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Depletion of FKBP51 in Female Mice Shapes HPA Axis Activity
Lianne Hoeijmakers, Daniela Harbich, Bianca Schmid, Paul J. Lucassen, Klaus V. Wagner, Mathias V. Schmidt, Jakob Hartmann
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095796
Abstract: Psychiatric disorders such as depressive disorders and posttraumatic stress disorder are a major disease burden worldwide and have a higher incidence in women than in men. However, the underlying mechanism responsible for the sex-dependent differences is not fully understood. Besides environmental factors such as traumatic life events or chronic stress, genetic variants contribute to the development of such diseases. For instance, variations in the gene encoding the FK506 binding protein 51 (FKBP51) have been repeatedly associated with mood and anxiety. FKBP51 is a negative regulator of the glucocorticoid receptor and thereby of the hypothalamic–pituitary–adrenal axis that also interacts with other steroid hormone receptors such as the progesterone and androgen receptors. Thus, the predisposition of women to psychiatric disorders and the interaction of female hormones with FKBP51 and the glucocorticoid receptor implicate a possible difference in the regulation of the hypothalamic–pituitary–adrenal axis in female FKBP51 knockout (51KO) mice. Therefore, we investigated neuroendocrine, behavioural and physiological alterations relevant to mood disorders in female 51KO mice. Female 51KOs and wild type littermates were subjected to various behavioural tests, including the open field, elevated plus maze and forced swim test. The neuroendocrine profile was investigated under basal conditions and in response to an acute stressor. Furthermore, we analysed the mRNA expression levels of the glucocorticoid receptor and corticotrophin release hormone in different brain regions. Overall, female 51KO mice did not display any overt behavioural phenotype under basal conditions, but showed a reduced basal hypothalamic–pituitary–adrenal axis activity, a blunted response to, and an enhanced recovery from, acute stress. These characteristics strongly overlap with previous studies in male 51KO mice indicating that FKBP51 shapes the behavioural and neuroendocrine phenotype independent of the sex of the individual.
The Failure of Fast Ferry Catamaran Operations in New Zealand and Hawaii  [PDF]
Gui Lohmann, Jakob Trischler
Journal of Transportation Technologies (JTTs) , 2012, DOI: 10.4236/jtts.2012.22012
Abstract: Fast ferry catamarans have been in use for several decades. They possess the advantage of overcoming one of the major deficiencies of water transportation: low speed. Although their operation has spread throughout different parts of the world, an overall analysis of the implementation and failures of this technology remains underdeveloped in the transport literature. This paper presents and compares two unsuccessful experiences of the use of fast ferry catamarans in New Zealand and Hawaii. Although both attempts possess major differences in terms of their contexts, particularly regarding competition, regulatory and environmental issues, some of the common lessons learned from both experiences can significantly contribute to a better understanding of this water transport technology and the challenges involved in its operation.
Analytical and Numerical Investigations of Probabilistic Monochromatic Problem  [PDF]
Stefan Schmuck, Jakob Svensson
Journal of Applied Mathematics and Physics (JAMP) , 2019, DOI: 10.4236/jamp.2019.74054
Abstract: A probabilistic formalism, relying on Bayes’ theorem and linear Gaussian inversion, is adapted, so that a monochromatic problem can be investigated. The formalism enables an objective test in probabilistic terms of the quantities and model concepts involved in the problem at hand. With this formalism, an amplitude (linear parameter), a frequency (non-linear parameter) and a hyperparameter of the Gaussian amplitude prior are inferred jointly given simulated data sets with Gaussian noise contributions. For the amplitude, an analytical normal posterior follows which is conditional on the frequency and the hyperparameter. The remaining posterior estimates the frequency with an uncertainty of MHz, while the convolution of a standard approach would achieve an uncertainty of some GHz. This improvement in the estimation is investigated analytically and numerically, revealing for instance the positive effect of a high signal-to-noise ratio and/or a large number of data points. As a fixed choice of the hyperparameter imposes certain results on the amplitude and frequency, this parameter is estimated and, thus, tested for plausibility as well. From abstract point of view, the model posterior is investigated as well.
Hippocampal Homer1 Levels Influence Motivational Behavior in an Operant Conditioning Task
Klaus V. Wagner, Alexander S. H?usl, Max L. P?hlmann, Jakob Hartmann, Christiana Labermaier, Marianne B. Müller, Mathias V. Schmidt
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0085975
Abstract: Loss of motivation and learning impairments are commonly accepted core symptoms of psychiatric disorders such as depression and schizophrenia. Reward-motivated learning is dependent on the hippocampal formation but the molecular mechanisms that lead to functional incentive motivation in this brain region are still largely unknown. Recent evidence implicates neurotransmission via metabotropic glutamate receptors and Homer1, their interaction partner in the postsynaptic density, in drug addiction and motivational learning. As previous reports mainly focused on the prefrontal cortex and the nucleus accumbens, we now investigated the role of hippocampal Homer1 in operant reward learning in the present study. We therefore tested either Homer1 knockout mice or mice that overexpress Homer1 in the hippocampus in an operant conditioning paradigm. Our results show that deletion of Homer1 leads to a diverging phenotype that either displays an inability to perform the task or outstanding hyperactivity in both learning and motivational sessions. Due to the apparent bimodal distribution of this phenotype, the overall effect of Homer1 deletion in this paradigm is not significantly altered. Overexpression of hippocampal Homer1 did not lead to a significantly altered learning performance in any stage of the testing paradigm, yet may subtly contribute to emerging motivational deficits. Our results indicate an involvement of Homer1-mediated signaling in the hippocampus in motivation-based learning tasks and encourage further investigations regarding the specific molecular underpinnings of the phenotypes observed in this study. We also suggest to cautiously interpret the results of this and other studies regarding the phenotype following Homer1 manipulations in animals, since their behavioral phenotype appears to be highly diverse. Future studies would benefit from larger group sizes that would allow splitting the experimental groups in responders and non-responders.
Capacity Building for the Integration of Climate Adaptation into Urban Planning Processes: The Dutch Experience  [PDF]
Thomas Hartmann, Tejo Spit
American Journal of Climate Change (AJCC) , 2014, DOI: 10.4236/ajcc.2014.33023
Abstract: The institutions of the Dutch (urban) planning system face four challenging characteristics of climate adaptation measures. These measures are uncertain in their effects, in competition with other interests, multifaceted, and inherently complex. Capacity building is a key issue for the implementation of climate adaptation measures in urban planning processes, which aim to achieve Climate-Proof Cities (CPC). For successful capacity building, it is important to define the relevant stakeholders and tailor the adaptation strategies first to (the position of) these stakeholders and next to the specific urban conditions and issues. In addition, scientific insights and tools can be of assistance, and the use of climate maps can help to create a common language. Such common understanding of climate problems can lead to “goal entwinement” between actors, which can support the implementation of climate adaptation strategies in urban planning. Awareness, recognition and urgency are the most important components of this common understanding, which may differ for each stage in every urban planning process. In order to overcome the pragmatism that rules in day-to-day urban planning processes, multi-level arrangements between different tiers of government must be employed to improve the penetration of climate adaptation measures. After all, it still remains a soft interest in a hard process.
PHY·FI: fast and easy online creation and manipulation of phylogeny color figures
Jakob Fredslund
BMC Bioinformatics , 2006, DOI: 10.1186/1471-2105-7-315
Abstract: This paper presents an online tool, PHY·FI, which encompasses all the qualities of existing online programs and adds functionality to hopefully eliminate the need for post-processing the phylogeny figure in some other general-purpose graphics program. PHY·FI is versatile, easy-to-use and fast, and supports comprehensive graphical control, several download image formats, and the possibility of dynamically collapsing groups of nodes into named subtrees (e.g. "Primates"). The user can create a color figure from any phylogeny, or other kind of tree, represented in the widely used parenthesized Newick format.PHY·FI is fast and easy to use, yet still offers full color control, tree manipulation, and several image formats. It does not require any downloading and installing, and thus any internet user regardless of computer skills, and computer platform, can benefit from it. PHY·FI is free for all and is available from this web address: http://cgi-www.daimi.au.dk/cgi-chili/phyfi/go webciteMany researchers from a wide range of biological and computational disciplines have a recurrent need for depicting trees of various forms, e.g. phylogenies. Often, the tree is represented as a text string or file in the parenthesized Newick format. This is true for phylogenies produced by software such as the Phylip package [1] or ClustalW [2]. For example, when performing a multiple alignment of sequences with ClustalW, apart from the alignment itself a dendrogram file is produced with extension .dnd, and this file contains a Newick representation of the phylogeny inferred from aligning the sequences.From the rather incomprehensible textual description of a Newick tree, humans can learn little about the overall tree structure or of the relationship between particular nodes:(Bovine:0.69395,(Gibbon:0.36079, (Orangutan:0.33636,(Gorilla:0.17147, (Chimpanzee:0.19268,Human:0.11927):0.08386):0.06124):0.15057):0.54939,Mouse:1.2146);Hence, for full comprehension of the tree structure, researchers
DATFAP: A Database of Primers and Homology Alignments for Transcription Factors from 13 Plant Species
Jakob Fredslund
BMC Genomics , 2008, DOI: 10.1186/1471-2164-9-140
Abstract: DATFAP is a free, web-based, very user-friendly browsing tool based on a new database of more than 55,000 EST sequences from 13 plant species, classified as transcription factors. Further, the database offers primers designed for RealTime-PCR as well as homology alignments and phylogenies for the sequences. The provided PCR primers are designed so that they have a perfect sequence alignment to their target only and not to any other sequences in the database from the same species. Via a direct link to a helper tool, the user may also design a general primer set targeting all sequences in any hand-picked group of homologs. A sophisticated search facility enables the user to find exactly the relevant sequences which subsequently may be easily downloaded. All homologies among the more than one billion possible pairwise sequence comparisons of DATFAP have been charted in advance. Thus, the user may quickly display the alignment of any sequence and all its database homologs.Because of the comprehensive homology analysis, it is very easy to find related transcription factors from different species, i.e. to navigate the network of inter-related transcription factors from the different species, and to find specific or general primers for them. DATFAP is found at the project homepage.Transcription factors are proteins acting to regulate expression of genes by binding to their regulatory regions. Activated in signal transduction pathways, they are essential in the production of the right cellular response to some stimulus. Hence, specific transcription factors are the topic of study in hundreds of research projects, including projects dealing with plant breeding. Such studies can be very different in nature, ranging from the precise, functional characterization of certain proteins [1] over identification and classification of families of related proteins [2] to genetic modification [3].When examining cDNA samples for the presence or expression levels of transcripts, one very o
Mehr als Marginalien - das E-Book als gemeinsamer Zettelkasten
Jakob Vo?
Libreas : Library Ideas , 2005,
Zur Neubestimmung des Dokumentbegriffs im rein Digitalen
Jakob Vo?
Libreas : Library Ideas , 2009,
Abstract: Obgleich der Wandel vom gedrucktem zum digitalen Wort noch immer nicht abgeschlossen ist und viele Medien weiterhin gedruckt erscheinen, vertrieben und gesammelt werden, ist absehbar, dass in Zukunft alle wesentliche Publikation und Kommunikation digital stattfinden wird. Dieser Wandel, dessen Bedeutung noch am ehesten mit der Einführung des Buchdrucks mit beweglichen Lettern verglichen werden kann, erfordert eine Neubestimmung mehrerer Grundbegriffe der Bibliotheks- und Informationswissenschaft. Eine zentrale Rolle spielen dabei die Begriffe der Information, der Publikation und des Dokumentes.
Review: Elmar Stahl (2001). Hyper – Text – Schreiben Review: Elmar Stahl (2001). Hyper – Text – Schreiben [Writing Hypertext] Rese a: Elmar Stahl (2001). Hyper – Text – Schreiben [Escritura en Hipertexto]
Jakob Marti
Forum : Qualitative Social Research , 2004,
Abstract: In letzter Zeit wurde das Internet als Mittel des Lernens an Schulen und Universit ten entdeckt. Das Lernen durch Lesen von Hypertexten hat aber nicht immer Vorteile gegenüber Büchern. Diese Studie untersucht deshalb, ob die SchülerInnen durch Erstellen von Hypertexten einen gr eren Lernerfolg aufweisen k nnen. Anhand von drei Experimenten zeigt der Autor, dass durch die Raummetapher gegenüber der Buchmetapher und durch die Angabe von Linktypen deutlich vernetztere Texte entstehen. Die Menge des Wissens ver ndert sich aber dadurch nicht. Zusammen mit den Vorarbeiten handelt es sich um eine sehr aufw ndige Studie. Die Ergebnisse werden etwas eingeschr nkt, weil die Testpersonen nicht wirklich neue Texte verfassen, sondern nur vorgegebene Texte untereinander verlinken. Auch wenn die Studie selbst quantitativ ausgerichtet ist, ist erkennbar, dass in einer qualitativen Auswertung der von STAHL in seinen Untersuchungen erhobenen Daten noch gro es Potential liegt. URN: urn:nbn:de:0114-fqs0401160 Lately, the Internet has been discovered as a tool for studying at schools and universities. Studying by means of hypertext, though, is not always advantageous over studying through the use of paper books. The author examines if students can improve their learning results by writing in hypertext. He investigates whether different instructions by teachers can improve learning results. He shows in three experimental studies that hypertexts become more interlinked by means of the room metaphor, compared to the book metaphor, and by means of categorizing hyperlinks. The amount of knowledge, though, does not change. Together with the preparatory studies, the author presents an impressively detailed study. The scope of the results is, however, somewhat restricted: the subjects do not really write new texts. Instead, they transform the texts that are presented to them into hypertexts. The study is based on quantitative statistical research, but its great potential lies in the evaluation of the subjects' thoughts and commentaries. URN: urn:nbn:de:0114-fqs0401160 Recientemente Internet ha sido descubierta en las escuelas y universidades como una herramienta para el estudio. Estudiar a través de los significados del hipertexto, sin embargo, no siempre es una ventaja sobre el estudio mediante el uso de libros impresos. El autor examina si los estudiantes pueden mejorar sus resultados de aprendizaje al escribir en hipertexto. El investiga si las distintas instrucciones de los docentes pueden mejorar los resultados de aprendizaje. Muestra en tres estudios experimentales que el hi
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