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Sample records for sungkyunkwan university htt

  1. HTT-DB: horizontally transferred transposable elements database.

    Science.gov (United States)

    Dotto, Bruno Reis; Carvalho, Evelise Leis; Silva, Alexandre Freitas; Duarte Silva, Luiz Fernando; Pinto, Paulo Marcos; Ortiz, Mauro Freitas; Wallau, Gabriel Luz

    2015-09-01

    Horizontal transfer of transposable (HTT) elements among eukaryotes was discovered in the mid-1980s. As then, >300 new cases have been described. New findings about HTT are revealing the evolutionary impact of this phenomenon on host genomes. In order to provide an up to date, interactive and expandable database for such events, we developed the HTT-DB database. HTT-DB allows easy access to most of HTT cases reported along with rich information about each case. Moreover, it allows the user to generate tables and graphs based on searches using Transposable elements and/or host species classification and export them in several formats. This database is freely available on the web at http://lpa.saogabriel.unipampa.edu.br:8080/httdatabase. HTT-DB was developed based on Java and MySQL with all major browsers supported. Tools and software packages used are free for personal or non-profit projects. bdotto82@gmail.com or gabriel.wallau@gmail.com. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Rolling Bearing Fault Diagnosis Based on an Improved HTT Transform.

    Science.gov (United States)

    Pang, Bin; Tang, Guiji; Tian, Tian; Zhou, Chong

    2018-04-14

    When rolling bearing failure occurs, vibration signals generally contain different signal components, such as impulsive fault feature signals, background noise and harmonic interference signals. One of the most challenging aspects of rolling bearing fault diagnosis is how to inhibit noise and harmonic interference signals, while enhancing impulsive fault feature signals. This paper presents a novel bearing fault diagnosis method, namely an improved Hilbert time-time (IHTT) transform, by combining a Hilbert time-time (HTT) transform with principal component analysis (PCA). Firstly, the HTT transform was performed on vibration signals to derive a HTT transform matrix. Then, PCA was employed to de-noise the HTT transform matrix in order to improve the robustness of the HTT transform. Finally, the diagonal time series of the de-noised HTT transform matrix was extracted as the enhanced impulsive fault feature signal and the contained fault characteristic information was identified through further analyses of amplitude and envelope spectrums. Both simulated and experimental analyses validated the superiority of the presented method for detecting bearing failures.

  3. Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Choudhury, Kamalika Roy [Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Centre for Neuroscience, Indian Institute of Science, Bangalore 560012 (India); Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com [Biomedical Genomics Centre, PG Polyclinic Building, 5, Suburbun Hospital Road, Kolkata 700020 (India)

    2015-01-02

    Highlights: • HYPK reduces mutant HTT-mediated aggregate formation and cytotoxicity. • Interaction of HYPK with HTT requires N-terminal 17 amino acid of HTT (HTT-N17). • Deletion of HTT-N17 leads to SDS-soluble, smaller, nuclear aggregates. • These smaller aggregates do not associate with HYPK and are more cytotoxic. • Maybe, interaction of HYPK with amphipathic HTT-N17 block HTT aggregate formation. - Abstract: Huntington’s disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK.

  4. The personality trait openness is related to cerebral 5-HTT levels

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Frøkjær, Vibe G.; Erritzøe, David

    2009-01-01

    Potentiation of serotonergic transmission increases cognitive flexibility, but can in other circumstances increase sensitivity to stressful environmental cues. The personality trait Openness to Experience reflects and is also associated with an increased risk for mood disorders. We hypothesized...... that the personality trait has an association with a biomarker of serotonergic transmission, the plasma membrane serotonin transporter (5-HTT). In 50 healthy volunteers, we tested for correlations between scores on the NEO-PI-R scale Openness to Experience and its subscales, and cerebral binding of the 5-HTT selective...... in openness scores. Thus, high scores in personality facets indicative of cognitive flexibility and openness to change are associated with lower [11C]DASB binding. Lower abundance of 5-HTT sites may result in potentiation of serotonergic signaling, which occurs during treatment with SSRIs. We speculate...

  5. [The value of 5-HTT gene polymorphism for the assessment and prediction of male adolescence violence].

    Science.gov (United States)

    Yu, Yue; Liu, Xiang; Yang, Zhen-xing; Qiu, Chang-jian; Ma, Xiao-hong

    2012-08-01

    To establish an adolescent violence crime prediction model, and to assess the value of serotonin transporter (5-HTT) gene polymorphism for the assessment and prediction of violent crime. Investigative tools were used to analyze the difference in personality dimensions, social support, coping styles, aggressiveness, impulsivity, and family condition scale between 223 adolescents with violence behavior and 148 adolescents without violence behavior. The distribution of 5-HTT gene polymorphisms (5-HTTLPR and 5-HTTVNTR) was compared between the two groups. The role of 5-HTT gene polymorphism on adolescent personality, impulsion and aggression scale also was also analyzed. Stepwise logistic regression was used to establish a predictive model for adolescent violent crime. Significant difference was found between the violence group and the control group on multiple dimensions of psychology and environment scales. However, no statistical difference was found with regard to the 5-HTT genotypes and alleles between adolescents with violent behaviors and normal controls. The rate of prediction accuracy was not significantly improved when 5-HTT gene polymorphism was taken into the model. The violent crime of adolescents was closely related with social and environmental factors. No association was found between 5-HTT polymorphisms and adolescent violence criminal behavior.

  6. Aggression and 5HTT polymorphism in females: study of synchronized swimming and control groups.

    Science.gov (United States)

    Sysoeva, Olga V; Maluchenko, Natalia V; Timofeeva, Marina A; Portnova, Galina V; Kulikova, Maria A; Tonevitsky, Alexandr G; Ivanitsky, Alexey M

    2009-05-01

    Aggression is a heterogeneous heritable psychological trait, also influenced by environmental factors. Previous studies, mostly conducted on male population, have found some associations of the aggression with the polymorphisms of genes, regulating the activity of serotonin (5-HT) in the brain. However, psychological as well as biochemical manifestations of the aggression are different in males and females. Our study aimed to investigate the association of 5-HTT gene polymorphism with different facets of aggression (BDHI) in females. Two groups: the synchronized swimming and non-athlete control, - were examined to study the possible modulation effect of sport on the association between 5-HTT gene polymorphism and aggression. It was found that in both groups the low-active 5-HTT polymorphism (SS) was associated with increased scores on Indirect Hostility scale and decreased scores on Negativism scale, compared to LL genotype. No interaction effect between sport and 5-HTT polymorphism was found. The higher percentage of LL-carriers and lower of LS-carriers in the synchronized swimming group compared to the control one was observed. This may be the sign of the importance of LL polymorphism of 5-HTT gene, previously associated with higher resistance to stress factors, for being an athlete, although this result has to be taken cautiously keeping in mind the stratification problem. Synchronized swimmers had lower scores on Assault, Negativism, Irritability and Verbal Hostility compared to age-matched control girls (in general and for each 5-HTT genotype separately), suggesting that they may have more matured emotional system (older control group has also lower scores on these scales).

  7. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease.

    Science.gov (United States)

    Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J; Kay, Chris; Collins, Jennifer A; Arenillas, David; Lilja, Tobias; Gaudenzi, Giulia; Manoharan, Shiana; Doty, Crystal N; Beck, Jessalyn; Lahiri, Nayana; Portales-Casamar, Elodie; Warby, Simon C; Connolly, Colúm; De Souza, Rebecca A G; Tabrizi, Sarah J; Hermanson, Ola; Langbehn, Douglas R; Hayden, Michael R; Wasserman, Wyeth W; Leavitt, Blair R

    2015-06-01

    Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset. HTT promoter analysis identified a NF-κB binding site that regulates HTT promoter transcriptional activity. A non-coding SNP, rs13102260:G > A, in this binding site impaired NF-κB binding and reduced HTT transcriptional activity and HTT protein expression. The presence of the rs13102260 minor (A) variant on the HD disease allele was associated with delayed age of onset in familial cases, whereas the presence of the rs13102260 (A) variant on the wild-type HTT allele was associated with earlier age of onset in HD patients in an extreme case-based cohort. Our findings suggest a previously unknown mechanism linking allele-specific effects of rs13102260 on HTT expression to HD age of onset and have implications for HTT silencing treatments that are currently in development.

  8. A polymorphism in the 5'-flanking region of the serotonin transporter (5-HTT) gene affects fear-related behaviors of adult domestic chickens.

    Science.gov (United States)

    Krause, E Tobias; Kjaer, Joergen B; Lüders, Carolin; van, Loc Phi

    2017-07-14

    The neural serotonin (5-HT)/serotonin transporter (5-HTT) system is involved in the regulation of physiological processes and emotional states. In humans, the short (S) allele in the 5-HTT gene-linked polymorphic region, which decreases 5-HTT expression, has been shown to be associated with behavioral changes including an increased level of anxiety. Also in birds a polymorphism in the 5-HTT gene is described, a deletion (D) has been found to have functional consequences on growth and locomotion. Furthermore, the D-allele leads to an increased 5-HTT expression compared to the wild type (W), a feature which is linked to lower levels of fear in mammalian species. Thus, we aimed here to test whether the polymorphism in the chicken 5-HTT gene also leads to respective alternations of fear-related behaviors. We tested 268 hens of three genotypes (W/W, W/D, D/D) in two behavioral paradigms (open field, light-dark test) to assess fear-related behavior. Both tests revealed that hens possessing the D-allele showed lower levels of fear than those having the W-allele. These similar outcomes in fear-related behaviors in an avian and a mammalian species are associated with an increased 5-HTT expression. In the human 5-HTT gene, the long (L) allele is linked to such increased expression, whereas in chickens it is the D-allele. Thus, increased 5-HTT expression causing decreased fear may be a general mechanism in vertebrates. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease

    DEFF Research Database (Denmark)

    Aziz, N A; Jurgens, C K; Landwehrmeyer, G B

    2009-01-01

    OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). We aimed to assess whether interaction between CAG repeat sizes in the mutant and normal allele could affect disease severity and progression. METHODS: Using...... with less severe symptoms and pathology. CONCLUSIONS: Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease. The underlying mechanism may involve interaction of the polyglutamine domains of normal...

  10. [Relationship between genetic polymorphisms of 3 SNP loci in 5-HTT gene and paranoid schizophrenia].

    Science.gov (United States)

    Xuan, Jin-Feng; Ding, Mei; Pang, Hao; Xing, Jia-Xin; Sun, Yi-Hua; Yao, Jun; Zhao, Yi; Li, Chun-Mei; Wang, Bao-Jie

    2012-12-01

    To investigate the population genetic data of 3 SNP loci (rs25533, rs34388196 and rs1042173) of 5-hydroxytryptamine transporter (5-HTT) gene and the association with paranoid schizophrenia. Three SNP loci of 5-HTT gene were examined in 132 paranoid schizophrenia patients and 150 unrelated healthy individuals of Northern Chinese Han population by PCR-RFLP technique. The Hardy-Weinberg equilibrium test was performed using the chi-square test and the data of haplotype frequency and population genetics parameters were statistically analyzed. Among these three SNP loci, four haplotypes were obtained. There were no statistically significant differences between the patient group and the control group (P > 0.05). The DP values of the 3 SNP loci were 0.276, 0.502 and 0.502. The PIC of them were 0.151, 0.281 and 0.281. The PE of them were 0.014, 0.072 and 0.072. The three SNP loci and four haplotypes of 5-HTT gene have no association with paranoid schizophrenia, while the polymorphism still have high potential application in forensic practice.

  11. 5-HT2C Receptor Desensitization Moderates Anxiety in 5-HTT Deficient Mice: From Behavioral to Cellular Evidence

    Science.gov (United States)

    Martin, Cédric BP; Martin, Vincent S.; Trigo, José M.; Chevarin, Caroline; Maldonado, Rafael; Fink, Latham H.; Cunningham, Kathryn A.; Hamon, Michel; Lanfumey, Laurence

    2015-01-01

    Background: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT-/-) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR–induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos–induced expression) levels. Results: Although 5-HTT-/- mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR–mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR–mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT-/- mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT-/- mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR–like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT-/- mutants. Conclusions: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT-/- mice. PMID:25522398

  12. ADHD and Disruptive behavior scores – associations with MAO-A and 5-HTT genes and with platelet MAO-B activity in adolescents

    Directory of Open Access Journals (Sweden)

    Larsson Jan-Olov

    2008-04-01

    Full Text Available Abstract Background Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of Attention Deficit Hyperactivity Disorder (ADHD and Disruptive Behavior Disorder (DBD. We have, in a population-based sample, studied associations between dimensions of the ADHD/DBD phenotype and Monoamine Oxidase B (MAO-B activity in platelets and polymorphisms in two serotonergic genes: the Monoamine Oxidase A Variable Number of Tandem Repeats (MAO-A VNTR and the 5-Hydroxytryptamine Transporter gene-Linked Polymorphic Region (5-HTT LPR. Methods A population-based sample of twins, with an average age of 16 years, was assessed for ADHD/DBD with a clinical interview; Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL. Blood was drawn from 247 subjects and analyzed for platelet MAO-B activity and polymorphisms in the MAO-A and 5-HTT genes. Results We found an association in girls between low platelet MAO-B activity and symptoms of Oppositional Defiant Disorder (ODD. In girls, there was also an association between the heterozygote long/short 5-HTT LPR genotype and symptoms of conduct disorder. Furthermore the heterozygote 5-HTT LPR genotype in boys was found to be associated with symptoms of Conduct Disorder (CD. In boys, hemizygosity for the short MAO-A VNTR allele was associated with disruptive behavior. Conclusion Our study suggests that the serotonin system, in addition to the dopamine system, should be further investigated when studying genetic influences on the development of Disruptive Behavior Disorders.

  13. Travelling wave solutions for (N+ 1)-dimensional nonlinear evolution ...

    Indian Academy of Sciences (India)

    Author Affiliations. Jonu Lee1 Rathinasamy Sakthivel2. Department of Applied Mathematics, Kyung Hee University, Suwon, South Korea; Department of Mathematics, Sungkyunkwan University, Suwon 440-746, South Korea ...

  14. Pre-clinical evaluation of AAV5-miHTT gene therapy of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Konstantinová, P.; Miniarikova, J.; Blits, B.; Zimmer, V.; Spoerl, A.; Southwell, A.; Hayden, M.; van Deventer, S.; Deglon, N.; Motlík, Jan; Juhás, Štefan; Juhásová, Jana; Richard, Ch.; Petry, H.

    2015-01-01

    Roč. 78, Supl 2 (2015), s. 8-8 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * gene therapy * AAV5-miHTT Subject RIV: EB - Genetics ; Molecular Biology

  15. Hydrothermal Treatment (HTT) of Microalgae: Evaluation of the Process As Conversion Method in an Algae Biorefinery Concept

    NARCIS (Netherlands)

    Garcia Alba, Laura; Torri, C.; Samori, C.; van der Spek, J.J.; Fabbri, D.; Kersten, Sascha R.A.; Brilman, Derk Willem Frederik

    2012-01-01

    The hydrothermal treatment (HTT) technology is evaluated for its potential as a process to convert algae and algal debris into a liquid fuel, within a sustainable algae biorefinery concept in which, next to fuels (gaseous and liquid), high value products are coproduced, nutrients and water are

  16. A map of taste neuron projections in the Drosophila CNS

    Indian Academy of Sciences (India)

    Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 Republic of Korea; Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA; These authors contributed equally to the work. Department of Entomology, University of California, Riverside, ...

  17. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease

    DEFF Research Database (Denmark)

    Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J

    2015-01-01

    Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset....

  18. Life satisfaction in the new country: a multilevel longitudinal analysis of effects of culture and 5-HTT allele frequency distribution in country of origin.

    Science.gov (United States)

    Kashima, Emiko S; Kent, Stephen; Kashima, Yoshihisa

    2015-01-01

    Life satisfaction of migrants to Australia from 17 countries, assessed at 4-5 months, 16-17 months and 3½ years after arrival, was analyzed with a longitudinal, multilevel analysis. The results indicated that migrants were more satisfied, if the national average life satisfaction was higher in their country of origin, after adjustment for individual-level income, age, and sex and a linear temporal trend. Simultaneously, the migrants were also happier if people in their country of origin had a higher frequency of 5-HTT long allele, a genotype known to be associated with resilience under life stresses. These two relationships were independent, suggesting that both culture and gene matter in international transitions. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  19. New exact travelling wave solutions of bidirectional wave equations

    Indian Academy of Sciences (India)

    Department of Mathematics, Sungkyunkwan University, Suwon 440-746, Republic of Korea. ∗ ... exact travelling wave solutions of system (1) using the modified tanh–coth function method ... The ordinary differential equation is then integrated.

  20. Negative social acts and pain: evidence of a workplace bullying and 5-HTT genotype interaction.

    Science.gov (United States)

    Jacobsen, Daniel Pitz; Nielsen, Morten Birkeland; Einarsen, Ståle; Gjerstad, Johannes

    2018-05-01

    Objectives Long-term exposure to systematic negative acts at work, usually labeled workplace bullying, is a prevalent problem at many workplaces. The adverse effects of such exposure may range from psychological symptoms, such as depression and anxiety to somatic ailments like cardiovascular disease and musculoskeletal complaints. In this study, we examined the relationships among exposure to negative acts, genetic variability in the 5-HTT gene SLC6A4 and pain. Methods The study was based on a nationally representative survey of 987 Norwegian employees drawn from the Norwegian Central Employee Register by Statistics Norway. Exposure to bullying in the workplace was measured with the 9-item version of the Negative Acts Questionnaire - Revised (NAQ-R) inventory. Pain was rated using an 11-point (0-10) numeric rating scale (NRS). Genotyping with regard to SLC6A4 was carried out using a combination of gel-electrophoresis and TaqMan assay. Results The data revealed a significant interaction between exposure to negative acts and the SLC6A4 genotype with regard to pain (linear regression with 5000 resamples; age, sex, tobacco use and education were included as covariates). The relationship between negative acts and pain intensity was significantly stronger for subjects with the LALA genotype than for subjects with the SLA/LALG/SLG genotype. No significant difference between subjects with the LALA genotype and SS genotype was observed. Conclusions Our data demonstrated that the relationship between bullying and pain was modified by the 5-HTT genotype, ie, genetic variation in SLC6A4. The association between negative acts and health among vulnerable individuals appeared more potent than previously reported.

  1. Generation of KCL028 research grade human embryonic stem cell line carrying a mutation in the HTT gene

    Directory of Open Access Journals (Sweden)

    Laureen Jacquet

    2016-03-01

    Full Text Available The KCL028 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation affecting one allele of the HTT gene encoding huntingtin (43 trinucleotide repeats; 21 for the normal allele. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro and in vivo assays.

  2. Serotonin Transporter (5-HTT) and gamma-Aminobutyric Acid Receptor Subunit beta3 (GABRB3) Gene Polymorphisms are not Associated with Autism in the IMGSA Families

    DEFF Research Database (Denmark)

    Maestrini, E.; Lai, C.; Marlow, A.

    1999-01-01

    Previous studies have suggested that the serotonin transporter (5-HTT) gene and the gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene, or other genes in the 15q11-q13 region, are possibly involved in susceptibility to autism. To test this hypothesis we performed an association study on...

  3. Impact of Institutional Care on Attachment Disorganization and Insecurity of Ukrainian Preschoolers: Protective Effect of the Long Variant of the Serotonin Transporter Gene (5HTT)

    Science.gov (United States)

    Bakermans-Kranenburg, Marian J.; Dobrova-Krol, Natasha; van IJzendoorn, Marinus

    2012-01-01

    Institutional care has been shown to lead to insecure and disorganized attachments and indiscriminate friendliness. Some children, however, are surprisingly resilient to the adverse environment. Here the protective role of the long variant of the serotonin receptor gene (5HTT) is explored in a small hypothesis-generating study of 37 Ukrainian…

  4. Calculus teaching and learning in South Korea

    OpenAIRE

    Natanael Karjanto

    2013-01-01

    This article discusses an experience of teaching Calculus classes for the freshmen students enrolled at Sungkyunkwan University, one of the private universities in South Korea. The teaching and learning approach is a balance combination between the teacher-oriented traditional style of lecturing and other activities that encourage students for active learning and classroom participation. Based on the initial observation during several semesters, some anecdotal evidences show that students'...

  5. Calculus teaching and learning in South Korea

    OpenAIRE

    Karjanto, N.

    2015-01-01

    This article discusses an experience of teaching Calculus classes for the freshmen students enrolled at Sungkyunkwan University, one of the private universities in South Korea. The teaching and learning approach is a balance combination between the teacher-oriented traditional style of lecturing and other activities that encourage students for active learning and classroom participation. Based on the initial observation during several semesters, some anecdotal evidences show that students' le...

  6. Infectious Disease and National Security: Strategic Information Needs

    Science.gov (United States)

    2006-01-01

    to the National Security Council. Most current federal employees we interviewed offered one or more specific sugges- tions for a centralized, time...and preparedness information for health professionals Open 156 Ministry of Health Malaysia Government of Malaysia http://dph.gov.my/ddc/index. html...Open 206 Asian Network for Surveillance of Resistant Pathogens (ANSORP) Various (primary: Samsung Medical Center, Sungkyunkwan University, Seoul

  7. Maintenance of Chronic Fatigue Syndrome (CFS in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype.

    Directory of Open Access Journals (Sweden)

    Benedicte Meyer

    Full Text Available Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT may be important for the re-uptake of serotonin (5-HT in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S versus long (L 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS. All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12-18 years. Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI. Patients with the 5-HTT SS or SLG genotype had a significantly lower number of steps per day than patients with the 5-HTT LALG, SLA or LALA genotype. Patients with the 5-HTT SS or SLG genotype also had a significantly higher FDI score than patients with the 5-HTT LALG, SLA or LALA genotype. Thus, CFS patients with the 5-HTT SS or SLG genotype had worse 30 weeks outcome than CFS patients with the 5-HTT LALG, SLA or LALA genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS.

  8. 2011 Asia Pacific Few-Body Conference Summary Remarks

    International Nuclear Information System (INIS)

    Gibson, B. F.

    2013-01-01

    These remarks represent the author’s personal perspective regarding ideas presented at this fifth Asia Pacific Conference on Few-Body Problems in Physics. They are not intended as a comprehensive summary of what we witnessed during this week of stimulating presentations and intense discussions. However, these remarks do characterize some of the physics we heard and some of the key questions raised. The ideas presented will hopefully outlive the rapporteurs who brought their work and that of others to our attention here in the International Hall of the Sungkyunkwan University in Seoul, Republic of Korea. (author)

  9. Influence of 5-HTT variation, childhood trauma and self-efficacy on anxiety traits: a gene-environment-coping interaction study.

    Science.gov (United States)

    Schiele, Miriam A; Ziegler, Christiane; Holitschke, Karoline; Schartner, Christoph; Schmidt, Brigitte; Weber, Heike; Reif, Andreas; Romanos, Marcel; Pauli, Paul; Zwanzger, Peter; Deckert, Jürgen; Domschke, Katharina

    2016-08-01

    Environmental vulnerability factors such as adverse childhood experiences in interaction with genetic risk variants, e.g., the serotonin transporter gene linked polymorphic region (5-HTTLPR), are assumed to play a role in the development of anxiety and affective disorders. However, positive influences such as general self-efficacy (GSE) may exert a compensatory effect on genetic disposition, environmental adversity, and anxiety traits. We, thus, assessed childhood trauma (Childhood Trauma Questionnaire, CTQ) and GSE in 678 adults genotyped for 5-HTTLPR/rs25531 and their interaction on agoraphobic cognitions (Agoraphobic Cognitions Questionnaire, ACQ), social anxiety (Liebowitz Social Anxiety Scale, LSAS), and trait anxiety (State-Trait Anxiety Inventory, STAI-T). The relationship between anxiety traits and childhood trauma was moderated by self-efficacy in 5-HTTLPR/rs25531 LALA genotype carriers: LALA probands maltreated as children showed high anxiety scores when self-efficacy was low, but low anxiety scores in the presence of high self-efficacy despite childhood maltreatment. Our results extend previous findings regarding anxiety-related traits showing an interactive relationship between 5-HTT genotype and adverse childhood experiences by suggesting coping-related measures to function as an additional dimension buffering the effects of a gene-environment risk constellation. Given that anxiety disorders manifest already early in childhood, this insight could contribute to the improvement of psychotherapeutic interventions by including measures strengthening self-efficacy and inform early targeted preventive interventions in at-risk populations, particularly within the crucial time window of childhood and adolescence.

  10. Huntingtin Protein is Essential for Mitochondrial Metabolism, Bioenergetics and Structure in Murine Embryonic Stem Cells

    Science.gov (United States)

    Ismailoglu, Ismail; Chen, Qiuying; Popowski, Melissa; Yang, Lili; Gross, Steven S.; Brivanlou, Ali H.

    2014-01-01

    Mutations in the Huntington locus (htt) have devastating consequences. Gain-of-poly-Q repeats in Htt protein causes Huntington's disease (HD), while htt-/- mutants display early embryonic lethality. Despite its importance, the function of Htt remains elusive. To address this, we compared more than 3,700 compounds in three syngeneic mouse embryonic stem cell (mESC) lines: htt-/-, extended poly-Q (Htt-Q140/7), and wildtype mESCs (Htt-Q7/7) using untargeted metabolite profiling. While Htt-Q140/7 cells, did not show major differences in cellular bioenergetics, we find extensive metabolic aberrations in htt-/- mESCs, including: (i) complete failure of ATP production despite preservation of the mitochondrial membrane potential; (ii) near-maximal glycolysis, with little or no glycolytic reserve; (iii) marked ketogenesis; (iv) depletion of intracellular NTPs; (v) accelerated purine biosynthesis and salvage; and (vi) loss of mitochondrial structural integrity. Together, our findings reveal that Htt is necessary for mitochondrial structure and function from the earliest stages of embryogenesis, providing a molecular explanation for htt-/- early embryonic lethality. PMID:24780625

  11. Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease.

    Science.gov (United States)

    Ehrnhoefer, Dagmar E; Martin, Dale D O; Schmidt, Mandi E; Qiu, Xiaofan; Ladha, Safia; Caron, Nicholas S; Skotte, Niels H; Nguyen, Yen T N; Vaid, Kuljeet; Southwell, Amber L; Engemann, Sabine; Franciosi, Sonia; Hayden, Michael R

    2018-03-06

    Huntington disease (HD) is caused by the expression of mutant huntingtin (mHTT) bearing a polyglutamine expansion. In HD, mHTT accumulation is accompanied by a dysfunction in basal autophagy, which manifests as specific defects in cargo loading during selective autophagy. Here we show that the expression of mHTT resistant to proteolysis at the caspase cleavage site D586 (C6R mHTT) increases autophagy, which may be due to its increased binding to the autophagy adapter p62. This is accompanied by faster degradation of C6R mHTT in vitro and a lack of mHTT accumulation the C6R mouse model with age. These findings may explain the previously observed neuroprotective properties of C6R mHTT. As the C6R mutation cannot be easily translated into a therapeutic approach, we show that a scheduled feeding paradigm is sufficient to lower mHTT levels in YAC128 mice expressing cleavable mHTT. This is consistent with a previous model, where the presence of cleavable mHTT impairs basal autophagy, while fasting-induced autophagy remains functional. In HD, mHTT clearance and autophagy may become increasingly impaired as a function of age and disease stage, because of gradually increased activity of mHTT-processing enzymes. Our findings imply that mHTT clearance could be enhanced by a regulated dietary schedule that promotes autophagy.

  12. Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression

    DEFF Research Database (Denmark)

    Pouladi, Mahmoud A; Xie, Yuanyun; Skotte, Niels Henning

    2010-01-01

    of the IGF-1 pathway in mediating the effect of htt on body weight. IGF-1 expression was examined in transgenic mouse lines expressing different levels of FL wild-type (WT) htt (YAC18 mice), FL mutant htt (YAC128 and BACHD mice) and truncated mutant htt (shortstop mice). We demonstrate that htt influences...... body weight by modulating the IGF-1 pathway. Plasma IGF-1 levels correlate with body weight and htt levels in the transgenic YAC mice expressing human htt. The effect of htt on IGF-1 expression is independent of CAG size. No effect on body weight is observed in transgenic YAC mice expressing...... and decreases the body weight of YAC128 animals to WT levels. Furthermore, given the ubiquitous expression of IGF-1 within the central nervous system, we also examined the impact of FL htt levels on IGF-1 expression in different regions of the brain, including the striatum, cerebellum of YAC18, YAC128...

  13. Hyalinizing trabecular tumor of the thyroid: Diagnosed of a rare tumor using ultrasonography, cytology, and intraoperative frozen sections

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Hyun Sik; Kim, Eun Kyung; Kwak, Jin Young; Moon, Hee Jung; Yoon, Jung Hyun [Dept. of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul (Korea, Republic of); Park, Cheol Keun; Son, Eun Ju [Gangnam Severance Hospital, Yonsei University, College of Medicine, Seoul (Korea, Republic of)

    2016-03-15

    The goal of this study was to evaluate the clinicopathological and imaging features of thyroid nodules surgically diagnosed as hyaline trabecular tumor (HTT), and to assess the role of cytology and frozen sections (FS) in the diagnosis of HTT. This study included 21 thyroid nodules in 21 patients treated from August 2005 to March 2015 (mean age, 53.3 years) who were either diagnosed as HTT or had HTT suggested as a possible diagnosis based on cytology, FS, or the final pathology report. Patients' medical records were retrospectively reviewed for cytopathologic results and outcomes during the course of follow-up. Sonograms were reviewed and categorized. Twelve nodules from 12 patients were surgically confirmed as HTT. Ultrasonography (US)-guided fine needle aspiration (FNA) was performed on 11 nodules, of which six (54.5%) were papillary thyroid carcinoma (PTC) or suspicious for PTC and three (27.3%) were HTT or suspicious for HTT. Intraoperative FS suggested the possibility of HTT in seven nodules, of which four (57.1%) were confirmed as HTT. US-FNA suggested the diagnosis of HTT in 10 nodules, of which three (30.0%) were confirmed as HTT. Common US features of the 12 pathologically confirmed cases of HTT were hypoechogenicity or marked hypoechogenicity (83.4%), absence of calcifications (91.7%), parallel shape (100.0%), presence of vascularity (75.0%), and probable benignity (58.3%). HTT should be included in the differential diagnosis of solid tumors with hypoechogenicity or marked hypoechogenicity and otherwise benign US features that have been diagnosed as PTC through cytology.

  14. Hyalinizing trabecular tumor of the thyroid: Diagnosed of a rare tumor using ultrasonography, cytology, and intraoperative frozen sections

    International Nuclear Information System (INIS)

    Jang, Hyun Sik; Kim, Eun Kyung; Kwak, Jin Young; Moon, Hee Jung; Yoon, Jung Hyun; Park, Cheol Keun; Son, Eun Ju

    2016-01-01

    The goal of this study was to evaluate the clinicopathological and imaging features of thyroid nodules surgically diagnosed as hyaline trabecular tumor (HTT), and to assess the role of cytology and frozen sections (FS) in the diagnosis of HTT. This study included 21 thyroid nodules in 21 patients treated from August 2005 to March 2015 (mean age, 53.3 years) who were either diagnosed as HTT or had HTT suggested as a possible diagnosis based on cytology, FS, or the final pathology report. Patients' medical records were retrospectively reviewed for cytopathologic results and outcomes during the course of follow-up. Sonograms were reviewed and categorized. Twelve nodules from 12 patients were surgically confirmed as HTT. Ultrasonography (US)-guided fine needle aspiration (FNA) was performed on 11 nodules, of which six (54.5%) were papillary thyroid carcinoma (PTC) or suspicious for PTC and three (27.3%) were HTT or suspicious for HTT. Intraoperative FS suggested the possibility of HTT in seven nodules, of which four (57.1%) were confirmed as HTT. US-FNA suggested the diagnosis of HTT in 10 nodules, of which three (30.0%) were confirmed as HTT. Common US features of the 12 pathologically confirmed cases of HTT were hypoechogenicity or marked hypoechogenicity (83.4%), absence of calcifications (91.7%), parallel shape (100.0%), presence of vascularity (75.0%), and probable benignity (58.3%). HTT should be included in the differential diagnosis of solid tumors with hypoechogenicity or marked hypoechogenicity and otherwise benign US features that have been diagnosed as PTC through cytology

  15. A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal huntingtin’s polyglutamine stretch on CAG140 mouse model pathogenesis

    Directory of Open Access Journals (Sweden)

    Zheng Shuqiu

    2012-08-01

    Full Text Available Abstract Background Huntington’s disease (HD is an autosomal dominant neurodegenerative disease that is caused by the expansion of a polyglutamine (polyQ stretch within Huntingtin (htt, the protein product of the HD gene. Although studies in vitro have suggested that the mutant htt can act in a potentially dominant negative fashion by sequestering wild-type htt into insoluble protein aggregates, the role of the length of the normal htt polyQ stretch, and the adjacent proline-rich region (PRR in modulating HD mouse model pathogenesis is currently unknown. Results We describe the generation and characterization of a series of knock-in HD mouse models that express versions of the mouse HD gene (Hdh encoding N-terminal hemaglutinin (HA or 3xFlag epitope tagged full-length htt with different polyQ lengths (HA7Q-, 3xFlag7Q-, 3xFlag20Q-, and 3xFlag140Q-htt and substitution of the adjacent mouse PRR with the human PRR (3xFlag20Q- and 3xFlag140Q-htt. Using co-immunoprecipitation and immunohistochemistry analyses, we detect no significant interaction between soluble full-length normal 7Q- htt and mutant (140Q htt, but we do observe N-terminal fragments of epitope-tagged normal htt in mutant htt aggregates. When the sequences encoding normal mouse htt’s polyQ stretch and PRR are replaced with non-pathogenic human sequence in mice also expressing 140Q-htt, aggregation foci within the striatum, and the mean size of htt inclusions are increased, along with an increase in striatal lipofuscin and gliosis. Conclusion In mice, soluble full-length normal and mutant htt are predominantly monomeric. In heterozygous knock-in HD mouse models, substituting the normal mouse polyQ and PRR with normal human sequence can exacerbate some neuropathological phenotypes.

  16. Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and lysosomes

    Science.gov (United States)

    Caviston, Juliane P.; Zajac, Allison L.; Tokito, Mariko; Holzbaur, Erika L.F.

    2011-01-01

    Huntingtin (Htt) is a membrane-associated scaffolding protein that interacts with microtubule motors as well as actin-associated adaptor molecules. We examined a role for Htt in the dynein-mediated intracellular trafficking of endosomes and lysosomes. In HeLa cells depleted of either Htt or dynein, early, recycling, and late endosomes (LE)/lysosomes all become dispersed. Despite altered organelle localization, kinetic assays indicate only minor defects in intracellular trafficking. Expression of full-length Htt is required to restore organelle localization in Htt-depleted cells, supporting a role for Htt as a scaffold that promotes functional interactions along its length. In dynein-depleted cells, LE/lysosomes accumulate in tight patches near the cortex, apparently enmeshed by cortactin-positive actin filaments; Latrunculin B-treatment disperses these patches. Peripheral LE/lysosomes in dynein-depleted cells no longer colocalize with microtubules. Htt may be required for this off-loading, as the loss of microtubule association is not seen in Htt-depleted cells or in cells depleted of both dynein and Htt. Inhibition of kinesin-1 relocalizes peripheral LE/lysosomes induced by Htt depletion but not by dynein depletion, consistent with their detachment from microtubules upon dynein knockdown. Together, these data support a model of Htt as a facilitator of dynein-mediated trafficking that may regulate the cytoskeletal association of dynamic organelles. PMID:21169558

  17. Effects of amoxicillin/clavulanic acid on the pharmacokinetics of valproic acid

    Directory of Open Access Journals (Sweden)

    Lee SY

    2015-08-01

    Full Text Available Soo-Yun Lee,1 Wooseong Huh,2 Jin Ah Jung,3 Hye Min Yoo,2 Jae-Wook Ko,1,2 Jung-Ryul Kim2,4 1Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 2Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, 3Department of Clinical Pharmacology, Inje University, Busan Paik Hospital, Busan, 4Department of Clinical Research and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea Abstract: Valproic acid (VPA is mainly metabolized via glucuronide, which is hydrolyzed by β-glucuronidase and undergoes enterohepatic circulation. Amoxicillin/clavulanic acid (AMC administration leads to decreased levels of β-glucuronidase-producing bacteria, suggesting that these antibiotics could interrupt enterohepatic circulation and thereby alter the pharmacokinetics of VPA. This study aimed to evaluate the effects of AMC on the pharmacokinetics of VPA. This was an open-label, two-treatment, one-sequence study in 16 healthy volunteers. Two treatments were evaluated; treatment VPA, in which a single dose of VPA 500 mg was administered, and treatment AMC + VPA, in which multiple doses of AMC 500/125 mg were administered three times daily for 7 days and then a single dose of VPA was administered. Blood samples were collected up to 48 hours. Pharmacokinetic parameters were calculated using noncompartmental methods. Fifteen subjects completed the study. Systemic exposures and peak concentrations of VPA were slightly lower with treatment AMC + VPA than with treatment VPA (AUClast, 851.0 h·mg/L vs 889.6 h·mg/L; Cmax, 52.1 mg/L vs 53.0 mg/L. There were no significant between-treatment effects on pharmacokinetics (95% confidence interval [CI] of AUClast and Cmax (95.7 [85.9–106.5] and 98.3 [91.6–105.6], respectively. Multiple doses of AMC had no significant effects on the pharmacokinetics of VPA; thus, no dose adjustment is necessary. Keywords: drug–drug interaction, pharmacokinetics

  18. The cryo-electron microscopy structure of huntingtin

    Science.gov (United States)

    Guo, Qiang; Bin Huang; Cheng, Jingdong; Seefelder, Manuel; Engler, Tatjana; Pfeifer, Günter; Oeckl, Patrick; Otto, Markus; Moser, Franziska; Maurer, Melanie; Pautsch, Alexander; Baumeister, Wolfgang; Fernández-Busnadiego, Rubén; Kochanek, Stefan

    2018-03-01

    Huntingtin (HTT) is a large (348 kDa) protein that is essential for embryonic development and is involved in diverse cellular activities such as vesicular transport, endocytosis, autophagy and the regulation of transcription. Although an integrative understanding of the biological functions of HTT is lacking, the large number of identified HTT interactors suggests that it serves as a protein-protein interaction hub. Furthermore, Huntington’s disease is caused by a mutation in the HTT gene, resulting in a pathogenic expansion of a polyglutamine repeat at the amino terminus of HTT. However, only limited structural information regarding HTT is currently available. Here we use cryo-electron microscopy to determine the structure of full-length human HTT in a complex with HTT-associated protein 40 (HAP40; encoded by three F8A genes in humans) to an overall resolution of 4 Å. HTT is largely α-helical and consists of three major domains. The amino- and carboxy-terminal domains contain multiple HEAT (huntingtin, elongation factor 3, protein phosphatase 2A and lipid kinase TOR) repeats arranged in a solenoid fashion. These domains are connected by a smaller bridge domain containing different types of tandem repeats. HAP40 is also largely α-helical and has a tetratricopeptide repeat-like organization. HAP40 binds in a cleft and contacts the three HTT domains by hydrophobic and electrostatic interactions, thereby stabilizing the conformation of HTT. These data rationalize previous biochemical results and pave the way for improved understanding of the diverse cellular functions of HTT.

  19. Scalable production in human cells and biochemical characterization of full-length normal and mutant huntingtin.

    Directory of Open Access Journals (Sweden)

    Bin Huang

    Full Text Available Huntingtin (Htt is a 350 kD intracellular protein, ubiquitously expressed and mainly localized in the cytoplasm. Huntington's disease (HD is caused by a CAG triplet amplification in exon 1 of the corresponding gene resulting in a polyglutamine (polyQ expansion at the N-terminus of Htt. Production of full-length Htt has been difficult in the past and so far a scalable system or process has not been established for recombinant production of Htt in human cells. The ability to produce Htt in milligram quantities would be a prerequisite for many biochemical and biophysical studies aiming in a better understanding of Htt function under physiological conditions and in case of mutation and disease. For scalable production of full-length normal (17Q and mutant (46Q and 128Q Htt we have established two different systems, the first based on doxycycline-inducible Htt expression in stable cell lines, the second on "gutless" adenovirus mediated gene transfer. Purified material has then been used for biochemical characterization of full-length Htt. Posttranslational modifications (PTMs were determined and several new phosphorylation sites were identified. Nearly all PTMs in full-length Htt localized to areas outside of predicted alpha-solenoid protein regions. In all detected N-terminal peptides methionine as the first amino acid was missing and the second, alanine, was found to be acetylated. Differences in secondary structure between normal and mutant Htt, a helix-rich protein, were not observed in our study. Purified Htt tends to form dimers and higher order oligomers, thus resembling the situation observed with N-terminal fragments, although the mechanism of oligomer formation may be different.

  20. Reduced availability of serotonin transporters in obsessive-compulsive disorder correlates with symptom severity - a [11C]DASB PET study

    International Nuclear Information System (INIS)

    Reimold, M.; Smolka, M.N.; Zimmer, A.

    2007-01-01

    Reduced availability of brainstem serotonin transporters (5-HTT) has been observed in vivo in obsessive-compulsive disorder (OCD). However, results vary and may be influenced by competition with endogenous serotonin. Using positron emission tomography (PET) and [ 11 C]DASB, a specific 5-HTT ligand that showed no competition with serotonin for 5-HTT binding in vitro, we tested the hypothesis that 5-HTT availability is reduced in OCD patients and correlated with OCD severity. 5-HTT availability in the thalamus and the midbrain was measured in nine drug-free OCD patients and compared with 19 healthy controls, matched for the individual combination of 5-HTT genotype, gender and smoking status. OCD severity was assessed with the Yale-Brown obsessive compulsive scale (Y-BOCS). 5-HTT availability was significantly reduced in the thalamus and midbrain of OCD patients. Age and 5-HTT in the thalamus explained 83 % of OCD severity in patients that were drug-free for at least 1 year. This PET study confirms a central role of the serotonergic system, particularly the thalamus in the pathogenesis of obsessive compulsive disorder. (author)

  1. Calcium Handling by Endoplasmic Reticulum and Mitochondria in a Cell Model of Huntington’s Disease

    Science.gov (United States)

    De Mario, Agnese; Scarlatti, Chiara; Costiniti, Veronica; Primerano, Simona; Lopreiato, Raffaele; Calì, Tito; Brini, Marisa; Giacomello, Marta; Carafoli, Ernesto

    2016-01-01

    Huntington disease (HD) is caused by the CAG (Q) expansion in exon 1 of the IT15 gene encoding a polyglutamine (poly-Q) stretch of the Huntingtin protein (Htt). In the wild type protein, the repeats specify a stretch of up 34 Q in the N-terminal portion of Htt. In the pathological protein (mHtt) the poly-Q tract is longer. Proteolytic cleavage of the protein liberates an N-terminal fragment containing the expanded poly-Q tract becomes harmful to cells, in particular to striatal neurons. The fragments cause the transcriptional dysfunction of genes that are essential for neuronal survival. Htt, however, could also have non-transcriptional effects, e.g. it could directly alter Ca2+ homeostasis and/or mitochondrial morphology and function. Ca2+ dyshomeostasis and mitochondrial dysfunction are considered important in the molecular aetiology of the disease. Here we have analyzed the effect of the overexpression of Htt fragments (18Q, wild type form, wtHtt and 150Q mutated form, mHtt) on Ca2+ homeostasis in striatal neuronal precursor cells (Q7/7). We have found that the transient overexpression of the Htt fragments increases Ca2+ transients in the mitochondria of cells stimulated with Ca2+-mobilizing agonists. The bulk Ca2+ transients in the cytosol were unaffected, but the Ca2+ content of the endoplasmic reticulum was significantly decreased in the case of mHtt expression. To rule out possible transcriptional effects due to the presence of mHtt, we have measured the mRNA level of a subunit of the respiratory chain complex II, whose expression is commonly altered in many HD models. No effects on the mRNA level was found suggesting that, in our experimental condition, transcriptional action of Htt is not occurring and that the effects on Ca2+ homeostasis were dependent to non-transcriptional mechanisms. PMID:26819834

  2. Calcium Handling by Endoplasmic Reticulum and Mitochondria in a Cell Model of Huntington's Disease.

    Science.gov (United States)

    De Mario, Agnese; Scarlatti, Chiara; Costiniti, Veronica; Primerano, Simona; Lopreiato, Raffaele; Calì, Tito; Brini, Marisa; Giacomello, Marta; Carafoli, Ernesto

    2016-01-06

    Huntington disease (HD) is caused by the CAG (Q) expansion in exon 1 of the IT15 gene encoding a polyglutamine (poly-Q) stretch of the Huntingtin protein (Htt). In the wild type protein, the repeats specify a stretch of up 34 Q in the N-terminal portion of Htt. In the pathological protein (mHtt) the poly-Q tract is longer. Proteolytic cleavage of the protein liberates an N-terminal fragment containing the expanded poly-Q tract becomes harmful to cells, in particular to striatal neurons. The fragments cause the transcriptional dysfunction of genes that are essential for neuronal survival. Htt, however, could also have non-transcriptional effects, e.g. it could directly alter Ca2+ homeostasis and/or mitochondrial morphology and function. Ca2+ dyshomeostasis and mitochondrial dysfunction are considered important in the molecular aetiology of the disease. Here we have analyzed the effect of the overexpression of Htt fragments (18Q, wild type form, wtHtt and 150Q mutated form, mHtt) on Ca2+ homeostasis in striatal neuronal precursor cells (Q7/7). We have found that the transient overexpression of the Htt fragments increases Ca2+ transients in the mitochondria of cells stimulated with Ca2+-mobilizing agonists. The bulk Ca2+ transients in the cytosol were unaffected, but the Ca2+ content of the endoplasmic reticulum was significantly decreased in the case of mHtt expression. To rule out possible transcriptional effects due to the presence of mHtt, we have measured the mRNA level of a subunit of the respiratory chain complex II, whose expression is commonly altered in many HD models. No effects on the mRNA level was found suggesting that, in our experimental condition, transcriptional action of Htt is not occurring and that the effects on Ca2+ homeostasis were dependent to non-transcriptional mechanisms.

  3. A new model for separation between brain dopamine and serotonin transporters in {sup 123}I-{beta}-CIT SPECT measurements: normal values and sex and age dependence

    Energy Technology Data Exchange (ETDEWEB)

    Ryding, Erik; Rosen, Ingmar [Department of Clinical Neurophysiology, University Hospital, Lund (Sweden); Lindstroem, Mats; Bosson, Peter; Traeskman-Bendz, Lil [Department of Psychiatry, University Hospital, Lund (Sweden); Braadvik, Bjoern; Grabowski, Martin [Department of Neurology, University Hospital, Lund (Sweden)

    2004-08-01

    {sup 123}I-{beta}-CIT is a radioactive ligand for single-photon emission computed tomography (SPECT) imaging of the pre-synaptic (transporter) re-uptake sites for dopamine (DAT) and serotonin (5HTT), and it is widely used to visualize monoamine turnover. Since {sup 123}I-{beta}-CIT uptake occurs at 5HTT and DAT sites in conjunction with the presence of freely soluble {sup 123}I-{beta}-CIT in brain tissue, adequate separation of these three components is necessary. However, only partial separation is possible with current methods. Two main strategies have previously been used for {sup 123}I-{beta}-CIT component separation, based on the following considerations: (1) the faster uptake rate for 5HTT compared with DAT enables temporal separation by performing 5HTT imaging at 1-2 h and DAT imaging at 20-24 h; (2) blocking the 5HTT re-uptake with citalopram renders {sup 123}I-{beta}-CIT imaging DAT (non-5HTT) specific. In a new analytical model, we combined these two approaches with methods to isolate the passively dissolved {sup 123}I-{beta}-CIT in brain tissue from the monoamine transporter uptake, and to correct the 5HTT and DAT values for concomitant uptake. The new analytical model was used to study brain 5HTT and DAT in 23 normal subjects, with the aim of clarifying the effect of age and sex. A significant correlation between 5HTT and DAT values was found only in the thalamus, indicating successful component separation. Negative correlations between age and DAT were found for basal ganglia, thalami, brain stem and temporal lobes, but not for the frontal, parietal or occipital regions. No correlation with age was found for 5HTT. We found no sex difference for 5HTT or DAT. (orig.)

  4. Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype

    International Nuclear Information System (INIS)

    Reimold, M.; Bares, R.; Reischl, G.; Solbach, C.; Machulla, H.-J.; Smolka, M.N.; Mann, K.; Schumann, G.; Zimmer, A.; Wrase, J.; Hu, X.-Z.; Goldman, D.; Heinz, A.

    2007-01-01

    Homozygote carriers of two long (L) alleles of the serotonin transporter (5-HTT) regulatory region displayed in vitro a twofold increase in 5-HTT expression compared with carriers of one or two short (S) alleles. However, in vivo imaging studies yielded contradictory results. Recently, an A > G exchange leading to differential transcriptional activation of 5-HTT mRNA in lymphobalstoid cell lines was discovered in the 5-HTT regulatory region. In vitro and in vivo evidence suggests that [ 11 C]DASB, a new 5-HTT ligand offers some advantages over the ligands used in previous studies in measuring 5-HTT density independent of synaptic levels of serotonin. We assessed 5-HTT binding potential (BP 2) in the midbrain of 19 healthy subjects with positron emission tomography and [ 11 C]DASB. Accounting for the hypothesized functional similarity of L G and S in driving 5-HTT transcription, we assessed whether L A L A homozygotes display increased midbrain BP 2 compared with carriers of at least one S allele. BP 2 in the midbrain was significantly increased in L A L A homozygotes compared with carriers of at least one S allele. Interestingly, the genotype effect on the midbrain was significantly different from that on the thalamus and the amygdala where no group differences were detected. This in vivo study provides further evidence that subjects homozygous for the L A allele display increased expression of 5-HTT in the midbrain, the origin of central serotonergic projections. (author)

  5. SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation

    Directory of Open Access Journals (Sweden)

    Jacqueline Gire O’Rourke

    2013-07-01

    Full Text Available A key feature in Huntington disease (HD is the accumulation of mutant Huntingtin (HTT protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression.

  6. Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is cell-type-specific

    NARCIS (Netherlands)

    Jansen, Anne H. P.; van Hal, Maurik; Op den Kelder, Ilse C.; Meier, Romy T.; de Ruiter, Anna-Aster; Schut, Menno H.; Smith, Donna L.; Grit, Corien; Brouwer, Nieske; Kamphuis, Willem; Boddeke, H. W. G. M.; den Dunnen, Wilfred F. A.; van Roon, Willeke M. C.; Bates, Gillian P.; Hol, Elly M.; Reits, Eric A.

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions

  7. Frequency of Nuclear Mutant Huntingtin Inclusion Formation in Neurons and Glia is Cell-Type-Specific

    NARCIS (Netherlands)

    Jansen, Anne H P; van Hal, Maurik; op den Kelder, Ilse C.; Meier, Romy T.; de Ruiter, Anna-Aster; Schut, Menno H.; Smith, Donna L.; Grit, Corien; Brouwer, Nieske; Kamphuis, Willem; Boddeke, H. W. G. M.; den Dunnen, Wilfred F. A.; van Roon, Willeke M. C.; Bates, Gillian P.; Hol, Elly M.; Reits, Eric A.

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions

  8. Ensiling and hydrothermal pretreatment of grass: Consequences for enzymatic biomass conversion and total monosaccharide yields

    DEFF Research Database (Denmark)

    Ambye-Jensen, Morten; Johansen, Katja Salomon; Didion, Thomas

    2014-01-01

    Ensiling may act as a pretreatment of fresh grass biomass and increase the enzymatic conversion of structural carbohydrates to fermentable sugars. However, ensiling does not provide sufficient severity to be a standalone pretreatment method. Here, ensiling of grass is combined with hydrothermal...... treatment (HTT) with the aim of improving the enzymatic biomass convertibility and decrease the required temperature of the HTT. Results: Grass silage (Festulolium Hykor) was hydrothermally treated at temperatures of 170, 180, and 190°C for 10 minutes. Relative to HTT treated dry grass, ensiling increased...... convertibility). The effect of ensiling of grass prior to HTT improved the enzymatic conversion of cellulose for HTT at 170 and 180°C, but the increased glucose release did not make up for the loss of water soluble carbohydrates (WSC) during ensiling. Overall, sugar yields (C6 + C5) were similar for HTT of grass...

  9. 2305-7432. htt

    African Journals Online (AJOL)

    Peter Berglez

    film actor Hope Chisanu expressing the feeling commonly shared in the country about ... David Kerr's Dance, Media, Entertainment and Performance in south east Africa (Kerr, ... Africanus Aveh in the Rise of video film industry & its social .... commonly known as adventures of Sam Mperu (Magalasi, personal experience).

  10. A novel humanized mouse model of Huntington disease for preclinical development of therapeutics targeting mutant huntingtin alleles

    DEFF Research Database (Denmark)

    Southwell, Amber L; Skotte, Niels H; Villanueva, Erika B

    2017-01-01

    transgenes in Hu128/21 mice match the human HTT exon 1 reference sequence. Conversely, the BACHD transgene carries a floxed, synthetic exon 1 sequence. Hu128/21 mice will be useful for investigations of human HTT that cannot be addressed in Hu97/18 mice, for developing therapies targeted to exon 1......Huntington disease (HD) is a neurodegenerative disease caused by a mutation in the huntingtin (HTT) gene. HTT is a large protein, interacts with many partners and is involved in many cellular pathways, which are perturbed in HD. Therapies targeting HTT directly are likely to provide the most global......-length, genomic human HTT transgenes heterozygous for the HD mutation and polymorphisms associated with HD in populations of East Asian descent and in a minority of patients from other ethnic groups. Hu128/21 mice display a wide variety of HD-like phenotypes that are similar to YAC128 mice. Additionally, both...

  11. Expression analysis for inverted effects of serotonin transporter inactivation

    International Nuclear Information System (INIS)

    Ichikawa, Manabu; Okamura-Oho, Yuko; Shimokawa, Kazuro; Kondo, Shinji; Nakamura, Sakiko; Yokota, Hideo; Himeno, Ryutaro; Lesch, Klaus-Peter; Hayashizaki, Yoshihide

    2008-01-01

    Inactivation of serotonin transporter (HTT) by pharmacologically in the neonate or genetically increases risk for depression in adulthood, whereas pharmacological inhibition of HTT ameliorates symptoms in depressed patients. The differing role of HTT function during early development and in adult brain plasticity in causing or reversing depression remains an unexplained paradox. To address this we profiled the gene expression of adult Htt knockout (Htt KO) mice and HTT inhibitor-treated mice. Inverted profile changes between the two experimental conditions were seen in 30 genes. Consistent results of the upstream regulatory element search and the co-localization search of these genes indicated that the regulation may be executed by Pax5, Pax7 and Gata3, known to be involved in the survival, proliferation, and migration of serotonergic neurons in the developing brain, and these factors are supposed to keep functioning to regulate downstream genes related to serotonin system in the adult brain

  12. Different impacts of respiratory symptoms and comorbidities on COPD-specific health-related quality of life by COPD severity

    Directory of Open Access Journals (Sweden)

    Lee H

    2017-11-01

    Full Text Available Hyun Lee,1,* Byung Woo Jhun,1,* Juhee Cho,2–4 Kwang Ha Yoo,5 Jin Hwa Lee,6 Deog Kyeom Kim,7 Jong Deog Lee,8 Ki-Suck Jung,9 Jung Yeon Lee,10 Hye Yun Park1 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 2Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 4Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea; 6Division of Pulmonary and Critical Care Medicine, School of Medicine, Ewha Womans University, Seoul, South Korea; 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, South Korea; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungju Hospital, Konkuk University School of Medicine, Chungju, South Korea *These authors contributed equally to this work Background: Patients with chronic obstructive pulmonary disease (COPD often have poor health-related quality of life (HRQoL that is disproportionate to their degree of airflow limitation. This study evaluated the association between St

  13. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin

    DEFF Research Database (Denmark)

    Carroll, Jeffrey B; Warby, Simon C; Southwell, Amber L

    2011-01-01

    Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild...

  14. Discovery of novel isoforms of huntingtin reveals a new hominid-specific exon.

    Directory of Open Access Journals (Sweden)

    Albert Ruzo

    Full Text Available Huntington's disease (HD is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT. HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease.

  15. Discovery of Novel Isoforms of Huntingtin Reveals a New Hominid-Specific Exon

    Science.gov (United States)

    Popowski, Melissa; Haremaki, Tomomi; Croft, Gist F.; Deglincerti, Alessia; Brivanlou, Ali H.

    2015-01-01

    Huntington’s disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC) lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease. PMID:26010866

  16. Normal aging modulates the neurotoxicity of mutant huntingtin.

    Directory of Open Access Journals (Sweden)

    Elsa Diguet

    Full Text Available Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD, a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt, the role of aging is unclear. For a given tract length, the probability of disease onset increases with age. There are mainly two hypotheses that could explain adult onset in HD: Either mutant Htt progressively produces cumulative defects over time or "normal" aging renders neurons more vulnerable to mutant Htt toxicity. In the present study, we directly explored whether aging affected the toxicity of mutant Htt in vivo. We studied the impact of aging on the effects produced by overexpression of an N-terminal fragment of mutant Htt, of wild-type Htt or of a beta-Galactosidase (beta-Gal reporter gene in the rat striatum. Stereotaxic injections of lentiviral vectors were performed simultaneously in young (3 week and old (15 month rats. Histological evaluation at different time points after infection demonstrated that the expression of mutant Htt led to pathological changes that were more severe in old rats, including an increase in the number of small Htt-containing aggregates in the neuropil, a greater loss of DARPP-32 immunoreactivity and striatal neurons as assessed by unbiased stereological counts.The present results support the hypothesis that "normal" aging is involved in HD pathogenesis, and suggest that age-related cellular defects might constitute potential therapeutic targets for HD.

  17. Prior fear conditioning does not impede enhanced active avoidance in serotonin transporter knockout rats.

    Science.gov (United States)

    Schipper, Pieter; Henckens, Marloes J A G; Borghans, Bart; Hiemstra, Marlies; Kozicz, Tamas; Homberg, Judith R

    2017-05-30

    Stressors can be actively or passively coped with, and adequate adaption of the coping response to environmental conditions can reduce their potential deleterious effects. One major factor influencing stress coping behaviour is serotonin transporter (5-HTT) availability. Abolishment of 5-HTT is known to impair fear extinction but facilitates acquisition of signalled active avoidance (AA), a behavioural task in which an animal learns to avoid an aversive stimulus that is predicted by a cue. Flexibility in adapting coping behaviour to the nature of the stressor shapes resilience to stress-related disorders. Therefore, we investigated the relation between 5-HTT expression and ability to adapt a learned coping response to changing environmental conditions. To this end, we first established and consolidated a cue-conditioned passive fear response in 5-HTT -/- and wildtype rats. Next, we used the conditioned stimulus (CS) to signal oncoming shocks during signalled AA training in 5-HTT -/- and wildtype rats to study their capability to acquire an active coping response to the CS following fear conditioning. Finally, we investigated the behavioural response to the CS in a novel environment and measured freezing, exploration and self-grooming, behaviours reflective of stress coping strategy. We found that fear conditioned and sham conditioned 5-HTT -/- animals acquired the signalled AA response faster than wildtypes, while prior conditioning briefly delayed AA learning similarly in both genotypes. Subsequent exposure to the CS in the novel context reduced freezing and increased locomotion in 5-HTT -/- compared to wildtype rats. This indicates that improved AA performance in 5-HTT -/- rats resulted in a weaker residual passive fear response to the CS in a novel context. Fear conditioning prior to AA training did not affect freezing upon re-encountering the CS, although it did reduce locomotion in 5-HTT -/- rats. We conclude that independent of 5-HTT signalling, prior fear

  18. Loss of Huntingtin stimulates capture of retrograde dense-core vesicles to increase synaptic neuropeptide stores.

    Science.gov (United States)

    Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

    2017-08-01

    The Huntington's disease protein Huntingtin (Htt) regulates axonal transport of dense-core vesicles (DCVs) containing neurotrophins and neuropeptides. DCVs travel down axons to reach nerve terminals where they are either captured in synaptic boutons to support later release or reverse direction to reenter the axon as part of vesicle circulation. Currently, the impact of Htt on DCV dynamics in the terminal is unknown. Here we report that knockout of Drosophila Htt selectively reduces retrograde DCV flux at proximal boutons of motoneuron terminals. However, initiation of retrograde transport at the most distal bouton and transport velocity are unaffected suggesting that synaptic capture rate of these retrograde DCVs could be altered. In fact, tracking DCVs shows that retrograde synaptic capture efficiency is significantly elevated by Htt knockout or knockdown. Furthermore, synaptic boutons contain more neuropeptide in Htt knockout larvae even though bouton size, single DCV fluorescence intensity, neuropeptide release in response to electrical stimulation and subsequent activity-dependent capture are unaffected. Thus, loss of Htt increases synaptic capture as DCVs travel by retrograde transport through boutons resulting in reduced transport toward the axon and increased neuropeptide in the terminal. These results therefore identify native Htt as a regulator of synaptic capture and neuropeptide storage. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Sequestration of Sup35 by aggregates of huntingtin fragments causes toxicity of [PSI+] yeast.

    Science.gov (United States)

    Zhao, Xiaohong; Park, Yang-Nim; Todor, Horia; Moomau, Christine; Masison, Daniel; Eisenberg, Evan; Greene, Lois E

    2012-07-06

    Expression of huntingtin fragments with 103 glutamines (HttQ103) is toxic in yeast containing either the [PIN(+)] prion, which is the amyloid form of Rnq1, or [PSI(+)] prion, which is the amyloid form of Sup35. We find that HttQP103, which has a polyproline region at the C-terminal end of the polyQ repeat region, is significantly more toxic in [PSI(+)] yeast than in [PIN(+)], even though HttQP103 formed multiple aggregates in both [PSI(+)] and [PIN(+)] yeast. This toxicity was only observed in the strong [PSI(+)] variant, not the weak [PSI(+)] variant, which has more soluble Sup35 present than the strong variant. Furthermore, expression of the MC domains of Sup35, which retains the C-terminal domain of Sup35, but lacks the N-terminal prion domain, almost completely rescued HttQP103 toxicity, but was less effective in rescuing HttQ103 toxicity. Therefore, the toxicity of HttQP103 in yeast containing the [PSI(+)] prion is primarily due to sequestration of the essential protein, Sup35.

  20. Cardiac mTORC1 Dysregulation Impacts Stress Adaptation and Survival in Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Daniel D. Child

    2018-04-01

    Full Text Available Summary: Huntington’s disease (HD is a dominantly inherited neurological disorder caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT. But in addition to the neurological disease, mutant HTT (mHTT, which is ubiquitously expressed, impairs other organ systems. Indeed, epidemiological and animal model studies suggest higher incidence of and mortality from heart disease in HD. Here, we show that the protein complex mTORC1 is dysregulated in two HD mouse models through a mechanism that requires intrinsic mHTT expression. Moreover, restoring cardiac mTORC1 activity with constitutively active Rheb prevents mortality and relieves the mHTT-induced block to hypertrophic adaptation to cardiac stress. Finally, we show that chronic mTORC1 dysregulation is due in part to mislocalization of endogenous Rheb. These data provide insight into the increased cardiac-related mortality of HD patients, with cardiac mHTT expression inhibiting mTORC1 activity, limiting heart growth, and decreasing the heart’s ability to compensate to chronic stress. : Child et al. demonstrate that mTORC1 dysregulation is a key molecular mechanism in the Huntington’s disease (HD heart phenotype. Impaired cardiac mTORC1 activity in HD mouse models requires intrinsic mHTT expression and explains the limited adaptation to cardiac stress. Keywords: Huntington’s disease, heart, mTOR, Rheb

  1. Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer.

    Directory of Open Access Journals (Sweden)

    Bankanidhi Sahoo

    Full Text Available Expansion of the polyglutamine (polyQ track of the Huntingtin (HTT protein above 36 is associated with a sharply enhanced risk of Huntington's disease (HD. Although there is general agreement that HTT toxicity resides primarily in N-terminal fragments such as the HTT exon1 protein, there is no consensus on the nature of the physical states of HTT exon1 that are induced by polyQ expansion, nor on which of these states might be responsible for toxicity. One hypothesis is that polyQ expansion induces an alternative, toxic conformation in the HTT exon1 monomer. Alternative hypotheses posit that the toxic species is one of several possible aggregated states. Defining the nature of the toxic species is particularly challenging because of facile interconversion between physical states as well as challenges to identifying these states, especially in vivo. Here we describe the use of fluorescence correlation spectroscopy (FCS to characterize the detailed time and repeat length dependent self-association of HTT exon1-like fragments both with chemically synthesized peptides in vitro and with cell-produced proteins in extracts and in living cells. We find that, in vitro, mutant HTT exon1 peptides engage in polyQ repeat length dependent dimer and tetramer formation, followed by time dependent formation of diffusible spherical and fibrillar oligomers and finally by larger, sedimentable amyloid fibrils. For expanded polyQ HTT exon1 expressed in PC12 cells, monomers are absent, with tetramers being the smallest molecular form detected, followed in the incubation time course by small, diffusible aggregates at 6-9 hours and larger, sedimentable aggregates that begin to build up at 12 hrs. In these cell cultures, significant nuclear DNA damage appears by 6 hours, followed at later times by caspase 3 induction, mitochondrial dysfunction, and cell death. Our data thus defines limits on the sizes and concentrations of different physical states of HTT exon1 along the

  2. Analysis of proteolytic processes and enzymatic activities in the generation of huntingtin n-terminal fragments in an HEK293 cell model.

    Directory of Open Access Journals (Sweden)

    Andrew T N Tebbenkamp

    Full Text Available N-terminal fragments of mutant huntingtin (htt that terminate between residues 90-115, termed cleavage product A or 1 (cp-A/1, form intracellular and intranuclear inclusion bodies in the brains of patients with Huntington's disease (HD. These fragments appear to be proteolytic products of the full-length protein. Here, we use an HEK293 cell culture model to investigate huntingtin proteolytic processing; previous studies of these cells have demonstrated cleavage of htt to cp-A/1 like htt fragments.Recombinant N-terminal htt fragments, terminating at residue 171 (also referred to as cp-B/2 like, were efficiently cleaved to produce cp-A/1 whereas fragments representing endogenous caspase, calpain, and metalloproteinase cleavage products, terminating between residues 400-600, were inefficiently cleaved. Using cysteine-labeling techniques and antibody binding mapping, we localized the C-terminus of the cp-A/1 fragments produced by HEK293 cells to sequences minimally limited by cysteine 105 and an antibody epitope composed of residues 115-124. A combination of genetic and pharmacologic approaches to inhibit potential proteases, including γ-secretase and calpain, proved ineffective in preventing production of cp-A/1.Our findings indicate that HEK293 cells express a protease that is capable of efficiently cleaving cp-B/2 like fragments of htt with normal or expanded glutamine repeats. For reasons that remain unclear, this protease cleaves longer htt fragments, with normal or expanded glutamine expansions, much less efficiently. The protease in HEK293 cells that is capable of generating a cp-A/1 like htt fragment may be a novel protease with a high preference for a cp-B/2-like htt fragment as substrate.

  3. Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington’s disease

    Science.gov (United States)

    Paul, Bindu D.; Sbodio, Juan I.; Xu, Risheng; Vandiver, M. Scott; Cha, Jiyoung Y.; Snowman, Adele M.; Snyder, Solomon H.

    2015-01-01

    Huntington’s disease is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and behavioural changes1. Huntington’s disease is characterized by highly selective and profound damage to the corpus striatum, which regulates motor function. Striatal selectivity of Huntington’s disease may reflect the striatally selective small G protein Rhes binding to mHtt and enhancing its neurotoxicity2. Specific molecular mechanisms by which mHtt elicits neurodegeneration have been hard to determine. Here we show a major depletion of cystathionine γ-lyase (CSE), the biosynthetic enzyme for cysteine, in Huntington’s disease tissues, which may mediate Huntington’s disease pathophysiology. The defect occurs at the transcriptional level and seems to reflect influences of mHtt on specificity protein 1, a transcriptional activator for CSE. Consistent with the notion of loss of CSE as a pathogenic mechanism, supplementation with cysteine reverses abnormalities in cultures of Huntington’s disease tissues and in intact mouse models of Huntington’s disease, suggesting therapeutic potential. PMID:24670645

  4. Evidence for the Association of a Deleted Variant in the 5′-Flanking Region of the Chicken serotonin transporter (5-HTT Gene with a Temporary Increase in Feed Intake and Growth Rate

    Directory of Open Access Journals (Sweden)

    Joergen B. Kjaer

    2016-10-01

    Full Text Available The serotonergic system has been shown to be implicated in the regulation of mood and feeding behavior. Previous studies have identified a polymorphism in the 5′-flanking region of the serotonin transporter ( 5 - HTT gene of Lohmann Brown (LB laying hens. The deleted variant D was found to be associated with increased body weight. The objective of this study was to address whether the increased body weight may be due to an increased feed intake. After hatching, hens were kept under ad libitum feeding conditions, and their body weight and feed intake were weekly determined. From 5 weeks of age, the body weight of hens with the D/D and W/D genotypes was significantly greater than that of W/W carrying hens. Interestingly, we found that the feed intake of D/D carrying hens, relative to body weight, was transiently increased only between 4 and 7 weeks of age ( p < 0.05, leading to a higher growth rate ( p < 0.05, compared with that of W/W carrying hens. These results suggest that the presence of variant D may be correlated with a transiently increased appetite of D/D carrying hens.

  5. Sensitivity and Specificity of Clinical and Laboratory Otolith Function Tests.

    Science.gov (United States)

    Kumar, Lokesh; Thakar, Alok; Thakur, Bhaskar; Sikka, Kapil

    2017-10-01

    To evaluate clinic based and laboratory tests of otolith function for their sensitivity and specificity in demarcating unilateral compensated complete vestibular deficit from normal. Prospective cross-sectional study. Tertiary care hospital vestibular physiology laboratory. Control group-30 healthy adults, 20-45 years age; Case group-15 subjects post vestibular shwannoma excision or post-labyrinthectomy with compensated unilateral complete audio-vestibular loss. Otolith function evaluation by precise clinical testing (head tilt test-HTT; subjective visual vertical-SVV) and laboratory testing (headroll-eye counterroll-HR-ECR; vesibular evoked myogenic potentials-cVEMP). Sensitivity and specificity of clinical and laboratory tests in differentiating case and control subjects. Measurable test results were universally obtained with clinical otolith tests (SVV; HTT) but not with laboratory tests. The HR-ECR test did not indicate any definitive wave forms in 10% controls and 26% cases. cVEMP responses were absent in 10% controls.HTT test with normative cutoff at 2 degrees deviations from vertical noted as 93.33% sensitive and 100% specific. SVV test with normative cutoff at 1.3 degrees noted as 100% sensitive and 100% specific. Laboratory tests demonstrated poorer specificities owing primarily to significant unresponsiveness in normal controls. Clinical otolith function tests, if conducted with precision, demonstrate greater ability than laboratory testing in discriminating normal controls from cases with unilateral complete compensated vestibular dysfunction.

  6. Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in human lung cells

    International Nuclear Information System (INIS)

    Tsukahara, Tamotsu; Matsuda, Yoshikazu; Usui, Yuki; Haniu, Hisao

    2013-01-01

    Highlights: •HTT2800-treated BEAS-2B cells induced LC3B in a time-dependent manner. •HTT2800-treated BEAS-2B cells showed decreased cell proliferation that was both time- and dose-dependent. •Addition of 3-MA, LC3B-II protein and mRNA levels were significantly decreased. •3-MA and E64-d + pepstatin A, but not brefeldin A, provided protection against HTT2800-induced cell death. •These results suggest that HTT2800 predominantly causes autophagy rather than apoptotic cell death in BEAS-2B cells. -- Abstract: Bronchial epithelial cells are targets of inhalation and play a critical role in the maintenance of mucosal integrity as mechanical barriers against various particles. Our previous result suggest that vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. Increasing evidence suggests that autophagy may critically influence vital cellular processes such as apoptosis, cell proliferation and inflammation and thereby may play a critical role in pulmonary diseases. Autophagy was recently recognized as a critical cell death pathway, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles. In this study, the authors focus on the autophagic responses of HTT2800 exposure. The HTT2800-exposed cells induced LC3B expression and induced cell growth inhibition

  7. Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in human lung cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsukahara, Tamotsu, E-mail: ttamotsu@kanazawa-med.ac.jp [Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Matsuda, Yoshikazu [Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama 362-0806 (Japan); Usui, Yuki [Research Center for Exotic Nanocarbons, Shinshu University, 4-17-1 Wakasato, Nagano-shi, Nagano 380-8553 (Japan); Haniu, Hisao [Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan)

    2013-10-18

    Highlights: •HTT2800-treated BEAS-2B cells induced LC3B in a time-dependent manner. •HTT2800-treated BEAS-2B cells showed decreased cell proliferation that was both time- and dose-dependent. •Addition of 3-MA, LC3B-II protein and mRNA levels were significantly decreased. •3-MA and E64-d + pepstatin A, but not brefeldin A, provided protection against HTT2800-induced cell death. •These results suggest that HTT2800 predominantly causes autophagy rather than apoptotic cell death in BEAS-2B cells. -- Abstract: Bronchial epithelial cells are targets of inhalation and play a critical role in the maintenance of mucosal integrity as mechanical barriers against various particles. Our previous result suggest that vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. Increasing evidence suggests that autophagy may critically influence vital cellular processes such as apoptosis, cell proliferation and inflammation and thereby may play a critical role in pulmonary diseases. Autophagy was recently recognized as a critical cell death pathway, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles. In this study, the authors focus on the autophagic responses of HTT2800 exposure. The HTT2800-exposed cells induced LC3B expression and induced cell growth inhibition.

  8. "Lomonosov" Satellite—Space Observatory to Study Extreme Phenomena in Space

    Science.gov (United States)

    Sadovnichii, V. A.; Panasyuk, M. I.; Amelyushkin, A. M.; Bogomolov, V. V.; Benghin, V. V.; Garipov, G. K.; Kalegaev, V. V.; Klimov, P. A.; Khrenov, B. A.; Petrov, V. L.; Sharakin, S. A.; Shirokov, A. V.; Svertilov, S. I.; Zotov, M. Y.; Yashin, I. V.; Gorbovskoy, E. S.; Lipunov, V. M.; Park, I. H.; Lee, J.; Jeong, S.; Kim, M. B.; Jeong, H. M.; Shprits, Y. Y.; Angelopoulos, V.; Russell, C. T.; Runov, A.; Turner, D.; Strangeway, R. J.; Caron, R.; Biktemerova, S.; Grinyuk, A.; Lavrova, M.; Tkachev, L.; Tkachenko, A.; Martinez, O.; Salazar, H.; Ponce, E.

    2017-11-01

    The "Lomonosov" space project is lead by Lomonosov Moscow State University in collaboration with the following key partners: Joint Institute for Nuclear Research, Russia, University of California, Los Angeles (USA), University of Pueblo (Mexico), Sungkyunkwan University (Republic of Korea) and with Russian space industry organizations to study some of extreme phenomena in space related to astrophysics, astroparticle physics, space physics, and space biology. The primary goals of this experiment are to study: Ultra-high energy cosmic rays (UHECR) in the energy range of the Greizen-Zatsepin-Kuzmin (GZK) cutoff; Ultraviolet (UV) transient luminous events in the upper atmosphere; Multi-wavelength study of gamma-ray bursts in visible, UV, gamma, and X-rays; Energetic trapped and precipitated radiation (electrons and protons) at low-Earth orbit (LEO) in connection with global geomagnetic disturbances; Multicomponent radiation doses along the orbit of spacecraft under different geomagnetic conditions and testing of space segments of optical observations of space-debris and other space objects; Instrumental vestibular-sensor conflict of zero-gravity phenomena during space flight. This paper is directed towards the general description of both scientific goals of the project and scientific equipment on board the satellite. The following papers of this issue are devoted to detailed descriptions of scientific instruments.

  9. Fluorinated Nucleotide Modifications Modulate Allele Selectivity of SNP-Targeting Antisense Oligonucleotides

    Directory of Open Access Journals (Sweden)

    Michael E. Østergaard

    2017-06-01

    Full Text Available Antisense oligonucleotides (ASOs have the potential to discriminate between subtle RNA mismatches such as SNPs. Certain mismatches, however, allow ASOs to bind at physiological conditions and result in RNA cleavage mediated by RNase H. We showed that replacing DNA nucleotides in the gap region of an ASO with other chemical modification can improve allele selectivity. Herein, we systematically substitute every position in the gap region of an ASO targeting huntingtin gene (HTT with fluorinated nucleotides. Potency is determined in cell culture against mutant HTT (mtHTT and wild-type HTT (wtHTT mRNA and RNase H cleavage intensities, and patterns are investigated. This study profiled five different fluorinated nucleotides and showed them to have predictable, site-specific effects on RNase H cleavage, and the cleavage patterns were rationalized from a published X-ray structure of human RNase H1. The results herein can be used as a guide for future projects where ASO discrimination of SNPs is important.

  10. Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [11C] DASB positron emission tomography study

    International Nuclear Information System (INIS)

    Hesse, Swen; Sabri, Osama; Rullmann, Michael; Luthardt, Julia; Becker, Georg-Alexander; Bresch, Anke; Patt, Marianne; Meyer, Philipp M.; Winter, Karsten; Hankir, Mohammed K.; Zientek, Franziska; Reissig, Georg; Drabe, Mandy; Regenthal, Ralf; Schinke, Christian; Arelin, Katrin; Lobsien, Donald; Fasshauer, Mathias; Fenske, Wiebke K.; Stumvoll, Michael; Blueher, Matthias

    2016-01-01

    The role of the central serotonin (5-hydroxytryptamine, 5-HT) system in feeding has been extensively studied in animals with the 5-HT family of transporters (5-HTT) being identified as key molecules in the regulation of satiety and body weight. Aberrant 5-HT transmission has been implicated in the pathogenesis of human obesity by in vivo positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging techniques. However, results obtained thus far from studies of central 5-HTT availability have been inconsistent, which is thought to be brought about mainly by the low number of individuals with a high body mass index (BMI) previously used. The aim of this study was therefore to assess 5-HTT availability in the brains of highly obese otherwise healthy individuals compared with non-obese healthy controls. We performed PET using the 5-HTT selective radiotracer [ 11 C] DASB on 30 highly obese (BMI range between 35 and 55 kg/m 2 ) and 15 age- and sex-matched non-obese volunteers (BMI range between 19 and 27 kg/m 2 ) in a cross-sectional study design. The 5-HTT binding potential (BP ND ) was used as the outcome parameter. On a group level, there was no significant difference in 5-HTT BP ND in various cortical and subcortical regions in individuals with the highest BMI compared with non-obese controls, while statistical models showed minor effects of age, sex, and the degree of depression on 5-HTT BP ND . The overall finding of a lack of significantly altered 5-HTT availability together with its high variance in obese individuals justifies the investigation of individual behavioral responses to external and internal cues which may further define distinct phenotypes and subgroups in human obesity. (orig.)

  11. Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [{sup 11}C] DASB positron emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Hesse, Swen; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); Rullmann, Michael [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Leipzig (Germany); Luthardt, Julia; Becker, Georg-Alexander; Bresch, Anke; Patt, Marianne; Meyer, Philipp M. [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Winter, Karsten [University of Leipzig, Centre for Translational Regenerative Medicine, Leipzig (Germany); University of Leipzig, Institute for Medical Informatics, Statistics, and Epidemiology, Leipzig (Germany); Hankir, Mohammed K.; Zientek, Franziska; Reissig, Georg; Drabe, Mandy [Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); Regenthal, Ralf [University of Leipzig, Division of Clinical Pharmacology, Rudolf Boehm Institute of Pharmacology and Toxicology, Leipzig (Germany); Schinke, Christian [University of Leipzig, Department of Neurology, Leipzig (Germany); Arelin, Katrin [Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Leipzig (Germany); University of Leipzig, Day Clinic for Cognitive Neurology, Leipzig (Germany); Lobsien, Donald [University of Leipzig, Department of Neuroradiology, Leipzig (Germany); Fasshauer, Mathias; Fenske, Wiebke K.; Stumvoll, Michael [Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); University of Leipzig, Medical Department III, Leipzig (Germany); Blueher, Matthias [University of Leipzig, Medical Department III, Leipzig (Germany); University of Leipzig, Collaborative Research Centre 1052 Obesity Mechanisms, Leipzig (Germany)

    2016-06-15

    The role of the central serotonin (5-hydroxytryptamine, 5-HT) system in feeding has been extensively studied in animals with the 5-HT family of transporters (5-HTT) being identified as key molecules in the regulation of satiety and body weight. Aberrant 5-HT transmission has been implicated in the pathogenesis of human obesity by in vivo positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging techniques. However, results obtained thus far from studies of central 5-HTT availability have been inconsistent, which is thought to be brought about mainly by the low number of individuals with a high body mass index (BMI) previously used. The aim of this study was therefore to assess 5-HTT availability in the brains of highly obese otherwise healthy individuals compared with non-obese healthy controls. We performed PET using the 5-HTT selective radiotracer [{sup 11}C] DASB on 30 highly obese (BMI range between 35 and 55 kg/m{sup 2}) and 15 age- and sex-matched non-obese volunteers (BMI range between 19 and 27 kg/m{sup 2}) in a cross-sectional study design. The 5-HTT binding potential (BP{sub ND}) was used as the outcome parameter. On a group level, there was no significant difference in 5-HTT BP{sub ND} in various cortical and subcortical regions in individuals with the highest BMI compared with non-obese controls, while statistical models showed minor effects of age, sex, and the degree of depression on 5-HTT BP{sub ND}. The overall finding of a lack of significantly altered 5-HTT availability together with its high variance in obese individuals justifies the investigation of individual behavioral responses to external and internal cues which may further define distinct phenotypes and subgroups in human obesity. (orig.)

  12. Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin.

    Science.gov (United States)

    Grison, Alice; Mantovani, Fiamma; Comel, Anna; Agostoni, Elena; Gustincich, Stefano; Persichetti, Francesca; Del Sal, Giannino

    2011-11-01

    Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediating mHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with phosphorylation-dependent prolyl isomerase Pin1 and consequent dissociation from the apoptosis inhibitor iASPP, thereby inducing the expression of apoptotic target genes. Inhibition of Ser46 phosphorylation by targeting homeodomain-interacting protein kinase 2 (HIPK2), PKCδ, or ataxia telangiectasia mutated kinase, as well as inhibition of the prolyl isomerase Pin1, prevents mHtt-dependent apoptosis of neuronal cells. These results provide a rationale for the use of small-molecule inhibitors of stress-responsive protein kinases and Pin1 as a potential therapeutic strategy for HD treatment.

  13. Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington’s disease

    OpenAIRE

    Paul, Bindu D.; Sbodio, Juan I.; Xu, Risheng; Vandiver, M. Scott; Cha, Jiyoung Y.; Snowman, Adele M.; Snyder, Solomon H.

    2014-01-01

    Huntington’s disease is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and behavioural changes1. Huntington’s disease is characterized by highly selective and profound damage to the corpus striatum, which regulates motor function. Striatal selectivity of Huntington’s disease may reflect the striatally selective small G protein Rh...

  14. Combination therapy of inhaled steroids and long-acting beta2-agonists in asthma–COPD overlap syndrome

    Directory of Open Access Journals (Sweden)

    Lee SY

    2016-11-01

    Full Text Available Suh-Young Lee,1,* Hye Yun Park,2,* Eun Kyung Kim,3 Seong Yong Lim,4 Chin Kook Rhee,5 Yong Il Hwang,6 Yeon-Mok Oh,7 Sang Do Lee,7 Yong Bum Park1 On behalf of the KOLD Study Group 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 3Department of Internal Medicine, Bundang CHA Medical Center, CHA University College of Medicine, Seongnam, 4Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 5Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Gyeonggido, 7Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Ulsan, Republic of Korea *These authors contributed equally to this work Background: The efficacy of inhaled corticosteroids (ICSs/long-acting beta2-agonist (LABA treatment in patients with asthma–chronic obstructive pulmonary disease (COPD overlap syndrome (ACOS compared to patients with COPD alone has rarely been examined. This study aimed to evaluate the clinical efficacy for the improvement of lung function after ICS/LABA treatment in patients with ACOS compared to COPD alone patients. Methods: Patients with stable COPD were selected from the Korean Obstructive Lung Disease (KOLD cohort. Subjects began a 3-month ICS/LABA treatment after a washout period. ACOS was defined when the patients had 1 a personal history of asthma, irrespective of age, and wheezing in the last 12 months in a self-reported survey

  15. Design of 6 MeV X-band electron linac for dual-head gantry radiotherapy system

    Science.gov (United States)

    Shin, Seung-wook; Lee, Seung-Hyun; Lee, Jong-Chul; Kim, Huisu; Ha, Donghyup; Ghergherehchi, Mitra; Chai, Jongseo; Lee, Byung-no; Chae, Moonsik

    2017-12-01

    A compact 6 MeV electron linac is being developed at Sungkyunkwan University, in collaboration with the Korea atomic energy research institute (KAERI). The linac will be used as an X-ray source for a dual-head gantry radiotherapy system. X-band technology has been employed to satisfy the size requirement of the dual-head gantry radiotherapy machine. Among the several options available, we selected a pi/2-mode, standing-wave, side-coupled cavity. This choice of radiofrequency (RF) cavity design is intended to enhance the shunt impedance of each cavity in the linac. An optimum structure of the RF cavity with a high-performance design was determined by applying a genetic algorithm during the optimization procedure. This paper describes the detailed design process for a single normal RF cavity and the entire structure, including the RF power coupler and coupling cavity, as well as the beam dynamics results.

  16. Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder.

    Science.gov (United States)

    Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S; Lee, Jong-Min; Alonso, Isabel; Gusella, James F; Smoller, Jordan W; Sklar, Pamela; MacDonald, Marcy E; Perlis, Roy H

    2015-06-01

    Huntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTT CAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease. We assessed the distribution of HTT CAG repeat alleles in a cohort of individuals with bipolar disorder. HTT CAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts. We found that HTT CAG repeat alleles > 35 units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects. These findings do not support an association between bipolar disorder and Huntington's disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells

    Directory of Open Access Journals (Sweden)

    Tewin Tencomnao

    2011-10-01

    Full Text Available Serotonin (5-HT is a monoamine neurotransmitter and plays important roles in several of the human body’s systems. Known as a primary target for psychoactive drug development, the 5-HT transporter (5-HTT, SERT plays a critical role in the regulation of serotonergic function by reuptaking 5-HT. The allelic variation of 5-HTT expression is caused by functional gene promoter polymorphism with two principal variant alleles, 5-HTT gene-linked polymorphic region (5-HTTLPR. It has been demonstrated that 5-HTTLPR is associated with numerous neuropsychiatric disorders. The functional roles of 5-HTTLPR have been reported in human choriocarcinoma (JAR, lymphoblast and raphe cells. To date, the significance of 5-HTTLPR in gastrointestinal tract-derived cells has never been elucidated. Thus, the impact of 5-HTTLPR on 5-HTT transcription was studied in SW480 human colon carcinoma cells, which were shown to express 5-HTT. We found 42-bp fragment in long (L allele as compared to short (S allele, and this allelic difference resulted in 2-fold higher transcriptional efficiency of L allele (P < 0.05 as demonstrated using a functional reporter gene assay. Nevertheless, the transcriptional effect of estrogen and glucocorticoid on 5-HTT expression via 5-HTTLPR was not found in this cell line. Our study was the first to demonstrate the molecular role of this allelic variation in gastrointestinal tract cells.

  18. The role of polyglutamine expansion and protein context in disease-related huntingtin/lipid interactions

    Science.gov (United States)

    Burke, Kathleen Anne

    Huntington's Disease (HD) is a neurodegenerative disorder that is defined by the accumulation of nanoscale aggregates comprised of the huntingtin (htt) protein. Aggregation is directly caused by an expanded polyglutamine (polyQ) domain in htt, leading to a diverse population of aggregate species, such as oligomers, fibrils, and annular aggregates. Furthermore, the length of this polyQ domain is directly related to onset and severity of disease. The first 17 amino acids on the N-terminus (N17) and the polyproline domain on the C-terminal side of the polyQ domain have been shown to further modulate the aggregation process. Additionally, N17 appears to have lipid binding properties as htt interacts with a variety of membrane-containing structures present in cells, such as organelles, and interactions with these membrane surfaces may further modulate htt aggregation. To investigate the interaction between htt exon1 and lipid bilayers, in situ atomic force microscopy (AFM) was used to directly monitor the aggregation of htt exon1 constructs with varying Q-length (35Q, 46Q, 51Q, and myc- 53Q) or synthetic peptides with different polyQ domain flanking sequences (KK-Q35-KK, KK-Q 35-P10-KK, N17-Q35-KK, and N 17-Q35-P10-KK) on supported lipid membranes comprised of total brain lipid extract. The exon1 fragments accumulated on the lipid membranes, causing disruption of the membrane, in a polyQ dependent manner. By adding N-terminal tags to the htt exon1 fragments, the interaction with the lipid bilayer was impeded. The KK-Q35-KK and KK-Q 35-P10-KK peptides had no appreciable interaction with lipid bilayers. Interestingly, polyQ peptides with the N17 flanking sequence interacted with the bilayer. N17-Q35-KK formed discrete aggregates on the bilayer, but there was minimal membrane disruption. The N17-Q35-P10-KK peptide interacted more aggressively with the lipid bilayer in a manner reminiscent of the htt exon1 proteins.

  19. Acute inescapable stress alleviates fear extinction recall deficits caused by serotonin transporter abolishment.

    Science.gov (United States)

    Schipper, Pieter; Henckens, Marloes J A G; Lopresto, Dora; Kozicz, Tamas; Homberg, Judith R

    2018-07-02

    Life stress increases risk for developing post-traumatic stress disorder (PTSD), and more prominently so in short-allele carriers of the serotonin transporter linked polymorphic region (5-HTTLPR). Serotonin transporter knockout (5-HTT -/- ) rats show compromised extinction (recall) of conditioned fear, which might mediate the increased risk for PTSD and reduce the therapeutic efficacy of exposure therapy. Here, we assessed whether acute inescapable stress (IS) differentially affects fear extinction and extinction recall in 5-HTT -/- rats and wildtype controls. Surprisingly, IS experience improved fear extinction recall in 5-HTT -/- rats to the level of wildtype animals, while wildtypes were unaffected by this IS. Thus, whereas 5-HTT -/- rats evidently were more responsive to the stressor, the behavioral consequences presented themselves as adaptive. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  20. ROCK and PRK-2 Mediate the Inhibitory Effect of Y-27632 on Polyglutamine Aggregation

    Science.gov (United States)

    Shao, Jieya; Welch, William J.; Diamond, Marc I.

    2009-01-01

    Polyglutamine expansion in huntingtin (Htt) and the androgen receptor (AR) causes untreatable neurodegenerative diseases. Y-27632, a therapeutic lead, reduces Htt and AR aggregation in cultured cells, and Htt-induced neurodegeneration in Drosophila. Y-27632 inhibits both Rho-associated kinases ROCK and PRK-2, making its precise intracellular target uncertain. Over-expression of either kinase increases Htt and AR aggregation. Three ROCK inhibitors (Y-27632, H-1077, HA-1152), and a specific ROCK inhibitory peptide reduce polyglutamine protein aggregation, as does knockdown of ROCK or PRK-2 by RNAi. RNAi also indicates that each kinase is required for the inhibitory effects of Y-27632 to manifest fully. These two actin regulatory kinases are thus involved in polyglutamine aggregation, and their simultaneous inhibition may be an important therapeutic goal. PMID:18423405

  1. Anorexigen-induced pulmonary hypertension and the serotonin (5-HT hypothesis: lessons for the future in pathogenesis

    Directory of Open Access Journals (Sweden)

    Adnot Serge

    2002-01-01

    Full Text Available Abstract Epidemiological studies have established that fenfluramine, D-fenfluramine, and aminorex, but not other appetite suppressants, increase the risk of primary pulmonary hypertension (PH. One current hypothesis suggests that fenfluramine-like medications may act through interactions with the serotonin (5-hydroxytryptamine [5-HT] transporter (5-HTT located on pulmonary artery smooth muscle cells and responsible for the mitogenic action of 5-HT. Anorexigens may contribute to PH by boosting 5-HT levels in the bloodstream, directly stimulating smooth muscle cell growth, or altering 5-HTT expression. We suggest that individuals with a high basal level of 5-HTT expression related to the presence of the long 5-HTT gene promoter variant may be particularly susceptible to one or more of these potential mechanisms of appetite-suppressant-related PH.

  2. CTG repeat-targeting oligonucleotides for down-regulating Huntingtin expression

    DEFF Research Database (Denmark)

    Zaghloul, Eman M; Gissberg, Olof; Moreno, Pedro M D

    2017-01-01

    Huntington's disease (HD) is a fatal, neurodegenerative disorder in which patients suffer from mobility, psychological and cognitive impairments. Existing therapeutics are only symptomatic and do not significantly alter the disease progression or increase life expectancy. HD is caused by expansion....... Thus, reduction of both muHTT mRNA and protein levels would ideally be the most useful therapeutic option. We herein present a novel strategy for HD treatment using oligonucleotides (ONs) directly targeting the HTT trinucleotide repeat DNA. A partial, but significant and potentially long-term, HTT...

  3. Environmental enrichment reduces innate anxiety with no effect on depression-like behaviour in mice lacking the serotonin transporter.

    Science.gov (United States)

    Rogers, Jake; Li, Shanshan; Lanfumey, Laurence; Hannan, Anthony J; Renoir, Thibault

    2017-08-14

    Along with being the main target of many antidepressant medications, the serotonin transporter (5-HTT) is known to be involved in the pathophysiology of depression and anxiety disorders. In line with this, mice with varying 5-HTT genotypes are invaluable tools to study depression- and anxiety-like behaviours as well as the mechanisms mediating potential therapeutics. There is clear evidence that both genetic and environmental factors play a role in the aetiology of psychiatric disorders. In that regard, housing paradigms which seek to enhance cognitive stimulation and physical activity have been shown to exert beneficial effects in animal models of neuropsychiatric disorders. In the present study, we examined the effects of environmental enrichment on affective-like behaviours and sensorimotor gating function of 5-HTT knock-out (KO) mice. Using the elevated-plus maze and the light-dark box, we found that environmental enrichment ameliorated the abnormal innate anxiety of 5-HTT KO mice on both tests. In contrast, environmental enrichment did not rescue the depression-like behaviour displayed by 5-HTT KO mice in the forced-swim test. Finally, measuring pre-pulse inhibition, we found no effect of genotype or treatment on sensorimotor gating. In conclusion, our data suggest that environmental enrichment specifically reduces innate anxiety of 5-HTT KO mice with no amelioration of the depression-like behaviour. This has implications for the current use of clinical interventions for patients with symptoms of both anxiety and depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. A new Caenorhabditis elegans model of human huntingtin 513 aggregation and toxicity in body wall muscles.

    Directory of Open Access Journals (Sweden)

    Amy L Lee

    Full Text Available Expanded polyglutamine repeats in different proteins are the known determinants of at least nine progressive neurodegenerative disorders whose symptoms include cognitive and motor impairment that worsen as patients age. One such disorder is Huntington's Disease (HD that is caused by a polyglutamine expansion in the human huntingtin protein (htt. The polyglutamine expansion destabilizes htt leading to protein misfolding, which in turn triggers neurodegeneration and the disruption of energy metabolism in muscle cells. However, the molecular mechanisms that underlie htt proteotoxicity have been somewhat elusive, and the muscle phenotypes have not been well studied. To generate tools to elucidate the basis for muscle dysfunction, we engineered Caenorhabditis elegans to express a disease-associated 513 amino acid fragment of human htt in body wall muscle cells. We show that this htt fragment aggregates in C. elegans in a polyglutamine length-dependent manner and is toxic. Toxicity manifests as motor impairment and a shortened lifespan. Compared to previous models, the data suggest that the protein context in which a polyglutamine tract is embedded alters aggregation propensity and toxicity, likely by affecting interactions with the muscle cell environment.

  5. 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...

  6. Helmet Sensor - Transfer Function and Model Development

    Science.gov (United States)

    2010-09-01

    that helmets be examined forensically when estimating the impact direction and location and the electronic HMSS data not be used in that determination... forensic analysis of the helmet itself is therefore recommended to determine the direction and severity of the ballistic impact 5. The helmet shell does...ot83 HTI l ot 8J HT1 lot S ,HTt IOt S , HTI l otiH HTt lotSS HTt l vt85 HTI l o)t 85 HT1 Front Level Acceleration ~~,--~----~--,30’p~g

  7. The Role of Heat Tolerance Testing in Recovery and Return to Duty

    Science.gov (United States)

    2008-10-01

    CV diseases Hyperthyroidism Pheochromocytoma Infectious diseases Diabetes mellitus Psychiatric illness Parkinsonism Congenital abnormalities: CF...environments. To assess the heat tolerance status of prior heat stroke patient. Heat tolerance test (HTT) “HTT was effective in evaluating the heat tolerance

  8. Brain Networks Implicated in Seasonal Affective Disorder

    DEFF Research Database (Denmark)

    Nørgaard, Martin; Ganz, Melanie; Svarer, Claus

    2017-01-01

    , patients with SAD fail to globally downregulate their cerebral serotonin transporter (5-HTT) in winter, and that this effect seemed to be particularly pronounced in female S-carriers of the 5-HTTLPR genotype. The purpose of this study was to identify a 5-HTT brain network that accounts for the adaption...... without SAD; it included the right superior frontal gyrus, brainstem, globus pallidus (bilaterally) and the left hippocampus. Across seasons, female S' carriers without SAD showed nominally higher 5-HTT levels in these regions compared to female S' carriers with SAD, but the group difference was only...... winter compared to female S' carriers without SAD. Limitations: The study is preliminary and limited by small sample size in the SAD group (N = 6). Conclusions: These findings provide novel exploratory evidence for a wintertime state-dependent difference in 5-HTT levels that may leave SAD females...

  9. Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutant huntingtin phenotypes in Huntington's disease knock-in mice.

    Directory of Open Access Journals (Sweden)

    Marina Kovalenko

    Full Text Available The CAG trinucleotide repeat mutation in the Huntington's disease gene (HTT exhibits age-dependent tissue-specific expansion that correlates with disease onset in patients, implicating somatic expansion as a disease modifier and potential therapeutic target. Somatic HTT CAG expansion is critically dependent on proteins in the mismatch repair (MMR pathway. To gain further insight into mechanisms of somatic expansion and the relationship of somatic expansion to the disease process in selectively vulnerable MSNs we have crossed HTT CAG knock-in mice (HdhQ111 with mice carrying a conditional (floxed Msh2 allele and D9-Cre transgenic mice, in which Cre recombinase is expressed specifically in MSNs within the striatum. Deletion of Msh2 in MSNs eliminated Msh2 protein in those neurons. We demonstrate that MSN-specific deletion of Msh2 was sufficient to eliminate the vast majority of striatal HTT CAG expansions in HdhQ111 mice. Furthermore, MSN-specific deletion of Msh2 modified two mutant huntingtin phenotypes: the early nuclear localization of diffusely immunostaining mutant huntingtin was slowed; and the later development of intranuclear huntingtin inclusions was dramatically inhibited. Therefore, Msh2 acts within MSNs as a genetic enhancer both of somatic HTT CAG expansions and of HTT CAG-dependent phenotypes in mice. These data suggest that the selective vulnerability of MSNs may be at least in part contributed by the propensity for somatic expansion in these neurons, and imply that intervening in the expansion process is likely to have therapeutic benefit.

  10. Huntingtin gene repeat size variations affect risk of lifetime depression.

    Science.gov (United States)

    Gardiner, Sarah L; van Belzen, Martine J; Boogaard, Merel W; van Roon-Mom, Willeke M C; Rozing, Maarten P; van Hemert, Albert M; Smit, Johannes H; Beekman, Aartjan T F; van Grootheest, Gerard; Schoevers, Robert A; Oude Voshaar, Richard C; Roos, Raymund A C; Comijs, Hannie C; Penninx, Brenda W J H; van der Mast, Roos C; Aziz, N Ahmad

    2017-12-11

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

  11. Association of blood eosinophils and plasma periostin with FEV1 response after 3-month inhaled corticosteroid and long-acting beta2-agonist treatment in stable COPD patients

    Directory of Open Access Journals (Sweden)

    Park HY

    2015-12-01

    Full Text Available Hye Yun Park,1 Hyun Lee,1 Won-Jung Koh,1 Seonwoo Kim,2 Ina Jeong,3 Hyeon-Kyoung Koo,4 Tae-Hyung Kim,5 Jin Woo Kim,6 Woo Jin Kim,7 Yeon-Mok Oh,8 Don D Sin,9 Seong Yong Lim,10,* Sang-Do Lee8,* On behalf of the KOLD Study Group 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Biostatistics Team, Samsung Biomedical Research Institute, Seoul, Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Medical Center, Seoul, Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea; 5Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Gyeonggi-do, Korea; 6Division of Pulmonology, Department of Internal Medicine, Uijeongbu St Mary’s Hospital, Gyunggi-do, Korea; 7Department of Internal Medicine, Kangwon National University, Chuncheon-si, Gangwon-do, Korea; 8Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 9Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; 10Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea *These authors contributed equally to this work Background: COPD patients with increased airway eosinophilic inflammation show a favorable response to inhaled corticosteroids (ICS in combination with a long-acting bronchodilator. Recent studies have demonstrated a significant correlation of sputum eosinophilia with blood eosinophils and periostin. We investigated whether high blood eosinophils and plasma periostin were associated

  12. Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD: results from a national database

    Directory of Open Access Journals (Sweden)

    Lee H

    2016-04-01

    Full Text Available Hyun Lee,1 Chin Kook Rhee,2 Byung-Jae Lee,3 Dong-Chull Choi,3 Jee-Ae Kim,4 Sang Hyun Kim,5 Yoolwon Jeong,6 Tae-Hyung Kim,7 Gyu Rak Chon,8 Ki-Suck Jung,9 Sang Haak Lee,10 David Price,11 Kwang Ha Yoo,12,* Hye Yun Park1,* 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 3Division of Allergy, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 4Pharmaceutical Policy Evaluation Research Team, Research Institution, Health Insurance Review and Assessment Service, 5Big Data Division, Health Insurance Review and Assessment Service, Seoul, 6Division of Chronic Disease Control, Korea Centers for Disease Control and Prevention, Osong, 7Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Gyeonggi-do, 8Department of Pulmonary and Critical Care Medicine, Chungju Hospital, Konkuk University School of Medicine, Chungju City, 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, 10Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 11Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 12Division of Pulmonary, Allergy and Critical Care Medicine Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea *These authors contributed equally to this work Backround: Acute exacerbations are major drivers of COPD deterioration. However, limited data are available for the

  13. Synthesis, radiolabeling and baboon SPECT imaging of 2β-carbomethoxy-3β-(3'-[123I]iodophenyl)tropane ([123I]YP256) as a serotonin transporter radiotracer

    International Nuclear Information System (INIS)

    Bois, Frederic; Baldwin, Ronald M.; Amici, Louis; Al-Tikriti, Mohammed S.; Kula, Nora; Baldessarini, Ross; Innis, Robert B.; Staley, Julie K.; Tamagnan, Gilles D.

    2008-01-01

    To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson's disease, Alzheimer's disease and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2β-carbomethoxy-3β-(3'-[ 123 I]iodophenyl) tropane (YP256, ). The radiolabeling was performed by iododestannylation using sodium [ 123 I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo

  14. Early life stress predicts negative urgency through brooding, depending on 5-HTTLPR genotype: A pilot study with 6-month follow-up examining suicide ideation.

    Science.gov (United States)

    Valderrama, Jorge; Miranda, Regina

    2017-12-01

    The present study examined the interaction between early life stress and 5-HTT genotypes in predicting two risk factors for suicidal behavior - the brooding subtype of rumination and impulsivity, in the form of negative urgency - over time. Furthermore, we examined early life stress, brooding, and impulsivity as predictors of suicidal ideation over time. Participants with and without a history of early life stress were genotyped for the 5-HTTLPR polymorphism and completed assessments assessing brooding and negative urgency at baseline and 6-month follow up. Early life emotional abuse was associated with negative urgency at follow-up. We found an indirect effect of early life emotional abuse on negative urgency through brooding among individuals with 5-HTT low expressing genotypes but not among individuals with 5-HTT high expressing genotypes. Further, a logistic regression analysis revealed that negative urgency was associated with higher odds (O.R. = 16.2) of reporting suicide ideation (versus no ideation) at follow-up. Our findings suggest that brooding and negative urgency may result from the interaction between early life emotional abuse and 5-HTT low expressing genotypes. Further research is necessary to understand how early life stress interacts with 5-HTT genotypes to confer risk for suicidal behavior through psychological mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Hydrothermal emergence model for ripgut brome (Bromus diandrus)

    Science.gov (United States)

    A model that describes the emergence of ripgut brome (Bromus diandrus) was developed using a two-season data set from a no-tilled field in northeastern Spain. The relationship between cumulative emergence and hydrothermal time (HTT) was described by a sigmoid growth function (Chapman equation). HTT ...

  16. Assessment of motor function, sensory motor gating and recognition memory in a novel BACHD transgenic rat model for Huntington disease

    NARCIS (Netherlands)

    Abada, Yah-se K.; Nguyen, Huu Phuc; Schreiber, Rudy; Ellenbroek, Bart

    2013-01-01

    Rationale: Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97

  17. Huntingtin gene repeat size variations affect risk of lifetime depression

    DEFF Research Database (Denmark)

    Gardiner, Sarah L.; van Belzen, Martine J.; Boogaard, Merel W.

    2017-01-01

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect...

  18. Cellular cytotoxic response induced by highly purified multi-wall carbon nanotube in human lung cells.

    Science.gov (United States)

    Tsukahara, Tamotsu; Haniu, Hisao

    2011-06-01

    Carbon nanotubes, a promising nanomaterial with unique characteristics, have applications in a variety of fields. The cytotoxic effects of carbon nanotubes are partially due to the induction of oxidative stress; however, the detailed mechanisms of nanotube cytotoxicity and their interaction with cells remain unclear. In this study, the authors focus on the acute toxicity of vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) by high-temperature thermal treatment. The authors exposed human bronchial epithelial cells (BEAS-2B) to HTT2800 and measured the cellular uptake, mitochondrial function, cellular LDH release, apoptotic signaling, reactive oxygen species (ROS) generation and pro-inflammatory cytokine release. The HTT2800-exposed cells showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. However, the exposed cells showed no obvious intracellular ROS generation. These cellular and molecular findings suggest that HTT2800 could cause a potentially adverse inflammatory response in BEAS-2B cells.

  19. A pharmacokinetic and pharmacodynamic drug interaction between rosuvastatin and valsartan in healthy subjects

    Directory of Open Access Journals (Sweden)

    Jung JA

    2015-03-01

    Full Text Available Jin Ah Jung,1 Soo-Yun Lee,2 Jung-Ryul Kim,1 Jae-Wook Ko,1,2 Seong Bok Jang,3 Su Youn Nam,3 Wooseong Huh1,41Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 2Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 3Yuhan Research Institute, Yuhan Corporation, 4Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaPurpose: Valsartan, an angiotensin-receptor blocker, and rosuvastatin, a competitive inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, are frequently coadministered to treat patients with hypertension and dyslipidemia. The study reported here sought to evaluate the pharmacokinetic and pharmacodynamic interactions between rosuvastatin and valsartan in healthy Korean subjects. Subjects and methods: Thirty healthy male Korean subjects were administered with rosuvastatin (20 mg/day, valsartan (160 mg/day, and both drugs concomitantly for 4 days in a randomized, open-label, multiple-dose, three-treatment, three-period crossover study. Plasma concentrations of rosuvastatin, N-desmethyl rosuvastatin, and valsartan were determined using validated high-performance liquid chromatography with tandem mass spectrometry. Lipid profiles and vital signs (systolic and diastolic blood pressure and pulse rate were measured for the pharmacodynamic assessment.Results: For rosuvastatin, the geometric mean ratios (90% confidence intervals [CIs] of coadministration to mono-administration were 0.8809 (0.7873-0.9857 for maximum plasma concentration at steady state and 0.9151 (0.8632-0.9701 for area under the concentration–time curve (AUC over a dosing interval at steady state. For valsartan, the geometric mean ratios (90% CIs of those were 0.9300 (0.7946-1.0884 and 1.0072 (0.8893-1.1406, respectively. There were no significant differences in the metabolic ratio of N

  20. Electrochemical reversibility of reticulated vitreous carbon electrodes heat treated at different carbonization temperatures

    Directory of Open Access Journals (Sweden)

    Emerson Sarmento Gonçalves

    2006-06-01

    Full Text Available Electrochemical response of ferri/ferrocyanide redox couple is discussed for a system that uses reticulated vitreous carbon (RVC three dimensional electrodes prepared at five different Heat Treatment Temperatures (HTT in the range of 700 °C to 1100 °C. Electrical resistivity, scanning electron microscopy and X ray Diffraction analyses were performed for all prepared samples. It was observed that the HTT increasing promotes an electrical conductivity increasing while the Bragg distance d002 decreases. The correlation between reversibility behavior of ferri/ferrocyanide redox couple and both surface morphology and chemical properties of the RVC electrodes demonstrated a strong dependence on the HTT used to prepare the RVC.

  1. Synthesis, radiolabeling and baboon SPECT imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl)tropane ([{sup 123}I]YP256) as a serotonin transporter radiotracer

    Energy Technology Data Exchange (ETDEWEB)

    Bois, Frederic; Baldwin, Ronald M.; Amici, Louis; Al-Tikriti, Mohammed S. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Kula, Nora; Baldessarini, Ross [Department of Psychiatry and Neuroscience Program, Harvard Medical School, Mailman Research Center McLean Division of Massachusetts General Hospital, Belmont, MA 02478 (United States); Innis, Robert B.; Staley, Julie K. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Tamagnan, Gilles D. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Institute for Neurodegenerative Disorders, New Haven, CT 06510 (United States)], E-mail: gtamagnan@indd.org

    2008-01-15

    To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson's disease, Alzheimer's disease and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl) tropane (YP256, ). The radiolabeling was performed by iododestannylation using sodium [{sup 123}I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo.

  2. (Online & Print): 2305-7432. htt

    African Journals Online (AJOL)

    Peter Berglez

    could afford after working for a good five years in the public service as a teacher. ... image of the Life President, the Malawi Congress Party and the Ngwazi's diplomatic friends. Note that ... too close to be bribed and corrupted by that friendship.

  3. Impaired heat shock response in cells expressing full-length polyglutamine-expanded huntingtin.

    Directory of Open Access Journals (Sweden)

    Sidhartha M Chafekar

    Full Text Available The molecular mechanisms by which polyglutamine (polyQ-expanded huntingtin (Htt causes neurodegeneration in Huntington's disease (HD remain unclear. The malfunction of cellular proteostasis has been suggested as central in HD pathogenesis and also as a target of therapeutic interventions for the treatment of HD. We present results that offer a previously unexplored perspective regarding impaired proteostasis in HD. We find that, under non-stress conditions, the proteostatic capacity of cells expressing full length polyQ-expanded Htt is adequate. Yet, under stress conditions, the presence of polyQ-expanded Htt impairs the heat shock response, a key component of cellular proteostasis. This impaired heat shock response results in a reduced capacity to withstand the damage caused by cellular stress. We demonstrate that in cells expressing polyQ-expanded Htt the levels of heat shock transcription factor 1 (HSF1 are reduced, and, as a consequence, these cells have an impaired a heat shock response. Also, we found reduced HSF1 and HSP70 levels in the striata of HD knock-in mice when compared to wild-type mice. Our results suggests that full length, non-aggregated polyQ-expanded Htt blocks the effective induction of the heat shock response under stress conditions and may thus trigger the accumulation of cellular damage during the course of HD pathogenesis.

  4. Silica nanoparticle-based dual imaging colloidal hybrids: cancer cell imaging and biodistribution

    Directory of Open Access Journals (Sweden)

    Lee H

    2015-08-01

    Full Text Available Haisung Lee,1 Dongkyung Sung,2 Jinhoon Kim,3 Byung-Tae Kim,3 Tuntun Wang,4 Seong Soo A An,5 Soo-Won Seo,6 Dong Kee Yi4 1Molecular Diagnostics, In Vitro Diagnostics Unit, New Business Division, SK Telecom, 2Department of Life Sciences, Graduate School of Korea University, 3Interdisciplinary Graduate Program of Biomedical Engineering, School of Medicine, Sungkyunkwan University, Samsung Medical Center, 4Department of Chemistry, Myongji University, Seoul, 5Department of Bionanotechnology, Gachon Medical Research Institute, Gachon University, Seongnam, 6Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea Abstract: In this study, fluorescent dye-conjugated magnetic resonance (MR imaging agents were investigated in T mode. Gadolinium-conjugated silica nanoparticles were successfully synthesized for both MR imaging and fluorescence diagnostics. Polyamine and polycarboxyl functional groups were modified chemically on the surface of the silica nanoparticles for efficient conjugation of gadolinium ions. The derived gadolinium-conjugated silica nanoparticles were investigated by zeta potential analysis, transmission electron microscopy, inductively coupled plasma mass spectrometry, and energy dispersive x-ray spectroscopy. MR equipment was used to investigate their use as contrast-enhancing agents in T1 mode under a 9.4 T magnetic field. In addition, we tracked the distribution of the gadolinium-conjugated nanoparticles in both lung cancer cells and organs in mice. Keywords: dual bioimaging, MR imaging, silica colloid, T1 contrast imaging, nanohybrid

  5. Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT4 receptor levels

    DEFF Research Database (Denmark)

    Jennings, Katie Ann; Licht, Cecilie Löe; Bruce, Aynsley

    2012-01-01

    +/+ mice in all brain regions. Compared to wild-type (WT) littermate controls, 5-HTT OE mice had increased 5-HT4 binding density across all brain regions, except amygdala (118-164% of WT) and this difference between genotypes was reduced by the 5-HTT inhibitor, fluoxetine (20 mg/kg twice daily, 3 d...

  6. AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington’s disease

    International Nuclear Information System (INIS)

    Zuleta, Amparo; Vidal, Rene L.; Armentano, Donna; Parsons, Geoffrey; Hetz, Claudio

    2012-01-01

    Highlights: ► The contribution of ER stress to HD has not been directly addressed. ► Expression of XBP1s using AAVs decreases Huntingtin aggregation in vivo. ► We describe a new in vivo model of HD based on the expression of a large fragment of mHtt-RFP. -- Abstract: Huntington’s disease (HD) is caused by mutations that expand a polyglutamine region in the amino-terminal domain of Huntingtin (Htt), leading to the accumulation of intracellular inclusions and progressive neurodegeneration. Recent reports indicate the engagement of endoplasmic reticulum (ER) stress responses in human HD post mortem samples and animal models of the disease. Adaptation to ER stress is mediated by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates protein folding stress by controlling the expression of distinct transcription factors including X-Box binding protein 1 (XBP1). Here we targeted the expression of XBP1 on a novel viral-based model of HD. We delivered an active form of XBP1 locally into the striatum of adult mice using adeno-associated vectors (AAVs) and co-expressed this factor with a large fragment of mutant Htt as a fusion protein with RFP (Htt588 Q95 -mRFP) to directly visualize the accumulation of Htt inclusions in the brain. Using this approach, we observed a significant reduction in the accumulation of Htt588 Q95 -mRFP intracellular inclusion when XBP1 was co-expressed in the striatum. These results contrast with recent findings indicating a protective effect of XBP1 deficiency in neurodegeneration using knockout mice, and suggest a potential use of gene therapy strategies to manipulate the UPR in the context of HD.

  7. Short G-rich oligonucleotides as a potential therapeutic for Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Parekh-Olmedo Hetal

    2006-10-01

    Full Text Available Abstract Background Huntington's Disease (HD is an inherited autosomal dominant genetic disorder in which neuronal tissue degenerates. The pathogenesis of the disease appears to center on the development of protein aggregates that arise initially from the misfolding of the mutant HD protein. Mutant huntingtin (Htt is produced by HD genes that contain an increased number of glutamine codons within the first exon and this expansion leads to the production of a protein that misfolds. Recent studies suggest that mutant Htt can nucleate protein aggregation and interfere with a multitude of normal cellular functions. Results As such, efforts to find a therapy for HD have focused on agents that disrupt or block the mutant Htt aggregation pathway. Here, we report that short guanosine monotonic oligonucleotides capable of adopting a G-quartet structure, are effective inhibitors of aggregation. By utilizing a biochemical/immunoblotting assay as an initial screen, we identified a 20-mer, all G-oligonucleotide (HDG as an active molecule. Subsequent testing in a cell-based assay revealed that HDG was an effective inhibitor of aggregation of a fusion protein, comprised of a mutant Htt fragment and green fluorescent protein (eGFP. Taken together, our results suggest that a monotonic G-oligonucleotide, capable of adopting a G-quartet conformation is an effective inhibitor of aggregation. This oligonucleotide can also enable cell survival in PC12 cells overexpressing a mutant Htt fragment fusion gene. Conclusion Single-stranded DNA oligonucleotides capable of forming stable G-quartets can inhibit aggregation of the mutant Htt fragment protein. This activity maybe an important part of the pathogenecity of Huntington's Disease. Our results reveal a new class of agents that could be developed as a therapeutic approach for Huntington's Disease.

  8. Hydrothermal time models for conidial germination and mycelial growth of the seed pathogen Pyrenophora semeniperda

    Science.gov (United States)

    Connor W. Barth; Susan E. Meyer; Julie Beckstead; Phil S. Allen

    2015-01-01

    Population-based threshold models using hydrothermal time (HTT) have been widely used to model seed germination. We used HTT to model conidial germination and mycelial growth for the seed pathogen Pyrenophora semeniperda in a novel approach to understanding its interactions with host seeds. Germination time courses and mycelial growth rates for P.semeniperda were...

  9. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Zeng YX

    2016-04-01

    Full Text Available Yixuan Zeng,1,2,* Wenyuan Guo,1,* Guangqing Xu,3 Qinmei Wang,4 Luyang Feng,1,2 Simei Long,1 Fengyin Liang,1 Yi Huang,1 Xilin Lu,1 Shichang Li,5 Jiebin Zhou,5 Jean-Marc Burgunder,6 Jiyan Pang,5 Zhong Pei1,2 1Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, 2Guangzhou Center, Chinese Huntington’s Disease Network, 3Department of Rehabilitation, The First Affiliated Hospital, 4Key laboratory on Assisted Circulation, Ministry of Health, Department of Cardiovascular Medicine of the First Affiliated Hospital, 5School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Swiss Huntington’s Disease Center, Department of Neurology, University of Bern, Bern, Switzerland *These authors contributed equally to this work Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt. Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a

  10. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

    LENUS (Irish Health Repository)

    Bull, S J

    2009-12-01

    Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King\\'s College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The \\'low IL-6\\' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The \\'high transcription\\' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the \\'protective\\' effect of the 5-HTTLPR polymorphism was evident only in the presence of the \\'low IL-6\\' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the \\'high IL-6\\' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role

  11. CAG Expansions Are Genetically Stable and Form Nontoxic Aggregates in Cells Lacking Endogenous Polyglutamine Proteins

    Directory of Open Access Journals (Sweden)

    Ashley A. Zurawel

    2016-09-01

    Full Text Available Proteins containing polyglutamine (polyQ regions are found in almost all eukaryotes, albeit with various frequencies. In humans, proteins such as huntingtin (Htt with abnormally expanded polyQ regions cause neurodegenerative diseases such as Huntington’s disease (HD. To study how the presence of endogenous polyQ aggregation modulates polyQ aggregation and toxicity, we expressed polyQ expanded Htt fragments (polyQ Htt in Schizosaccharomyces pombe. In stark contrast to other unicellular fungi, such as Saccharomyces cerevisiae, S. pombe is uniquely devoid of proteins with more than 10 Q repeats. We found that polyQ Htt forms aggregates within S. pombe cells only with exceedingly long polyQ expansions. Surprisingly, despite the presence of polyQ Htt aggregates in both the cytoplasm and nucleus, no significant growth defect was observed in S. pombe cells. Further, PCR analysis showed that the repetitive polyQ-encoding DNA region remained constant following transformation and after multiple divisions in S. pombe, in contrast to the genetic instability of polyQ DNA sequences in other organisms. These results demonstrate that cells with a low content of polyQ or other aggregation-prone proteins can show a striking resilience with respect to polyQ toxicity and that genetic instability of repetitive DNA sequences may have played an important role in the evolutionary emergence and exclusion of polyQ expansion proteins in different organisms.

  12. Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of huntington disease.

    Directory of Open Access Journals (Sweden)

    Mei Li

    Full Text Available Huntington disease (HD is an inherited neurodegenerative disease that affects multiple brain regions. It is caused by an expanded polyglutamine tract in huntingtin (Htt. The development of therapies for HD and other neurodegenerative diseases has been hampered by multiple factors, including the lack of clear therapeutic targets, and the cost and complexity of testing lead compounds in vivo. The R6/2 HD mouse model is widely used for pre-clinical trials because of its progressive and robust neural dysfunction, which includes retinal degeneration. Profilin-1 is a Htt binding protein that inhibits Htt aggregation. Its binding to Htt is regulated by the rho-associated kinase (ROCK, which phosphorylates profilin at Ser-137. ROCK is thus a therapeutic target in HD. The ROCK inhibitor Y-27632 reduces Htt toxicity in fly and mouse models. Here we characterized the progressive retinopathy of R6/2 mice between 6-19 weeks of age to determine an optimal treatment window. We then tested a clinically approved ROCK inhibitor, HA-1077, administered intravitreally via liposome-mediated drug delivery. HA-1077 increased photopic and flicker ERG response amplitudes in R6/2 mice, but not in wild-type littermate controls. By targeting ROCK with a new inhibitor, and testing its effects in a novel in vivo model, these results validate the in vivo efficacy of a therapeutic candidate, and establish the feasibility of using the retina as a readout for CNS function in models of neurodegenerative disease.

  13. A dual-process account of auditory change detection.

    Science.gov (United States)

    McAnally, Ken I; Martin, Russell L; Eramudugolla, Ranmalee; Stuart, Geoffrey W; Irvine, Dexter R F; Mattingley, Jason B

    2010-08-01

    Listeners can be "deaf" to a substantial change in a scene comprising multiple auditory objects unless their attention has been directed to the changed object. It is unclear whether auditory change detection relies on identification of the objects in pre- and post-change scenes. We compared the rates at which listeners correctly identify changed objects with those predicted by change-detection models based on signal detection theory (SDT) and high-threshold theory (HTT). Detected changes were not identified as accurately as predicted by models based on either theory, suggesting that some changes are detected by a process that does not support change identification. Undetected changes were identified as accurately as predicted by the HTT model but much less accurately than predicted by the SDT models. The process underlying change detection was investigated further by determining receiver-operating characteristics (ROCs). ROCs did not conform to those predicted by either a SDT or a HTT model but were well modeled by a dual-process that incorporated HTT and SDT components. The dual-process model also accurately predicted the rates at which detected and undetected changes were correctly identified.

  14. A modifier of Huntington's disease onset at the MLH1 locus.

    Science.gov (United States)

    Lee, Jong-Min; Chao, Michael J; Harold, Denise; Abu Elneel, Kawther; Gillis, Tammy; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F

    2017-10-01

    Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in HTT. Many clinical characteristics of HD such as age at motor onset are determined largely by the size of HTT CAG repeat. However, emerging evidence strongly supports a role for other genetic factors in modifying the disease pathogenesis driven by mutant huntingtin. A recent genome-wide association analysis to discover genetic modifiers of HD onset age provided initial evidence for modifier loci on chromosomes 8 and 15 and suggestive evidence for a locus on chromosome 3. Here, genotyping of candidate single nucleotide polymorphisms in a cohort of 3,314 additional HD subjects yields independent confirmation of the former two loci and moves the third to genome-wide significance at MLH1, a locus whose mouse orthologue modifies CAG length-dependent phenotypes in a Htt-knock-in mouse model of HD. Both quantitative and dichotomous association analyses implicate a functional variant on ∼32% of chromosomes with the beneficial modifier effect that delays HD motor onset by 0.7 years/allele. Genomic DNA capture and sequencing of a modifier haplotype localize the functional variation to a 78 kb region spanning the 3'end of MLH1 and the 5'end of the neighboring LRRFIP2, and marked by an isoleucine-valine missense variant in MLH1. Analysis of expression Quantitative Trait Loci (eQTLs) provides modest support for altered regulation of MLH1 and LRRFIP2, raising the possibility that the modifier affects regulation of both genes. Finally, polygenic modification score and heritability analyses suggest the existence of additional genetic modifiers, supporting expanded, comprehensive genetic analysis of larger HD datasets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Application of hybrid organic/inorganic polymers as coatings on metallic substrates

    Science.gov (United States)

    Augustinho, T. R.; Motz, G.; Ihlow, S.; Machado, R. A. F.

    2016-09-01

    Acrylic polymers, particularly poly (methyl methacrylate) (PMMA), have certain specific properties, such as good film formation, transparency, and good mechanical properties, which have been widely used in paints, coatings and adhesives. However, the limited chemical and physical stability of these pure polymers limits their applications when exposed to hostile conditions, as in ship hulls, for example. A suitable way to enhance PMMA properties is the addition of silicon polymers with very good protective characteristics. In this study, a PMMA and HTT 1800 (commercial silazane) copolymer were applied on metallic substrate and compared to pure PMMA and HTT 1800. All the materials were applied as coatings. They were applied on stainless steel via dip-coating to investigate the coating properties. Thermal cycling was employed to analyze coating durability at high temperatures (50 °C to 600 °C). Optical microscopy (OM) and scanning electron microscopy (SEM) were used to characterize the coated surfaces, and the adhesion of pure PMMA, pure HTT 1800 and PMMA/HTT 1800 coatings on metallic substrate was investigated by Cross-Cut-Test (ASTM D 3359). The sessile drop method was used to determine the contact angle. PMMA coatings presented complete degradation from 250 °C, while hybrid coatings of PMMA and HTT 1800 have good protection until 400 °C. The adherence of the coating on metallic substrate showed improvement in all synthesized materials when compared to pure PMMA, obtaining the best adherence possible. The contact angle test showed that the hydrophobicity of the hybrid coatings is higher than that of the pure coatings.

  16. The Human Terrain System: Achieving a Competitive Advantage Through Enhanced Population-Centric Knowledge Flows

    Science.gov (United States)

    2008-09-01

    of behavior ( Fetterman , 1998, p. 35). Moreover, the goal of the participating observer is to internalize fundamental “beliefs, fears, hopes and...expectations of the people under study” ( Fetterman , 1998, p. 35). Additionally, HTT members frequently conduct informal interviews (open ended casual...techniques, and questionnaires ( Fetterman , 1998, p. 35). The third principle method HTT members use to learn the population is the semi- structured

  17. Huntingtin interacting proteins are genetic modifiers of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Linda S Kaltenbach

    2007-05-01

    Full Text Available Huntington's disease (HD is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%-4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to

  18. Genetic Moderators of the Impact of Physical Activity on Depressive Symptoms.

    Science.gov (United States)

    Dotson, V M; Hsu, F C; Langaee, T Y; McDonough, C W; King, A C; Cohen, R A; Newman, A B; Kritchevsky, S B; Myers, V; Manini, T M; Pahor, M

    2016-01-01

    Converging evidence suggests that physical activity is an effective intervention for both clinical depression and sub-threshold depressive symptoms; however, findings are not always consistent. These mixed results might reflect heterogeneity in response to physical activity, with some subgroups of individuals responding positively, but not others. 1) To examine the impact of genetic variation and sex on changes in depressive symptoms in older adults after a physical activity (PA) intervention, and 2) to determine if PA differentially improves particular symptom dimensions of depression. Randomized controlled trial. Four field centers (Cooper Institute, Stanford University, University of Pittsburgh, and Wake Forest University). 396 community-dwelling adults aged 70-89 years who participated in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). 12-month PA intervention compared to an education control. Polymorphisms in the serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF), and apolipoprotein E (APOE) genes; 12-month change in the Center for Epidemiologic Studies Depression Scale total score, as well as scores on the depressed affect, somatic symptoms, and lack of positive affect subscales. Men randomized to the PA arm showed the greatest decreases in somatic symptoms, with a preferential benefit in male carriers of the BDNF Met allele. Symptoms of lack of positive affect decreased more in men compared to women, particularly in those possessing the 5-HTT L allele, but the effect did not differ by intervention arm. APOE status did not affect change in depressive symptoms. Results of this study suggest that the impact of PA on depressive symptoms varies by genotype and sex, and that PA may mitigate somatic symptoms of depression more than other symptoms. The results suggest that a targeted approach to recommending PA therapy for treatment of depression is viable.

  19. Functions of huntingtin in germ layer specification and organogenesis.

    Directory of Open Access Journals (Sweden)

    Giang D Nguyen

    Full Text Available Huntington's disease (HD is a neurodegenerative disease caused by abnormal polyglutamine expansion in the huntingtin protein (Htt. Although both Htt and the HD pathogenic mutation (mHtt are implicated in early developmental events, their individual involvement has not been adequately explored. In order to better define the developmental functions and pathological consequences of the normal and mutant proteins, respectively, we employed embryonic stem cell (ESC expansion, differentiation and induction experiments using huntingtin knock-out (KO and mutant huntingtin knock-in (Q111 mouse ESC lines. In KO ESCs, we observed impairments in the spontaneous specification and survival of ectodermal and mesodermal lineages during embryoid body formation and under inductive conditions using retinoic acid and Wnt3A, respectively. Ablation of BAX improves cell survival, but failed to correct defects in germ layer specification. In addition, we observed ensuing impairments in the specification and maturation of neural, hepatic, pancreatic and cardiomyocyte lineages. These developmental deficits occurred in concert with alterations in Notch, Hes1 and STAT3 signaling pathways. Moreover, in Q111 ESCs, we observed differential developmental stage-specific alterations in lineage specification and maturation. We also observed changes in Notch/STAT3 expression and activation. Our observations underscore essential roles of Htt in the specification of ectoderm, endoderm and mesoderm, in the specification of neural and non-neural organ-specific lineages, as well as cell survival during early embryogenesis. Remarkably, these developmental events are differentially deregulated by mHtt, raising the possibility that HD-associated early developmental impairments may contribute not only to region-specific neurodegeneration, but also to non-neural co-morbidities.

  20. OF MICE, RATS AND MEN: REVISITING THE QUINOLINIC ACID HYPOTHESIS OF HUNTINGTON’S DISEASE

    Science.gov (United States)

    Schwarcz, R.; Guidetti, P.; Sathyasaikumar, K. V.; Muchowski, P. J.

    2009-01-01

    The neurodegenerative disease Huntington’s Disease (HD) is caused by an expanded polyglutamine (polyQ) tract in the protein huntingtin (htt). Although the gene encoding htt was identified and cloned more than 15 years ago, and in spite of impressive efforts to unravel the mechanism(s) by which mutant htt induces nerve cell death, these studies have so far not led to a good understanding of pathophysiology or an effective therapy. Set against a historical background, we review data supporting the idea that metabolites of the kynurenine pathway (KP) of tryptophan degradation provide a critical link between mutant htt and the pathophysiology of HD. New studies in HD brain and genetic model organisms suggest that the disease may in fact be causally related to early abnormalities in KP metabolism, favoring the formation of two neurotoxic metabolites, 3-hydroxykynurenine and quinolinic acid, over the related neuroprotective agent kynurenic acid. These findings not only link the excitotoxic hypothesis of HD pathology to an impairment of the KP but also define new drug targets and therefore have direct therapeutic implications. Thus, pharmacological normalization of the imbalance in brain KP metabolism may provide clinical benefits, which could be especially effective in the early stages of the disease. PMID:19394403

  1. How the cerebral serotonin homeostasis predicts environmental changes

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Kalbitzer, Urs; Knudsen, Gitte Moos

    2013-01-01

    Molecular imaging studies with positron emission tomography have revealed that the availability of serotonin transporter (5-HTT) in the human brain fluctuates over the course of the year. This effect is most pronounced in carriers of the short allele of the 5-HTT promoter region (5-HTTLPR), which...... has in several previous studies been linked to an increased risk to develop mood disorders. We argue that long-lasting fluctuations in the cerebral serotonin transmission, which is regulated via the 5-HTT, are responsible for mediating responses to environmental changes based on an assessment...... of cerebral serotonin transmission to seasonal and other forms of environmental change imparts greater behavioral flexibility, at the expense of increased vulnerability to stress. This model may explain the somewhat higher prevalence of the s-allele in some human populations dwelling at geographic latitudes...

  2. Orphan drugs in development for Huntington's disease: challenges and progress

    Directory of Open Access Journals (Sweden)

    Burgunder JM

    2015-02-01

    Full Text Available Jean-Marc Burgunder1–4 1Swiss Huntington’s Disease Centre, Department of Neurology, University of Bern, Bern, Switzerland; 2Department of Neurology, West China Hospital, Sichuan University, Chengdu, 3Department of Neurology, Xiangya Hospital, Central South University, Changsha, 4Department of Neurology, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Huntington’s disease is a monogenic disorder encompassing a variable phenotype with progressive cognitive, psychiatric, and movement disorders. Knowledge of the mechanisms involved in this disorder has made substantial advances since the discovery of the gene mutation. The dynamic mutation is the expansion of a CAG (cytosine-adenine-guanine repeat in the huntingtin (HTT gene, which is transcribed into an abnormal protein with an elongated polyglutamine tract. Polyglutamine HTT accumulates and is changed in its function in multifaceted ways related to the numerous roles of the normal protein. The protein is expressed in numerous areas of the brain and also in other organs. The major brain region involved in the disease process is the striatum, but it is clear that other systems are involved as well. This accumulated knowledge has now led to the development of treatment strategies based on specific molecular pathways for symptomatic and disease course-modifying treatment. The most proximal way to handle the disturbed protein is to hinder the gene transcription, translation, and/or to increase protein clearance. Other mechanisms now being approached include modulation of energy and intracellular signaling, induction of factors potentially leading to neuroprotection, as well as modulation of glial function. Several clinical trials based on these approaches are now under way, and it is becoming clear that a future disease-modifying therapy will be a combination of several approaches harmonized with symptomatic treatments. In this review, some of the most promising and

  3. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans

    OpenAIRE

    Schalling Martin; Lonsdorf Tina B; Jensen Karin B; Kosek Eva; Ingvar Martin

    2009-01-01

    Abstract Background There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expressio...

  4. Dysregulation of gene expression in the striatum of BACHD rats expressing full-length mutant huntingtin and associated abnormalities on molecular and protein levels.

    Science.gov (United States)

    Yu-Taeger, Libo; Bonin, Michael; Stricker-Shaver, Janice; Riess, Olaf; Nguyen, Hoa Huu Phuc

    2017-05-01

    Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the huntingtin protein (HTT). Mutant HTT (mHTT) has been proposed to cause neuronal dysfunction and neuronal loss through multiple mechanisms. Transcriptional changes may be a core pathogenic feature of HD. Utilizing the Affymetrix platform we performed a genome-wide RNA expression analysis in two BACHD transgenic rat lines (TG5 and TG9) at 12 months of age, both of which carry full-length human mHTT but with different expression levels. By defining the threshold of significance at p < 0.01, we found 1608 genes and 871 genes differentially expressed in both TG5 and TG9 rats when compared to the wild type littermates, respectively. We only chose the highly up-/down-regulated genes for further analysis by setting an additional threshold of 1.5 fold change. Comparing gene expression profiles of human HD brains and BACHD rats revealed a high concordance in both functional and IPA (Ingenuity Pathway Analysis) canonical pathways relevant to HD. In addition, we investigated the causes leading to gene expression changes at molecular and protein levels in BACHD rats including the involvement of polyQ-containing transcription factors TATA box-binding protein (TBP), Sp1 and CBP as well as the chromatin structure. We demonstrate that the BACHD rat model recapitulates the gene expression changes of the human disease supporting its role as a preclinical research animal model. We also show for the first time that TFIID complex formation is reduced, while soluble TBP is increased in an HD model. This finding suggests that mHTT is a competitor instead of a recruiter of polyQ-containing transcription factors in the transcription process in HD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The effects of smoking and nicotine ingestion on exercise heat tolerance.

    Science.gov (United States)

    Druyan, Amit; Atias, Danit; Ketko, Itay; Cohen-Sivan, Yoav; Heled, Yuval

    2017-03-01

    Smoking has a thermogenic effect and is associated with low physical performance. Nevertheless, a direct, quantitative effect of acute smoking on exercise heat tolerance has not been reported. Sixteen healthy young male volunteers, eight cigarette smokers, and eight non-smokers participated in the study. All subjects performed a maximal oxygen consumption test (VO2max) and a standardized heat tolerance test (HTT) after at least 12 h without smoking under the following conditions: no nicotine exposure, 10 min after nicotine exposure (2 mg nicotine lozenge), and 10 min after smoking two cigarettes (0.8 mg nicotine in each cigarette, smokers only). There was no significant effect of nicotine exposure on physiological performance and heat tolerance in the non-smokers group. In the smokers group, cigarette smoking, but not nicotine ingestion, resulted with higher heart rate (by 9±9 bpm) at the end of the HTT (psmoking and nicotine ingestion increased smokers' rectal temperature at the end of the HTT (by 0.24±0.16°C and 0.21±0.26°C, respectively, psmoking in the smokers group compared with no exposure (2.13±2.57 and 2.48±2.76, respectively, psmoking and nicotine ingestion increase the physiological strain during a HTT in smokers. Acute smoking may, therefore, increase heat intolerance and the risk to heat injuries.

  6. Development of the RF cavity for the SKKUCY-9 compact cyclotron

    International Nuclear Information System (INIS)

    Shin, Seungwook; Lee, Jongchul; LEE, Byeong-No; Ha, Donghyup; Namgoong, Ho; Chai, Jongseo

    2015-01-01

    A 9 MeV compact cyclotron, named SKKUCY-9, for a radiopharmaceutical compound especially fludeoxyglucose (FDG) production for a positron emission tomography (PET) machine was developed at Sungkyunkwan University. H − ions which are produced from a Penning Ionization Gauge(PIG) ion source, travel through a normal conducting radio frequency (RF) cavity which operates at 83.2 MHz for an acceleration and electro-magnet for a beam focusing until the ions acquire energy of about 9 MeV. For installation at a small local hospital, our SKKUCY-9 cyclotron is developed to be compact and light-weight, comparable to conventional medical purpose cyclotrons. For compactness, we adapted a deep valley and large angle hill type for the electro-magnet design. Normally a RF cavity is installed inside of the empty space of the magnet valley region, which is extremely small in our case. We faced problems such as difficulties of installing the RF cavity, low Q-value. Despite of those difficulties, a compact RF cavity and its system including a RF power coupler to feed amplified RF power to the RF cavity and a fine tuner to compensate RF frequency variations was successfully developed and tested

  7. Development of the RF cavity for the SKKUCY-9 compact cyclotron

    Science.gov (United States)

    Shin, Seungwook; Lee, Jongchul; LEE, Byeong-No; Ha, Donghyup; Namgoong, Ho; Chai, Jongseo

    2015-09-01

    A 9 MeV compact cyclotron, named SKKUCY-9, for a radiopharmaceutical compound especially fludeoxyglucose (FDG) production for a positron emission tomography (PET) machine was developed at Sungkyunkwan University. H- ions which are produced from a Penning Ionization Gauge(PIG) ion source, travel through a normal conducting radio frequency (RF) cavity which operates at 83.2 MHz for an acceleration and electro-magnet for a beam focusing until the ions acquire energy of about 9 MeV. For installation at a small local hospital, our SKKUCY-9 cyclotron is developed to be compact and light-weight, comparable to conventional medical purpose cyclotrons. For compactness, we adapted a deep valley and large angle hill type for the electro-magnet design. Normally a RF cavity is installed inside of the empty space of the magnet valley region, which is extremely small in our case. We faced problems such as difficulties of installing the RF cavity, low Q-value. Despite of those difficulties, a compact RF cavity and its system including a RF power coupler to feed amplified RF power to the RF cavity and a fine tuner to compensate RF frequency variations was successfully developed and tested.

  8. Mitochondrial fragmentation in neuronal degeneration: Toward an understanding of HD striatal susceptibility

    International Nuclear Information System (INIS)

    Cherubini, Marta; Ginés, Silvia

    2017-01-01

    Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disorder that primarily affects medium spiny neurons within the striatum. HD is caused by inheritance of an expanded CAG repeat in the HTT gene, resulting in a mutant huntingtin (mHtt) protein containing extra glutamine residues. Despite the advances in understanding the molecular mechanisms involved in HD the preferential vulnerability of the striatum remains an intriguing question. This review discusses current knowledge that links altered mitochondrial dynamics with striatal susceptibility in HD. We also highlight how the modulation of mitochondrial function may constitute an attractive therapeutic approach to reduce mHtt-induced toxicity and therefore prevent the selective striatal neurodegeneration. - Highlights: • Mitochondrial dynamics is unbalanced towards fission in HD. • Excessive mitochondrial fragmentation plays a critical role in the selective vulnerability of the striatum in HD. • Therapeutic approaches aimed to inhibit mitochondrial fission could contribute to prevent striatal neurodegeneration in HD.

  9. Hydrothermal treatment and enzymatic hydrolysis of Tamarix ramosissima: evaluation of the process as a conversion method in a biorefinery concept.

    Science.gov (United States)

    Xiao, Ling-Ping; Shi, Zheng-Jun; Xu, Feng; Sun, Run-Cang

    2013-05-01

    The present work investigated the effects of hydrothermal treatment (HTT) of Tamarix ramosissima by determination of sugar and inhibitor formation in the liquid fraction, and chemical and morphological changes of the pretreated solid material coupled with an evaluation of enzymatic hydrolysis. HTT was carried out in a batch reactor system at a maximal temperature (TMAX 180-240 °C) and evaluated for severities logRo ranging from 2.40 to 4.17. The liquid fractions were analyzed by HPLC, GPC, and GC-MS. The morphology and composition of the solid residues were characterized using an array of techniques, such as SEM, XRD, BET surface area, and CP/MAS (13)C NMR. Using a variety of tools, we have developed a better understanding of how HTT process affects biomass structure and cellulose properties that impact on its digestibility. These results provided new insights into the factors limiting enzymatic digestibility and mechanism of biomass deconstruction during hydrothermal process. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  10. Coordination preference and magnetic properties of FeII assemblies with a bis-azole bearing 1,2,4-triazole and tetrazole

    Science.gov (United States)

    Naik, Anil D.; Railliet, Antoine P.; Dîrtu, Marinela M.; Garcia, Yann

    2012-03-01

    With a new bis-azole molecular fragment ( Htt) bearing 1,2,4-triazole and tetrazole, a mononuclear complex [Fe(tt)2(H2O)4]·2H2O ( 1), a trinuclear complex [Fe3(tt)6(H2O)6]·2H2O ( 2) and a 1D coordination polymer [Fe(tt)(Htt)2]BF4·2CH3OH ( 3) were obtained by varying reaction conditions. Htt acts either as an anionic or neutral ligand depending upon the reaction medium and pH. Thermal variation of spin states of 1- 3 were investigated in the range 77-300 K by 57Fe Mössbauer spectroscopy. 1 totally remains in high-spin state over the entire temperature range whereas no spin crossover was evidenced in 2. Nearly 1:1 high-spin and low-spin population ratio is found in 3, which remains constant over the entire temperature range investigated.

  11. University Internationalization and University Autonomy

    DEFF Research Database (Denmark)

    Turcan, Romeo V.; Gulieva, Valeria

    2016-01-01

    Turcan and Gulieva deepen our theoretical understanding of the process of university internationalisation by exploring the relationship between university internationalisation and university autonomy. They conjecture that the process of university internationalisation and its sustainability are d......, dissimilar, and sometimes conflicting dimensions of the financial, legal, organisational, staffing, and academic autonomy of the host country, are compromising key aspects of their own autonomy and core mission?......Turcan and Gulieva deepen our theoretical understanding of the process of university internationalisation by exploring the relationship between university internationalisation and university autonomy. They conjecture that the process of university internationalisation and its sustainability...... are determined by the structure and exercise of university autonomy settings at home and in the host countries, and that the process itself cannot be successfully achieved and maintained without changes in the autonomy settings. The key question the authors ask is to what degree universities, in embracing new...

  12. Haplotype-based stratification of Huntington's disease.

    Science.gov (United States)

    Chao, Michael J; Gillis, Tammy; Atwal, Ranjit S; Mysore, Jayalakshmi Srinidhi; Arjomand, Jamshid; Harold, Denise; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F; Lee, Jong-Min

    2017-11-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat in HTT, resulting in an extended polyglutamine tract in huntingtin. We and others have previously determined that the HD-causing expansion occurs on multiple different haplotype backbones, reflecting more than one ancestral origin of the same type of mutation. In view of the therapeutic potential of mutant allele-specific gene silencing, we have compared and integrated two major systems of HTT haplotype definition, combining data from 74 sequence variants to identify the most frequent disease-associated and control chromosome backbones and revealing that there is potential for additional resolution of HD haplotypes. We have used the large collection of 4078 heterozygous HD subjects analyzed in our recent genome-wide association study of HD age at onset to estimate the frequency of these haplotypes in European subjects, finding that common genetic variation at HTT can distinguish the normal and CAG-expanded chromosomes for more than 95% of European HD individuals. As a resource for the HD research community, we have also determined the haplotypes present in a series of publicly available HD subject-derived fibroblasts, induced pluripotent cells, and embryonic stem cells in order to facilitate efforts to develop inclusive methods of allele-specific HTT silencing applicable to most HD patients. Our data providing genetic guidance for therapeutic gene-based targeting will significantly contribute to the developments of rational treatments and implementation of precision medicine in HD.

  13. Waste-to-energy: Dehalogenation of plastic-containing wastes.

    Science.gov (United States)

    Shen, Yafei; Zhao, Rong; Wang, Junfeng; Chen, Xingming; Ge, Xinlei; Chen, Mindong

    2016-03-01

    The dehalogenation measurements could be carried out with the decomposition of plastic wastes simultaneously or successively. This paper reviewed the progresses in dehalogenation followed by thermochemical conversion of plastic-containing wastes for clean energy production. The pre-treatment method of MCT or HTT can eliminate the halogen in plastic wastes. The additives such as alkali-based metal oxides (e.g., CaO, NaOH), iron powders and minerals (e.g., quartz) can work as reaction mediums and accelerators with the objective of enhancing the mechanochemical reaction. The dehalogenation of waste plastics could be achieved by co-grinding with sustainable additives such as bio-wastes (e.g., rice husk), recyclable minerals (e.g., red mud) via MCT for solid fuels production. Interestingly, the solid fuel properties (e.g., particle size) could be significantly improved by HTT in addition with lignocellulosic biomass. Furthermore, the halogenated compounds in downstream thermal process could be eliminated by using catalysts and adsorbents. Most dehalogenation of plastic wastes primarily focuses on the transformation of organic halogen into inorganic halogen in terms of halogen hydrides or salts. The integrated process of MCT or HTT with the catalytic thermal decomposition is a promising way for clean energy production. The low-cost additives (e.g., red mud) used in the pre-treatment by MCT or HTT lead to a considerable synergistic effects including catalytic effect contributing to the follow-up thermal decomposition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. When cytokinin, a plant hormone, meets the adenosine A2A receptor: a novel neuroprotectant and lead for treating neurodegenerative disorders?

    Directory of Open Access Journals (Sweden)

    Yi-Chao Lee

    Full Text Available It is well known that cytokinins are a class of phytohormones that promote cell division in plant roots and shoots. However, their targets, biological functions, and implications in mammalian systems have rarely been examined. In this study, we show that one cytokinin, zeatin riboside, can prevent pheochromocytoma (PC12 cells from serum deprivation-induced apoptosis by acting on the adenosine A(2A receptor (A(2A-R, which was blocked by an A(2A-R antagonist and a protein kinase A (PKA inhibitor, demonstrating the functional ability of zeatin riboside by mediating through A(2A-R signaling event. Since the A(2A-R was implicated as a therapeutic target in treating Huntington's disease (HD, a cellular model of HD was applied by transfecting mutant huntingtin in PC12 cells. By using filter retardation assay and confocal microscopy we found that zeatin riboside reversed mutant huntingtin (Htt-induced protein aggregations and proteasome deactivation through A(2A-R signaling. PKA inhibitor blocked zeatin riboside-induced suppression of mutant Htt aggregations. In addition, PKA activated proteasome activity and reduced mutant Htt protein aggregations. However, a proteasome inhibitor blocked both zeatin riboside-and PKA activator-mediated suppression of mutant Htt aggregations, confirming mediation of the A(2A-R/PKA/proteasome pathway. Taken together, zeatin riboside might have therapeutic potential as a novel neuroprotectant and a lead for treating neurodegenerative disorders.

  15. 5-HTTLPR modulates the recognition accuracy and exploration of emotional facial expressions

    Directory of Open Access Journals (Sweden)

    Sabrina eBoll

    2014-07-01

    Full Text Available Individual genetic differences in the serotonin transporter-linked polymorphic region (5-HTTLPR have been associated with variations in the sensitivity to social and emotional cues as well as altered amygdala reactivity to facial expressions of emotion. Amygdala activation has further been shown to trigger gaze changes towards diagnostically relevant facial features. The current study examined whether altered socio-emotional reactivity in variants of the 5-HTTLPR promoter polymorphism reflects individual differences in attending to diagnostic features of facial expressions. For this purpose, visual exploration of emotional facial expressions was compared between a low (n=39 and a high (n=40 5-HTT expressing group of healthy human volunteers in an eye tracking paradigm. Emotional faces were presented while manipulating the initial fixation such that saccadic changes towards the eyes and towards the mouth could be identified. We found that the low versus the high 5-HTT group demonstrated greater accuracy with regard to emotion classifications, particularly when faces were presented for a longer duration. No group differences in gaze orientation towards diagnostic facial features could be observed. However, participants in the low 5-HTT group exhibited more and faster fixation changes for certain emotions when faces were presented for a longer duration and overall face fixation times were reduced for this genotype group. These results suggest that the 5-HTT gene influences social perception by modulating the general vigilance to social cues rather than selectively affecting the pre-attentive detection of diagnostic facial features.

  16. Association of the 5-HTT gene-linked promoter region (5-HTTLPR polymorphism with psychiatric disorders: review of psychopathology and pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Kenna GA

    2012-01-01

    Full Text Available George A Kenna1, Nick Roder-Hanna2, Lorenzo Leggio3, William H Zywiak4, James Clifford5, Steven Edwards3, John A Kenna6, Jessica Shoaff1, Robert M Swift11Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence; 2College of Pharmacy, University of Rhode Island, Kingston; 3Center for Alcohol and Addiction Studies, Department of Community Health, Brown University, Providence; 4Butler Hospital, Providence, RI; 5Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA; 6College of Nursing, University of Rhode Island, Kingston, RI, USAAbstract: Serotonin (5-HT regulates important biological and psychological processes including mood, and may be associated with the development of several psychiatric disorders. An association between psychopathology and genes that regulate 5-HT neurotransmission is a robust area of research. Identification of the genes responsible for the predisposition, development, and pharmacological response of various psychiatric disorders is crucial to the advancement of our understanding of their underlying neurobiology. This review highlights research investigating 5-HT transporter (5-HTTLPR polymorphism, because studies investigating the impact of the 5-HTTLPR polymorphism have demonstrated significant associations with many psychiatric disorders. Decreased transcriptional activity of the S allele (“risk allele” may be associated with a heightened amygdala response leading to anxiety-related personality traits, major depressive disorder, suicide attempts, and bipolar disorder. By contrast, increased transcriptional activity of the L allele is considered protective for depression but is also associated with completed suicide, nicotine dependence, and attention deficit hyperactivity disorder. For some disorders, such as post-traumatic stress disorder and major depressive disorder, the research suggests that treatment

  17. Desorption of cesium ions from vermiculite with sea water by hydrothermal process

    International Nuclear Information System (INIS)

    Yin, Xiangbiao; Takahashi, Hideharu; Inaba, Yusuke; Takeshita, Kenji

    2016-01-01

    Cesium ions (Cs + ) strongly intercalated in vermiculite clay (Verm) had been effectively removed using sea water for its free utility, totally environmental friendly feature, and within containing numerous salt by the hydrothermal treatment process (HTT), which can help significantly promote desorption by the cation-exchange mechanism in subcritical condition. >74-100% removal was achieved to the interacted Cs + for a loading capacity of 4.8-50 mg g −1 . XRD results indicated that cation exchange proceeded between the intercalated Cs + and various cations in sea water during HTT. (author)

  18. Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Ivan Rattray

    Full Text Available Huntington's disease (HD is caused by the expansion of a CAG repeat in the huntingtin (HTT gene. The R6 mouse models of HD express a mutant version of exon 1 HTT and typically develop motor and cognitive impairments, a widespread huntingtin (HTT aggregate pathology and brain atrophy. Unlike the more commonly used R6/2 mouse line, R6/1 mice have fewer CAG repeats and, subsequently, a less rapid pathological decline. Compared to the R6/2 line, fewer descriptions of the progressive pathologies exhibited by R6/1 mice exist. The association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood in many models of HD. In attempt to link these factors in the R6/1 mouse line, we have performed detailed assessments of behavior and of regional brain abnormalities determined through longitudinal, in vivo magnetic resonance imaging (MRI, as well as an end-stage, ex vivo MRI study and histological assessment. We found progressive decline in both motor and non-motor related behavioral tasks in R6/1 mice, first evident at 11 weeks of age. Regional brain volumes were generally unaffected at 9 weeks, but by 17 weeks there was significant grey matter atrophy. This age-related brain volume loss was validated using a more precise, semi-automated Tensor Based morphometry assessment. As well as these clear progressive phenotypes, mutant HTT (mHTT protein, the hallmark of HD molecular pathology, was widely distributed throughout the R6/1 brain and was accompanied by neuronal loss. Despite these seemingly concomitant, robust pathological phenotypes, there appeared to be little correlation between the three main outcome measures: behavioral performance, MRI-detected brain atrophy and histopathology. In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear.

  19. Serotonin Transporter Gene 5-HTTLPR Polymorphism as a Protective Factor Against the Progression of Post-Stroke Depression.

    Science.gov (United States)

    Zhao, Qiang; Guo, Yi; Yang, Dong; Yang, Tiansong; Meng, Xianghui

    2016-04-01

    Polymorphisms in the 5-HTT and BDNF genes are shown to affect their function at the molecular and serum level. Prior work has tried to correlate the polymorphisms with post-stroke depression (PSD), the results nevertheless remain indefinitive. A plausible reason accounting for the uncertainty relates to the small sample of each published trial. In this study, we have performed a comprehensive meta-analysis in order to evaluate the effects of 5-HTT and BDNF polymorphisms (5-HTTLPR, STin2 VNTR, 5-HTR2a 102 T/C, Val66Met) on genetic risk of PSD. Human case-control trials were identified by computer-assisted and manual searches. The article search was performed until October 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effects meta-analysis to measure the effects 5-HTT and BDNF polymorphisms exerted on PSD. We also performed test of heterogeneity, test of publication bias, and sensitivity analysis to examine the reliability and stability of combined effects. 5-HTTLPR was clearly associated with genetic risk of PSD. The association seemed to be more pronounced in the homozygous model (OR = 0.34, 95% CI = 0.23-0.51, P(Q-test) = 0.63). Both the heterozygous model and the recessive model showed 50% decreased risk of PSD (OR = 0.50, 95% CI = 0.37-0.67, P(Q-test) = 0.91; OR = 0.50, 95% CI = 0.36-0.70, P(Q-test) = 0.43, respectively). Such significant association was also detected for Caucasian and Asian. These results were reliable and stable based on related analyses. Taken together, 5-HTTLPR polymorphism of the 5-HTT gene seems to protect against the occurrence of PSD. Small sample size for the polymorphisms within 5-HTT and BDNF genes may have caused underestimated associations, and a larger study is required to further assess the relations.

  20. The Unexpected Effects of Beneficial and Adverse Social Experiences during Adolescence on Anxiety and Aggression and Their Modulation by Genotype

    Science.gov (United States)

    Meyer, Neele; Richter, S. Helene; Schreiber, Rebecca S.; Kloke, Vanessa; Kaiser, Sylvia; Lesch, Klaus-Peter; Sachser, Norbert

    2016-01-01

    Anxiety and aggression are part of the behavioral repertoire of humans and animals. However, in their exaggerated form both can become maladaptive and result in psychiatric disorders. On the one hand, genetic predisposition has been shown to play a crucial modulatory role in anxiety and aggression. On the other hand, social experiences have been implicated in the modulation of these traits. However, so far, mainly experiences in early life phases have been considered crucial for shaping anxiety-like and aggressive behavior, while the phase of adolescence has largely been neglected. Therefore, the aim of the present study was to elucidate how levels of anxiety-like and aggressive behavior are shaped by social experiences during adolescence and serotonin transporter (5-HTT) genotype. For this purpose, male mice of a 5-HTT knockout mouse model including all three genotypes (wildtype, heterozygous and homozygous 5-HTT knockout mice) were either exposed to an adverse social situation or a beneficial social environment during adolescence. This was accomplished in a custom-made cage system where mice experiencing the adverse environment were repeatedly introduced to the territory of a dominant opponent but had the possibility to escape to a refuge cage. Mice encountering beneficial social conditions had free access to a female mating partner. Afterwards, anxiety-like and aggressive behavior was assessed in a battery of tests. Surprisingly, unfavorable conditions during adolescence led to a decrease in anxiety-like behavior and an increase in exploratory locomotion. Additionally, aggressive behavior was augmented in animals that experienced social adversity. Concerning genotype, homozygous 5-HTT knockout mice were more anxious and less aggressive than heterozygous 5-HTT knockout and wildtype mice. In summary, adolescence is clearly an important phase in which anxiety-like and aggressive behavior can be shaped. Furthermore, it seems that having to cope with challenge during

  1. Size distribution of carbon layer planes in biochar from different plant type of feedstock with different heating temperatures.

    Science.gov (United States)

    Lu, Guan-Yang; Ikeya, Kosuke; Watanabe, Akira

    2016-11-01

    Biochar application to soil is a strategy to decelerate the increase in the atmospheric carbon concentration. The composition of condensed aromatic clusters appears to be an important determinant of the degradation rate of char in soil. The objective of the present study was to determine the size distribution of carbon layer planes in biochars produced from different types of feedstock (a broadleaf and a coniferous tree and two herbs) using different heating treatment temperatures (HTT; 400 °C-800 °C) using X-ray diffraction 11 band profile analysis. (13)C nuclear magnetic resonance with the phase-adjusted spinning side bands of the chars indicated different spectral features depending on the HTT and similar carbon composition among the plant types at each HTT. Both the content and composition of carbon layer planes in biochar produced using the same HTT were also similar among the plant types. The carbon layer plane size in the 400 °C and 600 °C chars was distributed from 0.24 to 1.68 or 1.92 nm (corresponding to 37 or 52 rings) with the mean size of 0.79-0.92 and 0.80-1.14 nm, respectively. The carbon layer planes in the 800 °C chars ranged from 0.72-0.96 nm (7-14 rings) to 2.64-3.60 nm (91-169 rings) and the mean values were 1.47-1.89 nm. The relative carbon layer plane content in the 600 °C and 800 °C chars was typically 2 and 3 times that in the 400 °C chars. These results indicate the progression of the formation and/or the size development of graphite-like structures, suggesting that a char produced at a higher HTT would have better carbon sequestrating characteristics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The unexpected effects of beneficial and adverse social experiences during adolescence on anxiety and aggression and their modulation by genotype.

    Directory of Open Access Journals (Sweden)

    Neele eMeyer

    2016-05-01

    Full Text Available Anxiety and aggression are part of the behavioral repertoire of humans and animals. However, in their exaggerated form both can become maladaptive and result in psychiatric disorders. On the one hand, genetic predisposition has been shown to play a crucial modulatory role in anxiety and aggression. On the other hand, social experiences have been implicated in the modulation of these traits. However, so far, mainly experiences in early life phases have been considered crucial for shaping anxiety-like and aggressive behavior while the phase of adolescence has mainly been neglected. Therefore, the aim of the present study was to elucidate how levels of anxiety-like and aggressive behavior are shaped by social experiences during adolescence and serotonin transporter (5-HTT genotype. For this purpose, male mice of a 5-HTT knockout mouse model including all three genotypes (wildtype, heterozygous and homozygous 5-HTT knockout mice were either exposed to an adverse social situation or a beneficial social environment during adolescence. This was accomplished in a custom-made cage system where mice experiencing the adverse environment were repeatedly introduced to the territory of a dominant opponent but had the possibility to escape to a refuge cage. Mice encountering beneficial social conditions had free access to a female mating partner. Afterwards, anxiety-like and aggressive behavior was assessed in a battery of tests. Surprisingly, unfavorable conditions during adolescence led to a decrease in anxiety-like behavior and an increase in exploratory locomotion. Additionally, aggressive behavior was augmented in animals that experienced social adversity. Concerning genotype, homozygous 5-HTT knockout mice were more anxious and less aggressive than heterozygous 5-HTT knockout and wildtype mice. In summary, adolescence is clearly an important phase in which anxiety-like and aggressive behavior can be shaped. Furthermore, it seems that having to cope with

  3. Modulating Neurotrophin Receptor Signaling as a Therapeutic Strategy for Huntington’s Disease

    Science.gov (United States)

    Simmons, Danielle A.

    2017-01-01

    Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in the IT15 gene which encodes the huntingtin (HTT) protein. Currently, no treatments capable of preventing or slowing disease progression exist. Disease modifying therapeutics for HD would be expected to target a comprehensive set of degenerative processes given the diverse mechanisms contributing to HD pathogenesis including neuroinflammation, excitotoxicity, and transcription dysregulation. A major contributor to HD-related degeneration is mutant HTT-induced loss of neurotrophic support. Thus, neurotrophin (NT) receptors have emerged as therapeutic targets in HD. The considerable overlap between NT signaling networks and those dysregulated by mutant HTT provides strong theoretical support for this approach. This review will focus on the contributions of disrupted NT signaling in HD-related neurodegeneration and how targeting NT receptors to augment pro-survival signaling and/or to inhibit degenerative signaling may combat HD pathologies. Therapeutic strategies involving NT delivery, peptidomimetics, and the targeting of specific NT receptors (e.g., Trks or p75NTR), particularly with small molecule ligands, are discussed. PMID:29254102

  4. Length and sequence dependence in the association of Huntingtin protein with lipid membranes

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    Jawahery, Sudi; Nagarajan, Anu; Matysiak, Silvina

    2013-03-01

    There is a fundamental gap in our understanding of how aggregates of mutant Huntingtin protein (htt) with overextended polyglutamine (polyQ) sequences gain the toxic properties that cause Huntington's disease (HD). Experimental studies have shown that the most important step associated with toxicity is the binding of mutant htt aggregates to lipid membranes. Studies have also shown that flanking amino acid sequences around the polyQ sequence directly affect interactions with the lipid bilayer, and that polyQ sequences of greater than 35 glutamine repeats in htt are a characteristic of HD. The key steps that determine how flanking sequences and polyQ length affect the structure of lipid bilayers remain unknown. In this study, we use atomistic molecular dynamics simulations to study the interactions between lipid membranes of varying compositions and polyQ peptides of varying lengths and flanking sequences. We find that overextended polyQ interactions do cause deformation in model membranes, and that the flanking sequences do play a role in intensifying this deformation by altering the shape of the affected regions.

  5. Possible association between serotonin transporter promoter region polymorphism and extremely violent crime in Chinese males.

    Science.gov (United States)

    Liao, Ding-Lieh; Hong, Chen-Jee; Shih, Hao-Ling; Tsai, Shih-Jen

    2004-01-01

    The neurotransmitter, serotonin, has been implicated in aggressive behavior. The serotonin transporter (5-HTT), which reuptakes serotonin into the nerve terminal, plays a critical role in the regulation of serotonergic function. Previous western reports have demonstrated that the low-activity short (S) allele of the 5-HTT gene-linked polymorphic-region (5-HTTLPR) polymorphism is associated with aggressive behavior and associated personality traits. In the present study, we investigated this 5-HTTLPR genetic polymorphism in a group of Chinese males who had been convicted for extremely violent crime (n = 135) and a normal control group (n = 111). The proportion of S-allele carriers was significantly higher in the criminal group than in the controls (p = 0.006). A significant association was not demonstrated for the relationship between the 5-HTTLPR polymorphism and antisocial personality disorder, substance abuse or alcohol abuse in the criminal group. Our findings demonstrate that carriage of the low-activity S allele is associated with extremely violent criminal behavior in Chinese males, and suggests that the 5-HTT may be implicated in the mechanisms underlying violent behaviors.

  6. Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein.

    Science.gov (United States)

    Al-Ramahi, Ismael; Panapakkam Giridharan, Sai Srinivas; Chen, Yu-Chi; Patnaik, Samarjit; Safren, Nathaniel; Hasegawa, Junya; de Haro, Maria; Wagner Gee, Amanda K; Titus, Steven A; Jeong, Hyunkyung; Clarke, Jonathan; Krainc, Dimitri; Zheng, Wei; Irvine, Robin F; Barmada, Sami; Ferrer, Marc; Southall, Noel; Weisman, Lois S; Botas, Juan; Marugan, Juan Jose

    2017-12-26

    The discovery of the causative gene for Huntington's disease (HD) has promoted numerous efforts to uncover cellular pathways that lower levels of mutant huntingtin protein (mHtt) and potentially forestall the appearance of HD-related neurological defects. Using a cell-based model of pathogenic huntingtin expression, we identified a class of compounds that protect cells through selective inhibition of a lipid kinase, PIP4Kγ. Pharmacological inhibition or knock-down of PIP4Kγ modulates the equilibrium between phosphatidylinositide (PI) species within the cell and increases basal autophagy, reducing the total amount of mHtt protein in human patient fibroblasts and aggregates in neurons. In two Drosophila models of Huntington's disease, genetic knockdown of PIP4K ameliorated neuronal dysfunction and degeneration as assessed using motor performance and retinal degeneration assays respectively. Together, these results suggest that PIP4Kγ is a druggable target whose inhibition enhances productive autophagy and mHtt proteolysis, revealing a useful pharmacological point of intervention for the treatment of Huntington's disease, and potentially for other neurodegenerative disorders.

  7. Transcriptomic study to understand thermal adaptation in a high temperature-tolerant strain of Pyropia haitanensis.

    Science.gov (United States)

    Wang, Wenlei; Teng, Fei; Lin, Yinghui; Ji, Dehua; Xu, Yan; Chen, Changsheng; Xie, Chaotian

    2018-01-01

    Pyropia haitanensis, a high-yield commercial seaweed in China, is currently undergoing increasing levels of high-temperature stress due to gradual global warming. The mechanisms of plant responses to high temperature stress vary with not only plant type but also the degree and duration of high temperature. To understand the mechanism underlying thermal tolerance in P. haitanensis, gene expression and regulation in response to short- and long-term temperature stresses (SHS and LHS) was investigated by performing genome-wide high-throughput transcriptomic sequencing for a high temperature tolerant strain (HTT). A total of 14,164 differential expression genes were identified to be high temperature-responsive in at least one time point by high-temperature treatment, representing 41.10% of the total number of unigenes. The present data indicated a decrease in the photosynthetic and energy metabolic rates in HTT to reduce unnecessary energy consumption, which in turn facilitated in the rapid establishment of acclimatory homeostasis in its transcriptome during SHS. On the other hand, an increase in energy consumption and antioxidant substance activity was observed with LHS, which apparently facilitates in the development of resistance against severe oxidative stress. Meanwhile, ubiquitin-mediated proteolysis, brassinosteroids, and heat shock proteins also play a vital role in HTT. The effects of SHS and LHS on the mechanism of HTT to resist heat stress were relatively different. The findings may facilitate further studies on gene discovery and the molecular mechanisms underlying high-temperature tolerance in P. haitanensis, as well as allow improvement of breeding schemes for high temperature-tolerant macroalgae that can resist global warming.

  8. First molecular modeling report on novel arylpyrimidine kynurenine monooxygenase inhibitors through multi-QSAR analysis against Huntington's disease: A proposal to chemists!

    Science.gov (United States)

    Amin, Sk Abdul; Adhikari, Nilanjan; Jha, Tarun; Gayen, Shovanlal

    2016-12-01

    Huntington's disease (HD) is caused by mutation of huntingtin protein (mHtt) leading to neuronal cell death. The mHtt induced toxicity can be rescued by inhibiting the kynurenine monooxygenase (KMO) enzyme. Therefore, KMO is a promising drug target to address the neurodegenerative disorders such as Huntington's diseases. Fiftysix arylpyrimidine KMO inhibitors are structurally explored through regression and classification based multi-QSAR modeling, pharmacophore mapping and molecular docking approaches. Moreover, ten new compounds are proposed and validated through the modeling that may be effective in accelerating Huntington's disease drug discovery efforts. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Effects of personality traits on collaborative performance in problem-based learning tutorials.

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    Jang, Hye Won; Park, Seung Won

    2016-12-01

    To examine the relationship between students' collaborative performance in a problem-based learning (PBL) environment and their personality traits. Methods:This retrospective, cross-sectional study was conducted using student data of a PBL program between 2013 and 2014 at Sungkyunkwan University School of Medicine, Seoul, South Korea. Eighty students were included in the study. Student data from the Temperament and Character Inventory were used as a measure of their personality traits. Peer evaluation scores during PBL were used as a measure of students' collaborative performance. Results: Simple regression analyses indicated that participation was negatively related to harm avoidance and positively related to persistence, whereas preparedness for the group work was negatively related to reward dependence. On multiple regression analyses, low reward dependence remained a significant predictor of preparedness. Grade-point average (GPA)  was negatively associated with novelty seeking and cooperativeness and was positively associated with persistence.  Conclusion: Medical students who are less dependent on social reward are more likely to complete assigned independent work to prepare for the PBL tutorials. The findings of this study can help educators better understand and support medical students who are at risk of struggling in collaborative learning environments.

  10. Churg-Strauss Syndrome: The Clinical Features and Long-term Follow-up of 17 Patients

    Science.gov (United States)

    Oh, Mi-Jung; Lee, Jin-Young; Kwon, Nam-Hee

    2006-01-01

    Churg-Strauss syndrome (CSS) is a rare multi-system vasculitis; some cases have been reported in Korea. The aim of this study is to describe the clinical features, treatment outcome, and long-term follow-up of CSS from a single Korean medical center. Between 1995 and 2004, seventeen patients were diagnosed with CSS at the Department of Medicine of the Samsung Medical Center, Sungkyunkwan University School of Medicine. The diagnosis of CSS is based on the classification criteria of the American Collage of Rheumatology. All patients had asthma. As in other case series, the lung, peripheral nervous system, and skin were the most commonly involved organs. During the active stage of the disease, most of the patients exhibited peripheral blood eosinophilia and an elevated serum eosinophil cationic protein level. Ten patients were treated with pulses of methylprednisolone followed by tapering and cyclophosphamide, and the others were treated with corticosteroids alone. The outcomes after long-term follow-up were generally good. One patient who was refractory to initial treatment died of heart failure during the follow-up period. CSS was highly variable in its presentation and course. The manifestations may range from mild symptoms to life-threatening conditions. The outcome after long-term follow-up was as good as that of previous studies. PMID:16614512

  11. Mid-infrared spectrometry of milk for dairy metabolomics: a comparison of two sampling techniques and effect of homogenization.

    Science.gov (United States)

    Aernouts, Ben; Polshin, Evgeny; Saeys, Wouter; Lammertyn, Jeroen

    2011-10-31

    Milk production is a dominant factor in the metabolism of dairy cows involving a very intensive interaction with the blood circulation. As a result, the extracted milk contains valuable information on the metabolic status of the cow. On-line measurement of milk components during milking two or more times a day would promote early detection of systemic and local alterations, thus providing a great input for strategic and management decisions. The objective of this study was to investigate the potential of mid-infrared (mid-IR) spectroscopy to measure the milk composition using two different measurement modes: micro attenuated total reflection (μATR) and high throughput transmission (HTT). Partial least squares (PLS) regression was used for prediction of fat, crude protein, lactose and urea after preprocessing IR data and selecting the most informative wavenumber variables. The prediction accuracies were determined separately for raw and homogenized copies of a wide range of milk samples in order to estimate the possibility for on-line analysis of the milk. In case of fat content both measurement modes resulted in an excellent prediction for homogenized samples (R(2)>0.92) but in poor results for raw samples (R(2)protein and lactose with both μATR and HTT, and urea with μATR spectroscopy. Excellent results were obtained for prediction of crude protein, lactose and urea content (R(2)>0.99, 0.98 and 0.86 respectively) in raw and homogenized milk using μATR IR spectroscopy. These results were significantly better than those obtained by HTT IR spectroscopy. However, the prediction performance of HTT was still good for crude protein and lactose content (R(2)>0.86 and 0.78 respectively) in raw and homogenized samples. However, the detection of urea in milk with HTT spectroscopy was significantly better (R(2)=0.69 versus 0.16) after homogenization of the milk samples. Based on these observations it can be concluded that μATR approach is most suitable for rapid at line

  12. Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA).

    Science.gov (United States)

    Young, Matthew B; Norrholm, Seth D; Khoury, Lara M; Jovanovic, Tanja; Rauch, Sheila A M; Reiff, Collin M; Dunlop, Boadie W; Rothbaum, Barbara O; Howell, Leonard L

    2017-10-01

    3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA's broad pharmacological profile, further investigation is warranted before moving to a complex clinical population. We aimed to inform clinical research by providing a translational model of MDMA's effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction. We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training. MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA's effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA's effect by 5-HTT inhibition also downregulated 5-HT 2A -mediated behavior, and 5-HT 2A antagonism disrupted MDMA's effect on extinction. We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT 2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

  13. Pathophysiology and molecular basis of selected metabolic abnormalities in Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Jolanta Krzysztoń-Russjan

    2016-12-01

    Full Text Available Huntington’s disease (HD is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed. HD symptoms include neurological disturbances, such as choreal movements with dystonia, speech and swallowing impairments, and additionally a variety of psychiatric and behavioral symptoms with cognitive decline have been described.They are the result of disturbances of several cellular pathways related to signal transmission, mitochondrial dysfunction and energy metabolism impairment shown by gene and protein expression and alteration of their functions. Impairment of energy processes demonstrated by a decrease of ATP production and increase of oxidative stress markers was determined in- and outside of the CNS in glycolysis, the Krebs cycle and the electron transport chain. A correlation between the increase of energy metabolism impairment level and the increase in number of CAG repeats in HTT has often been described. The energy metabolism study is an initial stage of sensitive biomarkers and a new therapeutic investigative option for early application in order to inhibit pathological processes in HD.Identification of pathological changes outside the CNS requires a reevaluation of diagnostic and therapeutic rules in HD.

  14. Pathophysiology and molecular basis of selected metabolic abnormalities in Huntington's disease.

    Science.gov (United States)

    Krzysztoń-Russjan, Jolanta

    2016-12-30

    Huntington's disease (HD) is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT) is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS) and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed. HD symptoms include neurological disturbances, such as choreal movements with dystonia, speech and swallowing impairments, and additionally a variety of psychiatric and behavioral symptoms with cognitive decline have been described. They are the result of disturbances of several cellular pathways related to signal transmission, mitochondrial dysfunction and energy metabolism impairment shown by gene and protein expression and alteration of their functions. Impairment of energy processes demonstrated by a decrease of ATP production and increase of oxidative stress markers was determined in- and outside of the CNS in glycolysis, the Krebs cycle and the electron transport chain. A correlation between the increase of energy metabolism impairment level and the increase in number of CAG repeats in HTT has often been described. The energy metabolism study is an initial stage of sensitive biomarkers and a new therapeutic investigative option for early application in order to inhibit pathological processes in HD. Identification of pathological changes outside the CNS requires a reevaluation of diagnostic and therapeutic rules in HD.

  15. The study of genetic polymorphisms related to serotonin in Alzheimer's disease: a new perspective in a heterogenic disorder

    Directory of Open Access Journals (Sweden)

    Oliveira J.R.M.

    1999-01-01

    Full Text Available Genetic and environmental factors have been implicated in the development of Alzheimer's disease (AD, the most common form of dementia in the elderly. Mutations in 3 genes mapped on chromosomes 21, 14 and 1 are related to the rare early onset forms of AD while the e4 allele of the apolipoprotein E (APOE gene (on chromosome 19 is the major susceptibility locus for the most common late onset AD (LOAD. Serotonin (5-hydroxytryptamine or 5-HT is a key neurotransmitter implicated in the control of mood, sleep, appetite and a variety of traits and behaviors. Recently, a polymorphism in the transcriptional control region upstream of the 5-HT transporter (5-HTT gene has been studied in several psychiatric diseases and personality traits. It has been demonstrated that the short variant(s of this 5-HTT gene-linked polymorphic region (5-HTTLPR is associated with a different transcriptional efficiency of the 5-HTT gene promoter resulting in decreased 5-HTT expression and 5-HT uptake in lymphocytes. An increased frequency of this 5-HTTLPR short variant polymorphism in LOAD was recently reported. In addition, another common polymorphic variation in the 5-HT2A and 5-HT2C serotonin receptor genes previously analyzed in schizophrenic patients was associated with auditory and visual hallucinations in AD. These observations suggest that the involvement of the serotonin pathway might provide an explanation for some aspects of the affective symptoms commonly observed in AD patients. In summary, research on genetic polymorphisms related to AD and involved in receptors, transporter proteins and the enzymatic machinery of serotonin might enhance our understanding of this devastating neurodegenerative disorder.

  16. Establishing whether the structural feature controlling the mechanical properties of starch films is molecular or crystalline.

    Science.gov (United States)

    Li, Ming; Xie, Fengwei; Hasjim, Jovin; Witt, Torsten; Halley, Peter J; Gilbert, Robert G

    2015-03-06

    The effects of molecular and crystalline structures on the tensile mechanical properties of thermoplastic starch (TPS) films from waxy, normal, and high-amylose maize were investigated. Starch structural variations were obtained through extrusion and hydrothermal treatment (HTT). The molecular and crystalline structures were characterized using size-exclusion chromatography and X-ray diffractometry, respectively. TPS from high-amylose maize showed higher elongation at break and tensile strength than those from normal maize and waxy maize starches when processed with 40% plasticizer. Within the same amylose content, the mechanical properties were not affected by amylopectin molecular size or the crystallinity of TPS prior to HTT. This lack of correlation between the molecular size, crystallinity and mechanical properties may be due to the dominant effect of the plasticizer on the mechanical properties. Further crystallization of normal maize TPS by HTT increased the tensile strength and Young's modulus, while decreasing the elongation at break. The results suggest that the crystallinity from the remaining ungelatinized starch granules has less significant effect on the mechanical properties than that resulting from starch recrystallization, possibly due to a stronger network from leached-out amylose surrounding the remaining starch granules. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

    Directory of Open Access Journals (Sweden)

    Kim JY

    2015-01-01

    Full Text Available Ju-Young Kim,1,* Sung-Hoon Lee,2,3,* Chun-Woong Park,4 Yun-Seok Rhee,5 Dong-Wook Kim,6 Junsang Park,3 Moonseok Lee,3 Jeong-Woong Seo,2 Eun-Seok Park2 1College of Pharmacy, Woosuk University, Wanju-gun, Republic of Korea; 2School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 3GL Pharmtech, Seongnam, Republic of Korea; 4College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea; 5College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea; 6Department of Pharmaceutical Engineering, Cheongju University, Cheongju, Republic of Korea *These authors contributed equally to this work Abstract: The aim of present study was to design oxycodone once-a-day controlled-release (CR tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day] or once-a-day CR tablets (20 mg were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. Keywords

  18. Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers

    Directory of Open Access Journals (Sweden)

    Lim CM

    2016-02-01

    Full Text Available Chaemin Lim,1,* Yu Seok Youn,2,* Kyung Soo Lee,1 Ngoc Ha Hoang,1 Taehoon Sim,1 Eun Seong Lee,3 Kyung Taek Oh1 1Department of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, 2Department of Pharmaceutical Sciences, School of Pharmacy, Sungkyunkwan University, Suwon, 3Division of Biotechnology, The Catholic University of Korea, Gyeonggi-do, South Korea *These authors contributed equally to this work Abstract: A polyelectrolyte ionomer complex (PIC composed of cationic and anionic polymers was developed for nanomedical applications. Here, a poly(ethylene glycol–poly(lactic acid–poly(ethylene imine triblock copolymer (PEG–PLA–PEI and a poly(aspartic acid (P[Asp] homopolymer were synthesized. These polyelectrolytes formed stable aggregates through electrostatic interactions between the cationic PEI and the anionic P(Asp blocks. In particular, the addition of a hydrophobic PLA and a hydrophilic PEG to triblock copolyelectrolytes provided colloidal aggregation stability by forming a tight hydrophobic core and steric hindrance on the surface of PIC, respectively. The PIC showed different particle sizes and zeta potentials depending on the ratio of cationic PEI and anionic P(Asp blocks (C/A ratio. The doxorubicin (dox-loaded PIC, prepared with a C/A ratio of 8, demonstrated pH-dependent behavior by the deprotonation/protonation of polyelectrolyte blocks. The drug release and the cytotoxicity of the dox-loaded PIC (C/A ratio: 8 increased under acidic conditions compared with physiological pH, due to the destabilization of the formation of the electrostatic core. In vivo animal imaging revealed that the prepared PIC accumulated at the targeted tumor site for 24 hours. Therefore, the prepared pH-sensitive PIC could have considerable potential as a nanomedicinal platform for anticancer therapy. Keywords: polyelectrolyte ionomer complex, PEG–PLA–PEI, nanomedicine, pH-sensitive, animal imaging

  19. Use of anti-depressants and the risk of fracture of the hip or femur.

    Science.gov (United States)

    van den Brand, M W M; Pouwels, S; Samson, M M; van Staa, T P; Thio, B; Cooper, C; Leufkens, H G M; Egberts, A C G; Verhaar, H J J; de Vries, F

    2009-10-01

    Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. Anti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use. A case-control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region. The risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (OR(adj)) 2.35 [95% confidence interval (CI) 1.94-2.84]) and TCAs (ORadj 1.76 [95% CI 1.45-2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from OR(adj) 1.64 [95% CI 1.14-2.35] for drugs with low 5-HTT inhibition to OR(adj) 2.31 [95% CI 1.94-2.76] for those with high 5-HTT inhibiting properties. Current use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

  20. Perturbation with intrabodies reveals that calpain cleavage is required for degradation of huntingtin exon 1.

    Directory of Open Access Journals (Sweden)

    Amber L Southwell

    2011-01-01

    Full Text Available Proteolytic processing of mutant huntingtin (mHtt, the protein that causes Huntington's disease (HD, is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD.We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1 clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V(L12.3, turnover of soluble mHDx-1 in living cells is blocked.These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications.

  1. Inhibition of serotonin but not norepinephrine transport during development produces delayed, persistent perturbations of emotional behaviors in mice.

    Science.gov (United States)

    Ansorge, Mark S; Morelli, Emanuela; Gingrich, Jay A

    2008-01-02

    Serotonin (5-HT) acts as a neurotransmitter, but also modulates brain maturation during early development. The demonstrated influence of genetic variants on brain function, personality traits, and susceptibility to neuropsychiatric disorders suggests a critical importance of developmental mechanisms. However, little is known about how and when developmentally perturbed 5-HT signaling affects circuitry and resulting behavior. The 5-HT transporter (5-HTT) is a key regulator of extracellular 5-HT levels and we used pharmacologic strategies to manipulate 5-HTT function during development and determine behavioral consequences. Transient exposure to the 5-HTT inhibitors fluoxetine, clomipramine, and citalopram from postnatal day 4 (P4) to P21 produced abnormal emotional behaviors in adult mice. Similar treatment with the norepinephrine transporter (NET) inhibitor, desipramine, did not adversely affect adult behavior, suggesting that 5-HT and norepinephrine (NE) do not share the same effects on brain development. Shifting our period of treatment/testing to P90/P185 failed to mimic the effect of earlier exposure, demonstrating that 5-HT effects on adult behavior are developmentally specific. We have hypothesized that early-life perturbations of 5-HT signaling affect corticolimbic circuits that do not reach maturity until the peri-adolescent period. In support of this idea, we found that abnormal behaviors resulting from postnatal fluoxetine exposure have a post-pubescent onset and persist long after reaching adult age. A better understanding of the underlying 5-HT sensitive circuits and how they are perturbed should lead to new insights into how various genetic polymorphisms confer their risk to carriers. Furthermore, these studies should help determine whether in utero exposure to 5-HTT blocking drugs poses a risk for behavioral abnormalities in later life.

  2. The association study between the interaction of serotonin and norepinephrine transporter gene polymorphisms and the effects of selective serotonin reuptake inhibitors%5-羟色胺和去甲肾上腺素转运体基因多态性的交互作用与重性抑郁障碍临床疗效的关联研究

    Institute of Scientific and Technical Information of China (English)

    孟亚琴; 孙宁; 王彦芳; 段慧君; 李素萍; 彭菊意; 杜巧荣; 张克让

    2013-01-01

    Objective To explore the relevance of the interaction of serotonin and norepinephrine transporter gene polymorphisms and the effects of selective serotonin reuptake inhibitors.Methods The subjects comprised 246 patients according to the diagnostic and statistical manual of mental disorders in the fourth edition (DSM-Ⅳ) criterion for major depressive disorder(MDD).The clinical efficacy were assessed by using 17 Hamilton depression quantity (HAMD) scale after selective serotonin reuptake inhibitors(SSRIs) citalopram (20 to 60 mg/d) or paroxetine (20 to 60 mg/d) were used randomly for 1,2,4,6 weeks.Polymerase chain reaction(PCR),sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE)and DNA sequencing analysis were used to detect the genotype of 5-HTT gene single nucleotide polymorphisms (SNP) of VNTR and LPR and SNPs at rs2242446 and rs5569 of NET.SPSS13.0 software were used for statistical analysis.Results (1) An association between 5-HTT LPR and the efficacy of SSRIs was found after 6 weeks in these samples (P =0.023).The clinical efficiency of LL genotype was higher than SS + LS genotype(OR =2.225,OR 95% CI=1.118,4.427).(2) The interaction of 5-HTT LPR and NET rs5569 and the SSRIs antidepressant effects was statistical significance (P =0.01).Conclusion Preliminary study found that the interaction of 5-HTT LPR and NET rs5569 may be related to SSRIs antidepressant effects in China' s patients with MDD.%目的 探讨5-羟色胺和去甲肾上腺素转运体基因多态性的交互作用与选择性5-羟色胺再摄取抑制剂临床疗效的关联研究.方法 收集符合美国精神障碍诊断与统计手册第四版(DSM-Ⅳ)重性抑郁障碍(MDD)诊断标准的患者246例,给予选择性5-羟色胺再摄取抑制剂(SSRIs)西酞普兰(20~ 60mg/d)或帕罗西汀(20 ~ 60 mg/d),在治疗后1,2,4,6周运用17

  3. Electron spin resonance and its application to heat treated carbonaceous materials

    International Nuclear Information System (INIS)

    Emmerich, Francisco Guilherme

    1993-01-01

    This work presents the basic characteristics of the electron spin resonance technique, also called paramagnetic resonance, being discussed its application to heat treated carbonaceous materials. In the low heat treatment temperature (HTT) range (below 700 deg C) the organic free radical are the predominant unpaired spin center, which play a key role in the process of carbonization and meso phase formation. At higher temperatures, it is possible to make correlations between the low H T T range and the high HTT range (above 130 deg C), where the predominant unpaired spin center are the free charge carriers (free electrons) of the graphite like crystallites of the material, which are formed by the carbonization process. (author)

  4. Electron spin resonance and its application to heat treated carbonaceous materials; A ressonancia de spin eletronico e sua aplicacao aos materiais carbonosos tratados termicamente

    Energy Technology Data Exchange (ETDEWEB)

    Emmerich, Francisco Guilherme [Espirito Santo Univ., Vitoria, ES (Brazil). Laboratorio de Materiais Carbonosos e Plasma Termico

    1994-12-31

    This work presents the basic characteristics of the electron spin resonance technique, also called paramagnetic resonance, being discussed its application to heat treated carbonaceous materials. In the low heat treatment temperature (HTT) range (below 700 deg C) the organic free radical are the predominant unpaired spin center, which play a key role in the process of carbonization and meso phase formation. At higher temperatures, it is possible to make correlations between the low H T T range and the high HTT range (above 130 deg C), where the predominant unpaired spin center are the free charge carriers (free electrons) of the graphite like crystallites of the material, which are formed by the carbonization process. (author) 10 refs., 3 figs.

  5. Assembly of Huntingtin headpiece into α-helical bundles.

    Science.gov (United States)

    Ozgur, Beytullah; Sayar, Mehmet

    2017-05-24

    Protein aggregation is a hallmark of neurodegenerative disorders. In this group of brain-related disorders, a disease-specific "host" protein or fragment misfolds and adopts a metastatic, aggregate-prone conformation. Often, this misfolded conformation is structurally and thermodynamically different from its native state. Intermolecular contacts, which arise in this non-native state, promote aggregation. In this regard, understanding the molecular principles and mechanisms that lead to the formation of such a non-native state and further promote the formation of the critical nucleus for fiber growth is essential. In this study, the authors analyze the aggregation propensity of Huntingtin headpiece (htt NT ), which is known to facilitate the polyQ aggregation, in relation to the helix mediated aggregation mechanism proposed by the Wetzel group. The authors demonstrate that even though htt NT displays a degenerate conformational spectrum on its own, interfaces of macroscopic or molecular origin can promote the α-helix conformation, eliminating all other alternatives in the conformational phase space. Our findings indicate that htt NT molecules do not have a strong orientational preference for parallel or antiparallel orientation of the helices within the aggregate. However, a parallel packed bundle of helices would support the idea of increased polyglutamine concentration, to pave the way for cross-β structures.

  6. A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

    Directory of Open Access Journals (Sweden)

    Sabine M Hölter

    Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

  7. Genetic exchange in eukaryotes through horizontal transfer: connected by the mobilome.

    Science.gov (United States)

    Wallau, Gabriel Luz; Vieira, Cristina; Loreto, Élgion Lúcio Silva

    2018-01-01

    All living species contain genetic information that was once shared by their common ancestor. DNA is being inherited through generations by vertical transmission (VT) from parents to offspring and from ancestor to descendant species. This process was considered the sole pathway by which biological entities exchange inheritable information. However, Horizontal Transfer (HT), the exchange of genetic information by other means than parents to offspring, was discovered in prokaryotes along with strong evidence showing that it is a very important process by which prokaryotes acquire new genes. For some time now, it has been a scientific consensus that HT events were rare and non-relevant for evolution of eukaryotic species, but there is growing evidence supporting that HT is an important and frequent phenomenon in eukaryotes as well. Here, we will discuss the latest findings regarding HT among eukaryotes, mainly HT of transposons (HTT), establishing HTT once and for all as an important phenomenon that should be taken into consideration to fully understand eukaryotes genome evolution. In addition, we will discuss the latest development methods to detect such events in a broader scale and highlight the new approaches which should be pursued by researchers to fill the knowledge gaps regarding HTT among eukaryotes.

  8. Sheet universes and the shapes of Friedmann universes

    International Nuclear Information System (INIS)

    Lynden-Bell, D.; Redmount, I.H.

    1989-01-01

    Unless Ω>1,the Big Bang did not start from a point. Consideration shows sheet universes in which matter is confined to a homogeneous universe. Sheet universes and the corresponding embeddings of FRW universes into Minkowski space are drawn. Their initial singularities are shown to be point-like for the 'closed' case, line-like for the 'flat' (Ω=1) case and surface-like for the 'open' case. In contrast to the cross-sections at constant comoving proper time, typical spacelike cross-sections of the 'flat' universes are closed and encounter their extensive singularities. All cross-sections of the 'closed' universe are closed and only very special cross-sections encounter the point singularities at the Big Bang or the Big Crunch. (author)

  9. University-Community Engagement: Case Study of University Social Responsibility

    Science.gov (United States)

    Chile, Love M.; Black, Xavier M.

    2015-01-01

    Corporatisation of universities has drawn parallels between contemporary universities and business corporations, and extended analysis of corporate social responsibility to universities. This article reports on a case study of university-community engagement with schools and school communities through youth engagement programmes to enhance…

  10. Clinical characteristics of patients with benign nonlesional temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Kim J

    2016-07-01

    Full Text Available Jiyeon Kim,1 Seong Hoon Kim,2 Sung Chul Lim,2 Woojun Kim,2 Young-Min Shon3 1Department of Neurology, Korea University Ansan Hospital, College of Medicine, Korea University, Ansan, 2Department of Neurology, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seocho-gu, 3Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Purpose: To evaluate the evolution of nonlesional temporal lobe epilepsy (TLE-NL in patients treated exclusively with antiepileptic drugs and to elucidate clinical phenotypes related to the prognosis of these patients.Methods: Clinical, radiological, and electroencephalographic (EEG findings in 84 patients with TLE-NL were reviewed. A good response group (GRG and a poor response group (PRG were defined if the duration of their seizure-free period was >1 year, or <1 year, respectively.Results: There were 46 (54.8% patients in the GRG and 38 (45.2% patients in the PRG. The number of antiepileptic drugs administered was significantly lower in the GRG than that in the PRG (1.3±0.8 vs 2.8±1.0, respectively; P<0.05. The GRG had a significantly older age of onset than the PRG and a lower occurrence of initial precipitating events, such as febrile seizures, central nervous system infection, and head trauma (P<0.05. The prevalence of EEG abnormality, presence of aura, generalized seizures, and automatism was less frequently observed in the GRG (P<0.05. Multivariate analysis showed that the presence of automatism and initial precipitating events were significantly associated with a poor prognosis (P<0.05.Conclusion: In contrast to the commonly assumed intractability of TLE, we found that more than 54% of patients with TLE-NL achieved a long seizure-free period. Older age at onset of TLE-NL was associated with a better prognosis. However, the presence of automatism and initial precipitating events were related to a poor prognosis. Future prospective

  11. Exploring the relationship between university internationalization and university autonomy

    DEFF Research Database (Denmark)

    Turcan, Romeo V.; Gullieva, Valeria

    This paper explores a research gap at the intersection of university internationalization and university autonomy. A process model of university internationalization is put forward whereby the process of university internationalization is mediated by university internationalization capacity...... and moderated by target country institutional autonomy and globalization; and entry modes, timing and pace, as well as product mix of internationalization define university’s internationalization pattern. A systematic review is conducted to identify empirical studies at this intersection. One of the questions...

  12. Study of university students' attitudes toward office space at universities

    Directory of Open Access Journals (Sweden)

    S.M. Eteadifard

    2017-06-01

    Full Text Available Office space is the space where students first experience the university. In this paper, the attitude of students toward office space in the public sphere of university is discussed. This article is the result of the research conducted for the “Institute for Social and Cultural Studies” by the author. The main issues in this paper are: university students' attitudes towards quality office space at the universities and mental basis of common issues among students at the universities. Data were collected through individual and group interviews. More than eighty interviews with activists and students of University of Tehran, Shahid Beheshti University, Allameh Tabataba’i University, Sharif University of Technology and Kharazmi University were done. The main indicators of office space in this study include: students’ satisfaction of office space, students’ welfare affairs and students’ feedback about this space. Problems and obstacles relating to the office space and their solutions were also studied in this paper.

  13. Protective effect of DA-9401 in finasteride-induced apoptosis in rat testis: inositol requiring kinase 1 and c-Jun N-terminal kinase pathway

    Directory of Open Access Journals (Sweden)

    Soni KK

    2017-10-01

    Full Text Available Kiran Kumar Soni,1,* Yu Seob Shin,1,* Bo Ram Choi,1 Keshab Kumar Karna,1 Hye Kyung Kim,2 Sung Won Lee,3 Chul Young Kim,4 Jong Kwan Park1 1Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, Jeonju, 2College of Pharmacy, Kyungsung University, Busan, 3Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University Medical School, Seoul, 4College of Pharmacy, Hangyang University, Ansan, Republic of Korea *These authors contributed equally to this work Abstract: Finasteride is used to treat male pattern baldness and benign prostatic hyperplasia. This study investigated the toxicity of finasteride and recovery by DA-9401 using Sprague Dawley (SD rats. Forty adult male SD rats were assigned to four groups: control (CTR, finasteride 1 mg/kg/day (F, finasteride 1 mg/kg + DA-9401 100 mg/kg/day (F + DA 100 and finasteride 1 mg/kg + DA-9401 200 mg/kg/day (F + DA 200. Treatments were by oral delivery once daily for 90 consecutive days. The gross anatomical parameters assessed included: genital organ weight; vas deferens sperm count and sperm motility; testosterone, dihydrotestosterone (DHT and malondialdehyde levels; and histological and terminal deoxynucleotidyl transferase enzyme mediated dUTP nick-end labeling (TUNEL staining of testis for spermatogenic cell density, Johnsen’s score and apoptosis. Testicular tissue was also used for evaluating endoplasmic reticulum (ER stress and apoptotic proteins. Epididymis weight, seminal vesicle weight, prostate weight, penile weight and vas deferens sperm motility showed significant differences between the F group and the CTR, F + DA 100 and F + DA 200 groups. There was no significant change in the testosterone level. DHT level decreased significantly in the F group compared with the CTR

  14. Our Universe

    Science.gov (United States)

    Stern, Alan

    2001-03-01

    The Universe in which we live is unimaginably vast and ancient, with countless star systems, galaxies, and extraordinary phenomena such as black holes, dark matter, and gamma ray bursts. What phenomena remain mysteries, even to seasoned scientists? Our Universe is a fascinating collection of essays by some of the world's foremost astrophysicists. Some are theorists, some computational modelers, some observers, but all offer their insights into the most cutting-edge, difficult, and curious aspects of astrophysics. Compiled, the essays describe more than the latest techniques and findings. Each of the ten contributors offers a more personal perspective on their work, revealing what motivates them and how their careers and lives have been shaped by their desire to understand our universe. S. Alan Stern is Director of the Department of Space Studies at Southwest Research Institute in Boulder, Colorado. He is a planetary scientist and astrophysicist with both observational and theoretical interests. Stern is an avid pilot and a principal investigator in NASA's planetary research program, and he was selected to be a NASA space shuttle mission specialist finalist. He is the author of more than 100 papers and popular articles. His most recent book is Pluto & Charon (Wiley, 1997). Contributors: Dr. John Huchra, Harvard University Dr. Esther Hu, University of Hawaii, Honolulu Dr. John Mather, NASA Goddard Space Flight Center Dr. Nick Gnedin, University of Colorado, Boulder Dr. Doug Richstone, University of Michigan, Ann Arbor Dr. Bohdan Paczynski, Princeton University, NJ Dr. Megan Donahue, Space Telescope Science Institute, Baltimore, MD Dr. Jerry Ostriker, Princeton University, New Jersey G. Bothun, University of Oregon, Eugene

  15. The Learning University.

    Science.gov (United States)

    Patterson, Glenys

    1999-01-01

    As universities make cross-sectoral alliances, various models for integrating postsecondary education into universities arise: contract, brokerage, collaborative, validation, joint program, dual-sector institution, tertiary university, metaphoric, and federal. The integrated, comprehensive university is the learning university of the 21st century.…

  16. Between universalism and regionalism: universal systematics from imperial Japan.

    Science.gov (United States)

    Lee, Jung

    2015-12-01

    Historiographic discussions of the universality and regionality of science have to date focused on European cases for making regional science universal. This paper presents a new perspective by moving beyond European origins and illuminating a non-European scientist's engagement with the universality and regionality of science. It will examine the case of the Japanese botanist Nakai Takenoshin (1882-1952), an internationally recognized authority on Korean flora based at Tokyo Imperial University. Serving on the International Committee on Botanical Nomenclature in 1926, Nakai endorsed and acted upon European claims of universal science, whilst simultaneously unsettling them with his regionally shaped systematics. Eventually he came to promote his own systematics, built regionally on Korean flora, as the new universal. By analysing his shifting claims in relation to those of other European and non-European botanists, this paper makes two arguments. First, universalism and regionalism were not contradictory foundations of scientific practice but useful tools used by this non-European botanist in maintaining his scientific authority as a representative Japanese systematist. Second, his claims to universality and regionalism were both imperially charged. An imperially monopolized study of Korean plants left a regional imprint on Nakai's systematics. In order to maintain his scientific authority beyond its region of origin he had to assert either the expanding regionalism of 'East Asia' or universalism.

  17. Universe symmetries

    International Nuclear Information System (INIS)

    Souriau, J.M.

    1984-01-01

    The sky uniformity can be noticed in studying the repartition of objects far enough. The sky isotropy description uses space rotations. The group theory elements will allow to give a meaning at the same time precise and general to the word a ''symmetry''. Universe models are reviewed, which must have both of the following qualities: - conformity with the physic known laws; - rigorous symmetry following one of the permitted groups. Each of the models foresees that universe evolution obeys an evolution equation. Expansion and big-bang theory are recalled. Is universe an open or closed space. Universe is also electrically neutral. That leads to a work hypothesis: the existing matter is not given data of universe but it appeared by evolution from nothing. Problem of matter and antimatter is then raised up together with its place in universe [fr

  18. Characterisation of the ruminal fermentation and microbiome in lambs supplemented with hydrolysable and condensed tannins.

    Science.gov (United States)

    Salami, Saheed A; Valenti, Bernardo; Bella, Marco; O'Grady, Michael N; Luciano, Giuseppe; Kerry, Joseph P; Jones, Eleanor; Priolo, Alessandro; Newbold, Charles J

    2018-05-01

    This study characterised the response of ruminal fermentation and the rumen microbiome in lambs fed commercial vegetal sources of hydrolysable tannins (HT) and condensed tannins (CT). Forty-four lambs (19.56 ± 2.06 kg) were randomly assigned to either a concentrate diet (CON, n = 8) or CON supplemented with 4% of two HT [chestnut (Castanea sativa, HT-c) and tara (Caesalpinia spinosa, HT-t)] and CT [mimosa (Acacia negra, CT-m) and gambier (Uncaria gambir, CT-g)] extracts (all, n = 9) for 75 days pre-slaughter. Tannin supplementation did not influence ruminal fermentation traits. Quantitative PCR demonstrated that tannins did not affect the absolute abundance of ruminal bacteria or fungi. However, CT-m (-12.8%) and CT-g (-11.5%) significantly reduced the abundance of methanogens, while HT-t (-20.7%) and CT-g (-20.8%) inhibited protozoal abundance. Ribosomal amplicon sequencing revealed that tannins caused changes in the phylogenetic structure of the bacterial and methanogen communities. Tannins inhibited the fibrolytic bacterium, Fibrobacter and tended to suppress the methanogen genus, Methanosphaera. Results demonstrated that both HT and CT sources could impact the ruminal microbiome when supplemented at 4% inclusion level. HT-t, CT-m and CT-g extracts displayed specific antimicrobial activity against methanogens and protozoa without compromising ruminal fermentation in a long-term feeding trial.

  19. The Wnt receptor Ryk reduces neuronal and cell survival capacity by repressing FOXO activity during the early phases of mutant huntingtin pathogenicity.

    Directory of Open Access Journals (Sweden)

    Cendrine Tourette

    2014-06-01

    Full Text Available The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD. Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT in several models of Huntington's disease (HD. Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD.

  20. Oxidative metabolism and Ca2+ handling in isolated brain mitochondria and striatal neurons from R6/2 mice, a model of Huntington's disease.

    Science.gov (United States)

    Hamilton, James; Pellman, Jessica J; Brustovetsky, Tatiana; Harris, Robert A; Brustovetsky, Nickolay

    2016-07-01

    Alterations in oxidative metabolism and defects in mitochondrial Ca 2+ handling have been implicated in the pathology of Huntington's disease (HD), but existing data are contradictory. We investigated the effect of human mHtt fragments on oxidative metabolism and Ca 2+ handling in isolated brain mitochondria and cultured striatal neurons from the R6/2 mouse model of HD. Non-synaptic and synaptic mitochondria isolated from the brains of R6/2 mice had similar respiratory rates and Ca 2+ uptake capacity compared with mitochondria from wild-type (WT) mice. Respiratory activity of cultured striatal neurons measured with Seahorse XF24 flux analyzer revealed unaltered cellular respiration in neurons derived from R6/2 mice compared with neurons from WT animals. Consistent with the lack of respiratory dysfunction, ATP content of cultured striatal neurons from R6/2 and WT mice was similar. Mitochondrial Ca 2+ accumulation was also evaluated in cultured striatal neurons from R6/2 and WT animals. Our data obtained with striatal neurons derived from R6/2 and WT mice show that both glutamate-induced increases in cytosolic Ca 2+ and subsequent carbonilcyanide p-triflouromethoxyphenylhydrazone-induced increases in cytosolic Ca 2+ were similar between WT and R6/2, suggesting that mitochondria in neurons derived from both types of animals accumulated comparable amounts of Ca 2+ Overall, our data argue against respiratory deficiency and impaired Ca 2+ handling induced by human mHtt fragments in both isolated brain mitochondria and cultured striatal neurons from transgenic R6/2 mice. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. University Teachers' Perception of Inclusion of Visually Impaired in Ghanaian Universities

    Science.gov (United States)

    Mamah, Vincent; Deku, Prosper; Darling, Sharon M.; Avoke, Selete K.

    2011-01-01

    This study was undertaken to examine the university teachers' perception of including students with Visual Impairment (VI) in the public universities of Ghana. The sample consisted of 110 teachers from the University of Cape Coast (UCC), the University of Education, Winneba, (UEW), and the University of Ghana (UG). Data were collected through…

  2. Private Universities in Zimbabwe: The Case of Africa University ...

    African Journals Online (AJOL)

    Whilst many of these challenges are shared with other private universities in Zimbabwe, a few are peculiar to Africa University. This paper discusses Africa University's experience with regard to establishment, nature, institutional marketing and student recruitment, programmes, governance, finding and other external factors ...

  3. File list: Unc.Kid.50.AllAg.Nephrectomy_sample [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Kid.50.AllAg.Nephrectomy_sample hg19 Unclassified Kidney Nephrectomy sample htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Kid.50.AllAg.Nephrectomy_sample.bed ...

  4. File list: Unc.Kid.10.AllAg.Nephrectomy_sample [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Kid.10.AllAg.Nephrectomy_sample hg19 Unclassified Kidney Nephrectomy sample htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Kid.10.AllAg.Nephrectomy_sample.bed ...

  5. File list: Unc.Kid.20.AllAg.Nephrectomy_sample [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Kid.20.AllAg.Nephrectomy_sample hg19 Unclassified Kidney Nephrectomy sample htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Kid.20.AllAg.Nephrectomy_sample.bed ...

  6. Interaction between genetic polymorphisms and stressful life events in first episode depression

    DEFF Research Database (Denmark)

    Bukh, Jens Drachmann; Bock, Camilla; Vinberg, Maj

    2009-01-01

    of depression among participants. METHOD: We applied a case-only design, including 290 ethnically homogeneous patients suffering exclusively from first episode depression. Psychiatric mo-morbidity, personality traits and disorders and stressful life events in a six months period preceding onset of depression......BACKGROUND: A polymorphism in the serotonin transporter (5-HTT) gene seems to moderate the influence of stressful life events on depression. However, the results from previous studies of gene-environment interactions in depression are inconsistent and might be confounded by the history......A, 2A, and 2C. RESULTS: The low activity variants of the 5-HTT-linked polymorphic region in the serotonin transporter gene and the Met-allele of a single nucleotide polymorphism (Val66Met) in the gene encoding brain derived neurotrophic factor were independently associated with the presence...

  7. Behavioral medicine in Teikyo University and Toho University

    OpenAIRE

    Takeuchi, Takeaki; Hashizume, Masahiro

    2016-01-01

    Behavioral medicine has increased in importance to become a promising field in medical education. The Teikyo University Graduate School of Public Health and Toho University School of Medicine were evaluated in terms of their educational emphasis on behavioral medicine. The Teikyo University Graduate School of Public Health has the following five core requirements, as in the global standards: behavioral medicine, biostatistics, epidemiology, occupational health, and health policy management. B...

  8. Early Predictors of First-Year Academic Success at University: Pre-University Effort, Pre-University Self-Efficacy, and Pre-University Reasons for Attending University

    Science.gov (United States)

    van Herpen, Sanne G. A.; Meeuwisse, Marieke; Hofman, W. H. Adriaan; Severiens, Sabine E.; Arends, Lidia R.

    2017-01-01

    Given the large number of dropouts in the 1st year at university, it is important to identify early predictors of 1st-year academic success. The present study (n = 453 first-year students) contributes to literature on the transition from secondary to higher education by investigating how the non-cognitive factors "pre-university" effort…

  9. Towards a University of the Common: Reimagining the University in Order to Abolish It with the Really Open University

    Directory of Open Access Journals (Sweden)

    Andre Pusey

    2017-07-01

    Full Text Available The autumn of 2010, in the UK, was characterised by a series of protests against the proposed tripling of university tuition fees and the removal of the Education Maintenance Allowance (EMA. These protests were set within a broader international background of contestation around universities and higher education reforms. This article focuses on the activities of a group, which emerged within this context, called the Really Open University (ROU, and its efforts to engender a reimagining of the university. Specifically, this article argues that the activities of the ROU were attempts to create new, radical imaginaries of the university and were linked to broader efforts to re-conceptualise knowledge production and pedagogy. The central point is that ultimately the ROU’s invitation to ‘reimagine the university’ was a provocation to abolish the university in its capitalist form, through a process of reimagining the university, exodus from the university machine and creation of a university of the common.

  10. A lightweight universe?

    Science.gov (United States)

    Bahcall, Neta A.; Fan, Xiaohui

    1998-01-01

    How much matter is there in the universe? Does the universe have the critical density needed to stop its expansion, or is the universe underweight and destined to expand forever? We show that several independent measures, especially those utilizing the largest bound systems known—clusters of galaxies—all indicate that the mass-density of the universe is insufficient to halt the expansion. A promising new method, the evolution of the number density of clusters with time, provides the most powerful indication so far that the universe has a subcritical density. We show that different techniques reveal a consistent picture of a lightweight universe with only ∼20–30% of the critical density. Thus, the universe may expand forever. PMID:9600898

  11. File list: His.Dig.50.AllAg.Intestine,_Small [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Dig.50.AllAg.Intestine,_Small hg19 Histone Digestive tract Intestine, Small htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Dig.50.AllAg.Intestine,_Small.bed ...

  12. The Alien University

    DEFF Research Database (Denmark)

    Bengtsen, Søren Smedegaard

    2018-01-01

    - they are alien. The conditions of universities today is not one of crisis and upheaval, as with the postmodern universities, it is one of night travel and exile. The alien university leaves behind the epistemological skirmishes of the postmodern university with all its rhetoric and knowledge activism. Thinking...... in the alien university is a move into a whirlpool of nothingness, a “nocturnal space”, where “[d]arkness fills it like a content; it is full, but full of the nothingness of everything.” (Levinas, 2001, p.53). In the alien university thinking is not situated, and instead of rhizomes, and assemblages of thought......, there is merely an imposing and nightly “swarming of points.” (ibid.). There is no place for the alien university, and exactly this exile of thought makes possible the move beyond postmodernism and the mentality of political crisis. The alien university is not in the future as such, but it is not entirely...

  13. Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress

    Directory of Open Access Journals (Sweden)

    Soni KK

    2016-12-01

    Full Text Available Kiran Kumar Soni,1 Hye Kyung Kim,2 Bo Ram Choi,1 Keshab Kumar Karna,1 Jae Hyung You,1 Jai Seong Cha,1 Yu Seob Shin,1 Sung Won Lee,3 Chul Young Kim,4 Jong Kwan Park1 1Department of Urology, Institute for Medical Sciences, Chonbuk National University Medical School – Biomedical Research and Institute and Clinical Trial Center for Medical Devices, Chonbuk National University Hospital, Jeonju, 2College of Pharmacy, Kyungsung University, Busan, 3Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University Medical School, Seoul, 4College of Pharmacy, Hanyang University, Ansan, Republic of Korea Abstract: Cisplatin (CIS is used in the treatment of cancer, but its nonspecific systemic actions lead to toxic effects on other parts of the body. This study investigated the severity of CIS toxicity by increasing its dose over a constant time period. Sprague Dawley rats were divided into five treatment groups and control group with CIS (2, 4, 6, 8, and 10 mg/kg administered intraperitoneally for 5 days. The body and organs were weighed, epididymal sperm was counted, and sperm motility and sperm apoptosis were evaluated. Blood samples were evaluated for complete blood count, reactive oxygen and nitrogen species, malondialdehyde levels, and total testosterone. The testicular tissue was examined for steroidogenic acute regulatory protein and endoplasmic reticulum stress protein. Epididymal sperm was collected for CatSper Western blot. The toxic effects of different doses of CIS on the testis and kidney were compared histologically. The weights of body, testis, epididymis, prostate, seminal vesicle, and kidney; sperm count; sperm motility; steroidogenic acute regulatory protein level; and epididymal sperm count were significantly lower in the CIS-treated groups than in the control group. In contrast, sperm apoptosis, plasma reactive oxygen and nitrogen species, and malondialdehyde, testosterone, red blood cell

  14. File list: DNS.Emb.20.AllAg.Embryonic_trunk [Chip-atlas[Archive

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  15. Universics: a Theory of Universes of Discourse for Metamathematics and Foundations

    Directory of Open Access Journals (Sweden)

    Ioachim Drugus

    2016-04-01

    Full Text Available A new type of structures called ``universes'' is introduced to subsume the ``von Neumann universe'', ``Grothendieck universes'' and ``universes of discourse'' of various theories. Theories are also treated as universes, ``universes of ideas'', where ``idea" is a common term for assertions and terms. A dualism between induction and deduction and their treatment on a common basis is provided. The described approach referenced as ``universics'' is expected to be useful for metamathematical analysis and to serve as a foundation for mathematics. As a motivation for this research served the Harvey Friedman's desideratum to develop a foundational theory based on ``induction construction'', possibly comprising set theory. This desideratum emerged due to ``foundational incompleteness'' of set theory. The main results of this paper are an explication of the notion ``foundational completeness'', and a generalization of well-founded-ness.

  16. Runaway universe

    Energy Technology Data Exchange (ETDEWEB)

    Davies, P

    1978-01-01

    The subject is covered in chapters entitled: the emerging universe (general introduction, history of astronomical and cosmological research, origins, the expanding universe, stars, galaxies, electromagnetic radiation); primeval fire (the big bang model, origin of the elements, properties of the elements and of sub-atomic particles); order out of chaos (galactic evolution, star formation, nuclear fusion, the solar system, origin of life on Earth); a star called Sol (properties of the sun and of other stars); life in the universe; the catastrophe principle (the rise and fall of cosmic order); stardoom (star evolution, neutron stars); black holes and superholes (gravitational collapse); technology and survival; the dying universe (second law of thermodynamics); worlds without end (cosmological models).

  17. University Pedagogy for Assistant Professors at Aalborg University (Part 2)

    DEFF Research Database (Denmark)

    Kolmos, Anette; Krogh, Lone

    2003-01-01

    In issue 1-2003, Anette Kolmos and Lone Krogh reported on the two-semester study course " University Pedagogy for Assistant Professors at Aalborg University (DK)". Now, in part 2, they are adressing guidelines for supervison and advising of assistant professors in the university teacher education...

  18. Competitive universities need to internationalize learning: Perspectives from three European universities

    Directory of Open Access Journals (Sweden)

    Ana Maria Lara

    2009-07-01

    Full Text Available The process of restructuring European universities in order to harmonize their educational systems is rapidly approaching a key milestone as 2010 looms large on the horizon. This paper describes an approach to the European Higher Education Area (EHEA based on a real case study of students that belong to five European Universities (University of Burgos, Technical University of Valencia, University of Valladolid, University of Basque Country and University of Applied Sciences Cologne. The objective of this paper is two-fold: on the one hand, to analyze from the student’s point of view how they value the restructuring of teaching as a result of the Bologna process and what are the implications for students with regards to both their academic qualifications and their future incorporation into the labour market; and, on the other hand, to deduce from the results obtained recommendations which may help to guide teachers towards successful internationalization and collaboration between interuniversity networks, as well as achieving greater standards of quality within university teaching. Only this would permit an environment in which students are capable of developing the necessary competences, and put into practice learning outcomes. The results show that students value communication, innovative proposals and cooperation between universities; the internationalization of knowledge between universities has been positively accepted and this has motivated research to place a stronger focus on this aspect; it impacts strongly on scientific productivity, improves the quality of education offered by the teaching staff, and leads to greater student mobility. This strategy is intrinsically linked to learning from local experiences shared by members of the same university as well as from more global experiences made available through inter-university networks. It implies being willing to listen, to communicate, to engage in dialogue and means that we must

  19. University Performance Management

    DEFF Research Database (Denmark)

    For the last two decades the Danish Universities have felt the impact of the international trend towards implementation of New Public Management. The results are seen in the implementation of new hierarchical governance structures and contractual governance system including market based quantitat......For the last two decades the Danish Universities have felt the impact of the international trend towards implementation of New Public Management. The results are seen in the implementation of new hierarchical governance structures and contractual governance system including market based...... quantitative measurement systems for resource allocation and performance evaluation. Compared to other countries the changes in performance measurements and governance of the Danish universities are radical and the Minister of Science heralded them as "the greatest change in university management since...... the founding of Copenhagen University in 1479". The changes took place with surprisingly little resistance from university scholars. The articles in this anthology investigate the origins and rationales for the silent managerial revolution at Danish Universities and the radical implications for the identity...

  20. [Changes in body weight of the university students at university].

    Science.gov (United States)

    Soto Ruiz, María Nelia; Aguinaga Ontonso, Inés; Canga Armayor, Navidad; Guillén-Grima, Francisco; Hermoso de Mendoza, Juana; Serrano Monzo, Inmaculada; Marín Fernández, Blanca

    2015-06-01

    One of the strategies for the prevention of the obesity is the identification of critical periods of gain weight. Some studies confirm gain weight during the university period. The purpose of the present study was to determine the changes in the body weight of the university students in Navarre. Prospective cohort study. Public University of Navarre and the University of Navarre, in Pamplona. Study examined weight change among 452 students attending at university in Pamplona, during first and third course. Four hundred and fifty two students completed the questionnaire. Weight and height were measures and body mass index was calculated. The mean body weight increased 0,600 kg, 1,8 kg for males and no change in body weight was observed in female. 44,7 % of students gained weight (60,8 % of men and 36,8 % of women), and the gain weight was of 3,4 kg. University years are a critical factor for the gain weight, particularly males. Consideration of this, is necessary the development of effective weight gain prevention strategies during the university. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  1. Sustaining Community-University Collaborations: The Durham University Model

    Directory of Open Access Journals (Sweden)

    Andrew Russell

    2011-11-01

    Full Text Available Durham University has initiated a community outreach and engagement program based on an evolving multifaceted model. This article analyses the components of the model and looks at how our work at Durham has become increasingly embedded in the structures and processes of the university as it has developed. The strengths and weaknesses in what has been achieved are highlighted, as is the future vision for the further development of this innovative community-university program. Keywords Public engagement; community partnerships; employer supported volunteering; corporate social responsibility

  2. University IPRs and knowledge transfer : is university ownership more efficient?

    NARCIS (Netherlands)

    Crespi, G.A.; Geuna, A.; Nomaler, Z.O.; Verspagen, B.

    2010-01-01

    This paper addresses an issue that has been largely ignored so far in the empirical literature on the role of patents in university-industry knowledge transfer: does it matter who owns the patents on university research? We observe that especially in Europe, many patents in which university

  3. Early-onset sleep defects in Drosophila models of Huntington's disease reflect alterations of PKA/CREB signaling

    Science.gov (United States)

    Gonzales, Erin D.; Tanenhaus, Anne K.; Zhang, Jiabin; Chaffee, Ryan P.; Yin, Jerry C.P.

    2016-01-01

    Huntington's disease (HD) is a progressive neurological disorder whose non-motor symptoms include sleep disturbances. Whether sleep and activity abnormalities are primary molecular disruptions of mutant Huntingtin (mutHtt) expression or result from neurodegeneration is unclear. Here, we report Drosophila models of HD exhibit sleep and activity disruptions very early in adulthood, as soon as sleep patterns have developed. Pan-neuronal expression of full-length or N-terminally truncated mutHtt recapitulates sleep phenotypes of HD patients: impaired sleep initiation, fragmented and diminished sleep, and nighttime hyperactivity. Sleep deprivation of HD model flies results in exacerbated sleep deficits, indicating that homeostatic regulation of sleep is impaired. Elevated PKA/CREB activity in healthy flies produces patterns of sleep and activity similar to those in our HD models. We were curious whether aberrations in PKA/CREB signaling were responsible for our early-onset sleep/activity phenotypes. Decreasing signaling through the cAMP/PKA pathway suppresses mutHtt-induced developmental lethality. Genetically reducing PKA abolishes sleep/activity deficits in HD model flies, restores the homeostatic response and extends median lifespan. In vivo reporters, however, show dCREB2 activity is unchanged, or decreased when sleep/activity patterns are abnormal, suggesting dissociation of PKA and dCREB2 occurs early in pathogenesis. Collectively, our data suggest that sleep defects may reflect a primary pathological process in HD, and that measurements of sleep and cAMP/PKA could be prodromal indicators of disease, and serve as therapeutic targets for intervention. PMID:26604145

  4. Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study

    Science.gov (United States)

    Sanhueza, Jorge A.; Zambrano, Tomás; Bahamondes-Avila, Carlos; Salazar, Luis A.

    2016-01-01

    Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety (5HTT, CRH2R, ACE, NK1R, 5HT1AR and CRF-BP) on the physical capability and sports performance in triathletes. One hundred and ninety two (192) unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11) with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders. Key points Genetic factors influencing sports performance in the Chilean population are unknown. Differential outcomes from athletes who completed a triathlon competition were associated with five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11). We show that genetic variants within stress- and anxiety-related genes affect athletic performance. PMID:27928199

  5. Horizontal transfer of transposons between and within crustaceans and insects.

    Science.gov (United States)

    Dupeyron, Mathilde; Leclercq, Sébastien; Cerveau, Nicolas; Bouchon, Didier; Gilbert, Clément

    2014-01-29

    Horizontal transfer of transposable elements (HTT) is increasingly appreciated as an important source of genome and species evolution in eukaryotes. However, our understanding of HTT dynamics is still poor in eukaryotes because the diversity of species for which whole genome sequences are available is biased and does not reflect the global eukaryote diversity. In this study we characterized two Mariner transposable elements (TEs) in the genome of several terrestrial crustacean isopods, a group of animals particularly underrepresented in genome databases. The two elements have a patchy distribution in the arthropod tree and they are highly similar (>93% over the entire length of the element) to insect TEs (Diptera and Hymenoptera), some of which were previously described in Ceratitis rosa (Crmar2) and Drosophila biarmipes (Mariner-5_Dbi). In addition, phylogenetic analyses and comparisons of TE versus orthologous gene distances at various phylogenetic levels revealed that the taxonomic distribution of the two elements is incompatible with vertical inheritance. We conclude that the two Mariner TEs each underwent at least three HTT events. Both elements were transferred once between isopod crustaceans and insects and at least once between isopod crustacean species. Crmar2 was also transferred between tephritid and drosophilid flies and Mariner-5 underwent HT between hymenopterans and dipterans. We demonstrate that these various HTTs took place recently (most likely within the last 3 million years), and propose iridoviruses and/or Wolbachia endosymbionts as potential vectors of these transfers.

  6. KIDS Nuclear Energy Density Functional: 1st Application in Nuclei

    Science.gov (United States)

    Gil, Hana; Papakonstantinou, Panagiota; Hyun, Chang Ho; Oh, Yongseok

    We apply the KIDS (Korea: IBS-Daegu-Sungkyunkwan) nuclear energy density functional model, which is based on the Fermi momentum expansion, to the study of properties of lj-closed nuclei. The parameters of the model are determined by the nuclear properties at the saturation density and theoretical calculations on pure neutron matter. For applying the model to the study of nuclei, we rely on the Skyrme force model, where the Skyrme force parameters are determined through the KIDS energy density functional. Solving Hartree-Fock equations, we obtain the energies per particle and charge radii of closed magic nuclei, namely, 16O, 28O, 40Ca, 48Ca, 60Ca, 90Zr, 132Sn, and 208Pb. The results are compared with the observed data and further improvement of the model is shortly mentioned.

  7. Stemcell Information: SKIP000385 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available Teratoma formation ... Yes ... Yes ... National Research Institute for Child Health and Development htt...p://www.ncbi.nlm.nih.gov/geo/ Akihiro Umezawa 梅澤 明弘 Available National Research Institute for Child Health a

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  18. The expanding universe

    CERN Document Server

    Lew, Kristi

    2011-01-01

    People have always been fascinated with the stars above and the universe that contains them. Over the years, astronomers have developed numerous theories to explain how the universe began, how it works, and what its ultimate fate will be. But all of the scientists' questions are far from answered. The Expanding Universe goes beyond the creation of the universe to explain how scientists think the universe works, grows, and changes, including what great thinkers Isaac Newton and Albert Einstein had to say about its fate. Readers will also learn about how researchers are slowly shedding light on

  19. A probabilistic approach to delineating functional brain regions

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Svarer, Claus; Frokjaer, Vibe G

    2009-01-01

    The purpose of this study was to develop a reliable observer-independent approach to delineating volumes of interest (VOIs) for functional brain regions that are not identifiable on structural MR images. The case is made for the raphe nuclei, a collection of nuclei situated in the brain stem known...... to be densely packed with serotonin transporters (5-hydroxytryptaminic [5-HTT] system). METHODS: A template set for the raphe nuclei, based on their high content of 5-HTT as visualized in parametric (11)C-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile PET images, was created for 10...... healthy subjects. The templates were subsequently included in the region sets used in a previously published automatic MRI-based approach to create an observer- and activity-independent probabilistic VOI map. The probabilistic map approach was tested in a different group of 10 subjects and compared...

  20. Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD.

    Science.gov (United States)

    Wang, Yajie; Jiang, Xue; Zhang, Lihai; Wang, Lihong; Li, Zhu; Sun, Wuzhuang

    2014-01-01

    This study is conducted to investigate an effect of simvastatin on cigarette smoke-induced COPD. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of simvastatin. Heart and lung tissues were harvested for histopathologic and morphometric analysis. Body weight of rat, mean liner intercept (MLI), mean alveolar number (MAN), lung function test, mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and 5-HTT level in serum and BALF were examined in experimental rats, respectively. Application of simvastatin mitigated peribronchiolar inflammation and pulmonary bullae formed in the smoke-exposed lungs with weight gain as compared to the smoking rats (P reversal of lung function decline (all P reverses lung function decline and attenuates structural impairments of lung and right ventricle possibly through reducing 5-HTT content in the model of COPD.

  1. Research-University Governance in Thailand: The Case of Chulalongkorn University

    Science.gov (United States)

    Rungfamai, Kreangchai

    2017-01-01

    This specific case of Chulalongkorn University (CU), Thailand, is useful to readers who are interested in comparative aspect of the experiences of research universities in the South East Asian context. This paper aims to provide a description of the environments, changes, and university stakeholders' perceptions in terms of governance arrangements…

  2. University Technology Transfer

    Directory of Open Access Journals (Sweden)

    Mike Cox

    2004-09-01

    Full Text Available This article describes the experiences and general observations of the author at Heriot-Watt University and concerns the transfer of university technology for the purposes of commercialisation. Full commercial exploitation of a university invention generally requires transferring that technology into the industrial arena, usually either by formation of a new company or licensing into an existing company. Commercialisation activities need to be carried out in unison with the prime activities of the university of research and teaching. Responsibility for commercialising university inventions generally rests with a specific group within the university, typically referred to as the technology transfer group. Each technology transfer should be considered individually and appropriate arrangements made for that particular invention. In general, this transfer process involves four stages: identification, evaluation, protection and exploitation. Considerations under these general headings are outlined from a university viewpoint. A phased approach is generally preferred where possible for the evaluation, protection and exploitation of an invention to balance risk with potential reward. Evaluation of the potential opportunity for a university invention involves essentially the same considerations as for an industrial invention. However, there are a range of commercial exploitation routes and potential deals so that only general guidelines can be given. Naturally, the final deal achieved is that which can be negotiated. The potential rewards for the university and inventor are both financial (via licensing income and equity realisation and non-financial.

  3. Universe of constant

    Science.gov (United States)

    Yongquan, Han

    2016-10-01

    The ideal gas state equation is not applicable to ordinary gas, it should be applied to the Electromagnetic ``gas'' that is applied to the radiation, the radiation should be the ultimate state of matter changes or initial state, the universe is filled with radiation. That is, the ideal gas equation of state is suitable for the Singular point and the universe. Maybe someone consider that, there is no vessel can accommodate radiation, it is because the Ordinary container is too small to accommodate, if the radius of your container is the distance that Light through an hour, would you still think it can't accommodates radiation? Modern scientific determinate that the radius of the universe now is about 1027 m, assuming that the universe is a sphere whose volume is approximately: V = 4.19 × 1081 cubic meters, the temperature radiation of the universe (cosmic microwave background radiation temperature of the universe, should be the closest the average temperature of the universe) T = 3.15k, radiation pressure P = 5 × 10-6 N / m 2, according to the law of ideal gas state equation, PV / T = constant = 6 × 1075, the value of this constant is the universe, The singular point should also equal to the constant Author: hanyongquan

  4. File list: Oth.NoD.10.Epitope_tags.AllCell [Chip-atlas[Archive

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  8. File list: Oth.Adl.20.AllAg.Adult_male_fatbody [Chip-atlas[Archive

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  11. Experiment list: SRX122491 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ntibody=Atf3 || treatment=LPS || time=60 min || chip antibody manufacturer 1=Santa Cruz || chip antibody cat...alog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 htt

  12. Experiment list: SRX122468 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available antibody=Rela || treatment=LPS || time=0 min || chip antibody manufacturer 1=Bethyl || chip antibody catalo...g number 1=A301-824A || chip antibody manufacturer 2=Santa Cruz || chip antibody catalog number 2=sc-372 htt

  13. Experiment list: SRX122409 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ip antibody=Irf1 || treatment=LPS || time=60 min || chip antibody manufacturer 1=Abcam || chip antibody cata...log number 1=ab52520 || chip antibody manufacturer 2=Santa Cruz || chip antibody catalog number 2=sc-640 htt

  14. Experiment list: SRX122490 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ntibody=Atf3 || treatment=LPS || time=30 min || chip antibody manufacturer 1=Santa Cruz || chip antibody cat...alog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 htt

  15. Experiment list: SRX122492 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ntibody=Atf3 || treatment=LPS || time=60 min || chip antibody manufacturer 1=Santa Cruz || chip antibody cat...alog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 htt

  16. Avoiding student infection during a Middle East respiratory syndrome (MERS) outbreak: a single medical school experience.

    Science.gov (United States)

    Park, Seung Won; Jang, Hye Won; Choe, Yon Ho; Lee, Kyung Soo; Ahn, Yong Chan; Chung, Myung Jin; Lee, Kyu-Sung; Lee, Kyunghoon; Han, Taehee

    2016-06-01

    In outbreaks of infectious disease, medical students are easily overlooked in the management of healthcare personnel protection although they serve in clinical clerkships in hospitals. In the early summer of 2015, Middle East respiratory syndrome (MERS) struck South Korea, and students of Sungkyunkwan University School of Medicine (SKKUSOM) were at risk of contracting the disease. The purpose of this report is to share SKKUSOM's experience against the MERS outbreak and provide suggestions for medical schools to consider in the face of similar challenges. Through a process of reflection-on-action, we examined SKKUSOM's efforts to avoid student infection during the MERS outbreak and derived a few practical guidelines that medical schools can adopt to ensure student safety in outbreaks of infectious disease. The school leadership conducted ongoing risk assessment and developed contingency plans to balance student safety and continuity in medical education. They rearranged the clerkships to another hospital and offered distant lectures and tutorials. Five suggestions are extracted for medical schools to consider in infection outbreaks: instant cessation of clinical clerkships; rational decision making on a school closure; use of information technology; constant communication with hospitals; and open communication with faculty, staff, and students. Medical schools need to take the initiative and actively seek countermeasures against student infection. It is essential that medical schools keep constant communication with their index hospitals and the involved personnel. In order to assure student learning, medical schools may consider offering distant education with online technology.

  17. The inflationary universe

    International Nuclear Information System (INIS)

    Linde, A.D.

    1984-01-01

    According to the inflationary universe scenario the universe in the very early stages of its evolution was exponentially expanding in the unstable vacuum-like state. At the end of the exponential expansion the energy of the unstable vacuum transforms into the energy of hot dense matter. Recently it was realised that the exponential expansion of the universe naturally occurs in a wide class of realistic theories of elementary particles. The inflationary universe scenario makes it possible to obtain a simple solution to many longstanding cosmological problems and leads to a crucial modification of the standard point of view of the large-scale structure of the universe. (author)

  18. The inflationary universe

    International Nuclear Information System (INIS)

    Guth, A.; Steinhardt, P.

    1993-01-01

    According to the inflationary model, the universe had a brief period of extraordinary rapid expansion, or inflation, during which its diameter increased by a factor at least 10 25 times larger (and perhaps much larger still) than had been previously thought. All the matter and energy in the universe could have been created from virtually nothing. Features of this article are: comparison of standard and inflationary modes, the horizon problem, the geometry of the universe, spontaneous symmetry breaking and the Higgs mechanism (energy density of the Higgs fields), the flatness problem, the new inflationary universe (new Higgs fields and false vacuum), conserved quantities in the universe. 12 figs., 11 refs

  19. Improving University Ranking to Achieve University Competitiveness by Management Information System

    Science.gov (United States)

    Dachyar, M.; Dewi, F.

    2015-05-01

    One way to increase university competitiveness is through information system management. A literature review was done to find information system factors that affect university performance in Quacquarelli Symonds (QS) University Ranking: Asia evaluation. Information system factors were then eliminated using Delphi method through consensus of 7 experts. Result from Delphi method was used as measured variables in PLS-SEM. Estimation with PLS-SEM method through 72 respondents shows that the latent variable academic reputation and citation per paper have significant correlation to university competitiveness. In University of Indonesia (UI) the priority to increase university competitiveness as follow: (i) network building in international conference, (ii) availability of research data to public, (iii) international conference information, (iv) information on achievements and accreditations of each major, (v) ease of employment for alumni.

  20. University Autonomy in the Context of University-Society, State and Market/Capital Relations

    Directory of Open Access Journals (Sweden)

    Dicle ÖZCAN

    2016-05-01

    Full Text Available This study focuses on how the concept university autonomy which constitutes one of the most tangible indicators of academic freedom is positioned in the context of university's relations with state, society and market and concentrates on the possibility of university autonomy. From the emergence of universities in the Middle Age to the modern universities of the present, the concepts of university autonomy and academic freedom have been maintaining their actuality with a growing interest. In the light of studies in Turkey, the purpose of this study is to discuss the change of university autonomy in the historical process and where it can be positioned in the context of building blocks of university autonomy concept and the recent relationship between universities and market-industry-business world.

  1. PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy

    Directory of Open Access Journals (Sweden)

    Byeon HJ

    2015-01-01

    Full Text Available Hyeong Jun Byeon,1 Insoo Kim,1 Ji Su Choi,1 Eun Seong Lee,2 Beom Soo Shin,3 Yu Seok Youn11Department of Pharmaceutical Sciences, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 2Division of Biotechnology, The Catholic University of Korea, Bucheon-si, Republic of Korea; 3Department of Pharmacy, College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Republic of KoreaAbstract: The aim of the current study was to investigate the antitumor potential of poly(D,L-lactic-co-glycolic acid microspheres (PLGA MSs containing polyethylene glycol (PEG-conjugated (PEGylated tumor necrosis factor–related apoptosis-inducing ligand (PEG-TRAIL. PEG-TRAIL PLGA MSs were prepared by using a water-in-oil-in-water double-emulsion method, and the apoptotic activities of supernatants released from the PLGA MSs at days 1, 3, and 7 were examined. The antitumor effect caused by PEG-TRAIL PLGA MSs was evaluated in pancreatic Mia Paca-2 cell-xenografted mice. PEG-TRAIL PLGA MS was found to be spherical and 14.4±1.06 µm in size, and its encapsulation efficiency was significantly greater than that of TRAIL MS (85.7%±4.1% vs 43.3%±10.9%, respectively. The PLGA MS gradually released PEG-TRAIL for 14 days, and the released PEG-TRAIL was shown to have clear apoptotic activity in Mia Paca-2 cells, whereas TRAIL released after 1 day had a negligible activity. Finally, PEG-TRAIL PLGA MS displayed remarkably greater antitumor efficacy than blank or TRAIL PLGA MS in Mia Paca-2 cell-xenografted mice in terms of tumor volume and weight, apparently due to increased stability and well-retained apoptotic activity of PEG-TRAIL in PLGA MS. We believe that this PLGA MS system, combined with PEG-TRAIL, should be considered a promising candidate for treating pancreatic cancer.Keywords: Poly(D,L-lactic-co-glycolic acid, controlled release, PEGylation, TRAIL, pancreatic cancer

  2. Motivating University Researchers

    NARCIS (Netherlands)

    Hendriks, P.H.J.; Alves de Sousa, C.A.

    2008-01-01

    This paper presents an empirical investigation into how universities approach the need and means for motivating university researchers through their management practices. The role of work motivation for this group deserves attention because pressures from outside and within the universities are said

  3. File list: InP.Oth.20.AllAg.Pancreas_and_brain [Chip-atlas[Archive

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  6. Production of 2nd generation Bioethanol from Lucerne - Optimization of Hydrothermal Pretreatment

    DEFF Research Database (Denmark)

    Thomsen, Sune Tjalfe; Jensen, Morten; Schmidt, Jens Ejbye

    2012-01-01

    Lucerne (Medicago sativa) has many qualities associated with sustainable agriculture such as nitrogen fixation and high biomass yield. Therefore, there is interest in whether lucerne is a suitable biomass substrate for bioethanol production, and if hydrothermal pretreatment (HTT) of lucerne impro...

  7. Understanding the Biology and Technology of ToxCast and Tox21 Assays

    Science.gov (United States)

    The ToxCast high-throughput toxicity (HTT) testing methods have been developed to evaluate the hazard potential of diverse environmental, industrial and consumer product chemicals. The main goal is prioritizing the compounds of greatest concern for more detailed toxicological stu...

  8. Perseverative instrumental and Pavlovian responding to conditioned stimuli in serotonin transporter knockout rats

    NARCIS (Netherlands)

    Nonkes, L.J.P.; Homberg, J.R.

    2013-01-01

    Environmental stimuli can influence behavior via the process of Pavlovian conditioning. Recent genetic research suggests that some individuals are more sensitive to environmental stimuli for behavioral guidance than others. One important mediator of this effect is serotonin transporter (5-HTT)

  9. File list: InP.NoD.05.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: InP.NoD.20.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. 20180416 - Understanding the Biology and Technology of ToxCast and Tox21 Assays (SETAC Durham NC)

    Science.gov (United States)

    The ToxCast high-throughput toxicity (HTT) testing methods have been developed to evaluate the hazard potential of diverse environmental, industrial and consumer product chemicals. The main goal is prioritizing the compounds of greatest concern for more detailed toxicological stu...

  12. File list: InP.NoD.50.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: InP.NoD.20.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: NoD.Adl.10.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain

    NARCIS (Netherlands)

    Doelen, R.H.A. van der; Arnoldussen, I.A.C.; Ghareh, H.; Och, L. van; Homberg, J.R.; Kozicz, L.T.

    2015-01-01

    The interaction between childhood maltreatment and the serotonin transporter (5-HTT) gene linked polymorphic region has been associated with increased risk to develop major depression. This Gene x Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid

  1. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT...

  2. Experiment list: SRX122551 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available antibody=Stat1 || treatment=LPS || time=0 min || chip antibody manufacturer 1=Santa Cruz || chip antibody ca...talog number 1=sc-346 || chip antibody manufacturer 2=Bethyl || chip antibody catalog number 2=A302-753A htt

  3. Georgetown University and Hampton University Prostate Cancer Undergraduate Fellowship Program

    Science.gov (United States)

    2018-01-01

    goals. The first goal was to integrate upper level undergraduate students from Hampton University into the Georgetown Lombardi Comprehensive Cancer...upper level undergraduate Biology and Biochemistry Majors from Hampton University to work throughout the summer participating in prostate cancer...Dominican Republic summer 2017 Marissa Willis HU-GU Fellow Summer 2016 (Notario lab) Biology Major Hampton University, class of 2018, Math and

  4. Collaboration Between Universities: An effective way of sustaining community-university partnerships?

    Directory of Open Access Journals (Sweden)

    Jonathan Pratt

    2011-11-01

    Full Text Available This article highlights some of the opportunities and challenges that collaboration between higher education institutions (HEIs can bring to the development of sustainable community-university partnerships. In particular, it explores the potential for universities to collaborate on building effective engagement mechanisms (such as helpdesks, ‘hub and spoke’ contact models, and research groups to review ideas for activities that will support an ongoing flow of new projects and partnerships over time. It draws on evidence gathered from the evaluation and coordination of the South East Coastal Communities (SECC program, an almost unique experiment in collaboration between English universities. In an ‘age of austerity’, opportunities to reduce costs without damaging core services are of particular interest to public funding bodies. The article suggests that collaboration between universities may be an efficient and effective way of engaging with local communities, but that it is not cost-free, and high-level strategic buy-in within HEIs is required if community-university partnerships are to thrive in the current higher education funding environment. The article also suggests that there may be a geographic dimension to effective collaboration between universities in both community-university partnership work and the mechanisms that support community engagement. Inter-university collaboration across the whole region covered by the SECC program has been much weaker than collaboration at a subregional level and within ‘city-regions’ in particular. This raises a key question: does the natural geography for effective collaboration between universities need to reflect, at least in part, the geographies of communities themselves, in terms of lived experiences and/or community representation? Such a debate has interesting and timely parallels in the United Kingdom, where the new coalition government is bringing about a fundamental shift in the

  5. Intelligent Universe

    Energy Technology Data Exchange (ETDEWEB)

    Hoyle, F

    1983-01-01

    The subject is covered in chapters, entitled: chance and the universe (synthesis of proteins; the primordial soup); the gospel according to Darwin (discussion of Darwin theory of evolution); life did not originate on earth (fossils from space; life in space); the interstellar connection (living dust between the stars; bacteria in space falling to the earth; interplanetary dust); evolution by cosmic control (microorganisms; genetics); why aren't the others here (a cosmic origin of life); after the big bang (big bang and steady state); the information rich universe; what is intelligence up to; the intelligent universe.

  6. An extension of hypotheses regarding rapid-acting, treatment-refractory, and conventional antidepressant activity of dextromethorphan and dextrorphan.

    Science.gov (United States)

    Lauterbach, Edward C

    2012-06-01

    It was previously hypothesized that dextromethorphan (DM) and dextrorphan (DX) may possess antidepressant properties, including rapid and conventional onsets of action and utility in treatment-refractory depression, based on pharmacodynamic similarities to ketamine. These similarities included sigma-1 (σ(1)) agonist and NMDA antagonist properties, calcium channel blockade, muscarinic binding, serotonin transporter (5HTT) inhibition, and μ receptor potentiation. Here, six specific hypotheses are developed in light of additional mechanisms and evidence. Comparable potencies to ketamine for DM and DX are detailed for σ(1) (DX>DM>ketamine), NMDA PCP site (DX>ketamine>DM), and muscarinic (DX>ketamine>DM) receptors, 5HTT (DM>DX≫ketamine), and NMDA antagonist potentiation of μ receptor stimulation (DM>ketamine). Rapid acting antidepressant properties of DM include NMDA high-affinity site, NMDR-2A, and functional NMDR-2B receptor antagonism, σ(1) stimulation, putative mTOR activation (by σ(1) stimulation, μ potentiation, and 5HTT inhibition), putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, σ(1) stimulation, μ potentiation, and 5HTT inhibition), and dendritogenesis, spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and σ(1) and mTOR signaling. Those for dextrorphan include NMDA high-affinity site and NMDR-2A antagonism, σ(1) stimulation, putative mTOR activation (by σ(1) stimulation and ß adrenoreceptor stimulation), putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, σ(1) stimulation, ß stimulation, and μ antagonism), and dendritogenesis, spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and σ(1) and mTOR signaling. Conventional antidepressant properties for dextromethorphan and dextrorphan include 5HTT and norepinephrine transporter inhibition, σ(1) stimulation, NMDA and PCP antagonism, and possible serotonin 5HT1b/d receptor stimulation. Additional properties for

  7. Our Particle Universe

    Indian Academy of Sciences (India)

    and “why is the universe the way it is?” Not long before ... to each other. The interactions of particles in the universe ... theory by Jean Perrin in 1908 convinced people that atoms and ..... ing the origin and evolution of our universe13. This is an ...

  8. The rotating universe

    International Nuclear Information System (INIS)

    Ruben, G.; Treder, H.J.

    1987-01-01

    For a long time the question whether the universe rotates or not is discussed. Aspects of Huygens, Newton, Mach and other important historical scientists in this field are reported. The investigations of the mathematician Kurt Groedel in order to prove the rotation of the universe are illustrated. Kurt Groedel has shown that Einstein's gravitational equations of general relativity theory and the cosmological postulate of global homogeneity of cosmic matter (that is the Copernical principle) are not contradictionary to a rotating universe. Abberation measurements, position determination by means of radiointerferometry and methods for the determination of the rotation of the universe from the isotropy of the background radiation are presented. From these experiments it can be concluded that the universe seems not to rotate as already Einstein expected

  9. CHINA‘S RADIO AND TV UNIVERSITIES AND THE BRITISH OPEN UNIVERSITY: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Reviewed by Desmond KEEGAN

    2010-01-01

    Full Text Available This book is a major contribution to the fields of distance education research, the field of comparative education and to the history of Chinese and British education.The book undertakes an impossible task: the comparative study of China‘s Radio and TV universities and of the British Open University. The task is impossible because the two entities to be compared are essentially disparate. The British Open University (OUUK is a single university set up at Milton Keynes in the United Kingdom by Royal Charter. China‘s Radio and TV universities, known as the Dianda system, is a network of 45 open universities set up all over China. The essence of the success of the British Open University was its creation as a full university, offering its own university degrees on the same level as all the other universities in the country. The Dianda institutions were set up in what Wei calls the ‗adult higher education sector‘ in China, offering what Wei calls sub-degrees and always regarded as inferior both to the great Chinese universities (Beijing University, Qinghua University, Fudan

  10. Mathematics at University

    DEFF Research Database (Denmark)

    Winsløw, Carl

    2015-01-01

    Mathematics is studied in universities by a large number of students. At the same time it is a field of research for a (smaller) number of university teachers. What relations, if any, exist between university research and teaching of mathematics? Can research “support” teaching? What research...... and what teaching? In this presentation we propose a theoretical framework to study these questions more precisely, based on the anthropological theory of didactics. As a main application, the links between the practices of mathematical research and university mathematics teaching are examined...

  11. Quantitative fluorescence loss in photobleaching for analysis of protein transport and aggregation

    Directory of Open Access Journals (Sweden)

    Wüstner Daniel

    2012-11-01

    Full Text Available Abstract Background Fluorescence loss in photobleaching (FLIP is a widely used imaging technique, which provides information about protein dynamics in various cellular regions. In FLIP, a small cellular region is repeatedly illuminated by an intense laser pulse, while images are taken with reduced laser power with a time lag between the bleaches. Despite its popularity, tools are lacking for quantitative analysis of FLIP experiments. Typically, the user defines regions of interest (ROIs for further analysis which is subjective and does not allow for comparing different cells and experimental settings. Results We present two complementary methods to detect and quantify protein transport and aggregation in living cells from FLIP image series. In the first approach, a stretched exponential (StrExp function is fitted to fluorescence loss (FL inside and outside the bleached region. We show by reaction–diffusion simulations, that the StrExp function can describe both, binding/barrier–limited and diffusion-limited FL kinetics. By pixel-wise regression of that function to FL kinetics of enhanced green fluorescent protein (eGFP, we determined in a user-unbiased manner from which cellular regions eGFP can be replenished in the bleached area. Spatial variation in the parameters calculated from the StrExp function allow for detecting diffusion barriers for eGFP in the nucleus and cytoplasm of living cells. Polyglutamine (polyQ disease proteins like mutant huntingtin (mtHtt can form large aggregates called inclusion bodies (IB’s. The second method combines single particle tracking with multi-compartment modelling of FL kinetics in moving IB’s to determine exchange rates of eGFP-tagged mtHtt protein (eGFP-mtHtt between aggregates and the cytoplasm. This method is self-calibrating since it relates the FL inside and outside the bleached regions. It makes it therefore possible to compare release kinetics of eGFP-mtHtt between different cells and

  12. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531 influences the analgesic response to the short acting opioid Remifentanil in humans

    Directory of Open Access Journals (Sweden)

    Schalling Martin

    2009-07-01

    Full Text Available Abstract Background There is evidence from animal studies that serotonin (5-HT can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531. The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS. All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. Results At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG as compared to those with high expression(LA/LA, p Conclusion This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of

  13. (Re)Discovering University Autonomy

    DEFF Research Database (Denmark)

    This book challenges traditional approach to university autonomy which is based on four pillars: organisational, financial, human resource, and academic. The main thesis is that a fuller understanding of university autonomy can only be obtained through a more holistic view of the complex inter......-relationships between stakeholders and policies which can reinforce and equally pull in opposite directions. The holistic view is expressed in a model of institutional university autonomy that brings together the traditional basic four pillars of autonomy, and five interfaces: government–university; university......–university staff; academic staff–students; university–business; and university–internationalisation. This model is explored through international case studies that give new insights and reinforce our understanding that the issues relating to institutional university autonomy are complex, interactive and genuinely...

  14. Kyoto University-National Taiwan University International Symposium "Social Cognitive Biology on Representation of Environment

    OpenAIRE

    Saiki, Jun

    2016-01-01

    Sponsored by Kyoto University, National Taiwan University; Cosponsored by Unit for Advanced Studies of the Human Mind, Kyoto University, Kokoro Research Center, Kyoto University, Supported by Supporting Program for InteRaction-based Initiative Team Studies (SPIRITS), Kyoto University

  15. Large normal-range TBP and ATXN7 CAG repeat lengths are associated with increased lifetime risk of depression

    DEFF Research Database (Denmark)

    Gardiner, S. L.; van Belzen, M. J.; Boogaard, M. W.

    2017-01-01

    Depression is one of the most prevalent and debilitating psychiatric disorders worldwide. Recently, we showed that both relatively short and relatively long cytosine–adenine–guanine (CAG) repeats in the huntingtin gene (HTT) are associated with an increased risk of lifetime depression. However, t...

  16. Hoare type theory, polymorphism and separation

    DEFF Research Database (Denmark)

    Nanevski, Alexandar; Morrisett, J. Gregory; Birkedal, Lars

    2008-01-01

    We consider the problem of reconciling a dependently typed functional language with imperative features such as mutable higher-order state, pointer aliasing, and nontermination. We propose Hoare type theory (HTT), which incorporates Hoare-style specifications into types, making it possible to sta...

  17. Early life adversity and serotonin transporter gene variation interact at the level of the adrenal gland to affect the adult hypothalamo-pituitary-adrenal axis

    NARCIS (Netherlands)

    Doelen, R.H.A. van der; Deschamps, W.; D'Annibale, C.; Peeters, D.; Wevers, R.A.; Zelena, D.; Homberg, J.R.; Kozicz, L.T.

    2014-01-01

    The short allelic variant of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) has been associated with the etiology of major depression by interaction with early life stress (ELS). Furthermore, 5-HTTLPR has been associated with abnormal functioning of the

  18. Serotonin Transporter Knockout Rats Show Improved Strategy Set-Shifting and Reduced Latent Inhibition

    Science.gov (United States)

    Nonkes, Lourens J. P.; van de Vondervoort, Ilse I. G. M.; de Leeuw, Mark J. C.; Wijlaars, Linda P.; Maes, Joseph H. R.; Homberg, Judith R.

    2012-01-01

    Behavioral flexibility is a cognitive process depending on prefrontal areas allowing adaptive responses to environmental changes. Serotonin transporter knockout (5-HTT[superscript -/-]) rodents show improved reversal learning in addition to orbitofrontal cortex changes. Another form of behavioral flexibility, extradimensional strategy set-shifting…

  19. Reversal learning and associative memory impairments in a BACHD rat model for Huntington disease

    NARCIS (Netherlands)

    Abada, Yah-se K.; Nguyen, Huu Phuc; Ellenbroek, Bart; Schreiber, Rudy

    2013-01-01

    Chorea and psychiatric symptoms are hallmarks of Huntington disease (HD), a neurodegenerative disorder, genetically characterized by the presence of expanded CAG repeats (>35) in the HUNTINGTIN (HTT) gene. HD patients present psychiatric symptoms prior to the onset of motor symptoms and we recently

  20. Plasma universe

    International Nuclear Information System (INIS)

    Alfven, H.

    1986-04-01

    Traditionally the views in our cosmic environment have been based on observations in the visual octave of the electromagnetic spectrum, during the last half-century supplemented by infrared and radio observations. Space research has opened the full spectrum. Of special importance are the X-ray-gamma-ray regions, in which a number of unexpected phenomena have been discovered. Radiations in these regions are likely to originate mainly from magnetised cosmic plasma. Such a medium may also emit synchrotron radiation which is observable in the radio region. If we try to base a model of the universe on the plasma phenomena mentioned we find that the plasma universe is drastically different from the traditional visual universe. Information about the plasma universe can also be obtained by extrapolation of laboratory experiments and magnetospheric in situ measurements of plasma. This approach is possible because it is likely that the basic properties of plasma are the same everywhere. In order to test the usefulness of the plasma universe model we apply it to cosmogony. Such an approach seems to be rather successful. For example, the complicated structure of the Saturnian C ring can be accounted for. It is possible to reconstruct certain phenomena 4-5 bilions years ago with an accuracy of better than 1 percent

  1. Analysis of Job Satisfaction of University Professors from Nine Chinese Universities

    Science.gov (United States)

    Du, Ping; Lai, Manhong; Lo, Leslie N. K.

    2010-01-01

    Research on work life and job satisfaction of university professors is becoming an important research issue in the field of higher education. This study used questionnaires administered to 1 770 teachers from different levels, types, and academic fields of Chinese universities to investigate job satisfaction among university professors and the…

  2. Study of the Effect of Brand Equity Drivers on University Brand Resonance (Case Study:Amir Kabir university, Sharif university, Tarbiat Modares university, Tehran university)

    OpenAIRE

    mojtaba karimian; Hamid khodadad hosseini; Asqar moshabaki

    2015-01-01

    Branding in business of institutions of higher education is one of the issues that recently have been attracted by many researchers and therefore administrators must conduct in depth studies and take effective steps in order to devise a brand strategy so that they can make a strong brand for universities. Thus, this article investigated the quality of branding and presented suggestions to improve the brand resonance of university. The main objective of the study is to show that how brand reso...

  3. The University Culture

    Science.gov (United States)

    Simplicio, Joseph

    2012-01-01

    In this article the author discusses the role university culture can play on a campus and how it can impact policy and practice. The article explores how a university's history, values, and vision form its culture and how this culture in turn affects its stability and continuity. The article discusses how newcomers within the university are…

  4. The Global University Press

    Science.gov (United States)

    Dougherty, Peter J.

    2012-01-01

    The modern world's understanding of American university press has long been shaped by university-press books. American university-press books are good international advertisements for the universities whose logos grace their spines. The growth of transnational scholarship and the expansion of digital communications networks are converging in ways…

  5. Thermal conductivity improvement in carbon nanoparticle doped PAO oil: An experimental study

    Science.gov (United States)

    Shaikh, S.; Lafdi, K.; Ponnappan, R.

    2007-03-01

    The present work involves a study on the thermal conductivity of nanoparticle-oil suspensions for three types of nanoparticles, namely, carbon nanotubes (CNTs), exfoliated graphite (EXG), and heat treated nanofibers (HTT) with PAO oil as the base fluid. To accomplish the above task, an experimental analysis is performed using a modern light flash technique (LFA 447) for measuring the thermal conductivity of the three types of nanofluids, for different loading of nanoparticles. The experimental results show a similar trend as observed in literature for nanofluids with a maximum enhancement of approximately 161% obtained for the CNT-PAO oil suspension. The overall percent enhancements for different volume fractions of the nanoparticles are highest for the CNT-based nanofluid, followed by the EXG and the HTT. The findings from this study for the three different types of carbon nanoparticles can have great potential in the field of thermal management.

  6. Performance Related Pay in Australian Universities: The Case of Swinburne University

    Science.gov (United States)

    Harkness, Peter; Schier, Mark

    2011-01-01

    Performance related pay is not common in Australian universities. A number of Australian universities have begun to show interest in implementing more individualised pay arrangements. Swinburne University of Technology, in Melbourne, has chosen, contrary to the wishes of many of its staff, to be a path-breaker and has introduced a performance…

  7. University Social Responsibility and Brand Image of Private Universities in Bangkok

    Science.gov (United States)

    Plungpongpan, Jirawan; Tiangsoongnern, Leela; Speece, Mark

    2016-01-01

    Purpose: The purpose of this paper is to examine the effects of university social responsibility (USR) on the brand image of private universities in Thailand. Brand image is important for entry into the consideration set as prospective students evaluate options for university study. USR activities may be implicit or explicit, i.e., actively…

  8. The holographic universe

    CERN Document Server

    Talbot, Michael

    1991-01-01

    'There is evidence to suggest that our world and everything in it - from snowflakes to maple trees to falling stars and spinning electrons - are only ghostly images, projections from a level of reality literally beyond both space and time.' This is the astonishing idea behind the holographic theory of the universe, pioneered by two eminent thinkers: physicist David Bohm, a former protege of Albert Einstein, and quantum physicist Karl Pribram. The holographic theory of the universe encompasses consciousness and reality as we know them, but can also explain such hitherto unexplained phenomena as telepathy, out-of-body experiences and even miraculous healing. In this remarkable book, Michael Talbot reveals the extraordinary depth and power of the holographic theory of the universe, illustrating how it makes sense of the entire range of experiences within our universe - and in other universes beyond our own.

  9. The Transformation of Traditional Universities into Entrepreneurial Universities to Ensure Sustainable Higher Education

    Science.gov (United States)

    Bikse, Veronika; Lusena-Ezera, Inese; Rivza, Baiba; Volkova, Tatjana

    2016-01-01

    This paper aims to investigate the experience and to identify the drivers of transforming traditional universities into Entrepreneurial Universities for ensuring sustainable higher education in Latvia. Due to the wide scope, Entrepreneurial University characteristics, the present research study is limited and focuses on the university providing…

  10. Insulin and IGF-1 improve mitochondrial function in a PI-3K/Akt-dependent manner and reduce mitochondrial generation of reactive oxygen species in Huntington's disease knock-in striatal cells.

    Science.gov (United States)

    Ribeiro, Márcio; Rosenstock, Tatiana R; Oliveira, Ana M; Oliveira, Catarina R; Rego, A Cristina

    2014-09-01

    Oxidative stress and mitochondrial dysfunction have been described in Huntington's disease, a disorder caused by expression of mutant huntingtin (mHtt). IGF-1 was previously shown to protect HD cells, whereas insulin prevented neuronal oxidative stress. In this work we analyzed the role of insulin and IGF-1 in striatal cells derived from HD knock-in mice on mitochondrial production of reactive oxygen species (ROS) and related antioxidant and signaling pathways influencing mitochondrial function. Insulin and IGF-1 decreased mitochondrial ROS induced by mHtt and normalized mitochondrial SOD activity, without affecting intracellular glutathione levels. IGF-1 and insulin promoted Akt phosphorylation without changing the nuclear levels of phosphorylated Nrf2 or Nrf2/ARE activity. Insulin and IGF-1 treatment also decreased mitochondrial Drp1 phosphorylation, suggesting reduced mitochondrial fragmentation, and ameliorated mitochondrial function in HD cells in a PI-3K/Akt-dependent manner. This was accompanied by increased total and phosphorylated Akt, Tfam, and mitochondrial-encoded cytochrome c oxidase II, as well as Tom20 and Tom40 in mitochondria of insulin- and IGF-1-treated mutant striatal cells. Concomitantly, insulin/IGF-1-treated mutant cells showed reduced apoptotic features. Hence, insulin and IGF-1 improve mitochondrial function and reduce mitochondrial ROS caused by mHtt by activating the PI-3K/Akt signaling pathway, in a process independent of Nrf2 transcriptional activity, but involving enhanced mitochondrial levels of Akt and mitochondrial-encoded complex IV subunit. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. General Topology of the Universe

    OpenAIRE

    Pandya, Aalok

    2002-01-01

    General topology of the universe is descibed. It is concluded that topology of the present universe is greater or stronger than the topology of the universe in the past and topology of the future universe will be stronger or greater than the present topology of the universe. Consequently, the universe remains unbounded.

  12. Building Effective Community-University Partnerships: Are Universities Truly Ready?

    Science.gov (United States)

    Curwood, Susan Eckerle; Munger, Felix; Mitchell, Terry; Mackeigan, Mary; Farrar, Ashley

    2011-01-01

    Community service learning and community-based research necessitate the development of strong community-university partnerships. In this paper, students, faculty, and a community partner critically reflect upon the process of establishing a long-term community-university partnership through the integration of a community service learning component…

  13. Universities scale like cities.

    Directory of Open Access Journals (Sweden)

    Anthony F J van Raan

    Full Text Available Recent studies of urban scaling show that important socioeconomic city characteristics such as wealth and innovation capacity exhibit a nonlinear, particularly a power law scaling with population size. These nonlinear effects are common to all cities, with similar power law exponents. These findings mean that the larger the city, the more disproportionally they are places of wealth and innovation. Local properties of cities cause a deviation from the expected behavior as predicted by the power law scaling. In this paper we demonstrate that universities show a similar behavior as cities in the distribution of the 'gross university income' in terms of total number of citations over 'size' in terms of total number of publications. Moreover, the power law exponents for university scaling are comparable to those for urban scaling. We find that deviations from the expected behavior can indeed be explained by specific local properties of universities, particularly the field-specific composition of a university, and its quality in terms of field-normalized citation impact. By studying both the set of the 500 largest universities worldwide and a specific subset of these 500 universities--the top-100 European universities--we are also able to distinguish between properties of universities with as well as without selection of one specific local property, the quality of a university in terms of its average field-normalized citation impact. It also reveals an interesting observation concerning the working of a crucial property in networked systems, preferential attachment.

  14. Universities scale like cities.

    Science.gov (United States)

    van Raan, Anthony F J

    2013-01-01

    Recent studies of urban scaling show that important socioeconomic city characteristics such as wealth and innovation capacity exhibit a nonlinear, particularly a power law scaling with population size. These nonlinear effects are common to all cities, with similar power law exponents. These findings mean that the larger the city, the more disproportionally they are places of wealth and innovation. Local properties of cities cause a deviation from the expected behavior as predicted by the power law scaling. In this paper we demonstrate that universities show a similar behavior as cities in the distribution of the 'gross university income' in terms of total number of citations over 'size' in terms of total number of publications. Moreover, the power law exponents for university scaling are comparable to those for urban scaling. We find that deviations from the expected behavior can indeed be explained by specific local properties of universities, particularly the field-specific composition of a university, and its quality in terms of field-normalized citation impact. By studying both the set of the 500 largest universities worldwide and a specific subset of these 500 universities--the top-100 European universities--we are also able to distinguish between properties of universities with as well as without selection of one specific local property, the quality of a university in terms of its average field-normalized citation impact. It also reveals an interesting observation concerning the working of a crucial property in networked systems, preferential attachment.

  15. The early universe

    International Nuclear Information System (INIS)

    Steigman, G.

    1989-01-01

    The author discusses the physics of the early universe: the production and survival of relics from the big bang. The author comments on relic WIMPs as the dark matter in the universe. The remainder of this discussion is devoted to a review of the status of the only predictions from the early evolution of the universe that are accessible to astronomical observation: primordial nucleosynthesis

  16. Looking on the bright side of serotonin transporter gene variation.

    NARCIS (Netherlands)

    Homberg, J.R.; Lesch, K.P.

    2011-01-01

    Converging evidence indicates an association of the short (s), low-expressing variant of the repeat length polymorphism, serotonin transporter-linked polymorphic region (5-HTTLPR), in the human serotonin transporter gene (5-HTT, SERT, SLC6A4) with anxiety-related traits and increased risk for

  17. Experiment list: SRX1084162 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available 0 GSM1811344: P2 HA ChIPSeq; Drosophila melanogaster; ChIP-Seq source_name=Female whole animal_paraquat || tissue=whole animal || gen...der=female || age=1-3 days || genotype=k6801/k6801;gHA-KDM5 || chip antibody=HA htt

  18. Phenotype abnormality: 251 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available lant flowering stage in environment of long day length regimen in environment of long day length regimen htt... 251 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u757i delayed whole p

  19. Surpluses and Deficits: How University Partners Perceive University-Community Partnerships at One Ivy League Institution

    Directory of Open Access Journals (Sweden)

    Alison Klebanoff Cohen

    2012-07-01

    Full Text Available University-community partnerships are a critical method for how universities can serve the public interest.  Yet key questions remain: how do these partnerships work in practice, and how can university and fill reciprocal and mutual needs effectively?  A participatory evaluation of university-community partnerships in education at an Ivy League university found that university partners had a surplus perspective of the university and a deficit perspective of community partners; practitioners must shift our paradigm towards mutually beneficial, asset-driven university-community partnerships to ensure success.

  20. Rectors of European universities

    CERN Multimedia

    Maximilien Brice

    2003-01-01

    Several rectors of European universities visited CERN recently while in Geneva for a conference on coordination between their institutions. The visit began with a welcome by Roger Cashmore, CERN Director of Collider Programmes,and continued with tours of CMS, ALICE and the LHC magnet assembly hall. Photos 01, 02: The visitors in the ALICE assembly hall: (left to right) Dr. Raymond Werlen, Deputy Secretary-General of the Conference of Rectors of Swiss Universities; visit guide Prof. Alain Blondel, Department of Nuclear and Corpuscular Physics, University of Geneva; Prof. Adriano Pimpão, Rector of the University of Algarve, President of the Council of Rectors of Portuguese Universities; Prof. Jean-Pierre Finance, Conference of University Presidents, France; Prof. Jean-Paul Lehners, Vice-President of the Centre Universitaire, Luxemburg.

  1. Universities Cooperate in Online Teaching. The Experience of the Bavarian Virtual University

    Directory of Open Access Journals (Sweden)

    Paul RÜHL

    2010-01-01

    Full Text Available The Bavarian Virtual University (BVU is an institute set up by the universities and universities of Applied Sciences of the Free State of Bavaria, one of the 16 German Länder. The BVU is supported by the Bavarian Ministry of Higher Education. At present, there are more than 60,000 course enrolments by more than 25,000 Bavarian students per academic year. The BVU provides online-courses with an equivalent of two to six credit points (by ECTS standards which the member universities, all of them traditional brick-and-mortar universities, can integrate into their courses of study. Students of the member universities can attend the courses free of charge. The BVU offers neither complete courses of study nor degrees of its own. The basic and most important principles of the BVU are: Blended learning at the macro level of the course of study, not at the micro-level of the single course, priority given to asynchronous forms of communication; offering courses which are completely online, thus facilitating the import and export of online-courses between all 31 member universities and allowing a maximum of flexibility to the students. The BVU finances the developing as well as the conducting of its courses. This supports teachers in providing tuition to students from other universities.

  2. How much we know about university internationalization and university autonomy

    DEFF Research Database (Denmark)

    Turcan, Romeo V.; Gullieva, Valeria

    2013-01-01

    in their mission statements and strategic plans. Conventional wisdom suggests that universities should adapt their strategies, resources, and structures and organizations to international environments. However, recent examples of university internationalization failures and withdrawals from international markets...

  3. University Pedagogy for Assistant Professors at Aalborg University (Part 1)

    DEFF Research Database (Denmark)

    Kolmos, Anette; Krogh, Lone

    2003-01-01

    The article describes a course for assistant professors within the University Teacher Education at Aalborg University. The course focus is to develop knowledge, skills and methods from within the didactic, pedagogical, and learning theory-based fields....

  4. The Cooperation between Savonia University of Applied Sciences and West Anhui University

    OpenAIRE

    Tang, Guangjing; Xie, Jiajuan

    2016-01-01

    The aim of this thesis was to find out how to renew the double degree of Savonia University of Ap-plied Sciences and West Anhui University and listed some advantages and disadvantages of a cooperation project. Also the relevant responsible people were interviewed to get the reasons for the termination of this cooperation. The two universities signed the agreement of university cooperation projects in 2005 and the first group students went to Savonia in 2008. The contents of cooperation were a...

  5. The isotropic Universe

    International Nuclear Information System (INIS)

    Raine, D.J.

    1981-01-01

    This introduction to contemporary ideas in cosmology differs from other books on the 'expanding Universe' in its emphasis on physical cosmology and on the physical basis of the general theory of relativity. It is considered that the remarkable degree of isotropy, rather than the expansion, can be regarded as the central observational feature of the Universe. The various theories and ideas in 'big-bang' cosmology are discussed, providing an insight into current problems. Chapter headings are: quality of matter; expanding Universe; quality of radiation; quantity of matter; general theory of relativity; cosmological models; cosmological tests; matter and radiation; limits of isotropy; why is the Universe isotropic; singularities; evolution of structure. (U.K.)

  6. How academic entrepreneurship meets the university: university spin-offs in stakeholder networks

    NARCIS (Netherlands)

    Rasmussen, Einar; Benneworth, Paul Stephen; Gulbrandsen, Magnus

    2015-01-01

    Some universities and departments have been very successful in stimulating university spin-off firms (USOs). It remains an open question whether this is due to unique abilities and circumstances or if it can be stimulated at many universities. This paper seeks to discuss this question by integrating

  7. Loss aversion and 5HTT gene variants in adolescent anxiety.

    Science.gov (United States)

    Ernst, Monique; Plate, Rista C; Carlisi, Christina O; Gorodetsky, Elena; Goldman, David; Pine, Daniel S

    2014-04-01

    Loss aversion, a well-documented behavioral phenomenon, characterizes decisions under risk in adult populations. As such, loss aversion may provide a reliable measure of risky behavior. Surprisingly, little is known about loss aversion in adolescents, a group who manifests risk-taking behavior, or in anxiety disorders, which are associated with risk-avoidance. Finally, loss aversion is expected to be modulated by genotype, particularly the serotonin transporter (SERT) gene variant, based on its role in anxiety and impulsivity. This genetic modulation may also differ between anxious and healthy adolescents, given their distinct propensities for risk taking. The present work examines the modulation of loss aversion, an index of risk-taking, and reaction-time to decision, an index of impulsivity, by the serotonin-transporter-gene-linked polymorphisms (5HTTLPR) in healthy and clinically anxious adolescents. Findings show that loss aversion (1) does manifest in adolescents, (2) does not differ between healthy and clinically anxious participants, and (3), when stratified by SERT genotype, identifies a subset of anxious adolescents who are high SERT-expressers, and show excessively low loss-aversion and high impulsivity. This last finding may serve as preliminary evidence for 5HTTLPR as a risk factor for the development of comorbid disorders associated with risk-taking and impulsivity in clinically anxious adolescents. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Loss aversion and 5HTT gene variants in adolescent anxiety

    Directory of Open Access Journals (Sweden)

    Monique Ernst

    2014-04-01

    Full Text Available Loss aversion, a well-documented behavioral phenomenon, characterizes decisions under risk in adult populations. As such, loss aversion may provide a reliable measure of risky behavior. Surprisingly, little is known about loss aversion in adolescents, a group who manifests risk-taking behavior, or in anxiety disorders, which are associated with risk-avoidance. Finally, loss aversion is expected to be modulated by genotype, particularly the serotonin transporter (SERT gene variant, based on its role in anxiety and impulsivity. This genetic modulation may also differ between anxious and healthy adolescents, given their distinct propensities for risk taking. The present work examines the modulation of loss aversion, an index of risk-taking, and reaction-time to decision, an index of impulsivity, by the serotonin-transporter-gene-linked polymorphisms (5HTTLPR in healthy and clinically anxious adolescents. Findings show that loss aversion (1 does manifest in adolescents, (2 does not differ between healthy and clinically anxious participants, and (3, when stratified by SERT genotype, identifies a subset of anxious adolescents who are high SERT-expressers, and show excessively low loss-aversion and high impulsivity. This last finding may serve as preliminary evidence for 5HTTLPR as a risk factor for the development of comorbid disorders associated with risk-taking and impulsivity in clinically anxious adolescents.

  9. The universe a biography

    CERN Document Server

    Gribbin, John

    2008-01-01

    The Universe: A Biography makes cosmology accessible to everyone. John Gribbin navigates the latest frontiers of scientific discovery to tell us what we really know about the history of the universe. Along the way, he describes how the universe began; what the early universe looked like; how its structure developed; and what emerged to hold it all together. He describes where the elements came from; how stars and galaxies formed; and the story of how life emerged. He even looks to the future: is the history of the universe going to end with a Big Crunch or a Big Rip.

  10. Enlistment Propensities of University Students

    National Research Council Canada - National Science Library

    Moskos, Charles

    2004-01-01

    Enlistment propensities of undergraduates were assessed through surveys conducted at Northwestern University, University of Arizona, University of California-Los Angeles, and University of Illinois-Chicago...

  11. University Program Management Information System: NASA's University Program Active Projects

    Science.gov (United States)

    Gans, Gary (Technical Monitor)

    2003-01-01

    As basic policy, NASA believes that colleges and universities should be encouraged to participate in the nation's space and aeronautics program to the maximum extent practicable. Indeed, universities are considered as partners with government and industry in the nation's aerospace program. NASA's objective is to have them bring their scientific, engineering, and social research competence to bear on aerospace problems and on the broader social, economic, and international implications of NASA's technical and scientific programs. It is expected that, in so doing, universities will strengthen both their research and their educational capabilities to contribute more effectively to the national well being. This annual report is one means of documenting the NASA-university relationship, frequently denoted, collectively, as NASA's University Program. This report is consistent with agency accounting records, as the data is obtained from NASA's Financial and Contractual Status (FACS) System, operated by the Financial Management Division and the Procurement Office. However, in accordance with interagency agreements, the orientation differs from that required for financial or procurement purposes. Any apparent discrepancies between this report and other NASA procurement or financial reports stem from the selection criteria for the data. This report was prepared by the Office of Education/N.

  12. From Eminent Men to Excellent Universities: University Rankings as Calculative Devices.

    Science.gov (United States)

    Hammarfelt, Björn; de Rijcke, Sarah; Wouters, Paul

    2017-01-01

    Global university rankings have become increasingly important 'calculative devices' for assessing the 'quality' of higher education and research. Their ability to make characteristics of universities 'calculable' is here exemplified by the first proper university ranking ever, produced as early as 1910 by the American psychologist James McKeen Cattell. Our paper links the epistemological rationales behind the construction of this ranking to the sociopolitical context in which Cattell operated: an era in which psychology became institutionalized against the backdrop of the eugenics movement, and in which statistics of science became used to counter a perceived decline in 'great men.' Over time, however, the 'eminent man,' shaped foremost by heredity and upbringing, came to be replaced by the excellent university as the emblematic symbol of scientific and intellectual strength. We also show that Cattell's ranking was generative of new forms of the social, traces of which can still be found today in the enactment of 'excellence' in global university rankings.

  13. The Universe of Fluctuations The Architecture of Spacetime and the Universe

    CERN Document Server

    Sidharth, B G

    2005-01-01

    The Universe of Fluctuations: The Architecture of Spacetime and the Universe is a path-breaking work which proposes solutions to the impasse and crisis facing fundamental physics and cosmology. It describes a cosmological model based on fuzzy spacetime that has correctly predicted a dark-energy-driven acceleration of our expanding universe - with a small cosmological constant - at a time when the popular belief was quite the contrary. It describes how the Universe is made up of an underpinning of Planck oscillators in a Quantum Vacuum. This leads to, amongst other things, a characterization of gravitation as being distributional over the entire Universe, thereby providing an answer to a puzzle brought to light by Weinberg years ago and since overlooked. There is also a simple formula for the mass spectrum of all known elementary particles, based on QCD dynamics. Many other interesting ramifications and experimental tests for the future are also discussed. This apart, there is a brief survey of some of the exi...

  14. Inflation in the Universe

    International Nuclear Information System (INIS)

    Barrow, J.D.; California Univ., Berkeley; Turner, M.S.; Chicago Univ., IL

    1981-01-01

    The problems of explaining the observed isotropy, homogeneity, flatness and specific entropy of the Universe are discussed in the context of an inflationary Universe which has recently been suggested. It is shown that the isotropy cannot be ignored as a Universe with a large amount of anisotropy will not undergo the inflationary phase. A Universe with only moderate anistropy will undergo inflation and will be rapidly isotropized. (U.K.)

  15. Peculiarities of the early Universe (Universes) birth and positron annihilation

    International Nuclear Information System (INIS)

    Svetlov-Prokop'ev, E.P.

    2003-01-01

    Works on the problem of quantum birth of the Universe are reviewed. Possible peculiarities of electron-positron annihilation at the early stages of the Universe (s) birth in connection with black holes are considered. Possible concept of Eternity is discussed. (author)

  16. Association between a genetic variant in the serotonin transporter gene (SLC6A4) and suicidal behavior in patients with schizophrenia

    DEFF Research Database (Denmark)

    Lindholm Carlstrom, Eva; Saetre, Peter; Rosengren, Anders

    2012-01-01

    ABSTRACT: BACKGROUND: The serotonin (5-hydroxytryptamin; 5-HT) system has a central role in the circuitry of cognition and emotions. Multiple lines of evidence suggest that genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT) is associated with schizophrenia and suicidal behavior. ...

  17. Gambling with the Universe

    Science.gov (United States)

    Hawking, Stephen

    2002-05-01

    This is an excerpt from Stephen Hawking's book The Universe in a Nutshell. Roger Penrose and Stephen Hawking, Lucasian Professor of Mathematics at the University of Cambridge, were able to show that Einstein's General Theory of Relativity implied that the universe and time itself must have had a beginning in a tremendous explosion. The discovery of the expansion of the universe is one of the great intellectual revolutions of the twentieth century.

  18. Universities as Development Hubs

    DEFF Research Database (Denmark)

    Hansen, Jens Aage; Lindegaard, Klaus; Lehmann, Martin

    2005-01-01

    Capacity-building in environment and development has been implemented and tested over the last decade through university and university consortia networking. Universities from Africa (Botswana and South Africa), Asia (Malaysia and Thailand), Central America (Costa Rica, El Salvador and Nicaragua...

  19. Politics, Markets, and University Costs: Financing Universities in the Current Era

    OpenAIRE

    Geiger, Roger L.

    2000-01-01

    The purpose of this study is to determine the factors shaping the financing of the principal universities of the United States, and to explore the consequences for institutions and for students. Revenues are the lifeblood of these or any other universities. The level of resources that universities command from society determines the level and scope of their activities, and who provides these resources greatly affects their behavior. Moreover, where resources are concerned, both inequality and...

  20. Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress.

    Science.gov (United States)

    Li-Tempel, Ting; Larra, Mauro F; Winnikes, Ulrike; Tempel, Tobias; DeRijk, Roel H; Schulz, André; Schächinger, Hartmut; Meyer, Jobst; Schote, Andrea B

    2016-09-01

    The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice

    Directory of Open Access Journals (Sweden)

    Jack C. Reidling

    2018-01-01

    Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP-grade human embryonic stem cell-derived neural stem cell (hNSC line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF in both models. These findings hold promise for future development of stem cell-based therapies.

  2. Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure?

    Science.gov (United States)

    Morea, Veronica; Bidollari, Eris; Colotti, Gianni; Fiorillo, Annarita; Rosati, Jessica; De Filippis, Lidia; Squitieri, Ferdinando; Ilari, Andrea

    2017-07-01

    Huntington's disease (HD) or Huntington's chorea is the most common inherited, dominantly transmitted, neurodegenerative disorder. It is caused by increased CAG repeats number in the gene coding for huntingtin (Htt) and characterized by motor, behaviour and psychiatric symptoms, ultimately leading to death. HD patients also exhibit alterations in glucose and energetic metabolism, which result in pronounced weight loss despite sustained calorie intake. Glucose metabolism decreases in the striatum of all the subjects with mutated Htt, but affects symptom presentation only when it drops below a specific threshold. Recent evidence points at defects in glucose uptake by the brain, and especially by neurons, as a relevant component of central glucose hypometabolism in HD patients. Here we review the main features of glucose metabolism and transport in the brain in physiological conditions and how these processes are impaired in HD, and discuss the potential ability of strategies aimed at increasing intracellular energy levels to counteract neurological and motor degeneration in HD patients.

  3. Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease

    Directory of Open Access Journals (Sweden)

    Piotr Hadaczek

    2016-01-01

    Full Text Available Huntington's disease (HD is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV, AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP, with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease.

  4. Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

    Science.gov (United States)

    Cui, Shi-Shuang; Ren, Ru-Jing; Wang, Ying; Wang, Gang; Chen, Sheng-Di

    2017-08-08

    Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

  5. Enhancing the gene-environment interaction framework through a quasi-experimental research design: evidence from differential responses to September 11.

    Science.gov (United States)

    Fletcher, Jason M

    2014-01-01

    This article uses a gene-environment interaction framework to examine the differential responses to an objective external stressor based on genetic variation in the production of depressive symptoms. This article advances the literature by utilizing a quasi-experimental environmental exposure design, as well as a regression discontinuity design, to control for seasonal trends, which limit the potential for gene-environment correlation and allow stronger causal claims. Replications are attempted for two prominent genes (5-HTT and MAOA), and three additional genes are explored (DRD2, DRD4, and DAT1). This article provides evidence of a main effect of 9/11 on reports of feelings of sadness and fails to replicate a common finding of interaction using 5-HTT but does show support for interaction with MAOA in men. It also provides new evidence that variation in the DRD4 gene modifies an individual's response to the exposure, with individuals with no 7-repeats found to have a muted response.

  6. A Study of the Standard Model Higgs Boson Decaying to a Pair of Tau Leptons with the CMS Detector at the LHC

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00398807; Smith, Wesley H.; Herndon, Matthew F.

    This thesis presents a 5.5 standard deviation observation of the Higgs boson decaying to fermions using the data collected at the LHC at 13\\TeV center-of-mass energy. The studied dataset corresponds to an integrated luminosity of 35.9\\fbinv. The best fit signal strength for the $\\htt$ process is measured to be $\\mu = 1.24 ^{+0.29} _{-0.27}$, consistent with standard model predictions. Unique event categories are used targeting the leading Higgs boson production processes, gluon fusion, vector boson fusion, and associated production. This provides signal regions sensitive to Higgs boson couplings to both fermions and vector bosons. These two Higgs boson couplings are measured and are consistent with standard model predictions within one standard deviation. This 5.5 standard deviation observation of the $\\htt$ process and the consistency of the Higgs boson couplings with the standard model provide confirmation of the Higgs boson Yukawa couplings to fermions. This is evidence that the Higgs field provides mass f...

  7. Hybrid Universities in Malaysia

    Science.gov (United States)

    Lee, Molly; Wan, Chang Da; Sirat, Morshidi

    2017-01-01

    Are Asian universities different from those in Western countries? Premised on the hypothesis that Asian universities are different because of hybridization between Western academic models and local traditional cultures, this paper investigates the hybrid characteristics in Malaysian universities resulting from interaction between contemporary…

  8. Inspired by CERN

    CERN Multimedia

    2004-01-01

    Art students inspired by CERN will be returning to show their work 9 to 16 October in Building 500, outside the Auditorium. Seventeen art students from around Europe visited CERN last January for a week of introductions to particle physics and astrophysics, and discussions with CERN scientists about their projects. A CERN scientist "adopted"each artist so they could ask questions during and after the visit. Now the seeds planted during their visit have come to fruition in a show using many media and exploring varied concepts, such as how people experience the online world, the sheer scale of CERN's equipment, and the abstractness of the entities scientists are looking for. "The work is so varied, people are going to love some pieces and detest others," says Andrew Charalambous, the project coordinator from University College London who is also curating the exhibition. "It's contemporary modern art, and that's sometimes difficult to take in." For more information on this thought-provoking show, see: htt...

  9. The Multi-Universe Cosmos. The Origin and Fate of our Universe

    Science.gov (United States)

    Velan, Karel

    18 billion yers ago our Universe, one of many in the Cosmos, emerged from a hot, dense fireball of matter and energy created in the 4-dimensional cosmic space-time from virtual particles receiving their rest mass from a powerful primordial radiation field, the missing link to any viable theory of creation. The cloud of elementary particles and radiation collapsed by gravity into a fireball until its trappped thermal radiation caused a titanic explosion that initiated the expansion and evolution of ours universe. As the universe expanded and cooled it spawned galaxies, stars, planets and life. Proven laws of physics, observationsl data and mathematical computations support the new cosmological model which proposes a large number of universes in the cosmos in varying stages of evolution

  10. Transition from AdS universe to DS universe in the BPP model

    International Nuclear Information System (INIS)

    Kim, Wontae; Yoon, Myungseok

    2007-01-01

    It can be shown that in the BPP model the smooth phase transition from the asymptotically decelerated AdS universe to the asymptotically accelerated DS universe is possible by solving the modified semiclassical equations of motion. This transition comes from noncommutative Poisson algebra, which gives the constant curvature scalars asymptotically. The decelerated expansion of the early universe is due to the negative energy density with the negative pressure induced by quantum back reaction, and the accelerated late-time universe comes from the positive energy and the negative pressure which behave like dark energy source in recent cosmological models

  11. The University in a Fragmented World. A Contribution from Sophia University Institute

    Directory of Open Access Journals (Sweden)

    Callebaut Bernhard

    2016-12-01

    Full Text Available The John Paul II Catholic University of Lublin (KUL was the very first University to honor the Italian religious leader Chiara Lubich, with a honorary degree. In 2007, Chiara Lubich who shared with Henry cardinal Newman some very similar intuitions on the task of a University, founded on the basis of the charism the Church recognized in her the University Institute Sophia (IUS in Tuscany (Italy. This was to be the very last initiative of her long life as the foundress of the Focolare Movement, Chiara Lubich wanted it to be an interdisciplinary institute bringing together life and studies in harmony. Now, after more than eight years of life, the author dresses a ‘state of the union’ of this University Institute, in the context of the crisis of the universitarian world today.

  12. The Wider Impacts of Universities: Habermas on Learning Processes and Universities

    Directory of Open Access Journals (Sweden)

    Jesper Eckhardt Larsen

    2013-06-01

    Full Text Available The discourse of reform in higher education tends to focus narrowly on employability and the relationship between higher education and the labor market. Universities as research institutions are now considered solely in the dominant discourse of innovation. This way of conceiving universities is inspired by functionalist theory that focuses on the imperatives of a knowledge economy. Taking a departure in the theory of society developed by Jürgen Habermas this paper seeks to provide a theoretical framework for an empirical comparative analysis on the wider societal impact of universities. It is the argument that the wider impacts of higher education and research at universities must be seen in a more complex vision of modern societies. The paper is thus primarily a re-reading of Habermas’ critique of functionalist views of the university and an application of Habermas’ critique on current issues in the debates on higher education. A special discussion will be taken on issues of the self in view of the current tendencies to regard all education from the standpoint of the economic outputs.

  13. The University of Stuttgart IKE/University of Arizona student research program

    International Nuclear Information System (INIS)

    Seale, R.L.

    1988-01-01

    The University of Stuttgart's Institut fuer Kernenergetik und Energiesysteme (IKE) and the University of Arizona have had a joint program in which graduate students from the IKE spend 1 yr on the University of Arizona campus. This program started in 1982 largely as the result of an initiative begun by K.H. Hoecker, then director of IKE. Since 1985, Alfred Voss has been director and the program has continued without interruption. Under the program, the Deutscher Akademisher Austauschdienst, a government agency of the Federal Republic of Germany has funded scholarships for students from IKE, which provide support for 1 yr during which they attend the University of Arizona as visiting student scholars and engage in a research project under the direction of one of our faculty, which satisfies a part of the requirements for the Ingenieur-Diplom Fachrichtung Maschinenbau. The students get credit for their research from the University of Stuttgart. The topics have a broad range and include software development, artificial intelligence, radiation transport, and energy management studies

  14. Financial Report of Ontario Universities, 1993-94. Volume I - Universities.

    Science.gov (United States)

    Council of Ontario Universities, Toronto.

    This report provides detailed financial information for provincially-assisted colleges and universities in Ontario (Canada) for the fiscal year ended April 30, 1994. It describes university accounting procedures, principles for reporting financial data, and definitions. Nine tables provide summary information on revenue, expenses, fund balances,…

  15. Financial Report of Ontario Universities 1996-97. Volume I-Universities.

    Science.gov (United States)

    Council of Ontario Universities, Toronto.

    This annual report presents 1996-97 financial information on 20 degree-granting universities and related institutions in Ontario, Canada. The report first explains the general guidelines and reporting requirements used in compiling the report, including university accounting procedures, the principles of fund accounting involved, and definitions…

  16. A Universal Reactive Machine

    DEFF Research Database (Denmark)

    Andersen, Henrik Reif; Mørk, Simon; Sørensen, Morten U.

    1997-01-01

    Turing showed the existence of a model universal for the set of Turing machines in the sense that given an encoding of any Turing machine asinput the universal Turing machine simulates it. We introduce the concept of universality for reactive systems and construct a CCS processuniversal...

  17. Undulant Universe

    Energy Technology Data Exchange (ETDEWEB)

    Barenboim, Gabriela; /Valencia U.; Mena, Olga; Quigg, Chris; /Fermilab

    2004-12-01

    If the equation of state for ''dark energy'' varies periodically, the expansion of the Universe may have undergone alternating eras of acceleration and deceleration. We examine a specific form that survives existing observational tests, does not single out the present state of the Universe as exceptional, and suggests a future much like the matter-dominated past: a smooth expansion without a final inflationary epoch.

  18. Taiwan Universities: Where to Go?

    Directory of Open Access Journals (Sweden)

    Yu-Ying Kuo

    2016-02-01

    Full Text Available The dramatic expansion of Taiwan universities/colleges from about 100 to 160 from the late 1980s has encountered problems due to social and global changes. What should Taiwan universities move toward and how? This research relies on secondary data to explore the issues Taiwan universities currently face—a low birth rate and global competition. The decreasing number of incoming students will result in a lower registration rate and less tuition revenue, which will make some universities struggle to survive. Hence, government policies, proposed by the Ministry of Education, have been implemented to assist Taiwan universities to adjust to external changes. The Innovative Transformation Policy, adopted in 2015, consists of strategies for university–industry cooperation, university mergers, university closures, and a re-shaping of the university paradigm. This policy has begun to be implemented and its initial outcome will be continually evaluated. In accordance with the Innovative Transformation Policy, this study encourages Taiwan universities to improve governance, set prominent unique characteristics of development, and enhance global competitiveness.

  19. Medical universities educational and research online services: benchmarking universities' website towards e-government.

    Science.gov (United States)

    Farzandipour, Mehrdad; Meidani, Zahra

    2014-06-01

    Websites as one of the initial steps towards an e-government adoption do facilitate delivery of online and customer-oriented services. In this study we intended to investigate the role of the websites of medical universities in providing educational and research services following the E-government maturity model in the Iranian universities. This descriptive and cross- sectional study was conducted through content analysis and benchmarking the websites in 2012. The research population included the entire medical university website (37). Delivery of educational and research services through these university websites including information, interaction, transaction, and Integration were investigated using a checklist. The data were then analyzed by means of descriptive statistics and using SPSS software. Level of educational and research services by websites of the medical universities type I and II was evaluated medium as 1.99 and 1.89, respectively. All the universities gained a mean score of 1 out of 3 in terms of integration of educational and research services. Results of the study indicated that Iranian universities have passed information and interaction stages, but they have not made much progress in transaction and integration stages. Failure to adapt to e-government in Iranian medical universities in which limiting factors such as users' e-literacy, access to the internet and ICT infrastructure are not so crucial as in other organizations, suggest that e-government realization goes beyond technical challenges.

  20. Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate

    Directory of Open Access Journals (Sweden)

    Yousaf AM

    2016-01-01

    Full Text Available Abid Mehmood Yousaf,1,2 Omer Mustapha,1 Dong Wuk Kim,1 Dong Shik Kim,1 Kyeong Soo Kim,1 Sung Giu Jin,1 Chul Soon Yong,3 Yu Seok Youn,4 Yu-Kyoung Oh,5 Jong Oh Kim,3 Han-Gon Choi1 1College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, South Korea; 2Faculty of Pharmacy, University of Central Punjab, Johar, Lahore, Pakistan; 3College of Pharmacy, Yeungnam University, Gyongsan, North Gyeongsang, 4School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi, 5College of Pharmacy, Seoul National University, Seoul, South Korea Purpose: The purpose of the present research was to develop a novel electrosprayed nanospherule providing the most optimized aqueous solubility and oral bioavailability for poorly water-soluble fenofibrate.Methods: Numerous fenofibrate-loaded electrosprayed nanospherules were prepared with polyvinylpyrrolidone (PVP and Labrafil® M 2125 as carriers using the electrospray technique, and the effect of the carriers on drug solubility and solvation was assessed. The solid state characterization of an optimized formulation was conducted by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopic analyses. Oral bioavailability in rats was also evaluated for the formulation of an optimized nanospherule in comparison with free drug and a conventional fenofibrate-loaded solid dispersion.Results: All of the electrosprayed nanospherule formulations had remarkably enhanced aqueous solubility and dissolution compared with free drug. Moreover, Labrafil M 2125, a surfactant, had a positive influence on the solubility and dissolution of the drug in the electrosprayed nanospherule. Increases were observed as the PVP/drug ratio increased to 4:1, but higher ratios gave no significant increases. In particular, an electrosprayed nanospherule composed of fenofibrate, PVP, and Labrafil M 2125 at the weight ratio of 1

  1. Wikipedia ranking of world universities

    Science.gov (United States)

    Lages, José; Patt, Antoine; Shepelyansky, Dima L.

    2016-03-01

    We use the directed networks between articles of 24 Wikipedia language editions for producing the wikipedia ranking of world Universities (WRWU) using PageRank, 2DRank and CheiRank algorithms. This approach allows to incorporate various cultural views on world universities using the mathematical statistical analysis independent of cultural preferences. The Wikipedia ranking of top 100 universities provides about 60% overlap with the Shanghai university ranking demonstrating the reliable features of this approach. At the same time WRWU incorporates all knowledge accumulated at 24 Wikipedia editions giving stronger highlights for historically important universities leading to a different estimation of efficiency of world countries in university education. The historical development of university ranking is analyzed during ten centuries of their history.

  2. The accidental universe

    International Nuclear Information System (INIS)

    Davies, P.C.W.

    1982-01-01

    Is our universe an accident of nature. The mysterious coincidences underlying the structure and properties of the universe that we inhabit are examined. This is the first book for the non-specialist reader to present in depth the provocative hypothesis that the structure of the physical world is exceedingly contrived in its appearance. A survey is presented of the range of apparently miraculous accidents of nature that have enabled the universe to evolve its familiar structures: atoms, stars, galaxies, and life itself. This book concludes with an investigation of the so-called 'anthropic principle' which postulates that 'miraculous coincidences' are inevitable in any universe containing conscious observers. This thesis of a cosmic biological selection effect will both reassure and enrage readers, the very existence of whom may be related to fine tuning in the laws of physics. (author)

  3. A Mutually Beneficial Relationship: University of the Third Age and a regional university campus

    Directory of Open Access Journals (Sweden)

    Bronwyn Ellis

    2011-11-01

    Full Text Available A mutually beneficial relationship has developed over the past 15 years between a regional South Australian branch of the University of the Third Age (U3A and the local university campus. Arising from the initiative of a community member, the group sought assistance from the university, and has now become integrated into campus life. The university has provided a venue for meetings and access to other facilities, and university staff have contributed to the program of classes. The U3A has undoubtedly benefited from these inputs. However, the university has also benefited from these opportunities to engage with the wider community, the presence of willing volunteers to contribute in various ways to university classes and other activities, and favourable word-of-mouth marketing. Beginning with background information on U3A, the local branch and its setting, we reflect on the sustainability of this relationship with the university and the factors that have contributed to this. We draw on our U3A experience and on two qualitative research projects in which U3A members have taken part: projects which have investigated their motivation for participation in U3A classes and activities, and the contributions of U3A to the university and vice versa. Not only has the relationship itself been sustained thus far, it has also contributed to sustaining U3A members in their active involvement in learning and community activities, and has been a significant part of community engagement activities of the campus. Keywords University of the Third Age; university-community engagement; mutual benefit; lifelong learning; retirement; productive ageing

  4. Entrepreneurship in Finnish Universities

    Science.gov (United States)

    Nurmi, Piia; Paasio, Kaisu

    2007-01-01

    Purpose: The purpose of this paper is to discuss the role of universities in fostering and promoting entrepreneurship in Finland. In particular it seeks to examine the university-entrepreneurship relationship: its nature and how universities are addressing the entrepreneurship agenda. Design/methodology/approach: The paper is based on a large…

  5. Universal (Global Evolutionism

    Directory of Open Access Journals (Sweden)

    Arkady Ursul

    2018-02-01

    Full Text Available In this article investigate a general scientific concept of a global (universal evolution, in which selforganization of the material systems acts as a common ground and a permanent process of progressive development in the visible Universe. The main problem of research of this type of evolution is seen as a superhighway trajectory of evolutionary processes in the Universe, in which there is a continuous selforganization of the material systems, ranging from the Big Bang and to the social level of evolution, which may have an indefinite continuation of society and nature

  6. The Scholarly Communication Process within the University Research Corridor (Michigan State University, the University of Michigan, and Wayne State University): A Case Study in Cooperation

    Science.gov (United States)

    Utter, Timothy; Holley, Robert P.

    2009-01-01

    The growth of open access publishing, the development of institutional repositories, and the availability of millions of digitized monographs and journals are rapidly changing scholarly communication. This case study looks at the current and possible uses of these tools by Michigan's three largest universities: Michigan State University, the…

  7. Improving Innovation in University Spin-Offs. The Fostering Role of University and Region

    Directory of Open Access Journals (Sweden)

    Antonio Prencipe

    2016-06-01

    Full Text Available University spin-offs (USOs are companies created to commercialize knowledge or technology developed in academia; thus, their major contribution to the knowledge economy is their ability to generate innovation. Following the Resource-Based View of the Firm and the Knowledge Spillover Theory of Entrepreneurship, it was stated that fostering mechanisms at university level and at regional level may positively influence the USOs innovation. Based on a sample of 621 Italian USOs, we show that the positive impact of the university context is more crucial compared with those of the regional context. In particular, the university affiliated business incubators and Science Parks, jointly with the university financial resources, seem to promote the innovation efforts of USOs. These evidences rise the need of a resilient partnership among all the contextual players involved in the spillover processes, mainly at regional level, in order to effectively exploit the potential innovative efforts of the university start-ups.

  8. Imagining the Future University

    DEFF Research Database (Denmark)

    Bengtsen, Søren Smedegaard; Barnett, Ronald

    'Imagining the Future University' is a special issue in the journal Philosophy and Theory in Higher Education, published by Peter Lang. Editor in Chief of the journal is John Petrovic, University of Alabama. The speciale issue is edited by Søren Bengtsen and Ronald Barnett.......'Imagining the Future University' is a special issue in the journal Philosophy and Theory in Higher Education, published by Peter Lang. Editor in Chief of the journal is John Petrovic, University of Alabama. The speciale issue is edited by Søren Bengtsen and Ronald Barnett....

  9. The future of the universe

    CERN Document Server

    Meadows, AJ

    2007-01-01

    Many books have described how the universe became the way it is today. But what about the future of the universe? How long might the universe as we recognize it survive? The Future of the Universe takes the reader on a journey through space and time, beginning with a long look at the Earth and solar system, voyaging to the outermost galaxies, and finishing with speculations about the life and fate of the entire universe.

  10. Life at a Teaching University

    Science.gov (United States)

    Marineau, Josiah F.

    2018-01-01

    Many new political science faculty at teaching universities are recent PhD recipients, and are coming to these institutions from research-oriented universities. There are considerable differences between the training for graduate students received at research universities and the expectations for faculty at teaching universities. This essay…

  11. Universities Venture into Venture Capitalism.

    Science.gov (United States)

    Desruisseaux, Paul

    2000-01-01

    Reports that some universities are starting their own venture-capital funds to develop campus companies, or are investing endowment funds with established venture-capital firms inclined to finance potential spinoffs from campus research. Examples cited are from the University of Alabama, Vanderbilt University (Tennessee), University of…

  12. RESEARCH UNIVERSITIES IN MALAYSIA: WHAT BEHOLDS?

    Directory of Open Access Journals (Sweden)

    Nooraini Mohamad Sheriff

    2017-12-01

    Full Text Available The National Higher Education Strategic Plan Beyond 2020 aims at further strengthening Malaysian research universities and envisions that two Malaysian universities will be among the Top 100 world universities. To date there are 5 research universities in Malaysia, namely University of Malaya (UM, Universiti Kebangsaan Malaysia (UKM, Universiti Sains Malaysia (USM, Universiti Putra Malaysia (UPM and Universiti Teknologi Malaysia (UTM being the latest addition. These research universities are required to focus primarily on research and innovation activities, driven by highly competent academics and competitive student admissions. Research universities too are expected to explore their intellectual capacity and become models of Malaysian universities in conducting research activities aimed at knowledge advancement. Apart from this research universities are entrusted to generate their own income and establish holding companies responsible for conducting business ventures through the commercialization of their research products. Quality and quantity of researchers, research and postgraduates are also expected to increase in these research driven institutions. This calls for a visionary university leadership and the application of a new image and organizational principles. Education, training and employment policies too have to be reviewed, to ensure staff have the skills necessary for the development of research activities.

  13. Quantum entanglement of baby universes

    International Nuclear Information System (INIS)

    Aganagic, Mina; Okuda, Takuya; Ooguri, Hirosi

    2007-01-01

    We study quantum entanglements of baby universes which appear in non-perturbative corrections to the OSV formula for the entropy of extremal black holes in type IIA string theory compactified on the local Calabi-Yau manifold defined as a rank 2 vector bundle over an arbitrary genus G Riemann surface. This generalizes the result for G=1 in hep-th/0504221. Non-perturbative terms can be organized into a sum over contributions from baby universes, and the total wave-function is their coherent superposition in the third quantized Hilbert space. We find that half of the universes preserve one set of supercharges while the other half preserve a different set, making the total universe stable but non-BPS. The parent universe generates baby universes by brane/anti-brane pair creation, and baby universes are correlated by conservation of non-normalizable D-brane charges under the process. There are no other source of entanglement of baby universes, and all possible states are superposed with the equal weight

  14. Quantum entanglement of baby universes

    International Nuclear Information System (INIS)

    Essman, Eric P.; Aganagic, Mina; Okuda, Takuya; Ooguri, Hirosi

    2006-01-01

    We study quantum entanglements of baby universes which appear in non-perturbative corrections to the OSV formula for the entropy of extremal black holes in type IIA string theory compactified on the local Calabi-Yau manifold defined as a rank 2 vector bundle over an arbitrary genus G Riemann surface. This generalizes the result for G=1 in hep-th/0504221. Non-perturbative terms can be organized into a sum over contributions from baby universes, and the total wave-function is their coherent superposition in the third quantized Hilbert space. We find that half of the universes preserve one set of supercharges while the other half preserve a different set, making the total universe stable but non-BPS. The parent universe generates baby universes by brane/anti-brane pair creation, and baby universes are correlated by conservation of non-normalizable D-brane charges under the process. There are no other source of entanglement of baby universes, and all possible states are superposed with the equal weight

  15. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans.

    Science.gov (United States)

    Kosek, Eva; Jensen, Karin B; Lonsdorf, Tina B; Schalling, Martin; Ingvar, Martin

    2009-07-01

    There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on micro-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG) as compared to those with high expression(LA/LA), p desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.

  16. Architecture of polyglutamine-containing fibrils from time-resolved fluorescence decay.

    Science.gov (United States)

    Röthlein, Christoph; Miettinen, Markus S; Borwankar, Tejas; Bürger, Jörg; Mielke, Thorsten; Kumke, Michael U; Ignatova, Zoya

    2014-09-26

    The disease risk and age of onset of Huntington disease (HD) and nine other repeat disorders strongly depend on the expansion of CAG repeats encoding consecutive polyglutamines (polyQ) in the corresponding disease protein. PolyQ length-dependent misfolding and aggregation are the hallmarks of CAG pathologies. Despite intense effort, the overall structure of these aggregates remains poorly understood. Here, we used sensitive time-dependent fluorescent decay measurements to assess the architecture of mature fibrils of huntingtin (Htt) exon 1 implicated in HD pathology. Varying the position of the fluorescent labels in the Htt monomer with expanded 51Q (Htt51Q) and using structural models of putative fibril structures, we generated distance distributions between donors and acceptors covering all possible distances between the monomers or monomer dimensions within the polyQ amyloid fibril. Using Monte Carlo simulations, we systematically scanned all possible monomer conformations that fit the experimentally measured decay times. Monomers with four-stranded 51Q stretches organized into five-layered β-sheets with alternating N termini of the monomers perpendicular to the fibril axis gave the best fit to our data. Alternatively, the core structure of the polyQ fibrils might also be a zipper layer with antiparallel four-stranded stretches as this structure showed the next best fit. All other remaining arrangements are clearly excluded by the data. Furthermore, the assessed dimensions of the polyQ stretch of each monomer provide structural evidence for the observed polyQ length threshold in HD pathology. Our approach can be used to validate the effect of pharmacological substances that inhibit or alter amyloid growth and structure. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Asking for an extra photon in Higgs production at the LHC and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Gabrielli, Emidio [Dipartimento di Fisica Teorica, Università di Trieste,Strada Costiera 11, I-34151 Trieste (Italy); INFN, Sezione di Trieste,Via Valerio 2, I-34127 Trieste (Italy); National Institute Of Chemical Physics And Biophysics (NICPB),Ravala 10, Tallinn 10143 (Estonia); Mele, Barbara [INFN, Sezione di Roma, c/o Dipartimento di Fisica, “Sapienza' Università di Roma, P.le Aldo Moro 2, I-00185 Rome (Italy); Piccinini, Fulvio [INFN, Sezione di Pavia,Via A. Bassi 6, I-27100 Pavia (Italy); Pittau, Roberto [Departamento de Física Teórica y del Cosmos and CAFPE, Universidad de Granada, Campus Fuentenueva s.n., E-18071 Granada (Spain)

    2016-07-01

    We study the inclusive production of a Higgs boson in association with a high-p{sub T} photon at the LHC, detailing the leading-order features of the main processes contributing to the Hγ final state. Requiring an extra hard photon in Higgs production upsets the cross-section hierarchy for the dominant channels. The Hγ inclusive production comes mainly from photons radiated in vector-boson fusion (VBF), which accounts for about 2/3 of the total rate, for p{sub T}{sup γ,j}>30 GeV, at leading order. On the other hand, radiating a high-p{sub T} photon in the main top-loop Higgs channel implies an extra parton in the final state, which suppresses the production rate by a further α{sub S} power. As a result, the Hγ production via top loops at the LHC has rates comparable with the ones arising from either the Htt̄ production or the HW(Z)γ associated production. Then, in order of decreasing cross section, comes the single-top-plus-Higgs channel, followed in turn by the heavy-flavor fusion processes bb̄→Hγ and cc̄→Hγ. The Hγ production via electroweak loops has just a minor role. At larger c.m. energies, the Htt̄γ channel surpasses the total contribution of top-loop processes. In particular, requiring p{sub T}{sup γ,j}>30 GeV at √S≃100 TeV, Htt̄γ accounts for about 1/4 of the inclusive Hγ production at leading order, about half of the total being due to VBF production.

  18. Granular model, percolation-resistivity, ESR and elastic modulus of carbonaceous materials application to the babassu endocarp heat treated up to 22000C

    International Nuclear Information System (INIS)

    Emmerich, F.G.

    1987-01-01

    A microscopic model (granular model) is presented to study heat treated carbons. A granular structure is defined in the carbon matrix, composed of turbostratic graphite-like microcrystallites, cross-linkings and micropores. A general expression is developed to calculate the volume fraction X of the conducting phase of the granular structure as a function of structural parameters obtained from X-ray diffraction small angle X-ray scattering. The granular model and the percolation theory are used to explain the electrical resistivity behaviour with the heat treatment temperature (HTT), where X is the fundamental parameter. An electron spin resonance (ESR) study of the low and high HTT ranges is presented, including the transition range (700-1300 0 C). The elucitation of the spin center nature in this range and the liking with the two adjacent ranges has been pursued. An expression to calculate the elastic modulus (Young's modulus), based on the microscopic granular model with the fundamental participation of the cross-linkings, is derived to account for the behavior of the modulus with the HTT. The granular model with the expression of X, the percolation-resistivity theory, the ESR study, and the expression of the elastic modulus are applied to the babassu endocarp carbon heat treated up to 2200 0 C. This material can be classified as a tipical non-graphitic carbon, being useful to search the validity of the model and the proposed expressions. It is observed that the theoretical expressions describe with reasonable accuracy the respective experimental behaviours. The measurements of physical and chemical parameters of the babassu endocarp treated up to 2200 0 C area also included. (author) [pt

  19. Establishing a University Foundation.

    Science.gov (United States)

    Lemish, Donald L.

    A handbook on how to establish a university foundation is presented. It presupposes that a foundation will be used as the umbrella organization for receiving all private gifts, restricted and unrestricted, for the benefit of a public college or university; and hence it chiefly addresses readers from public colleges and universities. Information is…

  20. Avoiding student infection during a Middle East respiratory syndrome (MERS outbreak: a single medical school experience

    Directory of Open Access Journals (Sweden)

    Seung Won Park

    2016-06-01

    Full Text Available Purpose: In outbreaks of infectious disease, medical students are easily overlooked in the management of healthcare personnel protection although they serve in clinical clerkships in hospitals. In the early summer of 2015, Middle East respiratory syndrome (MERS struck South Korea, and students of Sungkyunkwan University School of Medicine (SKKUSOM were at risk of contracting the disease. The purpose of this report is to share SKKUSOM’s experience against the MERS outbreak and provide suggestions for medical schools to consider in the face of similar challenges. Methods: Through a process of reflection-on-action, we examined SKKUSOM’s efforts to avoid student infection during the MERS outbreak and derived a few practical guidelines that medical schools can adopt to ensure student safety in outbreaks of infectious disease. Results: The school leadership conducted ongoing risk assessment and developed contingency plans to balance student safety and continuity in medical education. They rearranged the clerkships to another hospital and offered distant lectures and tutorials. Five suggestions are extracted for medical schools to consider in infection outbreaks: instant cessation of clinical clerkships; rational decision making on a school closure; use of information technology; constant communication with hospitals; and open communication with faculty, staff, and students. Conclusion: Medical schools need to take the initiative and actively seek countermeasures against student infection. It is essential that medical schools keep constant communication with their index hospitals and the involved personnel. In order to assure student learning, medical schools may consider offering distant education with online technology.

  1. A business strategy formulation for commercializing university-created technology: A university spin-offs

    Science.gov (United States)

    Saputra, Iqbal Wahyu; Sutopo, Wahyudi; Zakaria, Roni

    2018-02-01

    There are some mechanism to commercialize the innovations that have been developed by academic scientists in universities, i.e. patenting, licensing, start-up creation, and university-industry partnerships. The start-up creations or university spin-offs (USOs) company is a very special start-up company that is founded by an academic inventor and the university with the aim to commercialize the technological innovation that created by the university. However, it is not always as smooth as expected. The market competitiveness of the USOs obviously has many challenges to be able to compete with the existing companies, analysis need to be done to get the right business step so the business strategy will be efficient. In this article, we discuss a real case study of a university spin-off that owned by Sebelas Maret University for Commercializing Battery Lithium. The aim of our research is twofold: first, to identify the gap in the literature of business strategy formulation between a conventional and USOs. Second, to propose a business strategy formulation for commercializing university-created technology, i.e. battery lithium as core business of a university spin-off as a case study. We conduct surveys, observation and FGD in order to collect the data and information to build the company objective and goals. The analytical tools to generate the solution of business strategy are SWOT analysis, IFE-EFE matrix, and QSPM model so the result will be the most attractive and suitable for the company. The result shows that the case study of USO company is classified on conservative continuous improvement phase so the suitable strategy for this company are product development and business strategy integration.

  2. Building Human Resources Management Capacity for University Research: The Case at Four Leading Vietnamese Universities

    Science.gov (United States)

    Nguyen, T. L.

    2016-01-01

    At research-intensive universities, building human resources management (HRM) capacity has become a key approach to enhancing a university's research performance. However, despite aspiring to become a research-intensive university, many teaching-intensive universities in developing countries may not have created effective research-promoted HRM…

  3. The deep universe

    CERN Document Server

    Sandage, AR; Longair, MS

    1995-01-01

    Discusses the concept of the deep universe from two conflicting theoretical viewpoints: firstly as a theory embracing the evolution of the universe from the Big Bang to the present; and secondly through observations gleaned over the years on stars, galaxies and clusters.

  4. The Triad Research University or a Post 20th Century Research University Model

    Science.gov (United States)

    Tadmor, Zehev

    2006-01-01

    In this paper, a model for the future research university is proposed, which answers some of the key challenges facing universities. It consists of three independent yet closely knitted entities: a research institute, a university teaching college and a business unit creating a "triad" structure. The possible inevitability, the advantages and…

  5. Antimatter in the universe

    Science.gov (United States)

    Stigman, G.

    1973-01-01

    The means of detecting the presence of antimatter in the universe are discussed. Both direct, annihilation processes, and indirect, cosmic ray particles, were analyzed. All results were negative and it was concluded that no antimatter exists, if the universe is in fact symmetric. If the universe is not symmetric then matter and antimatter are well separated from each other.

  6. College student bereavement, scholarship, and the university: a call for university engagement.

    Science.gov (United States)

    Balk, D E

    2001-01-01

    The prevalence of bereavement among traditional-aged college students should impel universities to assist bereaved students on their campuses. Dealing with bereavement can not only challenge a college student's completing the developmental tasks that our society sets for the later adolescent years, but also imperil the student's remaining in school and graduating. It is in the best interests of the university to develop and implement a variety of effective interventions to assist bereaved students. The author argues that universities are communities devoted to scholarly endeavors and should explicitly incorporate the dimension of compassion and caring. An abbreviated case study is used to illustrate the situations in which one grieving student found herself when she returned to school following the death of her father. A call is made for greater university engagement by forming a university-based bereavement center to coordinate and conduct coherent inquiry that fulfills the scholarly functions of discovery, application, and instruction. Four specific actions for a bereavement center are to train nonbereaved students to provide peer support, to provide structured interventions for college students at risk of bereavement complications, to raise consciousness about bereavement on the university campus, and to conduct research into various bereavement populations and bereavement topics.

  7. The intelligent Universe

    International Nuclear Information System (INIS)

    Hoyle, F.

    1983-01-01

    The subject is covered in chapters, entitled: chance and the universe (synthesis of proteins; the 'primordial soup'); the gospel according to Darwin (discussion of Darwin theory of evolution); life did not originate on earth (fossils from space; life in space); the interstellar connection (living dust between the stars; bacteria in space falling to the earth; interplanetary dust); evolution by cosmic control (microorganisms; genetics); why aren't the others here (a cosmic origin of life); after the big bang (big bang and steady state); the information rich universe; what is intelligence up to; the intelligent universe. (U.K.)

  8. University of Maryland MRSEC - Collaborations

    Science.gov (United States)

    . University of Maryland Materials Research Science and Engineering Center Home About Us Leadership , National Nanotechnology Lab, Neocera, NIST, Rowan University, Rutgers University, Seagate, Tokyo Tech

  9. Self-image and Missions of Universities: An Empirical Analysis of Japanese University Executives

    Directory of Open Access Journals (Sweden)

    Masataka Murasawa

    2014-05-01

    Full Text Available As universities in Japan gain institutional autonomy in managing internal organizations, independent of governmental control as a result of deregulation and decentralizing reforms, it is becoming increasingly important that the executives and administrators of each institution demonstrate clear and strategic vision and ideas to external stakeholders, in order to maintain financially robust operations and attractiveness of their institutions. This paper considers whether and how the self-image, mission, and vision of universities are perceived and internalized by the management of Japanese universities and empirically examines the determinants of shaping such individual perceptions. The result of our descriptive analysis indicates that the recent government policy to internationalize domestic universities has not shown much progress in the view of university executives in Japan. An increasing emphasis on the roles of serving local needs in research and teaching is rather pursued by these universities. Individual perceptions among Japanese university executives with regard to the missions and functional roles to be played by their institutions are influenced by managerial rank as well as the field of their academic training. A multiple regression analysis reveals that the economy of scale brought out by an expanded undergraduate student enrollment gradually slows down and decelerate executive perceptions, with regard to establishing a globally recognized status in research and teaching. Moreover, Japanese universities with a small proportion of graduate student enrollment, likely opted out from competitions for gaining a greater respect in the global community of higher education between 2005 and 2012. Finally, the management in universities granted with the same amount of external research funds in both studied years responded more passively in 2012 than did in 2005 on the self-assessment of whether having established a status as a global

  10. Age of the universe

    International Nuclear Information System (INIS)

    Parker, B.

    1981-01-01

    The age of the universe is the time that has elapsed since the Big Bang. To calculate the age, the expansion rate of the universe and distance to the galaxies must be determined. Unfortunately, it appears that the expansion rate is not constant but is decelerating. In the 1920's and 30's, Edwin Hubble set out to estimate the age of universe based on the expansion rate and distance to the galaxies. His method is described along with its flaw. Since that time several others have estimated the age of the universe. Their methods as well as results vary. These are discussed in the article. The ages determined from the various methods range from 10 to 20 billion years. There are two independent ways to determine the age of the universe. What they actually do is determine the age of our galaxy which would give a lower limit to the age of the universe. The first method calculates age of globular clusters which yields as age range from 8 to 18 billion years. The second method involves observing the speed at which radioactive substances decay. This also yields and age greater than 10 billion years. It is clear that there is still a lot of work to do before the true age of the universe can be determied

  11. On universality in ergoregion mergers

    International Nuclear Information System (INIS)

    Elvang, Henriette; Figueras, Pau; Hubeny, Veronika E; Rangamani, Mukund; Horowitz, Gary T

    2009-01-01

    We study non-dynamical mergers of ergoregions in d + 1-dimensional vacuum gravity. At the merger point, where the ergosurfaces bounding each ergoregion just touch, solutions exhibit universal behavior when there is rotation only in one plane: the angle between the merging ergosurfaces depends only on the symmetries of the solution, not on any other details of the configuration. We show that universality follows from the fact that the relevant component of Einstein's equation reduces to Laplace's equation at the point of merger. Thus ergoregion mergers mimic mergers of Newtonian equipotentials and have similar universal behavior. For solutions with rotation in more than one plane, universality is lost. We demonstrate universality and non-universality in several explicit examples.

  12. Dipolar flow theory of the universe in relation to astronomical observations and universe axis

    International Nuclear Information System (INIS)

    Mullick, U.P.

    1975-01-01

    An attempt has been made to establish Dipolar continuous flow theory of the universe through corroborations from astronomical observations of the positions of nebulae made earlier by astronomers. It is shown that the line through groups of nebulae in Nubecula Major in Southern Sky Region 5, passing through Earth points towards the near side pole A of the universe. Also the angles the plane parallel to universe polar plane x-x and passing through Earth, makes with the Milky Way disc is about 70 0 towards universe pole B, and about 110 0 towards nearside universe pole A. It is also shown that the two nebulae M 31 and M 33 and the groups of nebulae in Megallenic clouds, in Nebecula Major are between planes passing through universe equatorial axis y-y and plant Ysub(E)-Ysub(E) passing through Earth and parallel to universe equatorial plane Y-Y. Besides, the huge red star Betelgeux and the great Nebula in Orion in sky Region 9 are also between these two planes. These observations the author claims accord with his Dipolar Theory. (author)

  13. From Universal Access to Universal Proficiency.

    Science.gov (United States)

    Lewis, Anne C.

    2003-01-01

    Panel of five education experts--Elliot Eisner, John Goodlad, Patricia Graham, Phillip Schlechty, and Warren Simons--answer questions related to recent school reform efforts, such as the No Child Left Behind Act, aimed at achieving universal educational proficiency. (PKP)

  14. Cultural universals: So what?

    Directory of Open Access Journals (Sweden)

    M. Elaine Botha

    1989-03-01

    Full Text Available The search for the elusive "cultural universal s” in a variety of academic disciplines has been motivated b y the spectre of relativism in its diverse guises. The problem of relativism has been thrust upon us inter alia by the inability of our epistemological models to account for social and cultural, moral and cognitive diversity and to provide us with criteria by means of which to judge aberrations like ideologies. Contrary to the general trend I would like to argue that it is not the spectre of relativism in its various guises which necessitates the search for cultural universals, nor is this the only motivation for a Christian to argue in favour of the recognition of cultural universals. Various authors have suggested that such universal structures do exist; that they condition human and societal behaviour and that it would in principle be possible to construct a theory of these structural universals or a "biogrammar" or "geography ” of the universal cultural acquisition device of humankind (cf. Harre,1976, 32; Johnson, 1987: xxxvii ; Tige r and Fox, 1974:17,30. Cross -cu ltural research in both psychology and anthropology has pointed to the existence of such traits, and in recent philosophical discussions Apel and others have pointed to the necessity of recognizing the existence of some sort of " transcendentalia" . These arguments emphasize elements that are common to diverse approaches to the problem of cultural universals. Christian scholars could accept most of these arguments as valid and yet argue in favour of a very specifically modified version of the notion of cultural universals. This essay attempts to develop such a position.

  15. The university with conditions

    Directory of Open Access Journals (Sweden)

    José María Ripalda Crespo

    2013-03-01

    Full Text Available The model of the national university is being substituted by that of the global university. At the same time, new dogmas that appear with economic labels are being imposed. All this is accompanied by important cultural changes. The Spanish university was one of the instances that was taken care of by the post-Francoist regime. Now, this regime feels strong against it, and on the other hand this university – as the whole of the productive structure – requires a reform. It is not expected that this reform will go in the direction of the university having more social presence, but rather more presence of companies. It is neither expected that it will imply more internal democracy, but more discipline. All resistance or alternative has to take into account the new situation and join the still dispersed forces that still have, however, a constitutive capacity.

  16. Dropout Phenomena at Universities

    DEFF Research Database (Denmark)

    Larsen, Michael Søgaard; Kornbeck, Kasper Pihl; Kristensen, Rune

    Dropout from university studies comprises a number of complex phenomena with serious complex consequences and profound political attention. Further analysis of the field is, therefore, warranted. Such an analysis is offered here as a systematic review which gives answers based on the best possible...... such dropout phenomena occur at universities? What can be done by the universities to prevent or reduce such dropout phenomena?...

  17. Possible physical universes

    Directory of Open Access Journals (Sweden)

    Gordon McCabe

    2005-12-01

    Full Text Available The purpose of this paper is to discuss the various types of physical universe which could exist according to modern mathematical physics. The paper begins with an introduction that approaches the question from the viewpoint of ontic structural realism. Section 2 takes the case of the 'multiverse' of spatially homogeneous universes, and analyses the famous Collins-Hawking argument, which purports to show that our own universe is a very special member of this collection. Section 3 considers the multiverse of all solutions to the Einstein field equations, and continues the discussion of whether the notions of special and typical can be defined within such a collection.

  18. University of Aarhus - the stepping stones

    DEFF Research Database (Denmark)

    Nielsen, Kent T.

    is currently facing major challenges. Changes in the Danish University Act and a strong political wish for closer partnerships between the private business community, the public sector and the country's universities have gradually altered the role of the universities in Denmark today. This paper looks more...... closely at the history of the University of Aarhus, the importance of the University for the Aarhus region, and the opportunities and barriers facing an "old" comprehensive University in its attempts to adapt to the new role of universities in the knowledge society....

  19. The Pragmatic University: A Feasible Utopia?

    Science.gov (United States)

    Badley, Graham

    2016-01-01

    "Imaginings" of the modern university include such ideas as "the ecological university" and "the pragmatic university". In his attempt to separate utopian from dystopian visions of the university, Ronald Barnett concentrates on an analysis of the ecological university and ignores, for example, the case of the…

  20. University involvement in sustainability initiatives

    DEFF Research Database (Denmark)

    Lehmann, Martin; Christensen, Per; Thrane, Mikkel

    2007-01-01

    With an outset in the case of Aalborg University, the linkages (actual, potential and missing) between academic work in research & education and sustainability initiatives are explored. The focus is both on the university's core activities as a provider of research and education and on the univer......With an outset in the case of Aalborg University, the linkages (actual, potential and missing) between academic work in research & education and sustainability initiatives are explored. The focus is both on the university's core activities as a provider of research and education...... and on the university's activities as an organisation, i.e. its own operation and its accounting for this. Sustainability is defined as a continuous process requiring balance between (the emergence of) problems and our ability and capability to solve them. Some core questions that this paper seeks to answer are: "How...... is Sustainable Development understood at executive level at the university? How (if at all) is sustainable development integrated in the core activities of the university? How is the university attached to ‘real life outside the ivory tower', e.g. through the establishing of Public-Private-Academic Partnerships...

  1. Managing the research university : Clark Kerr and the University of California

    NARCIS (Netherlands)

    Soo, M; Carson, C

    In the 1950s and 1960s, Clark Kerr led the University of California's Berkeley campus, and then the University of California as a whole. Throughout these years, he developed a system of managerial strategies. This paper shows how Kerr's administrative views drew upon his background in industrial

  2. Oscillating universe with quintom matter

    International Nuclear Information System (INIS)

    Xiong Huahui; Cai Yifu; Qiu Taotao; Piao Yunsong; Zhang Xinmin

    2008-01-01

    In this Letter, we study the possibility of building a model of the oscillating universe with quintom matter in the framework of 4-dimensional Friedmann-Robertson-Walker background. Taking the two-scalar-field quintom model as an example, we find in the model parameter space there are five different types of solutions which correspond to: (I) a cyclic universe with the minimal and maximal values of the scale factor remaining the same in every cycle, (II) an oscillating universe with its minimal and maximal values of the scale factor increasing cycle by cycle, (III) an oscillating universe with its scale factor always increasing, (IV) an oscillating universe with its minimal and maximal values of the scale factor decreasing cycle by cycle, and (V) an oscillating universe with its scale factor always decreasing

  3. The universe strikes back

    International Nuclear Information System (INIS)

    Steigman, G.

    1983-01-01

    The approach to particle physics via cosmology may meet with an obstacle in a series of cosmological puzzles studied in this paper: the flatness-longevity puzzle, the horizon-homogenity puzzle, and the cosmological constant puzzle. An analysis of the geometry and dynamics of the universe leads to an understanding (but not solution) of the flatness-longevity puzzle: possible universes are distinguished by the value of the dimensionless quantity N, the coordinate density of ER particles, such that the longevity of the universe is fixed by N. Universes where nonrelativistic particles dominate are then studied. An inflationary scenario proposed as a solution to these puzzles is studied, but found to have some difficulties

  4. University Environment Experience of the First Two Years of University Graduates at a Newly Established Small University Located in Suburban Area in Taiwan

    Science.gov (United States)

    Lin, Yii-Nii

    2011-01-01

    The purpose of this study is to describe students' university environment experience from the perspectives of the first two years of university graduates of a newly established small university located in suburban area in Taiwan. A qualitative method of phenomenology with in-depth interviews is adopted. Fourteen male and sixteen female seniors,…

  5. Phenotype-gene: 399 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available rescence for quantity of chlorophyll for AT5G51545 Ma Jinfang et al. 2007 Jun. Plant Cell 19(6):1980-93. htt...p://metadb.riken.jp/db/SciNetS_ria224i/cria224u4ria224u17601825i increased fluorescence for quantity of chloroph

  6. The development of high-temperature reactors in the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Engelmann, P.; Krings, F.

    1980-01-01

    The principal features of high-temperature reactors are recalled, then the current state of technology of the line in the Federal Republic of Germany is described. Reference is made to the experience of operating the AVR reactor, the construction of the THTR-300 reactor as well as the HTT and PNP projects [fr

  7. The Antinomic Condition of the University: "Universal Labour" beyond "Academic Capitalism"

    Science.gov (United States)

    Pavlidis, Periklis

    2012-01-01

    This paper aims at identifying the characteristics acquired by the university under the regime of academic capitalism. It also attempts to put forward their antinomic relationship to the essential properties of academic activity, perceived in the light of the concept of "universal labour" introduced by Karl Marx. (Contains 1 note.)

  8. Universal Majorana thermoelectric noise

    Science.gov (United States)

    Smirnov, Sergey

    2018-04-01

    Thermoelectric phenomena resulting from an interplay between particle flows induced by electric fields and temperature inhomogeneities are extremely insightful as a tool providing substantial knowledge about the microscopic structure of a given system. By tuning, e.g., parameters of a nanoscopic system coupled via tunneling mechanisms to two contacts, one may achieve various situations where the electric current induced by an external bias voltage competes with the electric current excited by the temperature difference of the two contacts. Even more exciting physics emerges when the system's electronic degrees freedom split to form Majorana fermions which make the thermoelectric dynamics universal. Here, we propose revealing these unique universal signatures of Majorana fermions in strongly nonequilibrium quantum dots via noise of the thermoelectric transport beyond linear response. It is demonstrated that whereas mean thermoelectric quantities are only universal at large-bias voltages, the noise of the electric current excited by an external bias voltage and the temperature difference of the contacts is universal at any bias voltage. We provide truly universal, i.e., independent of the system's parameters, thermoelectric ratios between nonlinear response coefficients of the noise and mean current at large-bias voltages where experiments may easily be performed to uniquely detect these truly universal Majorana thermoelectric signatures.

  9. A Closed Universe Expanding Forever

    Directory of Open Access Journals (Sweden)

    Silva N. P.

    2014-07-01

    Full Text Available In a recent paper, the expression a ( t = e H 0 T 0 [ ( t T 0 where = 0 : 5804, was proposed for the expansion factor of our Universe. According to it, gravity dominates the expan- sion ( matter era until the age of T ⋆ = 3 : 214 Gyr and, after that, dark energy dominates ( dark energy era leading to an eternal expansion, no matter if the Universe is closed, flat or open. In this paper we consider only the closed version and show that there is an upper limit for the size of the radial comoving coordinate, beyond which nothing is observed by our fundamental observer, on Earth. Our observable Universe may be only a tiny portion of a much bigger Universe most of it unobservable to us. This leads to the idea that an endless number of other fundamental observers may live on equal number of Universes similar to ours. Either we talk about many Universes — Multiverse — or about an unique Universe, only part of it observable to us.

  10. Universities as Research Partners

    OpenAIRE

    Hall, Bronwyn; Link, Albert; Scott, John

    2010-01-01

    Universities are a key institution in the U.S. innovation system, and an important aspect of their involvement is the role they play in public-private partnerships. This note offers insights into the performance of industry-university research partnerships, using a survey of precommercial research projects funded by the Advanced Technology Program. Although results must be interpreted cautiously because of the small size of the sample, the study finds that projects with university involvement...

  11. [Comparison of biomedical engineering education between Southeast University (China) and American universities].

    Science.gov (United States)

    Wang, Xi; Huang Ningping; Sun Xiao; Gu Ning

    2011-06-01

    Taking Duke University as an example, this article makes a comparison between the major of biomedical engineering in the Southeast University and that in American universities in term of subject direction, faculty, teaching principle and status of publishing academic papers. Through the comparison and analysis, the problems we face were explored. From the comparison and summary the future improvements in four aspects, such as strengthening the interdisciplinary among different majors, etc. so as to provide an inspiration on the future perspectives of research and teaching in biomedical engineering in China.

  12. Is our Universe typical?

    International Nuclear Information System (INIS)

    Gurzadyan, V.G.

    1988-01-01

    The problem of typicalness of the Universe - as a dynamical system possessing both regular and chaotic regions of positive measure of phase space, is raised and discussed. Two dynamical systems are considered: 1) The observed Universe as a hierarchy of systems of N graviting bodies; 2) (3+1)-manifold with matter evolving to Wheeler-DeWitt equation in superspace with Hawking boundary condition of compact metrics. It is shown that the observed Universe is typical. There is no unambiguous answer for the second system yet. If it is typical too then the same present state of the Universe could have been originated from an infinite number of different initial conditions the restoration of which is practically impossible at present. 35 refs.; 2 refs

  13. University Advertising and Universality in Messaging

    Science.gov (United States)

    Diel, Stan R.; Katsinas, Stephen

    2018-01-01

    University and college institutional advertisements, which typically are broadcast as public service announcements during the halftime of football games, were the subject of a quantitative analysis focused on commonality in messaging and employment of the semiotic theory of brand advertising. Findings indicate advertisements focus on students'…

  14. Geometry of the Universe

    International Nuclear Information System (INIS)

    Gurevich, L.Eh.; Gliner, Eh.B.

    1978-01-01

    Problems of investigating the Universe space-time geometry are described on a popular level. Immediate space-time geometries, corresponding to three cosmologic models are considered. Space-time geometry of a closed model is the spherical Riemann geonetry, of an open model - is the Lobachevskij geometry; and of a plane model - is the Euclidean geometry. The Universe real geometry in the contemporary epoch of development is based on the data testifying to the fact that the Universe is infinitely expanding

  15. Inter-Universal Quantum Entanglement

    Science.gov (United States)

    Robles-Pérez, S. J.; González-Díaz, P. F.

    2015-01-01

    The boundary conditions to be imposed on the quantum state of the whole multiverse could be such that the universes would be created in entangled pairs. Then, interuniversal entanglement would provide us with a vacuum energy for each single universe that might be fitted with observational data, making testable not only the multiverse proposal but also the boundary conditions of the multiverse. Furthermore, the second law of the entanglement thermodynamics would enhance the expansion of the single universes.

  16. Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Kim J

    2015-09-01

    Full Text Available Joohae Kim,1 Ho Il Yoon,2 Yeon-Mok Oh,3 Seong Yong Lim,4 Ji-Hyun Lee,5 Tae-Hyung Kim,6 Sang Yeub Lee,7 Jin Hwa Lee,8 Sang-Do Lee,3 Chang-Hoon Lee11Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, 3Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 5Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, 6Division of Pulmonology, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, 7Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, 8Department of Internal Medicine, Ewha Womans University Mokdong Hospital, College of Medicine, Ewha Womans University, Seoul, Republic of KoreaBackground: Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD groups A-D were introduced, the lung function changes according to group have been evaluated rarely.Objective: We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines.Methods: Patients with COPD included in the Korean Obstructive Lung Disease (KOLD prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included. The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1, which was analyzed by

  17. Whither the African University

    African Journals Online (AJOL)

    Sam

    reform. 1. Associate Professor, Department of Philosophy, Addis Ababa University ..... reduce African universities to virtually vocational schools. The World ..... theories, established institutions, and widely held beliefs according to the cannons ...

  18. Recipes for the Universe

    CERN Multimedia

    2005-01-01

    As part of the World Year of Physics, the Physics Section of the University of Geneva is organising a series of conferences for the uninitiated. Each of the conferences will begin with a demonstration in the auditorium of the detection of cosmic rays and, in collaboration with Professor E. Ellberger of the Conservatoire de Musique de Genève, of how these signals from the farthest reaches of the Universe can be used to create "cosmic music". The third conference in the series, "How to build a universe?", will take place on Tuesday 15 March 2005 and the speaker will be the CERN theoretical physicist, John Ellis. A tiny number of elementary particles are responsible for the very diverse universe that surrounds us. These basic building blocks of matter interact by exchanging photons and other similar particles. After summing up what we know about these fundamental building blocks, their role in the history of the universe will be discussed. Where does matter come from? Where do the structures that ...

  19. In Search of Cultural Universals: Translation Universals. Case Studies

    Directory of Open Access Journals (Sweden)

    Gabriela DIMA

    2014-12-01

    Full Text Available Knowledge of the world is disclosed under various shapes, among which language is the best representative. Specific to humans, it renders feelings and thoughts concerning different communication contexts where words become dynamic primitives endowed with meanings, which recreate themes and reconfigure space and time as universal coordinates. The main objective of the paper is to provide a tentative analysis of the way in which translation universals are manifest in translating proverbs and sayings in the short novels Popa Tanda (Pope Tanda and Moara cu Noroc (The Lucky Mill by Ioan Slavici.

  20. A Model of Nonsingular Universe

    Directory of Open Access Journals (Sweden)

    Changjun Gao

    2012-07-01

    Full Text Available In the background of Friedmann–Robertson–Walker Universe, there exists Hawking radiation which comes from the cosmic apparent horizon due to quantum effect. Although the Hawking radiation on the late time evolution of the universe could be safely neglected, it plays an important role in the very early stage of the universe. In view of this point, we identify the temperature in the scalar field potential with the Hawking temperature of cosmic apparent horizon. Then we find a nonsingular universe sourced by the temperature-dependent scalar field. We find that the universe could be created from a de Sitter phase which has the Planck energy density. Thus the Big-Bang singularity is avoided.

  1. Factors Affecting Individual Education Demand at the Entrance to University: Adnan Menderes University Sample

    Science.gov (United States)

    Sarpkaya, Ruhi

    2010-01-01

    The aim of this research is to determine the factors affecting individual education demands at the entrance to university. The research is in survey model. The universe of the study consists of 1630 freshmen at the faculties and vocational schools of Adnan Menderes University, Aydin. 574 students from 7 schools were included in the sample. The…

  2. Origin (?) of the Universe

    Indian Academy of Sciences (India)

    cal models of the universe are based on the idea, which is supported by ... Only the continuous distribution was clearly ... displaced from their natural locations, their observed wave- .... universe? Mathematical Models: Basic Assumptions.

  3. Graphitization kinetics of fluidized-bed pyrolytic carbons

    International Nuclear Information System (INIS)

    Beatty, R.L.

    1975-08-01

    Graphitization of 12 fluidized-bed pyrocarbons was studied as a function of heat-treatment time and temperature (1350 to 3000 0 C) to investigate the effect of initial microstructure on the graphitization process. The term ''graphitization'' is defined to include any thermally induced structural change, whether or not any layer stacking order is attained. A broad range of CVD microstructures was prepared at temperatures from 1150 to 1900 0 C and various propylene and methane concentrations. The twelve carbons spanned a wide range of graphitizabilities, primarily as a function of deposition temperature. Hydrocarbon concentration was of much less importance except for deposition at 1900 0 C. Hydrogen content of the as-deposited carbons decreased with increasing temperature of deposition, and initial graphitization behavior of the low-temperature carbons appeared to be related to hydrogen content and evolution. Rates of change in the parameters varied widely throughout the range of heat-treatment times (HTt) and temperatures (HTT) for the different carbons showing differences between the more graphitizable or ''soft'' carbons from the nongraphitizing or ''hard'' carbons. ΔH for nongraphitizing carbons was 175 +- 15 kcal below 1950 0 C, 240 +- 35 kcal at 1950 to 2700 0 C, and 330 +- 20 kcal above 2700 0 C. For graphitizing carbons deposited at 1150 0 C, values near 245 kcal were obtained from anti chi data for the HTT range 1350 to 1650 0 C, while densification data yielded values of about 160 kcal in the same range. The behaviors observed for graphitizable carbons above 2000 0 C are consistent with literature. Different kinetic behaviors below 2000 0 C were shown to be due to different initial microstructures as well as to different parameters measured. (U.S.)

  4. Electrochemical performance of DVB-modified SiOC and SiCN polymer-derived negative electrodes for lithium-ion batteries

    International Nuclear Information System (INIS)

    Liu, Guanwei; Kaspar, Jan; Reinold, Lukas Mirko; Graczyk-Zajac, Magdalena; Riedel, Ralf

    2013-01-01

    Highlights: • Polymer-derived SiCN and SiOC ceramics are studied as anode for Li-ion batteries. • Ceramic precursors are modified in order to increase the carbon content. • Ceramic matrix stabilizes free carbon phase. • Stabilizing role is lost once the amount of carbon exceeds a threshold value. -- Abstract: Chemical modification of commercially available polyorganosilazane (HTT1800) and polyorganosiloxane (Polyramic RD-684a) with divinylbenzene (DVB) is accomplished via hydrosilylation reaction. The incorporation of DVB leads to an increase of the free carbon amount after pyrolysis within the corresponding SiCN and SiOC ceramics. The modification is carried out with lower, equal and higher stoichiometric ratios of the Si-H to C=C groups present in the Si-based polymer and DVB. FTIR results indicate a complete consumption of the Si-H bonds in the case of the stoichiometric amount of DVB and polymer RD-684a, while for HTT1800 neither the stoichiometric ratio nor DVB excess leads to a complete consumption of the Si-H groups. For both SiCN and SiOC ceramics the carbon content is found to increase with the amount of DVB. However, the most significant increase in free carbon content is registered for SiCN samples, namely of ca. 40%. The carbon content changed from 9.9 wt.% in the pure HTT1800-derived material up to 49.3 wt.% for the SiCN ceramic obtained with the highest amount of DVB addition. Accordingly, Li-ion storage and therefore charge storage capacity are simultaneously increased, for the first cycle from 136 to 574 mAh g −1 , while columbic efficiency is raised by 10% up to 60.4%

  5. A gene-environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder.

    Science.gov (United States)

    Jacob, Christian P; Nguyen, Thuy Trang; Dempfle, Astrid; Heine, Monika; Windemuth-Kieselbach, Christine; Baumann, Katarina; Jacob, Florian; Prechtl, Julian; Wittlich, Maike; Herrmann, Martin J; Gross-Lesch, Silke; Lesch, Klaus-Peter; Reif, Andreas

    2010-06-01

    While an interactive effect of genes with adverse life events is increasingly appreciated in current concepts of depression etiology, no data are presently available on interactions between genetic and environmental (G x E) factors with respect to personality and related disorders. The present study therefore aimed to detect main effects as well as interactions of serotonergic candidate genes (coding for the serotonin transporter, 5-HTT; the serotonin autoreceptor, HTR1A; and the enzyme which synthesizes serotonin in the brain, TPH2) with the burden of life events (#LE) in two independent samples consisting of 183 patients suffering from personality disorders and 123 patients suffering from adult attention deficit/hyperactivity disorder (aADHD). Simple analyses ignoring possible G x E interactions revealed no evidence for associations of either #LE or of the considered polymorphisms in 5-HTT and TPH2. Only the G allele of HTR1A rs6295 seemed to increase the risk of emotional-dramatic cluster B personality disorders (p = 0.019, in the personality disorder sample) and to decrease the risk of anxious-fearful cluster C personality disorders (p = 0.016, in the aADHD sample). We extended the initial simple model by taking a G x E interaction term into account, since this approach may better fit the data indicating that the effect of a gene is modified by stressful life events or, vice versa, that stressful life events only have an effect in the presence of a susceptibility genotype. By doing so, we observed nominal evidence for G x E effects as well as main effects of 5-HTT-LPR and the TPH2 SNP rs4570625 on the occurrence of personality disorders. Further replication studies, however, are necessary to validate the apparent complexity of G x E interactions in disorders of human personality.

  6. Characterization of neurophysiological and behavioral changes, MRI brain volumetry and 1H MRS in zQ175 knock-in mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Taneli Heikkinen

    Full Text Available Huntington's disease (HD is an autosomal neurodegenerative disorder, characterized by severe behavioral, cognitive, and motor deficits. Since the discovery of the huntingtin gene (HTT mutation that causes the disease, several mouse lines have been developed using different gene constructs of Htt. Recently, a new model, the zQ175 knock-in (KI mouse, was developed (see description by Menalled et al, [1] in an attempt to have the Htt gene in a context and causing a phenotype that more closely mimics HD in humans. Here we confirm the behavioral phenotypes reported by Menalled et al [1], and extend the characterization to include brain volumetry, striatal metabolite concentration, and early neurophysiological changes. The overall reproducibility of the behavioral phenotype across the two independent laboratories demonstrates the utility of this new model. Further, important features reminiscent of human HD pathology are observed in zQ175 mice: compared to wild-type neurons, electrophysiological recordings from acute brain slices reveal that medium spiny neurons from zQ175 mice display a progressive hyperexcitability; glutamatergic transmission in the striatum is severely attenuated; decreased striatal and cortical volumes from 3 and 4 months of age in homo- and heterozygous mice, respectively, with whole brain volumes only decreased in homozygotes. MR spectroscopy reveals decreased concentrations of N-acetylaspartate and increased concentrations of glutamine, taurine and creatine + phosphocreatine in the striatum of 12-month old homozygotes, the latter also measured in 12-month-old heterozygotes. Motor, behavioral, and cognitive deficits in homozygotes occur concurrently with the structural and metabolic changes observed. In sum, the zQ175 KI model has robust behavioral, electrophysiological, and histopathological features that may be valuable in both furthering our understanding of HD-like pathophyisology and the evaluation of potential therapeutic

  7. De-Internationalization of Universities

    DEFF Research Database (Denmark)

    Turcan, Romeo V.; Gulieva, Valeria

    Alongside student and staff mobility, universities these days get also actively involved in out-ward cross-border activities, such as licensing, entering joint ventures and establishing campuses. These cross-border activities are not without pitfalls however. A large number of universities de-int...... on withdrawals from franchise, joint venture, and branch campus operations. We use the concept of de-internationalization as a theoretical lens and conduct a review of available unobtrusive data to identify reasons and patterns of universities' withdrawals from international markets....

  8. Universal service policy in Vietnam

    DEFF Research Database (Denmark)

    Do Manh, Thai; Falch, Morten; Von Salakpi, Simeon

    2016-01-01

    Universal service provision is a key to bridge the digital divide. This paper provides an empirical examination of the Vietnamese universal policy introduced in 2015 for implementation up to 2020. Using the framework of King et al. (1994) the paper analyses the universal services policy in Vietna...

  9. Dopaminergic, Serotonergic, and Oxytonergic Candidate Genes Associated with Infant Attachment Security and Disorganization? In Search of Main and Interaction Effects

    Science.gov (United States)

    Luijk, Maartje P. C. M.; Roisman, Glenn I.; Haltigan, John D.; Tiemeier, Henning; Booth-LaForce, Cathryn; van IJzendoorn, Marinus H.; Belsky, Jay; Uitterlinden, Andre G.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Tharner, Anne; Bakermans-Kranenburg, Marian J.

    2011-01-01

    Background and methods: In two birth cohort studies with genetic, sensitive parenting, and attachment data of more than 1,000 infants in total, we tested main and interaction effects of candidate genes involved in the dopamine, serotonin, and oxytocin systems ("DRD4", "DRD2", "COMT", "5-HTT", "OXTR") on attachment security and disorganization.…

  10. Phenotype-gene: 454 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available stance in response to organism biotroph for AT5G60600 Gil M Jos辿 et al. 2005 Oct. Plant J. 44(1):155-66. htt...p://metadb.riken.jp/db/SciNetS_ria224i/cria224u4ria224u16167903i increased resistance in response to organism biotroph

  11. INCUBATORS WITHIN UNIVERSITY AND CLUSTERED CONTEXTS: CASES OF NATIONAL CHIAO TUNG UNIVERSITY (NCTU AND NATIONAL TSING HUA UNIVERSITY (NTHU INCUBATORS IN HSINCHU, TAIWAN

    Directory of Open Access Journals (Sweden)

    Khairul Akmaliah Adham

    2008-01-01

    Full Text Available Research literature on business incubators has highlighted the significance of clustered locational contexts and networking as key to an incubator's success. Using the case study approach, this study aimed to test the validity of this framework for explaining the level of success of the National Chiao Tung University (NCTU and National Tsing Hua University (NTHU Incubators in Hsinchu, Taiwan – both of which are highly-networked, cluster-centric and university-based. In-depth interviews were conducted with the managers of both incubators, and these were followed by information gathering on university patents and knowledge transfers from the research and development (R&D office at each university. Analysis found that the incubators' locational contexts determined the degree and manner of their networking, but their profitability and growth potential were influenced by many other factors working in combination. Satisfying their sponsors' requirements and serving their core functions through sound management and strategic planning appeared to be the key to achieving profitability and sustainability, with benefits for all stakeholders. These constructs provide directions for more research on the performance of incubators and other business entities that are located within university and clustered contexts.

  12. Factors Affecting University Library Website Design

    OpenAIRE

    Kim, Yongi-Mi; University of Oklahoma

    2011-01-01

    Existing studies have extensively explored factors that affect users’ intentions to use university library website resources (ULWR); yet little attention has been given to factors affecting university library website design. This paper investigates factors that affect university library website design and assesses the success of the university library website from both designers’ and users’ perspectives. The findings show that when planning a website, university web designers consider univers...

  13. ATLAS virtual visit features Birzeit University, first university in Palestine and a member of the International Association of Universities since 1977.

    CERN Multimedia

    claudia marcelloni

    2012-01-01

    This ATLAS virtual visit features Birzeit University, first university in Palestine and a member of the International Association of Universities since 1977. As part of the "Physics Without Frontiers" project, funded by the International Centre for Theoretical Physics (ICTP), Birzeit is hosting a one day particle physics masterclass. During the day the physics major students are given an introduction to experimental particle physics, the LHC and the ATLAS Experiment, before having the chance to analyze real LHC data. This virtual visit comprises of a live tour around the ATLAS control room and the opportunity to ask questions to the ATLAS physicists. The Department of Physics at Birzeit University provides an exciting environment for the training of both graduate and undergraduate students. Some of the Physics department graduates participated in the CERN Summer Program over the past few years.

  14. Baby universes

    International Nuclear Information System (INIS)

    Strominger, A.

    1988-01-01

    This paper discusses how the subject of baby universes and their effects on spacetime coupling constants is in its infancy and rapidly developing. The subject is based on the non-existent (even by physicists' standards) Euclidean formulation of quantum gravity, and it is therefore necessary to make a number of assumptions in order to proceed. Nevertheless, the picture which has emerged is quite appealing: all spacetime coupling constants become dynamical variables when the effects of baby universes are taken into account. This fact might even solve the puzzle of the cosmological constant. The subject therefore seems worth further investigation

  15. Construction of Agricultural University Students’ Entrepreneurship Incubation Base – Taking Sichuan Agricultural University as a Case Study

    OpenAIRE

    Xia Yao; Jianping Xie; Linchun He

    2013-01-01

    In the recent years, as an effective practice in university students’ entrepreneurship education, construction of university students’ entrepreneurship incubation base has been rapidly developed in different universities. This paper takes construction of the entrepreneurship incubation base in Sichuan Agricultural University as a case study, analyzes the current status of university students’ entrepreneurship incubation base and makes a discussion on establishment of management institution, f...

  16. Perceived discrimination, serotonin transporter linked polymorphic region status, and the development of conduct problems.

    Science.gov (United States)

    Brody, Gene H; Beach, Steven R H; Chen, Yi-Fu; Obasi, Ezemenari; Philibert, Robert A; Kogan, Steven M; Simons, Ronald L

    2011-05-01

    This study examined the prospective relations of adolescents' perceptions of discrimination and their genetic status with increases in conduct problems. Participants were 461 African American youths residing in rural Georgia (Wave 1 mean age = 15.5 years) who provided three waves of data and a saliva sample from which a polymorphism in the SCL6A4 (serotonin transporter [5-HTT]) gene polymorphism known as the 5-HTT linked promoter region (5-HTTLPR) was genotyped. Data analyses using growth curve modeling indicated that perceived discrimination was significantly related to the slope of conduct problems. As hypothesized, interactions between perceived discrimination and genetic status emerged for male but not female youths. Compared with those carrying two copies of the long allele variant of 5-HTTLPR, male youths carrying one or two copies of its short allele variant evinced higher rates of conduct problems over time when they perceived high levels of racial discrimination. These findings are consistent with resilience and differential susceptibility propositions stating that genes can both foster sensitivity to adverse events and confer protection from those events.

  17. Common variations in 4p locus are related to male completed suicide.

    Science.gov (United States)

    Must, Anne; Kõks, Sulev; Vasar, Eero; Tasa, Gunnar; Lang, Aavo; Maron, Eduard; Väli, Marika

    2009-01-01

    Suicidal behavior is a multifactorial phenomenon, with a significant genetic predisposition. To assess the contribution of genes in the 4p region to suicide risk, we genotyped 36 single nucleotide polymorphisms from a 49Mb region on the chromosome arm 4p11-16 in a total of 288 male suicide victims and 327 healthy male volunteers. The nonsynonymous variants rs1383180 in EVC gene, rs6811863 in TBC1D1 gene, rs362272 in HTT gene, and rs734312 in WFS1 gene were associated to the male completed suicide. However, only EVC polymorphism remained significant after correcting for multiple comparisons (P < .05 after 10 K permutations). The function of these genes is not clear yet. WFS1 and HTT are related to the unfolded protein response and endoplasmic reticulum stress, and TBC1D1 is a GTPase activator. EVC is a protein with transmembrane and leucine zipper domains, its function has not been elucidated yet. Further studies are required in order to reveal the role of these four polymorphisms in the pathoetiology of suicide.

  18. Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study.

    Science.gov (United States)

    Sanhueza, Jorge A; Zambrano, Tomás; Bahamondes-Avila, Carlos; Salazar, Luis A

    2016-12-01

    Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety ( 5HTT , CRH2R , ACE , NK1R , 5HT1AR and CRF-BP ) on the physical capability and sports performance in triathletes. One hundred and ninety two (192) unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms ( 5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11) with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders.

  19. Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Jorge A. Sanhueza, Tomás Zambrano, Carlos Bahamondes-Avila, Luis A. Salazar

    2016-12-01

    Full Text Available Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety (5HTT, CRH2R, ACE, NK1R, 5HT1AR and CRF-BP on the physical capability and sports performance in triathletes. One hundred and ninety two (192 unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11 with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders.

  20. Potentiometric application of boron- and phosphorus-doped glassy carbon electrodes

    Directory of Open Access Journals (Sweden)

    ZORAN V. LAUSEVIC

    2001-03-01

    Full Text Available Acomparative study was carried out of the potentiometric application of boronand phosphorus-doped and undoped glassy carbon samples prepared at the same heat treatment temperature (HTT 1000°C. The electrochemical activities of the obtained electrode materials were investigated on the example of argentometric titrations. It was found that the electrochemical behaviour of the doped glassy carbon samples are very similar to a Sigri (undoped glassy carbon sample (HTT 2400°C. The experiments showed that the potentiometric response depends on the polarization mode, the nature of the sample, the pretreatment of the electrode surface, and the nature of the supporting electrolyte. The amounts of iodide, bromide, and of chloridewere determined to be 1.27 mg, 0.80 mg and 0.54 mg, respectively, with a maximum relative standard deviation of less than 1.1%. The obtained results are in good agreement with the results of comparative potentiometric titrations using a silver indicator electrode. The titrationmethod was applied to the indirect determination of pyridoxine hydrochloride, i.e., vitamin B6.

  1. The RAE and University Efficiency.

    Science.gov (United States)

    Mace, John

    2000-01-01

    Evaluates effects of the new British funding formula for universities, based on the research assessment exercise (RAE). Compares effects of the RAE on two contrasting universities and finds the RAE has dramatically affected university organization, teaching, and research. RAE may have increased efficiency in teaching and research but encourages…

  2. History of the Universe Poster

    Science.gov (United States)

    History of the Universe Poster You are free to use these images if you give credit to: Particle Data Group at Lawrence Berkeley National Lab. New Version (2014) History of the Universe Poster Download: JPEG version PDF version Old Version (2013) History of the Universe Poster Download: JPEG version

  3. From Traditional to Modern Universities

    DEFF Research Database (Denmark)

    Nielsen, Anja Birch; Sort, Jesper Chrautwald; Nielsen, Christian

    concludes that the performance management used today in universities in form of publications is overlooking the industries’ need of growth from the university knowledge. Hence motivating the scientists to engage in collaborations only from the university point of view and only to a limited extent concerning...... about the companies....

  4. Education for university students, high school teachers and the general public using the Kinki University Reactor

    International Nuclear Information System (INIS)

    Tsuruta, T.

    2007-01-01

    Atomic Energy Research Institute of Kinki University is equipped with a nuclear reactor which is called UTR-KINKI. UTR is the abbreviation for University Teaching and Research Reactor. The reactor is the first one installed in Japanese universities. Though the reactor is owned and operated by Kinki University, its use is widely open to scientists and students from other universities and research institutions. The reactor is made the best of teaching instrument for the training of high school teachers. In addition, the reactor is utilized for general public education concerning atomic energy. (author)

  5. The Challenge of University Autonomy

    DEFF Research Database (Denmark)

    Reilly, John; Turcan, Romeo V.; Bugaian, Larisa

    2016-01-01

    The authors introduce the reader to the book, providing a historical perspective and a current understanding of university autonomy. While appreciating the central role of the four dimensions of university autonomy – organisational, financial, human resource, and academic – the authors conjecture...... that a fuller understanding of university autonomy can only be obtained through a holistic view of the complex inter-relationships between stakeholders and policies which can reinforce and, equally, pull in opposite directions. This holistic view is represented in a model of institutional university autonomy......, which is discussed at length in the chapter. The authors conclude by presenting international case studies that give new insights and reinforce our understanding that the issues relating to institutional university autonomy are genuinely global....

  6. The Emergent Universe scheme and tunneling

    Energy Technology Data Exchange (ETDEWEB)

    Labraña, Pedro [Departamento de Física, Universidad del Bío-Bío, Avenida Collao 1202, Casilla 5-C, Concepción, Chile and Departament d' Estructura i Constituents de la Matèria and Institut de Ciències del Cosmos, Universitat (Spain)

    2014-07-23

    We present an alternative scheme for an Emergent Universe scenario, developed previously in Phys. Rev. D 86, 083524 (2012), where the universe is initially in a static state supported by a scalar field located in a false vacuum. The universe begins to evolve when, by quantum tunneling, the scalar field decays into a state of true vacuum. The Emergent Universe models are interesting since they provide specific examples of non-singular inflationary universes.

  7. University related studies

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Over the years, opportunities for terrestrial ecology studies have attracted student researchers associated with Pacific Northwest colleges and universities. During the past year, four students have been involved with undergraduate or graduate thesis projects. Brief descriptions of these studies are included in this section. It is expected that university participation will be enhanced by designating parts of the Hanford Reservation as a National Environmental Research Park (NERP)

  8. Consciousness in the Universe

    Directory of Open Access Journals (Sweden)

    Khalil Chamcham

    2013-07-01

    Full Text Available So far we can identify at least three concepts within modern cosmology that bring into debate the question of consciousness in the universe: 1 Fine Tuning; 2 The Anthropic Principle and 3 The Multiverse. This does not exclude the question of the role of observer (i.e. consciousness in cosmology as developed within Quantum Physics: we observe the universe through quanta and any breakthrough in understanding the origin and nature of the universe will come only through a quantum theory of gravity […

  9. Universal Design for Instruction: Extending the Universal Design Paradigm to College Instruction

    Science.gov (United States)

    McGuire, Joan M.; Scott, Sally S.

    2006-01-01

    Universal design for instruction (UDI) represents the systematic application of universal design, the construct from architecture and product development, to instructional practices in higher education. In addition to a description of the deliberative process by which UDI was developed, this article provides confirmatory evidence of the validity…

  10. Positioning University as a Brand: Distinctions between the Brand Promise of Russell Group, 1994 Group, University Alliance, and Million+ Universities

    Science.gov (United States)

    Furey, Sheila; Springer, Paul; Parsons, Christine

    2014-01-01

    Branding is now widely used by higher education (HE) institutions, yet questions still surround the transference of private sector concepts to a university context. This article reports on findings from studies that investigated the brand promises of four UK universities--one from each of the HE "mission groups." The evidence indicated…

  11. Reliability of agriculture universal joint shafts based on temperature measuring in universal joint bearing assemblies

    Directory of Open Access Journals (Sweden)

    Аleksandar Asonja

    2015-03-01

    Full Text Available This paper presents a research into reliability calculations of agriculture double universal joint shafts based on temperature measuring in cardan-type universal joint bearing assemblies. Special laboratory equipment was developed for this research which is presented in the paper. The objective of this research was to test the real life span of universal joint shafts in the laboratory and in field, to obtain the results which can be used to improve the reliability of universal joint shafts. If the presented research were used along with maintenance measures recommended in the paper and with proper use, the level of reliability of the shafts would be 2.1 times higher. The presented results of the research showed that needle bearings, i.e. bearing assemblies of the joints, are the most critical elements on universal joint shafts and are possible causes of their lower reliability. The second universal joint is the part with the lowest reliability in the observed technical system.

  12. Baby universe theory

    International Nuclear Information System (INIS)

    Nielsen, H.B.; Ninomiya, Masao

    1989-12-01

    We give an elementary review of the so called 'the theory of baby universes' which is a series of ideas or speculations about some effects in quantum gravity, viz. the effect of a certain type of wormholes, representing the exchange of small 3-space universes called baby universes. We consider this 'theory' as being physically and scientifically a very promising candidate for a theory of everything. It is, however, mathematically lacking any strong foundation at all. It solves several fine-tuning problems: First of all the cosmological constant problem, and also the strong CP-problem and the hierarchy problem. We also speculate that it might predict the possibility of influencing the probability distributions of the outcome of quantum mechanical measurements at one time by acts at a later time. (orig.)

  13. Quantum and Universe

    International Nuclear Information System (INIS)

    Uiler, Dzh.

    1982-01-01

    General approach to the structure of the Universe is discussed. Two properties of physical laws: symmetry and changeability are considered from this view point. Each physical law permits simpler formulation in the notion of symmetry. But the simplicity of this description conceals interval mechanisms which make up the base of the physical law. The problem of physical law stability is analyzed. It is concluded that unrestricted changeability is the main property of physics. Primary attention is paid to the problem of ''quantum and Universe''. The effect of measuring process on the experimental results is the most difficult problem of quantum mechanisms. The quantum principle rejected an attempt to conceptually present the reality as it is pictured independently from its observation and it made the description of the Universe structure still more complicated and confused

  14. Electromagnetic Gowdy universe

    International Nuclear Information System (INIS)

    Charach, C.

    1979-01-01

    Following Gowdy and Berger we construct an inhomogeneous closed electromagnetic universe with three-torus topology. This model is obtained as a result of the homogeneity breaking in the electromagnetic Bianchi type-I universe and contains interacting gravitational and electromagnetic waves. This cosmological solution provides an exactly solvable model for the study of the nonlinear fully relativistic regime of coupled electromagnetic and gravitational fields in the early universe. The asymptotic behavior is considered (i) in the vicinity of the initial singularity and (ii) in the high-frequency limit. It is shown that the effects of coupling between electromagnetic and gravitational waves cause an evolution which is significantly different from that of the vacuum model. The influence of the primordial homogeneous electromagnetic field on the dynamics of the model is also discussed

  15. The Worldhood university

    DEFF Research Database (Denmark)

    Bengtsen, Søren Smedegaard; Nørgård, Rikke Toft

    Universities and higher education today are sites for entanglement of multiple forms of agency and lifeworlds. Enhanced focus is given to higher education strategies and frameworks that integrate more traditional forms of higher education curriculum with moral and political awareness, social agency...... the mode 2 university, where the university is ‘for sale’ (Shumar, 1997) and where higher education curricula are being defined and shaped by the needs and current drivers of the job market and the shifting neoliberalist company strategies. As Ronald Barnett underlines “the contemporary vocabulary...... politically, socially, ethically, and philosophically. It requires, among other things, new conceptions of academic citizenship, belonging in higher education, and what we have called ‘placeful universities’ where “academic citizenship emerges through dialogical integration and ‘Mitsein’ in the critically...

  16. The Openness of the University of the Philippines Open University: Issues and Prospects

    Directory of Open Access Journals (Sweden)

    Maria Fe Villamejor-Mendoza

    2013-05-01

    Full Text Available This paper is a self-reflection on the state of openness of the University of the Philippines Open University (UPOU. An exploratory and descriptive study, it aims not only to define the elements of openness of UPOU, but also to unravel the causes and solutions to the issues and concerns that limit its options to becoming a truly open university. It is based on four parameters of openness, which are widely universal in the literature, e.g., open admissions, open curricula, distance education at scale, and the co-creation, sharing and use of open educational resources (OER. It draws from the perception survey among peers, which the author conducted in UPOU in July and August 2012. It also relies on relevant secondary materials on the subject.

  17. University contracts summary book

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-08-01

    The principal objectives of the Fossil Energy Program are to seek new ideas, new data, fundamental knowledge that will support the ongoing programs, and new processes to better utilize the nation's fossil energy resources with greater efficiency and environmental acceptability. Toward this end, the Department of Energy supports research projects conducted by universities and colleges to: Ensure a foundation for innovative technology through the use of the capabilities and talents in our academic institutions; provide an effective, two-way channel of communication between the Department of Energy and the academic community; and ensure that trained technical manpower is developed to carry out basic and applied research in support of DOE's mission. Fossil Energy's university activities emphasize the type of research that universities can do best - research to explore the potential of novel process concepts, develop innovative methods and materials for improving existing processes, and obtain fundamental information on the structure of coal and mechanisms of reactions of coal, shale oil, and other fossil energy sources. University programs are managed by different Fossil Energy technical groups; the individual projects are described in greater detail in this book. It is clear that a number of research areas related to the DOE Fossil Energy Program have been appropriate for university involvement, and that, with support from DOE, university scientific and technical expertise can be expected to continue to play a significant role in the advancement of fossil energy technology in the years to come.

  18. Universities' Engagement with Vocationalism: Historical Perspective

    Directory of Open Access Journals (Sweden)

    Pericles 'asher' Rospigliosi

    2016-12-01

    Full Text Available The aim of this article is to explore the historical context of vocationalism in universities. It is based on an analysis of the history of the university from a vocational perspective. It looks for evidence of vocational engagement in the activities of universities over time, taking a long view from the birth of the Western University in the Middle Ages to the 1980s with the emergence of current issues of vocationalism in university education. It adopts a chronological perspective initially and then a thematic one. The main findings are: (1 vocationalism in university education is as old as the Western University itself, (2 there is evidence from the start of the Western University of vocational engagement in terms of the provision of vocationally relevant subjects, vocationally relevant skills and the development of vocationally relevant attitudes, (3 whereas most graduate employers used to be concerned with the vocationally relevant knowledge, skills and attitudes students acquired on their degree courses, most are now more concerned with graduate capacity and disposition to learn within their employment after graduation and (4 subject-centred education is compatible with university education that supports the vocational aspirations of students.

  19. University Reactor Instrumentation Program

    International Nuclear Information System (INIS)

    Vernetson, W.G.

    1992-11-01

    Recognizing that the University Reactor Instrumentation Program was developed in response to widespread needs in the academic community for modernization and improvement of research and training reactors at institutions such as the University of Florida, the items proposed to be supported by this grant over its two year period have been selected as those most likely to reduce foreed outages, to meet regulatory concerns that had been expressed in recent years by Nuclear Regulatory Commission inspectors or to correct other facility problems and limitations. Department of Energy Grant Number DE-FG07-90ER129969 was provided to the University of Florida Training Reactor(UFTR) facility through the US Department of Energy's University Reactor Instrumentation Program. The original proposal submitted in February, 1990 requested support for UFTR facility instrumentation and equipment upgrades for seven items in the amount of $107,530 with $13,800 of this amount to be the subject of cost sharing by the University of Florida and $93,730 requested as support from the Department of Energy. A breakdown of the items requested and total cost for the proposed UFTR facility instrumentation and equipment improvements is presented

  20. Examination of Psychological Counselor Candidates' University Satisfaction: The Case of Uludag University

    Science.gov (United States)

    Duran, Nagihan Oguz; Gökçe, Feyyat

    2017-01-01

    In the present study, Uludag University, Faculty of Education, Guidance and Psychological Counseling (GPC) undergraduate program students' expectations and satisfaction levels regarding the services and facilities provided by the university were investigated in a sample of 354 students (227 females and 127 males). The data collected by the…

  1. Tools to probe the universe

    International Nuclear Information System (INIS)

    Lagage, P.O.; Augueres, J.L.; Amiaux, J.; Cara, Ch.; Fontignie, J.; Rio, Y.; Fermon, C.; Pannetier-Lecoeur, M.; De Vismes, A.; Cordier, B.; Fesquet, M.; Ferrando, Ph.; Authier, M.; Pantin, E.; Glicenstein, J.F.; Boulade, O.; Refregier, A.; Stolarczyk, Th.; Agnese, P.; Rodriguez, L.; Agnese, P.; Pigot, C.; Duband, L.; Limousin, O.; Delagnes, E.; Turck-Chieze, S.; Carton, P.H.; Starck, J.L.; Bournaud, F.; Teyssier, R.; Audit, E.; Brun, A.S.; Leca, P.; Menache, Ch.; Pomarede, D.; Thooris, B.; Meis, C.

    2009-01-01

    This special issue of Clefs CEA journal is entirely devoted to astrophysics and to the exploration and probing of the Universe. The second part of this dossier, described here, makes a status of the tools used to probe the universe: telescopes, imaging spectrometers, data processing and simulation. Content: A - Telescopes of the future: 1. Seeing further out: JWST: looking back on a past 13 billion years old, Space specifics: the learning curve to know-how, Fabricating a corona-graph mask, SVOM, a satellite to detect the explosions of the first stars to be formed in the Universe; 2. Seeing more precisely: SIMBOL-X, pioneering formation flying, ELT/METIS, a 42-meter giant, One hundred telescopes for the CTA arrays; 3. Seeing wider: Euclid, mapping the extragalactic sky, ANTARES: the neutrino, another cosmic messenger; B - The new generation of imaging spectrometers: Observing the Universe in the submillimeter spectral region, The X-ray Universe, Space cryo-coolers, Out in the extreme, tumultuous Universe, Probing the Sun with GOLF-NG, Focus: From light to imagery; C - Data analysis in astrophysics; D - Numerical simulation in astrophysics: Information technology and theoretical predictions in astrophysics, Supercomputers for a better understanding of the Universe, The visualization of astrophysical simulations, Godunov, a numerical platform for education and research

  2. A Christian Critique of the University.

    Science.gov (United States)

    Malik, Charles Habib

    Views on the place and power of the university, the church's role in the university, and the sciences and humanities are presented. The secularization of western universities raises fundamental criticisms from the Christian point of view that the university atmosphere is not congenial to Christian spiritual values, and that higher education…

  3. On universal partial words

    OpenAIRE

    Chen, Herman Z. Q.; Kitaev, Sergey; Mütze, Torsten; Sun, Brian Y.

    2016-01-01

    A universal word for a finite alphabet $A$ and some integer $n\\geq 1$ is a word over $A$ such that every word in $A^n$ appears exactly once as a subword (cyclically or linearly). It is well-known and easy to prove that universal words exist for any $A$ and $n$. In this work we initiate the systematic study of universal partial words. These are words that in addition to the letters from $A$ may contain an arbitrary number of occurrences of a special `joker' symbol $\\Diamond\

  4. Faculties of Education in Traditional Universities and Universities of the Third Age: A Partnership Model in Gerontagogy

    Science.gov (United States)

    Lemieux, Andre; Boutin, Gerald; Riendeau, Jean

    2007-01-01

    This article discusses "Universities of the Third Age", whose function is quite distinct from established universities' traditional role in teaching, research, and community services. Consequently, there is an urgent need to develop a model of partnership between traditional universities and Universities of the Third Age, ensuring better…

  5. Early predictors of first-year academic success at university : Pre-university effort, pre-university self-efficacy, and pre-university reasons for attending university

    NARCIS (Netherlands)

    van Herpen, Sanne G.A.; Meeuwisse, Marieke; Hofman, W. H.Adriaan; Severiens, Sabine E.; Arends, Lidia R.

    Given the large number of dropouts in the 1st year at university, it is important to identify early predictors of 1st-year academic success. The present study (n = 453 first-year students) contributes to literature on the transition from secondary to higher education by investigating how the

  6. Universal computer interfaces

    CERN Document Server

    Dheere, RFBM

    1988-01-01

    Presents a survey of the latest developments in the field of the universal computer interface, resulting from a study of the world patent literature. Illustrating the state of the art today, the book ranges from basic interface structure, through parameters and common characteristics, to the most important industrial bus realizations. Recent technical enhancements are also included, with special emphasis devoted to the universal interface adapter circuit. Comprehensively indexed.

  7. How to Run a University

    Science.gov (United States)

    Evans, G. R.

    2006-01-01

    The Lambert Review of Business-University Collaboration proposed a business model for universities in 2003. Pressure to change university governance to make it match the business model remains strong, and it is being most actively applied to Oxford and Cambridge. The Oxford and Cambridge governance debates (which began in the 1990s) open up the…

  8. Collapse of simple harmonic universe

    International Nuclear Information System (INIS)

    Mithani, Audrey T.; Vilenkin, Alexander

    2012-01-01

    In a recent paper Graham et al constructed oscillating and static universe models which are stable with respect to all classical perturbations. Here we show that such universes are quantum-mechanically unstable and can collapse by quantum tunneling to zero radius. We also present instantons describing nucleation of oscillating and static universes from nothing

  9. Human universe

    CERN Document Server

    Cox, Brian

    2014-01-01

    Human life is a staggeringly strange thing. On the surface of a ball of rock falling around a nuclear fireball in the blackness of a vacuum the laws of nature conspired to create a naked ape that can look up at the stars and wonder where it came from. What is a human being? Objectively, nothing of consequence. Particles of dust in an infinite arena, present for an instant in eternity. Clumps of atoms in a universe with more galaxies than people. And yet a human being is necessary for the question itself to exist, and the presence of a question in the universe - any question - is the most wonderful thing. Questions require minds, and minds bring meaning. What is meaning? I don't know, except that the universe and every pointless speck inside it means something to me. I am astonished by the existence of a single atom, and find my civilisation to be an outrageous imprint on reality. I don't understand it. Nobody does, but it makes me smile. This book asks questions about our origins, our destiny, and our place i...

  10. Entropy and the Typicality of Universes

    OpenAIRE

    Barbour, Julian; Koslowski, Tim; Mercati, Flavio

    2015-01-01

    The universal validity of the second law of thermodynamics is widely attributed to a finely tuned initial condition of the universe. This creates a problem: why is the universe atypical? We suggest that the problem is an artefact created by inappropriate transfer of the traditional concept of entropy to the whole universe. Use of what we call the relational $N$-body problem as a model indicates the need to employ two distinct entropy-type concepts to describe the universe. One, which we call ...

  11. University of Nottingham Ningbo China and Xi'an Jiaotong-Liverpool University: Globalization of Higher Education in China

    Science.gov (United States)

    Feng, Yi

    2013-01-01

    This essay studies the University of Nottingham Ningbo China and Xi'an Jiaotong-Liverpool University--the two Chinese campuses established respectively by the University of Nottingham and the University of Liverpool. They represent successful models of globalization of higher education in China; however their rationale, strategies, curricula,…

  12. The Universe's First Fireworks

    Science.gov (United States)

    2006-01-01

    [figure removed for brevity, see original site] [figure removed for brevity, see original site] [figure removed for brevity, see original site] Poster VersionFigure 1Figure 2 This is an image from NASA's Spitzer Space Telescope of stars and galaxies in the Ursa Major constellation. This infrared image covers a region of space so large that light would take up to 100 million years to travel across it. Figure 1 is the same image after stars, galaxies and other sources were masked out. The remaining background light is from a period of time when the universe was less than one billion years old, and most likely originated from the universe's very first groups of objects -- either huge stars or voracious black holes. Darker shades in the image on the left correspond to dimmer parts of the background glow, while yellow and white show the brightest light. Brief History of the Universe In figure 2, the artist's timeline chronicles the history of the universe, from its explosive beginning to its mature, present-day state. Our universe began in a tremendous explosion known as the Big Bang about 13.7 billion years ago (left side of strip). Observations by NASA's Cosmic Background Explorer and Wilkinson Anisotropy Microwave Probe revealed microwave light from this very early epoch, about 400,000 years after the Big Bang, providing strong evidence that our universe did blast into existence. Results from the Cosmic Background Explorer were honored with the 2006 Nobel Prize for Physics. A period of darkness ensued, until about a few hundred million years later, when the first objects flooded the universe with light. This first light is believed to have been captured in data from NASA's Spitzer Space Telescope. The light detected by Spitzer would have originated as visible and ultraviolet light, then stretched, or redshifted, to lower-energy infrared wavelengths during its long voyage to reach us across expanding space. The light detected by the Cosmic Background Explorer and the

  13. Quantum creation of an inflationary Universe

    International Nuclear Information System (INIS)

    Linde, A.D.

    1984-01-01

    The problem of quantum creation of the Universe is discussed. It is shown that the process of quantum creation of the Universe in a wide class on elementary particle theories leads with a high probability to the creation of an exponentially expanding (inflationary) Universe. Universe size after expansion should exceed l approximately 10 28 cm

  14. Locus - ASTRA | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...URL: ftp://ftp.biosciencedbc.jp/archive/astra/LATEST/astra_locus.zip File size: 887 KB Simple search URL htt...icing type (ex. cassette) About This Database Database Description Download License Update History of This Database Site Policy | Contact Us Locus - ASTRA | LSDB Archive ...

  15. The Role and Responsibility of the University Library in Publishing in a University

    Directory of Open Access Journals (Sweden)

    Bas Savenije

    2000-06-01

    Full Text Available As a consequence of developments in information technology, the traditional information chain is subject to change: the separate functions in this chain become more and more integrated and the roles played by the traditional parties are most uncertain. Several new models in scholarly publishing and communication are emerging, in which the scientific community and the scientists themselves play a central role. It is more than natural for universities to support these developments in order to realise new models of scientific communication that are more in tune with the needs of the academic community than the traditional model, which has led to a serious serials crisis. An important step in this direction is that each university encourages scientists to make more use of ICT in their research publications. However, it is also necessary to give serious attention to organisational matters: in this respect every university should take responsibility for collecting, archiving and disclosing the scientific output of its own scientists. The provision of scientific information is the traditional core business of university libraries and it is a natural extension of this role for university libraries to support this development and to organise the processes needed. The paper describes the role that universities and their libraries have to play. It also gives some examples of library initiatives in this field, including an evaluation of their impact on the innovation of scientific communication.

  16. ULTRA: Universal Grammar as a Universal Parser.

    Science.gov (United States)

    Medeiros, David P

    2018-01-01

    A central concern of generative grammar is the relationship between hierarchy and word order, traditionally understood as two dimensions of a single syntactic representation. A related concern is directionality in the grammar. Traditional approaches posit process-neutral grammars, embodying knowledge of language, put to use with infinite facility both for production and comprehension. This has crystallized in the view of Merge as the central property of syntax, perhaps its only novel feature. A growing number of approaches explore grammars with different directionalities, often with more direct connections to performance mechanisms. This paper describes a novel model of universal grammar as a one-directional, universal parser. Mismatch between word order and interpretation order is pervasive in comprehension; in the present model, word order is language-particular and interpretation order (i.e., hierarchy) is universal. These orders are not two dimensions of a unified abstract object (e.g., precedence and dominance in a single tree); rather, both are temporal sequences, and UG is an invariant real-time procedure (based on Knuth's stack-sorting algorithm) transforming word order into hierarchical order. This shift in perspective has several desirable consequences. It collapses linearization, displacement, and composition into a single performance process. The architecture provides a novel source of brackets (labeled unambiguously and without search), which are understood not as part-whole constituency relations, but as storage and retrieval routines in parsing. It also explains why neutral word order within single syntactic cycles avoids 213-like permutations. The model identifies cycles as extended projections of lexical heads, grounding the notion of phase. This is achieved with a universal processor, dispensing with parameters. The empirical focus is word order in noun phrases. This domain provides some of the clearest evidence for 213-avoidance as a cross

  17. NETWORK UNIVERSITIES: INTERNATIONAL EXPERIENCE AND TRENDS

    Directory of Open Access Journals (Sweden)

    Г А Краснова

    2016-12-01

    Full Text Available The article is devoted to networking foreign universities, in particular, it considers the experience of cooperation of Vietnamese and Chinese universities with the leading universities of the world and the implementation of joint educational projects. The article deals with the basic characteristics of university networks that emerged in the last decade in developing countries. The authors analyzed the model, sources of financing, the organization of educational process, teaching of languages and the number of students in the university network, as well as the main mechanisms that allow open network structure of education in different countries of the world. The authors also address the main reasons for encouraging networking of foreign universities.

  18. Thalamo–cortical network underlying deep brain stimulation of centromedian thalamic nuclei in intractable epilepsy: a multimodal imaging analysis

    Directory of Open Access Journals (Sweden)

    Kim SH

    2017-10-01

    Full Text Available Seong Hoon Kim,1 Sung Chul Lim,1 Dong Won Yang,1 Jeong Hee Cho,1 Byung-Chul Son,2 Jiyeon Kim,3 Seung Bong Hong,4 Young-Min Shon4 1Department of Neurology, 2Department of Neurosurgery, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, 3Department of Neurology, Korea University Ansan Hospital, College of Medicine, Korea University, Ansan, 4Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Objective: Deep brain stimulation (DBS of the centromedian thalamic nucleus (CM can be an alternative treatment option for intractable epilepsy patients. Since CM may be involved in widespread cortico-subcortical networks, identification of the cortical sub-networks specific to the target stimuli may provide further understanding on the underlying mechanisms of CM DBS. Several brain structures have distinguishing brain connections that may be related to the pivotal propagation and subsequent clinical effect of DBS.Methods: To explore core structures and their connections relevant to CM DBS, we applied electroencephalogram (EEG and diffusion tensor imaging (DTI to 10 medically intractable patients – three generalized epilepsy (GE and seven multifocal epilepsy (MFE patients unsuitable for resective surgery. Spatiotemporal activation pattern was mapped from scalp EEG by delivering low-frequency stimuli (5 Hz. Structural connections between the CM and the cortical activation spots were assessed using DTI.Results: We confirmed an average 72% seizure reduction after CM DBS and its clinical efficiency remained consistent during the observation period (mean 21 months. EEG data revealed sequential source propagation from the anterior cingulate, followed by the frontotemporal regions bilaterally. In addition, maximal activation was found in the left cingulate gyrus and the right medial frontal cortex during the right and left CM stimulation, respectively

  19. Why Are There Dropouts among University Students? Experiences in a Thai University

    Science.gov (United States)

    Sittichai, Ruthaychonnee

    2012-01-01

    The purpose of this qualitative research study was to investigate premature dropping out of university study at Prince of Songkla University, Pattani Campus in southern Thailand. 21 Muslim and non-Muslim males and females and four senior staff were interviewed. The findings are discussed in terms of practical implications and also reflecting on…

  20. The Belonging to the University Scale

    Science.gov (United States)

    Karaman, Omer; Cirak, Yuksel

    2017-01-01

    The aim of the study is to develop a belonging to the university scale (BUS) in order to determine the level of fulfillment of the need to belong among university students at the higher education institutions they attend. The population of the investigation includes university students studying at the campus of Ordu University. A 5 point…

  1. Eternally existing self-reproducing inflationary universe

    International Nuclear Information System (INIS)

    Linde, A.D.

    1986-05-01

    It is shown that the large-scale quantum fluctuations of the scalar field φ generated in the chaotic inflation scenario lead to an infinite process of self-reproduction of inflationary mini-universes. A model of eternally existing chaotic inflationary universe is suggested. It is pointed out that whereas the universe locally is very homogeneous as a result of inflation, which occurs at the classical level, the global structure of the universe is determined by quantum effects and is highly non-trivial. The universe consists of exponentially large number of different mini-universes, inside which all possible (metastable) vacuum states and all possible types of compactification are realized. The picture differs crucially from the standard picture of a one-domain universe in a ''true'' vacuum state. Our results may serve as a justification of the anthropic principle in the inflationary cosmology. These results may have important implications for the elementary particle theory as well. Namely, since all possible types of mini-universes, in which inflation may occur, should exist in our universe, there is no need to insist (as it is usually done) that in realistic theories the vacuum state of our type should be the only possible one or the best one. (author)

  2. The anamorphic universe

    Science.gov (United States)

    Ijjas, Anna; Steinhardt, Paul J.

    2015-10-01

    We introduce ``anamorphic'' cosmology, an approach for explaining the smoothness and flatness of the universe on large scales and the generation of a nearly scale-invariant spectrum of adiabatic density perturbations. The defining feature is a smoothing phase that acts like a contracting universe based on some Weyl frame-invariant criteria and an expanding universe based on other frame-invariant criteria. An advantage of the contracting aspects is that it is possible to avoid the multiverse and measure problems that arise in inflationary models. Unlike ekpyrotic models, anamorphic models can be constructed using only a single field and can generate a nearly scale-invariant spectrum of tensor perturbations. Anamorphic models also differ from pre-big bang and matter bounce models that do not explain the smoothness. We present some examples of cosmological models that incorporate an anamorphic smoothing phase.

  3. The anamorphic universe

    International Nuclear Information System (INIS)

    Ijjas, Anna; Steinhardt, Paul J.

    2015-01-01

    We introduce ''anamorphic'' cosmology, an approach for explaining the smoothness and flatness of the universe on large scales and the generation of a nearly scale-invariant spectrum of adiabatic density perturbations. The defining feature is a smoothing phase that acts like a contracting universe based on some Weyl frame-invariant criteria and an expanding universe based on other frame-invariant criteria. An advantage of the contracting aspects is that it is possible to avoid the multiverse and measure problems that arise in inflationary models. Unlike ekpyrotic models, anamorphic models can be constructed using only a single field and can generate a nearly scale-invariant spectrum of tensor perturbations. Anamorphic models also differ from pre-big bang and matter bounce models that do not explain the smoothness. We present some examples of cosmological models that incorporate an anamorphic smoothing phase

  4. The anamorphic universe

    Energy Technology Data Exchange (ETDEWEB)

    Ijjas, Anna; Steinhardt, Paul J., E-mail: aijjas@princeton.edu, E-mail: steinh@princeton.edu [Princeton Center for Theoretical Science, Princeton University, Princeton, NJ, 08544 (United States)

    2015-10-01

    We introduce ''anamorphic'' cosmology, an approach for explaining the smoothness and flatness of the universe on large scales and the generation of a nearly scale-invariant spectrum of adiabatic density perturbations. The defining feature is a smoothing phase that acts like a contracting universe based on some Weyl frame-invariant criteria and an expanding universe based on other frame-invariant criteria. An advantage of the contracting aspects is that it is possible to avoid the multiverse and measure problems that arise in inflationary models. Unlike ekpyrotic models, anamorphic models can be constructed using only a single field and can generate a nearly scale-invariant spectrum of tensor perturbations. Anamorphic models also differ from pre-big bang and matter bounce models that do not explain the smoothness. We present some examples of cosmological models that incorporate an anamorphic smoothing phase.

  5. The Comparison Study of Six University Archives

    Directory of Open Access Journals (Sweden)

    Chun-Fen Liu

    2004-03-01

    Full Text Available The university archives is not only the extension of a building, but also includes the archival records, archivists and equipments. The university archives is the historical memory of a university, which could let people to predict the future by reviewing the past. The university archives has abundant collections, both teachers and students can review history of this university. This paper mainly compares six university archives of Taiwan, and the interviewing method is used in this research. After comparison of the six university archives, we have found the six university archives have different organizational structures, budgets, and functions. Finally the authors propose some suggestions.[Article content in Chinese

  6. Research collaboration 2011-2012: A joint publication highlighting the research partnerships between the CSIR and University of the Western Cape, University of Cape Town, Stellenbosch University

    CSIR Research Space (South Africa)

    CSIR

    2012-01-01

    Full Text Available CSIR’s partnerships with the University of the Western Cape (UWC), University of Cape Town (UCT) and Stellenbosch University (SU) seek to conduct research that improves the quality of the lives of the people of South Africa by responding...

  7. A New Cosmological Model: Black Hole Universe

    Directory of Open Access Journals (Sweden)

    Zhang T. X.

    2009-07-01

    Full Text Available A new cosmological model called black hole universe is proposed. According to this model, the universe originated from a hot star-like black hole with several solar masses, and gradually grew up through a supermassive black hole with billion solar masses to the present state with hundred billion-trillion solar masses by accreting ambient mate- rials and merging with other black holes. The entire space is structured with infinite layers hierarchically. The innermost three layers are the universe that we are living, the outside called mother universe, and the inside star-like and supermassive black holes called child universes. The outermost layer is infinite in radius and limits to zero for both the mass density and absolute temperature. The relationships among all layers or universes can be connected by the universe family tree. Mathematically, the entire space can be represented as a set of all universes. A black hole universe is a subset of the en- tire space or a subspace. The child universes are null sets or empty spaces. All layers or universes are governed by the same physics - the Einstein general theory of relativity with the Robertson-walker metric of spacetime - and tend to expand outward physically. The evolution of the space structure is iterative. When one universe expands out, a new similar universe grows up from its inside. The entire life of a universe begins from the birth as a hot star-like or supermassive black hole, passes through the growth and cools down, and expands to the death with infinite large and zero mass density and absolute temperature. The black hole universe model is consistent with the Mach principle, the observations of the universe, and the Einstein general theory of relativity. Its various aspects can be understood with the well-developed physics without any difficulty. The dark energy is not required for the universe to accelerate its expansion. The inflation is not necessary because the black hole universe

  8. Acceleration of black hole universe

    Science.gov (United States)

    Zhang, T. X.; Frederick, C.

    2014-01-01

    Recently, Zhang slightly modified the standard big bang theory and developed a new cosmological model called black hole universe, which is consistent with Mach's principle, governed by Einstein's general theory of relativity, and able to explain all observations of the universe. Previous studies accounted for the origin, structure, evolution, expansion, and cosmic microwave background radiation of the black hole universe, which grew from a star-like black hole with several solar masses through a supermassive black hole with billions of solar masses to the present state with hundred billion-trillions of solar masses by accreting ambient matter and merging with other black holes. This paper investigates acceleration of the black hole universe and provides an alternative explanation for the redshift and luminosity distance measurements of type Ia supernovae. The results indicate that the black hole universe accelerates its expansion when it accretes the ambient matter in an increasing rate. In other words, i.e., when the second-order derivative of the mass of the black hole universe with respect to the time is positive . For a constant deceleration parameter , we can perfectly explain the type Ia supernova measurements with the reduced chi-square to be very close to unity, χ red˜1.0012. The expansion and acceleration of black hole universe are driven by external energy.

  9. The University and Morality: A Revised Approach to University Autonomy and Its Limits.

    Science.gov (United States)

    Alexander, Jeffrey C.

    1986-01-01

    The "critical" and "established" positions on university morality leave important questions unanswered. A revised position distinguishing between the corporate and intellectual bodies of the university is offered. Three social conditions for maintaining a value-rational debate are proposed. (Author/MLW)

  10. Young people's experiences of managing Type 1 diabetes at university: a national study of UK university students.

    Science.gov (United States)

    Kellett, J; Sampson, M; Swords, F; Murphy, H R; Clark, A; Howe, A; Price, C; Datta, V; Myint, K S

    2018-04-23

    Little is known about the challenges of transitioning from school to university for young people with Type 1 diabetes. In a national survey, we investigated the impact of entering and attending university on diabetes self-care in students with Type 1 diabetes in all UK universities. Some 1865 current UK university students aged 18-24 years with Type 1 diabetes, were invited to complete a structured questionnaire. The association between demographic variables and diabetes variables was assessed using logistic regression models. In total, 584 (31%) students from 64 hospitals and 37 university medical practices completed the questionnaire. Some 62% had maintained routine diabetes care with their home team, whereas 32% moved to the university provider. Since starting university, 63% reported harder diabetes management and 44% reported higher HbA 1c levels than before university. At university, 52% had frequent hypoglycaemia, 9.6% reported one or more episodes of severe hypoglycaemia and 26% experienced diabetes-related hospital admissions. Female students and those who changed healthcare provider were approximately twice as likely to report poor glycaemic control, emergency hospital admissions and frequent hypoglycaemia. Females were more likely than males to report stress [odds ratio (OR) 4.78, 95% confidence interval (CI) 3.19-7.16], illness (OR 3.48, 95% CI 2.06-5.87) and weight management issues (OR 3.19, 95% CI 1.99-5.11) as barriers to self-care. Despite these difficulties, 91% of respondents never or rarely contacted university support services about their diabetes. The study quantifies the high level of risk experienced by students with Type 1 diabetes during the transition to university, in particular, female students and those moving to a new university healthcare provider. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Universality in heterogeneous catalysis

    DEFF Research Database (Denmark)

    Nørskov, Jens Kehlet; Pedersen, Thomas Bligaard; Logadottir, Ashildur

    2002-01-01

    Based on an extensive set of density functional theory calculations it is shown that for a class of catalytic reactions there is a universal, reactant independent relation between the reaction activation energy and the stability of reaction intermediates. This leads directly to a universal relati...

  12. (Re)Discovering University Autonomy

    DEFF Research Database (Denmark)

    This book challenges traditional approach to university autonomy which is based on four pillars: organisational, financial, human resource, and academic. The main thesis is that a fuller understanding of university autonomy can only be obtained through a more holistic view of the complex inter-re...

  13. Marketing University Outreach Programs.

    Science.gov (United States)

    Foster, Ralph S., Jr., Ed.; And Others

    A collection of 12 essays and model program descriptions addresses issues in the marketing of university extension, outreach, and distance education programs. They include: (1) "Marketing and University Outreach: Parallel Processes" (William I. Sauser, Jr. and others); (2) "Segmenting and Targeting the Organizational Market"…

  14. Interaction university and school

    Directory of Open Access Journals (Sweden)

    Gionara Tauchen

    2016-05-01

    Full Text Available Considering that the interaction between universities and middle schools is fundamental for organization and the qualification of the education system, we conducted a qualitative study on twenty public municipal schools of Rio Grande, RS, designed to investigate and understand the effectiveness of university activities (teaching, research and extension in regard to the promotion and strengthening of the interactions between these institutions. We highlight the activities related to Pibid, the Education Observatory, extension, supervised internships, and to undergraduate and postgraduate research. From comprehensions about these activities, we discuss the interaction between school and university.

  15. Motivation of university and non-university stakeholders to change medical education in Vietnam.

    NARCIS (Netherlands)

    Luu, H.N.; Nguyen, V.L.; van der Wilt, G.J.; Broerse, J.E.W.; Ruitenberg, E.J.; Wright, E.P.

    2009-01-01

    Background. Both university and non-university stakeholders should be involved in the process of curriculum development in medical schools, because all are concerned with the competencies of the graduates. That may be difficult unless appropriate strategies are used to motivate each stakeholder.

  16. Motivation of university and non-university stakeholders to change medical education in Vietnam

    NARCIS (Netherlands)

    Lu, H.; Nguyen, V; van der Wilt, G.J.; Broerse, J.E.W.; Ruitenberg, E.J.; Wright, P.

    2009-01-01

    Background. Both university and non-university stakeholders should be involved in the process of curriculum development in medical schools, because all are concerned with the competencies of the graduates. That may be difficult unless appropriate strategies are used to motivate each stakeholder.

  17. Food intake of university students

    Directory of Open Access Journals (Sweden)

    Greyce Luci BERNARDO

    Full Text Available ABSTRACT This narrative literature review aimed to analyze the results of studies on the food intake of university students. A literature search was conducted in July 2014 and updated in July 2016 in the Scopus, MedLine/PubMed, and SciELO databases, using descriptors related to university students and food intake in English and Portuguese. Overall, 37 studies that analyzed university students’ food intake were included in this review, eight of which were conducted in Brazil. The results demonstrated that most university students have unhealthy eating behaviors, such as high intake of fast foods, snacks, sweets, soft drinks, and alcoholic beverages, and low intake of fruits, vegetables, fish, whole grains, and legumes. Undergraduate students of health sciences, such as nursing, nutrition, and medicine, did not have healthier diets. University students’ food intake was characterized as unhealthy, regardless of undergraduate program or sex, especially among students who left the parents’ home and became responsible for their own food. Therefore, there is a need of developing public policies that promote healthy eating habits among students, such as interventions to change their eating habits and increase their access to healthy foods at the university environment.

  18. Reeducation at Heidelberg University.

    Science.gov (United States)

    Giles, Geoffrey J.

    1997-01-01

    Utilizes German archival records to illuminate crucial post-war events at Heidelberg University. The university became the focal point of attempts to define the theoretical and practical meaning of "geistige Umerziehung" (spiritual reeducation). Discusses the conflict between U.S. authorities and such esteemed German scholars as Karl…

  19. Strategic Issues in University Information Management

    Science.gov (United States)

    Roosendaal, Hans E.

    This chapter represents a specific view on university management. It sequentially discusses different organizational levels of e-teaching, starting with general management, e-science developments and what this means to universities, and business models followed by focusing on specific teaching issues. The chapter sets out to discuss the development of the university from a loose federation of faculties into a more integrated university, such as, e.g., an entrepreneurial university. This development is also driven by the introduction of the bachelors/masters system - a process which leads to the need for an institutional strategy introducing institutional quality management and has to be accompanied by the independent accreditation of research and teaching. Applying the model of strategic positioning to the university as a whole leads to the introduction of the university entrepreneur. The model is used to describe structural issues and the relations between the primary processes of research and teaching with the secondary processes. e-science is introduced as a further step toward the universal sharing of scientific results and to analyze the kind of incentives that will be required to attain this goal of making information an even more integral part of the research and teaching process.

  20. The Universe and Life

    Directory of Open Access Journals (Sweden)

    Eduard Kazantsev

    2016-02-01

    Full Text Available This article discusses some of the unsolved problems of modern cosmology, which lead to the need to consider the role of living matter in the evolution of the universe. The author proposes the hy- pothesis of the emergence, in the process of evolution of the universe, “biological vacuum” (physical antipode, which has a purpose of improving physical matter until the appearance of living matter. Substantiates the idea that the “biological vacuum” in the “live” dark matter with the participation of a living organism as an intermediary. The model of a stationary universe, as the local group of galaxies, placed in a halo of “live” dark matter. At the end of the article the author predicts the final evolution of the physical universe (after the collapse of the physical fields and particles as the begin- ning of a new stage of evolution of the “live” dark matter.

  1. Unceratainty of Heisenberg in Universe Destruction

    Directory of Open Access Journals (Sweden)

    Sri Jumini

    2017-12-01

    Full Text Available The Qur'an is a guidence which explaines all about the universe to human being. The discovery of science has been able to explain the truth of the Qur'an scientifically. One of which is the principle of Heisenberg's uncertainty in the event of the universe destruction. The purpose of this research is to know: 1 Science's view of the event of the universe destruction (Big Crunch in Qur’an [Al Infithaar]: 1-3, and How the relation of Heisenberg’s uncertainty principles and the law of thermodynamics II toward  the collapse of the universe (Big Crunch based on Scientific views and the Quran. This research is a qualitative research using library research method which analyzes the related books directly or indirectly. The results of the analysis stated that: 1 The concentration of mass, which is big enough, relates to some of the laws of physics, those are: Relativity, Heisenberg's uncertainty principles, and the law of Thermodynamic II; 2 The universe will return at its sole point, i.e; the absence of the universe; 3 The destruction of the universe is the destruction of the order of the universe which then the stars fall scatteredly because of the gravitational force that prevents them disappears, the balance of the universe diminishes, decreases and becomes uncertain, and eventually disappears.

  2. Mach's principle and rotating universes

    International Nuclear Information System (INIS)

    King, D.H.

    1990-01-01

    It is shown that the Bianchi 9 model universe satisfies the Mach principle. These closed rotating universes were previously thought to be counter-examples to the principle. The Mach principle is satisfied because the angular momentum of the rotating matter is compensated by the effective angular momentum of gravitational waves. A new formulation of the Mach principle is given that is based on the field theory interpretation of general relativity. Every closed universe with 3-sphere topology is shown to satisfy this formulation of the Mach principle. It is shown that the total angular momentum of the matter and gravitational waves in a closed 3-sphere topology universe is zero

  3. Self-esteem and organizational values in university students and not university students from Lima

    OpenAIRE

    Loli Pineda, Alejandro E.; López Vega, Ernestina

    2014-01-01

    The selfesteem and the organizationals values in university students and not university students of Lima, is a study developed in a sample of 3215 students belonging to four universities of Lima; and not students conformed by egressions, professional and postgraduados, many of which show off directive charges in public or private companies, with the purpose to know the existing relation among the selfesteem and the values organizational of the same, in Lima Metropolitan, and to determine the ...

  4. University writing

    Directory of Open Access Journals (Sweden)

    Miguel Zabalza Beraza

    2013-01-01

    Full Text Available Writing in the University is a basic necessity and a long-range educational purpose. One of the basic characteristics of the university context is that it requires writing both as a tool of communication and as a source of intellectual stimulation. After establishing the basic features of academic writing, this article analyzes the role of writing for students (writing to learn and for teachers (write to plan, to reflect, to document what has been done. The article also discusses the contributions of writing for both students and teachers together: writing to investigate. Finally, going beyond what writing is as academic tool, we conclude with a more playful and creative position: writing for pleasure and enjoyment.

  5. A unified universe

    DEFF Research Database (Denmark)

    Codello, Alessandro; Jain, Rajeev Kumar

    2018-01-01

    We present a unified evolution of the universe from very early times until the present epoch by including both the leading local correction R2 and the leading non-local term R1□2R to the classical gravitational action. We find that the inflationary phase driven by R2 term gracefully exits...... in a transitory regime characterized by coherent oscillations of the Hubble parameter. The universe then naturally enters into a radiation dominated epoch followed by a matter dominated era. At sufficiently late times after radiation–matter equality, the non-local term starts to dominate inducing an accelerated...... expansion of the universe at the present epoch. We further exhibit the fact that both the leading local and non-local terms can be obtained within the covariant effective field theory of gravity. This scenario thus provides a unified picture of inflation and dark energy in a single framework by means...

  6. Universe or Multiverse?

    Science.gov (United States)

    Carr, Bernard

    2009-08-01

    Part I. Overviews: 1. Introduction and overview Bernard Carr; 2. Living in the multiverse Steven Weinberg; 3. Enlightenment, knowledge, ignorance, temptation Frank Wilczek; Part II. Cosmology and Astrophysics: 4. Cosmology and the multiverse Martin J. Rees; 5. The anthropic principle revisited Bernard Carr; 6. Cosmology from the top down Stephen Hawking; 7. The multiverse hierarchy Max Tegmark; 8. The inflationary universe Andrei Linde; 9. A model of anthropic reasoning: the dark to ordinary matter ratio Frank Wilczek; 10. Anthropic predictions: the case of the cosmological constant Alexander Vilenkin; 11. The definition and classification of universes James D. Bjorken; 12. M/string theory and anthropic reasoning Renata Kallosh; 13. The anthropic principle, dark energy and the LHC Savas Dimopoulos and Scott Thomas; Part III. Particle Physics and Quantum Theory: 14. Quarks, electrons and atoms in closely related universes Craig J. Hogan; 15. The fine-tuning problems of particle physics and anthropic mechanisms John F. Donoghue; 16. The anthropic landscape of string theory Leonard Susskind; 17. Cosmology and the many worlds interpretation of quantum mechanics Viatcheslav Mukhanov; 18. Anthropic reasoning and quantum cosmology James B. Hartle; 19. Micro-anthropic principle for quantum theory Brandon Carter; Part IV. More General Philosophical Issues: 20. Scientific alternatives to the anthropic principle Lee Smolin; 21. Making predictions in a multiverse: conundrums, dangers, coincidences Anthony Aguirre; 22. Multiverses: description, uniqueness and testing George Ellis; 23. Predictions and tests of multiverse theories Don N. Page; 24. Observation selection theory and cosmological fine-tuning Nick Bostrom; 25. Are anthropic arguments, involving multiverses and beyond, legitimate? William R. Stoeger; 26. The multiverse hypothesis: a theistic perspective Robin Collins; 27. Living in a simulated universe John D. Barrow; 28. Universes galore: where will it all end? Paul

  7. Air University Style and Author Guide

    National Research Council Canada - National Science Library

    Bassett, Marvin

    2005-01-01

    The "Air University Style and Author Guide" is designed to unify the writing of faculty, staff, and students of Air University stylistically, and to give them information about publishing with Air University (AU) Press...

  8. [Issues related to national university medical schools: focusing on the low wages of university hospital physicians].

    Science.gov (United States)

    Takamuku, Masatoshi

    2015-01-01

    University hospitals, bringing together the three divisions of education, research, and clinical medicine, could be said to represent the pinnacle of medicine. However, when compared with physicians working at public and private hospitals, physicians working at university hospitals and medical schools face extremely poor conditions. This is because physicians at national university hospitals are considered to be "educators." Meanwhile, even after the privatization of national hospitals, physicians working for these institutions continue to be perceived as "medical practitioners." A situation may arise in which physicians working at university hospitals-performing top-level medical work while also being involved with university and postgraduate education, as well as research-might leave their posts because they are unable to live on their current salaries, especially in comparison with physicians working at national hospitals, who focus solely on medical care. This situation would be a great loss for Japan. This potential loss can be prevented by amending the classification of physicians at national university hospitals from "educators" to "medical practitioners." In order to accomplish this, the Japan Medical Association, upon increasing its membership and achieving growth, should act as a mediator in negotiations between national university hospitals, medical schools, and the government.

  9. Factors Affecting University Library Website Design

    Directory of Open Access Journals (Sweden)

    Yongi-Mi Kim

    2011-09-01

    Full Text Available Existing studies have extensively explored factors that affect users’ intentions to use university library website resources (ULWR; yet little attention has been given to factors affecting university library website design. This paper investigates factors that affect university library website design and assesses the success of the university library website from both designers’ and users’ perspectives. The findings show that when planning a website, university web designers consider university guidelines, review other websites, and consult with experts and other divisions within the library; however, resources and training for the design process are lacking. While website designers assess their websites as highly successful, user evaluations are somewhat lower. Accordingly, use is low, and users rely heavily on commercial websites. Suggestions for enhancing the usage of ULWR are provided.

  10. Interacting universes and the cosmological constant

    International Nuclear Information System (INIS)

    Alonso-Serrano, A.; Bastos, C.; Bertolami, O.; Robles-Pérez, S.

    2013-01-01

    In this Letter it is studied the effects that an interaction scheme among universes can have in the values of their cosmological constants. In the case of two interacting universes, the value of the cosmological constant of one of the universes becomes very close to zero at the expense of an increasing value of the cosmological constant of the partner universe. In the more general case of a chain of N interacting universes with periodic boundary conditions, the spectrum of the Hamiltonian splits into a large number of levels, each of them associated with a particular value of the cosmological constant, that can be occupied by single universes revealing a collective behavior that plainly shows that the multiverse is much more than the mere sum of its parts

  11. Interacting universes and the cosmological constant

    Energy Technology Data Exchange (ETDEWEB)

    Alonso-Serrano, A. [Centro de Física “Miguel Catalán”, Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas, Serrano 121, 28006 Madrid (Spain); Estación Ecológica de Biocosmología, Pedro de Alvarado 14, 06411 Medellín (Spain); Bastos, C. [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Avenida Rovisco Pais 1, 1049-001 Lisboa (Portugal); Bertolami, O. [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Avenida Rovisco Pais 1, 1049-001 Lisboa (Portugal); Departamento de Física e Astronomia, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto (Portugal); Robles-Pérez, S., E-mail: salvarp@imaff.cfmac.csic.es [Centro de Física “Miguel Catalán”, Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas, Serrano 121, 28006 Madrid (Spain); Estación Ecológica de Biocosmología, Pedro de Alvarado 14, 06411 Medellín (Spain); Física Teórica, Universidad del País Vasco, Apartado 644, 48080 Bilbao (Spain)

    2013-02-12

    In this Letter it is studied the effects that an interaction scheme among universes can have in the values of their cosmological constants. In the case of two interacting universes, the value of the cosmological constant of one of the universes becomes very close to zero at the expense of an increasing value of the cosmological constant of the partner universe. In the more general case of a chain of N interacting universes with periodic boundary conditions, the spectrum of the Hamiltonian splits into a large number of levels, each of them associated with a particular value of the cosmological constant, that can be occupied by single universes revealing a collective behavior that plainly shows that the multiverse is much more than the mere sum of its parts.

  12. Research universities for the 21st century

    Energy Technology Data Exchange (ETDEWEB)

    Gover, J. [Sandia National Labs., Albuquerque, NM (United States); Huray, P.G. [Univ. of South Carolina, Columbia, SC (United States)

    1998-05-01

    The `public outcomes` from research universities are educated students and research that extends the frontiers of knowledge. Measures of these `public outcomes` are inadequate to permit either research or education consumers to select research universities based on quantitative performance data. Research universities annually spend over $20 billion on research; 60% of these funds are provided by Federal sources. Federal funding for university research has recently grown at an annual rate near 6% during a time period when other performers of Federal research have experienced real funding cuts. Ten universities receive about 25% of the Federal funds spent on university research. Numerous studies of US research universities are reporting storm clouds. Concerns include balancing research and teaching, the narrow focus of engineering education, college costs, continuing education, and public funding of foreign student education. The absence of research on the `public outcomes` from university research results in opinion, politics, and mythology forming the basis of too many decisions. Therefore, the authors recommend studies of other nations` research universities, studies of various economic models of university research, analysis of the peer review process and how well it identifies the most capable research practitioners and at what cost, and studies of research university ownership of intellectual property that can lead to increased `public outcomes` from publicly-funded research performed by research universities. They advocate two practices that could increase the `public outcomes` from university research. These are the development of science roadmaps that link science research to `public outcomes` and `public outcome` metrics. Changes in the university research culture and expanded use of the Internet could also lead to increased `public outcomes`. They recommend the use of tax incentives to encourage companies to develop research partnerships with research

  13. University crisis and social responsibility

    Directory of Open Access Journals (Sweden)

    José Camilo dos Santos Filho

    2016-01-01

    Full Text Available The purpose of this study was to investigate the repercussion of the recent crisis of the university on its mission and responsibility and, from this reflection, to propose ways for the consolidation of this responsibility. The three main crisis faced by the university  from the middle of the XXth century identified by Boaventura Souza Santos as crisis of hegemony, of legitimacy and institutional, constituted the framework of discussion of the problem of social responsibility of the university. Although true for the universities of the advanced countries, the loss of hegemony in the area of research still does not occur in Brazilian university. To overcome the crisis of legitimacy, the creation of advanced academic and professional training institutions for the cultivation of the intellectual and professional elite of the country, as well as of non university institutions of mass higher education for the cultural and technological formation of the youth is justified. To make possible the access to these institutions by discriminated socioeconomic segments of society, the adoption of the policy of affirmative action in the form of quotas is justified.  The overcoming of the institutional crisis will be achieved when the State respect the specificity of the universities and when the evaluation criteria of her functions be adequate to her specific nature and the titularity of the evaluation belong to the institutions themselves assuring the external evaluation by effective pairs and not by pairs coopted by the State.

  14. Chaotic universe model.

    Science.gov (United States)

    Aydiner, Ekrem

    2018-01-15

    In this study, we consider nonlinear interactions between components such as dark energy, dark matter, matter and radiation in the framework of the Friedman-Robertson-Walker space-time and propose a simple interaction model based on the time evolution of the densities of these components. By using this model we show that these interactions can be given by Lotka-Volterra type equations. We numerically solve these coupling equations and show that interaction dynamics between dark energy-dark matter-matter or dark energy-dark matter-matter-radiation has a strange attractor for 0 > w de  >-1, w dm  ≥ 0, w m  ≥ 0 and w r  ≥ 0 values. These strange attractors with the positive Lyapunov exponent clearly show that chaotic dynamics appears in the time evolution of the densities. These results provide that the time evolution of the universe is chaotic. The present model may have potential to solve some of the cosmological problems such as the singularity, cosmic coincidence, big crunch, big rip, horizon, oscillation, the emergence of the galaxies, matter distribution and large-scale organization of the universe. The model also connects between dynamics of the competing species in biological systems and dynamics of the time evolution of the universe and offers a new perspective and a new different scenario for the universe evolution.

  15. Mapping International University Partnerships Identified by East African Universities as Strengthening Their Medicine, Nursing, and Public Health Programs.

    Science.gov (United States)

    Yarmoshuk, Aaron N; Guantai, Anastasia Nkatha; Mwangu, Mughwira; Cole, Donald C; Zarowsky, Christina

    International university partnerships are recommended for increasing the capacity of sub-Saharan African universities. Many publications describe individual partnerships and projects, and tools are available for guiding collaborations, but systematic mappings of the basic, common characteristics of partnerships are scarce. To document and categorize the international interuniversity partnerships deemed significant to building the capacity of medicine, nursing, and public health programs of 4 East African universities. Two universities in Kenya and 2 in Tanzania were purposefully selected. Key informant interviews, conducted with 42 senior representatives of the 4 universities, identified partnerships they considered significant for increasing the capacity of their institutions' medicine, nursing, and public health programs in education, research, or service. Interviews were transcribed and analyzed. Partners were classified by country of origin and corresponding international groupings, duration, programs, and academic health science components. One hundred twenty-nine university-to-university partnerships from 23 countries were identified. Each university reported between 25 and 36 international university partners. Seventy-four percent of partnerships were with universities in high-income countries, 15% in low- and middle-income countries, and 11% with consortia. Seventy percent included medicine, 37% nursing, and 45% public health; 15% included all 3 programs. Ninety-two percent included an education component, 47% research, and 24% service; 12% included all 3 components. This study confirms the rapid growth of interuniversity cross-border health partnerships this century. It also finds, however, that there is a pool of established international partnerships from numerous countries at each university. Most partnerships that seek to strengthen universities in East Africa should likely ensure they have a significant education component. Universities should make

  16. Polymer nanoparticles for cross-presentation of exogenous antigens and enhanced cytotoxic T-lymphocyte immune response

    Directory of Open Access Journals (Sweden)

    Song C

    2016-08-01

    Full Text Available Chanyoung Song,* Young-Woock Noh,* Yong Taik Lim SKKU Advanced Institute of Nanotechnology (SAINT, School of Chemical Engineering, Sungkyunkwan University, Suwon, South Korea *These authors contributed equally to this work Abstract: Effective induction of an antigen-specific cytotoxic T lymphocyte (CTL immune response is one of the key goals of cancer immunotherapy. We report the design and fabrication of polyethylenimine (PEI-coated polymer nanoparticles (NPs as efficient antigen-delivery carriers that can induce antigen cross-presentation and a strong CTL response. After synthesis of poly(d,l-lactide-co-glycolide (PLGA NPs containing ovalbumin (OVA by the double-emulsion solvent-evaporation method, cationic-charged PLGA NPs were generated by coating them with PEI. In a methyl tetrazolium salt assay, no discernible cytotoxic effect of PEI-coated PLGA (OVA NPs was observed. The capacity and mechanism of PEI-coated PLGA (OVA NPs for antigen delivery and cross-presentation on dendritic cells (DCs were determined by fluorescence microscopy and flow cytometry. PEI-coated PLGA (OVA NPs were internalized efficiently via phagocytosis or macropinocytosis in DCs and induced efficient cross-presentation of the antigen on MHC class I molecules via both endosome escape and a lysosomal processing mechanism. The DCs treated with PEI-coated PLGA (OVA NPs induced a release of IL-2 cytokine from OVA-specific CD8-OVA1.3 T cells more efficiently than DCs treated with PLGA (OVA NPs. Therefore, the PEI-coated PLGA (OVA NPs can induce antigen cross-presentation and are expected to be used for induction of a strong CTL immune response and for efficient anticancer immunotherapy. Keywords: antigen delivery, dendritic cells, polymer NPs, vaccine, cross-presentation

  17. Hybrid Single-Incision Laparoscopic Colon Cancer Surgery Using One Additional 5 mm Trocar.

    Science.gov (United States)

    Kim, Hyung Ook; Choi, Dae Jin; Lee, Donghyoun; Lee, Sung Ryol; Jung, Kyung Uk; Kim, Hungdai; Chun, Ho-Kyung

    2018-02-01

    Single-incision laparoscopic surgery (SILS) is a feasible and safe procedure for colorectal cancer. However, SILS has some technical limitations such as collision between instruments and inadequate countertraction. We present a hybrid single-incision laparoscopic surgery (hybrid SILS) technique for colon cancer that involves use of one additional 5 mm trocar. Hybrid SILS for colon cancer was attempted in 70 consecutive patients by a single surgeon between August 2014 and July 2016 at Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine. Using prospectively collected data, an observational study was performed on an intention-to-treat basis. Hybrid SILS was technically completed in 66 patients, with a failure rate of 5.7% (4/70). One patient was converted to open surgery for para-aortic lymph node dissection. Another was converted to open surgery due to severe peritoneal adhesion. An additional trocar was inserted for adhesiolysis in the other two cases. Median lengths of proximal and distal margins were 12.8 cm (interquartile range [IQR], 10.0-18.6), and 8.2 cm (IQR, 5.5-18.3), respectively. Median total number of lymph nodes harvested was 24 (IQR, 18-33). Overall rate of postoperative morbidity was 12.9%, but there were no Clavien-Dindo grade III or IV complications. There was no postoperative mortality or reoperation. Median postoperative hospital stay was 6 days (IQR, 5-7). Hybrid SILS using one additional 5 mm trocar is a safe and effective minimally invasive surgical technique for colon cancer. Experienced laparoscopic surgeons can perform hybrid SILS without a learning curve based on the formulaic surgical techniques presented in this article.

  18. Understanding University Technology Transfer

    Science.gov (United States)

    Association of American Universities, 2011

    2011-01-01

    Federal government agencies provide about $33 billion a year to universities to conduct scientific research. That continuing investment expands human knowledge and helps educate the next generation of science and technology leaders. New discoveries from university research also form the basis for many new products and processes that benefit the…

  19. Talent Management for Universities

    Science.gov (United States)

    Bradley, Andrew P.

    2016-01-01

    This paper explores human resource management practices in the university sector with a specific focus on talent pools and talent management more generally. The paper defines talent management in the context of the university sector and then explores its interdependence with organisational strategy, the metrics used to measure academic performance…

  20. What Does "International University" Mean at a European Bilingual University? the Role of Languages and Culture

    Science.gov (United States)

    Doiz, Aintzane; Lasagabaster, David; Sierra, Juan Manuel

    2014-01-01

    Internationalisation has brought about remarkable changes at universities all over the world. In the case of the University of the Basque Country (Spain) this is reflected in the increasing presence of English-medium instruction. This paper examines two issues: the university community's perception of (1) the term "international…