1,002 research outputs found
Treatment of unruptured intracranial aneurysms : a surgical long-term evaluation for preoperative predictive analytics
No full textAuthor Dr.med.univ. Nico Henrique Stroh-HollyDissertation Johannes Kepler Universität Linz 202
Changes in kynurenine metabolites in the gray and white matter of the dorsolateral prefrontal cortex of individuals affected by schizophrenia
No full textAbstract Alterations in the kynurenine pathway of tryptophan metabolism have been implicated in the pathophysiology of schizophrenia. Here, we performed an in-depth analysis of all metabolites of the kynurenine pathway, i.e., tryptophan (TRY), kynurenic acid (KYNA), L-kynurenine (KYN), 3-hydroxykynurenine (3-HK), anthranylic acid (ANA), 3-hydroxyanthranylic acid (3-HANA), xanthurenic acid (XA) and quinolinic acid (QUINA), in postmortem samples of the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46, 9) of individuals affected by schizophrenia and non-schizophrenic controls. The analysis was carried out in the gray and white matter. Levels of KYN, 3-HK, ANA, and 3-HANA were significantly increased in both the gray and white matter of the DLPFC of individuals affected by schizophrenia, whereas levels of TRY, KYNA, and QUINA were increased exclusively in the white matter and remained unchanged in the gray matter. These increases in kynurenine metabolites did not correlate with age, sex, duration of the disease, and duration and type of antipsychotic medication. These findings suggest that the two major branches of the kynurenine pathway, i.e., the transamination of KYN into KYNA, and hydroxylation of KYN into 3-HK are activated in the white matter of individuals affected by schizophrenia, perhaps as a result of neuroinflammation, and support the evidence that abnormalities of the white matter are consistenly associated with schizophrenia
Enough of 'tough': Youth Justice in Scotland
No full textHow can we build an effective youth justice system that enjoys public confidence while recognising that children must be redeemable?Nico Juetten presents a view from Scotland, considering the challenges to the children's hearings system Copyright (c) 2009 The Author. Journal compilation (c) 2009 ippr.
Ciò che resta della terza dimensione
No full textThe s.c. «third dimension» is one of the first definitions given in the sociological arena to define the development of a ate element that was not identifiable with generalist instances of the state or with those particularistic of the market. Deriving its conceptualization from the Husserlian theory, Ardigò through the use this approach emphasizing the need to reconstruct the crisis through new forms of transaction between the social system and life-worlds. The use of this conceptualization led to the identification of these intermediary organizations between different systems. The text takes a brief overview of the third dimension organizations and the way how they operate the reconciliation between inter-subjectivity and super-ordination present in the systemic sense. It is proposed a scheme of interpretation, drawn from the author in question, through which classifying not merely the organization but the possible interconnections between micro and macro and their consequences. It is concluded that the abandon of the analytical perspective proposed by Ardigò, primarily for the affirmation of a vision of an economic nature, was determined both by the theoretical vulgate established around of the 90, and the difficulty in operationalizing a definition that owed much to the knowledge from the phenomenology of the Bolognese scientist
Alla ricerca della sovranità nello studio di Carlo Lavagna sulle figure giuridiche soggettive
Get PDFIl presente contributo ripercorre il saggio di Carlo Lavagna, Basi per uno studio delle figure giuridiche soggettive contenute nella Costituzione italiana, allo scopo di ricercare il filo conduttore della sovranità in tutte le figure giuridiche soggettive sia che esse siano solo raccomandate, sia che siano garantite o anche tutelate dalla Costituzione, secondo la classificazione dell’Autore. Tale analisi è stata preceduta da un breve richiamo al metodo di indagine dell’Autore e alla sua concezione quadrangolare della democrazia.This contribution reinterprets the essay by Carlo Lavagna, Basis for a study of the subjective juridical figures contained in the Italian Constitution, in order to search for the sphere of sovereignty in all subjective legal figures whether they are only recommended, whether they are guaranteed or also protected by the Constitution, according to the classification of the Author. This analysis was preceded by a brief recall of the Author's method of investigation and its quadrangular concept of democracy
Distinct and common functions of mTORC1 and mTORC2 in Purkinje cells
Get PDFIn mammalian cells, the serine/threonine protein kinase mTOR (mammalian target of rapamycin) is present in two complexes, called mTORC1 and mTORC2. While several of the components are common to both complexes, raptor and rictor are only associated with mTORC1 or mTORC2, respectively. Due to differences in their molecular composition mTORC1 and mTORC2 possess distinct functions and properties (Laplante & Sabatini, 2012). For example, mTORC1 but not mTORC2 is sensitive to the immunosuppressive drug rapamycin. mTORC1 integrates various extracellular signals (e.g. growth factors, energy status or amino acid availability) to promote protein synthesis, to regulate lipogenesis and to inhibit autophagy (Shimobayashi & Hall, 2014). In line with these features, mTORC1 was found to be essential for cell growth and proliferation. In contrast, activation and function of mTORC2 is less well understood. It phosphorylates and activates members of the AGC kinase family, including Akt, SGK1 and PKC, suggesting a role in cell survival/metabolism and actin cytoskeleton organization.
In the brain, mTOR signalling has been implicated in several neurodevelopmental and neurodegenerative disorders like autism spectrum disorders (ASD) or Huntington’s disease. The availability of approved drugs, such as rapamycin and its analogs (called rapalogs), has made the mTOR signalling pathway an attractive target for the treatment of those diseases. Although rapamycin has been shown to preferentially target mTORC1, prolonged exposure also inhibits mTORC2 (Sarbassov et al., 2006). Thus, it is important to unravel the specific and the common functions of mTORC1 and mTORC2 in the central nervous system.
In this study, the roles of mTORC1 and mTORC2 were analysed in Purkinje cells by conditionally deleting floxed Rptor or Rictor genes, respectively, using an L7/Pcp-2-driven expression of the Cre recombinase. The resulting mouse lines are called RAPuKO or RIPuKO, which stands for raptor or rictor Purkinje knockout, respectively, and allowed to study the functions of mTORC1 and mTORC2 in developing and adult Purkinje cells and to investigate the effect on mouse behaviour.
We found that the phenotypes of RAPuKO and RIPuKO mice only sparsely overlapped but mostly differed, which assigns mTORC1 and mTORC2 distinct functions in these neurons. (I) mTORC1, but not mTORC2 abrogation in Purkinje cells reduced the social interest of mice. (II) Ablation of either mTORC1 or mTORC2 in Purkinje cells was sufficient to cause motor coordination deficits, yet, for RAPuKO mice the onset of these deficits was age-dependent while motor deficits of RIPuKO mice could be detected at any tested age. (III) The motor phenotype of RIPuKO mice was accompanied by developmental aberrations, such as impaired climbing fibre synapse elimination and hampered dendritic self-avoidance, while the age-dependent motor phenotype of RAPuKO mice seemed to be driven by Purkinje cell degeneration that finally led to apoptosis and a loss of these neurons. Vice versa, no signs for deficient climbing fibre elimination or Purkinje cell loss could be detected for RAPuKO or RIPuKO mice, respectively. (IV) mTORC1 and mTORC2 ablation in Purkinje cells both affected neuron morphology in a similar manner, which included multiple primary dendrites and a reduction of the neuron size, yet, last was more pronounced for raptor-deficient cells.
Altogether, both mTORC1 and mTORC2 ablation in Purkinje cells had a pronounced, yet distinct, effect on these neurons and the mouse behaviour, unlike in other tissues where inactivation of mTORC2 has been reported to result in a minor phenotype in comparison to mTORC1 ablation (Bentzinger et al., 2008; Godel et al., 2011).
While ablation of mTORC1 and mTORC2 in Purkinje cells resulted in mostly distinct phenotypes, we found that sustained mTORC1 activation in these neurons by a TSC1 knockout (TSCPuKO) caused a phenotype that was similar to the one of RAPuKO mice. In both RAPuKO and TSCPuKO mice an age-dependent loss of Purkinje cells due to apoptosis was observed, which was paralleled by reactive gliosis. Moreover, in both cases Purkinje cell apoptosis was preceded by signs of neurodegeneration in form of axonal swellings that accumulated neurofilaments. Also in terms of behaviour similar phenotypes were observed since both knockout mice showed reduced social interest (Tsai et al., 2012). These behavioural phenotypes support the growing notion that the cerebellum is important for non-motor related functions (Schmahmann et al., 2007; Wang et al., 2014) and that mTORC1 plays a role therein. TSC1 knockout in Purkinje cells has been reported to cause also repetitive behaviour in mice in addition to abnormal social behaviour and therefore it has been suggested that these mice show an autism-like phenotype (Tsai et al., 2012).
In summary, this study provides in vivo data for the importance of mTORC1 and mTORC2 in developing and adult Purkinje neurons. We find that both complexes are crucial for Purkinje cells, yet, in mostly distinct manners. This finding is in line with the model that mTORC1 and mTORC2 largely feed separate downstream effectors, although they share many molecular components. The knowledge of the function of mTORC1 and mTORC2 in adult neurons is important for the development of treatment options that target the mTOR pathway. This work clearly suggests that such drugs need to be highly selective for the different complexes. Moreover, this work highlights that a complete inhibition of mTORC1 may have detrimental effects on the survival of neurons and that this may also precipitate autism-like pathologies
The Understood Author: A hermeneutical exploration of audiences interpretation of the author as productive practices behind a text
No full textin English This project builds on the tradition of audience research that theoretically and empirically established that meaning is formed in the negotiation between the text and the reader, that the audiences are agentic, their interpretation of media is contextual and situated, and that they have the potential to resist the media. It argues that it is important to explore people's attention to different sources: who is listening, to whom, and why - and asks how people understand the notion of an author that they encounter in the interpretation of factual media texts, and how this interpretation is brought back into the interpretative act. The thesis subscribes to philosophical hermeneutics as an overarching theoretical as well as methodological framework to devise a concept of an understood author that is a result of the interpretative act, where the author imagined and anticipated by the reader (in the form of prior knowledge and prejudices) is encountered and actualised by the author inscribed into the text. I carried out 28 in-depth face-to-face interviews with Czechs born between 1948-1963 to explore participants' experiences and relationship with media and media authors. Employing hermeneutical analysis, the focus is not to capture what is an author, but how it happened to be so. The..
NILAI NILAI MORAL DALAM FILM NOBODY KNOWS KARYA SUTRADARA HIROKAZU KOREEDA KAJIAN SOSIOLOGI SASTRA 『是枝 裕和 が監督した『NOBODY KNOWS 』という映画における 道徳的価値『文芸社会学の研究』
Get PDFABSTRACT
Saragih, Nico Rinaldi. 2018. "Moral Values in the Nobody Knows Movie by Director of Hirokazu Koreeda in the Study of Sociology of Literature". A Thesis of Japanese Language and Culture, Faculty of Humanities Diponegoro University, Semarang. Consultant: Budi Mulyadi, S.Pd.,M.Hum.
This study aims to describe the narrative element of the film Nobody Knows and describe the moral values contained in the film Nobody Knows. The author uses the literature study method to obtain data and also data observations by viewing the Nobody Knows movie over and over. The theory used in this study is moral value by Andri Wicaksono.
Based on data analysis, it can be concluded that in the Nobody Knows film there are 8 moral values contained in human and self relations, and 5 moral values contained in human relations with other human beings in the social sphere
Keywords: Hirokazu Koreeda, Moral Value, Nobody Know
What's on a machine's mind? Models for reasoning with incomplete and uncertain knowledge
No full textElectrical Engineering, Mathematics and Computer Scienc
Vocabulary games: More than just wordplay
No full textGames offer more than just fun and play, and the analyses suggest that varying vocabulary activities is important if learners are to practice all the aspects of word knowledge. However, despite all the evidence, just claiming that playing games is a good way to practice the language is often not enough to win the argument. Because author Nico Lorenzutti's in-service teachers needed a specific rationale to explain what their learners achieve when they play games, he created a simple tool to explain what learners achieve when they play games. This article describes the procedures for several games and illustrates how to use this tool to assess their overall effectiveness for vocabulary development
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