaktewater te vergroten. Floatlands zijn echter mogelijk ook geschikt om nutriënten uit het

  19. Fijnstof te lijf met koolzaadolie

    NARCIS (Netherlands)

    Ogink, N.W.M.

    2010-01-01

    Wageningen UR Livestock Research onderzoekt een reeks aan maatregelen die de uitstoot van fijnstof bij pluimveebedrijven kunnen verminderen. Iedere dag wat koolzaadolie vernevelen is tot nu toe het meest hoopgevend, met als bijkomend voordeel dat het stalklimaat verbetert voor mens en dier.

  20. Water zuiveren met drijvende planten

    OpenAIRE

    Keizer-Vlek, H.E.; Verdonschot, P. F. M.; Verdonschot, R.C.M.; Dekkers, T.B.M.

    2013-01-01

    Drijvende moerassystemen met helofyten, ook wel floating treatment wetlands of floatlands genoemd, worden in Nederland uitsluitend toegepast om natuurbeleving te stimuleren en de biodiversiteit van het oppervlaktewater te vergroten. Floatlands zijn echter mogelijk ook geschikt om nutriënten uit het oppervlaktewater te verwijderen. Vooral in het stedelijk gebied is dit een aantrekkelijke optie. De gele lis is er uitermate voor geschikt.

  1. Leven met Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Duijvendijk J. van, [No Value

    2004-01-01

    Leven met Inflammatory Bowel Disease Inflammatory bowel disease (IBD) is de verzamelnaam voor Colitis ulcerosa en de ziekte van Crohn. Het zijn chronische darmontstekingen, waarvan de ziekteactiviteit wisselt en zich niet laat voorspellen. Door de lichamelijke klachten en het onvoorspelbare karakter

  2. Steeds preciezer met de sensor

    NARCIS (Netherlands)

    Houweling, van P.; PPO Akkerbouw, Groene Ruimte en Vollegrondsgroente

    2014-01-01

    Maurits Bax uit Luyksgestel werkt met de Yara N-sensor. Zo spuit hij minder dan een derde van de voorgeschreven dosering voor loofdodingsmiddel in aardappelen. Andere toepassingen zijn minder praktijkrijp, zoals aardappelen bijmesten. Daarvoor lijkt een app, ontwikkeld door het PPO, uitkomst te gaan

  3. Mogelijkheden voor notenteelt met tussengewas

    NARCIS (Netherlands)

    Oosterbaan, A.; Schepers, H.

    2005-01-01

    Er zijn enkele presentaties gehouden over de ervaringen met de teelt van walnoten in Nederland tijdens het vijfde Internationale Walnotencongres in Sorrento, Italië, gehouden in november 2004. De productie van walnoten in Nederland stelt nog niet veel voor. Er is dus ruimte voor eigen productie

  4. Motives for the Choice of StudiesUnique Study Programmes and Their Publication (the Survey of Vilnius Gediminas Technical University

    Directory of Open Access Journals (Sweden)

    Rasa Levickaitė

    2011-06-01

    Full Text Available In the school year of 2009–2010 Vilnius Gediminas Technical University initiated the the survey of motives for studies at this university. The aim of the research is to conduct a survey among first year undergraduate students and find out motives for their choise to study at Vilnius Gediminas Technical University. Due to weaknesses of national science and studies system, devaluation of diplomas, outdated teaching methods, scien- tific research unproductivity and simulation, lack of attention to the student, ineffective study loans system, discrimination of private study institutions and their students, etc., a new Science and Study Law was initiated in 2009. Thus new challenges to the country, universities, and university communities arise. Future students are becoming more aware studying opportunities both within the country and abroad. Motives and choices of studies are determined by more complex approaches and levers. The article analyses a survey is based on responses of first year undergraduates of Vilnius Gediminas Technical University. The objective of the survey is to find out why and how students have chosen to study at this university. The purpose of the article is to identify these motives, provide analysis and assessment of survey data.

  5. 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

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

    Directory of Open Access Journals (Sweden)

    Christoph Kuhn

    2008-03-01

    Full Text Available Christoph Kuhn1, Fiorenzo Angehrn1, Ortrud Sonnabend2, Axel Voss31Klinik Piano, Biel, Switzerland; 2Pathodiagnostics, Herisau, Switzerland; 3SwiTech Medical AG, Kreuzlingen, SwitzerlandAbstract: 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 acellulite 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.Keywords: cellulite, extracellular matrix, fat tissue, high-resolution ultrasound of skin, extracorporeal shock wave, histopathology, scaffolding of subcutaneous connective tissue

  7. Gezondheidsrisico's in verband met het werken met Dieldrin : een onderzoek

    OpenAIRE

    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

    Op basis van gegevens verkregen uit een oriënterende werkplekinventarisatie naar gegevens over produktie/gebruik, risicopopulatie en (mogelijke) blootstelling aan dieldrin en een literatuurstudie naar mogelijke schadelijke eigenschappen van dieldrin op het reproduktiesysteem en/of nageslacht (6000S-AIST-73/2) is een evaluatie gemaakt van het gezondheidsrisico van werken met dieldrin. Er zijn aanwijzingen voor reproduktierisico's m.b.t. tot blootstelling van volwassenen. Voor vrouwen in de vru...

  8. The double electrostatic ion ring experiment: A unique cryogenic electrostatic storage ring for merged ion-beams studies

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, R. D.; Schmidt, H. T.; Andler, G.; Bjoerkhage, M.; Blom, M.; Braennholm, L.; Baeckstroem, E.; Danared, H.; Das, S.; Haag, N.; Hallden, P.; Hellberg, F.; Holm, A. I. S.; Johansson, H. A. B.; Kaellberg, A.; Kaellersjoe, G.; Larsson, M.; Leontein, S.; Liljeby, L.; Loefgren, P. [Department of Physics, Stockholm University, SE-106 91 Stockholm (Sweden); and others

    2011-06-15

    We describe the design of a novel type of storage device currently under construction at Stockholm University, Sweden, using purely electrostatic focussing and deflection elements, in which ion beams of opposite charges are confined under extreme high vacuum cryogenic conditions in separate ''rings'' and merged over a common straight section. The construction of this double electrostatic ion ring experiment uniquely allows for studies of interactions between cations and anions at low and well-defined internal temperatures and centre-of-mass collision energies down to about 10 K and 10 meV, respectively. Position sensitive multi-hit detector systems have been extensively tested and proven to work in cryogenic environments and these will be used to measure correlations between reaction products in, for example, electron-transfer processes. The technical advantages of using purely electrostatic ion storage devices over magnetic ones are many, but the most relevant are: electrostatic elements which are more compact and easier to construct; remanent fields, hysteresis, and eddy-currents, which are of concern in magnetic devices, are no longer relevant; and electrical fields required to control the orbit of the ions are not only much easier to create and control than the corresponding magnetic fields, they also set no upper mass limit on the ions that can be stored. These technical differences are a boon to new areas of fundamental experimental research, not only in atomic and molecular physics but also in the boundaries of these fields with chemistry and biology. For examples, studies of interactions with internally cold molecular ions will be particular useful for applications in astrophysics, while studies of solvated ionic clusters will be of relevance to aeronomy and biology.

  9. Association study of a brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and personality trait and intelligence in healthy young females.

    Science.gov (United States)

    Tsai, Shih-Jen; Hong, Chen-Jee; Yu, Younger W-Y; Chen, Tai-Jui

    2004-01-01

    Brain-derived neurotrophic factor (BDNF), a member of the nerve-growth-factor family, plays an important role in neuronal survival and development, and it can modulate serotonergic activity. Further, BDNF has been implicated in the expression of personality traits and in cognitive function. We tested the associations between functional BDNF Val66Met genetic variants, and personality trait and intelligence in a cohort of 114 healthy young Chinese females. Subjects with the Val/Val genotype had a significantly higher mean performance IQ than Val/Met carriers, especially for the Object Assembly subtest. No significant association was demonstrated for the BDNF polymorphism and any of the Tridimensional Personality Questionnaire personality-factor scores, including harm avoidance. These results suggest that genetic variants of the BDNF gene may play a role in specific cognitive functions, but not in overall intelligence. In contrast to a recent report, however, this polymorphism does not appear to be associated with the neuroticism-related personality trait.

  10. 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.

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

    Science.gov (United States)

    Sayers, Susan M; Mackerras, Dorothy; Singh, Gurmeet; Bucens, Ingrid; Flynn, Kathryn; Reid, Alison

    2003-01-01

    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. PMID:12659639

  12. 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.

  13. Targeting MET Amplification as a New Oncogenic Driver

    Directory of Open Access Journals (Sweden)

    Hisato Kawakami

    2014-07-01

    Full Text Available 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.

  14. La metáfora

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2007-01-01

    cuestionamiento de la lógica y de las leyes establecidas se corresponde con lo que denominamos autonomía. Así pues, el proceso de autonomía zapatista consiste, por un lado, en la declaración y aplicación de los derechos indígenas y, por otro, en la creación de un sentido alternativo, donde la metáfora juega un...

  15. La metáfora

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2007-01-01

    cuestionamiento de la lógica y de las leyes establecidas se corresponde con lo que denominamos autonomía. Así pues, el proceso de autonomía zapatista consiste, por un lado, en la declaración y aplicación de los derechos indígenas y, por otro, en la creación de un sentido alternativo, donde la metáfora juega un...

  16. The Met-allele of the BDNF Val66Met polymorphism enhances task switching in elderly.

    Science.gov (United States)

    Gajewski, Patrick D; Hengstler, Jan G; Golka, Klaus; Falkenstein, Michael; Beste, Christian

    2011-12-01

    In this study we examined the relevance of the functional brain-derived neurotrophic factor (BDNF) Val66Met polymorphism as a modulator of task-switching performance in healthy elderly by using behavioral and event-related potential (ERP) measures. Task switching was examined in a cue-based and a memory-based paradigm. Val/Val carriers were generally slower, showed enhanced reaction time variability and higher error rates, particularly during memory-based task switching than the Met-allele individuals. On a neurophysiological level these dissociative effects were reflected by variations in the N2 and P3 ERP components. The task switch-related N2 was increased while the P3 was decreased in Met-allele carriers, while the Val/Val genotype group revealed the opposite pattern of results. In cue-based task-switching no behavioral and ERP differences were seen between the genotypes. These data suggest that superior memory-based task-switching performance in elderly Met-allele carriers may emerge due to more efficient response selection processes. The results implicate that under special circumstances the Met-allele renders cognitive processes more efficient than the Val/Val genotype in healthy elderly, corroborating recent findings in young subjects.

  17. Structural and functional studies on a unique linear neutralizing antigenic site (G5) of the rabies virus glycoprotein.

    NARCIS (Netherlands)

    R.W.J. van der Heijden (Roger); J.P.M. Langedijk; J. Groen (Jan); F.G.C.M. Uytdehaag (Fons); R.H. Meloen; A.D.M.E. Osterhaus (Albert)

    1993-01-01

    textabstractThe core of a unique linear neutralization epitope (G5) on the glycoprotein of rabies virus, recognized by a virus-neutralizing mouse monoclonal antibody (MAb 6-15C4), was determined by Pepscan analysis. The G5 epitope was defined as an octapeptide (LHDFRSDE). The contribution of the

  18. 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...

  19. Microarray analysis of prostate cancer progression to reduced androgen dependence: studies in unique models contrasts early and late molecular events.

    Science.gov (United States)

    Sirotnak, F M; She, Yuhong; Khokhar, Nushmia Z; Hayes, Paula; Gerald, William; Scher, Howard I

    2004-11-01

    Three unique variants of the CWR22 human prostate cancer xenograft model (CWR22LD1, LD2, and LD3) with a decrease in dependence on androgens were selected under noncastrate conditions, i.e., by outgrowth after transplantation into male NCR (AT) nu mice without testosterone supplementation. These variants were unable to grow in castrated male mice. For comparison, a second set of variants with even less dependence on androgens (castrate-resistant) were derived following outgrowth from CWR22 (CWR22Rv1 and RC) or CWRLD1 (CWR22RS) after transplantion in castrated male mice. The androgen receptor (AR) gene in the CWR22LD variants was transcriptionally active and was neither mutated nor significantly overexpressed compared to CWR22. Oligonucleotide microarray analysis showed distinctly different profiles of dysregulated gene expression among the CWR22LD variants. Groups of only 26-41 genes were dysregulated greater than threefold with a different proportion of up versus downregulated genes in each variant. Only one of the castrate-resistant variants (CWR22Rv1) had a highly overexpressed AR gene but AR in this variant and the two other castrate-resistant variants, CWR22 RS and RC, was not mutated beyond that seen in CWR22. In contrast to the CWR22LD variants, a total of 342, 295, and 222 genes were dysregulated at least threefold in CWR22Rv1, CWR22RS, and CWR22RC, respectively, differing as well in the proportion of up versus downregulated genes. Many of the genes dysregulated in CWR22LD1, LD2, and LD3 were further dysregulated in CWR22Rv1, RC, or RS. The most downregulated gene was microseminoprotein beta (MSPB). Along with cyclin D1, the most upregulated gene by an order of magnitude compared to other upregulated genes was hepatocyte growth factor (HGF) (scatter factor). These results suggest that the onset in the loss of androgen dependence in CWR22 proceeds through multiple pathways and does not require any direct change in the status of AR. However, upregulation of

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

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    Christensen James G

    2010-10-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer.

  1. Rapportage gewasbescherming 2007 Telen met toekomst - Champignons

    NARCIS (Netherlands)

    Haan, de J.J.

    2008-01-01

    Het praktijknetwerk Telen met toekomst organiseert groepen praktijkbedrijven met hun relaties rond de ontwikkeling van meer duurzame productiesystemen (milieutechnisch, ecologisch en economisch) in de plantaardige sectoren. Deze rapportage geeft het resultaat van een inventarisatie van de status van

  2. Groepshuisvesting zeugen: brijvoedering met lange trog

    NARCIS (Netherlands)

    Hoofs, A.I.J.; Mheen, van der H.

    2003-01-01

    Brijvoedering via een lange trog combineert de managementvoordelen van gelijktijdig vreten, en stabiele groepen met de economische voordelen van het voeren van brijvoedering met brijproducten. Dit voersysteem geniet dan ook veel belangstelling vanuit de praktijk.

  3. Physical Activity Pattern and Personal-Social Factors of Mothers During Pregnancy And Infant Birth Weight Based On MET Scale: A Case-Control Study.

    Science.gov (United States)

    Mahmoodi, Zohreh; Karimlou, Masoud; Sajjadi, Homeira; Dejman, Masoumeh; Vameghi, Meroe; Dolatian, Mahrokh; Baradarn Eftekhari, Monir

    2013-07-01

    Low birth weight is one of the most important public health issues in developing and developed countries and identifying its etiology is important for prevention. Considering the unknown impact of physical activity on low birth weight, this research was conducted to investigate the relationship between physical activity and low birth weight. This research was conducted using a case-control design. The control group was made of 500 women with normal birth weight infants and the case group included 250 women with low birth weight infants from the selected hospitals in city of Tehran. The information was gathered using a researcher-made questionnaire which was prepared for determining the relationship between mothers' lifestyle during pregnancy and infants' low birth weight using social determinants of health approach. In this questionnaire, scope of physical activity was investigated in three groups of athletic activities, activities at home and leisure activities. Activity intensity was determined using MET scale and the data were analyzed in SPSS software using independent t-test, Chi-square and logistic regression. In the present research, based on the results of multiple logistic regression test, an increase in the time spent on sport activities (OR = 2.20) and home activities (OR =1.44) (P = 0.003) was accompanied by increased chance of giving birth to low birth weight infants; in contrast, one hour increase of leisure activities decreased the probability of low birth weight infants by 0.32 (P = 0.008). An increase in the time spent on sport and home activities, even after considering other influential factors, was related to low birth weight.

  4. A phase-I study of lapatinib in combination with foretinib, a c-MET, AXL and vascular endothelial growth factor receptor inhibitor, in human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer.

    Science.gov (United States)

    Chia, Stephen K; Ellard, Susan L; Mates, Mihaela; Welch, Stephen; Mihalcioiu, Catalin; Miller, Wilson H; Gelmon, Karen; Lohrisch, Caroline; Kumar, Vikaash; Taylor, Sara; Hagerman, Linda; Goodwin, Rachel; Wang, Tao; Sakashita, Shingo; Tsao, Ming S; Eisenhauer, Elizabeth; Bradbury, Penelope

    2017-05-02

    The mechanisms of resistance to anti-human epidermal growth factor receptor 2 (HER 2) therapies are unclear but may include the tyrosine-protein kinase Met (c-Met), vascular endothelial growth factor (VEGF) and AXL pathways. Foretinib is an inhibitor of c-Met, VEGF receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFRB), AXL, Fms-like tyrosine kinase 3 (FLT3), angiopoiten receptor (TIE-2), RET and RON kinases. This phase Ib study sought to establish the associated toxicities, pharmacokinetics (PK) and recommended phase II doses (RP2D) of foretinib and lapatinib in a cohort of HER-2-positive patients with metastatic breast cancer (MBC). Women with HER-2 positive MBC, Performance status (PS 0-2), and no limit on number of prior chemotherapies or lines of anti-HER-2 therapies were enrolled. A 3 + 3 dose escalation design was utilized. Four dose levels were intended with starting doses of foretinib 30 mg and lapatinib 750 mg orally once a day (OD) on a 4-weekly cycle. Assessment of c-MET status from the primary archival tissue was performed. We enrolled 19 patients, all evaluable for toxicity assessment and for response evaluation. Median age was 60 years (34-86 years), 95% were PS 0-1, 53% were estrogen receptor-positive and 95% had at least one prior anti-HER-2-based regimen. The fourth dose level was reached (foretinib 45 mg/lapatinib 1250 mg) with dose-limiting toxicities of grade-3 diarrhea and fatigue. There was only one grade-4 non-hematological toxicity across all dose levels. There were no PK interactions between the agents. A median of two cycles was delivered across the dose levels (range 1-20) with associated progression-free survival of 3.2 months (95% CI 1.61-4.34 months). By immunohistochemical assessment with a specified cutoff, none of the 17 samples tested were classified as positive for c-Met. The RP2D of the combined foretinib and lapatinib is 45 mg and 1000 mg PO OD, respectively. Limited activity was seen with this

  5. Computergestuurde circulatieregelingen : optimaal bewaarklimaat met minimaal energieverbruik

    NARCIS (Netherlands)

    Wildschut, J.; Janssen, H.J.J.; Sapounas, A.; Gieling, T.H.

    2011-01-01

    Bij het bewaren van bloembollen in kuubskisten gestapeld voor een systeemwand in een bewaarcel wordt voor de ventilatie met buitenlucht, en voor de circulatie met cellucht veel energie verbruikt. Door het ventilatiedebiet met de klimaatcomputer te sturen op basis van ethyleenmeting wordt bij het bew

  6. MET and AKT genetic influence on facial emotion perception.

    Directory of Open Access Journals (Sweden)

    Ming-Teng Lin

    Full Text Available BACKGROUND: Facial emotion perception is a major social skill, but its molecular signal pathway remains unclear. The MET/AKT cascade affects neurodevelopment in general populations and face recognition in patients with autism. This study explores the possible role of MET/AKT cascade in facial emotion perception. METHODS: One hundred and eighty two unrelated healthy volunteers (82 men and 100 women were recruited. Four single nucleotide polymorphisms (SNP of MET (rs2237717, rs41735, rs42336, and rs1858830 and AKT rs1130233 were genotyped and tested for their effects on facial emotion perception. Facial emotion perception was assessed by the face task of Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT. Thorough neurocognitive functions were also assessed. RESULTS: Regarding MET rs2237717, individuals with the CT genotype performed better in facial emotion perception than those with TT (p = 0.016 by ANOVA, 0.018 by general linear regression model [GLM] to control for age, gender, and education duration, and showed no difference with those with CC. Carriers with the most common MET CGA haplotype (frequency = 50.5% performed better than non-carriers of CGA in facial emotion perception (p = 0.018, df = 1, F = 5.69, p = 0.009 by GLM. In MET rs2237717/AKT rs1130233 interaction, the C carrier/G carrier group showed better facial emotion perception than those with the TT/AA genotype (p = 0.035 by ANOVA, 0.015 by GLM, even when neurocognitive functions were controlled (p = 0.046 by GLM. CONCLUSIONS: To our knowledge, this is the first study to suggest that genetic factors can affect performance of facial emotion perception. The findings indicate that MET variances and MET/AKT interaction may affect facial emotion perception, implicating that the MET/AKT cascade plays a significant role in facial emotion perception. Further replication studies are needed.

  7. 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

  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. Estudo retrospectivo dos carcinomas epidermóides das vias aerodigestivas superiores com metástases bilaterais Squamous cell carcinoma of the upper aerodigestive tract with bilateral metastasis: a retrospective study

    Directory of Open Access Journals (Sweden)

    Ali Amar

    2005-06-01

    Full Text Available OBJETIVO: Estudo retrospectivo das características dos carcinomas epidermóides das vias aerodigestivas superiores relacionadas ao desenvolvimento de metástases cervicais bilaterais. MÉTODO: Foram revisados os prontuários de 150 pacientes com carcinoma epidermóide de boca, orofaringe, laringe e hipofaringe submetidos a esvaziamento cervical bilateral entre janeiro de 1979 e dezembro de 1996, dos quais foram selecionados 73 pacientes que apresentavam metástases bilaterais confirmadas no exame histológico. Foram considerados o estadiamento e a localização dos tumores, confrontando os achados com os estudos sobre drenagem linfática e distribuição das metástases cervicais neste tipo de tumor. RESULTADOS: Quatorze pacientes apresentaram tumor primário nos estádios T1 e T2, 57 nos estádios T3 e T4 e dois não foram estadiados (Tx. Nos cinco pacientes T1 ou T2 de laringe com metástases bilaterais, a lesão estava localizada na epiglote. CONCLUSÕES: Nos pacientes com lesões unilaterais que apresentaram disseminação bilateral, todos apresentavam lesões palpáveis unilaterais.BACKGROUND: A descriptive study of the characteristics of squamous cell carcinoma of upper aerodigestive tract related to bilateral neck metastasis is established. METHODS: Files of 150 patients with SCC of mouth, oropharynx, larynx and hypopharynx who underwent bilateral neck dissection between January 1979 and December 1996, were reviewed, and 73 with histologic bilateral neck metastasis pN+ were selected. Stage and location of the tumors were considered and results were analysed in front of lymphatic drainage and metastasis distribution studies. RESULTS: Fourteen patients with primary tumor in stages T1 and T2, 57 in stages T3 and T4 and 2 were staged as Tx. In 5 patients in stages T1 and T2 of the larynx with bilateral metastases, the lesion were localized in the epiglottis. CONCLUSION: In patients with unilateral lesions with bilateral dissemination, all

  10. Unique Regulatory Properties of Heterotetrameric Inositol 1,4,5-Trisphosphate Receptors Revealed by Studying Concatenated Receptor Constructs.

    Science.gov (United States)

    Chandrasekhar, Rahul; Alzayady, Kamil J; Wagner, Larry E; Yule, David I

    2016-03-01

    The ability of inositol 1,4,5-trisphosphate receptors (IP3R) to precisely initiate and generate a diverse variety of intracellular Ca(2+) signals is in part mediated by the differential regulation of the three subtypes (R1, R2, and R3) by key functional modulators (IP3, Ca(2+), and ATP). However, the contribution of IP3R heterotetramerization to Ca(2+) signal diversity has largely been unexplored. In this report, we provide the first definitive biochemical evidence of endogenous heterotetramer formation. Additionally, we examine the contribution of individual subtypes within defined concatenated heterotetramers to the shaping of Ca(2+) signals. Under conditions where key regulators of IP3R function are optimal for Ca(2+) release, we demonstrate that individual monomers within heteromeric IP3Rs contributed equally toward generating a distinct 'blended' sensitivity to IP3 that is likely dictated by the unique IP3 binding affinity of the heteromers. However, under suboptimal conditions where [ATP] were varied, we found that one subtype dictated the ATP regulatory properties of heteromers. We show that R2 monomers within a heterotetramer were both necessary and sufficient to dictate the ATP regulatory properties. Finally, the ATP-binding site B in R2 critical for ATP regulation was mutated and rendered non-functional to address questions relating to the stoichiometry of IP3R regulation. Two intact R2 monomers were sufficient to maintain ATP regulation in R2 homotetramers. In summary, we demonstrate that heterotetrameric IP3R do not necessarily behave as the sum of the constituent subunits, and these properties likely extend the versatility of IP3-induced Ca(2+) signaling in cells expressing multiple IP3R isoforms.

  11. A Unique Approach for Studying Venus’s Atmosphere: Technology Development for the Venus Atmospheric Maneuverable Platform (VAMP)

    Science.gov (United States)

    Samuele, Rocco; Lee, Greg; Sokol, Daniel; Polidan, Ron; Griffin, Kristen; Bolisay, Linden; Michi, Yuki; Barnes, Nathan

    2014-11-01

    We are investigating a novel, reduced-risk approach to long-duration upper atmosphere exploration of Venus. The Venus Atmospheric Maneuverable Platform (VAMP) concept is a semi-buoyant plane with a science payload that can perform in situ measurements of Venus’s atmosphere. VAMP is also capable of revisiting scientifically interesting locations. Designed with a low ballistic coefficient, VAMP deploys in space and enters Venus’s atmosphere without an aeroshell. Once in the atmosphere, it can engage in a variety of science campaigns while varying its altitude between 50 and 68 km as it circumnavigates Venus. During daytime, VAMP will be able to make continuous science measurements at a range of latitudes, longitudes, and altitudes, while at night the vehicle will descend to a fully-buoyant, lower-power state, capable of performing modest science measurements at the float altitude. Near the end of VAMP’s mission life, the vehicle may attempt an end-of-life trajectory into higher latitudes or descend to lower altitudes. This presentation focuses on the technology roadmap that will allow the vehicle to accomplish these science measurements. The roadmap is driven by high priority science measurements and the technology needed to implement VAMP’s main mission phases: deployment, entry into Venus’s atmosphere, and the transition to flight and science flight performance. The roadmap includes materials tests, planform aerodynamic characterization, various subscale and full-scale packaging and deployment tests, and a full-scale suborbital flight and is being produced with extensive science community interaction to define the science measurements that would be uniquely possible with this new science platform.

  12. 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

  13. The Role of Catechol-O-Methyl Transferase Val(108/158)Met Polymorphism (rs4680) in the Effect of Green Tea on Resting Energy Expenditure and Fat Oxidation: A Pilot Study

    Science.gov (United States)

    Hursel, Rick; Janssens, Pilou L. H. R.; Bouwman, Freek G.; Mariman, Edwin C.; Westerterp-Plantenga, Margriet S.

    2014-01-01

    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, COMTH(Val/Val genotype), and low-activity COMTL(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 COMTH-genotype and 7 with the COMTL-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 COMTH genotype, but not for subjects carrying the COMTL 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 COMTH genotype increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs, placebo, whereas COMTL 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-individual variability for EE

  14. c-Met in pancreatic cancer stem cells: Therapeutic implications

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Aizpea Zubia-Olascoaga; Luis Bujanda

    2012-01-01

    Pancreatic cancer is the deadliest solid cancer and currently the fourth most frequent cause of cancer-related deaths.Emerging evidence suggests that cancer stem cells (CSCs) play a crucial role in the development and progression of this disease.The identification of CSC markers could lead to the development of new therapeutic targets.In this study,the authors explore the functional role of c-Met in pancreatic CSCs,by analyzing self-renewal with sphere assays and tumorigenicity capacity in NOD SCID mice.They concluded that c-Met is a novel marker for identifying pancreatic CSCs and c-Methigh in a higher tumorigenic cancer cell population.Inhibition of c-Met with XL184 blocks self-renewal capacity in pancreatic CSCs.In pancreatic tumors established in NOD SCID mice,c-Met inhibition slowed tumor growth and reduced the population of CSCs,along with preventing the development of metastases.

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

    Energy Technology Data Exchange (ETDEWEB)

    Steiner, A.K.; Kirchengast, G. [Graz Univ. (Austria). Inst. fuer Meteorologie und Geophysik; Ladreiter, H.P.

    1999-01-01

    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. 28 refs.

  16. Unique selectivity reversal in Am(3+)-Eu(3+) extraction in a tripodal TREN-based diglycolamide in ionic liquid: extraction, luminescence, complexation and structural studies.

    Science.gov (United States)

    Leoncini, Andrea; Mohapatra, Prasanta K; Bhattacharyya, Arunasis; Raut, Dhaval R; Sengupta, Arijit; Verma, Parveen K; Tiwari, Nidhi; Bhattacharyya, Dibyendu; Jha, Sambhunath; Wouda, Anna M; Huskens, Jurriaan; Verboom, Willem

    2016-02-14

    An N-pivot diglycolamide extractant (DGA-TREN) was synthesized for the first time and its complexation behaviour was studied towards trivalent lanthanide/actinide ions. The solvent extraction studies suggested a unique selectivity reversal in the extraction of trivalent actinides versus trivalent lanthanides which was observed performing extraction studies in an ionic liquid vis-à-vis a molecular diluent for a tripodal TREN-based diglycolamide ligand (DGA-TREN) vs. a tripodal diglycolamide ligand (T-DGA) which may have great significance in radioactive waste remediation. The nature of the bonding to Eu(3+) ion was investigated by EXAFS as well as by DFT calculations.

  17. Bio-energy. An overview study of environmental aspects of techniques for biomass based generated energy; Bio-energiecentrales. Inventariserend onderzoek naar milieu-aspecten bij diverse energieopwekkingtechnieken met behulp van biomassa

    Energy Technology Data Exchange (ETDEWEB)

    Morgenstern, P.P.; De Groot, G.M.

    2010-11-15

    The RIVM conducted a short overview study of techniques applied in the Netherlands to produce biomass based fuel or biomass based generated energy. The study focuses on scale and potential emissions for different branches. Relevant laws are included in the study as well. The overview is made on behalf of the VROM-inspectorate and is meant as an overview of current developments regarding biomass based generated energy. The scope of this study was set in consultation with the VROM-Inspectorate. Most attention was given to combustion on small and average scale, gassing and pyrolysis. These techniques need different temperatures and doses of oxygen and result in different products, e.g. oil, coal and gas. The term fermentation in this study is mainly used for the fermentation of dung. If an additional organic product is added the term co-fermentation is used. [Dutch] Het RIVM heeft een overzicht gemaakt van technieken die in Nederland worden gebruikt om biobrandstoffen te produceren of energie op te wekken met behulp van biobrandstoffen. De aandacht gaat uit naar de schaal waarop dit plaatsvindt en de emissies van deze bedrijven die bij de desbetreffende technieken kunnen vrijkomen. Daarnaast is de relevante wet- en regelgeving in kaart gebracht. Het overzicht is gemaakt op verzoek van de VROM-Inspectie, die hiermee zicht wil krijgen op de huidige ontwikkelingen waarbij biomassa wordt gebruikt om energie op te wekken. In overleg met de VROM-Inspectie is het onderzoek verder afgebakend. De meeste aandacht gaat uit naar verbrandingsinstallaties op kleine of middelgrote schaal, vergassinginstallaties, pyrolyse-installaties en (co)-vergistinginstallaties. Pyrolyse, vergassing en verbranding zijn technieken waarbij verschillende temperaturen en hoeveelheden zuurstof tot verschillende producten leiden. Deze producten zijn bijvoorbeeld olie, kolen en gas. Bij vergisting wordt in dit onderzoek vooral de productie van biogas uit mest bedoeld. Er is sprake van co-vergisting als

  18. 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.

  19. Toepasbaarheid en effectiviteit van mindfulnesstraining bij volwassenen met AD(H)D; een open pilotonderzoek [Feasibility and effectiveness of mindfulness training in adults with ADHD: A pilot study

    NARCIS (Netherlands)

    Hepark, S.; Kan, C.C.; Speckens, A.E.M.

    2014-01-01

    BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a developmental disorder that often continues into adulthood. Stimulant medication is the common treatment for ADHD. However, there is a need for psychosocial interventions in addition to medication. AIM: To conduct a pilot study which e

  20. Effecten van rode fietssuggestiestroken in combinatie met plateaus op verkeers-gedrag in Hellendoorn : studie voor en na aanleg op de Poggenbeltweg. In opdracht van de Gemeente Hellendoorn.

    NARCIS (Netherlands)

    Kooi, R.M. van der

    2001-01-01

    This study of the effects of red non-compulsory cycle lanes in the borough of Hellendoorn has gained a place in the broader ‘Experimental data collection project - non-compulsory cycle lanes’ within the SWOV theme of ‘Road design and road safety’. Various road authorities participate in that experim

  1. 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 adequat

  2. 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.

  3. Berekeningsresultaten met het model galvanisch bedrijf

    NARCIS (Netherlands)

    Ros; J.P.M.

    1986-01-01

    Met het model galvanisch bedrijf zijn computerberekeningen uitgevoerd aan 24 modelbedrijven. Daarbij is met name nagegaan, welke kosten moeten worden gemaakt om welk rendement te verkrijgen bij diverse saneringsvarianten. Het blijkt, dat tegen kosten tussen nul en 300 gulden per verwijderde kilo

  4. Werken met een inflammatoire darmziekte in Nederland.

    NARCIS (Netherlands)

    Netjes, J.; Borst, J. de; Rijken, M.

    2011-01-01

    Mensen met de ziekte van Crohn of colitis ulcerosa zijn net zo vaak actief op de arbeidsmarkt als andere Nederlanders. Wel werken ze minder vaak fulltime en heeft het merendeel meer of minder last van de ziekte bij hun werk als gevolg van vermoeidheid, stress of spanning. Mensen met een chronische

  5. XML: De eend met de gouden eieren?

    NARCIS (Netherlands)

    Keulen, van Maurice

    2001-01-01

    XML is al een tijdje één van de hypes. Alles moet met XML. Als kritisch informaticus begint het dan bij mij te kriebelen. Hoezo alles moet met XML? Klinkt een beetje als ik heb een hamer en alles ziet er ineens uit als een spijker. Het kan toch niet waar zijn dat men werkelijk iets heeft uitgevonden

  6. Werken met een inflammatoire darmziekte in Nederland.

    NARCIS (Netherlands)

    Netjes, J.; Borst, J. de; Rijken, M.

    2011-01-01

    Mensen met de ziekte van Crohn of colitis ulcerosa zijn net zo vaak actief op de arbeidsmarkt als andere Nederlanders. Wel werken ze minder vaak fulltime en heeft het merendeel meer of minder last van de ziekte bij hun werk als gevolg van vermoeidheid, stress of spanning. Mensen met een chronische

  7. Bespuiten met calcium kan neusrot voorkomen

    NARCIS (Netherlands)

    Zandstra, G.B.; Marcelis, L.F.M.

    2000-01-01

    Oorzaak van neusrot bij paprika is een calciumtekort in de vrucht. Een bespuiting met calcium vlak na de bloei heeft een zeer gunstig effect. In bijgaande tabel gegevens over het effect van spuiten met calcium op het optreden van neusrot bij paprika

  8. Biobrandstof met het gemak van benzine

    NARCIS (Netherlands)

    Klein Lankhorst, R.M.

    2015-01-01

    Onderzoekers in Wageningen werken aan brandstoffen voor voertuigen die hernieuwbaar zijn en tegelijk hetzelfde gemak kennen als benzine en diesel. In het BioSolar Cellsconsortium werken ze met technieken die geïnspireerd zijn op fotosynthese in planten. Van water wordt met zonlicht waterstof gemaakt

  9. Met apps op eigen benen leren staan

    NARCIS (Netherlands)

    Jan-Pieter Teunisse

    2012-01-01

    Mensen met autisme kunnen in de toekomst zelfstandiger wonen, werken en studeren met behulp van `digitale coaches' op hun mobieltje, iPad of iPod. Bij het testen van deze apps en andere nieuwe technologische hulpmiddelen, is ook de HAN betrokken. `ICT-oplossingen kunnen iemand helpen om meer regie

  10. MET Suppresses Epithelial VEGFR2 via Intracrine VEGF-induced Endoplasmic Reticulum-associated Degradation

    Directory of Open Access Journals (Sweden)

    Tom T. Chen

    2015-05-01

    Full Text Available Hepatocyte growth factor (HGF and vascular endothelial growth factor (VEGF drive cancer through their respective receptors, MET and VEGF receptor 2 (VEGFR2. VEGFR2 inhibits MET by promoting MET dephosphorylation. However, whether MET conversely regulates VEGFR2 remains unknown. Here we show that MET suppresses VEGFR2 protein by inducing its endoplasmic-reticulum-associated degradation (ERAD, via intracrine VEGF action. HGF–MET signaling in epithelial cancer cells promoted VEGF biosynthesis through PI3-kinase. In turn, VEGF and VEGFR2 associated within the ER, activating inositol-requiring enzyme 1α, and thereby facilitating ERAD-mediated depletion of VEGFR2. MET disruption upregulated VEGFR2, inducing compensatory tumor growth via VEGFR2 and MEK. However, concurrent disruption of MET and either VEGF or MEK circumvented this, enabling more profound tumor inhibition. Our findings uncover unique cross-regulation between MET and VEGFR2—two RTKs that play significant roles in tumor malignancy. Furthermore, these results suggest rational combinatorial strategies for targeting RTK signaling pathways more effectively, which has potentially important implications for cancer therapy.

  11. Toepasbaarheid en effectiviteit van mindfulnesstraining bij volwassenen met AD(H)D; een open pilotonderzoek [Feasibility and effectiveness of mindfulness training in adults with ADHD: A pilot study

    OpenAIRE

    Hepark, S.; Kan, C C; Speckens, A.E.M.

    2014-01-01

    BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a developmental disorder that often continues into adulthood. Stimulant medication is the common treatment for ADHD. However, there is a need for psychosocial interventions in addition to medication. AIM: To conduct a pilot study which examines the feasibility and effectiveness of mindfulness training for adults with ADHD. METHOD: Eleven adults with ADHD participated in a mindfulness training scheme lasting 10 weeks. ADHD symptoms...

  12. Distinct severity stages of obstructive sleep apnoea are correlated with unique dyslipidaemia: large-scale observational study

    OpenAIRE

    Guan, Jian; YI, HONGLIANG; Zou, Jianyin; Meng, Lili; Tang, Xulan; Zhu, Huaming; Yu, Dongzhen; Zhou, Huiqun; Su, Kaiming; Yang, Mingpo; Chen, Haoyan; Shi, Yongyong; Wang, Yue; WANG Jian; YIN, SHANKAI

    2016-01-01

    Background Dyslipidaemia is an intermediary exacerbation factor for various diseases but the impact of obstructive sleep apnoea (OSA) on dyslipidaemia remains unclear. Methods A total of 3582 subjects with suspected OSA consecutively admitted to our hospital sleep centre were screened and 2983 (2422 with OSA) were included in the Shanghai Sleep Health Study. OSA severity was quantified using the apnoea–hypopnea index (AHI), the oxygen desaturation index and the arousal index. Biochemical indi...

  13. Met and its ligand HGF are associated with clinical outcome in breast cancer

    Science.gov (United States)

    Veenstra, Cynthia; Pérez-Tenorio, Gizeh; Stelling, Anna; Karlsson, Elin; Mirwani, Sanam Mirwani; Nordensköljd, Bo; Fornander, Tommy; Stål, Olle

    2016-01-01

    Few biomarkers exist to predict radiotherapy response in breast cancer. In vitro studies suggest a role for Met and its ligand HGF. To study this suggested role, MET and HGF gene copy numbers were determined by droplet digital PCR in tumours from 205 pre-menopausal and 184 post-menopausal patients, both cohorts randomised to receive either chemo- or radiotherapy. MET amplification was found in 8% of the patients in both cohorts and HGF amplification in 7% and 6% of the patients in the pre- and post-menopausal cohort, respectively. Met, phosphorylated Met (pMet), and HGF protein expression was determined by immunohistochemistry in the pre-menopausal cohort. Met, pMet, and HGF was expressed in 33%, 53%, and 49% of the tumours, respectively. MET amplification was associated with increased risk of distant recurrence for patients receiving chemotherapy. For the pre-menopausal patients, expression of cytoplasmic pMet and HGF significantly predicted benefit from radiotherapy in terms of loco-regional recurrence. Similar trends were seen for MET and HGF copy gain. In the post-menopausal cohort, no significant association of benefit from radiotherapy with neither genes nor proteins was found. The present results do not support that inhibition of Met prior to radiotherapy would be favourable for pre-menopausal breast cancer, as previously suggested. PMID:27175600

  14. Unusual and Unique Variant Branches of Lateral Cord of Brachial Plexus and its Clinical Implications- A Cadaveric Study

    Science.gov (United States)

    Padur, Ashwini Aithal; Shanthakumar, Swamy Ravindra; Shetty, Surekha Devadas; Prabhu, Gayathri Sharath; Patil, Jyothsna

    2016-01-01

    Introduction Adequate knowledge on variant morphology of brachial plexus and its branches are important in clinical applications pertaining to trauma and surgical procedures of the upper extremity. Aim Current study was aimed to report variations of the branches of the lateral cord of brachial plexus in the axilla and their possible clinical complications. Materials and Methods Total number of 82 upper limbs from 41 formalin embalmed cadavers was dissected. Careful observation was made to note the formation and branching pattern of lateral cord. Meticulous inspection for absence of branches, presence of additional or variant branches and presence of abnormal communications between its branches or with branches of other cords was carried out. Results In the present study, we noted varied branching pattern of lateral cord in 6 out of 82 limbs (7%). In one of the limb, the median nerve was formed by three roots; two from lateral cord and one from medial cord. Two limbs had absence of lateral pectoral nerve supplemented by medial pectoral nerves. One of which had an atypical ansa pectoralis. In 2 upper limbs, musculocutaneous nerve was absent and in both cases it was supplemented by median nerve. In one of the limb, coracobrachialis had dual nerve supply by musculocutaneous nerve and by an additional branch from the lateral cord. Conclusion Variations of brachial plexus and its branches could pose both intraoperative and postoperative complications which eventually affect the normal sensory and motor functions of the upper limb. PMID:27190783

  15. Songbird: a unique animal model for studying the molecular basis of disorders of vocal development and communication.

    Science.gov (United States)

    Mori, Chihiro; Wada, Kazuhiro

    2015-01-01

    Like humans, songbirds are one of the few animal groups that learn vocalization. Vocal learning requires coordination of auditory input and vocal output using auditory feedback to guide one's own vocalizations during a specific developmental stage known as the critical period. Songbirds are good animal models for understand the neural basis of vocal learning, a complex form of imitation, because they have many parallels to humans with regard to the features of vocal behavior and neural circuits dedicated to vocal learning. In this review, we will summarize the behavioral, neural, and genetic traits of birdsong. We will also discuss how studies of birdsong can help us understand how the development of neural circuits for vocal learning and production is driven by sensory input (auditory information) and motor output (vocalization).

  16. 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

  17. Unique Access to Learning

    Science.gov (United States)

    Goble, Don

    2009-01-01

    This article describes the many learning opportunities that broadcast technology students at Ladue Horton Watkins High School in St. Louis, Missouri, experience because of their unique access to technology and methods of learning. Through scaffolding, stepladder techniques, and trial by fire, students learn to produce multiple television programs,…

  18. 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.

  19. ξTauri: a unique laboratory to study the dynamic interaction in a compact hierarchical quadruple system

    Science.gov (United States)

    Nemravová, J. A.; Harmanec, P.; Brož, M.; Vokrouhlický, D.; Mourard, D.; Hummel, C. A.; Cameron, C.; Matthews, J. M.; Bolton, C. T.; Božić, H.; Chini, R.; Dembsky, T.; Engle, S.; Farrington, C.; Grunhut, J. H.; Guenther, D. B.; Guinan, E. F.; Korčáková, D.; Koubský, P.; Kříček, R.; Kuschnig, R.; Mayer, P.; McCook, G. P.; Moffat, A. F. J.; Nardetto, N.; Prša, A.; Ribeiro, J.; Rowe, J.; Rucinski, S.; Škoda, P.; Šlechta, M.; Tallon-Bosc, I.; Votruba, V.; Weiss, W. W.; Wolf, M.; Zasche, P.; Zavala, R. T.

    2016-10-01

    Context. Compact hierarchical systems are important because the effects caused by the dynamical interaction among its members occur ona human timescale. These interactions play a role in the formation of close binaries through Kozai cycles with tides. One such system is ξ Tauri: it has three hierarchical orbits: 7.14 d (eclipsing components Aa, Ab), 145 d (components Aa+Ab, B), and 51 yr (components Aa+Ab+B, C). Aims: We aim to obtain physical properties of the system and to study the dynamical interaction between its components. Methods: Our analysis is based on a large series of spectroscopic photometric (including space-borne) observations and long-baseline optical and infrared spectro-interferometric observations. We used two approaches to infer the system properties: a set of observation-specific models, where all components have elliptical trajectories, and an N-body model, which computes the trajectory of each component by integrating Newton's equations of motion. Results: The triple subsystem exhibits clear signs of dynamical interaction. The most pronounced are the advance of the apsidal line and eclipse-timing variations. We determined the geometry of all three orbits using both observation-specific and N-body models. The latter correctly accounted for observed effects of the dynamical interaction, predicted cyclic variations of orbital inclinations, and determined the sense of motion of all orbits. Using perturbation theory, we demonstrate that prominent secular and periodic dynamical effects are explainable with a quadrupole interaction. We constrained the basic properties of all components, especially of members of the inner triple subsystem and detected rapid low-amplitude light variations that we attribute to co-rotating surface structures of component B. We also estimated the radius of component B. Properties of component C remain uncertain because of its low relative luminosity. We provide an independent estimate of the distance to the system

  20. Unique and shared responses of the gut microbiota to prolonged fasting: a comparative study across five classes of vertebrate hosts.

    Science.gov (United States)

    Kohl, Kevin D; Amaya, James; Passement, Celeste A; Dearing, M Denise; McCue, Marshall D

    2014-12-01

    Many animals face unpredictable food sources and periods of prolonged fasting, which likely present significant challenges to gut microorganisms. While several studies have demonstrated that fasting impacts the gut microbiota, experiments have not been carried out in a comparative context. We used 16S rRNA gene sequencing to document changes in colonic and cecal microbiomes of animals representing five classes of vertebrates at four time points through prolonged fasting: tilapia, toads, geckos, quail, and mice. We found differences in the starvation-induced changes in the microbiome across host species and across gut regions. Microbial phylogenetic diversity increased as a result of fasting in the colons of fish, toads, and mice, while quail exhibited a decrease in diversity; geckos exhibited no change. Microbial diversity in the cecum decreased in fish and exhibited no change in mice. Alterations in relative abundances of microbial taxa varied across hosts. Fish exhibited the most significant changes due to fasting, while geckos maintained a stable community over 28 days of fasting. We uncovered several shared responses of the microbiota across hosts. For example, all tetrapods exhibited decreases in the abundances of Coprobacillus and Ruminococcus in response to fasting. We also discuss host-mediated physiological mechanisms that may underlie these community changes.

  1. 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.

  2. Case-control study of arsenic in drinking water and kidney cancer in uniquely exposed Northern Chile.

    Science.gov (United States)

    Ferreccio, Catterina; Smith, Allan H; Durán, Viviana; Barlaro, Teresa; Benítez, Hugo; Valdés, Rodrigo; Aguirre, Juan José; Moore, Lee E; Acevedo, Johanna; Vásquez, María Isabel; Pérez, Liliana; Yuan, Yan; Liaw, Jane; Cantor, Kenneth P; Steinmaus, Craig

    2013-09-01

    Millions of people worldwide are exposed to arsenic in drinking water. The International Agency for Research on Cancer has concluded that ingested arsenic causes lung, bladder, and skin cancer. However, a similar conclusion was not made for kidney cancer because of a lack of research with individual data on exposure and dose-response. With its unusual geology, high exposures, and good information on past arsenic water concentrations, northern Chile is one of the best places in the world to investigate the carcinogenicity of arsenic. We performed a case-control study in 2007-2010 of 122 kidney cancer cases and 640 population-based controls with individual data on exposure and potential confounders. Cases included 76 renal cell, 24 transitional cell renal pelvis and ureter, and 22 other kidney cancers. For renal pelvis and ureter cancers, the adjusted odds ratios by average arsenic intakes of 1,000 µg/day (median water concentrations of 60, 300, and 860 µg/L) were 1.00, 5.71 (95% confidence interval: 1.65, 19.82), and 11.09 (95% confidence interval: 3.60, 34.16) (Ptrend water arsenic causes renal pelvis and ureter cancer.

  3. "Systems Education Experiences: Transforming high school science education through unique partnerships, inquiry based modules, and ocean systems studies"

    Science.gov (United States)

    Ludwig, C.; Orellana, M. V.; Baliga, N. S.

    2012-12-01

    Recent advances in experimental practice, accompanying computational techniques and systems thinking, have advanced biological inquiry. However, current scientific practices do not typically resemble the science taught in schools. As a result, students are missing out on significant opportunities to develop the critical thinking that is needed both in science and many professions. As a potential solution to this ongoing problem in science education, we are using current scientific practices to create classroom activities, packaged in easy-to-use curriculum modules, which promote conceptual development of standards based instructional outcomes. By bringing together students, teachers, researchers, engineers, and programmers we bring needed systems thinking and engaging inquiry experiences to schools throughout Washington State and the nation. Teachers are trained and continuously supported as they learn needed content and methods to bring this new science into their classrooms. Current research on ocean acidification, changing biogeochemical cycles, and the complexity and interdisciplinary nature of ocean systems studies have been translated through our newest curriculum module. Developing this module presented a significant challenge due to the urgency and importance of instilling understanding in high school students as they prepare to make decisions on the highly charged political, economic, and scientific issues of climate change and ocean acidification. Challenges have been overcome through partnerships and through infusing the habits of sustainability, high level thinking, systems modeling, scientific design, and communication. The Next Generation Standards have opened the door for nationwide dissemination of the module as we embark enabling students to think, understand, and contribute to scientific research.

  4. 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.

  5. Predictors of heroin relapse: Personality traits, impulsivity, COMT gene Val158met polymorphism in a 5-year prospective study in Shanghai, China.

    Science.gov (United States)

    Su, Hang; Li, Zhibin; Du, Jiang; Jiang, Haifeng; Chen, Zhikang; Sun, Haiming; Zhao, Min

    2015-12-01

    Relapse is a typical feature of heroin addiction and rooted in genetic and psychological determinants. The aim of this study was to evaluate the effect of personality traits, impulsivity, and COMT gene polymorphism (rs4680) on relapse to heroin use during 5-year follow up. 564 heroin dependent patients were enrolled in compulsory drug rehabilitation center. 12 months prior to their release, personality traits were measured by BIS-11 (Barratt Impulsiveness Scale-11) and Temperament and Character Inventory (TCI). The COMT gene rs4680 polymorphism was genotyped using a DNA sequence detection system. The heroin use status was evaluated for 5 years after discharged. Among the 564 heroin-dependent patients, 500 were followed for 5 years after discharge and 53.0% (n = 265) were considered as relapsed to heroin use according to a strict monitor system. Univariate analysis showed that age, having ever been in methadone maintenance treatment (MMT), the total scores and non-planning scores of BIS-11, and the COMT rs4680 gene variants were different between relapse and abstinent groups. Logistic regression analysis showed higher BIS total score, having ever been in MMT and younger first heroin use age are the predictors of relapse to heroin use during 5 years follow-up, and the COMT rs4680 gene had an interaction with BIS scores. Our findings indicated that the impulsive personality traits, methadone use history, and onset age could predict relapse in heroin-dependent patients during 5 year's follow up. The COMT gene showed a moderational effect in part the relationship of impulsivity with heroin relapse.

  6. The Aiguille du Midi (Mont Blanc massif): a unique high-Alpine site to study bedrock permafrost

    Science.gov (United States)

    Deline, P.; Coviello, V.; Cremonese, E.; Gruber, S.; Krautblatter, M.; Malet, S. Jaillet (1), E.; Morra di Cella, U.; Noetzli, J.; Pogliotti, P.; Verleysdonk, S.

    2009-04-01

    Permafrost and its change in steep high-Alpine rock walls remain insufficiently understood because of the difficulties of in situ measurements. A large proportion of permafrost studies is mainly based on modelling, with a few existing instrumented sites and a resulting lack of process understanding. Yet, a number of rockfalls that occurred in the last decade in the Alps are likely related to climatically-driven permafrost degradation, as indicated by ice in starting zones, increased air temperature, and modelling studies. Starting off in the framework of the French-Italian PERMAdataROC project and presently under development within the EU co-funded project PermaNET (Permafrost long-term monitoring network: www.permanet-alpinespace.eu), our investigations at the Aiguille du Midi begin in 2005. The summit (3842 m a.s.l) is accessible from Chamonix by a cable car which was built at the end of the 1950s. Half a million tourists visit the site each year. Because of its elevation, geometry, and year-round accessibility to rock slopes of diverse aspects and to galleries, the site was chosen for: - Monitoring of the thermal regime in steep rock walls. Thermistors were installed at depths of 2, 10, 30 and 55 cm, at all aspects and with slope angles in the range 60-90° (determining e.g. the presence and influence of snow). - Measurements of high altitude climatic data (air temperature and humidity, incoming and outgoing solar radiation, wind speed and direction) perpendicular to the rockwall surface, by movable automatic weather stations. Together with the rock temperature measurements, these data (see Morra et al., poster in session CR4.1) can be used for physically-based model validation (see Pogliotti et al., oral presentation in session CR4.1) or statistical models construction of rock temperature distribution and variability in the rock walls. - Making a 3D-high-resolution DEM by long-range (rock walls) and short-range (galleries) terrestrial laser scanning

  7. 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.

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

    Science.gov (United States)

    Hogg, Oliver T; Barnes, David K A; Griffiths, Huw J

    2011-01-01

    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.

  9. Recent Developments of c-Met as a Therapeutic Target in Hepatocellular Carcinoma.

    Science.gov (United States)

    Bouattour, Mohamed; Raymond, Eric; Qin, Shukui; Cheng, Ann-Lii; Stammberger, Uz; Locatelli, Giuseppe; Faivre, Sandrine

    2017-09-01

    Aberrant c-Met activity is implicated in the development of hepatocellular carcinoma (HCC), suggesting that c-Met inhibition may have therapeutic potential. However, clinical trials of nonselective kinase inhibitors with c-Met activity (tivantinib, cabozantinib, foretinib, and golvatinib) in patients with HCC have failed so far to demonstrate significant efficacy. This is likely due to several factors, including trial design, lack of patient selection according to tumor c-Met status, and the prevalent off-target activity of these agents, which may mean that c-Met inhibition is incomplete. In contrast, selective c-Met inhibitors (tepotinib, capmatinib) can be dosed at a level predicted to achieve a complete inhibition of tumor c-Met activity. Moreover, results from early trials can be used to optimize the design of clinical trials of these agents. Preliminary results suggest that selective c-Met inhibitors have antitumor activity in HCC, with acceptable safety and tolerability in patients with Child-Pugh A liver function. Ongoing trials have been designed to assess the efficacy and safety of selective c-Met inhibition compared with standard therapy in patients with HCC selected based on tumor c-Met status. Thus, c-Met inhibition continues to be an active area of research in HCC, with well-designed trials in progress to investigate the benefit of selective c-Met inhibitors. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  10. Lake Baikal: a unique place to study evolution of sponges and their stress response in an environment nearly unimpaired by anthropogenic perturbation.

    Science.gov (United States)

    Efremova, Sofia M; Itskovich, Valeria B; Parfenova, Valentina; Drucker, Valentin V; Müller, Werner E G; Schröder, Heinz C

    2002-06-01

    Lake Baikal is considered as a unique place to study evolution. In this review, we report on recent data on the evolution of endemic freshwater sponges of this ancient lake. Nucleotide sequence data support the idea that these sponges are of monophyletic origin and evolved from Spongillidae. Baikalian sponges form the dominating biomass in the benthos of the lake. Data on the expression of the biomarker heat shock protein 70, revealed that the endemic sponge species of Lake Baikal are useful as bioindicators to assess the anthropogenic impact on the lake.

  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. LoVo colon cancer cells resistant to oxaliplatin overexpress c-MET and VEGFR-1 and respond to VEGF with dephosphorylation of c-MET.

    Science.gov (United States)

    Mezquita, Belén; Pineda, Estela; Mezquita, Jovita; Mezquita, Pau; Pau, Montserrat; Codony-Servat, Jordi; Martínez-Balibrea, Eva; Mora, Conchi; Maurel, Joan; Mezquita, Cristóbal

    2016-05-01

    Oxaliplatin-resistant LoVo colon cancer cells overexpressing c-MET and VEGFR-1 were selected to study several signaling pathways involved in chemoresistance, as well as the effect of increasing amounts of VEGF in the regulation of c-MET. In comparison with chemosensitive LoVo colon cancer cells, oxaliplatin-resistant cells (LoVoR) overexpress and phosphorylate c-MET, upregulate the expression of transmembrane and soluble VEGFR-1 and, unexpectedly, downregulate VEGF. In addition, LoVoR cells activate other transduction pathways involved in chemoresistance such as Akt, β-catenin-TCF4 and E-cadherin. While c-MET is phosphorylated in LoVoR cells expressing low levels of VEGF, c-MET phosphorylation decreases when recombinant VEGF is added into the culture medium. Inhibition of c-MET by VEGF is mediated by VEGFR-1, since phosphorylation of c-MET in the presence of VEGF is restored after silencing VEGFR-1. Dephosphorylation of c-MET by VEGF suggests that tumors coexpressing VEGFR-1 and c-MET may activate c-MET as a result of anti-VEGF therapy. © 2015 Wiley Periodicals, Inc.

  13. Analysis of peeling decoder for MET ensembles

    CERN Document Server

    Hinton, Ryan

    2009-01-01

    The peeling decoder introduced by Luby, et al. allows analysis of LDPC decoding for the binary erasure channel (BEC). For irregular ensembles, they analyze the decoder state as a Markov process and present a solution to the differential equations describing the process mean. Multi-edge type (MET) ensembles allow greater precision through specifying graph connectivity. We generalize the the peeling decoder for MET ensembles and derive analogous differential equations. We offer a new change of variables and solution to the node fraction evolutions in the general (MET) case. This result is preparatory to investigating finite-length ensemble behavior.

  14. Mars MetNet Mission Payload Overview

    Science.gov (United States)

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

    2012-09-01

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

  15. Brain-Derived Neurotrophic Factor (BDNF) Val66Met Polymorphism Differentially Predicts Hippocampal Function in Medication-Free Patients with Schizophrenia

    Science.gov (United States)

    Eisenberg, Daniel Paul; Ianni, Angela M.; Wei, Shau-Ming; Kohn, Philip D.; Kolachana, Bhaskar; Apud, José; Weinberger, Daniel R.; Berman, Karen F.

    2012-01-01

    A Val66Met single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene impairs activity-dependent BDNF release in cultured hippocampal neurons and predicts impaired memory and exaggerated basal hippocampal activity in healthy humans. Several clinical genetic association studies, along with multi-modal evidence for hippocampal dysfunction in schizophrenia indirectly suggest a relationship between schizophrenia and genetically-determined BDNF function in the hippocampus. To directly test this hypothesized relationship, we studied 47 medication-free patients with schizophrenia or schizoaffective disorder and 74 healthy comparison individuals with genotyping for the Val66Met SNP and [15O]H2O positron emission tomography (PET) to measure resting and working memory-related hippocampal regional cerebral blood flow (rCBF). In patients, harboring a Met allele was associated with significantly less hippocampal rCBF. This finding was opposite to the genotype effect seen in healthy participants, resulting in a significant diagnosis-by-genotype interaction. Exploratory analyses of interregional resting rCBF covariation revealed a specific and significant diagnosis-by-genotype interaction effect on hippocampal-prefrontal coupling. A diagnosis-by-genotype interaction was also found for working-memory related hippocampal rCBF change, which was uniquely attenuated in Met allele-carrying patients. Thus, both task-independent and task-dependent hippocampal neurophysiology accommodates a Met allelic background differently in patients with schizophrenia than in control subjects. Potentially consistent with the hypothesis that cellular sequelae of the BDNF Val66Met SNP interface with aspects of schizophrenic hippocampal and frontotemporal dysfunction, these results warrant future investigation to understand the contributions of unique patient trait or state variables to these robust interactions. PMID:23319002

  16. Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women.

    Science.gov (United States)

    Ahlström, Tommy; Hagström, Emil; Larsson, Anders; Rudberg, Claes; Lind, Lars; Hellman, Per

    2009-11-01

    In recent years, an association has been noted between several abnormalities that characterize the metabolic syndrome (MetS) and primary hyperparathyroidism (pHPT). These abnormalities include dyslipidaemia, obesity, insulin resistance and hypertension. The correlations between plasma calcium, parathyroid hormone (PTH) and the variables in the MetS in a normal population are still unclear. To describe correlations between plasma calcium and PTH and the various abnormalities present in the MetS in a healthy population. We studied 1016 healthy individuals from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) population of 70 years old, by means of plasma analyses of calcium, PTH, creatinine, lipids, insulin and glucose, as well as by standardized blood pressure measurements. Further, body mass index (BMI) and waist circumference were determined. The more National Cholesterol Education Program (NCEP) criteria for the MetS that were met, the higher the s-PTH and albumin-corrected s-calcium. Further, positive correlations between plasma calcium and BMI (P = 0.0003), waist circumference (P = 0.0009) and insulin resistance (P = 0.079) were found. PTH and BMI (P < 0.0001), waist circumference (P < 0.0001), systolic blood pressure (P = 0.0034), diastolic blood pressure (P = 0.0008), serum triglycerides (P = 0.0003) and insulin resistance (P = 0.0003) were positively correlated, whereas serum high density lipoproteins (HDL) (P = 0.036) and PTH were negatively correlated. We conclude that PTH correlates with several of the metabolic factors included in the MetS within a normocalcaemic population. In addition, individuals with mild pHPT present significantly more NCEP criteria for MetS. We postulate that increased levels of PTH in pHPT may be associated with the increased cardiovascular morbidity and mortality seen in pHPT.

  17. Alleen met een brandend geduld

    NARCIS (Netherlands)

    Staak, C.P.F. van der

    2008-01-01

    Verkorte afscheidsrede. De beroepsopleiding van psychologen in de Nederlandse gezondheidszorg kreeg de afgelopen 25 jaar gestalte. In vervolg op de universitaire studie psychologie zijn de duale beroepsopleidingen tot gezondheidszorgpsycholoog en klinisch psycholoog gerealiseerd. De bouw van deze br

  18. Prof. Zhu Zuoyan Met with ISI Delegation

    Institute of Scientific and Technical Information of China (English)

    Liu Xiuping; Chen Huai

    2007-01-01

    @@ On March 27, Prof. Zhu Zuoyan, Vice President of NSFC, met with a three-member delegation from the Institute for Scientific Information (ISI), USA headed by Dr. James Testa, Director of Editorial Development of ISI.

  19. Palmzaadkever opsporen met lichtval en alcohol

    NARCIS (Netherlands)

    Bloemhard, C.M.J.

    2006-01-01

    De palmzaadkever houdt er een verborgen levenswijze op na. Met een lichtval zijn de volwassenen, vliegende vrouwtjes goed te vangen. Tijdige signalering verbetert de bestrijding, maar vooral schoon uitgangsmateriaal importeren verlaagt de infectiedruk

  20. Ervaringen en perspectieven van zaadcoating met pesticiden

    NARCIS (Netherlands)

    Ester, A.; Huiting, H.; Putter, de H.

    2005-01-01

    Zaadbehandeling is doorgaans een uitgelezen kans om gebruik van gewasbeschermingsmiddelen fors terug te dringen. Coating van het zaad met insecticiden kan in een aantal situaties een effectieve bestrijdingsmethode zijn. Doordat de volvelds-, kweekplaat-, plantvoetbehandeling en soms een gewasbehande

  1. Roestvrij stalen trog met opstap voldoet goed

    NARCIS (Netherlands)

    Hoofs, A.

    1995-01-01

    Uit onderzoek op het Varkensproefbedrijf in Sterksel blijkt dat de roestvrij stalen trog met opstap en schuine voorkant, ondanks het hogere investeringsbedrag, perspectieven biedt voor toepassing in de vleesvarkenshouderij.

  2. 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.

  3. 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.

  4. Afvangen van fosfaat uit bloembollensector met ijzerzand

    NARCIS (Netherlands)

    Chardon, W.J.; Groenenberg, J.E.; Jansen, S.; Buijert, A.; Talens, R.; Krol, A.F.

    2014-01-01

    In het oppervlaktewater van de Bollenstreek is de fosfaatconcentratie veel hoger dan de norm van de Europese Kaderrichtlijn Water. Met ijzerzand, een nevenproduct van drinkwaterproductie, kan fosfaat worden afgevangen. Het hoogheemraadschap van Rijnland heeft drie maatregelen op basis van ijzerzand

  5. Met een Happy Meal duurzaam leren handelen

    NARCIS (Netherlands)

    Noorduyn, L.; Wals, A.E.J.

    2010-01-01

    Afgestudeerden van groene opleidingen moeten over duurzaamheidscompetenties beschikken, willen ze problemen echt op kunnen lossen. Bijvoorbeeld “omgaan met onzekerheid” en “inleven in een ander”. Maar hoe breng je een student die competenties bij?

  6. 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

  7. 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

  8. MetNet - Martian Network Mission

    Science.gov (United States)

    Harri, A.-M.

    2009-04-01

    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 actual practical mission development work started in January 2009 with participation from various countries and space agencies. The scientific rationale and goals as well as key mission solutions will be discussed. 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. This 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.

  9. Sequential EMT-MET induces neuronal conversion through Sox2.

    Science.gov (United States)

    He, Songwei; Chen, Jinlong; Zhang, Yixin; Zhang, Mengdan; Yang, Xiao; Li, Yuan; Sun, Hao; Lin, Lilong; Fan, Ke; Liang, Lining; Feng, Chengqian; Wang, Fuhui; Zhang, Xiao; Guo, Yiping; Pei, Duanqing; Zheng, Hui

    2017-01-01

    Direct neuronal conversion can be achieved with combinations of small-molecule compounds and growth factors. Here, by studying the first or induction phase of the neuronal conversion induced by defined 5C medium, we show that the Sox2-mediated switch from early epithelial-mesenchymal transition (EMT) to late mesenchymal-epithelial transition (MET) within a high proliferation context is essential and sufficient for the conversion from mouse embryonic fibroblasts (MEFs) to TuJ(+) cells. At the early stage, insulin and basic fibroblast growth factor (bFGF)-induced cell proliferation, early EMT, the up-regulation of Stat3 and Sox2, and the subsequent activation of neuron projection. Up-regulated Sox2 then induced MET and directed cells towards a neuronal fate at the late stage. Inhibiting either stage of this sequential EMT-MET impaired the conversion. In addition, Sox2 could replace sequential EMT-MET to induce a similar conversion within a high proliferation context, and its functions were confirmed with other neuronal conversion protocols and MEFs reprogramming. Therefore, the critical roles of the sequential EMT-MET were implicated in direct cell fate conversion in addition to reprogramming, embryonic development and cancer progression.

  10. Bodemmaterialen voor vrijloopstallen: eigenschappen in relatie tot compostering en gasvormige emissies bij menging met mest en urine = Exploratory study of bedding materials for freestall animal housing; their composting potential and gaseous emissions after mixing with dairy cattle excreta

    NARCIS (Netherlands)

    Smits, M.C.J.; Blanken, K.; Bokma, S.; Galama, P.J.; Dooren, van H.J.C.; Szanto, G.L.

    2012-01-01

    Tussen bodemmaterialen bestaan aanzienlijke verschillen in organische stofgehalten, koolstof- en stikstofgehalten, respiratiesnelheden, temperatuurontwikkelingen en emissies bij compostering met feces en urine van melkkoeien.Chemical characteristics of bedding materials, their composting potential a

  11. 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

  12. Rationale and protocol of the MetNET-1 trial, a prospective, single center, phase II study to evaluate the activity and safety of everolimus in combination with octreotide LAR and metformin in patients with advanced pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Pusceddu, Sara; de Braud, Filippo; Concas, Laura; Bregant, Cristina; Leuzzi, Livia; Formisano, Barbara; Buzzoni, Roberto

    2014-01-01

    Abnormal PI3K-AKT-mTOR pathway signalling and autocrine activation of the mTOR pathway, mediated through insulin-like growth factor-1, have been implicated in the proliferation of pancreatic neuroendocrine tumor (pNET) cells. Everolimus, an mTOR inhibitor, has shown antitumor benefit in pNETs alone and in combination with octreotide LAR in RADIANT-1 and RADIANT-3 studies. Although everolimus-based phase II/III trials have improved progression-free survival for pNET, its use has not impacted on prolonging overall survival. Metformin has recently shown some anti-cancer activity in both in vitro and in vivo studies by its indirect properties to decrease insulin and insulin-like growth factor-1 (IGF-1) levels and by its antitumour effect to promote AMPK activation and consequently inhibition to TSC1-2/mTOR complex. In light of even more retrospective evidence of metformin's anticancer activity, a prospective evaluation is required to either confirm or discard these preliminary findings. With the aim to evaluate the antiproliferative effect of metformin in combination with everolimus and octreotide LAR in pancreatic well-differentiated neuroendocrine tumor patients, a single arm, prospective, single center phase II study was designed (MetNET-1 trial, NCT 02294006). Forty-three patients are expected to be evaluated. The study is ongoing, and recruitment is estimated to be completed in August 2016. The results will be anticipated in 2017.

  13. NASA's unique networking environment

    Science.gov (United States)

    Johnson, Marjory J.

    1988-01-01

    Networking is an infrastructure technology; it is a tool for NASA to support its space and aeronautics missions. Some of NASA's networking problems are shared by the commercial and/or military communities, and can be solved by working with these communities. However, some of NASA's networking problems are unique and will not be addressed by these other communities. Individual characteristics of NASA's space-mission networking enviroment are examined, the combination of all these characteristics that distinguish NASA's networking systems from either commercial or military systems is explained, and some research areas that are important for NASA to pursue are outlined.

  14. Émission de photons uniques par un atome unique piégé

    Science.gov (United States)

    Darquié, B.; Beugnon, J.; Jones, M. P. A.; Dingjan, J.; Sortais, Y.; Browaeys, A.; Messin, G.; Grangier, P.

    2006-10-01

    En illuminant un atome unique piégé dans une pince optique de taille micrométrique à l'aide d'impulsions lumineuses résonantes d'une durée de 4 ns, nous avons réalisé une source efficace de photons uniques déclenchés, de polarisation bien définie. Nous avons mesuré la fonction d'autocorrélation temporelle en intensité qui met en évidence un dégroupement de photons presque parfait. Une telle source de photons uniques de haut flux possède des applications potentielles pour le traitement de l'information quantique.

  15. Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1.

    Science.gov (United States)

    Crider, Sarah E; Holbrook, Robert J; Franz, Katherine J

    2010-01-01

    Platinum therapeutic agents are widely used in the treatment of several forms of cancer. Various mechanisms for the transport of the drugs have been proposed including passive diffusion across the cellular membrane and active transport via proteins. The copper transport protein Ctr1 is responsible for high affinity copper uptake but has also been implicated in the transport of cisplatin into cells. Human hCtr1 contains two methionine-rich Mets motifs on its extracellular N-terminus that are potential platinum-binding sites: the first one encompasses residues 7-14 with amino acid sequence Met-Gly-Met-Ser-Tyr-Met-Asp-Ser and the second one spans residues 39-46 with sequence Met-Met-Met-Met-Pro-Met-Thr-Phe. In these studies, we use liquid chromatography and mass spectrometry to compare the binding interactions between cisplatin, carboplatin and oxaliplatin with synthetic peptides corresponding to hCtr1 Mets motifs. The interactions of cisplatin and carboplatin with Met-rich motifs that contain three or more methionines result in removal of the carrier ligands of both platinum complexes. In contrast, oxaliplatin retains its cyclohexyldiamine ligand upon platinum coordination to the peptide.

  16. Mars MetNet Mission Payload Overview

    Science.gov (United States)

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

    2012-04-01

    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 is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The main idea behind the MetNet landing vehicles is to use a state-of-the-art 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 and more mass and volume resources are spared for the science payload. The vehicle decelerates its entry speed using the inflatable structure and final landing sequence includes a cone headed body penetrating the Martian soil. 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. The payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: - Pressure device (MetBaro): mass 100g, measurement range 0..1015 hPa. - Humidity device (MetHumi): mass 15g, measurement range 0..100%RH. - Temperature sensors (MetTemp): mass 2g each, measurement range -110C..+30C. Optical devices: - Panoramic camera (PanCam): mass 100g, FOV 4 lenses mounted at 90 deg - Solar irradiance sensor (MetSIS) with optical wireless system (OWLS) for data transfer: mass 115g (MetSIS) and 7g (OWLS module), wavelength range 190..1100nm. MetSIS equipped with 28 optical detectors, two temperature sensors and two solar incidence angle detectors. - Dust sensor (DS): mass 42g, resolution: 10 particles / cm3. Composition and structure device: - Magnetometer (MOURA): mass 80g, measurement range: ±30uT. MetNet Mission payload instruments are specially designed to operate in very low power conditions. MNL flexible solar panels provides a total of

  17. 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

  18. 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.

  19. Determination of a novel anticancer c-Met inhibitor LS-177 in rat plasma and tissues with a validated UPLC-MS/MS method: application to pharmacokinetics and tissue distribution study.

    Science.gov (United States)

    Ju, Ping; Liu, Zhenzhen; Jiang, Yu; Zhao, Simin; Zhang, Lunhui; Zhang, Yuanyuan; Gu, Liqiang; Tang, Xing; Bi, Kaishun; Chen, Xiaohui

    2015-07-01

    LS-177 is a novel small-molecule kinase inhibitor employed to interrupt the c-Met signaling pathway. A rapid and sensitive ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determination of LS-177 in rat plasma and tissues. The biosamples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a C18 column (50 × 4.6 mm, 2.6 µm) using a gradient elution mobile phase consisting of acetonitrile-0.1% formic acid water. Under the optimal conditions, the selectivity of the method was satisfactory with no endogenous interference. The intraday and interday precisions (relative standard deviation) were LS-177 was stable during the preparation and analytical processes. The UPLC-MS/MS method was successfully applied to pharmacokinetic and tissue distribution studies. The results indicated that there was no significant drug accumulation after multiple-dose oral administration of LS-177. The tissue distribution study exhibited significant higher uptakes of LS-177 in stomach, intestine, lung and liver among all of the tissues. The results in pharmacokinetics and tissue distribution may provide a meaningful basis for clinical application.

  20. Luchtverontreiniging met CO aan de Amsterdamsestraatweg-Zuilen/Utrecht

    NARCIS (Netherlands)

    Hady MSA

    1989-01-01

    Het rapport beschrijft de resultaten van een modelmatige studie naar de bijdrage van de emissies van een industriegebied aan de westkand van Utrecht aan de CO-concentraties of leefniveau. Deze bijdrage is vergeleken met de bijdrage van het verkeer en die van bronnen binnenshuis. Vervolgens is ee

  1. 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...

  2. Computational study of pH-dependent oligomerization and ligand binding in Alt a 1, a highly allergenic protein with a unique fold

    Science.gov (United States)

    Garrido-Arandia, María; Bretones, Jorge; Gómez-Casado, Cristina; Cubells, Nuria; Díaz-Perales, Araceli; Pacios, Luis F.

    2016-05-01

    Alt a 1 is a highly allergenic protein from Alternaria fungi responsible for several respiratory diseases. Its crystal structure revealed a unique β-barrel fold that defines a new family exclusive to fungi and forms a symmetrical dimer in a butterfly-like shape as well as tetramers. Its biological function is as yet unknown but its localization in cell wall of Alternaria spores and its interactions in the onset of allergy reactions point to a function to transport ligands. However, at odds with binding features in β-barrel proteins, monomeric Alt a 1 seems unable to harbor ligands because the barrel is too narrow. Tetrameric Alt a 1 is able to bind the flavonoid quercetin, yet the stability of the aggregate and the own ligand binding are pH-dependent. At pH 6.5, which Alt a 1 would meet when secreted by spores in bronchial epithelium, tetramer-quercetin complex is stable. At pH 5.5, which Alt a 1 would meet in apoplast when infecting plants, the complex breaks down. By means of a combined computational study that includes docking calculations, empirical p Ka estimates, Poisson-Boltzmann electrostatic potentials, and Molecular Dynamics simulations, we identified a putative binding site at the dimeric interface between subunits in tetramer. We propose an explanation on the pH-dependence of both oligomerization states and protein-ligand affinity of Alt a 1 in terms of electrostatic variations associated to distinct protonation states at different pHs. The uniqueness of this singular protein can thus be tracked in the combination of all these features.

  3. 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.

  4. Dynamic expression and localization of c-MET isoforms in the developing rat pancreas.

    Science.gov (United States)

    Wu, Yulong; Cheng, Mei; Shi, Zhen; Feng, Zhenqing; Guan, Xiaohong

    2014-01-01

    Pancreata from Sprague Dawley rats of different developmental stages were studied to determine the expression and cellular localization of different c-MET isoforms in the developing rat pancreas. Pancreatic mRNA and protein expression levels of c-MET at different developmental stages from embryo to adult were detected by reverse transcription-polymerase chain reaction and by western blotting. To identify the cellular localization of c-MET protein in the developing rat pancreas, double immunofluorescent staining was performed using antibodies for cell type-specific markers and for c-MET. The expression of two isoforms of c-MET (190 kDa and 170 kDa) coincided with the development of the pancreas. The 190 kDa isoform of c-MET is expressed during embryonic stages, and its expression is replaced by the expression of the 170 kDa isoform as the pancreas develops. Only the 170 kDa isoform is expressed in the adult rat pancreas. Throughout all stages of pancreatic development, c-MET is expressed by vimentin-positive cells. In contrast, c-MET staining was stronger in rat pancreata from newborn to adult stages and overlapped with insulin-positive beta-cells. The dynamic expression and localization of different c-MET isoforms in the rat pancreas during different developmental stages indicates that distinct c-MET isoform might be involved in different aspects of pancreatic development.

  5. The BDNF Val66Met polymorphism impairs NMDA receptor-dependent synaptic plasticity in the hippocampus.

    Science.gov (United States)

    Ninan, Ipe; Bath, Kevin G; Dagar, Karishma; Perez-Castro, Rosalia; Plummer, Mark R; Lee, Francis S; Chao, Moses V

    2010-06-30

    The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene results in a defect in regulated release of BDNF and affects episodic memory and affective behaviors. However, the precise role of the BDNF Val66Met polymorphism in hippocampal synaptic transmission and plasticity has not yet been studied. Therefore, we examined synaptic properties in the hippocampal CA3-CA1 synapses of BDNF(Met/Met) mice and matched wild-type mice. Although basal glutamatergic neurotransmission was normal, both young and adult mice showed a significant reduction in NMDA receptor-dependent long-term potentiation. We also found that NMDA receptor-dependent long-term depression was decreased in BDNF(Met/Met) mice. However, mGluR-dependent long-term depression was not affected by the BDNF Val66Met polymorphism. Consistent with the NMDA receptor-dependent synaptic plasticity impairment, we observed a significant decrease in NMDA receptor neurotransmission in the CA1 pyramidal neurons of BDNF(Met/Met) mice. Thus, these results show that the BDNF Val66Met polymorphism has a direct effect on NMDA receptor transmission, which may account for changes in synaptic plasticity in the hippocampus.

  6. A novel antagonist anti-cMet antibody with antitumor activities targeting both ligand-dependent and ligand-independent c-Met receptors.

    Science.gov (United States)

    Gonzalez, Alexandra; Broussas, Matthieu; Beau-Larvor, Charlotte; Haeuw, Jean-François; Boute, Nicolas; Robert, Alain; Champion, Thierry; Beck, Alain; Bailly, Christian; Corvaïa, Nathalie; Goetsch, Liliane

    2016-10-15

    c-Met is a prototypic member of a sub-family of RTKs. Inappropriate c-Met activation plays a crucial role in tumor formation, proliferation and metastasis. Using a key c-Met dimerization assay, a set of 12 murine whole IgG1 monoclonal antibodies was selected and a lead candidate, m224G11, was humanized by CDR-grafting and engineered to generate a divalent full antagonist humanized IgG1 antibody, hz224G11. Neither m224G11 nor hz224G11 bind to the murine c-Met receptor. Their antitumor activity was investigated in vitro in a set of experiments consistent with the reported pleiotropic effects mediated by c-Met and, in vivo, using several human tumor xenograft models. Both m224G11 and hz224G11 exhibited nanomolar affinities for the receptor and inhibited HGF binding, c-Met phosphorylation, and receptor dimerization in a similar fashion, resulting in a profound inhibition of all c-Met functions in vitro. These effects were presumably responsible for the inhibition of c-Met's major functions including cell proliferation, migration, invasion scattering, morphogenesis and angiogenesis. In addition to these in vitro properties, hz224G11 dramatically inhibits the growth of autocrine, partially autophosphorylated and c-Met amplified cell lines in vivo. Pharmacological studies performed on Hs746T gastric cancer xenografts demonstrate that hz224G11 strongly downregulates c-Met expression and phosphorylation. It also decreases the tumor mitotic index (Ki67) and induces apoptosis. Taken together, the in vitro and in vivo data suggest that hz224G11 is a promising candidate for the treatment of tumors. This antibody, now known as ABT-700 and currently in Phase I clinical trials, may provide a novel therapeutic approach to c-Met-expressing cancers.

  7. Statin action favors normalization of the plasma lipidome in the atherogenic mixed dyslipidemia of MetS: potential relevance to statin-associated dysglycemia.

    Science.gov (United States)

    Meikle, Peter J; Wong, Gerard; Tan, Ricardo; Giral, Philippe; Robillard, Paul; Orsoni, Alexina; Hounslow, Neil; Magliano, Dianna J; Shaw, Jonathan E; Curran, Joanne E; Blangero, John; Kingwell, Bronwyn A; Chapman, M John

    2015-12-01

    The impact of statin treatment on the abnormal plasma lipidome of mixed dyslipidemic patients with metabolic syndrome (MetS), a group at increased risk of developing diabetes, was evaluated. Insulin-resistant hypertriglyceridemic hypertensive obese males (n = 12) displaying MetS were treated with pitavastatin (4 mg/day) for 180 days; healthy normolipidemic age-matched nonobese males (n = 12) acted as controls. Statin treatment substantially normalized triglyceride (-41%), remnant cholesterol (-55%), and LDL-cholesterol (-39%), with minor effect on HDL-cholesterol (+4%). Lipidomic analysis, normalized to nonHDL-cholesterol in order to probe statin-induced differences in molecular composition independently of reduction in plasma cholesterol, revealed increment in 132 of 138 lipid species that were subnormal at baseline and significantly shifted toward the control group on statin treatment. Increment in alkyl- and alkenylphospholipids (plasmalogens) was prominent, and consistent with significant statin-induced increase in plasma polyunsaturated fatty acid levels. Comparison of the statin-mediated lipidomic changes in MetS with the abnormal plasma lipidomic profile characteristic of prediabetes and T2D in the Australian Diabetes, Obesity, and Lifestyle Study and San Antonio Family Heart Study cohorts by hypergeometric analysis revealed a significant shift toward the lipid profile of controls, indicative of a marked trend toward a normolipidemic phenotype. Pitavastatin attenuated the abnormal plasma lipidome of MetS patients typical of prediabetes and T2D.

  8. Chronisch zieken bij de bedrijfsarts: ervaringen met en oordeel over samenwerking met de huisarts.

    NARCIS (Netherlands)

    Baanders, A.N.

    2004-01-01

    Dit artikel beschrijft de ervaringen met en het oordeel over arbocuratieve samenwerking (ACS) vanuit het perspectief van mensen met somatische chronische aandoeningen. Dit geeft een indruk van de mogelijkheden die ACS volgens chronisch zieken kan hebben bij het terugdringen van ziekteverzuimen en

  9. Portale hypertensie : een experimenteel model met dimethylnitrosamine

    NARCIS (Netherlands)

    O.T. Terpstra (Onno)

    1979-01-01

    textabstractDe behandeling van patiënten met een bloeding uit slokdarmvarices ten gevolge van portale hypertensie levert nog steeds geen bevredigende resultaten op (Sherlock 1978). Operaties die de druk in de vena portae verlagen, zoals een portocavale shunt, zijn effectief wanneer het er om gaat ee

  10. Paprika nog moeilijk te sturen met groeilicht

    NARCIS (Netherlands)

    Hogendonk, L.

    2005-01-01

    De resultaten van een op een paprikabedrijf uitgevoerde proef met drie belichtingssystemen van 5 duizend lux zijn in de afgelopen maanden omgezet in een aantal conclusies. Eén uitkomst was dat de effecten van vaste en bewegende belichting elkaar niet veel ontlopen. Een andere conclusie die kon

  11. Met uitloop meer kans op parasitaire infecties

    NARCIS (Netherlands)

    Eijck, I.A.J.M.

    2003-01-01

    Parasitaire infecties vormen een belangrijk probleem in de biologische- en scharrelhouderij. In een veldinventarisatie van het Praktijkonderzoek van ASG werden meer Ascaris suum (spoelwormen), coccidiën en Toxoplasma gondii gevonden op bedrijven met uitloop dan op bedrijven zonder uitloop. Nader ond

  12. 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...

  13. Inkoper Innoveer! : Kansen grijpen met innoveren

    NARCIS (Netherlands)

    Reijniers, J.J.A.M.; Gaspersz, J.B.R.; Marijnen, Y.; Roddeman, J.

    2009-01-01

    Dit boek biedt inkopers nieuwe perspectieven, praktische adviezen en kansrijke ideeën om succesvoller te zijn en bij te dragen aan de vernieuwingskracht van hun organisatie. Daarnaast bieden de auteurs een visie waarmee de kansen met inkoop volop zijn te benutten: innovatietalent van leveranciers, s

  14. Allergische consument is tevreden met Santana

    NARCIS (Netherlands)

    Maas, van der M.P.; Schenk, M.F.

    2008-01-01

    Nederland had twee jaar geleden de primeur: Santana, een hyperallergeen appelras voor mensen met appelallergie. Wageningen UR heeft de ervaringen van de consumenten over 2006 en 2007 onderzocht. De vermindering van de allergische reactie is ongeveer volgens verwachting en de tevredenheid blijkt hoog

  15. Met gezonde bijen naar de heide

    NARCIS (Netherlands)

    Cornelissen, B.; Calis, J.

    2010-01-01

    Op 22 maart 2010 kwam een bont gezelschap van bijenhouders van ABTB, ANI en NBV bijeen in Hoenderloo. Het onderwerp die avond was de vraag: “Hoe combineer ik varroabestrijding met de heidedracht?” Hieronder het antwoord en wel in de vorm van de basisprincipes van varroa bestrijding plus een concrete

  16. Consistentie met MS-DOS software

    NARCIS (Netherlands)

    Olsthoorn TN

    1988-01-01

    Zonder de keuze van een zekere standaard-lijn ten aanzien van de software die men zelf gebruikt, kan nauwelijks efficient met een computer worden gewerkt. Onder UNIX en op de Macintosh is het gebruik van programma's en de uitwisseling van gegevens daartussen gestandaardiseerd. Onder MS-DOS

  17. Behandeling non-vitale pulpa met formocresol

    NARCIS (Netherlands)

    Wijk, Pieter Harm

    1971-01-01

    Het principe van de endodontische behandeling volgens de richtlijnen van De Boer is gebaseerd op de gedachte dat het niet nodig is het gehele wortelkanaal te reinigen, mits men er voor zorgt dat de achtergelaten noxen met behulp van een chemischestof - in dit geval formaldehyde - onschadelijk worden

  18. Unique properties of the classical bovine spongiform encephalopathy strain and its emergence from H-type bovine spongiform encephalopathy substantiated by VM transmission studies.

    Science.gov (United States)

    Bencsik, Anna; Leboidre, Mikael; Debeer, Sabine; Aufauvre, Claire; Baron, Thierry

    2013-03-01

    In addition to classical bovine spongiform encephalopathy (C-BSE), which is recognized as being at the origin of the human variant form of Creutzfeldt-Jakob disease, 2 rare phenotypes of BSE (H-type BSE [H-BSE] and L-type BSE [L-BSE]) were identified in 2004. H-type BSE and L-BSE are considered to be sporadic forms of prion disease in cattle because they differ from C-BSE with respect to incubation period, vacuolar pathology in the brain, and biochemical properties of the protease-resistant prion protein (PrP) in natural hosts and in some mouse models that have been tested. Recently, we showed that H-BSE transmitted to C57Bl/6 mice resulted in a dissociation of the phenotypic features, that is, some mice showed an H-BSE phenotype, whereas others had a C-BSE phenotype. Here, these 2 phenotypes were further studied in VM mice and compared with cattle C-BSE, H-BSE, and L-BSE. Serial passages from the C-BSE-like phenotype on VM mice retained similarities with C-BSE. Moreover, our results indicate that strains 301V and 301C derived from C-BSE transmitted to VM and C57Bl/6 mice, respectively, are fundamentally the same strain. These VM transmission studies confirm the unique properties of the C-BSE strain and support the emergence of a strain that resembles C-BSE from H-BSE.

  19. NMR studies demonstrate a unique AAB composition and chain register for a heterotrimeric type IV collagen model peptide containing a natural interruption site.

    Science.gov (United States)

    Xiao, Jianxi; Sun, Xiuxia; Madhan, Balaraman; Brodsky, Barbara; Baum, Jean

    2015-10-02

    All non-fibrillar collagens contain interruptions in the (Gly-X-Y)n repeating sequence, such as the more than 20 interruptions found in chains of basement membrane type IV collagen. Two selectively doubly labeled peptides are designed to model a site in type IV collagen with a GVG interruption in the α1(IV) and a corresponding GISLK sequence within the α2(IV) chain. CD and NMR studies on a 2:1 mixture of these two peptides support the formation of a single-component heterotrimer that maintains the one-residue staggering in the triple-helix, has a unique chain register, and contains hydrogen bonds at the interruption site. Formation of hydrogen bonds at interruption sites may provide a driving force for self-assembly and chain register in type IV and other non-fibrillar collagens. This study illustrates the potential role of interruptions in the structure, dynamics, and folding of natural collagen heterotrimers and forms a basis for understanding their biological role.

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

    Directory of Open Access Journals (Sweden)

    Eisen Judith S

    2008-07-01

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

  1. Recent Progress and Advances in HGF/MET-Targeted Therapeutic Agents for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Yilong Zhang

    2015-03-01

    Full Text Available The hepatocyte growth factor (HGF: MET axis is a ligand-mediated receptor tyrosine kinase pathway that is involved in multiple cellular functions, including proliferation, survival, motility, and morphogenesis. Aberrancy in the HGF/MET pathway has been reported in multiple tumor types and is associated with tumor stage and prognosis. Thus, targeting the HGF/MET pathway has become a potential therapeutic strategy in oncology development in the last two decades. A number of novel therapeutic agents—either as therapeutic proteins or small molecules that target the HGF/MET pathway—have been tested in patients with different tumor types in clinical studies. In this review, recent progress in HGF/MET pathway-targeted therapy for cancer treatment, the therapeutic potential of HGF/MET-targeted agents, and challenges in the development of such agents will be discussed.

  2. OH-induced oxidation of cyclo-Met-Met. A search for a complexed OH-radical

    DEFF Research Database (Denmark)

    Holcman, J.; Bobrowski, K.; Schöneich, C.;

    1991-01-01

    In the OH radical-induced oxidation of cyclo-Met-Met an OH adduct, cyclo-Met-Met(S therefore OH), absorbing at lambda-max = 390 nm with epsilon-390 cyclo-Met-Met(S therefore OH) = 4500 dm3 mol-1 cm-1 is formed. This adduct reversibly eliminates hydroxide ion, pK(b) = 5.4 +/- 0.1, forming correspo...

  3. UNIQUE ORAL DRUG DELIVERY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Raphael M. Ottenbrite; ZHAO Ruifeng; Sam Milstein

    1995-01-01

    An oral drug delivery system using proteinoid microspheres is discussed with respect to its unique dependence on pH. It has been found that certain drugs such as insulin and heparin can be encapsulated in proteinoid spheres at stomach pH's (1-3). These spheres also dissemble at intestinal pH's (6-7) releasing the drug for absorption. Using this technique low molecular weight heparin and human growth hormone have been orally delivered successfully to several animal species. Future work has been proposed to study the interaction and binding of the specific drugs with synthesized oligopeptides.

  4. Evaluation of unique identifiers used as keys to match identical publications in Pure and SciVal - a case study from health science.

    Science.gov (United States)

    Madsen, Heidi Holst; Madsen, Dicte; Gauffriau, Marianne

    2016-01-01

    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 UIDs may become

  5. Evaluation of unique identifiers used as keys to match identical publications in Pure and SciVal – a case study from health science

    Science.gov (United States)

    Madsen, Heidi Holst; Madsen, Dicte; Gauffriau, Marianne

    2016-01-01

    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 UIDs may become

  6. As metáforas primárias na aquisição da linguagem: um estudo interlingüístico Primary metaphores in language acquisition an interlinguistic study

    Directory of Open Access Journals (Sweden)

    Maity Siqueira

    2007-01-01

    Full Text Available Este trabalho apresenta um estudo interlingüístico e evolutivo da compreensão de oito metáforas primárias sob a perspectiva da Teoria da Metáfora Conceitual. Os dados foram obtidos através de entrevistas com crianças de 3 a 10 anos de idade, monolíngües, falantes nativas de português brasileiro ou de inglês norte-americano, bem como com adultos das mesmas comunidades lingüísticas. Os resultados de duas tarefas (verbal e não-verbal aplicadas revelaram que a compreensão de metáforas primárias é uma habilidade que emerge cedo na infância e está relacionada ao tipo de mapeamento envolvido em cada metáfora conceitual. Tanto para os participantes brasileiros quanto para os participantes norte-americanos, a compreensão de metáforas primárias se deu em três estágios.Situated within the framework of the Conceptual Metaphor Theory, this research focuses on the comprehension of primary metaphors, using a crosslinguistic-developmental perspective. Data come from interviews with monolingual Brazilian Portuguese and American English native speakers at the ages of 3 to 10, along with adult native speakers. The results obtained from two tasks (verbal and non-verbal revealed that the comprehension of primary metaphors is an ability that emerges early in life and is linked to the kind of mapping involved in each conceptual metaphor. The comprehension of primary metaphors followed three stages both for the Brazilian and the American participants.

  7. 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.

  8. A case-control study of community-acquired Acinetobacter baumannii pneumonia and melioidosis pneumonia in northeast Thailand: an emerging fatal disease with unique clinical features.

    Science.gov (United States)

    Patamatamkul, Samadhi; Klungboonkrong, Voravan; Praisarnti, Pakawas; Jirakiat, Kittitouch

    2017-01-01

    Acinetobacter baumannii is the emerging cause of severe and often fatal gram-negative, community-acquired pneumonia (CAP-AB) in Thailand. Due to its rarity, its specific clinical features are ill defined. In this retrospective study, we compared the demographic data, risk factors, clinical characteristics, radiographic pattern, and microbiological data between CAP-AB and Burkholderia pseudomallei CAP (CAP-BP) to identify the clinical features and risk factors of CAP-AB. CAP-AB was associated with a more productive cough and a shorter duration of symptoms, while CAP-BP was associated with more musculoskeletal symptoms. The white blood cell and neutrophil counts were significantly lower in the CAP-AB group. Gram staining of the sputum revealed a significantly higher amount of bacteria in the CAP-AB group. Lobar infiltration and unilateral right lung involvement were the most common radiographic patterns in the CAP-AB group. CAP-AB is associated with severe pneumonia and has unique clinical features that distinguish it from CAP-BP.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

    2010-01-01

    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-11C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, 3 men and 3 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 (2.5mg) 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 (VT) values in both men and women followed the 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 and preoptic 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 non-invasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain. PMID:20842717

  13. Uniqueness is Important in Competition

    Institute of Scientific and Technical Information of China (English)

    FENG Ai-Xia; XV Xiu-Lian; HE Da-Ren

    2009-01-01

    We propose a quantitative network description on the function of uniqueness in a competition system. Two statistical parameters, competition ability and uniqueness are defined, and their relationship in ordinary cases is analytically discussed. The competition between Chinese regional universities is taken as an example. The empirical investigation results show that the uniqueness of a university is really important in competition. Also,uniqueness is very helpful in the promotion of the university overall quality.

  14. On Uniqueness of coalitional equilibria

    NARCIS (Netherlands)

    Finus, M.; Mouche, van P.H.M.; Rundshagen, B.

    2014-01-01

    For the so-called "new approach" of coalitio formation it is important that coalitional equilibria are unique. Uniqueness comes down to existene and to semi-uniqueness, i.e.\\\\that there exists at most one equilibrium. Although conditions for existence are not problematic, conditions for semi-uniquen

  15. Sphagnum peatlands as a unique habitat for the long-term survival of glacial relicts: a case study of Betula nana

    Science.gov (United States)

    Slowinski, M. M.; Slowinska, S.; Noryśkiewicz, A. M.; Lamentowicz, M.; Kołaczek, P.

    2014-12-01

    Sphagnum peatlands are characterized by distinctive vegetation, hydrology and local climate. They are very important areas for flora and fauna. In the last decade, much effort was made at better understanding of microrefugia and their important role in post-glacial migration of various plant species. The aim of this study is to explain a long-term persistence of the glacial relict Betula nana in a Sphagnum peatland in northern Poland far from the southern range of its natural distribution. We suppose that the persistence of Betula nana is driven by a) the morphology and geology of the catchment, b) the maintenance of open vegetation on the peatland surface and c) exceptional microclimatic and hydrological conditions. A detailed research was carried out on the peat profile using pollen analysis, to reconstruct the presence of open habitat on the mire during the Holocene. Furthermore, detailed monitoring of local climate, hydrology of the peatland and the surrounding area was conducted. The pollen analysis revealed a continuous presence of Betula nana in the postglacial history of the peatland. The results of local climate monitoring indicated that the mire possesses a typical microclimate, with air temperature amplitude much higher in relation to the open area, in particular during the growing season. This, in combination with the hydrology, which depends on the geology of the surrounding area, affects Betula nana population. Linje mire is a unique microrefugium sustained by local factors such as microclimate, geology, local relief and hydrology. However, it is still challenging to explain the intriguing case why this species still occurs within the study site. This work was funded by the National Science Centre grant NN306060940 and Polish-Swiss Research Programme PSPB-013/2010. This study is a contribution to the Virtual Institute of Integrated Climate and Landscape Evolution (ICLEA) of the Helmholtz Association.

  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. MET and Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gelsomino, Francesco, E-mail: francesco.gelsomino@istitutotumori.mi.it [Medical Oncology Unit 1, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milano (Italy); Rossi, Giulio [Operative Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Via del Pozzo 71, 41124 Modena (Italy); Tiseo, Marcello [Medical Oncology Unit, Azienda Ospedaliero-Universitaria, Viale A. Gramsci 14, 43126 Parma (Italy)

    2014-10-13

    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.

  18. MET and Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Gelsomino

    2014-10-01

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

  19. Angular MET sensor for precise azimuth determination

    Science.gov (United States)

    Zaitsev, Dmitry; Antonov, Alexander; Krishtop, Vladimir

    2016-12-01

    This paper describes using a MET-based low-noise angular motion sensor to precisely determine azimuth direction in a dynamic-scheme method of measuring Earth's rotation velocity vector. The scheme includes installing a sensor on a rotating platform so that it could scan a space and seek for the position of highest Earth's rotation vector projection on its axis. This method is very efficient provided a low-noise sensor is used. We take a low-cost angular sensor based on MET (molecular electronic transduction) technology. Sensors of this kind were originally developed for the seismic activity monitoring and are well-known for very good noise performance and high sensitivity. This approach, combined with use of special signal processing algorithms, allowed for reaching the accuracy of 0.07° for a measurement time of 200 seconds.

  20. 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

  1. The effect of using NHS number as the unique identifier for patients who self-harm: a multi-centre descriptive study

    Directory of Open Access Journals (Sweden)

    Lilley Rachael

    2007-09-01

    Full Text Available Abstract Background Processing personal data for research purposes and the requirement of anonymity has been the subject of recent debate. We aimed to determine the proportion of individuals who present to emergency departments with non-fatal suicidal behavior where an NHS number has been successfully traced and to investigate the characteristics of patients associated with non-capture. Method This was a descriptive study of people attending after self-harm using allocation of NHS numbers as main outcome measurement. Data from the Multicentre Monitoring of Self-Harm Project from 3 centres in England were used to identify consecutive patients (N = 3000 who were treated in six emergency departments in Oxford, Manchester and Leeds in 2004 and 2005 following self-harm. Results NHS number was available between 55–73% of individuals across centres. Characteristics associated with non-recording of NHS number in more than one centre included those from ethnic minority groups (Oxford: chi-squared statistic = 13.6, df = 3, p = 0.004; Manchester: chi-squared statistic = 13.6, df = 3, p ≤0.001 and the homeless or living in a hostel or other institution (Oxford: chi-squared statistic = 40.9, df = 7, p = Conclusion Basing research studies on NHS number as the unique identifier, as suggested by the Data Protection Act 1998 and the Patient Information Advisory Group, would exclude some of the most vulnerable groups for further self-harm or suicide. This bias may also affect other research registers.

  2. Structural and mechanistic studies on carboxymethylproline synthase (CarB), a unique member of the crotonase superfamily catalyzing the first step in carbapenem biosynthesis.

    Science.gov (United States)

    Sleeman, Mark C; Sorensen, John L; Batchelar, Edward T; McDonough, Michael A; Schofield, Christopher J

    2005-10-14

    The first step in the biosynthesis of the medicinally important carbapenem family of beta-lactam antibiotics is catalyzed by carboxymethylproline synthase (CarB), a unique member of the crotonase superfamily. CarB catalyzes formation of (2S,5S)-carboxymethylproline [(2S,5S)-t-CMP] from malonyl-CoA and l-glutamate semialdehyde. In addition to using a cosubstrate, CarB catalyzes C-C and C-N bond formation processes as well as an acyl-coenzyme A hydrolysis reaction. We describe the crystal structure of CarB in the presence and absence of acetyl-CoA at 2.24 A and 3.15 A resolution, respectively. The structures reveal that CarB contains a conserved oxy-anion hole probably required for decarboxylation of malonyl-CoA and stabilization of the resultant enolate. Comparison of the structures reveals that conformational changes (involving His(229)) in the cavity predicted to bind l-glutamate semialdehyde occur on (co)substrate binding. Mechanisms for the formation of the carboxymethylproline ring are discussed in the light of the structures and the accompanying studies using isotopically labeled substrates; cyclization via 1,4-addition is consistent with the observed labeling results (providing that hydrogen exchange at the C-6 position of carboxymethylproline does not occur). The side chain of Glu(131) appears to be positioned to be involved in hydrolysis of the carboxymethylproline-CoA ester intermediate. Labeling experiments ruled out the possibility that hydrolysis proceeds via an anhydride in which water attacks a carbonyl derived from Glu(131), as proposed for 3-hydroxyisobutyryl-CoA hydrolase. The structural work will aid in mutagenesis studies directed at altering the selectivity of CarB to provide intermediates for the production of clinically useful carbapenems.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Young H. Lee

    2014-11-01

    Full Text Available 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.

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

    Science.gov (United States)

    Lee, Young H; Apolo, Andrea B; Agarwal, Piyush K; Bottaro, Donald P

    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.

  6. Werken met taalportfolio's in het talenonderwijs aan volwassenen

    NARCIS (Netherlands)

    Broeder, P.; Sorce, M.R.

    2008-01-01

    Werken met portfolio’s is in het talenonderwijs (nog) een veelbelovend nieuw instrument om met leerlingen te werken aan taal. Met een taalportfolio kan de gebruiker de eigen taalkennis inschatten en bewijzen van zijn talenkennis verzamelen. Ook kan door het werken met een taalportfolio het verdere l

  7. Metáfora y novedad

    OpenAIRE

    Edeline, Francis

    2012-01-01

    Antes que nada, quisiera definirme como un semiótico cognoscitivo. Mi formación científica, por una parte, y mi pasado retórico en el sentido del Grupo μ, por otra, constituyen los puntos de partida de mi acercamiento al problema de la metáfora, que no podrá dejar de tocar, de paso, lo relazionado con el conocimiento, la cognición, el sentido.

  8. MET Standards for Electro-Technical Officers

    OpenAIRE

    Janusz Mindykowski

    2014-01-01

    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 ...

  9. Vice President Shen Wenqing Met JST Delegation

    Institute of Scientific and Technical Information of China (English)

    Zhang Yinglan

    2008-01-01

    @@ On May 19,2008,Prof.Shen Weqing,Vice President of NSFC,met with the delegation headed by Prof.Akira Fujishima,Director-General of China Research Center,Japan Science and Technology (JST).Prof.Fujishima is also the Chairman of Kanagawa Academy of Science and Technology,Japan and Foreign Member of the Chinese Academy of Sciences elected in 2003.

  10. 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.

  11. Mart Mets : "Mida rohkem ajaloolisi kihistusi, seda põnevam on aed" / Mart Mets

    Index Scriptorium Estoniae

    Mets, Mart

    2006-01-01

    Eesti elukutselisi aialoojaid tutvustavas sarjas vastab küsimustele maastikuarhitekt Mart Mets. M. Metsast, tema tähtsamad tööd. M. Mets endast, oma õpetajatest, lemmikstiilist, oma tulevasest aiast ja töödest, koostööst klientidega, uuselamurajoonide kruntide probleemidest, vana aia ümberkujundamisest, ilutaimedest, Eesti aiast jpm. Ill.: M. Metsa portreefoto, 6 ill. tema töödest

  12. 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

  13. XRCC3 Thr241Met polymorphism and risk of acute myeloid leukemia in a Romanian population.

    Science.gov (United States)

    Bănescu, Claudia; Tilinca, Mariana; Benedek, Erzsebeth Lazar; Demian, Smaranda; Macarie, Ioan; Duicu, Carmen; Dobreanu, Minodora

    2013-09-10

    DNA repair systems have a critical role in maintaining the genome integrity and stability. DNA repair gene polymorphisms may influence the capacity to repair DNA damage, and thus lead to an increased cancer susceptibility. X-ray repair cross-complementing groups 3 (XRCC3), a DNA repair gene, may be involved in acute myeloid leukemia susceptibility. The objective of the current study was to investigate the association of Thr241Met polymorphism of XRCC3 gene with the risk of acute myeloid leukemia (AML). This study included 78 AML patients and 121 healthy individuals without cancer. We used polymerase chain reaction-restriction fragment length polymorphism assay to determine XRCC3 genotypes. The XRCC3 variant genotype (Thr/Met+Met/Met) was more frequent in AML patients than in healthy controls (OR=2.76, 95% CI: 1.52-4.98, P=0.001). Our study revealed a statistically significant association between variant genotype (Thr/Met+Met/Met) and AML de novo compared to secondary AML (P=0.007). No significant associations were found between any genotype and age at diagnosis, number of white blood cells and subtype of AML. Overall survival of patients with Thr/Thr genotype was better than those of variant Thr/Met and Met/Met genotypes. Our findings indicate that the XRCC3 Thr241Met polymorphism may be a genetic risk factor for AML, particularly in male patients with de novo AML from the central part of Romania. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Environmental aspects in plant protection practices of non-agricultural pesticide users : case study of communes and the ministry of public works and transport (MET) of the Walloon region (Belgium)

    OpenAIRE

    Godeaux, Denis; Schiffers, Bruno; Culot, Marc

    2008-01-01

    In order to gain a better understanding of non-agricultural pesticide use and to prepare the legislative and technical dossiers required under the Water Framework Directive, between October 2006 and March 2007, two surveys were conducted of 97 Walloon communes and 65 districts of the Walloon Ministry of Public Works and Transport (MET) (General Directorates for Motorways and Roads and for Waterway Infrastructure). The questionnaire (26 questions on six topics) was sent by e-mail or fax, wi...

  15. An interpretive review of selective sweep studies in Bos taurus cattle populations: identification of unique and shared selection signals across breeds.

    Directory of Open Access Journals (Sweden)

    Beatriz eGutiérrez-Gil

    2015-05-01

    Full Text Available This review compiles the results of 21 genomic studies of European Bos taurus breeds and thus provides a general picture of the selection signatures in taurine cattle identified by genome-wide selection-mapping scans. By performing a comprehensive summary of the results reported in the literature, we compiled a list of 1,049 selection sweeps described across 37 cattle breeds (17 beef breeds, 14 dairy breeds and 6 dual-purpose breeds, and four different beef-vs-dairy comparisons, which we subsequently grouped into core selective sweep (CSS regions, defined as consecutive signals within 1 Mb of each other. We defined a total of 409 CSSs across the 29 bovine autosomes, 232 (57% of which were associated with a single-breed (Single-breed CSSs, 134 CSSs (33% were associated with a limited number of breeds (Two-to-four-breed CSSs and 39 CSSs (9% were associated with five or more breeds (Multi-breed CSSs. For each CSS, we performed a candidate gene survey that identified 291 genes within the CSS intervals (from the total list of 5,183 BioMart-extracted genes linked to dairy and meat production, stature and coat colour traits. A complementary functional enrichment analysis of the CSS positional candidates highlighted other genes related to pathways underlying behaviour, immune response and reproductive traits. The Single-breed CSSs revealed an over-representation of genes related to dairy and beef production, this was further supported by over-representation of production-related pathway terms in these regions based on a functional enrichment analysis. Overall, this review provides a comparative map of the selection sweeps reported in European cattle breeds and presents for the first time a characterization of the selection sweeps that are found in individual breeds. Based on their uniqueness, these breed-specific signals could be considered as divergence signals, which may be useful in characterising and protecting livestock genetic diversity.

  16. An interpretive review of selective sweep studies in Bos taurus cattle populations: identification of unique and shared selection signals across breeds

    Science.gov (United States)

    Gutiérrez-Gil, Beatriz; Arranz, Juan J.; Wiener, Pamela

    2015-01-01

    This review compiles the results of 21 genomic studies of European Bos taurus breeds and thus provides a general picture of the selection signatures in taurine cattle identified by genome-wide selection-mapping scans. By performing a comprehensive summary of the results reported in the literature, we compiled a list of 1049 selection sweeps described across 37 cattle breeds (17 beef breeds, 14 dairy breeds, and 6 dual-purpose breeds), and four different beef-vs.-dairy comparisons, which we subsequently grouped into core selective sweep (CSS) regions, defined as consecutive signals within 1 Mb of each other. We defined a total of 409 CSSs across the 29 bovine autosomes, 232 (57%) of which were associated with a single-breed (Single-breed CSSs), 134 CSSs (33%) were associated with a limited number of breeds (Two-to-Four-breed CSSs) and 39 CSSs (9%) were associated with five or more breeds (Multi-breed CSSs). For each CSS, we performed a candidate gene survey that identified 291 genes within the CSS intervals (from the total list of 5183 BioMart-extracted genes) linked to dairy and meat production, stature, and coat color traits. A complementary functional enrichment analysis of the CSS positional candidates highlighted other genes related to pathways underlying behavior, immune response, and reproductive traits. The Single-breed CSSs revealed an over-representation of genes related to dairy and beef production, this was further supported by over-representation of production-related pathway terms in these regions based on a functional enrichment analysis. Overall, this review provides a comparative map of the selection sweeps reported in European cattle breeds and presents for the first time a characterization of the selection sweeps that are found in individual breeds. Based on their uniqueness, these breed-specific signals could be considered as “divergence signals,” which may be useful in characterizing and protecting livestock genetic diversity. PMID:26029239

  17. Unique Structural Properties of the Mg-Al Hydrotalcite Solid Base Catalyst : An In Situ Study using Mg and Al K-edge XAFS during Calcination and Rehydration

    NARCIS (Netherlands)

    Koningsberger, D.C.; Bokhoven, J.A. van; Roelofs, J.C.A.A.; Jong, K.P. de

    2001-01-01

    The changes in the layered structure of Mg-Al hydrotalcite (Mg/Al=2) during heat treatment have been investigated by using in situ XAFS simultaneously at the Mg and Al K-edges. The development of unique in situ instrumentation allowed the coordination environments at both the Mg and Al centers to be

  18. 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

  19. Norwegian PUQE (Pregnancy-Unique Quantification of Emesis and nausea identifies patients with hyperemesis gravidarum and poor nutritional intake: a prospective cohort validation study.

    Directory of Open Access Journals (Sweden)

    Elisabeth Birkeland

    Full Text Available The English questionnaire Pregnancy-Unique Quantification of Emesis and nausea (PUQE identifies women with severe Hyperemesis Gravidarum. Our aim was to investigate whether scores from the translated Norwegian version; SUKK (SvangerskapsUtløst Kvalme Kvantifisering was associated with severity of hyperemesis and nutritional intake.A prospective cohort validation study.Hospital cohort of Hyperemesis Gravidarum (HG patients from western Norway and healthy pregnant women from Bergen, Norway.38 women hospitalized due to HG and 31 healthy pregnant controls attending routine antenatal check-up at health centers.Data were collected May 2013-January 2014. The study participants answered the Norwegian PUQE-questionnaire (scores ranging from 3 to 15 and registered prospectively 24-hours nutritional intake by a food list form.Differences of PUQE-scores, QOL-score and nutritional intake between hyperemesis patients and controls.Hyperemesis patients had shorter gestational age compared to controls (median 9.7 weeks; 95% CI 8.6-10.6 versus 11.9; 95% CI 10.1-12.9, p=0.004, and larger weight-change from pre-pregnant weight (loss of median 3 kg; 95% CI 3-4 versus gain of 2 kg; 95% CI 0.5-2, p<0.001 otherwise groups were similar regarding pre-pregnant BMI, age, gravidity, and inclusion weight. Compared to controls, hyperemesis patients had significant higher PUQE-score (median 13; 95% CI 11-14 vs. 7; 95% CI 4-8, lower QOL (median score 3; 95% CI 2-4 vs. 6; 95% CI 4.5-8 and lower nutritional intake (energy intake median 990 kcal/24 hours; 95% CI 709-1233 vs. 1652; 95% CI 1558-1880 all p<0.001. PUQE-score was inversely correlated to nutritional intake (-0.5, p<0.001. At discharge PUQE-score had fallen to median 6 (95% CI 5-8 and QOL score risen to 7 (95% CI 6-8 in the HG group, (both p<0.001 compared to admission values.PUQE-scoring has been validated as a robust indicator of severe hyperemesis gravidarum and insufficient nutritional intake in a Norwegian setting.

  20. Structural basis for DNA recognition by the transcription regulator MetR.

    Science.gov (United States)

    Punekar, Avinash S; Porter, Jonathan; Carr, Stephen B; Phillips, Simon E V

    2016-06-01

    MetR, a LysR-type transcriptional regulator (LTTR), has been extensively studied owing to its role in the control of methionine biosynthesis in proteobacteria. A MetR homodimer binds to a 24-base-pair operator region of the met genes and specifically recognizes the interrupted palindromic sequence 5'-TGAA-N5-TTCA-3'. Mechanistic details underlying the interaction of MetR with its target DNA at the molecular level remain unknown. In this work, the crystal structure of the DNA-binding domain (DBD) of MetR was determined at 2.16 Å resolution. MetR-DBD adopts a winged-helix-turn-helix (wHTH) motif and shares significant fold similarity with the DBD of the LTTR protein BenM. Furthermore, a data-driven macromolecular-docking strategy was used to model the structure of MetR-DBD bound to DNA, which revealed that a bent conformation of DNA is required for the recognition helix α3 and the wing loop of the wHTH motif to interact with the major and minor grooves, respectively. Comparison of the MetR-DBD-DNA complex with the crystal structures of other LTTR-DBD-DNA complexes revealed residues that may confer operator-sequence binding specificity for MetR. Taken together, the results show that MetR-DBD uses a combination of direct base-specific interactions and indirect shape recognition of the promoter to regulate the transcription of met genes.

  1. Plexin B1 inhibits MET through direct association and regulates Shp2 expression in melanocytes.

    Science.gov (United States)

    Soong, Joanne; Scott, Glynis

    2013-01-15

    Plexin B1, the receptor for Semaphorin 4D (Sema4D), is expressed by melanocytes in the skin. We recently showed that Sema4D suppresses activation of the hepatocyte growth factor receptor, MET, in melanocytes, and that knockdown of Plexin B1 results in activation of MET. MET signaling mediates proliferation, survival and migration in melanocytes, and its activation is associated with transformation of melanocytes to melanoma. In this report we investigated the mechanism by which Plexin B1 inhibits MET activation. Our results show that Plexin B1 and MET exist as an oligomeric receptor-receptor complex in melanocytes, and that receptor association is increased by Sema4D. MET and Plexin B1 receptor complexes were identified along the cell body of melanocytes, and Sema4D increased receptor association on dendrites, suggesting that Sema4D regulates MET-dependent processes at precise locations on the melanocyte. Despite activation of MET, Plexin B1 knockdowns proliferated slowly and showed increased apoptosis compared with controls. Shp2, a non-receptor protein tyrosine phosphatase, translates growth and survival signals from MET and other receptor tyrosine kinases. Plexin B1 knockdowns had markedly lower levels of Shp2 compared with controls, and Sema4D upregulated Shp2 expression at the protein and message level in normal melanocytes. Functional studies showed that blockade of Shp2 activity abrogated MET-dependent activation of Erk1/Erk2 and Akt in melanocytes. These results suggest a complex role for Sema4D and Plexin B1 in orchestrating signaling from the MET receptor in melanocytes. Because Shp2 is a downstream adaptor protein for multiple receptors, Sema4D may control the effects of several growth factors on melanocytes through regulation of Shp2.

  2. Photons uniques indiscernables à partir d'une boîte quantique unique dans un cristal photonique

    Science.gov (United States)

    Laurent, S.; Varoutsis, S.; Le Gratiet, L.; Lemaître, A.; Sagnes, I.; Raineri, F.; Levenson, A.; Robert-Philip, I.; Abram, I.

    2006-10-01

    Nous avons développé et caractérisé une source de photons uniques basée sur l'émission spontanée d'une boîte quantique unique insérée dans une cavité à bande interdite photonique bidimensionnelle. Ce système nous a d'abord permis de produire des photons uniques, puis des photons uniques indiscernables avec une indiscernabilité supérieure à 70%. L'observation de l'indiscernabilité des photons, impossible sans un raccourcissement important de la durée de vie, met en évidence un effet Purcell supérieur à 25 dans ce système.

  3. COMT Val158Met Polymorphism Modulates Huntington's Disease Progression

    Science.gov (United States)

    Rebeix, Isabelle; Dupoux, Emmanuel; Durr, Alexandra; Brice, Alexis; Charles, Perrine; Cleret de Langavant, Laurent; Youssov, Katia; Verny, Christophe; Damotte, Vincent; Azulay, Jean-Philippe; Goizet, Cyril; Simonin, Clémence; Tranchant, Christine; Maison, Patrick; Rialland, Amandine; Schmitz, David; Jacquemot, Charlotte; Fontaine, Bertrand; Bachoud-Lévi, Anne-Catherine

    2016-01-01

    Little is known about the genetic factors modulating the progression of Huntington’s disease (HD). Dopamine levels are affected in HD and modulate executive functions, the main cognitive disorder of HD. We investigated whether the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which influences dopamine (DA) degradation, affects clinical progression in HD. We carried out a prospective longitudinal multicenter study from 1994 to 2011, on 438 HD gene carriers at different stages of the disease (34 pre-manifest; 172 stage 1; 130 stage 2; 80 stage 3; 17 stage 4; and 5 stage 5), according to Total Functional Capacity (TFC) score. We used the Unified Huntington’s Disease Rating Scale to evaluate motor, cognitive, behavioral and functional decline. We genotyped participants for COMT polymorphism (107 Met-homozygous, 114 Val-homozygous and 217 heterozygous). 367 controls of similar ancestry were also genotyped. We compared clinical progression, on each domain, between groups of COMT polymorphisms, using latent-class mixed models accounting for disease duration and number of CAG (cytosine adenine guanine) repeats. We show that HD gene carriers with fewer CAG repeats and with the Val allele in COMT polymorphism displayed slower cognitive decline. The rate of cognitive decline was greater for Met/Met homozygotes, which displayed a better maintenance of cognitive capacity in earlier stages of the disease, but had a worse performance than Val allele carriers later on. COMT polymorphism did not significantly impact functional and behavioral performance. Since COMT polymorphism influences progression in HD, it could be used for stratification in future clinical trials. Moreover, DA treatments based on the specific COMT polymorphism and adapted according to disease duration could potentially slow HD progression. PMID:27657697

  4. 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

    2017-06-15

    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); 1-13. ©2017 AACR. ©2017 American Association for Cancer Research.

  5. Hepatocyte growth factor/cMET pathway activation enhances cancer hallmarks in adrenocortical carcinoma

    Science.gov (United States)

    Phan, Liem M.; Fuentes-Mattei, Enrique; Wu, Weixin; Velazquez-Torres, Guermarie; Sircar, Kanishka; Wood, Christopher G.; Hai, Tao; Jimenez, Camilo; Cote, Gilbert J.; Ozsari, Levent; Hofmann, Marie-Claude; Zheng, Siyuan; Verhaak, Roeland; Pagliaro, Lance; Cortez, Maria Angelica; Lee, Mong-Hong; Yeung, Sai-Ching J.; Habra, Mouhammed Amir

    2015-01-01

    Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis and limited response to chemotherapy. Hepatocyte growth factor (HGF) and its receptor cMET augment cancer growth and resistance to chemotherapy, but their role in ACC has not been examined. In this study, we investigated the association between HGF/cMET expression and cancer hallmarks of ACC. Transcriptomic and immunohistochemical analyses indicated that increased HGF/cMET expression in human ACC samples was positively associated with cancer-related biological processes including proliferation and angiogenesis, and negatively correlated with apoptosis. Accordingly, treatment of ACC cells with exogenous HCG resulted in increased cell proliferation in vitro and in vivo while short hairpin RNA-mediated knockdown or pharmacological inhibition of cMET suppressed cell proliferation and tumor growth. Moreover, exposure of cells to mitotane, cisplatin, or radiation rapidly induced pro-cMET expression and was associated with an enrichment of genes (e.g., CYP450 family) related to therapy resistance further implicating cMET in the anticancer drug response. Together, these data suggest an important role for HGF/cMET signaling in ACC growth and resistance to commonly used treatments. Targeting cMET, alone or in combination with other drugs, could provide a breakthrough in the management of this aggressive cancer. PMID:26282167

  6. BDNF Val66Met polymorphism and protein levels in Amniotic Fluid

    Directory of Open Access Journals (Sweden)

    Calabrese Francesca

    2010-02-01

    Full Text Available Abstract Background Brain-Derived Neurotrophic Factor (BDNF is a neurotrophin which plays survival- and growth-promoting activity in neuronal cells and it is involved in cellular plasticity mechanisms as it controls activity dependent synaptic transmission. A functional polymorphism (Val66Met in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF has been associated with memory and cognitive deficits as well as to an increased susceptibility for several psychiatric disorders especially those with a neurodevelopmental origin. To date, no study has evaluated the influence of the Val66Met polymorphism on BDNF levels in a peripheral system that may reflect fetal neurodevelopment. Therefore we investigated in amniotic fluids (AF obtained from 139 healthy women during 15-17 week of pregnancy, BDNF protein levels in correlation with the Val66Met polymorphism. Results Interestingly we found a significant BDNF protein levels reduction in 55 Met carriers (Val/Met and Met/Met (p = 0.002 as compared to 84 non carriers (Val/Val, and no effect of fetus gender, maternal age or gestation week on BDNF levels has been observed. Conclusion These results, although explorative, indicate that during fetal life the Val66Met genotype might influences BDNF protein levels in AF supporting the involvement of this polymorphism in behavioral and functional brain individual differences in the adulthood.

  7. Metástasis coroideas Choroidal metastases

    Directory of Open Access Journals (Sweden)

    C. Camarillo

    2008-01-01

    Full Text Available Las metástasis uveales son el tumor intraocular maligno más frecuente y de ellas, más del 80% se localizan en la coroides. Esto, unido al progresivo aumento de la incidencia, hace necesario su estudio y revisión para un correcto diagnóstico y tratamiento en la práctica clínica actual. La etiología varía según el sexo del paciente, siendo el carcinoma de pulmón el que con más frecuencia metastatiza en el varón y el de mama en la mujer. Tienden a la multifocalidad y generalmente se localizan en el polo posterior. En el 50% de los casos cursan de forma asintomática, pero pueden producir pérdida de visión, escotomas, metamorfopsias, y fotopsias. La exploración oftalmoscópica característica muestra una lesión coroidea placoide, homogénea y de aspecto cremoso. En el diagnóstico diferencial se debe considerar el nevus amelanótico, el melanoma amelanótico de coroides, el hemangioma coroideo, la escleritis posterior, el osteoma de coroides, las coriorretinitis, la enfermedad de Harada, el desprendimiento de retina rhegmatógeno, el síndrome de efusión uveal, y la coriorretinopatía serosa central. Una exhaustiva anamnesis y exploración oftalmológica completa son imprescindibles para el diagnóstico, a lo que se pueden añadir como pruebas complementarias la angiografía con fluoresceína, la ecografía ocular, la punción-aspiración con aguja fina (PAAF, la tomografía computarizada y la resonancia magnética. El tratamiento de estos tumores suele ser el tratamiento sistémico del tumor primario; las posibilidades de tratamiento local son la observación, la radioterapia externa, la braquiterapia, la termoterapia transpupilar y la enucleación.Uveal metastases are the most frequent malign intraocular tumour, of which more than 80% are localized in the choroids. This, together with the progressive increase in its incidence, makes its study and review necessary for a correct diagnosis and treatment in current clinical practice

  8. Targeting of the MET receptor tyrosine kinase by small molecule inhibitors leads to MET accumulation by impairing the receptor downregulation.

    Science.gov (United States)

    Leiser, Dominic; Pochon, Benoît; Blank-Liss, Wieslawa; Francica, Paola; Glück, Astrid A; Aebersold, Daniel M; Zimmer, Yitzhak; Medová, Michaela

    2014-03-03

    The MET receptor tyrosine kinase is deregulated primarily via overexpression or point mutations in various human cancers and different strategies for MET inhibition are currently evaluated in clinical trials. We observed by Western blot analysis and by Flow cytometry that MET inhibition by different MET small molecule inhibitors surprisingly increases in a dose-dependent manner total MET levels in treated cells. Mechanistically, this inhibition-related MET accumulation was associated with reduced Tyr1003 phosphorylation and MET physical association with the CBL ubiquitin ligase with concomitant decrease in MET ubiquitination. These data may suggest careful consideration for design of anti-MET clinical protocols. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  9. Fossil insects may provide unique information on structures and disturbances in past forest ecosystems - examples from Holocene studies in southern Sweden

    Science.gov (United States)

    Lemdahl, Geoffrey; Gustavsson, Gunnar; Olsson, Fredrik; Gaillard, Marie-José

    2010-05-01

    Insects are complex organisms that play an important role in all types of forest ecosystems. Insect remains are often abundant in waterlogged sediments and peat, and the majority of the fossils may be identified to species level, thus contributing with specific information. The occurrence of species feeding or confined to one or a few species of herbaceous plants, shrubs and trees may confirm or improve/refine the interpretations based on pollen and plant macrofossil analyses. Many insects, particularly ground living animals, select open, sun exposed habitats or closed shaded areas. Such indicators are valuable for reconstructions of forest/landscape openness. However, unique information can be provided by fossil insect assemblages. Insect studies carried out at two natural sites in southern Sweden with complete Holocene peat stratigraphies (Olsson and Lemdahl 2009) and a number of sites covering parts of the Holocene (e.g. Gaillard and Lemdahl 1994, Gustavsson et al. 2009) provide strong evidence on changes in forest structure and the occurrence and nature of disturbances. Studies in Britain have yielded similar results (e.g. Whitehouse 2006). Saproxylic beetles indicate the presence of dead wood, which clearly was a more prominent component in ancient woodlands than in present forests, and beetles confined to wood mould suggest the presence of large hollow trees. Finds of pyrophilic species, of which some are very rare in European woodlands today, together with layers of charcoal, suggest that fire was a major disturbance factor during most of the Holocene in southern Sweden. Whereas macroscopic charcoal fragments indicate local fires, the presence of pyrophilic insects is an indication of continuous fire activity at the regional spatial scale. Remains of dung beetles indicate extensive grazing by megaherbivores during early Holocene, and more intensive grazing during late Holocene, whereas such indicators are absent from mid Holocene records, which correlates

  10. 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.

  11. Right temporopolar activation associated with unique perception.

    Science.gov (United States)

    Asari, Tomoki; Konishi, Seiki; Jimura, Koji; Chikazoe, Junichi; Nakamura, Noriko; Miyashita, Yasushi

    2008-05-15

    Unique mode of perception, or the ability to see things differently from others, is one of the psychological resources required for creative mental activities. Behavioral studies using ambiguous visual stimuli have successfully induced diverse responses from subjects, and the unique responses defined in this paradigm were observed in higher frequency in the artistic population as compared to the nonartistic population. However, the neural substrates that underlie such unique perception have yet to be investigated. In the present study, ten ambiguous figures were used as stimuli. The subjects were instructed to say what the figures looked like during functional MRI scanning. The responses were classified as "frequent", "infrequent" or "unique" responses based on the appearance frequency of the same response in an independent age- and gender-matched control group. An event-related analysis contrasting unique vs. frequent responses revealed the greatest activation in the right temporal pole, which survived a whole brain multiple comparison. An alternative parametric modulation analysis was also performed to show that potentially confounding perceptual effects deriving from differences in visual stimuli make no significant contribution to this temporopolar activation. Previous neuroimaging and neuropsychological studies have shown the involvement of the temporal pole in perception-emotion linkage. Thus, our results suggest that unique perception is produced by the integration of perceptual and emotional processes, and this integration might underlie essential parts of creative mental activities.

  12. MDA-MET-conditioned-medium augments the chemoattractant-dependent migration of MDA-MET cells towards hFOB-conditioned medium and increases collagenase activity.

    Science.gov (United States)

    Chin-Quee, Karis; Donahue, Henry J

    2017-05-11

    Metastasis of breast cancer displays site-specificity towards bone. Recently, studies have emerged indicating that primary tumors may remotely influence creation of a pre-metastatic niche. In this study, we used human fetal osteoblastic cells and MDA-MET, a metastatic and preferentially bone homing derivative of the breast cancer cell line MDA-MB-231. We examined 1) whether secreted factors from MDA-MET cells increase generation of chemoattractants by human foetal osteoblastic cells 2) whether MDA-MET cells were responsive to these chemoattractants and 3) the identity of these chemoattractants. Human foetal osteoblastic cells were treated with conditioned medium of MDA-MET cells for 24 hours and then washed with phosphate-buffered saline. Serum-free replacement medium was conditioned by treated hFOB cells for 18 hours, before its use in in vitro quantification of MDA-MET migration. We also quantified collagen levels and collagenase activity in conditioned medium from human foetal osteoblastic cells. Conditioned medium from human foetal osteoblastic cells that had been treated with MDA-MET-conditioned medium attracted more MDA-MET cells than hFOB cells pre-exposed to their own medium. This conditioned medium had increased collagenase activity. The addition of bacterial collagenase removed the ability of conditioned medium from human foetal osteoblastic cells to attract MDA-MET cells. Our data suggest that an increase in collagenase activity in osteoblastic cells induced by their exposure to breast cancer cell-secreted factors may increase their ability to attract breast cancer cells.

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

    Science.gov (United States)

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

    2017-08-15

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

  14. Volwassenen met overgewicht in beweging: de rol van de gezondheidsattitude

    NARCIS (Netherlands)

    Wouters, Eveline

    2008-01-01

    Factoren die mensen met overgewicht belemmeren om met een fysiek trainingsprogramma te beginnen Achtergrond: Bij overgewicht heeft lichaamsbeweging (bijvoorbeeld sportbeoefening) gunstige effecten op het behoud van gewicht(svermindering) en op verschillende aan overgewicht gerelateerde aandoeningen

  15. Samenwerking Wageningen UR met: Faculteit Diergeneeskunde Universiteit Utrecht

    NARCIS (Netherlands)

    Noorduyn, L.

    2008-01-01

    Wageningen UR werkt in haar onderzoeksprogramma’s samen met andere kennis - instellingen. Zo werkt Wageningen UR samen met de Universiteit van Utrecht bij het ontwikkelen van het welzijnsprogramma op het gebied van gezelschapsdieren

  16. The clinical and functional significance of c-Met in breast cancer: a review.

    Science.gov (United States)

    Ho-Yen, Colan M; Jones, J Louise; Kermorgant, Stephanie

    2015-04-08

    c-Met is a receptor tyrosine kinase that upon binding of its ligand, hepatocyte growth factor (HGF), activates downstream pathways with diverse cellular functions that are important in organ development and cancer progression. Anomalous c-Met signalling has been described in a variety of cancer types, and the receptor is regarded as a novel therapeutic target. In breast cancer there is a need to develop new treatments, particularly for the aggressive subtypes such as triple-negative and basal-like cancer, which currently lack targeted therapy. Over the last two decades, much has been learnt about the functional role of c-Met signalling in different models of breast development and cancer. This work has been complemented by clinical studies, establishing the prognostic significance of c-Met in tissue samples of breast cancer. While the clinical trials of anti-c-Met therapy in advanced breast cancer progress, there is a need to review the existing evidence so that the potential of these treatments can be better appreciated. The aim of this article is to examine the role of HGF/c-Met signalling in in vitro and in vivo models of breast cancer, to describe the mechanisms of aberrant c-Met signalling in human tissues, and to give a brief overview of the anti-c-Met therapies currently being evaluated in breast cancer patients. We will show that the HGF/c-Met pathway is associated with breast cancer progression and suggest that there is a firm basis for continued development of anti-c-Met treatment, particularly for patients with basal-like and triple-negative breast cancer.

  17. MEK inhibitors against MET-amplified non-small cell lung cancer

    Science.gov (United States)

    Chiba, Masato; Togashi, Yosuke; Tomida, Shuta; Mizuuchi, Hiroshi; Nakamura, Yu; Banno, Eri; Hayashi, Hidetoshi; Terashima, Masato; De Velasco, Marco A.; Sakai, Kazuko; Fujita, Yoshihiko; Mitsudomi, Tetsuya; Nishio, Kazuto

    2016-01-01

    Several receptor tyrosine kinases (RTKs) including EGFR, ALK, and MET have been identified as therapeutic targets in non-small cell lung cancer (NSCLC). Among the downstream pathways of RTKs, the MAPK pathway is particularly important for cancer cell proliferation, differentiation, and survival. In this study, the effects of MEK inhibitors (trametinib and PD0325901) in several NSCLC cell lines with driver gene alterations, especially RTK genes, were tested in vitro using an MTT assay, and a wide range of sensitivities was found. In particular, all the EGFR-mutated cell lines were resistant to MEK inhibitors, whereas all the MET-amplified cell lines were sensitive. A bioinformatics technique and western blot analyses showed that the PI3K/AKT pathway is more activated in EGFR-mutated NSCLC than in MET-amplified NSCLC, and a PI3K inhibitor enhanced the sensitivity to trametinib in the EGFR-mutated cell lines, suggesting that this pathway is associated with resistance to MEK inhibitors. Although the HCC827 cell line (EGFR mutation) was resistant to MEK inhibitors, the HCC827CNXR cell line, whose driver gene shifts from EGFR to MET, exhibited enhanced sensitivity to MEK inhibitors, indicating the biological importance of the MAPK pathway for MET-amplified NCSLC. Furthermore, a synergistic effect of crizotinib (a MET inhibitor) and trametinib was observed in MET-amplified NCLC cell lines. Our findings indicate that the MAPK pathway is biologically important for MET-amplified NSCLC and strongly encourage the development of combination therapy with a MET inhibitor and a MEK inhibitor against MET-amplified NSCLC. PMID:27748834

  18. Onderzoek naar de mutagene werking van methylacrylaat met microorganismen

    NARCIS (Netherlands)

    Voogd CE; van der Stel JJ; Verharen HW

    1984-01-01

    Met methylacrylaat is geen mutagene werking gevonden in de fluctuatietest met Klebsiella pneumoniae bij 0,02 mol/l (0,172% w/v) of minder in de vloeistoffase of bij 0,0002 mol/l (17,2 mg/l) of minder in de lucht. Met de Salmonella typhimurium stammen TA 98, TA 100 en TA 1535 is met methylacrylaat g

  19. 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.

  20. Installing met towers in marine environments

    Energy Technology Data Exchange (ETDEWEB)

    Hanberg, Jackie [DNV Canada (Canada)

    2011-07-01

    Onshore measurements are taken to supplement offshore wind resource measurement campaigns. To maximize the quality of the measured data, the conditions presented by marine environments must be well understood and mitigated. This paper discusses the several factors that need attention prior to installation of the met towers. The towers experience high corrosion from their exposure to moist, salt-laden, marine air. Careful instrumentation and material selection can prevent or decrease corrosion. Stainless or galvanized hardware and coating sensor terminals with petroleum jelly are both helpful. Soil in the marine environment has variable moisture levels and is extremely wet, which makes grounding systems and backfill enhancers necessary. Weather conditions in these environments also tend to be unpredictable; hence, towers should be strong enough to handle typical marine weather. In conclusion, successful marine wind resource assessment campaigns require environmental research, careful planning, and awareness of the specific issues.

  1. Gevolgen nieuwe mineralen beleid : met aanvoernormen voor Telen met toekomst en BIOM bedrijven 6 bedrijven doorgerekend

    NARCIS (Netherlands)

    Wolf, de M.

    2004-01-01

    In 2006 gaat het nieuwe mestbeleid op basis van gebruiksnormen van start. In veel gevallen zullen de gebruiksnormen de totale aanvoer van mineralen sterker begrenzen dan Minas. PPO heeft voor een aantal Telen met Toekomst (TmT) en BIOM bedrijvendoorgerekend wat de gevolgen kunnen zijn.

  2. 'Gezond met haver' rapportage van het haverketenproject 'Gezond met haver' 2006-2008

    NARCIS (Netherlands)

    Gilissen, L.J.W.J.; Pinxterhuis, E.K.; Gremmen, H.G.J.

    2009-01-01

    In dit rapport wordt ingegaan op de resultaten en ervaringen van het project ‘Gezond met haver’. Het project betreft een innovatief Praktijkproject van TransForum. Het project is gestart in 2006 en afgerond in 2008. Het project heeft beoogd om een relevante bijdrage te leveren aan de maatschappelijk

  3. De eerste ervaringen van mensen met lichamelijke beperkingen met de Wmo.

    NARCIS (Netherlands)

    Klerk, M. de; Marangos, A.M.; Cardol, M.

    2009-01-01

    Op verzoek van het ministerie van Volksgezondheid, Welzijn en Sport (VWS) deed het SCP onderzoek naar de Wmo. Dit onderzoek bestaat uit twee sporen: onderzoek naar de effecten van de Wmo voor mensen met beperkingen en onderzoek naar gemeentelijk beleid. Onlangs verscheen een tussenrapport.

  4. Groei sturen en meer ruimte benutten met LED's in tulpenbroei (interview met Jeroen Wildschut)

    NARCIS (Netherlands)

    Bouwman-van Velden, P.; Wildschut, J.

    2010-01-01

    Bij blauw licht groeien tulpen omhoog en blijven langer dicht. Bij rood licht gaan ze hun blad juist spreiden. Lelies reageren heel anders. Het eerste oriënterende onderzoek met LED-belichting heeft aangetoond dat de kleuren van het licht straks mogelijk zijn in te zetten om de groei echt te sturen.

  5. 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

  6. Uniqueness property for quasiharmonic functions

    Directory of Open Access Journals (Sweden)

    Sevdiyor A. Imomkulov

    2014-10-01

    Full Text Available In this paper we consider a class of continuous functions, called quasiaharmonic functions, admitting best approximations by harmonic polynomials. In this class we prove a uniqueness theorem by analogy with the analytic functions.

  7. 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 ...

  8. Osteoporosis: Unique to Older Adults

    Science.gov (United States)

    ... our e-newsletter! Aging & Health A to Z Osteoporosis Unique to Older Adults This section provides information ... and widely-prescribed medications for the treatment of osteoporosis. Some serious side effects of these medication have ...

  9. Nutrition: Unique to Older Adults

    Science.gov (United States)

    ... our e-newsletter! Aging & Health A to Z Nutrition Unique to Older Adults This section provides information ... teeth that are needed for grinding up food, nutrition suffers. If you are unable to chew and ...

  10. Methionine uptake in Corynebacterium glutamicum by MetQNI and by MetPS, a novel methionine and alanine importer of the NSS neurotransmitter transporter family.

    Science.gov (United States)

    Trötschel, Christian; Follmann, Martin; Nettekoven, Jeannine A; Mohrbach, Tobias; Forrest, Lucy R; Burkovski, Andreas; Marin, Kay; Krämer, Reinhard

    2008-12-02

    The soil bacterium Corynebacterium glutamicum is a model organism in amino acid biotechnology. Here we present the identification of two different L-methionine uptake systems including the first characterization of a bacterial secondary methionine carrier. The primary carrier MetQNI is a high affinity ABC-type transporter specific for l-methionine. Its expression is under the control of the transcription factor McbR, the global regulator of sulfur metabolism in C. glutamicum. Besides MetQNI, a novel secondary methionine uptake system of the NSS (neurotransmitter:sodium symporter) family was identified and named MetP. The MetP system is characterized by a lower affinity for methionine and uses Na(+) ions for energetic coupling. It is also the main alanine transporter in C. glutamicum and is expressed constitutively. These observations are consistent with models of methionine, alanine, and leucine bound to MetP, derived from the X-ray crystal structure of the LeuT transporter from Aquifex aeolicus. Complementation studies show that MetP consists of two components, a large subunit with 12 predicted transmembrane segments and, surprisingly, an additional subunit with one predicted transmembrane segment only. Thus, this new member of the NSS transporter family adds a novel feature to this class of carriers, namely, the functional dependence on an additional small subunit.

  11. Putative PPAR target genes express highly in skeletal muscle of insulin-resistant MetS model SHR/NDmc-cp rats.

    Science.gov (United States)

    Hariya, Natsuyo; Miyake, Kunio; Kubota, Takeo; Goda, Toshinao; Mochizuki, Kazuki

    2015-01-01

    It is known that insulin resistance in skeletal muscle induces subsequent metabolic diseases such as metabolic syndrome (MetS). However, which genes are altered in the skeletal muscle by development of insulin resistance in animal models has not been examined. In this study, we performed microarray and subsequent real-time RT-PCR analyses using total RNA extracted from the gastrocnemius muscle of the MetS model, spontaneously hypertensive corpulent congenic (SHR/NDmc-cp) rats, and control Wistar Kyoto (WKY) rats. SHR/NDmc-cp rats displayed overt insulin resistance relative to WKY rats. The expression of many genes related to fatty acid oxidation was higher in SHR/NDmc-cp rats than in WKY rats. Among 18 upregulated genes, putative peroxisome proliferator responsive elements were found in the upstream region of 15 genes. The protein expression of ACOX2, an upregulated gene, and peroxisome proliferator-activated receptor (PPAR) G1, but not of PPARG2, PPARA or PPARD, was higher in the gastrocnemius muscle of SHR/NDmc-cp rats than that in WKY rats. These results suggest that insulin resistance in the MetS model, SHR/NDmc-cp rats, is positively associated with the expression of fatty acid oxidation-related genes, which are presumably PPARs’ targets, in skeletal muscle.

  12. Brucella melitensis Methionyl-tRNA-Synthetase (MetRS), a Potential Drug Target for Brucellosis

    Science.gov (United States)

    Ranade, Ranae M.; Zhang, Zhongsheng; Dranow, David M.; Myers, Janette B.; Choi, Ryan; Nakazawa Hewitt, Steve; Edwards, Thomas E.; Davies, Douglas R.; Lorimer, Donald; Boyle, Stephen M.; Barrett, Lynn K.; Buckner, Frederick S.; Fan, Erkang; Van Voorhis, Wesley C.

    2016-01-01

    We investigated Brucella melitensis methionyl-tRNA-synthetase (BmMetRS) with molecular, structural and phenotypic methods to learn if BmMetRS is a promising target for brucellosis drug development. Recombinant BmMetRS was expressed, purified from wild type Brucella melitensis biovar Abortus 2308 strain ATCC/CRP #DD-156 and screened by a thermal melt assay against a focused library of one hundred previously classified methionyl-tRNA-synthetase inhibitors of the blood stage form of Trypanosoma brucei. Three compounds showed appreciable shift of denaturation temperature and were selected for further studies on inhibition of the recombinant enzyme activity and cell viability against wild type B. melitensis strain 16M. BmMetRS protein complexed with these three inhibitors resolved into three-dimensional crystal structures and was analyzed. All three selected methionyl-tRNA-synthetase compounds inhibit recombinant BmMetRS enzymatic functions in an aminoacylation assay at varying concentrations. Furthermore, growth inhibition of B. melitensis strain 16M by the compounds was shown. Inhibitor-BmMetRS crystal structure models were used to illustrate the molecular basis of the enzyme inhibition. Our current data suggests that BmMetRS is a promising target for brucellosis drug development. However, further studies are needed to optimize lead compound potency, efficacy and safety as well as determine the pharmacokinetics, optimal dosage, and duration for effective treatment. PMID:27500735

  13. CYP1B1: a unique gene with unique characteristics.

    Science.gov (United States)

    Faiq, Muneeb A; Dada, Rima; Sharma, Reetika; Saluja, Daman; Dada, Tanuj

    2014-01-01

    CYP1B1, a recently described dioxin inducible oxidoreductase, is a member of the cytochrome P450 superfamily involved in the metabolism of estradiol, retinol, benzo[a]pyrene, tamoxifen, melatonin, sterols etc. It plays important roles in numerous physiological processes and is expressed at mRNA level in many tissues and anatomical compartments. CYP1B1 has been implicated in scores of disorders. Analyses of the recent studies suggest that CYP1B1 can serve as a universal/ideal cancer marker and a candidate gene for predictive diagnosis. There is plethora of literature available about certain aspects of CYP1B1 that have not been interpreted, discussed and philosophized upon. The present analysis examines CYP1B1 as a peculiar gene with certain distinctive characteristics like the uniqueness in its chromosomal location, gene structure and organization, involvement in developmentally important disorders, tissue specific, not only expression, but splicing, potential as a universal cancer marker due to its involvement in key aspects of cellular metabolism, use in diagnosis and predictive diagnosis of various diseases and the importance and function of CYP1B1 mRNA in addition to the regular translation. Also CYP1B1 is very difficult to express in heterologous expression systems, thereby, halting its functional studies. Here we review and analyze these exceptional and startling characteristics of CYP1B1 with inputs from our own experiences in order to get a better insight into its molecular biology in health and disease. This may help to further understand the etiopathomechanistic aspects of CYP1B1 mediated diseases paving way for better research strategies and improved clinical management.

  14. The association of XRCC3 Thr241Met genetic variant with risk of ...

    African Journals Online (AJOL)

    Methods: We identified three eligible studies, 499 prostate cancer cases and 571 ... Conclusions: Results from this meta-analysis indicate that the XRCC3 Thr241Met genetic variant is associated with prostate cancer risk. ... Article Metrics.

  15. MET: roles in epithelial-mesenchymal transition and cancer stemness

    Science.gov (United States)

    Jeon, Hye-Min

    2017-01-01

    In a number of cancers, deregulated MET pathway leads to aberrantly activated proliferative and invasive signaling programs that promote malignant transformation, cell motility and migration, angiogenesis, survival in hypoxia, and invasion. A better understanding of oncogenic MET signaling will help us to discover effective therapeutic approaches and to identify which tumors are likely to respond to MET-targeted cancer therapy. In this review, we will summarize the roles of MET signaling in cancer, with particular focus on epithelial-mesenchymal transition (EMT) and cancer stemness. Then, we will provide update on MET targeting agents and discuss the challenges that should be overcome for the development of an effective therapy. PMID:28164090

  16. Cranial computer assisted tomography and electroencephalography in children with acute lymphocytic leukemia : a longitudinal study : Computertomografie van de schedel en electroencephalografisch onderzoek bij kinderen met een acute lymfatische leukemie. Een longitudinale studie

    NARCIS (Netherlands)

    K. Hählen (Karel)

    1990-01-01

    textabstractThis longitudinal study was initiated in order to examine the nature and sequence of structural and functional cerebral abnormalities in children with acute lymphocytic leukemia (ALL). For this purpose computer assisted tomography scans of the brain ( CT scans ) and electroencephalograms

  17. I. Estructuras metálicas ligeras

    Directory of Open Access Journals (Sweden)

    Beer, Hermann

    1967-09-01

    Full Text Available The first part of this paper is being published in the present issue of «Informes de la Construcción», and will be followed by two further parts in the next two numbers of this magazine. It corresponds to the manuscript utilised for the two lecturers given at Costillares by professor Hermann Beer. These lectures were given on March 8 and 9th last. Professor Beer, professor of the High Technical School of Graz, Austria, is President of the Committee II of A.I.P.C. and of the Committee VIII of the European Convention on Metallic Construction, and has worldwide reputation in the field of metallic structures. The up to date nature of the subject and the abundant graphical documentation which illustrates it has led this Institute to believe that it will be of great interest to professionals to publish the text of these lectures. It should be emphasized that professor Beer knows Spanish very well. He learnt this language during the years he was professor at the University of Tucumán, in Argentina. In the following text the Institute has only introduced some slight adjustments of syntax and spelling.Este trabajo, cuya primera parte se publica en este número y continuará y terminará en los dos próximos de INFORMES DE LA CONSTRUCCIÓN, corresponde al texto escrito por el propio conferenciante de las dos conferencias pronunciadas, en el aula de Costillares, por el profesor Hermann Beer, los días 8 y 9 de marzo pasado. El profesor Beer, Catedrático de la Escuela Técnica Superior de Graz (Austria, Presidente de la Comisión II de la A.I.P.C. y de la Comisión VIII de la Convención Europea de la Construcción Metálica, goza de una reputación universal en el campo de las estructuras metálicas. La actualidad del tema elegido para sus conferencias y la abundante documentación gráfica con que las ilustró, han hecho pensar al Instituto en el gran interés que, para los profesionales, pueda tener su publicación. Es de destacar que el profesor

  18. 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.

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

    Science.gov (United States)

    Hall, Kathryn T; Lembo, Anthony J; Kirsch, Irving; Ziogas, Dimitrios C; Douaiher, Jeffrey; Jensen, Karin B; Conboy, Lisa A; Kelley, John M; Kokkotou, Efi; Kaptchuk, Ted J

    2012-01-01

    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.

  20. Catechol-O-Methyltransferase val158met Polymorphism Predicts Placebo Effect in Irritable Bowel Syndrome

    Science.gov (United States)

    Hall, Kathryn T.; Lembo, Anthony J.; Kirsch, Irving; Ziogas, Dimitrios C.; Douaiher, Jeffrey; Jensen, Karin B.; Conboy, Lisa A.; Kelley, John M.; Kokkotou, Efi; Kaptchuk, Ted J.

    2012-01-01

    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. PMID:23110189

  1. BDNF val66met genotype and schizotypal personality traits interact to influence probabilistic association learning.

    Science.gov (United States)

    Skilleter, Ashley Jayne; Weickert, Cynthia Shannon; Moustafa, Ahmed Abdelhalim; Gendy, Rasha; Chan, Mico; Arifin, Nur; Mitchell, Philip Bowden; Weickert, Thomas Wesley

    2014-11-01

    The brain derived neurotrophic factor (BDNF) val66met polymorphism rs6265 influences learning and may represent a risk factor for schizophrenia. Healthy people with high schizotypal personality traits display cognitive deficits that are similar to but not as severe as those observed in schizophrenia and they can be studied without confounds of antipsychotics or chronic illness. How genetic variation in BDNF may impact learning in individuals falling along the schizophrenia spectrum is unknown. We predicted that schizotypal personality traits would influence learning and that schizotypal personality-based differences in learning would vary depending on the BDNF val66met genotype. Eighty-nine healthy adults completed the Schizotypal Personality Questionnaire (SPQ) and a probabilistic association learning test. Blood samples were genotyped for the BDNF val66met polymorphism. An ANOVA was performed with BDNF genotype (val homozygotes and met-carriers) and SPQ score (high/low) as grouping variables and probabilistic association learning as the dependent variable. Participants with low SPQ scores (fewer schizotypal personality traits) showed significantly better learning than those with high SPQ scores. BDNF met-carriers displaying few schizotypal personality traits performed best, whereas BDNF met-carriers displaying high schizotypal personality traits performed worst. Thus, the BDNF val66met polymorphism appears to influence probabilistic association learning differently depending on the extent of schizotypal personality traits displayed. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  2. 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.

  3. Rationale and protocol of MetNET-2 trial: Lanreotide Autogel plus metformin in advanced gastrointestinal or lung neuroendocrine tumors.

    Science.gov (United States)

    Pusceddu, Sara; Prinzi, Natalie; Lo Russo, Giuseppe; Femia, Daniela; Milione, Massimo; Perrone, Federica; Tamborini, Elena; Concas, Laura; Pulice, Iolanda; Vernieri, Claudio; Corti, Francesca; Buzzoni, Roberto; de Braud, Filippo

    2017-08-01

    Metformin (MET) has recently emerged as a potentially active agent in cancer prevention and treatment. MET is thought to exert its antitumor effects either via modification of systemic metabolism or through cell-autonomous effects (e.g., activation of AMPK and inhibition of the mTOR pathway). Preliminary findings of the PRIME-NET study suggest that the addition of MET to treatment with everolimus (EVE) and/or somatostatin analogs (SSAs) can provide clinical benefit in diabetic neuroendocrine tumor (NET) patients. In light of this and other retrospective evidence of MET's anticancer activity in NETs, prospective studies are needed. A pilot, single-arm, open-label, prospective study (MetNET-2 trial, NCT02823691) was designed to evaluate the safety of MET in combination with lanreotide in well-differentiated gastrointestinal (WD GI) and lung NETs.

  4. 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.

  5. Amygdalar enlargement associated with unique perception.

    Science.gov (United States)

    Asari, Tomoki; Konishi, Seiki; Jimura, Koji; Chikazoe, Junichi; Nakamura, Noriko; Miyashita, Yasushi

    2010-01-01

    Interference by amygdalar activity in perceptual processes has been reported in many previous studies. Consistent with these reports, previous clinical studies have shown amygdalar volume change in multiple types of psychotic disease presenting with unusual perception. However, the relationship between variation in amygdalar volume in the normal population and the tendency toward unusual or unique perception has never been investigated. To address this issue, we defined an index to represent the tendency toward unique perception using ambiguous stimuli: subjects were instructed to state what the figures looked like to them, and "unique responses" were defined depending on the appearance frequency of the same responses in an age- and gender-matched control group. The index was defined as the ratio of unique responses to total responses per subject. We obtained structural brain images and values of the index from sixty-eight normal subjects. Voxel-based morphometry analyses revealed a positive correlation between amygdalar volume and the index. Since previous reports have indicated that unique responses were observed at higher frequency in the artistic population than in the nonartistic normal population, this positive correlation suggests that amygdalar enlargement in the normal population might be related to creative mental activity.

  6. Residues Met76 and Gln79 in HLA-G α1 domain involved in KIR2DL4 recognition

    Institute of Scientific and Technical Information of China (English)

    Wei Hua YAN; Li An FAN

    2005-01-01

    Human leukocyte antigen-G (HLA-G) has long been speculated as a beneficial factor for a successful pregnancy for its restricted expression on fetal-maternal extravillous cytotrophoblasts and its capability of modulating uterine natural killer cell (uNK) function such as cytotoxicity and cytokine production through NK cell receptors. HLA class I α1domain is an important killer cell Ig-like receptor (KIR) recognition site and the Met76 and Gln79 are unique to HLA-G in this region. NK cell receptor KIR2DL4 is a specific receptor for HLA-G, yet the recognition site on HLA-G remains unknown. In this study, retroviral transduction was applied to express the wild type HLA-G (HLA-wtG), mutant HLA-G (HLA-mG) on the chronic myelogenous leukemia cell line K562 cells and KIR2DL4 molecule on NK-92 cells,respectively. KIR2DL4-IgG Fc fusion protein was generated to determine the binding specificity between KIR2DL4and HLA-G. Our results showed that residue Met76, Gln79 mutated to Ala76,79 in the α1 domain of HLA-G protein could affect the binding affinity between KIR2DL4 and HLA-G, meanwhile, the KIR2DL4 transfected NK-92 cells (NK-92-2DL4) showed a considerably different cytolysis ability against the HLA-wtG and HLA-mG transfected K562 targets.Taken together, our data indicated that residue Met76 and Gln79 in HLA-G α1 domain plays a critical role in the recognition of KIR2DL4, which could be an explanation for the isoforms of HLA-G, all containing the α1 domain, with the potential to regulate NK functions.

  7. 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.

  8. Prevalence of 35delG and Met34Thr GJB2 variants in Portuguese samples.

    Science.gov (United States)

    Dória, Mariana; Neto, Ana Paula; Santos, Ana Cristina; Barros, Henrique; Fernandes, Susana; Moura, Carla Pinto

    2015-12-01

    To estimate the prevalence of 35delG and Met34Thr variants in a Portuguese children's community sample and to compare these frequencies with nonsyndromic hearing-loss patients. 502 children were randomly selected among the 8647 participants of the Portuguese birth cohort Generation XXI, and screened for Met34Thr and 35delG variants in the GJB2 gene. These variants were also studied on 89 index-cases, observed in the Clinic of "Hereditary Hearing-loss" in Saint John's Hospital Center, presenting a mild to profound nonsyndromic hearing-loss. Among the 502 children from Generation XXI, 10 were heterozygous for the 35delG variant (95% Confidence Interval 1.03-3.68) and 1 homozygous (95% Confidence Interval 0.01-1.24). Other 10 children presented heterozygosity for the Met34Thr variant (95% Confidence Interval 1.03-3.68). No homozygous for the Met34Thr or compound heterozygotes (35delG/Met34Thr) were found. In the total of 89 nonsyndromic hearing-loss patients, 5 (95% Confidence Interval 2.11-12.8) were heterozygous and 7 (95% Confidence Interval 3.61-15.6) were homozygous for the 35delG variant. The Met34Thr variant was found in 4 patients, 2 heterozygous (95% Confidence Interval 0.13-8.31) and 2 homozygous (95% Confidence Interval 0.13-8.31). The carrier frequency of 35delG and Met34Thr variants in a Portuguese sample was 1 in 50. Our data suggests that the 35delG mutation has an association with deafness. For the Met34Thr variant, no association was observed. However, Met34Thr seemed to conform to an additive model in hearing-loss. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with αα Domain Architecture That Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence.

    Science.gov (United States)

    Harris, Golda G; Lombardi, Patrick M; Pemberton, Travis A; Matsui, Tsutomu; Weiss, Thomas M; Cole, Kathryn E; Köksal, Mustafa; Murphy, Frank V; Vedula, L Sangeetha; Chou, Wayne K W; Cane, David E; Christianson, David W

    2015-12-01

    Geosmin synthase from Streptomyces coelicolor (ScGS) catalyzes an unusual, metal-dependent terpenoid cyclization and fragmentation reaction sequence. Two distinct active sites are required for catalysis: the N-terminal domain catalyzes the ionization and cyclization of farnesyl diphosphate to form germacradienol and inorganic pyrophosphate (PPi), and the C-terminal domain catalyzes the protonation, cyclization, and fragmentation of germacradienol to form geosmin and acetone through a retro-Prins reaction. A unique αα domain architecture is predicted for ScGS based on amino acid sequence: each domain contains the metal-binding motifs typical of a class I terpenoid cyclase, and each domain requires Mg(2+) for catalysis. Here, we report the X-ray crystal structure of the unliganded N-terminal domain of ScGS and the structure of its complex with three Mg(2+) ions and alendronate. These structures highlight conformational changes required for active site closure and catalysis. Although neither full-length ScGS nor constructs of the C-terminal domain could be crystallized, homology models of the C-terminal domain were constructed on the basis of ∼36% sequence identity with the N-terminal domain. Small-angle X-ray scattering experiments yield low-resolution molecular envelopes into which the N-terminal domain crystal structure and the C-terminal domain homology model were fit, suggesting possible αα domain architectures as frameworks for bifunctional catalysis.

  10. Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis.

    Directory of Open Access Journals (Sweden)

    Yoriko Yamashita

    Full Text Available Clear cell adenocarcinoma of the ovary (OCC is a chemo-resistant tumor with a relatively poor prognosis and is frequently associated with endometriosis. Although it is assumed that oxidative stress plays some role in the malignant transformation of this tumor, the characteristic molecular events leading to carcinogenesis remain unknown. In this study, an array-based comparative genomic hybridization (CGH analysis revealed Met gene amplification in 4/13 OCC primary tumors and 2/8 OCC cell lines. Amplification of the AKT2 gene, which is a downstream component of the Met/PI3K signaling pathway, was also observed in 5/21 samples by array-based CGH analysis. In one patient, both the Met and AKT2 genes were amplified. These findings were confirmed using fluorescence in situ hybridization, real-time quantitative PCR, immunoblotting, and immunohistochemistry. In total, 73 OCC cases were evaluated using real-time quantitative PCR; 37.0% demonstrated Met gene amplification (>4 copies, and 8.2% had AKT2 amplification. Furthermore, stage 1 and 2 patients with Met gene amplification had significantly worse survival than patients without Met gene amplification (p<0.05. Met knockdown by shRNA resulted in reduced viability of OCC cells with Met amplification due to increased apoptosis and cellular senescence, suggesting that the Met signaling pathway plays an important role in OCC carcinogenesis. Thus, we believe that targeted inhibition of the Met pathway may be a promising treatment for OCC.

  11. Distribution of the Val108/158Met polymorphism of the COMT gene in healthy Mexican population.

    Science.gov (United States)

    González-Castro, Thelma Beatriz; Tovilla-Zárate, Carlos; Juárez-Rojop, Isela; Pool García, Sherezada; Genis, Alma; Nicolini, Humberto; López Narváez, Lilia

    2013-09-10

    Catechol-O-methyltransferase (COMT) inactivates the catecholamines adrenaline, noradrenaline and dopamine. On the other hand, some studies have reported that the enzymatic activity of COMT is partly genetically determined. With regard to the COMT gene, the most studied polymorphism is the functional variant Val108/158Met (rs4680), which results in substantial three- to four-fold variations in enzyme activity. To date, the rs4680 polymorphism of COMT has been associated with a number of disorders. In addition, this polymorphism has been found to have important differences in frequency according to the studied population. Therefore, the aim of the present study was to evaluate the frequency of a common single nucleotide polymorphism (SNP) Val108/158Met of the COMT gene in the Mexican population. Accordingly, we recruited 431 healthy volunteers. Our sample consisted of 111 healthy individuals from Mexico City and 320 individuals from the state of Tabasco, Mexico. We observed that Met was the most common allele, ranging from 57% (Tabasco) to 85% (Mexico City). In addition, we analyzed the frequency of Val108/158Met polymorphism of Caucasian (54% Met allele), Asian (29% Met allele) and African (34% Met allele) populations separately and also in comparison with Mexican (63% Met allele) population. In conclusion, the distribution of the Val108/158Met polymorphism distinguishes the Mexican population studied from other populations, but it is necessary to increase the size of the sample to get more conclusive results.

  12. Environmental aspects in plant protection practices of non-agricultural pesticide users: case study of communes and the ministry of public works and transport (MET) of the Walloon Region (Belgium).

    Science.gov (United States)

    Godeaux, D; Schiffers, B; Culot, M

    2008-01-01

    In order to gain a better understanding of non-agricultural pesticide use and to prepare the legislative and technical dossiers required under the Water Framework Directive, between October 2006 and March 2007, two surveys were conducted of 97 Walloon communes and 65 districts of the Walloon Ministry of Public Works and Transport (MET) (General Directorates for Motorways and Roads and for Waterway Infrastructure). The questionnaire (26 questions on six topics) was sent by e-mail or fax, with a response rate of 60 out of 97 communes and 33 out of 65 districts. This article describes the environmental aspects of the surveys (health-related aspects are the subject of separate article). The surveys have brought to light a number of good practices (including zero pesticides) and a growing awareness of environmental issues among non-agricultural users. However, bad habits, legislation infringements and a failure to follow good plant protection practice are still a problem and pose major environmental risks (in the form of water pollution from pesticides). Information, awareness-raising and training therefore remain a priority for non-agricultural users.

  13. Rufus Choate: A Unique Orator.

    Science.gov (United States)

    Markham, Reed

    Rufus Choate, a Massachusetts lawyer and orator, has been described as a "unique and romantic phenomenon" in America's history. Born in 1799 in Essex, Massachusetts, Choate graduated from Dartmouth College and attended Harvard Law School. Choate's goal was to be the top in his profession. Daniel Webster was Choate's hero. Choate became well…

  14. Uniqueness of PL Minimal Surfaces

    Institute of Scientific and Technical Information of China (English)

    Yi NI

    2007-01-01

    Using a standard fact in hyperbolic geometry, we give a simple proof of the uniqueness of PL minimal surfaces, thus filling in a gap in the original proof of Jaco and Rubinstein. Moreover, in order to clarify some ambiguity, we sharpen the definition of PL minimal surfaces, and prove a technical lemma on the Plateau problem in the hyperbolic space.

  15. On the Nagumo uniqueness theorem

    OpenAIRE

    Octavian G. Mustafa; O'Regan, Donal

    2011-01-01

    By a convenient reparametrisation of the integral curves of a nonlinear ordinary differential equation (ODE), we are able to improve the conclusions of the recent contribution [A. Constantin, Proc. Japan Acad. {\\bf 86(A)} (2010), 41--44]. In this way, we establish a flexible uniqueness criterion for ODEs without Lipschitz-like nonlinearities.

  16. The Lasso Problem and Uniqueness

    CERN Document Server

    Tibshirani, Ryan J

    2012-01-01

    The lasso is a popular tool for sparse linear regression, especially for problems in which the number of variables p exceeds the number of observations n. But when p>n, the lasso criterion is not strictly convex, and hence it may not have a unique minimum. An important question is: when is the lasso solution well-defined (unique)? We review results from the literature, which show that if the predictor variables are drawn from a continuous probability distribution, then there is a unique lasso solution with probability one, regardless of the sizes of n and p. We also show that this result extends easily to $\\ell_1$ penalized minimization problems over a wide range of loss functions. A second important question is: how can we deal with the case of non-uniqueness in lasso solutions? In light of the aforementioned result, this case really only arises when some of the predictor variables are discrete, or when some post-processing has been performed on continuous predictor measurements. Though we certainly cannot c...

  17. Multi-frequency solar observations at Metsähovi Radio Observatory and KAIRA

    Science.gov (United States)

    Kallunki, J.; Uunila, M.; McKay-Bukowski, D.

    2015-08-01

    We describe solar observations carried out for the first time jointly with Kilpisjärvi Atmospheric Imaging Receiver Array (KAIRA) and Aalto University Metsähovi Radio Observatory (MRO). KAIRA is new radio antenna array observing the decimeter and meter wavelength range. It is located near Kilpisjärvi, Finland, and operated by the Sodankylä Geophysical Observatory, University of Oulu. We investigate the feasibility of KAIRA for solar observations, and the additional benefits of carrying out multi-instrument solar observations with KAIRA and the MRO facilities, which are already used for regular solar observations. The data measured with three instruments at MRO, and with KAIRA during time period 2014 April-October were analyzed. One solar radio event, measured on 2014 April 18, was studied in detail. Seven solar flares were recorded with at least two of the three instruments at MRO, and with KAIRA during the chosen time period. KAIRA is a great versatile asset as a new Finnish instrument that can also be used for solar observations. Collaboration observations with MRO instruments and KAIRA enable detailed multi-frequency solar flare analysis. Flare pulsations, flare statistics and radio spectra of single flares can be investigated due to the broad frequency range observations. The Northern locations of both MRO and KAIRA make as long as 15-hour unique solar observations possible during summer time.

  18. 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

  19. The ATLAS Z + MET Excess in the MSSM

    CERN Document Server

    Cahill-Rowley, M; Ismail, A; Rizzo, T G

    2015-01-01

    We demonstrate that the $3\\sigma$ excess observed by ATLAS in the Z + MET channel can be explained within the context of the MSSM. Using the freedom inherent in the pMSSM, we perform a detailed analysis of the parameter space and find a scenario that describes the excess while simultaneously complying with all other search constraints from the Run I data at 7 and 8 TeV, including the Z + MET analysis by CMS. We generate a small sample of simplified models, using promising models from our existing pMSSM sample as seeds, and study their properties. The successful region is described by the production of 1st/2nd generation squark pairs, followed by their decay into a bino-like neutralino which in turn decays into a Higgsino-like LSP triplet by emitting a Z boson, i.e., $\\tilde q\\to\\tilde B\\to\\tilde h$ with $\\tilde q = \\tilde Q_L,\\tilde u_R,$ or $\\tilde d_R$. The sweet spot for the sparticle spectrum is found to have squark masses in the 500-750 GeV range, with bino masses near 350 GeV with a mass splitting of 15...

  20. 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.

  1. Uniqueness of meromorphic functions concerning differential polynomials

    Institute of Scientific and Technical Information of China (English)

    QIAO Lei

    2007-01-01

    Based on a unicity theorem for entire funcitions concerning differential polynomials proposed by M. L. Fang and W. Hong, we studied the uniqueness problem of two meromorphic functions whose differential polynomials share the same 1-point by proving two theorems and their related lemmas. The results extend and improve given by Fang and Hong's theorem.

  2. The Uniqueness of Speech among Motor Systems

    Science.gov (United States)

    Kent, Ray

    2004-01-01

    This paper considers evidence that the speech muscles are unique in their genetic, developmental, functional and phenotypical properties. The literature was reviewed using PubMed, ScienceDirect, ComDisDome and other literature-retrieval systems to identify studies reporting on the craniofacial and laryngeal muscles. Particular emphasis was given…

  3. Art Libraries: Creating Access to Unique Collections

    Science.gov (United States)

    Falls, Sarah E.

    2009-01-01

    Art libraries face similar issues to other types of libraries during the digital transition but have unique twists driven by the needs of their collections. Art library information seekers may possess a sense of what an art library is: a library, set apart, to support the study of art and art history. For art libraries, it is the collection,…

  4. 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.

  5. DNA修复基因XRCC3 Thr241Met多态性在四川汉族人群的分布%STUDY ON GENETIC POLYMORPHISM OF DNA REPAIR GENE XRCC3 THR241MET IN SICHUAN HAN POPULATION

    Institute of Scientific and Technical Information of China (English)

    戴穹; 杨志惠

    2007-01-01

    目的:研究DNA修复基因X线修复交叉互补基因3(XRCC3)Thr241Met位点多态性在四川汉族人群的分布,并与其它种族比较其分布特点.方法:采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)方法检测四川泸州地区220例健康无血缘关系个体Thr241Met位点基因型和等位基因频率分布.结果:共检测出两种基因型,Thr/Thr和Thr/Met,其频率分布为91.82%和8.18%,基因型频率分布符合Hardy-Weinberg平衡定律,其基因型频率分布与比利时、法国、美国、芬兰人群比较有统计学意义(P<0.05),而与中国南京人群比较无统计学意义(P>0.05).结论:XRCC3Thr241Met位点多态性分布在中国人群中无统计学意义,但与欧美人群比较有统计学意义,证实了多态性分布的种族和地域差异.

  6. BDNF Val66Met, stress, and positive mothering: Differential susceptibility model of adolescent trait anxiety.

    Science.gov (United States)

    Chen, Jie; Yu, Jing; Liu, Yujie; Zhang, Leilei; Zhang, Jianxin

    2015-08-01

    Etiological research has indicated the gene-environment interaction (G × E) on adolescent anxiety. This study aimed to examine how the BDNF Val66Met polymorphism interacted with stressful life events and positive mothering to influence youth trait anxiety. The study sample included 780 community adolescents of Chinese Han ethnicity (M = 13.6, 51.3% females). Participants' trait anxiety, exposure to stressful life events, and mother's warmth-reasoning were assessed by self-reported questionnaires. We found that BDNF Val66Met polymorphism significantly moderated the influences of stressful life events and mother's warmth-reasoning on adolescent anxiety. The influences were significantly greater in adolescents carrying one or two Val allele than those with Met/Met genotype. Moreover, the G × E interactions were more consistent with the differential susceptibility than the diathesis-stress model. Adolescents carrying Val allele who were more susceptible to adversity were also more likely to benefit from supportive experiences. These findings provide novel evidence for the role of BDNF Val66Met as a genetic susceptibility modulating the influences of stressful life events and mother's warmth-reasoning on adolescent anxiety. We speculate that BDNF Val66Met may moderate anxious youths' responses to mindfulness-based stress reduction program and family-based treatment targeting the enhancement of positive parenting. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells

    Science.gov (United States)

    Kryeziu, Kushtrim; Pirker, Christine; Englinger, Bernhard; van Schoonhoven, Sushilla; Spitzwieser, Melanie; Mohr, Thomas; Körner, Wilfried; Weinmüllner, Regina; Tav, Koray; Grillari, Johannes; Cichna-Markl, Margit; Berger, Walter; Heffeter, Petra

    2016-01-01

    As an environmental poison, arsenic is responsible for many cancer deaths. Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to treat refractory acute promyelocytic leukemia (APL) and is intensively investigated for treatment of other cancer types. Noteworthy, cancer therapy is frequently hampered by drug resistance, which is also often associated with enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected cancer cells (A2780ATO) for the mechanisms underlying their enhanced tumorigenicity and aggressiveness. These cells were characterized by enhanced proliferation and spheroid growth as well as increased tumorigenicity of xenografts in SCID mice. Noteworthy, subsequent studies revealed that overexpression of Met receptor was the underlying oncogenic driver of these effects, as A2780ATO cells were characterized by collateral sensitivity against Met inhibitors. This finding was also confirmed by array comparative genomic hybridization (array CGH) and whole genome gene expression arrays, which revealed that Met overexpression by chronic ATO exposure was based on the transcriptional regulation via activation of AP-1. Finally, it was shown that treatment with the Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in vivo, indicating that targeting of Met presents a promising strategy for the treatment of Met-overexpressing tumors after either arsenic exposure or failure to ATO treatment. PMID:27036042

  8. 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.

  9. Association between the Catechol O-methyltransferase (COMT Val158met polymorphism and different dimensions of impulsivity.

    Directory of Open Access Journals (Sweden)

    Leandro Fernandes Malloy-Diniz

    Full Text Available BACKGROUND: Impulsivity is a multidimensional construct which has been associated with dopaminergic neurotransmission. Nonetheless, until this moment, few studies addressed the relationship between different types of impulsivity and the single nucleotide polymorphism caused by a substitution of valine (val with methionine (met in the 158 codon of the Catechol-o-Methyltransferase gene (COMT-val158met. The present study aimed to investigate the association between val158met COMT polymorphism and impulsive behavior measured by two neuropsychological tests. METHODOLOGY/PRINCIPAL FINDINGS: We administered two neuropsychological tests, a Continuous Performance Task and the Iowa Gambling Task were applied to 195 healthy participants to characterize their levels of motor, attentional and non-planning impulsivity. Then, subjects were grouped by genotype, and their scores on impulsivity measures were compared. There were no significant differences between group scores on attentional and motor impulsivity. Those participants who were homozygous for the met allele performed worse in the Iowa Gambling Task than val/val and val/met subjects. CONCLUSIONS/SIGNIFICANCE: Our results suggest that met allele of val158met COMT polymorphism is associated with poor performance in decision-making/cognitive impulsivity task. The results reinforce the hypothesis that val and met alleles of the val158met polymorphism show functional dissociation and are related to different prefrontal processes.

  10. Sequence-defined cMET/HGFR-targeted Polymers as Gene Delivery Vehicles for the Theranostic Sodium Iodide Symporter (NIS) Gene.

    Science.gov (United States)

    Urnauer, Sarah; Morys, Stephan; Krhac Levacic, Ana; Müller, Andrea M; Schug, Christina; Schmohl, Kathrin A; Schwenk, Nathalie; Zach, Christian; Carlsen, Janette; Bartenstein, Peter; Wagner, Ernst; Spitzweg, Christine

    2016-08-01

    The sodium iodide symporter (NIS) as well-characterized theranostic gene represents an outstanding tool to target different cancer types allowing noninvasive imaging of functional NIS expression and therapeutic radioiodide application. Based on its overexpression on the surface of most cancer types, the cMET/hepatocyte growth factor receptor serves as ideal target for tumor-selective gene delivery. Sequence-defined polymers as nonviral gene delivery vehicles comprising polyethylene glycol (PEG) and cationic (oligoethanoamino) amide cores coupled with a cMET-binding peptide (cMBP2) were complexed with NIS-DNA and tested for receptor-specificity, transduction efficiency, and therapeutic efficacy in hepatocellular cancer cells HuH7. In vitro iodide uptake studies demonstrated high transduction efficiency and cMET-specificity of NIS-encoding polyplexes (cMBP2-PEG-Stp/NIS) compared to polyplexes without targeting ligand (Ala-PEG-Stp/NIS) and without coding DNA (cMBP2-PEG-Stp/Antisense-NIS). Tumor recruitment and vector biodistribution were investigated in vivo in a subcutaneous xenograft mouse model showing high tumor-selective iodide accumulation in cMBP2-PEG-Stp/NIS-treated mice (6.6 ± 1.6% ID/g (123)I, biological half-life 3 hours) by (123)I-scintigraphy. Therapy studies with three cycles of polyplexes and (131)I application resulted in significant delay in tumor growth and prolonged survival. These data demonstrate the enormous potential of cMET-targeted sequence-defined polymers combined with the unique theranostic function of NIS allowing for optimized transfection efficiency while eliminating toxicity.

  11. Uniqueness and Non-uniqueness in the Einstein Constraints

    CERN Document Server

    Pfeiffer, H P; Pfeiffer, Harald P.; York, James W.

    2005-01-01

    We examine numerically a sequence of free data for the conformal thin sandwich (CTS) equations representing non-linearly perturbed Minkowski spacetimes. We find only one solution for the standard (four) CTS equations; however, we find {\\em two} distinct solutions for the same free data when the lapse is determined by a fifth elliptic equation arising from specification of the time derivative of the mean curvature. For a given {\\em physical} (conformally scaled) amplitude of the perturbation, the solution for the physical data $g_{ij}, K_{ij}$ nevertheless appears to be unique.

  12. The BDNF Val66Met polymorphism regulates glucocorticoid-induced corticohippocampal remodeling and behavioral despair.

    Science.gov (United States)

    Notaras, M; Du, X; Gogos, J; van den Buuse, M; Hill, R A

    2017-09-19

    The BDNF Val66Met polymorphism has been associated with sensitivity to stress and affective disorders. We therefore sought to model the inter-causality of these relationships under controlled laboratory conditions. We subjected humanized BDNF Val66Met (hBDNF(Val66Met)) transgenic mice to a history of stress, modeled by chronic late-adolescent corticosterone (CORT) exposure, before evaluating affective-related behavior using the forced-swim test (FST) in adulthood. While hBDNF(Met/Met) mice had a depression-like phenotype in the FST irrespective of CORT, hBDNF(Val/Val) wildtype mice had a resilient phenotype but developed an equally robust depressive-like phenotype following CORT. A range of stress-sensitive molecules were studied across the corticohippocampal axis, and where genotype differences occurred following CORT they tended to inversely coincide with the behavior of the hBDNF(Val/Val) group. Notably, tyrosine hydroxylase was markedly down-regulated in the mPFC of hBDNF(Val/Val) mice as a result of CORT treatment, which mimicked expression levels of hBDNF(Met/Met) mice and the FST behavior of both groups. The expression of calretinin, PSD-95, and truncated TrkB were also concomitantly reduced in the mPFC of hBDNF(Val/Val) mice by CORT. This work establishes BDNF(Val66Met) genotype as a regulator of behavioral despair, and identifies new biological targets of BDNF genetic variation relevant to stress-inducible disorders such as depression.

  13. Translational profiling of stress-induced neuroplasticity in the CA3 pyramidal neurons of BDNF Val66Met mice.

    Science.gov (United States)

    Gray, J D; Rubin, T G; Kogan, J F; Marrocco, J; Weidmann, J; Lindkvist, S; Lee, F S; Schmidt, E F; McEwen, B S

    2016-12-13

    Genetic susceptibility and environmental factors (such as stress) can interact to affect the likelihood of developing a mood disorder. Stress-induced changes in the hippocampus have been implicated in mood disorders, and mutations in several genes have now been associated with increased risk, such as brain-derived neurotrophic factor (BDNF). The hippocampus has important anatomical subdivisions, and pyramidal neurons of the vulnerable CA3 region show significant remodeling after chronic stress, but the mechanisms underlying their unique plasticity remain unknown. This study characterizes stress-induced changes in the in vivo translating mRNA of this cell population using a CA3-specific enhanced green fluorescent protein (EGFP) reporter fused to the L10a large ribosomal subunit (EGFPL10a). RNA-sequencing after isolation of polysome-bound mRNAs allows for cell-type-specific, genome-wide characterization of translational changes after stress. The data demonstrate that acute and chronic stress produce unique translational profiles and that the stress history of the animal can alter future reactivity of CA3 neurons. CA3-specific EGFPL10a mice were then crossed to the stress-susceptible BDNF Val66Met mouse line to characterize how a known genetic susceptibility alters both baseline translational profiles and the reactivity of CA3 neurons to stress. Not only do Met allele carriers exhibit distinct levels of baseline translation in genes implicated in ion channel function and cytoskeletal regulation, but they also activate a stress response profile that is highly dissimilar from wild-type mice. Closer examination of genes implicated in the mechanisms of neuroplasticity, such as the NMDA and AMPA subunits and the BDNF pathway, reveal how wild-type mice upregulate many of these genes in response to stress, but Met allele carriers fail to do so. These profiles provide a roadmap of stress-induced changes in a genetically homogenous population of hippocampal neurons and

  14. Oncogenic activation of the Met receptor tyrosine kinase fusion protein, Tpr-Met, involves exclusion from the endocytic degradative pathway.

    Science.gov (United States)

    Mak, H H L; Peschard, P; Lin, T; Naujokas, M A; Zuo, D; Park, M

    2007-11-01

    Multiple mechanisms of dysregulation of receptor tyrosine kinases (RTKs) are observed in human cancers. In addition to gain-of-function, loss of negative regulation also contributes to oncogenic activation of RTKs. Negative regulation of many RTKs involves their internalization and degradation in the lysosome, a process regulated through ubiquitination. RTK oncoproteins activated following chromosomal translocation, are no longer transmembrane proteins, and are predicted to escape lysosomal degradation. To test this, we used the Tpr-Met oncogene, generated following chromosomal translocation of the hepatocyte growth factor receptor (Met). Unlike Met, Tpr-Met is localized in the cytoplasm and also lacks the binding site for Cbl ubiquitin ligases. We determined whether subcellular localization of Tpr-Met, and/or loss of its Cbl-binding site, is important for oncogenic activity. Presence of a Cbl-binding site and ubiquitination of cytosolic Tpr-Met oncoproteins does not alter their transforming activity. In contrast, plasma membrane targeting allows Tpr-Met to enter the endocytic pathway, and Tpr-Met transforming activity as well as protein stability are decreased in a Cbl-dependent manner. We show that transformation by Tpr-Met is in part dependent on its ability to escape normal downregulatory mechanisms. This provides a paradigm for many RTK oncoproteins activated following chromosomal translocation.

  15. 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.

  16. The Unique Needs and Potential of Twice Exceptional Students: An Elementary School Resource Handbook

    Science.gov (United States)

    Lam, Bryan

    2014-01-01

    There has always been an understood expectation that gifted students excel through all aspects of school. Unbeknownst to many are those gifted students that do not have their unique needs met through an accelerated program. These students, defined as twice exceptional, have both intellectual gifts and a disability. This project sought to provide a…

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

    Science.gov (United States)

    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 and functional activity in the hippocampus during episodic and working memory tasks in healthy young adults. Specifically, studies have found that met carriers exhibit both poorer performance and reduced neural activity within the medial temporal lobe (MTL) when performing episodic memory tasks. However, these studies have not been well replicated and have not considered the role of behavioral differences in the interpretation of neural differences. The current study sought to control for cognitive performance in investigating the role of the BDNF val66met genotype on neural activity associated with episodic memory. Across item and relational memory tests, met carriers exhibited increased MTL activation during both encoding and retrieval stages, compared to non-carriers. The results suggest that met carriers are able to recruit MTL activity to support successful memory processes, and reductions in cognitive performance observed in prior studies are not a ubiquitous effect associated with variants of the BDNF val66met genotype. PMID:20865733

  18. Downsyndroom-kansbepaling met de eerstetrimestercombinatietest 2006-2008

    NARCIS (Netherlands)

    Schielen PCJI; Koster MPH; Elvers LH; Loeber JG; LIS

    2010-01-01

    Tussen 2006 en 2008 is 70 % van de zwangerschappen van een kind met downsyndroom correct voorspeld met de eerstetrimester-combinatietest. De test presteert daarmee iets minder dan in de vorige onderzochte periode, tussen 2004 en 2006. Het aantal aanvragen voor de test is in de onderzochte periode li

  19. Ringonderzoek : bepaling van coccidiostaticagehalte in diervoeders, met behulp van turbidimetrie

    NARCIS (Netherlands)

    Broex, N.J.G.; Huf, F.

    1988-01-01

    Voor de gehalte bepaling van monensin, salinomycine en narasin in diervoeders is de zg. turbidimetrische methode geringtest door 12 laboratoria. Ieder laboratorium heeft 9 monsters ontvangen, resp. 3 voormengsels en 6 diervoeders met monensin, salinomycine of narasin. De monsters zijn onderzocht met

  20. Wankel succes met druppelfertigatie in Franse prei : Op Proefboerderij Vredepeel

    NARCIS (Netherlands)

    Verstegen, S.; PPO Akkerbouw, Groene Ruimte en Vollegrondsgroente

    2007-01-01

    Bij PPO Vredepeel wordt in proeven prei geteeld met behulp van druppelfertigatie, met minder kunstmest en minder uitspoeling als doelen. In Frankrijk werken al sinds 2005 vijf preitelers in de streek Loire-Atlantique er mee op hun hele areaal. Eén van hen gebruikt 20 tot 40 procent minder kunst mest

  1. Massage bij verpleeghuisbewoners met ernstige dementie: een waardevolle interventie.

    NARCIS (Netherlands)

    Inhulsen, M.B.; Verkaik, R.; Busch, M.; Francke, A.

    2016-01-01

    Zorgverleners vinden dat massage een waardevolle bijdrage levert aan de zorg voor verpleeghuisbewoners met ernstige dementie. Met name in het maken van contact en het verminderen van onrust. Dit blijkt uit een pilot uitgevoerd door zorgorganisatie Laurens, het Van Praag Instituut en

  2. Alternatieve voedergewassen : ervaringen met erwten/graan, amarinth en snijsorghum

    NARCIS (Netherlands)

    Schooten, van H.A.

    2003-01-01

    In 2002 zijn door Praktijkonderzoek Veehouderij, in samenwerking met Stimuland Overijssel, drie demo's aangelegd met alternatieve voedergewassen voor de biologische melkveehouderij. De opbrengsten en voederwaarde-gegevens voor mengteelten gerst/erwten, gerst/rode klaver en triticale/erwten, en voor

  3. 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.

  4. 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 zi

  5. Massage bij verpleeghuisbewoners met ernstige dementie: een waardevolle interventie.

    NARCIS (Netherlands)

    Inhulsen, M.B.; Verkaik, R.; Busch, M.; Francke, A.

    2016-01-01

    Zorgverleners vinden dat massage een waardevolle bijdrage levert aan de zorg voor verpleeghuisbewoners met ernstige dementie. Met name in het maken van contact en het verminderen van onrust. Dit blijkt uit een pilot uitgevoerd door zorgorganisatie Laurens, het Van Praag Instituut en onderzoeksinstit

  6. Success, but Slowly, as Met School Redefines Learning

    Science.gov (United States)

    Pearson, George

    2012-01-01

    Seven Oaks Met School, the only high school in Canada that is part of the U.S.-based Big Picture Learning network of innovative schools, graduated its first class this spring. Internships with businesses and institutions in the community are a core element of the Met School experience. Students report on their internship experience, as well as on…

  7. Isolaatvorming en confessie in verband met de genetische bevolkingsstructuur

    NARCIS (Netherlands)

    1958-01-01

    In dit proefschrift is een onderzoek ingesteld bij een roomskatholieke enclave, gelegen in een gebied met een overwegend protestantse bevolking, in het noorden van de provincie Groningen in het noordelijkste deel van Nederland (Gemeente Leens). Door de beide bevolkingsgroepen met elkaar te vergelijk

  8. Unraveling the evolution of uniquely human cognition.

    Science.gov (United States)

    MacLean, Evan L

    2016-06-07

    A satisfactory account of human cognitive evolution will explain not only the psychological mechanisms that make our species unique, but also how, when, and why these traits evolved. To date, researchers have made substantial progress toward defining uniquely human aspects of cognition, but considerably less effort has been devoted to questions about the evolutionary processes through which these traits have arisen. In this article, I aim to link these complementary aims by synthesizing recent advances in our understanding of what makes human cognition unique, with theory and data regarding the processes of cognitive evolution. I review evidence that uniquely human cognition depends on synergism between both representational and motivational factors and is unlikely to be accounted for by changes to any singular cognitive system. I argue that, whereas no nonhuman animal possesses the full constellation of traits that define the human mind, homologies and analogies of critical aspects of human psychology can be found in diverse nonhuman taxa. I suggest that phylogenetic approaches to the study of animal cognition-which can address questions about the selective pressures and proximate mechanisms driving cognitive change-have the potential to yield important insights regarding the processes through which the human cognitive phenotype evolved.

  9. Genome-wide association studies reveal similar genetic architecture with shared and unique QTL for Bacterial Cold Water Disease resistance in two rainbow trout (Oncorhynchus mykiss) breeding populations

    Science.gov (United States)

    Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonid aquaculture. In previous studies, we identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a 57K SNP array and a genome phys...

  10. Increase in serum brain-derived neurotrophic factor in met allele carriers of the BDNF Val66Met polymorphism is specific to males.

    NARCIS (Netherlands)

    Bus, B.A.A.; Arias Vasquez, A.; Franke, B.; Prickaerts, J.; Graaf, J. de; Oude Voshaar, R.C.

    2012-01-01

    BACKGROUND: Association studies of the Val66Met polymorphism and serum brain-derived neurotrophic factor (BDNF) levels have yielded conflicting results. Recently, sex-specific differences in BDNF levels were demonstrated. As these might explain the reported inconsistencies, we tested sex interaction

  11. Lithium nephropathy: unique sonographic findings.

    Science.gov (United States)

    Di Salvo, Donald N; Park, Joseph; Laing, Faye C

    2012-04-01

    This case series describes a unique sonographic appearance consisting of numerous microcysts and punctate echogenic foci seen on renal sonograms of 10 adult patients receiving chronic lithium therapy. Clinically, chronic renal insufficiency was present in 6 and nephrogenic diabetes insipidus in 2. Sonography showed numerous microcysts and punctate echogenic foci. Computed tomography in 5 patients confirmed microcysts and microcalcifications, which were fewer in number than on sonography. Magnetic resonance imaging in 2 patients confirmed microcysts in each case. Renal biopsy in 1 patient showed chronic interstitial nephritis, microcysts, and tubular dilatation. The diagnosis of lithium nephropathy should be considered when sonography shows these findings.

  12. Mucormycosis in India: unique features.

    Science.gov (United States)

    Chakrabarti, Arunaloke; Singh, Rachna

    2014-12-01

    Mucormycosis remains a devastating invasive fungal infection, with high mortality rates even after active management. The disease is being reported at an alarming frequency over the past decades from India. Indian mucormycosis has certain unique features. Rhino-orbito-cerebral presentation associated with uncontrolled diabetes is the predominant characteristic. Isolated renal mucormycosis has emerged as a new clinical entity. Apophysomyces elegans and Rhizopus homothallicus are emerging species in this region and uncommon agents such as Mucor irregularis and Thamnostylum lucknowense are also being reported. This review focuses on these distinct features of mucormycosis observed in India.

  13. Analysis of unique beta transitions

    DEFF Research Database (Denmark)

    Eman, B.; Krmpotic, F.; Tadic, D;

    1967-01-01

    The Heidelberg group measurements [For abstr. see Phys. Rev. Nucl. Sci. Vol. 15 (1965)] of unique forbidden transitions have been analysed. It has been found that experimental shape factors can be reproduced only with the induced pseudoscalar form factor d ...-non-conserving tensor form factor b > 0. In the former case they contradict Daniel's results [See abstr. 1966A10720] for 0- rarr 0+ transitions, whereas in the latter they are in disagreement with other known analyses of mu-meson capture, allowed and forbidden transitions. The conclusion appears to be independent...

  14. Identifying the Unique Aspects of Adolescent and Young Adult Palliative Care: A Case Study to Propel Programmatic Changes in Pediatric Hospitals.

    Science.gov (United States)

    Humphrey, Lisa; Dell, Mary Lynn

    2015-09-01

    Using a case study, in this article we seek to highlight how the distinct developmental needs of adolescent and young adult patients facing a life-threatening condition require a different approach to patient care by pediatric health care workers. The case underscores pitfalls in using a pediatric construct of care in areas of pain management, social stressors, and advanced care planning, and suggests programs to implement for improvement, including partnership with psychiatry, substance abuse, and palliative care specialists.

  15. Intermediate CAG repeat expansion in the ATXN2 gene is a unique genetic risk factor for ALS--a systematic review and meta-analysis of observational studies.

    Directory of Open Access Journals (Sweden)

    Ming-Dong Wang

    Full Text Available Amyotrophic lateral sclerosis (ALS is a rare degenerative condition of the motor neurons. Over 10% of ALS cases are linked to monogenic mutations, with the remainder thought to be due to other risk factors, including environmental factors, genetic polymorphisms, and possibly gene-environmental interactions. We examined the association between ALS and an intermediate CAG repeat expansion in the ATXN2 gene using a meta-analytic approach. Observational studies were searched with relevant disease and gene terms from MEDLINE, EMBASE, and PsycINFO from January 2010 through to January 2014. All identified articles were screened using disease terms, gene terms, population information, and CAG repeat information according to PRISMA guidelines. The final list of 17 articles was further evaluated based on the study location, time period, and authors to exclude multiple usage of the same study populations: 13 relevant articles were retained for this study. The range 30-33 CAG repeats in the ATXN2 gene was most strongly associated with ALS. The meta-analysis revealed that the presence of an intermediate CAG repeat (30-33 in the ATXN2 gene was associated with an increased risk of ALS [odds ratio (OR = 4.44, 95%CI: 2.91-6.76] in Caucasian ALS patients. There was no significant difference in the association of this CAG intermediate repeat expansion in the ATXN2 gene between familial ALS cases (OR = 3.59, 1.58-8.17 and sporadic ALS cases (OR = 3.16, 1.88-5.32. These results indicate that the presence of intermediate CAG repeat expansion in the ATXN2 gene is a specific genetic risk factor for ALS, unlike monogenic mutations with an autosomal dominant transmission mode, which cause a more severe phenotype of ALS, with a higher prevalence in familial ALS.

  16. Intermediate CAG repeat expansion in the ATXN2 gene is a unique genetic risk factor for ALS--a systematic review and meta-analysis of observational studies.

    Science.gov (United States)

    Wang, Ming-Dong; Gomes, James; Cashman, Neil R; Little, Julian; Krewski, Daniel

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a rare degenerative condition of the motor neurons. Over 10% of ALS cases are linked to monogenic mutations, with the remainder thought to be due to other risk factors, including environmental factors, genetic polymorphisms, and possibly gene-environmental interactions. We examined the association between ALS and an intermediate CAG repeat expansion in the ATXN2 gene using a meta-analytic approach. Observational studies were searched with relevant disease and gene terms from MEDLINE, EMBASE, and PsycINFO from January 2010 through to January 2014. All identified articles were screened using disease terms, gene terms, population information, and CAG repeat information according to PRISMA guidelines. The final list of 17 articles was further evaluated based on the study location, time period, and authors to exclude multiple usage of the same study populations: 13 relevant articles were retained for this study. The range 30-33 CAG repeats in the ATXN2 gene was most strongly associated with ALS. The meta-analysis revealed that the presence of an intermediate CAG repeat (30-33) in the ATXN2 gene was associated with an increased risk of ALS [odds ratio (OR) = 4.44, 95%CI: 2.91-6.76)] in Caucasian ALS patients. There was no significant difference in the association of this CAG intermediate repeat expansion in the ATXN2 gene between familial ALS cases (OR = 3.59, 1.58-8.17) and sporadic ALS cases (OR = 3.16, 1.88-5.32). These results indicate that the presence of intermediate CAG repeat expansion in the ATXN2 gene is a specific genetic risk factor for ALS, unlike monogenic mutations with an autosomal dominant transmission mode, which cause a more severe phenotype of ALS, with a higher prevalence in familial ALS.

  17. Prospective Observational Study of Single-Site Multiport Per-umbilical Laparoscopic Endosurgery versus Conventional Multiport Laparoscopic Cholecystectomy: Critical Appraisal of a Unique Umbilical Approach

    Directory of Open Access Journals (Sweden)

    Priyadarshan Anand Jategaonkar

    2014-01-01

    Full Text Available Purpose. This prospective observational study compares an innovative approach of Single-Site Multi-Port Per-umbilical Laparoscopic Endo-surgery (SSMPPLE cholecystectomy with the gold standard—Conventional Multi-port Laparoscopic Cholecystectomy (CMLC—to assess the feasibility and efficacy of the former. Methods. In all, 646 patients were studied. SSMPPLE cholecystectomy utilized three ports inserted through three independent mini-incisions at the umbilicus. Only the day-to-day rigid laparoscopic instruments were used in all cases. The SSMPPLE cholecystectomy group had 320 patients and the CMLC group had 326 patients. The outcomes were statistically compared. Results. SSMPPLE cholecystectomy had average operative time of 43.8 min and blood loss of 9.4 mL. Their duration of hospitalization was 1.3 days (range, 1–5. Six patients (1.9% of this group were converted to CMLC. Eleven patients had controlled gallbladder perforations at dissection. The Visual Analogue Scores for pain on postoperative days 0 and 7, the operative time, and the scar grades were significantly better for SSMPPLE than CMLC. However, umbilical sepsis and seroma outcomes were similar. We had no bile-duct injuries or port-site hernias in this study. Conclusion. SSMPPLE cholecystectomy approach complies with the principles of laparoscopic triangulation; it seems feasible and safe method of minimally invasive cholecystectomy. Overall, it has a potential to emerge as an economically viable alternative to single-port surgery.

  18. Evidence of a unique and common genetic etiology between the CAR and the remaining part of the diurnal cycle: A study of 14 year-old twins.

    Science.gov (United States)

    Ouellet-Morin, Isabelle; Brendgen, Mara; Girard, Alain; Lupien, Sonia J; Dionne, Ginette; Vitaro, Frank; Boivin, Michel

    2016-04-01

    By and large, studies have reported moderate contributions of genetic factors to cortisol secreted in the early morning and even smaller estimates later in the day. In contrast, the cortisol awakening response (CAR) has shown much stronger heritability estimates, which prompted the hypothesis that the etiology of cortisol secretion may vary according to the time of day. A direct test of this possibility has, however, not yet been performed. To describe the specific and common etiology of the CAR, awakening level and cortisol change from morning to evening in an age-homogenous sample of twin adolescents. A total of 592 participants of the Québec Newborn Twin Study, a population-based 1995-1998 cohort of families with twins in Canada, have collected saliva at awakening, 30 min later, at the end of afternoon and in the evening over four collection days. Multivariate Cholesky models showed both specific and common sources of variance between the CAR, awakening and cortisol diurnal change. The CAR had the strongest heritability estimates, which, for the most part, did not overlap with the other indicators. Conversely, similar magnitudes of genetic and environmental contributions were detected at awakening and for diurnal change, which partially overlapped. Our study unraveled differences between the latent etiologies of the CAR and the rest of the diurnal cycle, which may contribute to identify regulatory genes and environments and detangle how these indicators each relate to physical and mental health. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Studies on magnetic properties of unique molecular magnet {[FeII(pyrazole)4]2[NbIV(CN)8]•4H2O}n

    Science.gov (United States)

    Konieczny, P.; Pełka, R.; Zieliński, P. M.; Wasiutyński, T.; Pinkowicz, D.; Sieklucka, B.

    2013-01-01

    In this paper magnetic properties of hybrid inorganic-organic compound {[FeII(pyrazole)4]2[NbIV(CN)8]•4H2O}n are presented. This is a three dimensional molecular magnet with well localized magnetic moments, which make it a suitable candidate for testing magnetic models. In order to characterize the magnetic properties of the above compound we performed the AC/DC magnetometry in the range 0-5 T. The special attention was paid to the phase transition at 7.9 K. The study in magnetic field supports magnetic ordering below 7.9 K.

  20. Experimental manipulation of sponge/bacterial symbiont community composition with antibiotics: sponge cell aggregates as a unique tool to study animal/microorganism symbiosis.

    Science.gov (United States)

    Richardson, Crystal; Hill, Malcolm; Marks, Carolyn; Runyen-Janecky, Laura; Hill, April

    2012-08-01

    Marine sponges can harbor dense and diverse bacterial communities, yet we have a limited understanding of important aspects of this symbiosis. We developed an experimental methodology that permits manipulating the composition of the microbial community. Specifically, we evaluated sponge cell aggregates (SCA) from Clathria prolifera that had been treated with different classes of antibiotics to determine whether this system might offer novel experimental approaches to the study of sponge/bacterial symbioses. Microscopic analysis of the SCA demonstrated that two distinct morphological types of microbiota existed on the external surface vs. the internal regions of the SCA. Denaturing gradient gel electrophoresis and sequence analysis of 16S rRNA gene clone libraries indicated that we were unable to create entirely aposymbiotic SCA but that different classes of antibiotics produced distinctive shifts in the SCA-associated bacterial community. After exposure to antibiotics, some bacterial species were 'revealed', thus uncovering novel components of the sponge-associated community. The antibiotic treatments used here had little discernible effect on the formation of SCA or subsequent development of the adult. The experimental approach we describe offers empirical options for studying the role symbionts play in sponge growth and development and for ascertaining relationships among bacterial species in communities residing in sponges.

  1. Association between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Manual Aiming Control in Healthy Subjects

    Science.gov (United States)

    Lage, Guilherme M.; Miranda, Débora M.; Romano-Silva, Marco A.; Campos, Simone B.; Albuquerque, Maicon R.; Corrêa, Humberto; Malloy-Diniz, Leandro F.

    2014-01-01

    Background Prefrontal dopamine is catabolized by the catechol-O-methyltransferase (COMT) enzyme. Current evidence suggests that the val/met single nucleotide polymorphism in the COMT gene can predict the efficiency of executive cognition in humans. Individuals carrying the val allele perform more poorly because less synaptic dopamine is available. Methodology/Principal Findings We investigated the influence of the COMT polymorphism on motor performance in a task that requires different executive functions. We administered a manual aiming motor task that was performed under four different conditions of execution by 111 healthy participants. Participants were grouped according to genotype (met/met, met/val, val/val), and the motor performance among groups was compared. Overall, the results indicate that met/met carriers presented lower levels of peak velocity during the movement trajectory than the val carriers, but met/met carriers displayed higher accuracy than the val carriers. Conclusions/Significance This study found a significant association between the COMT polymorphism and manual aiming control. Few studies have investigated the genetics of motor control, and these findings indicate that individual differences in motor control require further investigation using genetic studies. PMID:24956262

  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. RELATIONSHIP BETWEEN ACUPUNCTURE ANALGESIA AND MET- ENKEPHALIN OR DYNORPHIN

    Institute of Scientific and Technical Information of China (English)

    TsogoevAlanS; 王一菱; 吴景兰; 金辉

    2001-01-01

    subjective: The effect of 4~5 Hz electroacupuncture (EA) on alterations of both met-enkephalin (MEK) and dynorphin (Dyn) in the patient plasma or mouse spinal cord and its relation with analgesic effect were studied. Methods: In acupuncture clinic 10 patients with acute pain were treated with 4 Hz EA at Zusanli(ST 36) and/or Hegu(LI 4) acupoints for 30 min. 20 BALB/C mice were randomly divided into 2 groups: a. EA group(n=10), treated with 4~5 Hz EA at bilateral "Zusanli"(ST 36) for 15 min; b. control group(n=10) treated with no EA, but also restrained for 15 min. Before and after EA or restraining acupoints, the pain threshold of the patients or mice was detected. 10 μI of the patient plasma before and after EA and each mouse spinal cord suspension, of the 2 groups were blotted onto nitrocellulose membrane (NCM) respectively. The protein dot blot signals were detected by immunoreactivity (IR) and using Shimadu TLC Scanner and analyzed statistically. Results: The results showed that an increase in patient plasma MEK-IR or Dyn-IR and a decrease in mouse spinal MEK-IR or Dyn-IR could be detected, and the alteration of plasma or spinal MEK-IR was more significant than that of plasma or spinal Dyn-IR. There was a positive correlation in alteration between plasma or spinal MEK-IR and plasma or spinal Dyn-IR with respective parallel levels in individuals. The increased plasma MEK-IR or the decreased spinal MEK-IR was positively or negatively correlated with the analgesic effect, while the correlation between plasma or spinal Dyn-IR and analgesic effect was insignificant. Conclusion: The results suggest that under lower frequency EA the met-enkephalin may play an important role in analgesia.

  4. The global met need for emergency obstetric care: a systematic review.

    Science.gov (United States)

    Holmer, H; Oyerinde, K; Meara, J G; Gillies, R; Liljestrand, J; Hagander, L

    2015-01-01

    Of the 287,000 maternal deaths every year, 99% happen in low- and middle-income countries. The vast majority could be averted with timely access to appropriate emergency obstetric care (EmOC). The proportion of women with complications of pregnancy or childbirth who actually receive treatment is reported as 'Met need for EmOC'. To estimate the global met need for EmOC and to examine the correlation between met need, maternal mortality ratio and other indicators. A systematic review was performed according to the PRISMA guidelines. Searches were made in PubMed, EMBASE and Google Scholar. Studies containing data on met need in EmOC were selected. Analysis was performed with data extracted from 62 studies representing 51 countries. World Bank data were used for univariate and multiple linear regression. Global met need for EmOC was 45% (IQR: 28-57%), with significant disparity between low- (21% [12-31%]), middle- (32% [15-56%]), and high-income countries (99% [99-99%]), (P = 0.041). This corresponds to 11.4 million (8.8-14.8) untreated complications yearly and 951 million (645-1174 million) women without access to EmOC. We found an inverse correlation between met need and maternal mortality ratio (r = -0.42, P EmOC, with vast disparities between countries of different income levels. Met need is a powerful indicator of the response to maternal mortality and strategies to improve EmOC act in synergy with the expansion of skilled birth attendance. © 2014 Royal College of Obstetricians and Gynaecologists.

  5. 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.

  6. A unique quantitative method of acid value of edible oils and studying the impact of heating on edible oils by UV-Vis spectrometry.

    Science.gov (United States)

    Zhang, Wenle; Li, Na; Feng, Yuyan; Su, Shujun; Li, Tao; Liang, Bing

    2015-10-15

    UV-Vis spectroscopy coupled with chemometrics was used effectively to study the impact of heating on edible oils (corn oil, sunflower oil, rapeseed oil, peanut oil, soybean oil and sesame oil) and determine their acid value. Analysis of their first derivative spectra showed that the peak at 370 nm was a common indicator of the heated oils. Partial least squares regression (PLS) and principle component regression (PCR) were applied to building individual quantitative models of acid value for each kind of oil, respectively. The PLS models had a better performance than PCR models, with determination coefficients (R(2)) of 0.9904-0.9977 and root mean square errors (RMSE) of 0.0230-0.0794 for the prediction sets of each kind of oil, respectively. An integrate quantitative model built by support vector regression for all the six kinds of oils was also developed and gave a satisfactory prediction with a R(2) of 0.9932 and a RMSE of 0.0656. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. 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.

  8. Effect of Val66Met polymorphism in BDNF on attentional bias in an extroverted Chinese Han population.

    Science.gov (United States)

    Gong, Pingyuan; Xi, Shoumin; Li, She; Cao, Guochang; Zhang, Peizhe; Shen, Guomin; Zhang, Fuchang; Shen, Yan; Ma, Hua

    2013-01-01

    Studies have indicated that a functional polymorphism (Val66Met) in a brain-derived neurotrophic factor (BDNF) gene can influences human cognitive functions and mood disorders. In this study, we examined associations of BDNF Val66Met with attentional bias and personality in an unaffected population. The results showed that BDNF Val66Met was significantly associated with attentional disengagement for positive cueing words in extraverts. Moreover, there was a positive correlation between the dosages of Met allele and attentional disengagement, however, we did not observe any significant influences of BDNF Val66Met on personality traits. These preliminary results indicate that the individual differences in attentional bias for positive words are partially underpinned by BDNF.

  9. Study on the correlation between COMT gene Val158Met polymorphism and clinical efficacy of aripiprazole in the treatment of schizophrenic patients%儿茶酚胺氧位甲基转移酶基因 Val158Met 多态性与阿立哌唑治疗精神分裂症患者疗效的相关性研究

    Institute of Scientific and Technical Information of China (English)

    周鑫; 李康智; 秦群生

    2015-01-01

    Objective It is to approach the correlation of COMT gene Val 158Met polymorphism and clinical effect of aripi -prazole in treatment of schizophrenic patients .Methods 80 cases of schizophrenia patients received aripiprazole were selected as treatment group, 70 cases of healthy people who willing to volunteer spirit disease were selected as control group .The clini-cal data were retrospectively analyzed , as the treatment group.The genotyping were detected by Polymerase Chain Reaction re -striction fragment length polymorphism analysis (PCR -RFLP), the symptoms were evaluated by Positive and Negative Symp -tom Scale (PANSS).At the same time, the curative effects were observed.Results There was significant differences in the genotypes and allele frequency between both groups (all P 0.05).Conclusion COMT gene Val158Met polymorphism is not associated with the im -provement of clinical symptom , aripiprazole in treatment of schizophrenia patients to mental health , can effectively improve the patient's mental health and part of cognitive status .%目的:探讨儿茶酚胺氧位甲基转移酶(COMT)基因 Val158Met 多态性与阿立哌唑治疗精神分裂症患者疗效的相关性。方法选取接受阿立哌唑治疗的精神分裂症患者80例作为治疗组,选取同期愿意充当精神疾病志愿者的健康人70例作为对照组。应用即聚合酶链式反应-限制性片段长度多态分析(PCR -RFLP)与即阳性、阴性症状评定表(PAN-SS)进行基因分型与精神症状评定,同时观察应用阿立哌唑治疗的临床效果。结果2组的基因型及等位基因频率比较差异有统计学意义(P 均<0.05)。经阿立哌唑治疗后,患者PANSS 评分明显降低(P <0.05)。3种基因型应用阿立哌唑治疗后疗效比较差异无统计学意义(P 均>0.05)。结论COMT 基因 Val158Met 多态性并不关联于临床症状的改善,阿立哌唑治疗精神分裂,能够有效改善

  10. A meta-analysis of the Val158Met COMT polymorphism and violent behavior in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Jay P Singh

    Full Text Available We conducted a meta-analysis of studies examining the association between the Val158Met COMT polymorphism and violence against others in schizophrenia. A systematic search current to November 1, 2011 was conducted using MEDLINE, EMBASE, CINAHL, PsycINFO, ProQuest, and the National Criminal Justice Reference Service and identified 15 studies comprising 2,370 individuals with schizophrenia for inclusion. Bivariate analyses of study sensitivities and specificities were conducted. This methodology allowed for the calculation of pooled diagnostic odds ratios (DOR. Evidence of a significant association between the presence of a Met allele and violence was found such that men's violence risk increased by approximately 50% for those with at least one Met allele compared with homozygous Val individuals (DOR = 1.45; 95% CI = 1.05-2.00; z = 2.37, p = 0.02. No significant association between the presence of a Met allele and violence was found for women or when outcome was restricted to homicide. We conclude that male schizophrenia patients who carry the low activity Met allele in the COMT gene are at a modestly elevated risk of violence. This finding has potential implications for the pharmacogenetics of violent behavior in schizophrenia.

  11. The MET Receptor Tyrosine Kinase Confers Repair of Murine Pancreatic Acinar Cells following Acute and Chronic Injury

    Science.gov (United States)

    Gaziova, Ivana; Jackson, Daniel; Boor, Paul J.; Carter, Dwayne; Cruz-Monserrate, Zobeida; Elferink, Cornelis J.; Joshi, Aditya D.; Kaphalia, Bhupendra; Logsdon, Craig D.; Pereira de Castro, Karen; Soong, Lynn; Tao, Xinrong; Qiu, Suimin; Elferink, Lisa A.

    2016-01-01

    Acinar cells represent the primary target in necroinflammatory diseases of the pancreas, including pancreatitis. The signaling pathways guiding acinar cell repair and regeneration following injury remain poorly understood. The purpose of this study was to determine the importance of Hepatocyte Growth Factor Receptor/MET signaling as an intrinsic repair mechanism for acinar cells following acute damage and chronic alcohol-associated injury. Here, we generated mice with targeted deletion of MET in adult acinar cells (MET-/-). Acute and repetitive pancreatic injury was induced in MET-/- and control mice with cerulein, and chronic injury by feeding mice Lieber-DeCarli diets containing alcohol with or without enhancement of repetitive pancreatic injury. We examined the exocrine pancreas of these mice histologically for acinar death, edema, inflammation and collagen deposition and changes in the transcriptional program. We show that MET expression is relatively low in normal adult pancreas. However, MET levels were elevated in ductal and acinar cells in human pancreatitis specimens, consistent with a role for MET in an adaptive repair mechanism. We report that genetic deletion of MET in adult murine acinar cells was linked to increased acinar cell death, chronic inflammation and delayed recovery (regeneration) of pancreatic exocrine tissue. Notably, increased pancreatic collagen deposition was detected in MET knockout mice following repetitive injury as well alcohol-associated injury. Finally, we identified specific alterations of the pancreatic transcriptome associated with MET signaling during injury, involved in tissue repair, inflammation and endoplasmic reticulum stress. Together, these data demonstrate the importance of MET signaling for acinar repair and regeneration, a novel finding that could attenuate the symptomology of pancreatic injury. PMID:27798657

  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

    2017-01-05

    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 313K, 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)Å(3), Z=4, R=0.0314 for 4738 observed reflections). The centrosymmetric bis(N-phenylbiguanidium(1+)) oxalate (II) was obtained from an aqueous solution at 298K 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)Å(3), 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)Å(3), Z=4, R=0.0345 for 2367 observed reflections and a temperature of 110K), 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 90K 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 147K (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. Changes in total body bone mineral density following a common bone health plan with two versions of a unique bone health supplement: a comparative effectiveness research study

    Directory of Open Access Journals (Sweden)

    Dapilmoto Monika

    2011-04-01

    Full Text Available Abstract Background The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans that: (1 improve nutrition, (2 increase health literacy and, (3 increase physical activity. This study is a response to this call to action. Methods After signing an informed consent, 158 adults agreed to follow an open-label bone-health plan for six months after taking a DXA test of bone density, a 43-chemistry blood test panel and a quality of life inventory (AlgaeCal 1. Two weeks after the last subject completed, a second group of 58 was enrolled and followed the identical plan, but with a different bone-health supplement (AlgaeCal 2. Results There were no significant differences between the two groups in baseline bone mineral density (BMD or in variables related to BMD (age, sex, weight, percent body fat, fat mass, or fat-free mass. In both groups, no significant differences in BMD or related variables were found between volunteers and non-volunteers or between those who completed per protocol and those who were lost to attrition. Both groups experienced a significant positive mean annualized percent change (MAPC in BMD compared to expectation [AlgaeCal 1: 1.15%, p = 0.001; AlgaeCal 2: 2.79%, p = 0.001]. Both groups experienced a positive MAPC compared to baseline, but only AlgaeCal 2 experienced a significant change [AlgaeCal 1: 0.48%, p = 0.14; AlgaeCal 2: 2.18%, p p = 0.005. The MAPC contrast between compliant and partially compliant subjects was significant for both plans (p = 0.001 and p = 0.003 respectively. No clinically significant changes in a 43-panel blood chemistry test were found nor were there any changes in self-reported quality of life in either group. Conclusions Following The Plan for six months with either version of the bone health supplement was associated with significant increases in BMD as compared to expected and, in AlgaeCal 2, the increase from

  14. Combinatie van walnoten met grasproductie en reactie : verslag van resultaten en ervaringen van de eerste jaren met 'Multifunctionele beplantingen', als bouwsteen voor meervoudig duurzaam landgebruik

    NARCIS (Netherlands)

    Oosterbaan, A.; Berg, van den C.A.; Valk, H.

    2003-01-01

    In de omgeving van Winterswijk is vanaf 1999 10 ha multifunctionele beplantingen aangelegd, hoofdzakelijk van walnoot met gras. Overhoeken zijn ingeplant met vruchtstruiken. De eerste ervaringen met aanplant, grasbeheer, bijdrage aan recreatie en dergelijke zijn in dit rapport weergegeven.

  15. 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.

  16. Unique features of space reactors

    Science.gov (United States)

    Buden, David

    Space reactors 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.

  17. The probabilities of unique events.

    Directory of Open Access Journals (Sweden)

    Sangeet S Khemlani

    Full Text Available Many theorists argue that the probabilities of unique events, even real possibilities such as President Obama's re-election, are meaningless. As a consequence, psychologists have seldom investigated them. We propose a new theory (implemented in a computer program in which such estimates depend on an intuitive non-numerical system capable only of simple procedures, and a deliberative system that maps intuitions into numbers. The theory predicts that estimates of the probabilities of conjunctions should often tend to split the difference between the probabilities of the two conjuncts. We report two experiments showing that individuals commit such violations of the probability calculus, and corroborating other predictions of the theory, e.g., individuals err in the same way even when they make non-numerical verbal estimates, such as that an event is highly improbable.

  18. The Evolution of Human Uniqueness.

    Science.gov (United States)

    Boyd, Robert

    2017-01-09

    The human species is an outlier in the natural world. Two million years ago our ancestors were a slightly odd apes. Now we occupy the largest ecological and geographical range of any species, have larger biomass, and process more energy. Usually, this transformation is explained in terms of cognitive ability-people are just smarter than all the rest. In this paper I argue that culture, our ability to learn from each other, and cooperation, our ability to make common cause with large groups of unrelated individuals are the real roots of human uniqueness, and sketch an evolutionary account of how these crucial abilities co-evolved with each other and with other features of our life histories.

  19. 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.

  20. MetNet Precursor - Network Mission to Mars

    Science.gov (United States)

    Harri, Arri-Matti

    2010-05-01

    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 first MetNet vehicle, MetNet Precursor, slated for launch in 2011. The MetNet development work started already in 2001. The actual practical Precursor Mission development work started in January 2009 with participation from various space research institutes and agencies. The scientific rationale and goals as well as key mission solutions will be discussed. 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 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. Time-resolved in situ Martian meteorological measurements acquired by the Viking, Mars Pathfinder and Phoenix landers and remote sensing observations by the Mariner 9, Viking, Mars Global Surveyor, Mars Odyssey and the Mars Express orbiters have provided the basis for our current understanding of the behavior of weather and climate on Mars. However, the available amount of data is still scarce and a wealth of additional in situ observations are needed on varying types of Martian orography, terrain and altitude spanning all latitudes and longitudes to address microscale and mesoscale atmospheric phenomena. Detailed characterization of the Martian atmospheric circulation patterns and climatological cycles requires simultaneous in situ atmospheric observations. 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

  1. Metáfora e transferência

    OpenAIRE

    2007-01-01

    O presente artigo tem como fito apontar em que sentido a transferência, no processo analítico, pode ser compreendida como metáfora. Utilizando o esquema gráfico construído por Searle (1995) para explicitar o processo que ocorre nas metáforas mortas, construímos uma analogia para compreender a transferência como uma metáfora morta (ainda que viva, no sentido de Lakoff e Johnson), que pode ser trazida para o plano da fala no campo analítico, ali onde o analista deve manter-se na ressonância de ...

  2. 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

  3. 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 integreated mo

  4. COMT Val158Met genotypes differentially influence subgenual cingulate functional connectivity in healthy females

    Directory of Open Access Journals (Sweden)

    Chris eBaeken

    2014-06-01

    Full Text Available Brain imaging studies have consistently shown subgenual Anterior Cingulate Cortical (sgACC involvement in emotion processing. COMT Val158 and Met158 polymorphisms may influence such emotional brain processes in specific ways. Given that resting-state fMRI (rsfMRI may increase our understanding on brain functioning, we integrated genetic and rsfMRI data and focused on sgACC functional connections. No studies have yet investigated the influence of the COMT Val158Met polymorphism (rs4680 on sgACC resting-state functional connectivity (rsFC in healthy individuals. A homogeneous group of sixty-one Caucasian right-handed healthy female university students, all within the same age range, underwent rsfMRI. Compared to Met158 homozygotes, Val158 allele carriers displayed significantly stronger rsFC between the sgACC and the left parahippocampal gyrus, ventromedial parts of the inferior frontal gyrus, and the nucleus accumbens (NAc. On the other hand, compared to Val158 homozygotes, we found in Met158 allele carriers stronger sgACC rsFC with the medial frontal gyrus, more in particular the anterior parts of the medial orbitofrontal cortex. Although we did not use emotional or cognitive tasks, our sgACC rsFC results point to possible distinct differences in emotional and cognitive processes between Val158 and Met158 allele carriers. However, the exact nature of these directions remains to be determined.

  5. Brain-derived neurotrophic factor Val66Met polymorphism and early life adversity affect hippocampal volume.

    Science.gov (United States)

    Carballedo, Angela; Morris, Derek; Zill, Peter; Fahey, Ciara; Reinhold, Elena; Meisenzahl, Eva; Bondy, Brigitta; Gill, Michael; Möller, Hans-Jürgen; Frodl, Thomas

    2013-03-01

    The interaction between adverse life events during childhood and genetic factors is associated with a higher risk to develop major depressive disorder (MDD). One of the polymorphisms found to be associated with MDD is the Val66MET polymorphism of brain-derived neurotrophic factor (BDNF). The aim of our two-center study was to determine how the BDNF Val66Met polymorphism and childhood adversity affect the volumetric measures of the hippocampus in healthy individuals and people with MDD. In this two-center study, 62 adult patients with MDD and 71 healthy matched controls underwent high-resolution magnetic resonance imaging. We used manual tracing of the bilateral hippocampal structure with help of the software BRAINS2, assessed childhood adversity using the Childhood Trauma Questionnaire and genotyped Val66Met BDNF SNP (rs6265). MDD patients had smaller hippocampal volumes, both in the left and right hemispheres (F = 5.4, P = 0.022). We also found a significant interaction between BDNF allele and history of childhood adversity (F = 6.1, P = 0.015): Met allele carriers in our samples showed significantly smaller hippocampal volumes when they did have a history of childhood adversity, both in patients and controls. Our results highlight how relevant stress-gene interactions are for hippocampal volume reductions. Subjects exposed to early life adversity developed smaller hippocampal volumes when they carry the Met-allele of the BDNF polymorphism.

  6. Theory of uniqueness of Indian Caste System

    Directory of Open Access Journals (Sweden)

    Ashwin Kumar

    2006-08-01

    Full Text Available Classical studies on pre-modern Indian social structure have suggested apparent differences between the Indian caste system and social stratification as one can discern in other parts of the world. However, one needs to question such dogmatic assertions that such vast differences really existed. An endeavor is made in this research paper to reflect on the nature of caste hierarchy in pre-modern India. The caste system forms the significant basis of pre-modern Indian social structure. Early writers conceived the caste system of pre-modern India as something unique to India. An attempt is made to question this application of theory of uniqueness in the case of India.

  7. Theory of uniqueness of Indian Caste System

    Directory of Open Access Journals (Sweden)

    Ashwin Kumar

    2005-11-01

    Full Text Available Classical studies on pre-modern Indian social structure have suggested apparent differences between the Indian caste system and social stratification as one can discern in other parts of the world. However, one needs to question such dogmatic assertions that such vast differences really existed. An endeavor is made in this research paper to reflect on the nature of caste hierarchy in pre-modern India. The caste system forms the significant basis of pre-modern Indian social structure. Early writers conceived the caste system of pre-modern India as something unique to India. An attempt is made to question this application of theory of uniqueness in the case of India.

  8. The roles of COMT val158met status and aviation expertise in flight simulator performance and cognitive ability.

    Science.gov (United States)

    Kennedy, Q; Taylor, J L; Noda, A; Adamson, M; Murphy, G M; Zeitzer, J M; Yesavage, J A

    2011-09-01

    The polymorphic variation in the val158met position of the catechol-O-methyltransferase (COMT) gene is associated with differences in executive performance, processing speed, and attention. The purpose of this study is: (1) replicate previous COMT val158met findings on cognitive performance; (2) determine whether COMT val158met effects extend to a real-world task, aircraft navigation performance in a flight simulator; and (3) determine if aviation expertise moderates any effect of COMT val158met status on flight simulator performance. One hundred seventy two pilots aged 41-69 years, who varied in level of aviation training and experience, completed flight simulator, cognitive, and genetic assessments. Results indicate that although no COMT effect was found for an overall measure of flight performance, a positive effect of the met allele was detected for two aspects of cognitive ability: executive functioning and working memory performance. Pilots with the met/met genotype benefited more from increased levels of expertise than other participants on a traffic avoidance measure, which is a component of flight simulator performance. These preliminary results indicate that COMT val158met polymorphic variation can affect a real-world task.

  9. The BDNF Val66Met polymorphism enhances glutamatergic transmission but diminishes activity-dependent synaptic plasticity in the dorsolateral striatum.

    Science.gov (United States)

    Jing, Deqiang; Lee, Francis S; Ninan, Ipe

    2017-01-01

    The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene disrupts the activity-dependent release of BDNF, which might underlie its involvement in several neuropsychiatric disorders. Consistent with the potential role of regulated release of BDNF in synaptic functions, earlier studies have demonstrated that the BDNF Val66Met polymorphism impairs NMDA receptor-mediated synaptic transmission and plasticity in the hippocampus, the medial prefrontal cortex and the central amygdala. However, it is unknown whether the BDNF Val66Met polymorphism affects synapses in the dorsal striatum, which depends on cortical afferents for BDNF. Electrophysiological experiments revealed an enhanced glutamatergic transmission in the dorsolateral striatum (DLS) of knock-in mice containing the variant polymorphism (BDNF(Met/Met)) compared to the wild-type (BDNF(Val/Val)) mice. This increase in glutamatergic transmission is mediated by a potentiation in glutamate release and NMDA receptor transmission in the medium spiny neurons without any alterations in non-NMDA receptor-mediated transmission. We also observed an impairment of synaptic plasticity, both long-term potentiation and depression in the DLS neurons, in BDNF(Met/Met) mice. Thus, the BDNF Val66Met polymorphism exerts an increase in glutamatergic transmission but impairs synaptic plasticity in the dorsal striatum, which might play a role in its effect on neuropsychiatric symptoms. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.

  10. 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)

  11. Methoprene-tolerant (Met knockdown in the adult female cockroach, Diploptera punctata completely inhibits ovarian development.

    Directory of Open Access Journals (Sweden)

    Elisabeth Marchal

    Full Text Available Independent of the design of the life cycle of any insect, their growth and reproduction are highly choreographed through the action of two versatile hormones: ecdysteroids and juvenile hormones (JH. However, the means by which JH can target tissues and exert its pleiotropic physiological effects is currently still not completely elucidated. Although the identity of the one JH receptor is currently still elusive, recent evidence seems to point to the product of the Methoprene-tolerant gene (Met as the most likely contender in transducing the action of JH. Studies on the role of this transcription factor have mostly been focused on immature insect stages. In this study we used the viviparous cockroach Diploptera punctata, a favorite model in studying JH endocrinology, to examine the role of Met during reproduction. A tissue distribution and developmental profile of transcript levels was determined for Met and its downstream partners during the first gonadotropic cycle of this cockroach. Using RNA interference, our study shows that silencing Met results in an arrest of basal oocyte development; vitellogenin is no longer transcribed in the fat body and no longer taken up by the ovary. Patency is not induced in these animals which fail to produce the characteristic profile of JH biosynthesis typical of the first gonadotropic cycle. Moreover, the ultrastructure of the follicle cells showed conspicuous whorls of rough endoplasmic reticulum and a failure to form chorion. Our study describes the role of Met on a cellular and physiological level during insect reproduction, and confirms the role of Met as a key factor in the JH signaling pathway.

  12. Leren met behulp van strategieën

    NARCIS (Netherlands)

    Reijners, Pauline; Kester, Liesbeth; Wetzels, Sandra; Kirschner, Paul A.

    2012-01-01

    Reijners, P. B. G., Kester, L., Wetzels, S. A. J., & Kirschner, P. A. (2012, 9 March). Leren met behulp van strategieën. Presentation at mini conference 'The Testing Effect' from the master programme Learning Sciences, Eindhoven, The Netherlands.

  13. Skills Labs: Hoogwaardige e-practica Water Management met EMERGO

    NARCIS (Netherlands)

    Nadolski, Rob; Hummel, Hans; Slootmaker, Aad; Kurvers, Hub

    2010-01-01

    Nadolski, R. J., Hummel, H. G. K., Slootmaker, A., & Kurvers, H. (2010, 27 May). Skills Labs: Hoogwaardige e-practica Water Management met EMERGO. Presentatie tijdens de bijeenkomst: Surfen door Zeeland: e-learning delta innovaties, Vlissingen, Nederland. SURFFoundation.

  14. Onderzoek leert ook van praktijk : telen met toekomst

    NARCIS (Netherlands)

    Kool, de S.A.M.; Dwarswaard, A.

    2002-01-01

    Het project 'Telen met toekomst' is een leerproces van zowel de onderzoeker als de teler. In zes jaar gaan deelnemers na wat technisch en economisch mogelijk is om het gebruik van mineralen, gewasbeschermingmiddelen en energie terug te dringen

  15. 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.

  16. Samenwerking Wageningen UR met BayerCropScience

    NARCIS (Netherlands)

    Wijsmuller, J.

    2010-01-01

    Wageningen UR werkt in haar onderzoeksprogramma’s samen met andere kennisinstellingen. In dit artikel een nadere kennismaking meteen van deze partners: Bayer CropsScience. Bayer CropScience ontwikkelt bestrijdingsmiddelen voor de Nederlandse markt.

  17. 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

  18. Loss of embryonic MET signaling alters profiles of hippocampal interneurons.

    Science.gov (United States)

    Martins, Gabriela J; Plachez, Céline; Powell, Elizabeth M

    2007-01-01

    Hippocampal interneurons arise in the ventral forebrain and migrate dorsally in response to cues, including hepatocyte growth factor/scatter factor which signals via its receptor MET. Examination of the hippocampus in adult mice in which MET had been inactivated in the embryonic proliferative zones showed an increase in parvalbumin-expressing cells in the dentate gyrus, but a loss of these cells in the CA3 region. An overall loss of calretinin-expressing cells was seen throughout the hippocampus. A similar CA3 deficit of parvalbumin and calretinin cells was observed when MET was eliminated only in postmitotic cells. These data suggest that MET is required for the proper hippocampal development, and embryonic perturbations lead to long-term anatomical defects with possible learning and memory dysfunction.

  19. Nieuw Zorgaanbod: Gesloten jeugdzorg voor adolescenten met ernstige gedragsproblemen

    NARCIS (Netherlands)

    Nijhof, K.S.; Dam, C. van; Veerman, J.W.; Engels, R.C.M.E.; Scholte, R.H.J.

    2010-01-01

    Tot voor kort werd een toenemend aantal jongeren met ernstige gedragsproblemen in jeugdgevangenissen geplaatst. Deze jongeren, ook wel ‘civielrechtelijke’ jongeren genoemd, werden niet geplaatst vanwege veroordelingen voor criminele activiteiten, maar omdat zij beschermd dienden te worden tegen zich

  20. 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

  1. 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 Th

  2. Die verband van leerprosesveranderlikes met leersukses

    Directory of Open Access Journals (Sweden)

    D. F. Lotriet

    2002-09-01

    Full Text Available The relationship between learning process variables and study success. The main objective of this study was to determine the relationship between the constructs “meaning orientation” (in-depth approach to study, “transformational conception” and “self-regulation” in the distance education context (TV– learning. A random sample of 1951 participants taken from a large financial institution yielded 263 usable questionnaires. The responses obtained to the 167 items were subjected to factor analysis and item analysis. Opsomming Die hoofdoel van die onderhawige studie was om te bepaal of daar ‘n verband tussen die konstrukte“betekenisoriëntasie"? (dieptebenadering tot leer, “transformasionele begrip"? en “selfregulering"? in die afstandsonderrigkonteks (TV-leer bestaan. ‘n Ewekansige steekproef van 1951 deelnemers geneem uit ‘n groot finansiële instelling het 263 bruikbare vraelyste opgelewer. Die response op 167 items is aan faktor- en itemontledings onderwerp. Daarna is die interver-wantskappe tussen die leerprosesveranderlikes, naamlik “benadering tot leer"?, “begrip van leer"? en regulering-strategieë"? bepaal.

  3. Existence and uniqueness theorem for ODE: an overview

    OpenAIRE

    Poria, Swarup; Dhiman, Aman

    2016-01-01

    The study of existence and uniqueness of solutions became important due to the lack of general formula for solving nonlinear ordinary differential equations (ODEs). Compact form of existence and uniqueness theory appeared nearly 200 years after the development of the theory of differential equation. In the article, we shall discuss briefly the differences between linear and nonlinear first order ODE in context of existence and uniqueness of solutions. Special emphasis is given on the Lipschit...

  4. MMPM - Mission implementation of Mars MetNet Precursor

    Science.gov (United States)

    Harri, A.-M.

    2009-04-01

    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 key technical aspects and solutions of the mission will be discussed. 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. This 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.

  5. Metsänomistajien suhtautuminen suometsien hoidon kokonaispalveluun Pirkanmaan alueella

    OpenAIRE

    Viitanen, Matti

    2012-01-01

    Metsäojituksia on Suomen maaperällä tehty jo toistasataa vuotta. Tänä aikana uudisojittamisesta on siirrytty jo ojitettujen suometsien kunnostuksiin. Vaikka monille metsistään huolehtiminen on sydämen asia, toisaalla hakkuukypsiä metsiköitä lahoaa hiljalleen luonnontilaiseksi ennallistuviin suometsiin. Kunnostamattomien tai mahdollisesti vuosikymmeniä sitten edellisen kerran käsiteltyjen ojitusalueiden kartoittaminen ja kunnostaminen tarjoavat metsänomistajalle hyvän tilaisuuden reali...

  6. MetUM-GOML: a near-globally coupled atmosphere–ocean-mixed-layer model

    Directory of Open Access Journals (Sweden)

    L. C. Hirons

    2014-09-01

    Full Text Available Well-resolved air–sea interactions are simulated in a new Ocean Mixed Layer coupled configuration of the Met Office Unified Model (MetUM-GOML, comprising the MetUM coupled to the Multi-Column K Profile Parametrization ocean (MC-KPP. This is the first globally coupled system which provides a vertically resolved, high near-surface resolution ocean at comparable computational cost to running in atmosphere-only mode. As well as being computationally inexpensive, this modelling framework is adaptable – the independent MC-KPP columns can be applied selectively in space and time – and controllable – by using temperature and salinity corrections the model can be constrained to any ocean state. The framework provides a powerful research tool for process-based studies of the impact of air–sea interactions in the global climate system. MetUM simulations have been performed which separate the impact of introducing interannual variability in sea surface temperatures (SSTs from the impact of having atmosphere–ocean feedbacks. The representation of key aspects of tropical and extra-tropical variability are used to assess the performance of these simulations. Coupling the MetUM to MC-KPP is shown, for example, to reduce tropical precipitation biases, improve the propagation of, and spectral power associated with, the Madden–Julian Oscillation and produce closer-to-observed patterns of springtime blocking activity over the Euro-Atlantic region.

  7. Activation of the Met kinase confers acquired drug resistance in FGFR-targeted lung cancer therapy.

    Science.gov (United States)

    Kim, S-M; Kim, H; Yun, M R; Kang, H N; Pyo, K-H; Park, H J; Lee, J M; Choi, H M; Ellinghaus, P; Ocker, M; Paik, S; Kim, H R; Cho, B C

    2016-07-18

    Aberrant fibroblast growth factor receptor (FGFR) activation/expression is a common feature in lung cancer (LC). In this study, we evaluated the antitumor activity of and the mechanisms underlying acquired resistance to two potent selective FGFR inhibitors, AZD4547 and BAY116387, in LC cell lines. The antitumor activity of AZD4547 and BAY1163877 was screened in 24 LC cell lines, including 5 with FGFR1 amplification. Two cell lines containing FGFR1 amplifications, H1581 and DMS114, were sensitive to FGFR inhibitors (IC50FGFR1-amplified H1581 cells resistant to AZD4547 or BAY116387 (H1581AR and H1581BR cells, respectively) were established. Receptor tyrosine kinase (RTK) array and immunoblotting analyses showed strong overexpression and activation of Met in H1581AR/BR cells, compared with that in the parental cells. Gene set enrichment analysis against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed that cytokine-cytokine receptor interaction pathways were significantly enriched in H1581AR/BR cells, with Met contributing significantly to the core enrichment. Genomic DNA quantitative PCR and fluorescent in situ hybridization analyses showed MET amplification in H1581AR, but not in H1581BR, cells. Met amplification drives acquired resistance to AZD4547 in H1581AR cells by activating ErbB3. Combination treatment with FGFR inhibitors and an anaplastic lymphoma kinase (ALK)/Met inhibitor, crizotinib, or Met-specific short interfering RNA (siRNA) synergistically inhibited cell proliferation in both H1581AR and H1581BR cells. Conversely, ectopic expression of Met in H1581 cells conferred resistance to AZD4547 and BAY1163877. Acquired resistance to FGFR inhibitors not only altered cellular morphology, but also promoted migration and invasion of resistant clones, in part by inducing epithelial-to-mesenchymal transition. Taken together, our data suggest that Met activation is sufficient to bypass dependency on FGFR signaling. Concurrent inhibition of the Met

  8. Uniqueness, Self belonging and Intercourse in Nature

    OpenAIRE

    Kirsh, Dr. Marvin / E.

    2010-01-01

    This manuscript has ensued from my past studies in biochemistry (PhD, CUNY 1986) and my current endeavors in graduate study in philosophy and anthropology. The current research project began during my period as a graduate student in biochemistry with a professor of classical genetics comment that DNA was unique in the physical world. The paradox presented to relate this notion to existing natural law lead me to evolve and communicate a view that the world itself is a special case of a general...

  9. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Science.gov (United States)

    Harri, Ari-Matti; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Ponomarenko, Andrey; Apestigue, Victor; Genzer, Maria; Vazquez, Luis; Uspensky, Mikhail; Haukka, Harri

    2016-04-01

    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. 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. 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

  10. ‘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.

  11. Over zwijgen gesproken : een medisch-antropologische studie onder vluchtelingenvrouwen in Nederland, afkomstig uit Afghanistan, Bosnië-Herzegovina en Zuid-Soedan, naar het omgaan met ervaringen van aan oorlog gerelateerd seksueel geweld

    NARCIS (Netherlands)

    Tankink, Maria Theodora Antonia

    2009-01-01

    This study discusses the question of how refugee women in the Netherlands, as indi-viduals and as members of a family and a group, act in response to their experiences of sexual violence, and why they regard silence as the best coping strategy. The women who participated in the research have differe

  12. Evolutionary theory, human uniqueness and the image of God

    Directory of Open Access Journals (Sweden)

    Gijsbert van den Brink

    2012-09-01

    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

  13. The indole alkaloid meleagrin, from the olive tree endophytic fungus Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent breast cancer proliferation, migration and invasion.

    Science.gov (United States)

    Mady, Mohamed S; Mohyeldin, Mohamed M; Ebrahim, Hassan Y; Elsayed, Heba E; Houssen, Wael E; Haggag, Eman G; Soliman, Randa F; El Sayed, Khalid A

    2016-01-15

    Fungi of the genus Penicillium produce unique and chemically diverse biologically active secondary metabolites, including indole alkaloids. The role of dysregulated hepatocyte growth factor (HGF) and its receptor, c-Met, in the development and progression of breast carcinoma is documented. The goal of this work is to explore the chemistry and bioactivity of the secondary metabolites of the endophytic Penicillium chrysogenum cultured from the leaf of the olive tree Olea europea, collected in its natural habitat in Egypt. This fungal extract showed good inhibitory activities against the proliferation and migration of several human breast cancer lines. The CH2Cl2 extract of P. chrysogenum mycelia was subjected to bioguided chromatographic separation to afford three known indole alkaloids; meleagrin (1), roquefortine C (2) and DHTD (3). Meleagrin inhibited the growth of the human breast cancer cell lines MDA-MB-231, MDA-468, BT-474, SK BR-3, MCF7 and MCF7-dox, while similar treatment doses were found to have no effect on the growth and viability of the non-tumorigenic human mammary epithelial cells MCF10A. Meleagrin also showed excellent ATP competitive c-Met inhibitory activity in Z-Lyte assay, which was further confirmed via molecular docking studies and Western blot analysis. In addition, meleagrin treatment caused a dose-dependent inhibition of HGF-induced cell migration, and invasion of breast cancer cell lines. Meleagrin treatment potently suppressed the invasive triple negative breast tumor cell growth in an orthotopic athymic nude mice model, promoting this unique natural product from hit to a lead rank. The indole alkaloid meleagrin is a novel lead c-Met inhibitory entity useful for the control of c-Met-dependent metastatic and invasive breast malignancies.

  14. Targeting Met and VEGFR Axis in Metastatic Castration-Resistant Prostate Cancer: 'Game Over'?

    Science.gov (United States)

    Modena, Alessandra; Massari, Francesco; Ciccarese, Chiara; Brunelli, Matteo; Santoni, Matteo; Montironi, Rodolfo; Martignoni, Guido; Tortora, Giampaolo

    2016-08-01

    Despite recent advances that have been made in the therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC), effective management of bone metastases remains a key goal not yet reached. The receptor tyrosine kinase MET and the vascular endothelial growth factor receptor (VEGFR) seem to play an important role in prostate cancer progression and pathological bone turnover, representing potential targets for improving clinical outcomes in mCRPC. Studies evaluating agents that target one or both these pathways have demonstrated modest activity but no improvement in overall survival. Nevertheless, this therapeutic strategy seems to still be a promising and engaging area of prostate cancer research and the interest in better understanding the MET/VEGFR axis and the mechanism of action of these inhibitors is growing. This review describes the rationale for targeting MET and VEGFR pathway in mCRPC and provides the clinical data available to date and an update on ongoing trials.

  15. Meanings of being received and met by others as experienced by women with fibromyalgia.

    Science.gov (United States)

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

    2014-10-01

    Fibromyalgia (FM) is a common chronic pain syndrome that mostly affects middle-aged women. Our aim with this study was to elucidate meanings of being received and met by others as experienced by women with FM. Interviews with a narrative approach were conducted with 9 women. We analyzed the transcribed interviews with a phenomenological hermeneutical interpretation. The findings revealed two themes: being seen as a malingerer and being acknowledged. Meanings of being received and met by others, as experienced by women with FM, can be understood as a movement between the two perspectives. When they were acknowledged, their feelings of security and trust increased, but the women could not rely on this because others received and met them in such an unpredictable manner. © The Author(s) 2014.

  16. Intersectorale samenwerking in de biologische landbouw : mengvoergrondstoffen met binnen- of buitenlandse oorsprong: effect op energieverbruik met mengvoerproductie

    NARCIS (Netherlands)

    Bos, J.F.F.P.

    2006-01-01

    Plant Research International (PRI) gaat in het rapport 'Mengvoergrondstoffen met binnen- of buitenlandse oorsprong: effect op energieverbruik van mengvoerproductie' in op het energieverbruik van de productie van enkele mengvoeders voor biologisch gehouden vleesvarkens. De onderzochte mengvoeders ver

  17. Greguerías - da metáfora literária à metáfora visual

    OpenAIRE

    Amador, Constança Araújo

    2014-01-01

    A presente investigação visa a passagem da metáfora literária para a metáfora visual, através do resultado de um trabalho de ilustração, tendo como ponto de partida, as Greguerías de Ramón Gómez de la Serna (1888 - 1963). Reflectindo sobre a interpretação da metáfora, o objectivo passa por criar uma nova selecção de Greguerías ilustradas que também estabeleçam novas metáforas visuais, a partir da sua interacção com a palavra. Mas uma vez independentes, cada ilustração ou cada conjunto d...

  18. Nucleoporin Nup358 facilitates nuclear import of Methoprene-tolerant (Met) in an importin β- and Hsp83-dependent manner.

    Science.gov (United States)

    He, Qianyu; Zhang, Yuanxi; Zhang, Xu; Xu, DanDan; Dong, Wentao; Li, Sheng; Wu, Rui

    2017-02-01

    The bHLH-PAS transcription factor, Methoprene-tolerant (Met)(1), functions as a juvenile hormone (JH) receptor and transduces JH signals by directly binding to E-box like motifs in the regulatory regions of JH response genes. Nuclear localization of Met is crucial for its transcriptional activity. Our previous studies have shown that the chaperone protein Hsp83 facilitates JH-induced Met nuclear import in Drosophila melanogaster. However, the exact molecular mechanisms of Met nuclear transport are not fully elucidated. Using DNA affinity chromatography, we have previously detected binding of the nucleoporin Nup358, in the presence of JH, to the JH response region (JHRR) sequences isolated from the Krüppel-homolog 1 (Kr-h1) promoter. Here, we have demonstrated that Nup358 regulates JH-Hsp83-induced Met nuclear localization. RNAi-mediated knockdown of Nup358 expression in Drosophila fat body perturbs Met nuclear transport during the 3 h after initiation of wandering, when the JH titer is high. The accompanying reduced expression of the transport receptor importin β in Nup358 RNAi flies could be one of the reasons accounting for Met mislocalization. Furthermore, a tetratricopeptide repeat (TPR) domain at the N-terminal end of Nup358 interacts with Hsp83 and is indispensable for Met nuclear localization. Overexpression of the TPR domain in Drosophila fat body prevents Met nuclear localization resulting in a decrease in JHRR-driven reporter activity and Kr-h1 expression. These data show that Nup358 facilitates JH-induced Met nuclear transport in a manner dependent on importin β and Hsp83.

  19. XRCC3 Thr241Met is associated with response to platinum-based chemotherapy but not survival in advanced non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Mantang Qiu

    Full Text Available BACKGROUND: A lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3 Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC, while the conclusion is still conflicting. MATERIALS AND METHODS: We conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs and hazard ratios (HRs and corresponding 95% confidence intervals (95% CIs were used to estimate the association strength. RESULTS: A total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116-1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087-2.004, Pheterogeneity = 0.696. This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929-1.261, Pheterogeneity = 0.564, and there was no difference between Asian and Caucasian population. CONCLUSIONS: These findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism.

  20. 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.

  1. 2011 Compendium of Physical Activities: a second update of codes and MET values.

    Science.gov (United States)

    Ainsworth, Barbara E; Haskell, William L; Herrmann, Stephen D; Meckes, Nathanael; Bassett, David R; Tudor-Locke, Catrine; Greer, Jennifer L; Vezina, Jesse; Whitt-Glover, Melicia C; Leon, Arthur S

    2011-08-01

    The Compendium of Physical Activities was developed to enhance the comparability of results across studies using self-report physical activity (PA) and is used to quantify the energy cost of a wide variety of PA. We provide the second update of the Compendium, called the 2011 Compendium. The 2011 Compendium retains the previous coding scheme to identify the major category headings and specific PA by their rate of energy expenditure in MET. Modifications in the 2011 Compendium include cataloging measured MET values and their source references, when available; addition of new codes and specific activities; an update of the Compendium tracking guide that links information in the 1993, 2000, and 2011 compendia versions; and the creation of a Web site to facilitate easy access and downloading of Compendium documents. Measured MET values were obtained from a systematic search of databases using defined key words. The 2011 Compendium contains 821 codes for specific activities. Two hundred seventeen new codes were added, 68% (561/821) of which have measured MET values. Approximately half (317/604) of the codes from the 2000 Compendium were modified to improve the definitions and/or to consolidate specific activities and to update estimated MET values where measured values did not exist. Updated MET values accounted for 73% of all code changes. The Compendium is used globally to quantify the energy cost of PA in adults for surveillance activities, research studies, and, in clinical settings, to write PA recommendations and to assess energy expenditure in individuals. The 2011 Compendium is an update of a system for quantifying the energy cost of adult human PA and is a living document that is moving in the direction of being 100% evidence based.

  2. 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)

  3. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Science.gov (United States)

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

    2016-10-01

    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 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.Full Qualification Model (QM) of the MetNet landing unit with the Precursor Mission payload is currently under functional tests. In the near future the QM unit will be exposed to environmental tests with qualification levels including vibrations, thermal balance, thermal cycling and mechanical impact shock. One complete flight unit of the entry, descent and landing systems (EDLS) has been manufactured and tested with acceptance levels. Another flight-like EDLS has been exposed to most of the qualification tests, and hence it may be used for flight after refurbishments. Accordingly two flight-capable EDLS systems exist. The eventual goal is to create a network of atmospheric observational posts around the Martian surface. The next step in the MetNet Precursor Mission is the demonstration of the technical robustness and scientific capabilities of the MetNet type of landing vehicle. Definition of the Precursor Mission and discussions on launch opportunities are currently under way. The baseline program development funding exists for the next five years. Flight unit manufacture of the payload bay takes about 18 months, and it will be commenced after the Precursor Mission has been defined.

  4. Study on the effect of retrofit soot filters on the emission of diesel engine-fuelled passenger cars; Onderzoek naar het effect van retrofit roetfilters op de emissies van personenwagens met een dieselmotor

    Energy Technology Data Exchange (ETDEWEB)

    Verbeek, R.; Vermeulen, R.J. [TNO Industrie en Techniek, Delft (Netherlands); Krul, C.A.M. [TNO Kwaliteit van Leven, Delft (Netherlands); Kooter, I.M.; Houtzager, M.M.G. [TNO Bouw en Ondergrond, Delft (Netherlands); Cassee, F.R.; Gerlofs-Nijland, M.E. [National Institute for Public Health and the Environment RIVM, Bilthoven (Netherlands)

    2007-10-22

    TNO and RIVM have conducted comparative research of three different types of retrofit soot filters. During a test cycle in which a standard drive is imitated, measurements of particles and chemical components were conducted, both in relation to size and composition and concentration. Moreover, in vitro toxicity research was done for different types of samples of exhaust fumes. Based on this exploratory study an increase of the negative effects of diesel engine emissions on public health rising from the use of the retrofit soot filters subsidized by the Dutch Ministry of Housing, Spatial Planning and the Environment (VROM) is not expected. [mk]. [Dutch] TNO en RIVM hebben vergelijkend onderzoek gedaan aan drie verschillende soorten retrofit roetfilters. Tijdens een testcyclus waarbij een standaard autorit werd nagebootst zijn metingen gedaan naar deeltjes en chemische componenten, zowel naar grootte als samenstelling en concentratie. Er is tevens in vitro toxiciteitonderzoek gedaan aan verschillende type monsters van de uitlaatgassen. Samenvattend kan gesteld worden dat geen indicaties naar voren zijn gekomen dat bij toepassing van het retrofit roetfilter de toxiciteit van de uitlaatgassen zal toenemen. Op basis van dit verkennend onderzoek is vooralsnog geen toename te verwachten van de negatieve effecten van dieselmotoruitstoot op de volksgezondheid door toepassing van de door VROM gesubsidieerde retrofit roetfilters.

  5. Existence and Uniqueness of Solution to ODEs: Lipschitz Continuity

    Indian Academy of Sciences (India)

    Swarup Poria; Aman Dhiman

    2017-05-01

    The study of existence and uniqueness of solution of ordinarydifferential equation (ODE) became important due to the lack ofgeneral formula for solving nonlinear ODEs. In this article, weshall discuss briefly about the existence and uniqueness of solutionof a first order ODE. A special emphasis is given on theLipschitz continuous functions in the discussion.

  6. Valor do padrão de estimulaçao linfonodal da metástase no prognóstico do câncer da hipofaringe: estudo de 24 casos Metastatic lymph node reactivity pattern value in the prognosis of hypopharynx cancer: study of 24 cases

    Directory of Open Access Journals (Sweden)

    Marta Elizabeth Osório Fleitas

    1998-10-01

    Full Text Available Foram estudados 24 casos de pacientes portadores de carcinoma epidermóide da hipofaringe, sendo 13 deles sem metástase linfática (Pn0 e 11 com metástase linfática sem ruptura (pN+RC-, tratados no Serviço de Cirurgia de Cabeça e Pescoço do Hospital Heliópolis, São Paulo, no período de janeiro de 1977 a janeiro de 1993. Foram comparados parâmetros clínico-histopatológicos dos dois grupos com a sobrevida. As informações clínicas foram obtidas através da revisão dos prontuários dos pacientes, e as informações histológicas foram obtidas através da revisão das lâminas. Quando relacionadas às variáveis idade, sexo, categoria N, estadiamento clínico e recorrência cervical, não foi observada piora estatisticamente significativa no prognóstico dos pacientes com linfonodos positivos sem ruptura capsular (pN+RC- comparados aos pacientes com linfonodos negativos (pN. Quando os tipos de reações linfonodais foram agrupados em estimulados e não estimulados, foi observado que o grupo com linfonodos positivos sem ruptura capsular (pN+RC- apresentou maior porcentagem de linfonodos estimulados (Predomínio Linfocitário e de Centros Germinativos que o grupo sem metástase linfonodal (pNO, tendo sido estatisticamente significativo (p=0,0333.Twenty four patients with squamous cell carcinoma of the hypopharnx treated at the Head and Neck Surgery Service of the Heliópolis Hospital from January 1977 to January 1993. were studied. Thirteen cases had no lymphatic metastases (pNO and eleven had lymph nade metastases without extracapsular spread (pN+RC-. Clinical and histological standards of both groups were compared with survival. Clinical data were obtained by reviewing patients registers and histological data by reviewing histological slides. Age, sex, N stage, clinical stage and cervical recurrence had no statistically significant relation with prognosis in both groups. Patients were divided in two groups according to the lymph node

  7. c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Hongliang; Li, Xiaoying; Sun, Shaoqian [Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing (China); Gao, Xianshu, E-mail: xsgao777@hotmail.com [Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing (China); Zhou, Demin, E-mail: deminzhou@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer c-Met inhibition could significantly enhance the radiosensitivity of DU145 cells. Black-Right-Pointing-Pointer The mechanisms of the radiosensitization effect of c-Met inhibition on DU145 cells were also presented in this paper. Black-Right-Pointing-Pointer This is the first study demonstrating the effectiveness of c-Met inhibition on treating HRPC cells with radiotherapy. -- Abstract: Hormone-refractory prostate cancer shows substantial resistance to most conventional therapies including radiotherapy, constitutes a key impediment to curing patients with the disease. c-Met overexpression plays a key role in prostate cancer tumorigenesis and disease progression. Here, we demonstrate that c-Met inhibition by SU11274 could significantly suppress cell survival and proliferation as well as enhance the radiosensitivity of DU145 cells. The underlying mechanisms of the effects of SU11274 on DU145 cells may include the inhibition of c-Met signaling, depolarization of the mitochondrial membrane potential, impairment of DNA repair function, abrogation of cell cycle arrest, and enhancement of cell death. Our study is the first to show the effectiveness of combining c-Met inhibition with ionizing radiation to cure hormone-refractory prostate cancer.

  8. UNIQUENESS ON ZERO PRESSURE GAS DYNAMICS

    Institute of Scientific and Technical Information of China (English)

    黄飞敏; 王振

    2001-01-01

    By introducing a new idea, the authors prove the uniqueness of weak solution of pressureless gases with the large initial data. In particular, uniqueness theorem is obtained in the same functional space as the existence theorem.

  9. 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.

  10. 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.

  11. Agrarische handel van België met ontwikkelingslanden; Toets op duurzaamheid

    NARCIS (Netherlands)

    Meijerink, G.W.; Roza, P.; Berkum, van S.

    2008-01-01

    Deze studie voor het Vlaamse ministerie van Landbouw en Visserij belicht de economische, sociale en ecologische gevolgen van agrarische handel van België met ontwikkelingslanden. Het onderzoek spitst zich toe op een vijftal producten (banaan, cacao, koffie, soja en thee) en vier ontwikkelingslanden

  12. Wij vermarkten de Nederlandse kennis van en expertise over aquacultuur (interview met Arjo Rothuis)

    NARCIS (Netherlands)

    Lee, van der H.; Rothuis, A.J.

    2012-01-01

    IMARES, het Institute for Marine Resources and Ecosystem Studies, is onderdeel van Wageningen UR en hét expertisecentrum over visserij en aquacultuur binnen Nederland. Arjo Rothuis houdt zich er bezig met het ontwikkelen en managen van projecten in het niet-Europese buitenland. Hij is daarnaast een

  13. Kinderen met een motorische coördinatiestoornis (DCD) in de kinderrevalidatie: Motorische problematiek en comorbiditeit

    NARCIS (Netherlands)

    Flapper, Boudien C.T.; Scholten-Jaegers, S.; Schoemaker, M.M.

    2003-01-01

    The purpose of this study was to describe the developmental problems of children in school age, referred to the child rehabilitation centre because of clumsiness. The results show that 63% met the criteria for the classification of developmental coordination disorder and these children with DC:D sho

  14. 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.

    2015-01-01

    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,

  15. Levensvatbaarheid van Ralstonia en Clavibacter meetbaar met behulp van RNA-detectiemethoden

    NARCIS (Netherlands)

    Wolf, van der J.M.; Beckhoven, van J.R.C.M.

    2003-01-01

    Studie naar de epidemiologie van de bacterieziekten bruinrot (Ralstonia solacearum) en ringrot (Clavibacter michiganensis subsp. sepedonicus). De nieuwe methode is gebaseerd op amplificatie van 16S rRNA sequenties met behulp van NASBA (nucleic acid sequence based amplification). NASBA is een methode

  16. 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,

  17. 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...

  18. Kinderen met een motorische coördinatiestoornis (DCD) in de kinderrevalidatie: Motorische problematiek en comorbiditeit

    NARCIS (Netherlands)

    Flapper, Boudien C.T.; Scholten-Jaegers, S.; Schoemaker, M.M.

    2003-01-01

    The purpose of this study was to describe the developmental problems of children in school age, referred to the child rehabilitation centre because of clumsiness. The results show that 63% met the criteria for the classification of developmental coordination disorder and these children with DC:D

  19. Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Zhen-Wei; Wei, Donna; Schroeder, Gretchen M.; Cornelius, Lyndon A.M.; Kim, Kyoung; Chen, Xiao-Tao; Schmidt, Robert J.; Williams, David K.; Tokarski, John S.; An, Yongmi; Sack, John S.; Manne, Veeraswamy; Kamath, Amrita; Zhang, Yueping; Marathe, Punit; Hunt, John T.; Lombardo, Louis J.; Fargnoli, Joseph; Borzilleri, Robert M. (BMS)

    2008-09-10

    A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.

  20. Agrarische handel van België met ontwikkelingslanden; Toets op duurzaamheid

    NARCIS (Netherlands)

    Meijerink, G.W.; Roza, P.; Berkum, van S.

    2008-01-01

    Deze studie voor het Vlaamse ministerie van Landbouw en Visserij belicht de economische, sociale en ecologische gevolgen van agrarische handel van België met ontwikkelingslanden. Het onderzoek spitst zich toe op een vijftal producten (banaan, cacao, koffie, soja en thee) en vier ontwikkelingslanden