Targeting MET Amplification as a New Oncogenic Driver

International Nuclear Information System (INIS)

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

2014-01-01

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

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.

MMPM - Mars MetNet Precursor Mission

Science.gov (United States)

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

2008-09-01

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

COMT val108/158 met genotype affects neural but not cognitive processing in healthy individuals.

Science.gov (United States)

Dennis, Nancy A; Need, Anna C; LaBar, Kevin S; Waters-Metenier, Sheena; Cirulli, Elizabeth T; Kragel, James; Goldstein, David B; Cabeza, Roberto

2010-03-01

The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496-1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output.

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

Science.gov (United States)

Drinkwater, Diana; Bianco, Nina

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

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

NARCIS (Netherlands)

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

1989-01-01

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

Extraboard performance : TriMet case study.

Science.gov (United States)

2012-02-01

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

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

Science.gov (United States)

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

2017-11-01

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

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

Science.gov (United States)

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

2018-04-01

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

Creating a culture for information systems success

CERN Document Server

Belkhamza, Zakariya

2015-01-01

It has been widely reported that issues related to organizational context appear frequently in discussions of information systems success. The statement that the information system did not fit the behavioral context in an organization is often part of the explanation of why particular information system encountered unanticipated resistance and never met expectation. While this context has been intensively studied, we still lack evidence on how this organizational context is affecting the success of information system from a managerial action perspective. This type of managerial involvement is often neglected to the extent that it became an essential obstacle to organizational performance. The objective of Creating a Culture for Information Systems Success is to assist CIOs and IT managers on how to use their managerial actions to create a suitable cultural environment in the organization, which leads to a successful implementation of information systems. This  book will also provide guidelines fo...

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

Science.gov (United States)

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

2008-01-01

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

C-MET overexpression and amplification in gliomas.

Science.gov (United States)

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

2015-01-01

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

Met Ed gets reprieve: banks lend tax money

International Nuclear Information System (INIS)

Utroska, D.

1981-01-01

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

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

NARCIS (Netherlands)

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

2010-01-01

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

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

Science.gov (United States)

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

2010-08-06

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

BDNF Val66Met polymorphism as a moderator of exercise enhancement of smoking cessation treatment in anxiety vulnerable adults

NARCIS (Netherlands)

Smits, J.A.J.; Powers, M.B.; Rosenfield, D.; Zvolensky, M.J.; Jacquart, J.; Davis, M.L.; Beevers, C.G.; Marcus, B.H.; Church, T.S.; Otto, M.W.

2016-01-01

Background: Exercise interventions facilitate the odds of quit success among high-anxiety sensitive adults smokers. We examined the dependency of these benefits on the genetic BDNF Val66Met (rs6265) polymorphism; individuals who are Met carriers have lower BDNF responses and reduced associated

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

Science.gov (United States)

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

2017-12-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2018-04-15

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

Sereniteit met een dip

NARCIS (Netherlands)

dr Ed de Jonge

2015-01-01

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

SUPERCOLLIDER: String test success

International Nuclear Information System (INIS)

Anon.

1992-01-01

On 14 August at the Superconducting Supercollider (SSC) Laboratory in Ellis County, Texas, the Accelerator Systems String Test (ASST) successfully met its objective by operating a half-cell of five collider dipole magnets, one quadrupole magnet, and two spool pieces at the design current of 6500 amperes

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

Energy Technology Data Exchange (ETDEWEB)

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

2009-12-15

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

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.

Metsämaisema ulkoilijoiden kokemana

OpenAIRE

Vuohijoki, Jaana

2010-01-01

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

The Contribution of Counseling Providers to the Success or Failure of Marriages

Science.gov (United States)

Ansah-Hughes, Winifred

2015-01-01

This study is an investigation into the contribution of counseling providers to the success or failure of marriages. The purposive and the simple random sampling methods were used to select eight churches and 259 respondents (married people) in the Techiman Municipality. The instrument used to collect data was a 26-item questionnaire including a…

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

NARCIS (Netherlands)

Tom Langhorst

2010-01-01

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

Structural setting of the Metán Basin (NW Argentina): new insights from 2D seismic profiles

Science.gov (United States)

Conti, Alessia; Maffucci, Roberta; Bigi, Sabina; Corrado, Sveva; Giordano, Guido; Viramonte, José G.

2017-04-01

The Metán Basin is located in the sub-Andean foreland, in the southernmost portion of the Santa Barbara system structural province (NW Argentina). The upper crust in this region shows a strong segmentation due to inherited stratigraphic and structural discontinuities, related to a Palaeozoic orogenic event and to a Cretaceous to Paleogene rifting event (Kley et al., 1999; Iaffa et al., 2011). This study seeks to unravel the deep structural setting of the basin, in order to better understand the tectonic evolution of the area. Different seismic sections are analysed, located in the Metán basin and acquired by YPF (Yacimientos Petrolíferos Fiscales, former national oil company of Argentina) in different surveys during the '70s - '80s. Stratigraphic control for the seismic interpretation is provided by petroleum exploratory wells drilled in the basin; they show a stratigraphic succession of syn-rift and post-rift deposits, mainly constituted by a continental succession of red beds, with minor limestone intercalations (Salta Group), overlain by a thick continental foreland basin succession (Orán Group) (Salfity et al., 1981). From a structural point of view, the Metán basin is characterized by a variety of structural trends, with thrust faults and related folds mainly trending N-S, NE-SW and NNE-SSW. Different mechanism can be responsible for the folding of the sedimentary cover; hangingwall anticlines are represented both by high angle thrust faults produced by inversion of Cretaceous extensional faults (Maffucci et al., 2015), and by fault propagation folds formed during the Andean shortening event. The study of the interaction between the older reactivated faults and the newly generated ones could provide new insights to unravel the complex structural setting of the area. References Iaffa D. N., Sàbat, F., Muñoz, J.A., Mon, R., Gutierrez, A.A., 2011. The role of inherited structures in a foreland basin evolution. The Metán Basin in NW Argentina. Journal of

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

Science.gov (United States)

Granito, Alessandro; Guidetti, Elena; Gramantieri, Laura

2015-01-01

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

Operational Use of OGC Web Services at the Met Office

Science.gov (United States)

Wright, Bruce

2010-05-01

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

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

Directory of Open Access Journals (Sweden)

Levi Arnold

2017-12-01

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

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

77 FR 31153 - Providing an Order of Succession Within the Department of Agriculture

Science.gov (United States)

2012-05-24

... Providing an Order of Succession Within the Department of Agriculture By the authority vested in me as... set forth in the Act, the following officials of the Department of Agriculture, in the order listed, shall act as and perform the functions and duties of the office of Secretary of Agriculture (Secretary...

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

Science.gov (United States)

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

2015-12-01

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

75 FR 27921 - Providing an Order of Succession Within the Department of Agriculture

Science.gov (United States)

2010-05-18

... Providing an Order of Succession Within the Department of Agriculture By the authority vested in me as... Agriculture, in the order listed, shall act as and perform the functions and duties of the office of Secretary of Agriculture (Secretary) during any period in which both the Secretary and the Deputy Secretary of...

77 FR 31155 - Providing an Order of Succession Within the Department of Commerce

Science.gov (United States)

2012-05-24

... Providing an Order of Succession Within the Department of Commerce By the authority vested in me as... forth in the Act, the following officials of the Department of Commerce, in the order listed, shall act as and perform the functions and duties of the office of the Secretary of Commerce (Secretary) during...

A Canadian isotope success story

International Nuclear Information System (INIS)

Malkoske, G.

1997-01-01

This paper provides some historical background on the commercial production of radioisotopes in Canada, and the evolution of the present vendor, MDS Nordion. The chief isotopes are molybdenum 99, iodine 131, and cobalt 60. Cobalt 60 for medical sterilization and irradiation is considered to be a significant growing market. Food irradiation is believed to be a big marketing opportunity, although attempts to popularize it have so far met with limited success. Candu reactors supply the bulk of the world's 60 Co supply. Eighty percent of the world's 99 Mo supply for medical imaging comes from Canada, and is at present produced in NRU Reactor, which is to be replaced by two Maple reactors coming into production in 1999 and 2000

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

Hanford Site Welding Program Successfully Providing A Single Site Function For Use By Multiple Contractors

International Nuclear Information System (INIS)

Cannell, G.R.

2009-01-01

The Department of Energy, Richland Operations (DOE-RL) recently restructured its Hanford work scope, awarding two new contracts over the past several months for a total of three contracts to manage the sites cleanup efforts. DOE-RL met with key contractor personnel prior to and during contract transition to ensure site welding activities had appropriate oversight and maintained code compliance. The transition also provided an opportunity to establish a single site-wide function that would provide welding and materials engineering services to the Hanford site contractors: CH2M HILL Plateau Remediation Company (CHPRC); Mission Support Alliance (MSA); Washington River Protection Solutions (WRPS); and Washington Closure Hanford (WCH). Over the years, multiple and separate welding programs (amongst the several contractors) existed at the Hanford site leading to inefficiencies resulting from duplication of administrative efforts, maintenance of welding procedures, welder performance certifications, etc. The new, single program eliminates these inefficiencies. The new program, co-managed by two of the sites' new contractors, the CHPRC ('owner' of the program and responsible for construction welding services) and the MSA (provides maintenance welding services), provides more than just the traditional construction and maintenance welding services. Also provided, are welding engineering, specialty welding development/qualification for the closure of radioactive materials containers and materials evaluation/failure analysis. The following describes the new Hanford site welding program.

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

Science.gov (United States)

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

2017-04-01

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

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

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

Science.gov (United States)

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

2007-09-01

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

Improvement with insight. Healthier indoor climate and lower energy consumption with wireless Sensor networks; Verbeteren met inzicht. Gezonder binnenklimaat en lager energiegebruik met draadloze Sensor netwerken

Energy Technology Data Exchange (ETDEWEB)

Peekstok, E.J. [MakeMoreSense, Sommelsdijk (Netherlands)

2010-11-15

Wireless Sensor Networks connected to the internet will dramatically influence the future of Indoor Climate and Energy use. Munisense, a Dutch company, has developed a real-time and web-based monitoring tool called InSightNow. With Insight it is possible to improve the environment, often with very simple measures. The majority of things going wrong are caused by human interventions. For example engineers when programming installations and users adjusting settings. Giving people insight in their behaviour via a 'dashboard for buildings', creates awareness and makes it possible to improve. Installers are able to limit failure cost, improve quality of service and contribute to the customers success by limiting sick-leave, improve work performance, reduce energy cost and unused floor space. [Dutch] Het is noodzakelijk om in schoolgebouwen een blijvend gezond binnenklimaat te creeren, want binnenklimaat, ziekteverzuim en leerprestaties hebben volgens wetenschappelijk onderzoek een direct verband met elkaar. Netwerken met draadloze sensors kunnen daar een rol bij spelen.

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.

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

Directory of Open Access Journals (Sweden)

ramin saravani

2017-10-01

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

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

Science.gov (United States)

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

2012-09-11

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

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

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

Directory of Open Access Journals (Sweden)

Bozkaya Giray

2012-09-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-03-15

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

Impaction and Prediction: Does Ureteral Wall Thickness Affect the Success of Medical Expulsive Therapy in Pediatric Ureteral Stones?

Science.gov (United States)

Tuerxun, Aierken; Batuer, Abudukahaer; Erturhan, Sakip; Eryildirim, Bilal; Camur, Emre; Sarica, Kemal

2017-01-01

The study aimed to evaluate the predictive value of ureteral wall thickness (UWT) and stone-related parameters for medical expulsive therapy (MET) success with an alpha blocker in pediatric upper ureteral stones. A total of 35 children receiving MET ureteral stones (Hounsfield unit), degree of hydronephrosis, and UWT were evaluated with patient demographics and recorded. The possible predictive value of these parameters in success rates and time to stone expulsion were evaluated in a comparative manner between the 2 groups. The overall mean patient age and stone size values were 5.40 ± 0.51 years and 6.24 ± 0.28 mm, respectively. Regarding the predictive values of these parameters for the success of MET, while stone size and UWT were found to be highly predictive for MET success, patients age, body mass index, stone density, and degree of hydronephrosis had no predictive value on this aspect. Our findings indicated that some stone and anatomical factors may be used to predict the success of MET in pediatric ureteral stones in an effective manner. With this approach, unnecessary use of these drugs that may cause a delay in removing the stone will be avoided, and the possible adverse effects of obstruction as well as stone-related clinical symptoms could be minimized. © 2017 S. Karger AG, Basel.

Ervaringen met beeldverwerking.

NARCIS (Netherlands)

Meuleman, J.

1989-01-01

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

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

Science.gov (United States)

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

2008-01-01

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

Operational assimilation of ASCAT surface soil wetness at the Met Office

Directory of Open Access Journals (Sweden)

I. Dharssi

2011-08-01

Full Text Available Currently, no extensive, near real time, global soil moisture observation network exists. Therefore, the Met Office global soil moisture analysis scheme has instead used observations of screen temperature and humidity. A number of new space-borne remote sensing systems, operating at microwave frequencies, have been developed that provide a more direct retrieval of surface soil moisture. These systems are attractive since they provide global data coverage and the horizontal resolution is similar to weather forecasting models. Several studies show that measurements of normalised backscatter (surface soil wetness from the Advanced Scatterometer (ASCAT on the meteorological operational (MetOp satellite contain good quality information about surface soil moisture. This study describes methods to convert ASCAT surface soil wetness measurements to volumetric surface soil moisture together with bias correction and quality control. A computationally efficient nudging scheme is used to assimilate the ASCAT volumetric surface soil moisture data into the Met Office global soil moisture analysis. This ASCAT nudging scheme works alongside a soil moisture nudging scheme that uses observations of screen temperature and humidity. Trials, using the Met Office global Unified Model, of the ASCAT nudging scheme show a positive impact on forecasts of screen temperature and humidity for the tropics, North America and Australia. A comparison with in-situ soil moisture measurements from the US also indicates that assimilation of ASCAT surface soil wetness improves the soil moisture analysis. Assimilation of ASCAT surface soil wetness measurements became operational during July 2010.

Autorijden met ADHD

NARCIS (Netherlands)

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

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

Research progress in c-Met and hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

WANG Changqing

2015-06-01

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

Testing ATLAS Z+MET excess with LHC run 2

International Nuclear Information System (INIS)

Lu, Xiaochuan; Terada, Takahiro

2016-05-01

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

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

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

Science.gov (United States)

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

2018-04-08

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

Jeugd met beperkingen

NARCIS (Netherlands)

Sjoerd Kooiker

2006-01-01

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

SPSS met syntax

NARCIS (Netherlands)

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

2007-01-01

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

Science.gov (United States)

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

2017-06-01

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

Dissection of combinatorial control by the Met4 transcriptional complex.

Science.gov (United States)

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

2010-02-01

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

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

Adolescent and Adult HIV Providers' Definitions of HIV-Infected Youths' Successful Transition to Adult Care in the United States.

Science.gov (United States)

Philbin, Morgan M; Tanner, Amanda E; Ma, Alice; Chambers, Brittany D; Ware, Samuella; Kinnard, Elizabeth N; Hussen, Sophia A; Lee, Sonia; Fortenberry, J Dennis

2017-10-01

It is important for both individual- and population-level health that HIV-infected individuals progress through the Care Continuum. However, HIV-infected youth frequently disengage from care during transition from pediatric/adolescent to adult care; only 50% remain in adult care after 1 year. Understanding how providers define and approach a successful healthcare transition can improve the delivery of HIV-related services during critical years of HIV treatment. We conducted 58 staff interviews across 14 Adolescent Trials Network clinics (n = 30) and 20 adult clinics (n = 28). We used the constant comparative method to examine how providers defined and approached youths' successful transition. Providers identified four components critical to successful transition: (1) clinical outcomes (e.g., medication adherence and viral suppression); (2) youth knowing how to complete treatment-related activities (e.g., refilling prescriptions and making appointments); (3) youth taking responsibility for treatment-related activities and their overall health (e.g., "when they stop reaching out to the adolescent [clinic] to solve all their problems."); and (4) youth feeling a connection and trust toward the adult clinic (e.g., "they feel safe here"), with some providers even prioritizing connectedness over clinical outcomes (e.g., "Even if they're not taking meds but are connected [to care], …that's a success."). The identification of key components of successful transition can guide focused interventions and resources to improve youth maintenance in the HIV Care Continuum as they transition to adult care. Identifying what facilitates successful transitions, and the gaps that interventions can target, will help to ensure HIV-infected youth remain healthy across their lifespan.

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

Science.gov (United States)

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

2010-06-01

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

The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma

Directory of Open Access Journals (Sweden)

Luis J. Herrera

2005-01-01

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

Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody-"decoy" strategy.

Science.gov (United States)

Basilico, Cristina; Modica, Chiara; Maione, Federica; Vigna, Elisa; Comoglio, Paolo M

2018-04-25

MET, a master gene sustaining "invasive growth," is a relevant target for cancer precision therapy. In the vast majority of tumors, wild-type MET behaves as a "stress-response" gene and relies on the ligand (HGF) to sustain cell "scattering," invasive growth and apoptosis protection (oncogene "expedience"). In this context, concomitant targeting of MET and HGF could be crucial to reach effective inhibition. To test this hypothesis, we combined an anti-MET antibody (MvDN30) inducing "shedding" (i.e., removal of MET from the cell surface), with a "decoy" (i.e., the soluble extracellular domain of the MET receptor) endowed with HGF-sequestering ability. To avoid antibody/decoy interaction-and subsequent neutralization-we identified a single aminoacid in the extracellular domain of MET-lysine 842-that is critical for MvDN30 binding and engineered the corresponding recombinant decoyMET (K842E). DecoyMET K842E retains the ability to bind HGF with high affinity and inhibits HGF-induced MET phosphorylation. In HGF-dependent cellular models, MvDN30 antibody and decoyMET K842E used in combination cooperate in restraining invasive growth, and synergize in blocking cancer cell "scattering." The antibody and the decoy unbridle apoptosis of colon cancer stem cells grown in vitro as spheroids. In a preclinical model, built by orthotopic transplantation of a human pancreatic carcinoma in SCID mice engineered to express human HGF, concomitant treatment with antibody and decoy significantly reduces metastatic spread. The data reported indicate that vertical targeting of the MET/HGF axis results in powerful inhibition of ligand-dependent MET activation, providing proof of concept in favor of combined target therapy of MET "expedience." © 2018 UICC.

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

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

Science.gov (United States)

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

2012-01-01

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

Met1-linked Ubiquitination in Immune Signalling

DEFF Research Database (Denmark)

Fiil, Berthe Katrine; Gyrd-Hansen, Mads

2014-01-01

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

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

DEFF Research Database (Denmark)

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

2013-01-01

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

Hydrogen storage capacity of titanium met-cars

International Nuclear Information System (INIS)

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

2006-01-01

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

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.

Barriers and facilitators to successful transition from pediatric to adult inflammatory bowel disease care from the perspectives of providers

Science.gov (United States)

Paine, Christine Weirich; Stollon, Natalie B.; Lucas, Matthew S.; Brumley, Lauren D.; Poole, Erika S.; Peyton, Tamara; Grant, Anne W.; Jan, Sophia; Trachtenberg, Symme; Zander, Miriam; Mamula, Petar; Bonafide, Christopher P.; Schwartz, Lisa A.

2014-01-01

Background For adolescents and young adults (AYA) with inflammatory bowel disease (IBD), the transition from pediatric to adult care is often challenging and associated with gaps in care. Our study objectives were to (1) identify outcomes for evaluating transition success and (2) elicit the major barriers and facilitators of successful transition. Methods We interviewed pediatric and adult IBD providers from across the United States with experience caring for AYAs with IBD until thematic saturation was reached after 12 interviews. We elicited the participants' backgrounds, examples of successful and unsuccessful transition of AYAs for whom they cared, and recommendations for improving transition using the Social-ecological Model of Adolescent and Young Adult Readiness to Transition framework. We coded interview transcripts using the constant comparative method and identified major themes. Results Participants reported evaluating transition success and failure using healthcare utilization outcomes (e.g. maintaining continuity with adult providers), health outcomes (e.g. stable symptoms), and quality of life outcomes (e.g. attending school). The patients' level of developmental maturity (i.e. ownership of care) was the most prominent determinant of transition outcomes. The style of parental involvement (i.e. helicopter parent vs. optimally-involved parent) also influenced outcomes as well as the degree of support by providers (e.g. care coordination). Conclusion IBD transition success is influenced by a complex interplay of patient developmental maturity, parenting style, and provider support. Multidisciplinary IBD care teams should aim to optimize these factors for each patient to increase the likelihood of a smooth transfer to adult care. PMID:25137417

Barriers and facilitators to successful transition from pediatric to adult inflammatory bowel disease care from the perspectives of providers.

Science.gov (United States)

Paine, Christine W; Stollon, Natalie B; Lucas, Matthew S; Brumley, Lauren D; Poole, Erika S; Peyton, Tamara; Grant, Anne W; Jan, Sophia; Trachtenberg, Symme; Zander, Miriam; Mamula, Petar; Bonafide, Christopher P; Schwartz, Lisa A

2014-11-01

For adolescents and young adults (AYA) with inflammatory bowel disease (IBD), the transition from pediatric to adult care is often challenging and associated with gaps in care. Our study objectives were to (1) identify outcomes for evaluating transition success and (2) elicit the major barriers and facilitators of successful transition. We interviewed pediatric and adult IBD providers from across the United States with experience caring for AYAs with IBD until thematic saturation was reached after 12 interviews. We elicited the participants' backgrounds, examples of successful and unsuccessful transition of AYAs for whom they cared, and recommendations for improving transition using the Social-Ecological Model of Adolescent and Young Adult Readiness to Transition framework. We coded interview transcripts using the constant comparative method and identified major themes. Participants reported evaluating transition success and failure using health care utilization outcomes (e.g., maintaining continuity with adult providers), health outcomes (e.g., stable symptoms), and quality of life outcomes (e.g., attending school). The patients' level of developmental maturity (i.e., ownership of care) was the most prominent determinant of transition outcomes. The style of parental involvement (i.e., helicopter parent versus optimally involved parent) and the degree of support by providers (e.g., care coordination) also influenced outcomes. IBD transition success is influenced by a complex interplay of patient developmental maturity, parenting style, and provider support. Multidisciplinary IBD care teams should aim to optimize these factors for each patient to increase the likelihood of a smooth transfer to adult care.

Is neurofeedback effectief bij kinderen met ADHD?

NARCIS (Netherlands)

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

2008-01-01

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

Proef met duurzaam watergebruik in de bollenstreek

NARCIS (Netherlands)

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

2009-01-01

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

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.

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.

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

Science.gov (United States)

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

2017-12-01

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

Transition of NOAA's GPS-Met Data Acquisition and Processing System to the Commercial Sector

Science.gov (United States)

Jackson, M. E.; Holub, K.; Callahan, W.; Blatt, S.

2014-12-01

In April of 2014, NOAA/OAR/ESRL Global Systems Division (GSD) and Trimble, in collaboration with Earth Networks, Inc. (ENI) signed a Cooperative Research and Development Agreement (CRADA) to transfer the existing NOAA GPS-Met Data Acquisition and Processing System (GPS-Met DAPS) technology to a commercial Trimble/ENI partnership. NOAA's GPS-Met DAPS is currently operated in a pseudo-operational mode but has proven highly reliable and running at over 95% uptime. The DAPS uses the GAMIT software to ingest dual frequency carrier phase GPS/GNSS observations and ancillary information such as real-time satellite orbits to estimate the zenith-scaled tropospheric (ZTD) signal delays and, where surface MET data are available, retrieve integrated precipitable water vapor (PWV). The NOAA data and products are made available to end users in near real-time. The Trimble/ENI partnership will use the Trimble Pivot™ software with the Atmosphere App to calculate zenith tropospheric (ZTD), tropospheric slant delay, and integrated precipitable water vapor (PWV). Evaluation of the Trimble software is underway starting with a comparison of ZTD and PWV values determined from GPS stations located near NOAA Radiosonde Observation (Upper-Air Observation) launch sites. A success metric was established that requires Trimble's PWV estimates to match ESRL/GSD's to within 1.5 mm 95% of the time, which corresponds to a ZTD uncertainty of less than 10 mm 95% of the time. Initial results indicate that Trimble/ENI data meet and exceed the ZTD metric, but for some stations PWV estimates are out of specification. These discrepancies are primarily due to how offsets between MET and GPS stations are handled and are easily resolved. Additional test networks are proposed that include low terrain/high moisture variability stations, high terrain/low moisture variability stations, as well as high terrain/high moisture variability stations. We will present results from further testing along with a timeline

Transition of NOAA's GPS-Met Data Acquisition and Processing System to the Commercial Sector: Inital Results

Science.gov (United States)

Jackson, Michael; Blatt, Stephan; Holub, Kirk

2015-04-01

In April of 2014, NOAA/OAR/ESRL Global Systems Division (GSD) and Trimble, in collaboration with Earth Networks, Inc. (ENI) signed a Cooperative Research and Development Agreement (CRADA) to transfer the existing NOAA GPS-Met Data Acquisition and Processing System (GPS-Met DAPS) technology to a commercial Trimble/ENI partnership. NOAA's GPS-Met DAPS is currently operated in a pseudo-operational mode but has proven highly reliable and running at over 95% uptime. The DAPS uses the GAMIT software to ingest dual frequency carrier phase GPS/GNSS observations and ancillary information such as real-time satellite orbits to estimate the zenith-scaled tropospheric (ZTD) signal delays and, where surface MET data are available, retrieve integrated precipitable water vapor (PWV). The NOAA data and products are made available to end users in near real-time. The Trimble/ENI partnership will use the Trimble Pivot™ software with the Atmosphere App to calculate zenith tropospheric (ZTD), tropospheric slant delay, and integrated precipitable water vapor (PWV). Evaluation of the Trimble software is underway starting with a comparison of ZTD and PWV values determined from four sub networks of GPS stations located 1. near NOAA Radiosonde Observation (Upper-Air Observation) launch sites; 2. Stations with low terrain/high moisture variability (Gulf Coast); 3. Stations with high terrain/low moisture variability (Southern California); and 4. Stations with high terrain/high moisture variability (high terrain variability elev. > 1000m). For each network GSD and T/ENI run the same stations for 30 days, compare results, and perform an evaluation of the long-term solution accuracy, precision and reliability. Metrics for success include T/ENI PWV estimates within 1.5 mm of ESRL/GSD's estimates 95% of the time (ZTD uncertainty of less than 10 mm 95% of the time). The threshold for allowable variations in ZTD between NOAA GPS-Met and T/ENI processing are 10mm. The CRADA 1&2 Trimble processing

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.

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

Science.gov (United States)

Kwon, Youngjoo; Godwin, Andrew K

2017-04-01

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

Hounsfield unit density accurately predicts ESWL success.

Science.gov (United States)

Magnuson, William J; Tomera, Kevin M; Lance, Raymond S

2005-01-01

Extracorporeal shockwave lithotripsy (ESWL) is a commonly used non-invasive treatment for urolithiasis. Helical CT scans provide much better and detailed imaging of the patient with urolithiasis including the ability to measure density of urinary stones. In this study we tested the hypothesis that density of urinary calculi as measured by CT can predict successful ESWL treatment. 198 patients were treated at Alaska Urological Associates with ESWL between January 2002 and April 2004. Of these 101 met study inclusion with accessible CT scans and stones ranging from 5-15 mm. Follow-up imaging demonstrated stone freedom in 74.2%. The overall mean Houndsfield density value for stone-free compared to residual stone groups were significantly different ( 93.61 vs 122.80 p ESWL for upper tract calculi between 5-15mm.

Participatory action research: The key to successful implementation ...

African Journals Online (AJOL)

Unfortunately many of these innovative changes in training have met resistance from lecturers and students simply because they are just imposed on them. One way of ensuring acceptability and success of innovative and evidence-based training methods in health sciences could be the use of participatory action research ...

Verification of space weather forecasts at the UK Met Office

Science.gov (United States)

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

2017-12-01

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

Shared leadership in a medical practice: keys to success.

Science.gov (United States)

Daiker, Barbara L

2009-01-01

Medical practices are in a complex industry and require the expertise of both physician and business leaders to be successful. Sharing the leadership between these two professionals brings with it challenges that are best met if the environment is supportive. This support comes in the form of external aspects such as selection, role definition, organizational hierarchy, time, and process. Critical to shared leadership is communication, both frequency and quality. Conflicts are likely to occur, and how they are resolved is what determines the strength of a shared governance relationship. Reality is that finding the balance in shared governance is diffcult, but with effort and commitment, it can provide the organization with the performance it hopes to achieve.

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.

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-07-01

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

When Allport Met Freud: Using Anecdotes in the Teaching of Psychology.

Science.gov (United States)

Kaufman, James C.; Bristol, Adam S.

2001-01-01

Proposes using anecdotes in introductory psychology courses to teach key points, principles, and people. Offers theoretical and empirical support for anecdotes as teaching tools. Believes that anecdotes, such as when Gordon Allport met Sigmund Freud, provide an enjoyable experience and enable students to better remember information. (CMK)

Groen proceswater: zuivering brouwerijprocesafvalwater met microalgen : Resultaten onderzoek 2013

NARCIS (Netherlands)

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

2014-01-01

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

Wittgenstein, the body, its metaphors Wittgenstein, o corpo, suas metáforas

Directory of Open Access Journals (Sweden)

Helena Martins

2010-01-01

Full Text Available Contemporary theories of metaphor often give the body a foundational status, by claiming that it provides the universal ground upon which imagination engenders figurative thought. This paper goes against this idea, discussing the relationship between the body and metaphor from a non foundationalist point of view. Taking a Wittgensteinean stance on metaphor and on the body, it aims to provide elements to rethink the issue, exploring in particular the path open by the Austrian philosopher in his critique of traditional mental/ physical, inner/outer dichotomies.Teorias contemporâneas da metáfora amiúde incluem o corpo entre seus fundamentos últimos, sustentando que nossa experiência corpórea constitui o solo universal de onde a imaginação faz brotar o pensamento figurativo. Contrapondo-se a essa tese, este trabalho busca discutir a relação entre corpo e metáfora de uma perspectiva não fundacionalista. A partir de um ponto de vista wittgensteiniano quanto aos estatutos do corpo e da metáfora, busca fornecer elementos para repensar a questão, explorando em particular o caminho aberto pelo filósofo austríaco em sua crítica às dicotomias físico/mental, exterior/interior.

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

Science.gov (United States)

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

2015-04-01

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

Efficacy of c-Met inhibitor for advanced prostate cancer

International Nuclear Information System (INIS)

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

2010-01-01

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

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

Science.gov (United States)

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

2016-08-01

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

Advanced CerMet ceramic composites for medical applications.

Science.gov (United States)

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

2017-11-01

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

Studeren met Hans Rosenberg

NARCIS (Netherlands)

Rutten, R.J.

2001-01-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Klimaatverandering en de stadsboom (interview met Jitze Kopinga)

NARCIS (Netherlands)

Bennink, P.; Kopinga, J.

2010-01-01

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

MetNet Network Mission for Martian Atmospheric Investigations

Science.gov (United States)

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

2014-07-01

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

Requirements to be met by the operation manual

International Nuclear Information System (INIS)

1981-03-01

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

Dimensionering van de Uniqfill chemischer wasser met lamellen

NARCIS (Netherlands)

Starmans, D.A.J.

2006-01-01

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

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

Science.gov (United States)

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

2017-02-07

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

Mindfulness voor volwassenen met een licht verstandelijke beperking

NARCIS (Netherlands)

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

2016-01-01

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

Preproghrelin Leu72Met polymorphism in obese Korean children.

Science.gov (United States)

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

2005-11-01

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

Effect of MET on formation and vigor of wheat roots

International Nuclear Information System (INIS)

Wang Bingkui; Jin Ziyu; Zhao Miaozhen; Zhao Yanshen

1993-01-01

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

Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity.

Science.gov (United States)

Lo, Fu-Sun; Erzurumlu, Reha S; Powell, Elizabeth M

2016-03-30

Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated geneMETtyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAAreceptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAAreceptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis. A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAAreceptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention. Copyright © 2016 the authors 0270-6474/16/363691-07$15.00/0.

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

NARCIS (Netherlands)

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

2008-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-08-15

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

Geriatric hip fracture management: keys to providing a successful program.

Science.gov (United States)

Basu, N; Natour, M; Mounasamy, V; Kates, S L

2016-10-01

Hip fractures are a common event in older adults and are associated with significant morbidity, mortality and costs. This review examines the necessary elements required to implement a successful geriatric fracture program and identifies some of the barriers faced when implementing a successful program. The Geriatric Fracture Center (GFC) is a treatment model that standardizes the approach to the geriatric fracture patient. It is based on five principles: surgical fracture management; early operative intervention; medical co-management with geriatricians; patient-centered, standard order sets to employ best practices; and early discharge planning with a focus on early functional rehabilitation. Implementing a geriatric fracture program begins with an assessment of the hospital's data on hip fractures and standard care metrics such as length of stay, complications, time to surgery, readmission rates and costs. Business planning is essential along with the medical planning process. To successfully develop and implement such a program, strong physician leadership is necessary to articulate both a short- and long-term plan for implementation. Good communication is essential-those organizing a geriatric fracture program must be able to implement standardized plans of care working with all members of the healthcare team and must also be able to foster relationships both within the hospital and with other institutions in the community. Finally, a program of continual quality improvement must be undertaken to ensure that performance outcomes are improving patient care.

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

Science.gov (United States)

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

2016-01-01

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

Successful Climate Science Communication Strategies

Science.gov (United States)

Sinclair, P.

2016-12-01

In the past decade, efforts to communicate the facts of global change have not successfully moved political leaders and the general public to action. In response, a number of collaborative efforts between scientists and professional communicators, writers, journalists, bloggers, filmmakers, artists and others have arisen seeking to bridge that gap. As a result, a new cadre of science-literate communicators, and media-savvy scientists have made themselves visible across diverse mainstream, traditional, and social media outlets. Because of these collaborations, in recent years, misinformation, and disinformation have been successfully met with accurate and credible rebuttals within a single news cycle.Examples of these efforts is the Dark Snow Project, a science/communication collaboration focusing initially on accelerated arctic melt and sea level rise, and the Climate Science Rapid Response team, which matches professional journalists with appropriate science experts in order to respond within a single news cycle to misinformation or misunderstandings about climate science.The session will discuss successful examples and suggest creative approaches for the future.

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

NARCIS (Netherlands)

Hoeksema, B.W.

2003-01-01

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

Parents’ lived experience of providing kangaroo care to their preterm infants

Directory of Open Access Journals (Sweden)

Angela Leonard

2008-12-01

Full Text Available Premature and low birthweight infants pose particular challenges to health services in South Africa. While there is good evidence to demonstrate the benefits of kangaroo care in low birthweight infants, limited research has been conducted locally on the experiences of parents who provide kangaroo care to their preterm infants. This phenomenological study explores the lived experience of parents who provided their preterm infants with kangaroo care at a tertiary-level maternity centre in the Western Cape. In-depth interviews were conducted with six parents: four mothers and two fathers. Data was analysed using an adaptation of the approaches described by Colaizzi (1978:48-71 and Hycner (1985:280-294. To ensure trustworthiness, the trustworthiness criteria described by Guba and Lincoln (1989:242-243 were applied. Kangaroo care is a phased process, each phase bringing a unique set of experiences. The eight themes that emerged are described: unforeseen, unprepared and uncertain - the experience of birth; anxiety and barriers; an intimate connection; adjustments, roles and responsibilities; measuring success; a network of encouragement and support; living-in challenges; and living with the infant outside of hospital. Challenges facing health care providers are described and recommendations for information about kangaroo care and support for parents are made. Opsomming Vroeggebore babas en babas met ’n lae geboortegewig stel besondere uitdagings vir Suid-Afrikaanse gesondhiedsdienste. Daar bestaan goeie bewyse dat die kangaroesorgmetode voordelig is vir babas met ’n laegeboortegewig, dog is minimale plaaslike navorsing gedoen oor die ondervindinge van ouers wat hierdie metode gebruik om vir hul vroeggebore babas te sorg. Hierdie fenomenologiese studie verken die geleefde ervaringe van ouers wat vir hulle vroeggebore babas deur middel van die kangaroesorgmetode in ’n tersiêre kraamsentrum in die Weskaap gesorg het. Data is ingesamel deur in

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

OpenAIRE

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

2013-01-01

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

Semi-implicit semi-Lagrangian modelling of the atmosphere: a Met Office perspective

Directory of Open Access Journals (Sweden)

Benacchio Tommaso

2016-09-01

Full Text Available The semi-Lagrangian numerical method, in conjunction with semi-implicit time integration, provides numerical weather prediction models with numerical stability for large time steps, accurate modes of interest, and good representation of hydrostatic and geostrophic balance. Drawing on the legacy of dynamical cores at the Met Office, the use of the semi-implicit semi-Lagrangian method in an operational numerical weather prediction context is surveyed, together with details of the solution approach and associated issues and challenges. The numerical properties and performance of the current operational version of the Met Office’s numerical model are then investigated in a simplified setting along with the impact of different modelling choices.

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

OpenAIRE

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

2008-01-01

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

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

NARCIS (Netherlands)

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

2016-01-01

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

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

Science.gov (United States)

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

2016-03-01

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

How Providing Mentoring Relates to Career Success and Organizational Commitment: A Study in the General Managerial Population

Science.gov (United States)

Bozionelos, Nikos; Bozionelos, Giorgos; Kostopoulos, Konstantinos; Polychroniou, Panagiotis

2011-01-01

Purpose: This study aims to investigate the relationship of mentoring provided with career success and organizational commitment in the general managerial population. Design/methodology/approach: Participants were 194 native British who were employed in a variety of jobs, professions and industries in the United Kingdom. Findings: Mentoring…

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

Directory of Open Access Journals (Sweden)

Maaike Hermsen

2017-06-01

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

El acertijo de la metáfora visual

OpenAIRE

De la Rosa Alzate, Adriana; Universidad Autónoma de Occidente

2016-01-01

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

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

NARCIS (Netherlands)

Boois, de I.J.

2013-01-01

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

Using data mining to predict success in a weight loss trial.

Science.gov (United States)

Batterham, M; Tapsell, L; Charlton, K; O'Shea, J; Thorne, R

2017-08-01

Traditional methods for predicting weight loss success use regression approaches, which make the assumption that the relationships between the independent and dependent (or logit of the dependent) variable are linear. The aim of the present study was to investigate the relationship between common demographic and early weight loss variables to predict weight loss success at 12 months without making this assumption. Data mining methods (decision trees, generalised additive models and multivariate adaptive regression splines), in addition to logistic regression, were employed to predict: (i) weight loss success (defined as ≥5%) at the end of a 12-month dietary intervention using demographic variables [body mass index (BMI), sex and age]; percentage weight loss at 1 month; and (iii) the difference between actual and predicted weight loss using an energy balance model. The methods were compared by assessing model parsimony and the area under the curve (AUC). The decision tree provided the most clinically useful model and had a good accuracy (AUC 0.720 95% confidence interval = 0.600-0.840). Percentage weight loss at 1 month (≥0.75%) was the strongest predictor for successful weight loss. Within those individuals losing ≥0.75%, individuals with a BMI (≥27 kg m -2 ) were more likely to be successful than those with a BMI between 25 and 27 kg m -2 . Data mining methods can provide a more accurate way of assessing relationships when conventional assumptions are not met. In the present study, a decision tree provided the most parsimonious model. Given that early weight loss cannot be predicted before randomisation, incorporating this information into a post randomisation trial design may give better weight loss results. © 2017 The British Dietetic Association Ltd.

La metáfora

DEFF Research Database (Denmark)

Agustin, Oscar Garcia

2007-01-01

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

Successful aging: considering non-biomedical constructs

Directory of Open Access Journals (Sweden)

Carver LF

2016-11-01

Full Text Available Lisa F Carver,1 Diane Buchanan2 1Department of Sociology, Queen’s University Kingston, ON, Canada; 2School of Nursing, Queen’s University Kingston, ON, Canada Objectives: Successful aging continues to be applied in a variety of contexts and is defined using a number of different constructs. Although previous reviews highlight the multidimensionality of successful aging, a few have focused exclusively on non-biomedical factors, as was done here. Methods: This scoping review searched Ovid Medline database for peer-reviewed English-language articles published between 2006 and 2015, offering a model of successful aging and involving research with older adults. Results: Seventy-two articles were reviewed. Thirty-five articles met the inclusion criteria. Common non-biomedical constructs associated with successful aging included engagement, optimism and/or positive attitude, resilience, spirituality and/or religiosity, self-efficacy and/or self-esteem, and gerotranscendence. Discussion: Successful aging is a complex process best described using a multidimensional model. Given that the majority of elders will experience illness and/or disease during the life course, public health initiatives that promote successful aging need to employ non-biomedical constructs, facilitating the inclusion of elders living with disease and/or disability. Keywords: successful aging, resilience, gerotranscendence, engagement, optimism

Metáforas metalinguísticas de Euclides da Cunha

Directory of Open Access Journals (Sweden)

Carlos Antônio Magalhães Guedelha

2016-03-01

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

MetReS, an Efficient Database for Genomic Applications.

Science.gov (United States)

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

2018-02-01

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

Role of Met Axis in Head and Neck Cancer

Energy Technology Data Exchange (ETDEWEB)

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

2013-11-26

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

Quality of information about success rates provided on assisted reproductive technology clinic websites in Australia and New Zealand.

Science.gov (United States)

Hammarberg, Karin; Prentice, Tess; Purcell, Isabelle; Johnson, Louise

2018-06-01

Many factors influence the chance of having a baby with assisted reproductive technologies (ART). A 2016 Australian Competition and Consumer Commission (ACCC) investigation concluded that ART clinics needed to improve the quality of information they provide about chance of ART success. To evaluate changes in the quality of information about success rates provided on the websites of ART clinics in Australia and New Zealand before and after the ACCC investigation. Desktop audits of websites of ART clinics in Australia and New Zealand were conducted in 2016 and 2017 and available information about success rates was scored using a matrix with eight variables and a possible range of scores of 0-9. Of the 54 clinic websites identified in 2016, 32 had unique information and were eligible to be audited. Of these, 29 were also eligible to be audited in 2017. While there was a slight improvement in the mean score from 2016 to 2017 (4.93-5.28), this was not statistically significantly different. Of the 29 clinics, 14 had the same score on both occasions, 10 had a higher and five a lower information quality score in 2017. To allow people who consider ART to make informed decisions about treatment they need comprehensive and accurate information about what treatment entails and what the likely outcomes are. As measured by a scoring matrix, most ART clinics had not improved the quality of the information about success rates following the ACCC investigation. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Public-private partnership case studies: Profiles of success in providing environmental services (September 1990)

International Nuclear Information System (INIS)

1990-09-01

The report examines 23 case studies of public-private partnerships throughout the United States. They are organized by three environmental service areas: solid waste, wastewater treatment, and drinking water. The introduction explains the types and benefits of public-private partnerships and Chapter II lists the attributes of successful partnerships. The remainder of the report emphasizes case study examples in solid waste, wastewater treatment, and drinking water. Individual chapters are devoted to each of the three environmental service areas. Each case study is presented in a similar format which provides the reader with basic information on how the partnership was formed and implemented, as well as characteristics of the community

Public-private partnership case studies: Profiles of success in providing environmental services (September 1990)

Energy Technology Data Exchange (ETDEWEB)

1990-09-01

The report examines 23 case studies of public-private partnerships throughout the United States. They are organized by three environmental service areas: solid waste, wastewater treatment, and drinking water. The introduction explains the types and benefits of public-private partnerships and Chapter II lists the attributes of successful partnerships. The remainder of the report emphasizes case study examples in solid waste, wastewater treatment, and drinking water. Individual chapters are devoted to each of the three environmental service areas. Each case study is presented in a similar format which provides the reader with basic information on how the partnership was formed and implemented, as well as characteristics of the community.

De werkzame bestanddelen van de hulpverlening aan gezinnen met meervoudige problematiek

Directory of Open Access Journals (Sweden)

Isolde Driesen

2016-09-01

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

Invloed krachtvoerniveau op vleesproduktiekenmerken van Piemontese met zwartbont kruislingstieren

NARCIS (Netherlands)

Hanekamp, W.J.A.

1989-01-01

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

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

NARCIS (Netherlands)

Pastoors, M.A.

2014-01-01

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

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

Science.gov (United States)

Parikh, Palak K; Ghate, Manjunath D

2018-01-01

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

Tracking and orbit determination performance of the GRAS instrument on MetOp-A

NARCIS (Netherlands)

Montenbruck, O.; Andres, Y.; Bock, H.; Van Helleputte, T.; Van den IJssel, J.; Loiselet, M.; Marquardt, M.; Silvestrin, P.; Visser, P.; Yoon, Y.

2008-01-01

The global navigation satellite system receiver for atmospheric sounding (GRAS) on MetOp-A is the first European GPS receiver providing dual-frequency navigation and occultation measurements from a spaceborne platform on a routine basis. The receiver is based on ESA’s AGGA-2 correlator chip, which

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

Science.gov (United States)

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

2014-06-14

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

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.

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

Science.gov (United States)

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

2013-11-01

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

Compensatory stream and wetland mitigation in North Carolina: an evaluation of regulatory success.

Science.gov (United States)

Hill, Tammy; Kulz, Eric; Munoz, Breda; Dorney, John R

2013-05-01

Data from a probability sample were used to estimate wetland and stream mitigation success from 2007 to 2009 across North Carolina (NC). "Success" was defined as whether the mitigation site met regulatory requirements in place at the time of construction. Analytical results were weighted by both component counts and mitigation size. Overall mitigation success (including preservation) was estimated at 74 % (SE = 3 %) for wetlands and 75 % (SE = 4 %) for streams in NC. Compared to the results of previous studies, wetland mitigation success rates had increased since the mid-1990s. Differences between mitigation providers (mitigation banks, NC Ecosystem Enhancement Program's design-bid-build and full-delivery programs, NC Department of Transportation and private permittee-responsible mitigation) were generally not significant although permittee-responsible mitigation yielded higher success rates in certain circumstances. Both wetland and stream preservation showed high rates of success and the stream enhancement success rate was significantly higher than that of stream restoration. Additional statistically significant differences when mitigation size was considered included: (1) the Piedmont yielded a lower stream mitigation success rate than other areas of the state, and (2) recently constructed wetland mitigation projects demonstrated a lower success rate than those built prior to 2002. Opportunities for improvement exist in the areas of regulatory record-keeping, understanding the relationship between post-construction establishment and long-term ecological trajectories of stream and wetland restoration projects, incorporation of numeric ecological metrics into mitigation monitoring and success criteria, and adaptation of stream mitigation designs to achieve greater success in the Piedmont.

Mogelijkheden om vroeg tijdig bladrandproblemen te signaleren met MIPS bij Hortensia

NARCIS (Netherlands)

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

2010-01-01

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

BioM2MetDisease: a manually curated database for associations between microRNAs, metabolites, small molecules and metabolic diseases.

Science.gov (United States)

Xu, Yanjun; Yang, Haixiu; Wu, Tan; Dong, Qun; Sun, Zeguo; Shang, Desi; Li, Feng; Xu, Yingqi; Su, Fei; Liu, Siyao; Zhang, Yunpeng; Li, Xia

2017-01-01

BioM2MetDisease is a manually curated database that aims to provide a comprehensive and experimentally supported resource of associations between metabolic diseases and various biomolecules. Recently, metabolic diseases such as diabetes have become one of the leading threats to people’s health. Metabolic disease associated with alterations of multiple types of biomolecules such as miRNAs and metabolites. An integrated and high-quality data source that collection of metabolic disease associated biomolecules is essential for exploring the underlying molecular mechanisms and discovering novel therapeutics. Here, we developed the BioM2MetDisease database, which currently documents 2681 entries of relationships between 1147 biomolecules (miRNAs, metabolites and small molecules/drugs) and 78 metabolic diseases across 14 species. Each entry includes biomolecule category, species, biomolecule name, disease name, dysregulation pattern, experimental technique, a brief description of metabolic disease-biomolecule relationships, the reference, additional annotation information etc. BioM2MetDisease provides a user-friendly interface to explore and retrieve all data conveniently. A submission page was also offered for researchers to submit new associations between biomolecules and metabolic diseases. BioM2MetDisease provides a comprehensive resource for studying biology molecules act in metabolic diseases, and it is helpful for understanding the molecular mechanisms and developing novel therapeutics for metabolic diseases. http://www.bio-bigdata.com/BioM2MetDisease/. © The Author(s) 2017. Published by Oxford University Press.

Design and Implementation of Image Research for the Columbia Mets

Science.gov (United States)

1992-01-01

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

The BDNF Val66Met polymorphism moderates the relationship between Posttraumatic Stress Disorder and fear extinction learning.

Science.gov (United States)

Felmingham, Kim L; Zuj, Daniel V; Hsu, Ken Chia Ming; Nicholson, Emma; Palmer, Matthew A; Stuart, Kimberley; Vickers, James C; Malhi, Gin S; Bryant, Richard A

2018-05-01

The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism. Moderation analyses using PROCESS examined whether BDNF genotype (Val-Val vs Met carriers) moderated the relationship between PTSD symptom severity (and diagnostic status) and skin conductance response (SCR) amplitude during fear extinction. The PTSD group displayed significantly slower fear extinction learning compared to TC and NTC in the early extinction phase. The BDNF Val66Met polymorphism moderated the relationship between PTSD and fear extinction learning, such that poorer fear extinction learning was associated with greater PTSD symptom severity (and PTSD diagnostic status) in individuals with the low-expression Met allele, but no relationship was demonstrated in individuals with the Val-Val allele. This study reveals that impaired fear extinction learning is particularly evident in individuals with PTSD who carry the low-expression BDNF Met allele and importantly not in those with the Val-Val allele. This provides novel evidence of a link between BDNF and impaired fear extinction learning in PTSD, which may contribute to poorer response to exposure therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Na Song

2014-04-01

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

Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and induces cholestatic liver damage by aggravating oxidative stress

International Nuclear Information System (INIS)

Gomez-Quiroz, Luis E.; Seo, Daekwan; Lee, Yun-Han; Kitade, Mitsuteru; Gaiser, Timo; Gillen, Matthew; Lee, Seung-Bum; Gutierrez-Ruiz, Ma Concepcion; Conner, Elizabeth A.; Factor, Valentina M; Thorgeirsson, Snorri S.; Marquardt, Jens U.

2016-01-01

Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting. Loss of c-Met signaling amplified the extent of liver injury in MetKO mice fed with high-cholesterol diet for 30 days as evidenced by upregulation of liver enzymes and increased synthesis of total bile acids, aggravated inflammatory response and enhanced intrahepatic lipid deposition. Global transcriptomic changes confirmed the enrichment of networks involved in steatosis and cholestasis. In addition, signaling pathways related to glutathione and lipid metabolism, oxidative stress and mitochondria dysfunction were significantly affected by the loss of c-Met function. Mechanistically, exacerbation of oxidative stress in MetKO livers was corroborated by increased lipid and protein oxidation. Western blot analysis further revealed suppression of Erk, NF-kB and Nrf2 survival pathways and downstream target genes (e.g. cyclin D1, SOD1, gamma-GCS), as well as up-regulation of proapoptotic signaling (e.g. p53, caspase 3). Consistent with the observed steatotic and cholestatic phenotype, nuclear receptors RAR, RXR showed increased activation while expression levels of CAR, FXR and PPAR-alpha were decreased in MetKO. Collectively, our data provide evidence for the critical involvement of c-Met signaling in cholesterol and bile acids toxicity.

A Comparative Study of virtual and operational met mast data

International Nuclear Information System (INIS)

Orhan, Dr Ö Emre; Ahmet, Gökhan

2014-01-01

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

The 20S proteasome splicing activity discovered by SpliceMet.

Directory of Open Access Journals (Sweden)

Juliane Liepe

2010-06-01

Full Text Available The identification of proteasome-generated spliced peptides (PSP revealed a new unpredicted activity of the major cellular protease. However, so far characterization of PSP was entirely dependent on the availability of patient-derived cytotoxic CD8+ T lymphocytes (CTL thus preventing a systematic investigation of proteasome-catalyzed peptide splicing (PCPS. For an unrestricted PSP identification we here developed SpliceMet, combining the computer-based algorithm ProteaJ with in vitro proteasomal degradation assays and mass spectrometry. By applying SpliceMet for the analysis of proteasomal processing products of four different substrate polypeptides, derived from human tumor as well as viral antigens, we identified fifteen new spliced peptides generated by PCPS either by cis or from two separate substrate molecules, i.e., by trans splicing. Our data suggest that 20S proteasomes represent a molecular machine that, due to its catalytic and structural properties, facilitates the generation of spliced peptides, thereby providing a pool of qualitatively new peptides from which functionally relevant products may be selected.

Providing information and enabling transactions: which website function is more important for success?

NARCIS (Netherlands)

Hoekstra, Janny C.; Huizingh, Eelko K.R.E.; Bijmolt, Tammo H.A.; Krawczyk, Adriana

2015-01-01

In this study, we propose and test a chain of effects from website content, through informational and transactional success to overall website success and company performance. This framework enables us to determine the relative importance of the informational and transaction-related website

MetWAMer: eukaryotic translation initiation site prediction

Directory of Open Access Journals (Sweden)

Brendel Volker

2008-09-01

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

The Model for Understanding Success in Quality (MUSIQ): building a theory of context in healthcare quality improvement.

Science.gov (United States)

Kaplan, Heather C; Provost, Lloyd P; Froehle, Craig M; Margolis, Peter A

2012-01-01

BACKGROUND Quality improvement (QI) efforts have become widespread in healthcare, however there is significant variability in their success. Differences in context are thought to be responsible for some of the variability seen. To develop a conceptual model that can be used by organisations and QI researchers to understand and optimise contextual factors affecting the success of a QI project. 10 QI experts were provided with the results of a systematic literature review and then participated in two rounds of opinion gathering to identify and define important contextual factors. The experts subsequently met in person to identify relationships among factors and to begin to build the model. The Model for Understanding Success in Quality (MUSIQ) is organised based on the level of the healthcare system and identifies 25 contextual factors likely to influence QI success. Contextual factors within microsystems and those related to the QI team are hypothesised to directly shape QI success, whereas factors within the organisation and external environment are believed to influence success indirectly. The MUSIQ framework has the potential to guide the application of QI methods in healthcare and focus research. The specificity of MUSIQ and the explicit delineation of relationships among factors allows a deeper understanding of the mechanism of action by which context influences QI success. MUSIQ also provides a foundation to support further studies to test and refine the theory and advance the field of QI science.

Collegiate Schemas: The Influence of Institutional Met Expectations on Tenure-Track Faculty Job Satisfaction

Science.gov (United States)

Pontius, Jason Lewis

2012-01-01

"Met expectations" research into job satisfaction (Locke, 1976; Porter & Steers, 1973) has shown that the expectations employees bring to their jobs influence their overall job satisfaction. At colleges and universities, faculty job satisfaction is important because it can provide a measure of overall institutional effectiveness…

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

DEFF Research Database (Denmark)

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

2016-01-01

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

OTULIN antagonizes LUBAC signaling by specifically hydrolyzing met1-linked polyubiquitin

DEFF Research Database (Denmark)

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

2013-01-01

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

Distinct projection targets define subpopulations of mouse brainstem vagal neurons that express the autism-associated MET receptor tyrosine kinase.

Science.gov (United States)

Kamitakahara, Anna; Wu, Hsiao-Huei; Levitt, Pat

2017-12-15

Detailed anatomical tracing and mapping of the viscerotopic organization of the vagal motor nuclei has provided insight into autonomic function in health and disease. To further define specific cellular identities, we paired information based on visceral connectivity with a cell-type specific marker of a subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (nAmb) that express the autism-associated MET receptor tyrosine kinase. As gastrointestinal disturbances are common in children with autism spectrum disorder (ASD), we sought to define the relationship between MET-expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract. Using wholemount tissue staining and clearing, or retrograde tracing in a MET EGFP transgenic mouse, we identify three novel subpopulations of EGFP+ vagal brainstem neurons: (a) EGFP+ neurons in the nAmb projecting to the esophagus or laryngeal muscles, (b) EGFP+ neurons in the medial DMV projecting to the stomach, and (b) EGFP+ neurons in the lateral DMV projecting to the cecum and/or proximal colon. Expression of the MET ligand, hepatocyte growth factor (HGF), by tissues innervated by vagal motor neurons during fetal development reveal potential sites of HGF-MET interaction. Furthermore, similar cellular expression patterns of MET in the brainstem of both the mouse and nonhuman primate suggests that MET expression at these sites is evolutionarily conserved. Together, the data suggest that MET+ neurons in the brainstem vagal motor nuclei are anatomically positioned to regulate distinct portions of the gastrointestinal tract, with implications for the pathophysiology of gastrointestinal comorbidities of ASD. © 2017 Wiley Periodicals, Inc.

De Doop met de Heilige Geest

Directory of Open Access Journals (Sweden)

S. C.W. Duvenage.

1965-03-01

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

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

Science.gov (United States)

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

2018-03-02

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

Role of cMET in the Development and Progression of Colorectal Cancer

Directory of Open Access Journals (Sweden)

Ilaria Bossi

2013-09-01

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

Fosfaatwerking ogranische meststoffen vergelijkbaar met kunstmest

NARCIS (Netherlands)

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

2000-01-01

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

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

Science.gov (United States)

2018-04-01

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

Rocket experiment METS - Microwave Energy Transmission in Space

Science.gov (United States)

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

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

Rocket experiment METS Microwave Energy Transmission in Space

Science.gov (United States)

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

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

'Epistemology models ontology'− In gesprek met John Polkinghorne

African Journals Online (AJOL)

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

CRITICAL SUCCESS FACTORS FOR BROWN-FIELD CAPITAL AND RENEWAL PROJECTS

Directory of Open Access Journals (Sweden)

J. Warchol

2012-01-01

Full Text Available

ENGLISH ABSTRACT: Manufacturing companies operate in a business environment where incremental growth may be achieved through expansion and renewal of existing plant and facilities. Effective management of the critical success factors of such capital development projects may also provide competitive advantage. These projects tend to be of a brown-field nature, characterised by a significant level of risk arising from the interaction between the project implementation and concurrent operation of the existing physical asset base. So it is vital to understand the factors that influence the success of capital expansion and renewal projects in the brown-field context. Although each project has unique features, there are critical success factors that can be customised for successful outcomes in the brown-field environment. This study identifies five critical success factors applicable to brown-field capital expansion and renewal projects. Managerial focus on the critical factors, and the prospects for successful brown-field projects, are discussed in the paper.

AFRIKAANSE OPSOMMING: Vervaardigers funksioneer in ‘n sakeomgewing waar voortgesette groei bereik word via uitbreiding en hernuwing van bestaande fasiliteite. Die doeltreffende bestuur van kritiese suksesfaktore van sodanige kapitaalprojekte bied geleentheid vir mededingende voordeel. Projekte van hierdie aard neig om geklassifiseer te word as van herontwikkelingsaard, met betekenisvolle gepaardgaande risiko wat voortspruit uit die interaksie tussen projekimplementering en gelyktydige bedryf van bestaande fisiese bates. Derhalwe is dit belangrik om in die konteks van herontwikkeling aandag te gee aan die kritiese faktore wat ‘n rol speel in die bereiking van sukses. Die navorsing identifiseer vyf kritiese suksesfaktore van belang vir uitbreidings- en vernuwingsprojekte.

The applications of 11C-MET PET in brain tumor

International Nuclear Information System (INIS)

Hua Fengchun

2002-01-01

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

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

Bio-composiet : Thermoplastische kunsstof met natuurvezels

NARCIS (Netherlands)

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

2013-01-01

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

Technisch lego met een Duplo-interface

NARCIS (Netherlands)

Pimentel, A.; Schipper, D.

2008-01-01

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

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.

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

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

2006-03-01

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

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

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

2015-06-03

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

BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity.

Science.gov (United States)

Notaras, Michael J; Hill, Rachel A; Gogos, Joseph A; van den Buuse, Maarten

2017-05-01

Reduced expression of Brain-Derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of schizophrenia. The BDNF Val66Met polymorphism, which results in deficient activity-dependent secretion of BDNF, is associated with clinical features of schizophrenia. We investigated the effect of this polymorphism on Prepulse Inhibition (PPI), a translational model of sensorimotor gating which is disrupted in schizophrenia. We utilized humanized BDNFVal66Met (hBDNFVal66Met) mice which have been modified to carry the Val66Met polymorphism, as well as express humanized BDNF in vivo. We also studied the long-term effect of chronic corticosterone (CORT) exposure in these animals as a model of history of stress. PPI was assessed at 30ms and 100ms interstimulus intervals (ISI). Analysis of PPI at the commonly used 100ms ISI identified that, irrespective of CORT treatment, the hBDNFVal/Met genotype was associated with significantly reduced PPI. In contrast, PPI was not different between hBDNFMet/Met and hBDNFVal/Val genotype mice. At the 30ms ISI, CORT treatment selectively disrupted sensorimotor gating of hBDNFVal/Met heterozygote mice but not hBDNFVal/Val or hBDNFMet/Met mice. Analysis of startle reactivity revealed that chronic CORT reduced startle reactivity of hBDNFVal/Val male mice by 51%. However, this was independent of the effect of CORT on PPI. In summary, we provide evidence of a distinct BDNFVal66Met heterozygote-specific phenotype using the sensorimotor gating endophenotype of schizophrenia. These data have important implications for clinical studies where, if possible, the BDNFVal/Met heterozygote genotype should be distinguished from the BDNFMet/Met genotype. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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...

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

Directory of Open Access Journals (Sweden)

Parikh RA

2014-06-01

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

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

Science.gov (United States)

2010-01-07

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

Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

Science.gov (United States)

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

2017-05-30

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

MetExploreViz: web component for interactive metabolic network visualization.

Science.gov (United States)

Chazalviel, Maxime; Frainay, Clément; Poupin, Nathalie; Vinson, Florence; Merlet, Benjamin; Gloaguen, Yoann; Cottret, Ludovic; Jourdan, Fabien

2017-09-15

MetExploreViz is an open source web component that can be easily embedded in any web site. It provides features dedicated to the visualization of metabolic networks and pathways and thus offers a flexible solution to analyze omics data in a biochemical context. Documentation and link to GIT code repository (GPL 3.0 license)are available at this URL: http://metexplore.toulouse.inra.fr/metexploreViz/doc /. Tutorial is available at this URL. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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

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

2017-10-01

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

Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy: a Meta-analysis

Science.gov (United States)

Li, Hai-feng; Zou, Yan; Ding, Gangqiang

2013-01-01

Objective To systematically evaluate therapeutic success of the ketogenic diet (KD) as a treatment option for epilepsy. Methods Using MEDLINE and Google Scholar search, we searched for studies investigating the therapeutic success of ketogenic diet for epilepsy. We estimated therapeutic success rate for ketogenic diet as a treatment option for epilepsy and its 95% CIs using generic inverse variance method. Findings A total of 38 studies met the inclusion criteria. In retrospective studies, the weighted success rate of the patients who take the KD as a treatment option for epilepsy was 58.4% (95% confidence interval (95%CI)=48.7% – 69.9%) at 3 months (n=336); 42.8% (95%CI =36.3% – 50.3%) at 6 months (n=492), and 30.1% (95%CI =24.3% – 37.2%) at 12 months (n=387); in prospective studies, weighted success rate was 53.9% (95%CI 45.5% – 63.8%) at 3 months (n=474); 53.2% (95%CI =44.0% – 64.2%) at 6 months (n=321), and 55.0% (95%CI =45.9% – 65.9%) at 12 months (n=347). Conclusion This meta-analysis provides formal statistical support for the efficacy of the ketogenic diet in the treatment of epileptic patients. PMID:24910737

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders

Directory of Open Access Journals (Sweden)

Shih-Jen Tsai

2018-05-01

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

Activating mutation in MET oncogene in familial colorectal cancer

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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

Varroabestrijding met bijenbroed als mijtenval (2)

NARCIS (Netherlands)

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

1994-01-01

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

Groen proceswater: zuivering brouwerijprocesafvalwater met microalgen

NARCIS (Netherlands)

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

2016-01-01

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

Risicoanalyse voor buisleidingen met brandbare vloeistoffen

NARCIS (Netherlands)

van Vliet AAC; Laheij GMH; Wolting AG; CEV

2006-01-01

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

El sexo de las metáforas

Directory of Open Access Journals (Sweden)

Pérez Sedeño, Eulalia

2011-02-01

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

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

MetAssimulo:Simulation of Realistic NMR Metabolic Profiles

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De Iorio Maria

2010-10-01

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

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

Science.gov (United States)

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

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

Self-perceived met and unmet care needs of frail older adults in primary care

NARCIS (Netherlands)

Hoogendijk, Emiel O; Muntinga, Maaike E; van Leeuwen, Karen M; van der Horst, Henriëtte E; Deeg, Dorly J H; Frijters, Dinnus H M; Hermsen, Lotte A H; Jansen, Aaltje P D; Nijpels, Giel; van Hout, Hein P J

2013-01-01

In order to provide adequate care for frail older adults in primary care it is essential to have insight into their care needs. Our aim was to describe the met and unmet care needs as perceived by frail older adults using a multi-dimensional needs assessment, and to explore their associations with

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism interacts with gender to influence cortisol responses to mental stress.

Science.gov (United States)

Jiang, Rong; Babyak, Michael A; Brummett, Beverly H; Siegler, Ilene C; Kuhn, Cynthia M; Williams, Redford B

2017-05-01

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with cortisol responses to stress with gender differences reported, although the findings are not entirely consistent. To evaluate the role of Val66Met genotype and gender on cortisol responses to stress, we conducted a 45-min mental stress protocol including four tasks and four rest periods. Blood cortisol was collected for assay immediately before and after each task and rest period. A significant two-way interaction of Val66Met genotype×gender (P=0.022) was observed on the total area under the curve (AUC), a total cortisol response over time, such that the Val/Val genotype was associated with a larger cortisol response to stress as compared to the Met group in women but not in men. Further contrast analyses between the Val/Val and Met group for each stress task showed a similar increased cortisol pattern among women Val/Val genotype but not among men. The present findings indicate the gender differences in the effect of Val66Met genotype on the cortisol responses to stress protocol, and extend the evidence for the importance of gender and the role of Val66Met in the modulation of stress reactivity and subsequent depression prevalence. Further studies and the underlying mechanism need to be investigated, which may provide an insight for prevention, intervention, and treatment strategies that target those at high risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cobalamin-Independent Methionine Synthase (MetE): A Face-to-Face Double Barrel that Evolved by Gene Duplication

Energy Technology Data Exchange (ETDEWEB)

Pejcha, Robert; Ludwig, Martha L. (Michigan)

2010-03-08

Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two ({beta}{alpha}){sub 8} barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys){sub 3}Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E {center_dot} Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

Cobalamin-Independent Methionine Synthase (MetE): A Face-to-Face Double Barrel that Evolved by Gene Duplication

International Nuclear Information System (INIS)

Pejcha, Robert; Ludwig, Martha L.

2005-01-01

Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two (βα) 8 barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys) 3 Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E · Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

Cobalamin-independent methionine synthase (MetE: a face-to-face double barrel that evolved by gene duplication.

Directory of Open Access Journals (Sweden)

Robert Pejchal

2005-02-01

Full Text Available Cobalamin-independent methionine synthase (MetE catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH, both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two (betaalpha(8 barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys(3Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E.Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

Management competences become key factor for success. Competition market energy; Managementkompetenzen werden Schluesselfaktor fuer Erfolg. Wettbewerbsmarkt Energie

Energy Technology Data Exchange (ETDEWEB)

Bausch, A. [Allgemeine Betriebswirtschaftlehre/Internationales Management, Friedrich-Schiller-Univ. Jena (Germany); Strategisches Management und Controlling, Jacobs Univ. Bremen (Germany); Fritz, T. [Jacobs University Bremen (Germany); Werthschulte, S.; Schumacher, T.; Holst, A.; Schiegg, T. [Accenture GmbH (Germany)

2007-07-09

In view of deregulation, enhanced competition and a multitude of options for action, clear strategic positioning and a strong operative management have become key factors of success. The authors of the study 'Value Creator III' investigated the approaches that made current industrial leaders successful and the challenges to be met in the future. (orig.)

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.

Betere en efficiëntere zorg met Lean Six Sigma

NARCIS (Netherlands)

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

2009-01-01

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

Surgical treatment for obesity: ensuring success.

Science.gov (United States)

Andris, Deborah A

2005-01-01

In the United States, obesity has reached epidemic proportions. Serious medical complications, impaired quality of life, and premature mortality are all associated with obesity. Medical conditions such as type 2 diabetes mellitus, hypertension, hyperlipidemia, or sleep apnea can improve or be cured with weight loss. Medical treatment programs focused on diet, behavior modification, and/or pharmacologic intervention have met with limited long-term success. Although surgical treatments for obesity have become popular in recent years, they should only be used as a last resort for weight loss. Not all patients can be considered appropriate candidates for surgery; therefore, guidelines based on criteria from the National Institutes of Health should be used preoperatively to help identify suitable persons. Most individuals who opt for weight-loss surgery have usually struggled for many years with losing weight and keeping it off, but surgery alone will not ensure successful weight loss. Patient education is imperative for long-term success. Moreover, any such educational regimen should include information on diet, vitamin and mineral supplementation, and lifestyle changes, as well as expected weight-loss results and improvements in comorbid conditions. Patients must be willing to commit to a long-term follow-up program intended to promote successful weight loss and weight maintenance and to prevent metabolic and nutritional complications.

Synthesis of Tc-99m labeled 1,2,3-triazole-4-yl c-met binding peptide as a potential c-met receptor kinase positive tumor imaging agent.

Science.gov (United States)

Kim, Eun-Mi; Joung, Min-Hee; Lee, Chang-Moon; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee; Kim, Dong Wook

2010-07-15

The mesenchymal-epithelial transition factor (c-Met), which is related to tumor cell growth, angiogenesis and metastases, is known to be overexpressed in several tumor types. In this study, we synthesized technetium-99m labeled 1,2,3-triazole-4-yl c-Met binding peptide (cMBP) derivatives, prepared by solid phase peptide synthesis and the 'click-to-chelate' protocol for the introduction of tricarbonyl technetium-99m, as a potential c-Met receptor kinase positive tumor imaging agent, and evaluated their in vitro c-Met binding affinity, cellular uptake, and stability. The (99m)Tc labeled cMBP derivatives ([(99m)Tc(CO)(3)]12, [(99m)Tc(CO)(3)]13, and [(99m)Tc(CO)(3)]14) were prepared in 85-90% radiochemical yields. The cold surrogate cMBP derivatives, [Re(CO)(3)]12, [Re(CO)(3)]13, and [Re(CO)(3)]14, were shown to have high binding affinities (0.13 microM, 0.06 microM, and 0.16 microM, respectively) to a purified cMet/Fc chimeric recombinant protein. In addition, the in vitro cellular uptake and inhibition studies demonstrated the high specific binding of these (99m)Tc labeled cMBP derivatives ([(99m)Tc(CO)(3)]12-14) to c-Met receptor positive U87MG cells. 2010 Elsevier Ltd. All rights reserved.

Interview met Leon Deben: van tegenstellingen leer je het meeste

NARCIS (Netherlands)

van Diepen, A.; Huisman, C.

2008-01-01

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

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

NARCIS (Netherlands)

Voogd, Joanna Bernarda

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

Synergistic role of Sprouty2 inactivation and c-Met up-regulation in mouse and human hepatocarcinogenesis.

Science.gov (United States)

Lee, Susie A; Ladu, Sara; Evert, Matthias; Dombrowski, Frank; De Murtas, Valentina; Chen, Xin; Calvisi, Diego F

2010-08-01

Sprouty2 (Spry2), a negative feedback regulator of the Ras/mitogen-activated protein kinase (MAPK) pathway, is frequently down-regulated in human hepatocellular carcinoma (HCC). We tested the hypothesis that loss of Spry2 cooperates with unconstrained activation of the c-Met protooncogene to induce hepatocarcinogenesis via in vitro and in vivo approaches. We found coordinated down-regulation of Spry2 protein expression and activation of c-Met as well as its downstream effectors extracellular signal-regulated kinase (ERK) and v-akt murine thymoma viral oncogene homolog (AKT) in a subset of human HCC samples with poor outcome. Mechanistic studies revealed that Spry2 function is disrupted in human HCC via multiple mechanisms at both transcriptional and post-transcriptional level, including promoter hypermethylation, loss of heterozygosity, and proteosomal degradation by neural precursor cell expressed, developmentally down-regulated 4 (NEDD4). In HCC cell lines, Spry2 overexpression inhibits c-Met-induced cell proliferation as well as ERK and AKT activation, whereas loss of Spry2 potentiates c-Met signaling. Most importantly, we show that blocking Spry2 activity via a dominant negative form of Spry2 cooperates with c-Met to promote hepatocarcinogenesis in the mouse liver by sustaining proliferation and angiogenesis. The tumors exhibited high levels of activated ERK and AKT, recapitulating the subgroup of human HCC with a clinically aggressive phenotype. The occurrence of frequent genetic, epigenetic, and biochemical events leading to Spry2 inactivation provides solid evidence that Spry2 functions as a tumor suppressor gene in liver cancer. Coordinated deregulation of Spry2 and c-Met signaling may be a pivotal oncogenic mechanism responsible for unrestrained activation of ERK and AKT pathways in human hepatocarcinogenesis.

Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

Science.gov (United States)

Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

2017-05-11

During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.

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

Science.gov (United States)

Valladares, Maya

2017-01-01

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

MET Signaling Mediates Intestinal Crypt-Villus Development, Regeneration, and Adenoma Formation and Is Promoted by Stem Cell CD44 Isoforms.

Science.gov (United States)

Joosten, Sander P J; Zeilstra, Jurrit; van Andel, Harmen; Mijnals, R Clinton; Zaunbrecher, Joost; Duivenvoorden, Annet A M; van de Wetering, Marc; Clevers, Hans; Spaargaren, Marcel; Pals, Steven T

2017-10-01

/Met fl/fl /LacZ mice. Lgr5 Creert2 /Met fl/fl /LacZ mice had impaired regeneration of MET-deficient ISCs. Adenoma organoids stimulated with EGF or HGF expanded to almost twice the size of nonstimulated organoids. MET-deficient adenoma organoids did not respond to HGF stimulation, but did respond to EGF. ISC-specific disruption of Met (Lgr5 Creert2 /Met fl/fl /Apc fl/fl mice) caused a twofold increase in apoptosis in microadenomas, resulting in an approximately 50% reduction of microadenoma numbers and significantly reduced average adenoma size. Total epithelial disruption of Met (Ah Cre /Met fl/fl /Apc fl/+ mice) resulted in an approximate 50% reduction in (micro)adenoma numbers. Intestinal crypts from Cd44 -/- mice did not expand to the same extent as crypts from Cd44 +/+ mice on stimulation with HGF, but had the same response to EGF. The negative effect on HGF-mediated growth was overcome by expression of CD44v4-10, but not by CD44s. Similarly, HGF-mediated expansion of adenoma organoids required CD44v4-10. In studies of intestinal organoid cultures and mice with inducible deletion of MET, we found HGF receptor signaling to regulate intestinal homeostasis and regeneration, as well as adenoma formation. These activities of MET are promoted by the stem cell CD44 isoform CD44v4-10. Our findings provide rationale for targeting signaling via MET and CD44 during anti-EGF receptor therapy of patients with colorectal cancer or in patients resistant to EGF receptor inhibitors. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

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

Index Scriptorium Estoniae

Kurvits, Roosmarii, 1969-

2015-01-01

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

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

Science.gov (United States)

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

1997-05-15

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

Intern transport beter te plannen met computer

NARCIS (Netherlands)

Annevelink, E.

1999-01-01

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

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

NARCIS (Netherlands)

Pater, Mathieu; van Yperen, Tom

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

Beeldverwerking met de Micron Automatic Processor

OpenAIRE

Goyens, Frank

2017-01-01

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

Remembering the early days of the Met Lab

International Nuclear Information System (INIS)

Katz, J.J.

1990-01-01

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

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

Science.gov (United States)

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

2018-06-01

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

MetClass: A software for the visualization and exploitation of Dill's (2010) "chessboard" classification of mineral deposits

Science.gov (United States)

Kaabeche, Hamza; Chabou, Moulley Charaf; Bendaoud, Abderrahmane; Bodinier, Jean-Louis; Lobry, Olivier; Retif, Fabien

2016-06-01

Rising economic value of a large number of metals as a result of their importance for new technologies and industrial development has renewed worldwide interest for mineral exploration and detailed studies of ore deposits. The Dill's (2010) "chessboard" classification of mineral deposits is the most recent attempt to provide an exhaustive overview of all mineral deposits known to date. However, the voluminous Dills review paper is accessible only in print or as PDF file. In this article, we present MetClass, software that provides advanced solutions to perform efficient research and statistics using Dill's classification and the related database. MetClass allows to assemble all results relevant to a given ore deposit on a user-friendly interface. This software is therefore a valuable tool for mineral exploration and research on ore deposits, as well as an educational solution for students in metallogeny.

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

Science.gov (United States)

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

2012-03-01

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

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

Science.gov (United States)

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

2008-01-01

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

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

Science.gov (United States)

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

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

Peyda Korhan

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

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

NARCIS (Netherlands)

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

2008-01-01

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

Variant BDNF Val66Met polymorphism affects extinction of conditioned aversive memory.

Science.gov (United States)

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

2009-04-01

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

Critical success factors for BOT electric power projects in China: Thermal power versus wind power

Energy Technology Data Exchange (ETDEWEB)

Zhao, Zhen-Yu. [School of Business Administration, North China Electric Power University, Beijing 102206 (China); Zuo, Jian; Zillante, George [School of Natural and Built Environments, University of South Australia, Adelaide 5001 (Australia); Wang, Xin-Wei [Shandong Nuclear Power Equipment Manufacturing Co. Ltd, Haiyang, Shandong 265118 (China)

2010-06-15

Chinese electric power industry has adopted Build-Operate-Transfer (BOT) approach in a number of projects to alleviate the pressure of sole state-owned investment. The Chinese government has taken enormous efforts to create an environment to facilitate the application of BOT approach in electric power projects. Moreover, the growing attention on the sustainability issues puts the traditional major source of electricity - thermal power project under more strict scrutiny. As a result, various renewable energy projects, particularly the wind power projects have involved private sector funds. Both thermal power and wind power projects via BOT approach have met with a varying degree of success. Therefore, it is imperative to understand the factors contributing towards the success of both types of BOT power projects. Using an extensive literature survey, this paper identifies 31 success factors under 5 categories for Chinese BOT electric power projects. This is followed by a questionnaire survey to exam relative significance of these factors. The results reveal the different levels of significance of success factors for BOT thermal power projects versus wind power projects. Finally, survey results were analyzed to explore the underlying construction and distributions among the identified success factors. This study provides a valuable reference for all involved parties that are interested in developing BOT electric power projects in China. (author)

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

Something's Wrong Here and It's Not Me: Challenging the Dilemmas that Block Girls' Success.

Science.gov (United States)

Bell, Lee Anne

1989-01-01

A group of high-potential girls in grades three-six met with researchers to discuss internal barriers to female achievement. Dilemmas identified as blocking girls' success in school included: smart versus social, silence versus bragging, failure versus perfection, media beauty versus marginality, passive versus aggressive, conforming versus being…

Gesloten kringloop met omgekeerde osmose of membraandestilatie

NARCIS (Netherlands)

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

2011-01-01

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

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.

Recurrent MET fusion genes represent a drug target in pediatric glioblastoma

DEFF Research Database (Denmark)

Sehested, Astrid Marie

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Zhao Y

2015-08-01

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

Proefwonen voor mensen met een verstandelijke beperking en/of psychiatrische problemen

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Liesbeth Naessens

2015-09-01

Full Text Available SUMMARY Trying to live independently: social rented housing with support for vulnerable target groups In October 2010, the Flemish Ministers for Welfare and for Housing launched a joint call for experimental projects to improve cooperation between social care services and social rented housing providers. The selected projects were also encouraged to explore legal barriers. The “Proefwonen” project aimed to provide a solution to several difficulties that can stand in the way of successful cooperation between welfare and social renting services: (1 waiting lists for social housing services, which can prevent the smooth transition of a person with intellectual and/or psychological problems into a residential setting and an independent life with support in situations where the right timing is crucial; (2 there are few options for “trying out” independent living and taking a step back if necessary, two conditions for de-institutionalization; and (3 social rented housing providers have to work with vulnerable clients, but do not have the means to support them. In some cases, this may even lead to eviction.The “Proefwonen” project aims to facilitate access to social renting for two vulnerable groups - people with mild to moderate intellectual disabilities/learning difficulties and/or people with mental health issues - by providing a solution to the difficulties described above, which prevent many of these service users from living independently.Through closer collaboration and regular meetings between providers of housing and social services, the project aims to facilitate the transition and prevent evictions. The objective is to achieve structural cooperation and to lay a basis for mutual trust. Consensus and careful deliberation between the partners are essential to work towards community care and deinstitutionalization.In the project, social care service users can apply for social rented housing in combination with mobile support. The

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.

Association of BDNF Val66Met Polymorphism and Brain BDNF levels with Major Depression and Suicide.

Science.gov (United States)

Youssef, Mariam M; Underwood, Mark D; Huang, Yung-Yu; Hsiung, Shu-Chi; Liu, Yan; Simpson, Norman R; Bakalian, Mihran J; Rosoklija, Gorazd B; Dwork, Andrew J; Arango, Victoria; Mann, J John

2018-02-08

Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depressive disorder (MDD) and suicide. Both are partly caused by early life adversity (ELA) and ELA reduces BDNF protein levels. This study examines the association of BDNF Val66Met polymorphism and brain BDNF levels with depression and suicide. We hypothesized that both MDD and ELA would be associated with the Met allele and lower brain BDNF levels. Such an association would be consistent with low BDNF mediating the effect of ELA on adulthood suicide and MDD. BDNF Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 non-suicides. Additionally, BDNF protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9; BA9), anterior cingulate cortex (ACC, BA24), caudal brainstem and rostral brainstem. The relationships between these measures and MDD, death by suicide and reported ELA were examined. Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower BDNF levels in ACC and caudal brainstem compared with non-depressed subjects. No effect of history of suicide death or ELA was observed with genotype, but lower BDNF levels in ACC were found in subjects who had been exposed to ELA and/or died by suicide compared to non-suicide decedents and no reported ELA. This study provides further evidence implicating low brain BDNF and the BDNF Met allele in major depression risk. Future studies should seek to determine how altered BDNF expression contributes to depression and suicide. © The Author(s) 2018. Published by Oxford University Press on behalf of CINP.

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

Directory of Open Access Journals (Sweden)

Rosa Elise C

2010-09-01

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

From big data analysis in the cloud to robotic pot drumming: tales from the Met Office Informatics Lab

Science.gov (United States)

Robinson, Niall; Tomlinson, Jacob; Prudden, Rachel; Hilson, Alex; Arribas, Alberto

2017-04-01

The Met Office Informatics Lab is a small multidisciplinary team which sits between science, technology and design. Our mission is simply "to make Met Office data useful" - a deliberately broad objective. Our prototypes often trial cutting edge technologies, and so far have included projects such as virtual reality data visualisation in the web browser, bots and natural language interfaces, and artificially intelligent weather warnings. In this talk we focus on our latest project, Jade, a big data analysis platform in the cloud. It is a powerful, flexible and simple to use implementation which makes extensive use of technologies such as Jupyter, Dask, containerisation, Infrastructure as Code, and auto-scaling. Crucially, Jade is flexible enough to be used for a diverse set of applications: it can present weather forecast information to meteorologists and allow climate scientists to analyse big data sets, but it is also effective for analysing non-geospatial data. As well as making data useful, the Informatics Lab also trials new working practises. In this presentation, we will talk about our experience of making a group like the Lab successful.

Vigas de madera laminada Glulam reforzadas con pletinas metálicas dentadas

OpenAIRE

Cañola, Hernán Darío

2015-01-01

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

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

Science.gov (United States)

New Teacher Project, 2012

2012-01-01

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

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.

MET-RODOS: A comprehensive atmospheric dispersion module

DEFF Research Database (Denmark)

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

1997-01-01

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

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

Science.gov (United States)

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

2007-05-01

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

The CFTR Met 470 allele is associated with lower birth rates in fertile men from a population isolate.

Directory of Open Access Journals (Sweden)

Gülüm Kosova

2010-06-01

Full Text Available Although little is known about the role of the cystic fibrosis transmembrane regulator (CFTR gene in reproductive physiology, numerous variants in this gene have been implicated in etiology of male infertility due to congenital bilateral absence of the vas deferens (CBAVD. Here, we studied the fertility effects of three CBAVD-associated CFTR polymorphisms, the (TGm and polyT repeat polymorphisms in intron 8 and Met470Val in exon 10, in healthy men of European descent. Homozygosity for the Met470 allele was associated with lower birth rates, defined as the number of births per year of marriage (P = 0.0029. The Met470Val locus explained 4.36% of the phenotypic variance in birth rate, and men homozygous for the Met470 allele had 0.56 fewer children on average compared to Val470 carrier men. The derived Val470 allele occurs at high frequencies in non-African populations (allele frequency = 0.51 in HapMap CEU, whereas it is very rare in African population (Fst = 0.43 between HapMap CEU and YRI. In addition, haplotypes bearing Val470 show a lack of genetic diversity and are thus longer than haplotypes bearing Met470 (measured by an integrated haplotype score [iHS] of -1.93 in HapMap CEU. The fraction of SNPs in the HapMap Phase2 data set with more extreme Fst and iHS measures is 0.003, consistent with a selective sweep outside of Africa. The fertility advantage conferred by Val470 relative to Met470 may provide a selective mechanism for these population genetic observations.

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

Science.gov (United States)

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

1999-02-01

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

La metáfora como proceso cognitivo

Directory of Open Access Journals (Sweden)

Luz Amparo Fajardo Uribe

2006-01-01

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

More with thermal energy storage. Report 1. Coupling with policy. Coupling of research results MMB with policy aspects. Final report; Meer met bodemenergie. Rapport 1. Koppeling met beleid. Koppeling onderzoeksresultaten MMB met beleidsaspecten. Eindrapport

Energy Technology Data Exchange (ETDEWEB)

Luitwieler, M. [Bioclear, Groningen (Netherlands); Van Beek, D.; De Boer, S.; Koenders, M. [IF Technology, Arnhem (Netherlands)

2012-06-25

The project More With Thermal Energy Storage (MMB, abbreviated in Dutch) focuses on knowledge gaps and potential opportunities regarding open systems. The main questions to be answered are: (1) What effects (hydrological, thermal, microbiological and chemical) occur in the soil system by application of thermal energy storage; (2) Which technical options are available for a sustainable integration of thermal energy storage in the water and energy chain?; (3) Is it possible to achieve multiple objectives by using smart combinations? The project is organized in different work packages. In work package 2, the effects of individual and collective thermal energy storage storage systems on subsoils and the environment are determined. In work package 3 the opportunities for thermal energy storage and soil remediation are examined, while in work package 4 the focus is on new sustainable combinations of heat and cold storage. Work package is the umbrella part where communication and policy of and participation in MMB are the main subjects. This final report provides (a) an overview of the activities that have taken place in the context of work package 1, (b) the results of the other work packages in the light of four policy frameworks, and (c) a view on future policy [Dutch] Het project Meer Met Bodemenergie (MMB) richt zich op het invullen van kennisleemtes en mogelijke kansen ten aanzien van open systemen. De belangrijkste vragen waarop het onderzoeksprogramma MMB antwoord geeft zijn: (1) Welke effecten (hydrologisch, thermisch, microbiologisch en chemisch) treden op in het bodemsysteem bij toepassing van bodemenergie?; (2) Welke technische mogelijkheden zijn er voor het duurzaam inpassen van bodem-energie in de water- en energieketen?; (3) Is het mogelijk om meerdere doelstellingen tegelijk te verwezenlijken door slimme combinaties te maken? Het project is ingericht met verschillende werkpakketten. In werkpakket 2 worden de effecten van individuele en collectieve

Computational Simulations of the NASA Langley HyMETS Arc-Jet Facility

Science.gov (United States)

Brune, A. J.; Bruce, W. E., III; Glass, D. E.; Splinter, S. C.

2017-01-01

The Hypersonic Materials Environmental Test System (HyMETS) arc-jet facility located at the NASA Langley Research Center in Hampton, Virginia, is primarily used for the research, development, and evaluation of high-temperature thermal protection systems for hypersonic vehicles and reentry systems. In order to improve testing capabilities and knowledge of the test article environment, an effort is underway to computationally simulate the flow-field using computational fluid dynamics (CFD). A detailed three-dimensional model of the arc-jet nozzle and free-jet portion of the flow-field has been developed and compared to calibration probe Pitot pressure and stagnation-point heat flux for three test conditions at low, medium, and high enthalpy. The CFD model takes into account uniform pressure and non-uniform enthalpy profiles at the nozzle inlet as well as catalytic recombination efficiency effects at the probe surface. Comparing the CFD results and test data indicates an effectively fully-catalytic copper surface on the heat flux probe of about 10% efficiency and a 2-3 kpa pressure drop from the arc heater bore, where the pressure is measured, to the plenum section, prior to the nozzle. With these assumptions, the CFD results are well within the uncertainty of the stagnation pressure and heat flux measurements. The conditions at the nozzle exit were also compared with radial and axial velocimetry. This simulation capability will be used to evaluate various three-dimensional models that are tested in the HyMETS facility. An end-to-end aerothermal and thermal simulation of HyMETS test articles will follow this work to provide a better understanding of the test environment, test results, and to aid in test planning. Additional flow-field diagnostic measurements will also be considered to improve the modeling capability.

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NARCIS (Netherlands)

Thijs Waardenburg; Komala Mazerant

2018-01-01

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

Becoming successful entrepreneurs. Bangladesh. ADB supports pioneering family-based approach to provide micro-credit and skills training.

Science.gov (United States)

Molitor, C

1996-01-01

The Thana Resource Development and Employment Project (TRDEP), built upon the successful experience of the Grameen Bank and other nongovernmental organizations, is a comprehensive poverty alleviation scheme implemented by the government of Bangladesh and targeted to the poorest segment of Bangladeshi society. The project provides soft loans to landless poor for income-generating activities involving non-crop livelihoods and trades. The loans are granted at an 18% interest rate including a 2% charge which goes into a risk fund. The poorest of poor are eligible to receive loans as long as each borrowing unit is a self-help group comprised of five members of one family and each member of the group assumes the responsibility of paying each other member's loan. Each member of a borrowing group may receive loans in the amount of Taka 3000-5000 (US$75-125). The loans are then repayable in 50 equal installments over the course of 1 year. One member's default disqualifies all other group members from receiving future credit until the default is cleared. TRDEP borrowers have started small, successful entrepreneurial activities with their loans as capital.

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

Science.gov (United States)

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

2017-03-01

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

Physiological Signaling and Structure of the HGF Receptor MET

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Gianluca Baldanzi

2014-12-01

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

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

NARCIS (Netherlands)

Mogendorff, K.

2007-01-01

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

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

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Jesus Lozano

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

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.

The BDNF Val66Met Polymorphism Interacts with Maternal Parenting Influencing Adolescent Depressive Symptoms: Evidence of Differential Susceptibility Model.

Science.gov (United States)

Zhang, Leilei; Li, Zhi; Chen, Jie; Li, Xinying; Zhang, Jianxin; Belsky, Jay

2016-03-01

Although depressive symptoms are common during adolescence, little research has examined gene-environment interaction on youth depression. This study chose the brain-derived neurotrophic factor (BDNF) gene, tested the interaction between a functional polymorphism resulting amino acid substitution of valine (Val) to methionine (Met) in the proBDNF protein at codon 66 (Val66Met), and maternal parenting on youth depressive symptoms in a sample of 780 community adolescents of Chinese Han ethnicity (aged 11-17, M = 13.6, 51.3 % females). Participants reported their depressive symptoms and perceived maternal parenting. Results indicated the BDNF Val66Met polymorphism significantly moderated the influence of maternal warmth-reasoning, but not harshness-hostility, on youth depressive symptoms. Confirmatory model evaluation indicated that the interaction effect involving warmth-reasoning conformed to the differential-susceptibility rather than diathesis-stress model of person-X-environment interaction. Thus, Val carriers experienced less depressive symptoms than Met homozygotes when mothering was more positive but more symptoms when mothering was less positive. The findings provided evidence in support of the differential susceptibility hypothesis of youth depressive symptoms and shed light on the importance of examining the gene-environment interaction from a developmental perspective.

Fisetin suppresses malignant proliferation in human oral squamous cell carcinoma through inhibition of Met/Src signaling pathways.

Science.gov (United States)

Li, Yan-Shu; Qin, Xing-Jun; Dai, Wei

2017-01-01

Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonoid and has been indicated as a novel anti-cancer agent in several types of cancer cells. However, the mechanisms underlying the effect of fisetin in human oral squamous cell carcinoma (OSCC) remain unclear. Here, we report that fisetin significantly inhibits tumor cell proliferation and induces apoptosis in OSCC (UM-SCC-23 and Tca-8113) cancer cell lines. Further analysis demonstrates that fisetin also inhibits Met/Src signaling pathways using the PathScan ® receptor tyrosine kinases (RTK) Signaling Antibody Array Kit. Fisetin resulted in decreased basal expression of Met and Src protein in UM-SCC-23 cancer cell lines, which validated by western blot. A student's t -test (two-tailed) was used to compare differences between groups. Furthermore, fisetin significantly inhibited the expression of a disintegrin and metalloproteinase 9 (ADAM9) protein in OSCC cells. Taken together, these results provide novel insights into the mechanism of fisetin and suggest potential therapeutic strategies for human OSCC by blocking the Met/Src signaling pathways.

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

International Nuclear Information System (INIS)

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

1990-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1990-01-01

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

Ervaringen met ICT-onderzoek in het HBO.

NARCIS (Netherlands)

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

2011-01-01

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

Doulas' Perspectives about Providing Support to Incarcerated Women: A Feasibility Study.

Science.gov (United States)

Shlafer, Rebecca J; Hellerstedt, Wendy L; Secor-Turner, Molly; Gerrity, Erica; Baker, Rae

2015-01-01

To document the logistical feasibility of a doula program for pregnant incarcerated women and to assess doulas' perceptions of their achievements. Six doulas provided written case notes ("birth stories") about their experiences with 18 pregnant women in one Midwestern state prison. The birth stories were analyzed by two coders to identify major themes related to doulas' perceptions about providing support to incarcerated women. Analyses involved coder consensus about major themes and doula affirmation of findings. All doulas reported that they met key objectives for a successful relationship with each of their clients. Key themes were their ability to empower clients, establish a trusting relationship, normalize the delivery, and support women as they were separated from their newborns. The intervention was logistically feasible, suggesting that doulas can adapt their practice for incarcerated women. Doulas may need specific training to prepare themselves for institutional restrictions that may conflict with the traditional roles of doula care. It may be important for doulas to understand the level of personal and professional resources they may have to expend to support incarcerated women if they are separated from their infants soon after delivery. © 2014 Wiley Periodicals, Inc.

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

NARCIS (Netherlands)

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

2011-01-01

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

Preproghrelin Leu72Met polymorphism in patients with type 2 diabetes mellitus.

Science.gov (United States)

Ukkola, O; Kesäniemi, Y A

2003-10-01

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

Expression and prognostic relevance of MET and phospho-BAD in non-small cell lung cancer.

Science.gov (United States)

Sun, Wenze; Ai, Ting; Gao, Ying; Zhang, Yingbing; Cui, Jie; Song, Liping

2013-01-01

MET is involved in the progression of several types of human cancers, while phospho-BAD(Ser-136) is a key molecule in apoptosis and might be regulated by MET. The aim of this study was to investigate the correlation between altered expression of MET and phospho-BAD in non-small cell lung cancer (NSCLC) and their association with clinicopathologic parameters and overall survival. MET and phospho-BAD(Ser-136) proteins were evaluated by immunohistochemical analysis in 183 paraffin-embedded specimens and were also assessed by Western blotting analysis in 12 frozen tumor tissue samples, which were representative examples of immunohistochemical staining. Positive expression of MET and phospho-BAD(Ser-136) occurred in 67.2% and 49.2% of the 183 cases of NSCLC, respectively. However, neither MET expression nor phospho-BAD(Ser-136) expression was associated with any clinicopathologic parameter. A significant correlation was found between MET and phospho-BAD(Ser-136) expression levels evaluated by immunohistochemistry (r = 0.268, P BAD(Ser-136)+ phenotype had a poorer prognosis than others (P BAD(Ser-136) expression, and may be an adverse predictor for NSCLC. Activation of the MET/phospho-BAD(Ser-136) signaling pathway might play a role in the development and progression of NSCLC.

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

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Chang-hyun Park

2017-08-01

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

A metáfora na ensaística de Borges

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Gustavo Ponciano Cunha de Oliveira

2014-12-01

Full Text Available http://dx.doi.org/10.5007/2176-8552.2014n17p115 A metáfora é uma recorrência temática na ensaística de Jorge Luis Borges. Porém, o tratamento dado pelo autor portenho ao objeto ensaiado não foi sempre o mesmo. Do jovem poeta e ensaísta ultraísta ao maduro palestrante, as concepções foram profundamente alteradas. Neste ensaio, pretendemos passar por estas diversificadas concepções para nos concentrarmos em uma delas: a metáfora entendida como possibilidade de convergência de conceitos diversos, mesmo contraditórios. Mais do que tema, defendemos a tese de que esta metáfora é própria ao funcionamento ensaístico de Borges. Para promover o debate, nos apoiamos em textos de Paul Ricoeur, Jaime Alazraki, Joseph Hillis Miller, Joaquina Navarro, Álvaro Salvador, entre outros.

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

Science.gov (United States)

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

2018-01-05

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

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

NARCIS (Netherlands)

Greijdanus, T.

2005-01-01

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

Genetic modulation of training and transfer in older adults:BDNF Val66Met polymorphism is associated with wider useful field of view

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Lorenza S Colzato

2011-09-01

Full Text Available Western society has an increasing proportion of older adults. Increasing age is associated with a general decrease in the control over task-relevant mental processes. In the present study we investigated the possibility that successful transfer of game-based cognitive improvements to untrained tasks in elderly people is modulated by preexisting neuro-developmental factors as genetic variability related to levels of the brain-derived neurotrophic factor (BDNF, an important neuromodulator underlying cognitive processes. We trained participants, genotyped for the BDNF Val66Met polymorphism, on cognitive tasks developed to improve dynamic attention. Pre-training (baseline and post-training measures of attentional processes (divided and selective attention were acquired by means of the Useful Field of View (UFOV task. As expected, Val/Val homozygous individuals showed larger beneficial transfer effects than Met/-carriers. Our findings support the idea that genetic predisposition modulates transfer effects.

Radioimmunoassay of met-enkephalin in microdissected areas of paraformaldehyde-fixed rat brain

International Nuclear Information System (INIS)

Correa, F.M.A.; Saavedra, J.M.

1984-01-01

The effects were studied of various sample preparation procedures on rat brain met-enkephalin content, measured by radioimmunoassay. Whole brain met-enkephalin content of rats killed by decapitation followed by immediate tissue freezing was similar to that of rats killed by microwave irradiation and to those of rats anesthetized with pentobarbital or halothane before killing, whether previously perfused with paraformaldehyde or not. In contrast, a decrease (up to 80%) in met-enkephalin concentrations was observed when brain samples were frozen and thawed to mimic the procedure utilized in the ''punch'' technique for analysis of discrete brain nuclei. This decrease was totally prevented by paraformaldehyde perfusion of the brain prior to sacrifice. Brain perfusion did not alter the amount of immunoassayable met-enkephalin extracted from tissue or its profile after Sephadex chromatography. Paraformaldehyde perfusion results in better morphological tissue preservation and facilitates the ''punch'' dissecting technique. Paraformaldehyde perfusion may be the procedure of choice for the measurement of neuropeptides in specific brain nuclei dissected by the ''punch'' technique

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

OpenAIRE

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

2017-01-01

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

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

Science.gov (United States)

Thompson, Barbara L; Levitt, Pat

2015-01-01

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

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

Science.gov (United States)

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

2005-01-01

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

Comparison of GOME-2/MetOp total ozone data with Brewer spectroradiometer data over the Iberian Peninsula

Energy Technology Data Exchange (ETDEWEB)

Anton, M.; Serrano, A. [Universidad de Extremadura, Badajoz (Spain). Dept. de Fisica; Loyola, D.; Zimmer, W. [German Aerospace Center (DLR), Wessling (DE). Remote Sensing Technology Inst. (IMF); Lopez, M.; Banon, M. [Agencia Estatal de Meteorologia (AEMet), Madrid (Spain); Vilaplana, J.M. [Instituto Nacional de Tecnica Aeroespacial (INTA), Huelva (Spain). Estacion de Sondeos Atmosferico ' ' El Arenosillo' '

2009-07-01

The main objective of this article is to compare the total ozone data from the new Global Ozone Monitoring Experiment instrument (GOME-2/MetOp) with reliable ground-based measurement recorded by five Brewer spectroradiometers in the Iberian Peninsula. In addition, a similar comparison for the predecessor instrument GOME/ERS-2 is described. The period of study is a whole year from May 2007 to April 2008. The results show that GOME-2/MetOp ozone data already has a very good quality, total ozone columns are on average 3.05% lower than Brewer measurements. This underestimation is higher than that obtained for GOME/ERS-2 (1.46%). However, the relative differences between GOME-2/MetOp and Brewer measurements show significantly lower variability than the differences between GOME/ERS-2 and Brewer data. Dependencies of these relative differences with respect to the satellite solar zenith angle (SZA), the satellite scan angle, the satellite cloud cover fraction (CF), and the ground-based total ozone measurements are analyzed. For both GOME instruments, differences show no significant dependence on SZA. However, GOME-2/MetOp data show a significant dependence on the satellite scan angle (+1.5%). In addition, GOME/ERS-2 differences present a clear dependence with respect to the CF and ground-based total ozone; such differences are minimized for GOME-2/MetOp. The comparison between the daily total ozone values provided by both GOME instruments shows that GOME-2/MetOp ozone data are on average 1.46% lower than GOME/ERS-2 data without any seasonal dependence. Finally, deviations of a priori climatological ozone profile used by the satellite retrieval algorithm from the true ozone profile are analyzed. Although excellent agreement between a priori climatological and measured partial ozone values is found for the middle and high stratosphere, relative differences greater than 15% are common for the troposphere and lower stratosphere. (orig.)

Both COMT Val158Met single nucleotide polymorphism and sex-dependent differences influence response inhibition

Directory of Open Access Journals (Sweden)

Valentina eMione

2015-05-01

Full Text Available Reactive and proactive control of actions are cognitive abilities that allow to deal with a continuously changing environment by adjusting already programmed actions. They also set forthcoming acts by evaluating the outcome of the previous ones. Earlier studies highlighted sex related differences in the strategies and in the pattern of brain activation during cognitive tasks involving reactive and proactive control. To further identify sex-dependent characteristics in the cognitive control of actions, in this study we have assessed whether/how differences in reactive and proactive control were modulated by the COMT Val158Met single nucleotide polymorphism, a genetic factor known to influence the functionality of the dopaminergic system, in particular at the level of prefrontal cortex. Two groups of male and female participants were further sorted according to their genotype (Val/Met, Val/Val and Met/Met and tested in a stop signal task, a consolidated tool to measure reactive and proactive control in experimental and clinical settings. In each group of participants we estimated both a measure of the capacity to react to unexpected events and the ability of monitoring their performance. The between groups comparison of these measures indicated a poorer ability of male individuals carrying the Val/Val genotype in error-monitoring, suggesting that differences between sexes could be influenced by the efficiency of COMT and that other sex-specific factors have to be considered. The comprehension of inter-groups behavioral and physiological correlates of cognitive control will provide more accurate diagnostic tools for predicting the incidence and the development of pathologies like ADHD or deviant behaviors as drug or alcohol abuse.

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

Science.gov (United States)

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

2018-04-01

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

Genomic profiling of a Hepatocyte growth factor-dependent signature for MET-targeted therapy in glioblastoma.

Science.gov (United States)

Johnson, Jennifer; Ascierto, Maria Libera; Mittal, Sandeep; Newsome, David; Kang, Liang; Briggs, Michael; Tanner, Kirk; Marincola, Francesco M; Berens, Michael E; Vande Woude, George F; Xie, Qian

2015-09-17

Constitutive MET signaling promotes invasiveness in most primary and recurrent GBM. However, deployment of available MET-targeting agents is confounded by lack of effective biomarkers for selecting suitable patients for treatment. Because endogenous HGF overexpression often causes autocrine MET activation, and also indicates sensitivity to MET inhibitors, we investigated whether it drives the expression of distinct genes which could serve as a signature indicating vulnerability to MET-targeted therapy in GBM. Interrogation of genomic data from TCGA GBM (Student's t test, GBM patients with high and low HGF expression, p ≤ 0.00001) referenced against patient-derived xenograft (PDX) models (Student's t test, sensitive vs. insensitive models, p ≤ 0.005) was used to identify the HGF-dependent signature. Genomic analysis of GBM xenograft models using both human and mouse gene expression microarrays (Student's t test, treated vs. vehicle tumors, p ≤ 0.01) were performed to elucidate the tumor and microenvironment cross talk. A PDX model with EGFR(amp) was tested for MET activation as a mechanism of erlotinib resistance. We identified a group of 20 genes highly associated with HGF overexpression in GBM and were up- or down-regulated only in tumors sensitive to MET inhibitor. The MET inhibitors regulate tumor (human) and host (mouse) cells within the tumor via distinct molecular processes, but overall impede tumor growth by inhibiting cell cycle progression. EGFR (amp) tumors undergo erlotinib resistance responded to a combination of MET and EGFR inhibitors. Combining TCGA primary tumor datasets (human) and xenograft tumor model datasets (human tumor grown in mice) using therapeutic efficacy as an endpoint may serve as a useful approach to discover and develop molecular signatures as therapeutic biomarkers for targeted therapy. The HGF dependent signature may serve as a candidate predictive signature for patient enrollment in clinical trials using MET inhibitors

Activation of c-MET induces a stem-like phenotype in human prostate cancer.

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Geert J L H van Leenders

Full Text Available Prostate cancer consists of secretory cells and a population of immature cells. The function of immature cells and their mutual relation with secretory cells are still poorly understood. Immature cells either have a hierarchical relation to secretory cells (stem cell model or represent an inducible population emerging upon appropriate stimulation of differentiated cells. Hepatocyte Growth Factor (HGF receptor c-MET is specifically expressed in immature prostate cells. Our objective is to determine the role of immature cells in prostate cancer by analysis of the HGF/c-MET pathway.Gene-expression profiling of DU145 prostate cancer cells stimulated with HGF revealed induction of a molecular signature associated with stem cells, characterized by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 ('stem-like signature'. We confirmed the acquisition of a stem-like phenotype by quantitative PCR, FACS analysis and Western blotting. Further, HGF led to activation of the stem cell related Notch pathway by up-regulation of its ligands Jagged-1 and Delta-like 4. Small molecules SU11274 and PHA665752 targeting c-MET activity were both able to block the molecular and biologic effects of HGF. Knock-down of c-MET by shRNA infection resulted in significant reduction and delay of orthotopic tumour-formation in male NMRI mice. Immunohistochemical analysis in prostatectomies revealed significant enrichment of c-MET positive cells at the invasive front, and demonstrated co-expression of c-MET with stem-like markers CD49b and CD49f.In conclusion, activation of c-MET in prostate cancer cells induced a stem-like phenotype, indicating a dynamic relation between differentiated and stem-like cells in this malignancy. Its mediation of efficient tumour-formation in vivo and predominant receptor expression at the invasive front implicate that c-MET regulates tumour infiltration in surrounding tissues putatively by acquisition of a stem-like phenotype.

BDNF val66met polymorphism affects aging of multiple types of memory.

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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.

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

International Nuclear Information System (INIS)

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

2005-01-01

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

Participation needs of older adults having disabilities and receiving home care: met needs mainly concern daily activities, while unmet needs mostly involve social activities.

Science.gov (United States)

Turcotte, Pier-Luc; Larivière, Nadine; Desrosiers, Johanne; Voyer, Philippe; Champoux, Nathalie; Carbonneau, Hélène; Carrier, Annie; Levasseur, Mélanie

2015-08-01

Participation is a key determinant of successful aging and enables older adults to stay in their homes and be integrated into the community. Assessing participation needs involves identifying restrictions in the accomplishment of daily and social activities. Although meeting participation needs involves older adults, their caregivers and healthcare providers, little is known about their respective viewpoints. This study thus explored the participation needs of older adults having disabilities as perceived by the older adults themselves, their caregivers and healthcare providers. A qualitative multiple case study consisted of conducting 33 semi-structured interviews in eleven triads, each composed of an older adult, his/her caregiver and a healthcare provider recruited in a Health and Social Services Centre (HSSC) in Québec, Canada. Interview transcripts and reviews of clinical records were analyzed using content analysis and descriptive statistics based on thematic saliency analysis methods. Aged 66 to 88 years, five older adults had physical disabilities, five had mild cognitive impairment and one had psychological problems, leading to moderate to severe functional decline. Caregivers and healthcare providers were mainly women, respectively retired spouses and various professionals with four to 32 years of clinical experience. Participation needs reported by each triad included all domains of participation. Needs related to daily activities, such as personal care, nutrition, and housing, were generally met. Regarding social activities, few needs were met by various resources in the community and were generally limited to personal responsibilities, including making decisions and managing budgets, and some community life activities, such as going shopping. Unmet needs were mainly related to social activities, involving leisure, other community life activities and interpersonal relationships, and some daily activities, including fitness and mobility. This study

Day 4 good morula embryo transfer provided compatible live birth rate with day 5 blastocyst embryo in fresh IVF/ET cycles.

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Li, Ryh-Sheng; Hwu, Yuh-Ming; Lee, Robert Kuo-Kuang; Li, Sheng-Hsiang; Lin, Ming-Huei

2018-02-01

Embryo transfers during cleavage stage (day 2 or day 3) and blastocyst stages (day 5 or day 6) are common in current daily practice in fresh IVF/ET cycles. Data regarding transferring day 4 embryos, morula/compact stage, is still restricted and the grading system is also inconsistent, as between IVF clinics. This study provided a new detailed classification system for morula/compact stage embryos and compared successes rates between day 4 and day 5 ET. This was a retrospective study. A review of medical records from January 1st, 2013, to December 31st 2015, performed for all conventional insemination and ICSI cycles with a GnRH-antagonist protocol at the Infertility Division of MacKay Memorial Hospital in Taipei City, Taiwan. There were 427 cycles included in our study, 107 in study group (day 4 MET) and 320 in control group (day 5 BET). Pregnancy rates and live birth rate were compatible, as between morula embryo transfer (MET) and blastocyst embryo transfer (BET). The implantation rate (36.3% vs. 39.6%, respectively, p = 0.500), clinical pregnancy rate (49.5% vs. 51.9%, respectively, p = 0.737), and live birth rate (42.1% vs. 45.6%, respectively, p = 0.574) were statistically insignificant between groups. The term birth rate was statistically higher in the MET group than in the BET group (95.7% vs. 79.5%, respectively, p = 0.006). When the clinical outcomes between day 4 good MET and day 5 good BET were compared, the results were compatible. The implantation rate (48.8% vs. 41.1%, respectively, p = 0.335), clinical pregnancy rate (55.0% vs. 53.2%, respectively, p = 0.867), and live birth rate (47.5% vs. 47.1%, respectively, p = 1.000) showed no significant difference. The term birth rate was also higher in day 4 good MET group than in day 5 good BET group (100% vs. 78.3%, respectively, p = 0.025). In this study, we performed day 4 MET avoid BET on Sunday. The grading system we provided was more detailed for embryo selection and it was easier to

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

How to Identify Success Among Networks That Promote Active Living.

Science.gov (United States)

Litt, Jill; Varda, Danielle; Reed, Hannah; Retrum, Jessica; Tabak, Rachel; Gustat, Jeanette; O'Hara Tompkins, Nancy

2015-11-01

We evaluated organization- and network-level factors that influence organizations' perceived success. This is important for managing interorganizational networks, which can mobilize communities to address complex health issues such as physical activity, and for achieving change. In 2011, we used structured interview and network survey data from 22 states in the United States to estimate multilevel random-intercept models to understand organization- and network-level factors that explain perceived network success. A total of 53 of 59 "whole networks" met the criteria for inclusion in the analysis (89.8%). Coordinators identified 559 organizations, with 3 to 12 organizations from each network taking the online survey (response rate = 69.7%; range = 33%-100%). Occupying a leadership position (P Organizations' perceptions of success can influence decisions about continuing involvement and investment in networks designed to promote environment and policy change for active living. Understanding these factors can help leaders manage complex networks that involve diverse memberships, varied interests, and competing community-level priorities.

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice.

Science.gov (United States)

Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L; Lee, Francis S; Blendy, Julie A

2015-12-01

Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine withdrawal. Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For

Staff and consumer perspectives on defining treatment success and failure in assertive community treatment.

Science.gov (United States)

Stull, Laura G; McGrew, John H; Salyers, Michelle P

2010-09-01

Although assertive community treatment (ACT) has been consistently recognized as effective, there has been little research as to what constitutes success in ACT. The purpose of this study was to understand how ACT consumers and staff define treatment success and failure and to examine whether definitions varied between staff and consumers. Investigators conducted semistructured interviews with 25 staff and 23 consumers from four ACT teams. Across perspectives, success and failure were most clearly related to consumer factors. Other themes included having basic needs met, being socially involved, and taking medications. Reduced hospitalizations were mentioned infrequently. Consumers were more likely than staff to identify the level or type of treatment as defining success and failure, whereas staff were more likely than consumers to discuss substance abuse when defining failure and improved symptoms when defining success. Success in ACT should be viewed more broadly than reduced hospitalizations and include domains such as social involvement.

Role of PAX8 in the regulation of MET and RON receptor tyrosine kinases in non-small cell lung cancer

International Nuclear Information System (INIS)

Kanteti, Rajani; El-Hashani, Essam; Dhanasingh, Immanuel; Tretiakova, Maria; Husain, Aliya N; Sharma, Sherven; Sharma, Jay; Vokes, Everett E; Salgia, Ravi

2014-01-01

11274, had marginal additive effect on loss of NSCLC cell viability. PAX8 provides signals for growth and motility of NSCLC cells and is necessary for MET and RON expression. Further investigations are necessary to investigate the therapeutic potential of PA8 in NSCLC

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.

Remote Sensing of Volcanic ASH at the Met Office

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Marenco F.

2016-01-01

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

Estimation of METs by Accelerometers while Walking and Running

Science.gov (United States)

Kurihara, Yosuke; Watanabe, Kajiro; Yoneyama, Mitsuru

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-08-19

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

Integrated systematic review on educational strategies that promote academic success and resilience in undergraduate indigenous students.

Science.gov (United States)

Milne, T; Creedy, D K; West, R

2016-01-01

Despite numerous recommendations by governments, researchers, and education policymakers the recruitment, retention and success of undergraduate indigenous students in higher education is not commensurate of the wider student population. There is minimal evidence of valuing indigenous worldviews and perspectives in curricula, and effectiveness of educational strategies to strengthen indigenous student success rates in completing undergraduate studies. To conduct an integrative systematic review of educational strategies to promote academic success and resilience in undergraduate indigenous students. Major databases of Scopus, ProQuest, Informit and Web of Science were searched. Inclusion criteria were peer reviewed research articles from scholarly journals that referenced indigenous, aboriginal, First Nation or Māori students in undergraduate programs in higher education. The search was limited to English language and studies conducted from 1995 to 2014. The search yielded 156 research papers which reduced to 16 papers that met the inclusion criteria. The included papers were critiqued from a standpoint theory approach that reflects feminism, cultural respect, and humanism. Much of the literature describes issues, and provides qualitative analyses of experiences, but empirical evaluations of interventions are rare. There was a gap in current research evaluating strategies to improve indigenous student success and resilience. Key strategies for indigenous student success are multi-faceted, layered support, underpinned by the principles of respect, relationships, and responsibility. Implications for nursing and midwifery education, research and health care practice are outlined. Copyright © 2015 Elsevier Ltd. All rights reserved.

DMD reliability: a MEMS success story

Science.gov (United States)

Douglass, Michael

2003-01-01

The Digital Micromirror Device (DMD) developed by Texas Instruments (TI) has made tremendous progress in both performance and reliability since it was first invented in 1987. From the first working concept of a bistable mirror, the DMD is now providing high-brightness, high-contrast, and high-reliability in over 1,500,000 projectors using Digital Light Processing technology. In early 2000, TI introduced the first DMD chip with a smaller mirror (14-micron pitch versus 17-micron pitch). This allowed a greater number of high-resolution DMD chips per wafer, thus providing an increased output capacity as well as the flexibility to use existing package designs. By using existing package designs, subsequent DMDs cost less as well as met our customers' demand for faster time to market. In recent years, the DMD achieved the status of being a commercially successful MEMS device. It reached this status by the efforts of hundreds of individuals working toward a common goal over many years. Neither textbooks nor design guidelines existed at the time. There was little infrastructure in place to support such a large endeavor. The knowledge we gained through our characterization and testing was all we had available to us through the first few years of development. Reliability was only a goal in 1992 when production development activity started; a goal that many throughout the industry and even within Texas Instruments doubted the DMD could achieve. The results presented in this paper demonstrate that we succeeded by exceeding the reliability goals.

Evangelisch Commando, onze omgamg met de buitenkerkelijke ...

African Journals Online (AJOL)

Test

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

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

Science.gov (United States)

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

2017-10-01

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

With tactful policy towards sustainable mobility; Met beleid naar duurzame mobiliteit

Energy Technology Data Exchange (ETDEWEB)

Wagter, H. [Platform Duurzame Mobiliteit, Ministerie van Verkeer en Waterstaat VenW, Den Haag (Netherlands); Weterings, R. [TNO, Delft (Netherlands)

2009-11-12

This report offers a view on policy measures that may be needed to realize the CO2 reduction targets for traffic and transport in 2020 and beyond. It provides a summary of the results of a dialogue supervised by TNO between key persons from trade and industry, the government, social organizations and knowledge institutes. Four thematic work sessions were dedicated to identifying the measures that hold the largest reduction potential, an exploration was done to find out how the measures can realize maximum impact and what is needed for these measures to realize maximum impact. The result will be used as input for the evaluation of 'Clean and Efficient' and for further policy development. [Dutch] Het voorliggende rapport biedt zicht op de beleidsmaatregelen die mogelijk nodig zijn om de CO2-reductiedoelen voor verkeer en vervoer in 2020 en verder te behalen. Het vormt een samenvatting van de resultaten van een door TNO begeleidde dialoog tussen sleutelpersonen uit bedrijfsleven, overheid, maatschappelijke organisaties en kennisinstellingen. In vier thematische werksessies zijn de maatregelen met het grootste reductiepotentieel geidentificeerd, is verkend hoe de haalbaarheid gemaximaliseerd kan worden en wat er voor nodig is om met deze maatregelen maximale impact te realiseren. Het resultaat vormt input voor de evaluatie van 'Schoon en Zuinig' en voor verdere beleidsontwikkeling.

Reactions of Met-Cars

International Nuclear Information System (INIS)

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

1993-01-01

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

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

Science.gov (United States)

MetLife, Inc., 2013

2013-01-01

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

Successful removable partial dentures.

Science.gov (United States)

Lynch, Christopher D

2012-03-01

Removable partial dentures (RPDs) remain a mainstay of prosthodontic care for partially dentate patients. Appropriately designed, they can restore masticatory efficiency, improve aesthetics and speech, and help secure overall oral health. However, challenges remain in providing such treatments, including maintaining adequate plaque control, achieving adequate retention, and facilitating patient tolerance. The aim of this paper is to review the successful provision of RPDs. Removable partial dentures are a successful form of treatment for replacing missing teeth, and can be successfully provided with appropriate design and fabrication concepts in mind.

Pasarela metálica excéntrica suspendida y apoyada en un arco metálico en Orense, España

Directory of Open Access Journals (Sweden)

Besiga Díaz-Blanco, Julio

2007-12-01

Full Text Available The article explains the design and project of a steel footbridge, suspended and supported by an eccentric arc, situated in Orense. The footbridge, known as “Bellour”, has a main span of 20 meters, with a leaned steel eccentric arc that supports the deck. The deck was designed with a uniform slope of 8%, due the difference of level between each end. It is suspended from the arc in the Orense side and supported in the other boarder, because of the headway limitations. The deck is 2,80 meters wide. The cross section is composed of a steel eccentric tube with steel cantilever beams, of variable depth, and is joined at the other edge to a small steel tube. The pedestrian zone is narrower than the board, leaving individual empty spaces at both sides, and is constituted by a structural concrete slab of 7 centimeters thick and 2 meters wide, linked to the deck top sheet, with a steel profiles. The board was designed with a structural skeleton, spine shaped, suspended or supported from the arc, and it´s joined to the skin, a rough concrete surface that avoids frost and slides due to the rain.En este artículo se expone el diseño de una pasarela metálica excéntrica suspendida y apoyada en un arco metálico situada en la ciudad de Orense. La pasarela, conocida por «Bellour», tiene un único vano de 20 metros de luz, soportado excéntricamente por un arco metálico inclinado. Las cotas de inicio y fin de la pasarela obligaron a diseñar un tablero inclinado que está suspendido del arco en el lado Orense y apoyado en el otro extremo al permitirlo el gálibo de la carretera. La sección transversal del tablero está formada por un tubo excéntrico del que parten unas ménsulas metálicas de canto variable, unidas en su otro extremo por otro tubo más pequeño. El pavimento de la pasarela, que es más estrecho que el propio tablero, dejando sendos espacios vacíos a ambos lados, está formado por una losa de hormigón armado conectada a

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

NARCIS (Netherlands)

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

2014-01-01

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

The COMT val158met polymorphism and brain morphometry in healthy young adults

NARCIS (Netherlands)

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

2006-01-01

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

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

Science.gov (United States)

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

2011-03-31

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

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

Science.gov (United States)

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

2017-10-03

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

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

Science.gov (United States)

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

2017-02-01

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

Comportamento experimental de diferentes tipos de conectores metálicos

OpenAIRE

Valente, Isabel B.

2016-01-01

A realização de estruturas mistas de aço e betão requer o funcionamento conjunto destes dois materiais. A ligação entre eles é conseguida com a utilização de conectores metálicos. Neste âmbito, tem sido realizada uma considerável quantidade de estudos que abordam o comportamento de diversos tipos de conectores metálicos. O desejo de obter um comportamento óptimo com custos mínimos motivou o desenvolvimento de várias soluções. Neste artigo, procura-se descrever o comportamento de diferente...

Progress in switching technology for METS systems

International Nuclear Information System (INIS)

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

1977-01-01

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

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

Science.gov (United States)

Liston, G. E.; Elder, K.

2004-12-01

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

Beoordeling gezondheidsrisico's door sporten op kunstgrasvelden met rubbergranulaat

NARCIS (Netherlands)

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

2016-01-01

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

Aan de slag met honors : praktijklessen uit Europa

NARCIS (Netherlands)

Wolfensberger, Marca; Hogenstijn, Maarten

2015-01-01

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

Praktijkervaringen met de Venlow energy kas 2010-2012

NARCIS (Netherlands)

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

2013-01-01

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

The effect of an enriched learning community on success and retention in chemistry courses

Science.gov (United States)

Willoughby, Lois Jane

Since the mid-1990s, the United States has experienced a shortage of scientists and engineers, declining numbers of students choosing these fields as majors, and low student success and retention rates in these disciplines. Learning theorists, educational researchers, and practitioners believe that learning environments can be created so that an improvement in the numbers of students who complete courses successfully could be attained (Astin, 1993; Magolda & Terenzini, n.d.; O'Banion, 1997). Learning communities do this by providing high expectations, academic and social support, feedback during the entire educational process, and involvement with faculty, other students, and the institution (Ketcheson & Levine, 1999). A program evaluation of an existing learning community of science, mathematics, and engineering majors was conducted to determine the extent to which the program met its goals and was effective from faculty and student perspectives. The program provided laptop computers, peer tutors, supplemental instruction with and without computer software, small class size, opportunities for contact with specialists in selected career fields, a resource library, and Peer-Led Team Learning. During the two years the project has existed, success, retention, and next-course continuation rates were higher than in traditional courses. Faculty and student interviews indicated there were many affective accomplishments as well. Success and retention rates for one learning community class ( n = 27) and one traditional class (n = 61) in chemistry were collected and compared using Pearson chi square procedures ( p = .05). No statistically significant difference was found between the two groups. Data from an open-ended student survey about how specific elements of their course experiences contributed to success and persistence were analyzed by coding the responses and comparing the learning community and traditional classes. Substantial differences were found in their

MET-2-Dependent H3K9 Methylation Suppresses Transgenerational Small RNA Inheritance.

Science.gov (United States)

Lev, Itamar; Seroussi, Uri; Gingold, Hila; Bril, Roberta; Anava, Sarit; Rechavi, Oded

2017-04-24

In C. elegans, alterations to chromatin produce transgenerational effects, such as inherited increase in lifespan and gradual loss of fertility. Inheritance of histone modifications can be induced by double-stranded RNA-derived heritable small RNAs. Here, we show that the mortal germline phenotype, which is typical of met-2 mutants, defective in H3K9 methylation, depends on HRDE-1, an argonaute that carries small RNAs across generations, and is accompanied by accumulated transgenerational misexpression of heritable small RNAs. We discovered that MET-2 inhibits small RNA inheritance, and, as a consequence, induction of RNAi in met-2 mutants leads to permanent RNAi responses that do not terminate even after more than 30 generations. We found that potentiation of heritable RNAi in met-2 animals results from global hyperactivation of the small RNA inheritance machinery. Thus, changes in histone modifications can give rise to drastic transgenerational epigenetic effects, by controlling the overall potency of small RNA inheritance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Subtiel verleiden met nudging : Verhogen van enquêterespons

NARCIS (Netherlands)

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

2015-01-01

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

Randvoorwaarden ontwerp happy games voor ouderen met dementie

NARCIS (Netherlands)

Dr. A.L. Cordia

2014-01-01

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

Vers bloed voor spinazie (interview met C. Kik)

NARCIS (Netherlands)

Nijland, R.; Kik, C.

2011-01-01

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

BDNF VAL66MET Polymorphism Elevates the Risk of Bladder Cancer via MiRNA-146b in Micro-Vehicles

Directory of Open Access Journals (Sweden)

Cong Li

2018-01-01

Full Text Available Background/Aims: Emerging studies on brain-derived neurotrophic factor (BDNF have shown that might be novel biomarkers and therapeutic targets for cancer. We explore the role of BDNF in the tumorigenesis of bladder cancer and the underlying molecular mechanism. Methods: 368 patients with diagnosed bladder cancer and 352 healthy controls were enrolled to evaluate the association of BDNF and the miR-146b. Bioinformatics algorithm analysis and luciferase assay were performed to identify the target genes of miR-146b. Real-time PCR and western-blot were carried out to validate the relationship between miR-146b and CRK. MTT assay and FACS were used to evaluated the proliferation and apoptosis of cancer cells. MVs were isolated and transfect into the culture cells to confirm the above observation. Results: The clinical study shows that BDNF Met/Met was significantly associated with the risk of bladder cancer. In addition, comparing with Val/Val and Val/Met, Met/Met has lower miR-146b level. Luciferase assay shows that BDNF Val/Val is apparently enhanced miR-146b promoter-luciferase, but not BDNF Met/Met. Based on luciferase assay, CRK is a direct target gene of miR-146b. MiR-146b mimics significantly inhibited the expression of CRK and activation of AKT level. The expression of CRK and the activation of AKT (p-AKT were significantly inhibited by MV-BDNF Val/Val-miR-146b or MV-BDNF Val/Met-miR-146b, but not MV-BDNF Met/Met-miR-146b. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b obviously inhibited cell proliferation, which eliminated by CRK. Meanwhile, with MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not affect the proliferation. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b enhanced cell apoptosis, which could be eliminated by CRK. Meanwhile, MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not promote apoptosis. Conclusion: BDNF VAL66MET polymorphism is associated with miR-146b and its target gene CRK. MiR-146b and CRK mediated BDNF VAL66

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

NARCIS (Netherlands)

Marleen Hofman, [No Value

2013-01-01

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

Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations

Directory of Open Access Journals (Sweden)

Ahmet Yilmaz

2014-09-01

Full Text Available Cigarette smoking is one of the most significant public health issues and the most common environmental cause of preventable cancer deaths worldwide. EGFR (Epidermal Growth Factor Receptor-targeted therapy has been used in the treatment of LC (lung cancer, mainly caused by the carcinogens in cigarette smoke, with variable success. Presence of mutations in the KRAS (Kirsten rat sarcoma viral oncogene homolog driver oncogene may confer worse prognosis and resistance to treatment for reasons not fully understood. NQO1 (NAD(PH:quinone oxidoreductase, also known as DT-diaphorase, is a major regulator of oxidative stress and activator of mitomycins, compounds that have been targeted in over 600 pre-clinical trials for treatment of LC. We sequenced KRAS and investigated expression of NQO1 and five clinically relevant proteins (DNMT1, DNMT3a, ERK1/2, c-MET, and survivin in 108 patients with non-small cell lung carcinoma (NSCLC. NQO1, ERK1/2, DNMT1, and DNMT3a but not c-MET and survivin expression was significantly more frequent in patients with KRAS mutations than those without, suggesting the following: (1 oxidative stress may play an important role in the pathogenesis, worse prognosis, and resistance to treatment reported in NSCLC patients with KRAS mutations, (2 selecting patients based on their KRAS mutational status for future clinical trials may increase success rate, and (3 since oxidation of nucleotides also specifically induces transversion mutations, the high rate of KRAS transversions in lung cancer patients may partly be due to the increased oxidative stress in addition to the known carcinogens in cigarette smoke.

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

Science.gov (United States)

2010-07-01

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

The functional BDNF Val66Met polymorphism affects functions of pre-attentive visual sensory memory processes.

Science.gov (United States)

Beste, Christian; Schneider, Daniel; Epplen, Jörg T; Arning, Larissa

2011-01-01

The brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is involved in nerve growth and survival. Especially, a single nucleotide polymorphism (SNP) in the BDNF gene, Val66Met, has gained a lot of attention, because of its effect on activity-dependent BDNF secretion and its link to impaired memory processes. We hypothesize that the BDNF Val66Met polymorphism may have modulatory effects on the visual sensory (iconic) memory performance. Two hundred and eleven healthy German students (106 female and 105 male) were included in the data analysis. Since BDNF is also discussed to be involved in the pathogenesis of depression, we additionally tested for possible interactions with depressive mood. The BDNF Val66Met polymorphism significantly influenced iconic-memory performance, with the combined Val/Met-Met/Met genotype group revealing less time stability of information stored in iconic memory than the Val/Val group. Furthermore, this stability was positively correlated with depressive mood exclusively in the Val/Val genotype group. Thus, these results show that the BDNF Val66Met polymorphism has an effect on pre-attentive visual sensory memory processes. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Michael Watson

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

Slim in het verkeer met open data : adviesrapport

NARCIS (Netherlands)

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

2013-01-01

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

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

African Journals Online (AJOL)

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

The Hepatocyte Growth Factor (HGF/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

Directory of Open Access Journals (Sweden)

Marjorie Boissinot

2014-08-01

Full Text Available Met is the receptor of hepatocyte growth factor (HGF, a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML, and myeloproliferative neoplasms (MPNs. The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs.

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)

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

NARCIS (Netherlands)

Versluis, K.; Blacquiere, T.

2009-01-01

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

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

Science.gov (United States)

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

2012-04-01

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

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

Science.gov (United States)

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

2006-07-01

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

Energy expenditure during common sitting and standing tasks: examining the 1.5 MET definition of sedentary behaviour.

Science.gov (United States)

Mansoubi, Maedeh; Pearson, Natalie; Clemes, Stacy A; Biddle, Stuart Jh; Bodicoat, Danielle H; Tolfrey, Keith; Edwardson, Charlotte L; Yates, Thomas

2015-05-29

Sedentary behavior is defined as any waking behavior characterized by an energy expenditure of 1.5 METS or less while in a sitting or reclining posture. This study examines this definition by assessing the energy cost (METs) of common sitting, standing and walking tasks. Fifty one adults spent 10 min during each activity in a variety of sitting tasks (watching TV, Playing on the Wii, Playing on the PlayStation Portable (PSP) and typing) and non-sedentary tasks (standing still, walking at 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, and 1.6 mph). Activities were completed on the same day in a random order following an assessment of resting metabolic rate (RMR). A portable gas analyzer was used to measure oxygen uptake, and data were converted to units of energy expenditure (METs). Average of standardized MET values for screen-based sitting tasks were: 1.33 (SD: 0.24) METS (TV), 1.41 (SD: 0.28) (PSP), and 1.45 (SD: 0.32) (Typing). The more active, yet still seated, games on the Wii yielded an average of 2.06 (SD: 0.5) METS. Standing still yielded an average of 1.59 (SD: 0.37) METs. Walking MET values increased incrementally with speed from 2.17 to 2.99 (SD: 0.5 - 0.69) METs. The suggested 1.5 MET threshold for sedentary behaviors seems reasonable however some sitting based activities may be classified as non-sedentary. The effect of this on the definition of sedentary behavior and associations with metabolic health needs further investigation.

Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress

Directory of Open Access Journals (Sweden)

Tsuru J

2014-11-01

Full Text Available Jusen Tsuru,1 Yoshihiro Tanaka,1 Yoshinobu Ishitobi,1 Yoshihiro Maruyama,1 Ayako Inoue,1 Aimi Kawano,1 Rie Ikeda,1 Tomoko Ando,1 Harumi Oshita,2 Saeko Aizawa,1 Koji Masuda,1 Haruka Higuma,1 Masayuki Kanehisa,1 Taiga Ninomiya,1 Jotaro Akiyoshi1 1Department of Neuropsychiatry, 2Department of Applied Linguistics, Faculty of Medicine, Oita University, Oita, Japan Background: Decreased expression of brain-derived neurotrophic factor (BDNF is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder.Methods: To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men using a social stress procedure (Trier Social Stress Test [TSST] and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A.Results: A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; P<0.05 was demonstrated that revealed different salivary cortisol responses in the TSST but not in electrical stimulation. Met/Met women had stronger cortisol responses than Val/Met and Val/Val individuals in the TSST. Met/Met men exhibited stronger salivary cortisol responses than Val/Met and Val/Val individuals in the TSST.Conclusion: These results indicate that a common, functionally significant polymorphism in BDNF had different effects on hypothalamic–pituitary–adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests. Keywords: stress, brain-derived neurotrophic factor, cortisol, saliva

Metáfora, ciencia y cultura: Propuesta de una nueva tipología para el análisis de la metáfora científica

Directory of Open Access Journals (Sweden)

Georgina Cuadrado Esclapez

2004-04-01

Full Text Available Este artículo de carácter interdisciplinar establece una correlación entre los modos cognitivos (Buxó Rey, 1975; 1984 y la metáfora en la ciencia, lo que supone la incorporación de una importante aportación de la antropología cognitiva a la teoría del lenguaje y del conocimiento. Para establecer esta correlación, se parte del supuesto de que el modo de pensar y de estructurar la realidad de una determinada cultura no está separado de su manifestación en el lenguaje y, por tanto, de la construcción de concepciones metafóricas. Esta correlación sólo es posible partiendo de las premisas establecidas por la última generación cognitivista que asume que la metáfora es parte constituyente de nuestro sistema conceptual (Gleitman & Lieberman, 1995; Smith & Osherson, 1995. La tipología que propone espera ofrecer nuevas perspectivas para el análisis de la metáfora en el discurso científico-técnico.

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.

Medical Emergency Team: How do we play when we stay? Characterization of MET actions at the scene.

Science.gov (United States)

Silva, Raquel; Saraiva, Manuel; Cardoso, Teresa; Aragão, Irene C

2016-03-22

The creation, implementation and effectiveness of a medical emergency team (MET) in every hospital is encourage and supported by international bodies of quality certification. Issues such as what is the best composition of the team or the interventions performed by the MET at the scene and the immediate outcomes of the patients after MET intervention have not yet been sufficiently explored. The purpose of the study is to characterize MET actions at the scene and the immediate patient outcome. Retrospective cohort study, at a tertiary care, university-affiliated, 600-bed hospital, in the north of Portugal, over two years. There were 511 MET activations: 389 (76%) were for inpatients. MET activation rate was 8.6/1,000 inpatients. The main criteria for activation were airway threatening in 143 (36.8%), concern of medical staff in 121 (31.1%) and decrease in GCS > 2 in 98 (25.2%) patients; MET calls for cardiac arrest occurred in 68 patients (17.5%). The median (IQR) time the team stayed at the scene was 35 (20-50) minutes. At the scene, the most frequent actions were related to airway and ventilation, namely oxygen administration in 145 (37.3%); in circulation, fluid were administered in 158 (40.6%); overall medication was administered in 185 (47.5%) patients. End-of-life decisions were part of the MET actions in 94 (24.1%) patients. At the end of MET intervention, 73 (18.7%) patients died at the scene, 190 (60.7%) stayed on the ward and the remaining 123 patients were transferred to an increased level of care. Crude hospital mortality rate was 4.1% in the 3 years previously to MET implementation and 3.6% in the following 3 years (p residence. The team stayed on site for half an hour and during that time most of the actions were simple and nurse-driven, but in one third of all activations medical actions were taken, and in a forth (24%) end-of-life decisions made, reinforcing the inclusion of a doctor in the MET. A significant decrease in overall hospital

Constant Cremer, voetballer in Tilburg met Afrikaanse wortels

NARCIS (Netherlands)

Drs. Thijs Kemmeren

2012-01-01

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

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.

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

African Journals Online (AJOL)

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

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

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

2013-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

Metáfora y conceptos abstractos

OpenAIRE

Danesi, Marcel

2006-01-01

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

MetSigDis: a manually curated resource for the metabolic signatures of diseases.

Science.gov (United States)

Cheng, Liang; Yang, Haixiu; Zhao, Hengqiang; Pei, Xiaoya; Shi, Hongbo; Sun, Jie; Zhang, Yunpeng; Wang, Zhenzhen; Zhou, Meng

2017-08-22

Complex diseases cannot be understood only on the basis of single gene, single mRNA transcript or single protein but the effect of their collaborations. The combination consequence in molecular level can be captured by the alterations of metabolites. With the rapidly developing of biomedical instruments and analytical platforms, a large number of metabolite signatures of complex diseases were identified and documented in the literature. Biologists' hardship in the face of this large amount of papers recorded metabolic signatures of experiments' results calls for an automated data repository. Therefore, we developed MetSigDis aiming to provide a comprehensive resource of metabolite alterations in various diseases. MetSigDis is freely available at http://www.bio-annotation.cn/MetSigDis/. By reviewing hundreds of publications, we collected 6849 curated relationships between 2420 metabolites and 129 diseases across eight species involving Homo sapiens and model organisms. All of these relationships were used in constructing a metabolite disease network (MDN). This network displayed scale-free characteristics according to the degree distribution (power-law distribution with R2 = 0.909), and the subnetwork of MDN for interesting diseases and their related metabolites can be visualized in the Web. The common alterations of metabolites reflect the metabolic similarity of diseases, which is measured using Jaccard index. We observed that metabolite-based similar diseases are inclined to share semantic associations of Disease Ontology. A human disease network was then built, where a node represents a disease, and an edge indicates similarity of pair-wise diseases. The network validated the observation that linked diseases based on metabolites should have more overlapped genes. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

TFG-MET fusion in an infantile spindle cell sarcoma with neural features.

Science.gov (United States)

Flucke, Uta; van Noesel, Max M; Wijnen, Marc; Zhang, Lei; Chen, Chun-Liang; Sung, Yun-Shao; Antonescu, Cristina R

2017-09-01

An increasing number of congenital and infantile sarcomas displaying a primitive, monomorphic spindle cell phenotype have been characterized to harbor recurrent gene fusions, including infantile fibrosarcoma and congenital spindle cell rhabdomyosarcoma. Here, we report an unusual spindle cell sarcoma presenting as a large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The tumor resembled the morphology of an infantile fibrosarcoma with both fascicular and patternless growth, however, it expressed strong S100 protein immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression. Although this immunoprofile suggested partial neural/neuroectodermal differentiation, overall features were unusual and did not fit into any known tumor types (cellular schwannoma, MPNST), raising the possibility of a novel pathologic entity. The TFG-MET gene fusion expands the genetic spectrum implicated in the pathogenesis of congenital spindle cell sarcomas, with yet another example of kinase oncogenic activation through chromosomal translocation. The discovery of this new fusion is significant since the resulting MET activation can potentially be inhibited by targeted therapy, as MET inhibitors are presently available in clinical trials. © 2017 Wiley Periodicals, Inc.

Metáfora multimodal: representación mediática del despojo

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Neyla Graciela Pardo Abril

2012-01-01

Full Text Available La interacción comunicativa ocurre con frecuencia cuando se acude a sistemas de signos múltiples que se soportan, de manera significativa, en tecnologías y pretende interlocutores impredecibles. Desde esta perspectiva, la lengua es apenas un sistema sígnico y sus modos de significación se han amplificado. En este trabajo, de acuerdo con las teorías cognitivas, se entiende que la metáfora, como recurso semiótico, supera el uso de la lengua, se estructura en diversos sistemas de signos y formula saberes, pensamiento y acción social. Se estudia la metáfora producida y comprendida en diversos modos semióticos y se aplica a un proceso de investigación en curso, en el que se analizan cuatro caricaturas del periódico digital eltiempo.com y tres de elespectador.com, que forman parte de un corpus más amplio compilado en medios virtuales. Se proponen algunas reflexiones sobre la metáfora multimodal, su relación con la metáfora verbal y los procesos de amplificación de los significados que se derivan de una posible interpretación. Finalmente, se presentan algunas conclusiones sobre la representación mediática del despojo.

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

NARCIS (Netherlands)

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

2017-01-01

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

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

An integrated approach for a higher success rate in mergers and acquisitions

Directory of Open Access Journals (Sweden)

Andrej Bertoncelj

2007-05-01

Full Text Available The paper outlines the importance of balanced management of hard and soft key success factors, combining the economic logic of corporate performance and human capital through an integrated approach to mergers and acquisitions. The study, based on a questionnaire and interviews, suggests that the achievement level ofmergers and acquisitions’ objectives of acquiring companies in Slovenia should be comparable to findings of similar studies; namely, the objectives that drove the deal were met only half the time. The results indicate that five hard success factors – a professional target search and due diligence, a realistic assessment of synergies, theright mix of financial sources, a detailed post-acquisition integration plan already prepared in the pre-deal phase and its speedy implementation – and five soft success factors – a new “combined” organizational culture, a competent management team, innovative employees, efficient and consistent communication and a creative business environment – are becoming increasingly relevant. Even though they differ in their importance for individual companies in the sample, they are all considered essential to increasing the success rate of corporate combinations

Sustainable energy with thermochemical storage; Duurzame energie met thermochemische opslag

Energy Technology Data Exchange (ETDEWEB)

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

2010-03-15

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

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

NARCIS (Netherlands)

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

2010-01-01

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

Kenmerken en recidivecijfers van ex-terbeschikkinggestelden met een zedendelict

NARCIS (Netherlands)

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

2012-01-01

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

Providing Feedback, Orientation and Opportunities for Reflection as Key Elements for Successful Mentoring Programs: Reviewing a Program for Future Business Education Teachers

Directory of Open Access Journals (Sweden)

Elisabeth Riebenbauer

2017-12-01

Full Text Available The introduction to teaching is critical for novice teachers. Near the end of their master’s program, students of Business Education and Development in Austria spend one semester at an assigned school. They are introduced to teaching, while being assisted by peer students, mentoring teachers, and a companion course. Mentors receive special training and preparation in advance, thus contributing to a high quality mentoring program. The program is organized threefold: (1 providing feedback, (2 opportunities for reflection and (3 career orientation. The purpose of this paper is to assess key elements of successful mentoring programs and to question which competences of mentors contribute most to the success of those programs. Between 2012 and 2015, 188 persons (student teachers and their mentors responded to an online survey at the end of their mentoring program. Additionally, data from a study (1,245 questionnaires regarding the student teachers’ perception of their own competence was utilized, allowing for a comparison of student teacher confidence in their abilities before and after the mentoring program. The present results provide insight into the key elements of successful mentoring programs; both from a student teacher’s and mentor’s perspective. During the semester, students showed an increase regarding their self-perception of their professional competences. It was found that students and mentoring teachers valued feedback after each lesson more than feedback in regular meetings. Opportunities for reflection (e.g. exchange with peer students, learning diaries were considered helpful. The mentoring program helped students to decide whether to become a teacher or not.

Ginsenoside-Rg{sub 1} induces angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a

Energy Technology Data Exchange (ETDEWEB)

Kwok, Hoi-Hin [Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Chan, Lai-Sheung [Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Poon, Po-Ying [Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Yue, Patrick Ying-Kit [Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Wong, Ricky Ngok-Shun, E-mail: rnswong@hkbu.edu.hk [Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China)

2015-09-15

Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. Ginsenoside-Rg{sub 1} (Rg{sub 1}), one of the most abundant active components of ginseng, has been demonstrated as an angiogenesis-stimulating compound in different models. There is increasing evidence implicating microRNAs (miRNAs), a group of non-coding RNAs, as important regulators of angiogenesis, but the role of microRNAs in Rg{sub 1}-induced angiogenesis has not been fully explored. In this report, we found that stimulating endothelial cells with Rg{sub 1} could reduce miR-23a expression. In silico experiments predicted hepatocyte growth factor receptor (MET), a well-established mediator of angiogenesis, as the target of miR-23a. Transfection of the miR-23a precursor or inhibitor oligonucleotides validated the inverse relationship of miR-23a and MET expression. Luciferase reporter assays further confirmed the interaction between miR-23a and the MET mRNA 3′-UTR. Intriguingly, ginsenoside-Rg{sub 1} was found to increase MET protein expression in a time-dependent manner. We further demonstrated that ginsenoside-Rg{sub 1}-induced angiogenic activities were indeed mediated through the down-regulation of miR-23a and subsequent up-regulation of MET protein expression, as confirmed by gain- and loss-of-function angiogenic experiments. In summary, our results demonstrated that ginsenoside-Rg{sub 1} could induce angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a. This study has broadened our understanding of the non-genomic effects of ginsenoside-Rg{sub 1,} and provided molecular evidence that warrant further development of natural compound as novel angiogenesis-promoting therapy. - Highlights: • Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. • Ginsenoside-Rg{sub 1} (Rg{sub 1}) has been demonstrated as an angiogenesis-stimulating compound. • We found that Rg{sub 1} induces angiogenesis by

Metáforas para profesor y estudiante de pedagogía en un grupo de estudiantes de pedagogía chilenos

Directory of Open Access Journals (Sweden)

Paola Alarcón

2014-05-01

Full Text Available En este artículo se presentan los resultados de una investigación de tipo cualitativo, cuyo objetivo general es identificar los conceptos metafóricos los estudiantes de pedagogía acerca de cómo ellos creen que el profesor es representado por la sociedad, y como representan ellos a sí mismos. El marco de referencia lo constituyen la cognición docente y la metáfora conceptual. Para la elicitación de metáforas se aplicó un cuestionario a un grupo de 70 estudiantes de Pedagogía de la Universidad de Concepción, Chile. Se realizó un análisis de contenido que abarcó las siguientes etapas: etiquetado, clasificación, categorización y juicio de externos. Para las metáforas sobre cómo es representado el profesor por la sociedad, a través del análisis, se identificaron las siguientes categorías: Metáforas centradas en el profesor, Metáforas centradas en el estudiante, Metáforas centradas en la valoración social. Para las metáforas sobre cómo es representado el estudiante de pedagogía se identificaron las siguientes categorías: Metáforas centradas en el proceso de formación profesional, Metáforas centradas en el proceso de enseñanza aprendizaje, Metáforas centradas en la valoración social. Finalmente, se comentan los alcances y proyecciones del estudio, y se discute la pertinencia de algunas categorías en el contexto de la formación de profesores. This article provides the results of a qualitative study, whose main objective is to identify the metaphorical concepts through which teacher candidates believe how teachers are represented by society, and how they represent themselves. The referential framework of this study is given by teacher cognition and conceptual metaphor. A questionnaire was applied to elicit metaphors from 70 teacher candidates at the University of Concepción, Chile. Content analysis was used, following these stages: coding, classification, categorization and scholar review. For the metaphors on how

Summary Record of the First Meeting of the Radioactive Waste Repository Metadata Management (RepMet) Initiative

International Nuclear Information System (INIS)

2014-01-01

National radioactive waste repository programmes are collecting large amounts of data to support the long-term management of their nations' radioactive wastes. The data and related records increase in number, type and quality as programmes proceed through the successive stages of repository development: pre-siting, siting, characterisation, construction, operation and finally closure. Regulatory and societal approvals are included in this sequence. Some programmes are also documenting past repository projects and facing a challenge in allowing both current and future generations to understand actions carried out in the past. Metadata allows context to be stored with data and information so that it can be located, used, updated and maintained. Metadata helps waste management organisations better utilise their data in carrying out their statutory tasks and can also help verify and demonstrate that their programmes are appropriately driven. The NEA Radioactive Waste Repository Metadata Management (RepMet) initiative aims to bring about a better understanding of the identification and administration of metadata - a key aspect of data management - to support national programmes in managing their radioactive waste repository data, information and records in a way that is both harmonised internationally and suitable for long-term management and use. This is a summary record of the 1. meeting of the RepMet initiative. The actions and decisions from this meeting were sent separately to the group after the meeting, but are also included in this document (Annex A). The list of participants is attached as well (Annex B)

Evaluation of clinial usefulness of 11C-methionine positron emission tomography (11C-MET-PET) as a tool for liver functional imaging

International Nuclear Information System (INIS)

Enomoto, Kazuo; Matsui, Yoshifumi; Okazumi, Shinichi

1994-01-01

We studied 11 C-MET-PET in 17 clinical cases, 10 patients with obstructive jaundice and 7 normal volunteers, and analyzed its efficacy for the evaluation of hepatic functional reserve in major hepatectomy candidates. Differential absorption ratio (DAR) of 11 C was compared to the hepatic protein synthesis rate (HPS), which is measured as the incorporation rate of 3 H-labeled leucine in protein fraction, using needle biopsied liver specimen obtained from each hepatic segment. In the cases of normal liver function, DAR was well correlated with HPS. Also in jaundice cases with two exceptions, low HPS segment was demonstrated as low DAR segment. Consequently, MET-PET images could clearly provide functional liver imaging. After injection of 11 C-MET, the increase in rate of radioactivity of 11 C in plasma protein fraction was higher in jaundice cases than in normal volunteers, which is in accord with the results of our former study that cholestatic liver has accelerated protein synthesis rate. In summary, since 11 C-MET-PET could demonstrate liver functional imaging, it might be a possible tool for liver function assessment in major hepatectomy candidates. (author)

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

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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.

Leven met de varroamijt in de 21ste eeuw

NARCIS (Netherlands)

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

2002-01-01

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

Preparation, crystallization and preliminary X-ray analysis of the methionine synthase (MetE) from Streptococcus mutans

International Nuclear Information System (INIS)

Fu, Tian-Min; Zhang, Xiao-Yan; Li, Lan-Fen; Liang, Yu-He; Su, Xiao-Dong

2006-01-01

Methionine synthase (MetE) from S. mutans was expressed, purified and crystallized. Diffraction data have been collected to 2.2 Å resolution. The Streptococcus mutans metE gene encodes methionine synthase (MetE), which catalyzes the direct transfer of a methyl group from methyltetrahydrofolate to homocysteine in the last step of methionine synthesis. metE was cloned into pET28a and the gene product was expressed at high levels in the Escherichia coli strain BL21 (DE3). MetE was purified to homogeneity using Ni 2+ -chelating chromatography followed by size-exclusion chromatography. Crystals of the protein were obtained by the hanging-drop vapour-diffusion method and diffracted to 2.2 Å resolution. The crystal belongs to space group P2 1 , with unit-cell parameters a = 52.85, b = 99.48, c = 77.88 Å, β = 94.55°

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.

Metástasis hipofisaria Hypophyseal metastasis

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Miguel Ángel Yanes Quesada

2009-04-01

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

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

Science.gov (United States)

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

2012-08-10

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

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

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Samuel Brocklehurst

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

A review of the success and failure characteristics of resin-bonded bridges.

Science.gov (United States)

Miettinen, M; Millar, B J

2013-07-01

This literature review was designed to assess and compare the success rates and modes of failure of metal-framed, fibre-reinforced composite and all-ceramic resin-bonded bridges. A Medline search (Ovid), supplemented by hand searching, was conducted to identify prospective and retrospective cohort studies on different resin-bonded bridges within the last 16 years. A total of 49 studies met the pre-set inclusion criteria. Success rates of 25 studies on metal-framed, 17 studies on fibre-reinforced composite and 7 studies on all-ceramic resin-bonded bridges were analysed and characteristics of failures were identified. The analysis of the studies indicated an estimation of annual failure rates per year to be 4.6% (±1.3%, 95% CI) for metal-framed, 4.1% (±2.1%, 95% CI) for fibre-reinforced and 11.7% (±1.8%, 95% CI) for all-ceramic resin-bonded bridges. The most frequent complications were: debonding for metal-framed, resin-bonded bridges (93% of all failures); delamination of the composite veneering material for the fibre-reinforced bridges (41%) and fracture of the framework for the all-ceramic bridges (57%). All types of resin-bonded bridges provide an effective short- to medium-term option, with all-ceramic performing least well and having the least favourable mode of failure. The methods of failures were different for different bridges with metal frameworks performing the best over time.

E-referral Solutions: Successful Experiences, Key Features and Challenges- a Systematic Review.

Science.gov (United States)

Naseriasl, Mansour; Adham, Davoud; Janati, Ali

2015-06-01

around the world health systems constantly face increasing pressures which arise from many factors, such as an ageing population, patients and providers demands for equipment's and services. In order to respond these challenges and reduction of health system's transactional costs, referral solutions are considered as a key factor. This study was carried out to identify referral solutions that have had successes. relevant studies identified using keywords of referrals, consultation, referral system, referral model, referral project, electronic referral, electronic booking, health system, healthcare, health service and medical care. These searches were conducted using PubMed, ProQuest, Google Scholar, Scopus, Emerald, Web of Knowledge, Springer, Science direct, Mosby's index, SID, Medlib and Iran Doc data bases. 4306 initial articles were obtained and refined step by step. Finally, 27 articles met the inclusion criteria. we identified seventeen e-referral systems developed in UK, Norway, Finland, Netherlands, Denmark, Scotland, New Zealand, Canada, Australia, and U.S. Implemented solutions had variant degrees of successes such as improved access to specialist care, reduced wait times, timeliness and quality of referral communication, accurate health information transfer and integration of health centers and services. each one of referral solutions has both positive and changeable aspects that should be addressed according to sociotechnical conditions. These solutions are mainly formed in a small and localized manner.

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

DEFF Research Database (Denmark)

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

2012-01-01

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

Biases of the MET Temperature and Relative Humidity Sensor (HMP45) Report

Energy Technology Data Exchange (ETDEWEB)

Kyrouac, Jenni [Argonne National Lab. (ANL), Argonne, IL (United States); Theisen, Adam [Univ. of Oklahoma, Norman, OK (United States)

2017-06-30

The U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility Data Quality (DQ) Office was alerted to a potential bias in the surface meteorological instrumentation (MET) temperature when compared with a nearby Mesonet station. This led to an investigation into this problem that was expanded to include many of the other extended facilities (EF) and both the temperature and relative humidity (RH) variables. For this study, the Mesonet was used as the standard reference due to results that showed an increased accuracy in high-humidity environments along with the fact that the Mesonet had previous documented a problem with the HMP45C sensors. Some differences between the sites were taken into account during the analysis: 1. ARM MET sensors were upgraded from an HMP35 to an HMP45 throughout 2007 2. Mesonet switched to aspirated shields in 2009 – To mitigate the differences between aspirated and non-aspirated measurements, data were only analyzed when the wind speed was higher than 3 m/s. This reduced the uncertainty for the non-aspirated measurements from 1.51 ºC to 0.4 ºC. 3. ARM MET is mounted 0.5m higher than the Mesonet station (2.0m versus 1.5m) – This is assumed to have a negligible effect on the differences. 4. Sites were not co-located – For some locations, the distances between sites were as much as 45 km. As part of the investigation into the differences, the Mesonet had reported that the HMP45 sensors had a low-temperature bias in high-humidity environments. This was verified at two different sites where the ARM measurements were compared with the Mesonet measurements. The Mesonet provided redundant temperature measurements from two different sensors at each site. These measurements compared fairly well, while the ARM sensor showed a bias overnight when the humidities were higher. After reviewing the yearly average differences in the data and analyzing the RH data during fog events when we assume it should be

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

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Roko Martinić

2014-08-01

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

Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress.

Science.gov (United States)

Tsuru, Jusen; Tanaka, Yoshihiro; Ishitobi, Yoshinobu; Maruyama, Yoshihiro; Inoue, Ayako; Kawano, Aimi; Ikeda, Rie; Ando, Tomoko; Oshita, Harumi; Aizawa, Saeko; Masuda, Koji; Higuma, Haruka; Kanehisa, Masayuki; Ninomiya, Taiga; Akiyoshi, Jotaro

2014-01-01

Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder. To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A). A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; PBDNF had different effects on hypothalamic-pituitary-adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests.

CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling

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Matous Hrdinka

2016-03-01

Full Text Available Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub is assembled by the linear ubiquitin assembly complex (LUBAC, and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation.

Preparation, crystallization and preliminary X-ray analysis of the methionine synthase (MetE) from Streptococcus mutans

Energy Technology Data Exchange (ETDEWEB)

Fu, Tian-Min; Zhang, Xiao-Yan; Li, Lan-Fen; Liang, Yu-He, E-mail: liangyh@pku.edu.cn; Su, Xiao-Dong [National Laboratory of Protein Engineering and Plant Genetic Engineering, Peking University, Beijing 100871 (China); Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing 100871 (China)

2006-10-01

Methionine synthase (MetE) from S. mutans was expressed, purified and crystallized. Diffraction data have been collected to 2.2 Å resolution. The Streptococcus mutans metE gene encodes methionine synthase (MetE), which catalyzes the direct transfer of a methyl group from methyltetrahydrofolate to homocysteine in the last step of methionine synthesis. metE was cloned into pET28a and the gene product was expressed at high levels in the Escherichia coli strain BL21 (DE3). MetE was purified to homogeneity using Ni{sup 2+}-chelating chromatography followed by size-exclusion chromatography. Crystals of the protein were obtained by the hanging-drop vapour-diffusion method and diffracted to 2.2 Å resolution. The crystal belongs to space group P2{sub 1}, with unit-cell parameters a = 52.85, b = 99.48, c = 77.88 Å, β = 94.55°.

An Analysis of Factors Affecting Mature Age Students' Academic Success in Undergraduate Nursing Programs: A Critical Literature Review.

Science.gov (United States)

Hayden, Lisa J; Jeong, Sarah Y; Norton, Carol A

2016-01-01

The population of mature age students entering university nursing programs has steadily increased in both Australia and worldwide. The objective of the literature review was to explore how mature age students perform academically and to analyse the factors associated with their academic performance in nursing programs. A literature search was conducted in the following databases: CINAHL, ProQuest, Medline, Cochrane, Mosby's Index, Joanna Briggs Institute (JBI), and Scopus. Twenty-six (26) research papers published between 2000 and 2014 have met the selection criteria of this review. The key themes identified include; 1) ambiguity in definition of mature age and academic success, 2) age and academic success, 3) intrinsic factors (life experiences, emotional intelligence, and motivation and volition), and 4) extrinsic factors (peer, academic and family support; and learning style, components of the modules and mode of delivery). Current literature provides evidence that mature age nursing students perform at a higher level within the methodological issues discussed in this paper. Future research is warranted to advance the understanding of the complex relationship between extrinsic and intrinsic factors of mature age students and their academic success in higher education. Nursing educators will benefit from novel evidence, ideas and opportunities to explore and implement in nursing education.

Impact of BDNF Val66Met and 5-HTTLPR polymorphism variants on neural substrates related to sadness and executive function.

Science.gov (United States)

Wang, L; Ashley-Koch, A; Steffens, D C; Krishnan, K R R; Taylor, W D

2012-04-01

The brain-derived neurotrophic factor (BDNF) Val(66) Met allelic variation is linked to both the occurrence of mood disorders and antidepressant response. These findings are not universally observed, and the mechanism by which this variation results in increased risk for mood disorders is unclear. One possible explanation is an epistatic relationship with other neurotransmitter genes associated with depression risk, such as the serotonin-transporter-linked promotor region (5-HTTLPR). Further, it is unclear how the coexistence of the BDNF Met and 5-HTTLPR S variants affects the function of the affective and cognitive control systems. To address this question, we conducted a functional magnetic resonance imaging (fMRI) study in 38 older adults (20 healthy and 18 remitted from major depressive disorder). Subjects performed an emotional oddball task during the fMRI scan and provided blood samples for genotyping. Our analyses examined the relationship between genotypes and brain activation to sad distractors and attentional targets. We found that 5-HTTLPR S allele carriers exhibited stronger activation in the amygdala in response to sad distractors, whereas BDNF Met carriers exhibited increased activation to sad stimuli but decreased activation to attentional targets in the dorsolateral prefrontal and dorsomedial prefrontal cortices. In addition, subjects with both the S allele and Met allele genes exhibited increased activation to sad stimuli in the subgenual cingulate and posterior cingulate. Our results indicate that the Met allele alone or in combination with 5-HTTLPR S allele may increase reactivity to sad stimuli, which might represent a neural mechanism underlying increased depression vulnerability. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Factors contributing to migraine headache surgery failure and success.

Science.gov (United States)

Larson, Kelsey; Lee, Michelle; Davis, Janine; Guyuron, Bahman

2011-11-01

The purpose of this study was to identify factors that contribute to migraine headache surgery failure and success. A retrospective chart review was conducted of patients who underwent surgery for migraine headaches performed by the senior author (B.G.) and had at least 11 months of follow-up. The study population included three groups: migraine surgery success, improvement, and failure. Thirty-six unique data points were collected for each patient. A total of 169 patients met inclusion criteria. Of these, 66 patients comprised the migraine surgery success group (S, complete elimination of migraine headaches); 67 comprised the migraine surgery improvement group (I, >50 percent reduction in migraine frequency, intensity, or duration); and 36 comprised the migraine surgery failure group (F, I, p=0.02), migraine frequency (SI, p=0.003; S>F, p=0.04), history of head or neck injury (SI, p=0.02), increased intraoperative bleeding (SF, p=0.0006; I>F, p=0.0004), site II (S>F, p=0.015), single operative site (SI, p=0.05; S>F, p=0.04). Factors associated with migraine surgery failure include increased intraoperative bleeding and surgery on fewer trigger sites. Factors associated with migraine surgery success are older age of migraine onset, higher rate of visual symptoms versus improvement group, surgery at site I or II, and deactivating all four operative sites. Risk, III.

Association between COMT Polymorphism Val158Met and Opioid Consumption in Patients with Postoperative Pain: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Bo Hu

2018-01-01

Full Text Available Background/Aims: Several factors influencing postoperative pain and the effect of opioid analgesics have been investigated on an individual level. The aim of this study was to clarify the impact of catecholamine-O-methyltransferase (COMT gene Val158Met on opioid consumption in postoperative patients. Methods: A systematic review and meta-analysis of the literature up to September 30, 2017, were performed by using PubMed, Cochrane Library, ISI Web of Science, and Chinese National Knowledge Infrastructure (CNKI database. The meta-analysis examined all studies involving the association between genetic polymorphisms of COMT Val158Met and opioid consumption during the acute postoperative period. Results: Of the 153 identified studies, 23 studies were retrieved for systematic review and 10 studies were retrieved for meta-analysis. However, it was impossible to conduct meta-analysis on the association between COMT Val158Met polymorphism and postoperative pain because of heterogeneity of the data. Overall, meta-analysis showed that COMT Val/Met carriers consumed less opioid for analgesia within the first 24 hours after surgery (SMD = 0.14, 95% CI = [0.03, 0.25], P = 0.01 but not within 48 hours (SMD = 0.14, 95% CI = [0.08, 0.36], P = 0.21. There was no significant difference in opioid consumption between Val/ Val and Met/Met patients. Conclusion: Patients with Val/Met but not Met/Met allele variant consumed less opioid, though larger and better-designed studies are required to obtain an exclusive conclusion about the correlation between postoperative pain and COMT Val158Met polymorphism.

Redefining reproductive success in songbirds: Moving beyond the nest success paradigm

Science.gov (United States)

Streby, Henry M.; Refsnider, Jeanine M.; Andersen, David E.

2014-01-01

One of the most commonly estimated parameters in studies of songbird ecology is reproductive success, as a measure of either individual fitness or population productivity. Traditionally, the “success” in reproductive success refers to whether, or how many, nestlings leave nests. Here, we advocate that “reproductive success” in songbirds be redefined as full-season productivity, or the number of young raised to independence from adult care in a breeding season. A growing body of evidence demonstrates interdependence between nest success and fledgling survival, and emphasizes that data from either life stage alone can produce misleading measures of individual fitness and population productivity. Nest success, therefore, is an insufficient measure of reproductive success, and songbird ecology needs to progress beyond this long-standing paradigm. Full-season productivity, an evolutionarily rational measure of reproductive success, provides the framework for appropriately addressing unresolved questions about the adaptive significance of many breeding behaviors and within which effective breeding-grounds conservation and management can be designed.

Establishing predictors for successfully planned endotracheal extubation.

Science.gov (United States)

Lai, Chih-Cheng; Chen, Chin-Ming; Chiang, Shyh-Ren; Liu, Wei-Lun; Weng, Shih-Feng; Sung, Mei-I; Hsing, Shu-Chen; Cheng, Kuo-Chen

2016-10-01

The aim of this study was to establish predictors for successfully planned extubation, which can be followed by medical personnel. The patients who were admitted to the adult intensive care unit of a tertiary hospital and met the following criteria between January 2005 and December 2014 were collected retrospectively: intubation > 48 hours; and candidate for extubation. The patient characteristics, including disease severity, rapid shallow breath index (RSBI), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), cuff leak test (CLT) before extubation, and outcome, were recorded. The CLT was classified as 2+ with audible flow without a stethoscope, 1+ with audible flow using a stethoscope, and negative (N) with no audible flow, even with a stethoscope. Failure to extubate was defined as reintubation within 48 hours. In total, 6583 patients were enrolled and 403 patients (6.1%) had extubation failures. Male patients dominated the patient cohort (4261 [64.7%]). The mean age was 64.5±16.3 years. The overall in-hospital mortality rate was 11.3%. The extubation failure rate for females was greater than males (7.7% vs 5.3%, P respiratory capacity, was developed to better predict extubation success.

The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress.

Science.gov (United States)

Alexander, Nina; Osinsky, Roman; Schmitz, Anja; Mueller, Eva; Kuepper, Yvonne; Hennig, Juergen

2010-07-01

Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date. Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity. Healthy male adults (N=100) were genotyped and exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol and self-reported mood levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Furthermore, heart rate reactivity as an indicator of sympathetic activation was monitored continuously during the experimental procedure. We report a small, but significant effect of the BDNF Val66Met polymorphism on stress reactivity. More precisely, carriers of the met-allele showed a significantly attenuated HPA-axis and cardiovascular reactivity to the psychosocial stressor compared to subjects with the val/val genotype. Furthermore, the diminished physiological response in met-allele carriers was also attended by significantly lower self-reported ratings of perceived stress and nervousness. Our findings of a diminished endocrine and cardiovascular stress response in healthy male adults is consistent with a previously published study and adds further evidence for a crucial role of the BDNF Val66Met polymorphism in the modulation of stress reactivity. Copyright 2010. Published by Elsevier Ltd.

Zuivering brouwerijprocesafvalwater met behulp van microalgen: Resultaten onderzoek 2012

NARCIS (Netherlands)

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

2013-01-01

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

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

NARCIS (Netherlands)

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

2014-01-01

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

Successful projects subsidized by the ROB-programme; Succesvolle ROB-gesubsidieerde projecten

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-03-15

In the past years the Dutch program Reduction Other Greenhouse Gases (ROB) focused on the enhancement, development and implementation of measures aimed at reducing emissions of non-CO2 greenhouse gases. The main focus was directed to agriculture. Cooling and landfills. SenterNovem (currently named NL Agency) offered options for subsidies, knowledge and advice to start working on the reduction of non-CO2 greenhouse gases. A few examples of successful projects financed by ROB subsidy are briefly discussed. [Dutch] Het programma Reductie Overige Broeikasgassen (ROB) richtte zich de afgelopen jaren op het bevorderen, ontwikkelen en toepassen van maatregelen ter vermindering van de uitstoot van niet-CO2 broeikasgassen. De aandacht ging hierbij vooral uit naar de emissies van overige broeikasgassen afkomstig uit de landbouw, koeling en stortplaatsen. SenterNovem (nu het Agentschap NL) bood subsidiemogelijkheden, kennis en advies om met de reductie van niet-CO2 broeikasgassen aan de slag te gaan. Een paar voorbeelden van succesvolle projecten die met ROB-subsidies zijn gefinancierd worden in dit artikel kort besproken.

Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway

Directory of Open Access Journals (Sweden)

Su M

2017-11-01

Full Text Available Meng Su,1 Baoli Qin,1 Fang Liu,2 Yuze Chen,2 Rui Zhang2 1Department of Internal Medicine, 2Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Liaoning, China Abstract: Colorectal cancer (CRC is the third most common malignant neoplasm worldwide. 5-Fluorouracil (5-Fu is the most important chemotherapeutic drug used for the treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in CRC clinical practice recently. Andrographolide (Andro is a main bioactive constituent of the herb Andrographis paniculata, which has various biological effects including anti-inflammation and antitumor activities. In the present study, we investigated the effects of combined Andro with 5-Fu against CRC HCT-116 cells. In vitro studies showed that Andro synergistically enhanced the anti-proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells. Meanwhile, results of the enzyme linked immunosorbent assay indicated that the level of phosphorylated cellular-mesenchymal to epithelial transition factor (p-MET was decreased by the combination treatment. Further study suggested that Andro promoted the antitumor effect of 5-Fu by downregulating the level of p-MET. In conclusion, these results confirmed the synergistic antitumor activity of Andro on CRC and provide evidence for possible clinical application of Andro for enhancing the antitumor effect of 5-Fu in CRC treatment. Keywords: Andro, 5-Fu, HCT-116 cells, apoptosis, p-MET

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

OpenAIRE

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

2017-01-01

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

Metátese na linguagem infantil: “porfessora” é bom, “professora” é melhor

Directory of Open Access Journals (Sweden)

Rosa M. Lima

2013-12-01

Full Text Available A leitura e a escrita são ensinadas a crianças cuja linguagem oral contém ainda, muitas vezes, desvios subtis. A metátese é um desses desvios, consistindo na troca da ordem de fonemas na palavra, tal como acontece em “corcodilo”. Analisámos a presença da metátese na linguagem infantil. Num primeiro estudo, investigámos a aquisição da linguagem oral dos 3 aos 7 anos de idade. A metátese mostrou um peso crescente ao longo da idade. Num segundo estudo, analisámos o desempenho de crianças do 4º ano na deteção auditiva e visual da metátese, e na escrita de palavras passíveis de induzir a metátese. A deteção visual da metátese foi inferior ao nível do acaso. Na escrita de palavras, a metátese deu conta de 69% a 75% dos erros observados. Os resultados sugerem que a metátese constitui um processo indicador de domínio da linguagem oral, revelando formas de gestão de estruturas silábicas complexas. Contudo, essas formas de gestão podem cristalizar-se durante o primeiro ciclo, afetando negativamente a aquisição da linguagem escrita. Children often learn to read and write when their oral language is still marked by subtle errors. Metathesis is one such error. It is a phonological process whereby the order of phonemes is interchanged in the word, such as “corcodilo” instead of “crocodilo”. We investigated metathesis in child language. In a first study, we investigated spoken language acquisition from 3 to7 and half years of age. Metathesis increased with age. In a second study, we analysed the performance of children attending the 4th grade, in auditory and visual detection of metathesis, as well as in spelling words prone to metathesis. Performance in the visual detection of metathesis was significantly below chance. In word spelling tasks, metathesis accounted for 69% to 75% of errors. Results suggest that metathesis indexes some mastery of spoken language, and that it reveals the ability to deal with complex

Development and Initial Validation of a Client-Rated MET-CBT Adherence Measure

Directory of Open Access Journals (Sweden)

Wendy R. Ulaszek

2012-01-01

Full Text Available Traditional mechanisms for rating adherence or fidelity are labor-intensive. We developed and validated a tool to rate adherence to Motivational Enhancement Therapy–-Cognitive Behavioral Treatment (MET-CBT through anonymous client surveys. The instrument was used to survey clients in 3 methadone programs over 2 waves. Explanatory and Confirmatory Factor Analyses were used to establish construct validity for both MET and CBT. Internal consistency based on Cronbach's alpha was within adequate range (α > 0.70 for all but 2 of the subscales in one of the samples. Consensus between clients’ ratings (r wg(j scores were in the range of 0.6 and higher, indicating a moderate to strong degree of agreement among clients’ ratings of the same counselor. These results suggest that client surveys could be used to measure adherence to MET-CBT for quality monitoring that is more objective than counselor self-report and less resource-intensive than supervisor review of taped sessions. However, additional work is needed to develop this scale.

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

Science.gov (United States)

Bill & Melinda Gates Foundation, 2010

2010-01-01

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

Auditing Marketing Strategy Implementation Success

OpenAIRE

Herhausen, Dennis; Egger, Thomas; Oral, Cansu

2014-01-01

What makes a marketing strategy implementation successful and how can managers measure this success? To answer these questions, we developed a two-step audit approach. First, managers should measure the implementation success regarding effectiveness, efficiency, performance outcomes, and strategic embeddedness. Second, they should explore the reasons that have led to success or failure by regarding managerial, leadership, and environmental traps. Doing so will also provide corrective action p...

Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH test results in depressed patients.

Science.gov (United States)

Schüle, Cornelius; Zill, Peter; Baghai, Thomas C; Eser, Daniela; Zwanzger, Peter; Wenig, Nadine; Rupprecht, Rainer; Bondy, Brigitta

2006-09-01

Data suggest that both neurotrophic and hypothalamic-pituitary-adrenocortical (HPA) systems are involved in the pathophysiology of depression. The aim of the present study was to investigate whether the non-conservative brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has an impact on HPA axis activity in depressed patients. At admission, the dexamethasone/CRH (DEX/CRH) test was performed in 187 drug-free in-patients suffering from major depression or depressed state of bipolar disorder (DSM-IV criteria). Moreover, genotyping of BDNF Val66Met polymorphism was carried out using the fluorescence resonance energy transfer method (FRET). Homozygous carriers of the Met/Met genotype showed a significantly higher HPA axis activity during the DEX/CRH test than patients carrying the Val/Val or Val/Met genotype (ACTH, cortisol). Our results further contribute to the hypothesized association between HPA axis dysregulation and reduced neuroplasticity in depression and are consistent with the assumption that BDNF is a stress-responsive intercellular messenger modifying HPA axis activity.

Enfocando la metáfora visual: ópticas cognitivas I

Directory of Open Access Journals (Sweden)

Oquitzin Aguilar Leyva

2012-01-01

Full Text Available La reflexión en torno a la metáfora ha acompañado el devenir del pensamiento occidental desde sus orígenes. Desde las tentativas iniciales de su elucidación, acuñadas en la Retórica y Poética aristotélicas, hasta las modernas teorías de la interacción emergidas ya bien entrado el siglo veinte, se ha acumulado un gran número de acercamientos cuyo censo y comentario constituyen materia prima de no pocas monografías, como las de Hawkes (1972 y Ricoeur (1980, por citar algunas destacadas. Lejos de buscar prolongar dichos esfuerzos, nuestra aportación se inspira en el creciente auge de iconos en la comunicación mediática contemporánea para desarrollar una reflexión, tanto sobre la plausible existencia de la metáfora visual y/o audiovisual, como de los términos teórico-metodológicos con los que su análisis podría ser encarado. De corte teórico, la pesquisa que aquí avanzamos busca acercarnos a un encuadramiento para explorar la metáfora visual en tanto instrumento de comunicación, describriendo los procesos fundamentalmente cognitivos que su actualización en todo momento presupone…

Prestatiekenmerken van een TotalQuant-elementanalyse met ICP-MS

NARCIS (Netherlands)

Velde-Koerts T van der; LAC

1998-01-01

TotalQuant-analyse met ICP-MS is een geschikte methode om snel oplossingen van diverse materialen te scannen op alle elementen van het periodieke systeem, behalve H, N, O, F, edelgassen en kortlevende (radio-actieve) elementen. Bij een TotalQuant-analyse wordt gebruik gemaakt van een standaard

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

Science.gov (United States)

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

2015-01-01

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

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

Science.gov (United States)

MetLife, Inc., 2013

2013-01-01

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

Patients' family satisfaction with needs met at the medical intensive care unit.

Science.gov (United States)

Khalaila, Rabia

2013-05-01

The current study investigated the perceived importance and the perceived met needs of family members in the medical intensive care unit and assessed family members' satisfaction with needs met. Studies conducted throughout the world over the past 30 years indicate that family needs are still neglected. Unmet needs of family members of patients in the intensive care unit lead to dissatisfaction with care. A cross-sectional study. A total of 70 family members of critically ill patients were included in this study conducted in a medical intensive care unit in Israel between October 2007-September 2008, using a structured interview. Three outcomes measured by the Family Satisfaction in the Intensive Care Unit Inventory were regressed separately for baseline variables and family needs met subscales as measured by the Critical Care Family Needs Inventory. Multivariate linear regression analysis was used to detect factors that could have predicted each outcome. The results showed differences between the perceived importance and the perceived met needs of family members. Satisfaction with care was positively related to meeting all needs domains except the information need. However, satisfaction with information and decision-making was related only to meeting information and emotional support needs. Continued unmet needs of family members of intensive care unit patients have a negative impact on family satisfaction. Only sweeping changes in clinical practice will succeed in meeting the unmet needs of patients' families. © 2012 Blackwell Publishing Ltd.

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

Science.gov (United States)

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

2018-06-01

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

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.

Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

Science.gov (United States)

Trovato, Maria; D'Armiento, Maria; Lavra, Luca; Ulivieri, Alessandra; Dominici, Roberto; Vitarelli, Enrica; Grosso, Maddalena; Vecchione, Raffaella; Barresi, Gaetano; Sciacchitano, Salvatore

2007-02-01

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Kim, In-Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Lee, Jae-Ha [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo-Yoen; Kim, Jeong-Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cho, Eun-Wie [Epigenomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

2014-11-21

Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

International Nuclear Information System (INIS)

Kim, In-Gyu; Lee, Jae-Ha; Kim, Seo-Yoen; Kim, Jeong-Yul; Cho, Eun-Wie

2014-01-01

Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation

Stalboekje varkens : natuurlijk gezond met kruiden en andere natuurproducten

NARCIS (Netherlands)

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

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

Chunghau Lee

2006-01-01

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

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

Science.gov (United States)

Peng, Y; Lu, Z; Li, G; Piechowicz, M; Anderson, M; Uddin, Y; Wu, J; Qiu, S

2016-07-01

The human MET gene imparts a replicated risk for autism spectrum disorder (ASD), and is implicated in the structural and functional integrity of brain. MET encodes a receptor tyrosine kinase, MET, which has a pleiotropic role in embryogenesis and modifies a large number of neurodevelopmental events. Very little is known, however, on how MET signaling engages distinct cellular events to collectively affect brain development in ASD-relevant disease domains. Here, we show that MET protein expression is dynamically regulated and compartmentalized in developing neurons. MET is heavily expressed in neuronal growth cones at early developmental stages and its activation engages small GTPase Cdc42 to promote neuronal growth, dendritic arborization and spine formation. Genetic ablation of MET signaling in mouse dorsal pallium leads to altered neuronal morphology indicative of early functional maturation. In contrast, prolonged activation of MET represses the formation and functional maturation of glutamatergic synapses. Moreover, manipulating MET signaling levels in vivo in the developing prefrontal projection neurons disrupts the local circuit connectivity made onto these neurons. Therefore, normal time-delimited MET signaling is critical in regulating the timing of neuronal growth, glutamatergic synapse maturation and cortical circuit function. Dysregulated MET signaling may lead to pathological changes in forebrain maturation and connectivity, and thus contribute to the emergence of neurological symptoms associated with ASD.

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

OpenAIRE

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

2000-01-01

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

BDNF val66met association with serotonin transporter binding in healthy humans

DEFF Research Database (Denmark)

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

2017-01-01

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

Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice

Science.gov (United States)

Ieraci, Alessandro; Madaio, Alessandro I; Mallei, Alessandra; Lee, Francis S; Popoli, Maurizio

2016-01-01

Several studies have shown that exercise improves cognitive functions and emotional behaviors. Positive effects of exercise have been associated with enhanced brain plasticity, adult hippocampal neurogenesis, and increased levels of brain-derived neurotrophic factor (BDNF). However, a substantial variability of individual response to exercise has been described, which may be accounted for by individual genetic variants. Here, we have assessed whether and how the common human BDNF Val66Met polymorphism influences the neurobiological effects modulated by exercise in BDNF Val66Met knock-in male mice. Wild-type (BDNFVal/Val) and homozygous BDNF Val66Met (BDNFMet/Met) male mice were housed in cages equipped with or without running wheels for 4 weeks. Changes in behavioral phenotype, hippocampal adult neurogenesis, and gene expression were evaluated in exercised and sedentary control mice. We found that exercise reduced the latency to feed in the novelty suppressed feeding and the immobility time in the forced swimming test in BDNFVal/Val but not in BDNFMet/Met mice. Hippocampal neurogenesis was reduced in BDNFMet/Met mice compared with BDNFVal/Val mice. BDNFMet/Met mice had lower basal BDNF protein levels in the hippocampus, which was not recovered following exercise. Moreover, exercise-induced expression of total BDNF, BDNF splice variants 1, 2, 4, 6 and fibronectin type III domain-containing protein 5 (FNDC5) mRNA levels were absent or reduced in the dentate gyrus of BDNFMet/Met mice. Exercise failed to enhance PGC-1α and FNDC5 mRNA levels in the BDNFMet/Met muscle. Overall these results indicate that, in adult male mice, the BDNF Val66Met polymorphism impairs the beneficial behavioral and neuroplasticity effects induced by physical exercise. PMID:27388329

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

Science.gov (United States)

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

2017-05-03

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

In vivo detection of c-MET expression in a rat hepatocarcinogenesis model using molecularly targeted magnetic resonance imaging.

Science.gov (United States)

Towner, Rheal A; Smith, Nataliya; Tesiram, Yasvir A; Abbott, Andrew; Saunders, Debbie; Blindauer, Rebecca; Herlea, Oana; Silasi-Mansat, Robert; Lupu, Florea

2007-01-01

The multifunctional growth factor scatter factor/hepatocyte growth factor and its tyrosine kinase receptor, c-MET, have been implicated in the genesis and malignant progression of numerous human malignancies, including hepatocellular carcinomas. The incidence of hepatocellular carcinomas in the United States has increased noticeably over the past two decades and is listed as the fifth major cancer in men worldwide. In this study, we used a choline-deficient l-amino acid (CDAA)-defined rat hepatocarcinogenesis model to visualize increased in vivo expression of the c-MET antigen in neoplastic lesion formation with the use of a super paramagnetic iron oxide (SPIO)-anti-c-MET molecularly targeted magnetic resonance imaging (MRI) contrast agent. SPIO-anti-c-MET was used for the first time to detect overexpression of c-MET in neoplastic nodules and tumors within the livers of CDAA-treated rats, as determined by a decrease in MRI signal intensity and a decrease in regional T(2) values. Specificity for the binding of the molecularly targeted anti-c-MET contrast agent was determined using rat hepatoma (H4-II-E-C3) cell cultures and immunofluorescence microscopic imaging of the targeting agents within neoplastic liver tissue 1 to 2 hours following intravenous administration of SPIO-anti-c-MET and MRI investigation. This method has the ability to visualize in vivo the overexpression of c-MET at early developmental stages of tumor formation.

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

NARCIS (Netherlands)

Gijselaers, Jérôme; De Groot, Renate

2015-01-01

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

Determining Success Criteria and Success Factors for International Construction Projects for Malaysian Contractors

Directory of Open Access Journals (Sweden)

Ali Mohammed Alashwal

2017-06-01

Full Text Available The success of international construction projects is fraught with various challenges such as competitiveness, lack of resources, versatile global economy, and specific conditions in the host country. Malaysian contractors have been venturing into global construction market since early 1980s. However, their venturing was not successful all the time. The number of international projects awarded to Malaysian contractors has reduced drastically during the past decade. Taking advantage of this experience, this paper aims to identify the success criteria and success factors of international construction projects. The data was collected from 120 respondents using a questionnaire survey and analysed using principal component analysis and regression analysis. The results revealed three principal criteria of project success namely, Management Success, Functional Success, and Organisation Success. The main components of success factors include Team Power and Skills, Resource Availability, External Environment, Organisation Capability, Project Support, and Project Organisation. Further analysis emphasized the importance of strong financing capacity of contractors, project social environment, and competence of the project manager in achieving project success. The results of this paper can serve as a guideline for contractors and project managers to achieve success in this context. Future studies may provide in-depth analysis of success criteria and success factors specific for construction project type and host-country location.

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

NARCIS (Netherlands)

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

2009-01-01

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

Regulating Abortion: Impact on Patients and Providers in Texas

Science.gov (United States)

Colman, Silvie; Joyce, Ted

2011-01-01

The State of Texas began enforcement of the Woman's Right to Know (WRTK) Act on January 1, 2004. The law requires that all abortions at or after 16 weeks' gestation be performed in an ambulatory surgical center (ASC). In the month the law went into effect, not one of Texas's 54 nonhospital abortion providers met the requirements of a surgical…

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

Science.gov (United States)

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

2017-01-01

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

Strategies for a Successful Anatomic Pathology Subspecialty Workgroup

Directory of Open Access Journals (Sweden)

2016-06-01

Full Text Available From 1990 to present, 14 liver pathologists and 2 clinical hepatologists from 9 countries have met annually to hold thematic 2.5-day meetings centered on case-based discussion. The goal of these meetings has been to identify gaps in knowledge in our field and fuel scholarly effort to address these gaps. The founding principles were worldwide representation, good representation of women, compatibility of participants, commitment to stable membership and regular attendance, mutual education and friendship, and free exchange of ideas. A summary report of the 2.5-day meeting constituted an enduring document that captured the free flow of ideas discussed. These ideas were open to all participants for the pursuit of scholarship back at their home institutions. However, any idea borne out of an Elves meeting merits open invitation for other Elves to participate in, using established standards for meaningful coauthorship. Over 26 consecutive meetings (1990-2015, themes covered the breadth of liver pathology. With retirement of 2 individuals, resignation of 3, and death of 1, six new members were nominated and voted into membership. Over these same 26 years, active members published 2025 articles indexed in PubMEd Central under the topic “liver;” 3% of these articles represented collaborations between members. This international group represents a successful model in a subspecialty of anatomic pathology for open exchange of ideas, mutual education, and generation of topics worthy of scholarly investigation. We conclude that a self-selected group of subspecialty pathologists can meet successfully over 26 years, maintain a high state of engagement through each annual meeting, self-renew as a result of retirement or resignation, and provide a creative stimulus for highly productive academic careers.

Genetic Nrf2 Overactivation Inhibits the Deleterious Effects Induced by Hepatocyte-Specific c-met Deletion during the Progression of NASH

Directory of Open Access Journals (Sweden)

Pierluigi Ramadori

2017-01-01

Full Text Available We have recently shown that hepatocyte-specific c-met deficiency accelerates the progression of nonalcoholic steatohepatitis in experimental murine models resulting in augmented production of reactive oxygen species and accelerated development of fibrosis. The aim of this study focuses on the elucidation of the underlying cellular mechanisms driven by Nrf2 overactivation in hepatocytes lacking c-met receptor characterized by a severe unbalance between pro-oxidant and antioxidant functions. Control mice (c-metfx/fx, single c-met knockouts (c-metΔhepa, and double c-met/Keap1 knockouts (met/Keap1Δhepa were then fed a chow or a methionine-choline-deficient (MCD diet, respectively, for 4 weeks to reproduce the features of nonalcoholic steatohepatitis. Upon MCD feeding, met/Keap1Δhepa mice displayed increased liver mass albeit decreased triglyceride accumulation. The marked increase of oxidative stress observed in c-metΔhepa was restored in the double mutants as assessed by 4-HNE immunostaining and by the expression of genes responsible for the generation of free radicals. Moreover, double knockout mice presented a reduced amount of liver-infiltrating cells and the exacerbation of fibrosis progression observed in c-metΔhepa livers was significantly inhibited in met/Keap1Δhepa. Therefore, genetic activation of the antioxidant transcription factor Nrf2 improves liver damage and repair in hepatocyte-specific c-met-deficient mice mainly through restoring a balance in the cellular redox homeostasis.

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

NARCIS (Netherlands)

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

2013-01-01

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

Expression of hepatocyte growth factor and the proto-oncogenic receptor c-Met in canine osteosarcoma

NARCIS (Netherlands)

Fieten, H; Spee, B; Ijzer, J; Kik, M J; Penning, L C; Kirpensteijn, J

Hepatocyte growth factor (HGF) and the proto-oncogenic receptor c-Met are implicated in growth, invasion, and metastasis in human cancer. Little information is available on the expression and role of both gene products in canine osteosarcoma. We hypothesized that the expression of c-Met is

Sturen met LED-licht maakt potplant niet zomaar compacter : onderzoek bij kalanchoë en potchrysant

NARCIS (Netherlands)

Velden, van P.; Eveleens-Clark, B.A.

2015-01-01

LED-licht kan als energiebesparende techniek extra meerwaarde krijgen als het ook lukt om met de verschillende kleuren binnen het spectrum de plantkwaliteit te sturen. Voor potplanten zou met name sturen op compactheid een uitkomst zijn. Daarom heeft een onderzoeksteam de korte dag planten kalanchoë

Reconstruction of 3D structures of MET antibodies from electron microscopy 2D class averages.

Directory of Open Access Journals (Sweden)

Qi Chen

Full Text Available Dynamics of three MET antibody constructs (IgG1, IgG2, and IgG4 and the IgG4-MET antigen complex was investigated by creating their atomic models with an integrative experimental and computational approach. In particular, we used two-dimensional (2D Electron Microscopy (EM images, image class averaging, homology modeling, Rapidly exploring Random Tree (RRT structure sampling, and fitting of models to images, to find the relative orientations of antibody domains that are consistent with the EM images. We revealed that the conformational preferences of the constructs depend on the extent of the hinge flexibility. We also quantified how the MET antigen impacts on the conformational dynamics of IgG4. These observations allow to create testable hypothesis to investigate MET biology. Our protocol may also help describe structural diversity of other antigen systems at approximately 5 Å precision, as quantified by Root-Mean-Square Deviation (RMSD among good-scoring models.

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

OpenAIRE

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

2016-01-01

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

Human capital and career success

DEFF Research Database (Denmark)

Frederiksen, Anders; Kato, Takao

capital formally through schooling for career success, as well as the gender gap in career success rates. Second, broadening the scope of human capital by experiencing various occupations (becoming a generalist) is found to be advantageous for career success. Third, initial human capital earned through......Denmark’s registry data provide accurate and complete career history data along with detailed personal characteristics (e.g., education, gender, work experience, tenure and others) for the population of Danish workers longitudinally. By using such data from 1992 to 2002, we provide rigorous...... formal schooling and subsequent human capital obtained informally on the job are found to be complements in the production of career success. Fourth, though there is a large body of the literature on the relationship between firm-specific human capital and wages, the relative value of firm-specific human...

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

Science.gov (United States)

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

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

Studies of key success factors of product development success: A reinterpretation of results

DEFF Research Database (Denmark)

Plichta, Kirsten; Harmsen, Hanne

In this paper the general validity of the research area of key factors of success in product development is discussed. To be more specific we argue that validity hinges on the causal relation between success and success factrors ­ a relation that unaccounted for in the empirical studies....... The theoretical tradition of the resource-based perspective provides ­ at least to some extent ­ an account of this causality. An important point in the paper is that the key factors of success in the empi studies are not factors causally related to success, but at the most a number of valuable resources and thus......, but in the studies problems concerning implementation are not discussed. When the lists factors of success are interprested as valuable resources and capabilities, we show that some implications on the implementability might be deduced from the resource-based perspective....

The BDNF Val66Met polymorphism: relation to familiar risk of affective disorder, BDNF levels and salivary cortisol.

Science.gov (United States)

Vinberg, Maj; Trajkovska, Viktorija; Bennike, Bente; Knorr, Ulla; Knudsen, Gitte M; Kessing, Lars V

2009-10-01

Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are considered to play an important role in the pathophysiology of affective disorders. The aim of the present study was to investigate whether the BDNF Val66Met polymorphism is associated with a familiar risk of affective disorder and whether these genotypes affect whole blood BDNF level and salivary cortisol. In a high-risk study, healthy monozygotic and dizygotic twins with and without a co-twin (high- and low-risk twins, respectively) history of affective disorder were identified through nationwide registers. Familiar predisposition to unipolar and bipolar disorder was not associated with any specific genotype pattern of the BDNF Val66Met polymorphism, not in this sample of 124 val/val, 58 val/met and 8 met/met individuals. However, the combination of having a high familiar risk of affective disorder and the met allele was associated with a higher whole blood BDNF (p=0.02) and a higher evening cortisol level (p=0.01), but not with awakening cortisol. Individuals at high risk of affective disorders and who are carriers of the met allele of the Val66Met polymorphism may present with an enhanced stress response. The presence of a specific genotype alone may not enhance the risk of developing an affective episode. Rather, the altered stress response may be expressed only in combination with other risk variants through interactions with the environment.

In Vivo Detection of c-MET Expression in a Rat Hepatocarcinogenesis Model Using Molecularly Targeted Magnetic Resonance Imaging

Directory of Open Access Journals (Sweden)

Rheal A. Towner

2007-01-01

Full Text Available The multifunctional growth factor scatter factor/hepatocyte growth factor and its tyrosine kinase receptor, c-MET, have been implicated in the genesis and malignant progression of numerous human malignancies, including hepatocellular carcinomas. The incidence of hepatocellular carcinomas in the United States has increased noticeably over the past two decades and is listed as the fifth major cancer in men worldwide. In this study, we used a choline-deficient l-amino acid (CDAA-defined rat hepatocarcinogenesis model to visualize increased in vivo expression of the c-MET antigen in neoplastic lesion formation with the use of a super paramagnetic iron oxide (SPIO–anti-c-MET molecularly targeted magnetic resonance imaging (MRI contrast agent. SPIO–anti-c-MET was used for the first time to detect overexpression of c-MET in neoplastic nodules and tumors within the livers of CDAA-treated rats, as determined by a decrease in MRI signal intensity and a decrease in regional T2 values. Specificity for the binding of the molecularly targeted anti-c-MET contrast agent was determined using rat hepatoma (H4-II-E-C3 cell cultures and immunofluorescence microscopic imaging of the targeting agents within neoplastic liver tissue 1 to 2 hours following intravenous administration of SPIO–anti-c-MET and MRI investigation. This method has the ability to visualize in vivo the overexpression of c-MET at early developmental stages of tumor formation.

Paving the Road to Success: A Framework for Implementing the Success Tutoring Approach

Directory of Open Access Journals (Sweden)

Spark Linda

2017-12-01

Full Text Available The exponential growth of higher education enrolment in South Africa has resulted in increased diversity of the student body, leading to a proliferation of factors that affect student performance and success. Various initiatives have been adopted by tertiary institutions to mitigate the negative impact these factors may have on student success, and it is suggested that interventions that include aspects of social integration are the most successful. This paper outlines an approach called Success Tutoring (a non-academic tutorial approach used as part of a student success and support programme in the Faculty of Commerce, Law, and Management at the University of the Witwatersrand, which is underscored by empirical evidence drawn from evaluation data collected during Success Tutor symposia. The authors draw conclusions and make recommendations based on a thematic analysis of the dataset, and ultimately provide readers with a framework for implementing Success Tutoring at their tertiary institutions.

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.

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

NARCIS (Netherlands)

Mette, Christian; Zielke, Annika; Groen, Yvonne

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

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.

Receptor-type Protein Tyrosine Phosphatase β Regulates Met Phosphorylation and Function in Head and Neck Squamous Cell Carcinoma

Directory of Open Access Journals (Sweden)

Yiru Xu

2012-11-01

Full Text Available Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer and has a high rate of mortality. Emerging evidence indicates that hepatocyte growth factor receptor (or Met pathway plays a pivotal role in HNSCC metastasis and resistance to chemotherapy. Met function is dependent on tyrosine phosphorylation that is under direct control by receptor-type protein tyrosine phosphatase β (RPTP-β. We report here that RPTP-β expression is significantly downregulated in HNSCC cells derived from metastatic tumors compared to subject-matched cells from primary tumors. Knockdown of endogenous RPTP-β in HNSCC cells from primary tumor potentiated Met tyrosine phosphorylation, downstream mitogen-activated protein (MAP kinase pathway activation, cell migration, and invasion. Conversely, restoration of RPTP-β expression in cells from matched metastatic tumor decreased Met tyrosine phosphorylation and downstream functions. Furthermore, we observed that six of eight HNSCC tumors had reduced levels of RPTP-β protein in comparison with normal oral tissues. Collectively, the results demonstrate the importance of RPTP-β in tumor biology of HNSCC through direct dephosphorylation of Met and regulation of downstream signal transduction pathways. Reduced RPTP-β levels, with or without Met overexpression, could promote Met activation in HNSCC tumors.

The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese heroin-dependent patients.

Science.gov (United States)

Chen, Shiou-Lan; Lee, Sheng-Yu; Chang, Yun-Hsuan; Wang, Tzu-Yun; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2015-02-02

BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of long-term heroin use. Thus, we investigated the relationships between brain-derived neurotrophic factor (BDNF) plasma concentrations and the BDNF Val66Met nucleotide polymorphism (SNP) in heroin-dependent patients. The pretreatment expression levels of plasma BDNF and the BDNF Val66Met SNP in 172 heroin-dependent patients and 102 healthy controls were checked. BDNF levels were significantly lower in patients (F = 52.28, p BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not affect plasma BDNF levels in our participants. In heroin-dependent patients, plasma BDNF levels were negatively correlated with the length of heroin dependency. Long-term (>15 years) users had significantly lower plasma BDNF levels than did short-term (BDNF concentration in habitual heroin users are not affected by BDNF Val66Met gene variants, but by the length of the heroin dependency.

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

Science.gov (United States)

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

2012-05-28

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

Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells

Energy Technology Data Exchange (ETDEWEB)

Husmann, Knut, E-mail: khusmann@research.balgrist.ch [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland); Ducommun, Pascal [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland); Division of Plastic Surgery and Hand Surgery, Department of Surgery, University Hospital Zurich, Zurich (Switzerland); Sabile, Adam A.; Pedersen, Else-Marie; Born, Walter; Fuchs, Bruno [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland)

2015-09-04

The poor outcome of osteosarcoma (OS), particularly in patients with metastatic disease and a five-year survival rate of only 20%, asks for more effective therapeutic strategies targeting malignancy-promoting mechanisms. Dysregulation of C-MET, its ligand hepatocyte growth factor (HGF) and the fusion oncogene product TPR-MET, first identified in human MNNG-HOS OS cells, have been described as cancer-causing factors in human cancers. Here, the expression of these molecules at the mRNA and the protein level and of HGF-stimulated signaling and downregulation of C-MET was compared in the parental low metastatic HOS and MG63 cell lines and the respective highly metastatic MNNG-HOS and 143B and the MG63-M6 and MG63-M8 sublines. Interestingly, expression of TPR-MET was only observed in MNNG-HOS cells. HGF stimulated the phosphorylation of Akt and Erk1/2 in all cell lines investigated, but phospho-Stat3 remained at basal levels. Downregulation of HGF-stimulated Akt and Erk1/2 phosphorylation was much faster in the HGF expressing MG63-M8 cells than in HOS cells. Degradation of HGF-activated C-MET occurred predominantly through the proteasomal and to a lesser extent the lysosomal pathway in the cell lines investigated. Thus, HGF-stimulated Akt and Erk1/2 signaling as well as proteasomal degradation of HGF activated C-MET are potential therapeutic targets in OS. - Highlights: • Expression of TPR-MET was only observed in MNNG-HOS cells. • HGF stimulated the phosphorylation of Akt and Erk1/2 but not of Stat3 in osteosarcoma cell lines. • Degradation of HGF-activated C-MET occurred predominantly through the proteasomal pathway.

Key successes and challenges in providing mental health care in an urban male remand prison: a qualitative study.

Science.gov (United States)

Samele, Chiara; Forrester, Andrew; Urquía, Norman; Hopkin, Gareth

2016-04-01

This study aimed to describe the workings of an urban male remand prison mental health service exploring the key challenges and successes, levels of integration and collaboration with other services. A purposive sampling was used to recruit key prison and healthcare professionals for in-depth interviews. A thematic analysis was used to analyse transcripts based on an initial coding frame of several predefined themes. Other key themes were also identified. Twenty-eight interviews were conducted. Prisoners referred to the service had complex, sometimes acute mental illness requiring specialist assessment and treatment. Key successes of the in-reach service included the introduction of an open referral system, locating a mental health nurse at reception to screen all new prisoners and a zoning system to prioritise urgent or non-urgent cases. Achieving an integrated system of healthcare was challenging because of the numerous internal and external services operating across the prison, a highly transient population, limited time and space to deliver services and difficulties with providing inpatient care (e.g., establishing the criteria for admission and managing patient flow). Collaborative working between prison and healthcare staff was required to enable best care for prisoners. The prison mental health in-reach service worked well in assessing and prioritising those who required specialist mental health care. Although the challenges of working within the prison context limited what the in-reach team could achieve. Further work was needed to improve the unit environment and how best to target and deliver inpatient care within the prison.

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

NARCIS (Netherlands)

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

2013-01-01

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

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

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Kaja K Jasińska

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

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

Science.gov (United States)

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

2016-01-01

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

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

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

2015-05-01

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

BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction.

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Zhao, Mingzhe; Chen, Lu; Yang, Jiarun; Han, Dong; Fang, Deyu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Ma, Jingsong; Wang, Lin; Jiang, Shixiang; Song, Xuejia; Zhou, Jiawei; Zhang, Jian; Chen, Mingqi; Qi, Dong; Yang, Yanjie; Pan, Hui

2018-02-01

Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential impact of Met receptor gene interaction with early-life stress on neuronal morphology and behavior in mice.

Science.gov (United States)

Heun-Johnson, Hanke; Levitt, Pat

2018-02-01

Early adversity in childhood increases the risk of anxiety, mood, and post-traumatic stress disorders in adulthood, and specific gene-by-environment interactions may increase risk further. A common functional variant in the promoter region of the gene encoding the human MET receptor tyrosine kinase (rs1858830 ' C' allele) reduces expression of MET and is associated with altered cortical circuit function and structural connectivity. Mice with reduced Met expression exhibit changes in anxiety-like and conditioned fear behavior, precocious synaptic maturation in the hippocampus, and reduced neuronal arbor complexity and synaptogenesis. These phenotypes also can be produced independently by early adversity in wild-type mice. The present study addresses the outcome of combining early-life stress and genetic influences that alter timing of maturation on enduring functional and structural phenotypes. Using a model of reduced Met expression ( Met +/- ) and early-life stress from postnatal day 2-9, social, anxiety-like, and contextual fear behaviors in later life were measured. Mice that experienced early-life stress exhibited impairments in social interaction, whereas alterations in anxiety-like behavior and fear learning were driven by Met haploinsufficiency, independent of rearing condition. Early-life stress or reduced Met expression decreased arbor complexity of ventral hippocampal CA1 pyramidal neurons projecting to basolateral amygdala. Paradoxically, arbor complexity in Met +/- mice was increased following early-life stress, and thus not different from arbors in wild-type mice raised in control conditions. The changes in dendritic morphology are consistent with the hypothesis that the physiological state of maturation of CA1 neurons in Met +/- mice influences their responsiveness to early-life stress. The dissociation of behavioral and structural changes suggests that there may be phenotype-specific sensitivities to early-life stress.

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

NARCIS (Netherlands)

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

2009-01-01

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

Een bepalingsmethode voor thallium in regenwater met behulp van voltammetrie

NARCIS (Netherlands)

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

1985-01-01

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

The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment

DEFF Research Database (Denmark)

Schofield, J.T.; Barnes, J.R.; Crisp, D.

1997-01-01

The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment measured the vertical density, pressure, and temperature structure of the martian atmosphere from the surface to 160 km, and monitored surface meteorology and climate for 83 sols (1 sol = 1 martian day = 24...

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

Science.gov (United States)

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

2017-01-01

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

Met-myoglobin formation, accumulation, degradation, and myoglobin oxygenation monitoring based on multiwavelength attenuance measurement in porcine meat

Science.gov (United States)

Nguyen, Thien; Phan, Kien Nguyen; Lee, Jee-Bum; Kim, Jae Gwan

2016-05-01

We propose a simple, rapid, and nondestructive method to investigate formation, accumulation, and degradation of met-myoglobin (met-Mb) and myoglobin oxygenation from the interior of porcine meat. For the experiment, color photos and attenuance spectra of porcine meat (well-bled muscle, fat, and mixed) were collected daily to perform colorimetric analysis and to obtain the differences of attenuance between 578 and 567 nm (A578-A567) and between 615 and 630 nm (A630-A615), respectively. Oxy-, deoxy-, and met-myoglobin concentration changes over storage time were also calculated using Beer-Lamberts' law with reflectance intensities at 557, 582, and 630 nm. The change of A578-A567 was well matched with the change of myoglobin oxygenation, and the change of A630-A615 corresponded well with the formation and degradation of met-Mb. In addition, attenuation differences, A578-A567 and A630-A615, were able to show the formation of met-Mb earlier than colorimetric analysis. Therefore, the attenuance differences between wavelengths can be indicators for estimating myoglobin oxygenation and met-Mb formation, accumulation, and degradation, which enable us to design a simple device to monitor myoglobin activities in porcine meat.

San Diego Met High School: Personalization as a Foundation

Science.gov (United States)

Principal Leadership, 2010

2010-01-01

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

Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

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Davis Rodney

2006-07-01

Full Text Available Abstract Background Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF, was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. Methods We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. Results We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM or nucleolin (on the cell surfaces eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of

Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

International Nuclear Information System (INIS)

Tate, Amanda; Isotani, Shuji; Bradley, Michael J; Sikes, Robert A; Davis, Rodney; Chung, Leland WK; Edlund, Magnus

2006-01-01

Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF), was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF) were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM) and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM) or nucleolin (on the cell surfaces) eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of laminin-binding integrins, nor can they be linked to

Design and implementation of the infrastructure of HadGEM3: the next-generation Met Office climate modelling system

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H. T. Hewitt

2011-04-01

Full Text Available This paper describes the development of a technically robust climate modelling system, HadGEM3, which couples the Met Office Unified Model atmosphere component, the NEMO ocean model and the Los Alamos sea ice model (CICE using the OASIS coupler. Details of the coupling and technical solutions of the physical model (HadGEM3-AO are documented, in addition to a description of the configurations of the individual submodels. The paper demonstrates that the implementation of the model has resulted in accurate conservation of heat and freshwater across the model components. The model performance in early versions of this climate model is briefly described to demonstrate that the results are scientifically credible. HadGEM3-AO is the basis for a number of modelling efforts outside of the Met Office, both within the UK and internationally. This documentation of the HadGEM3-AO system provides a detailed reference for developers of HadGEM3-based climate configurations.