Behavioural analysis of mouse mutants with altered neuronal and glial genes

Im ersten Teil dieser Doktorarbeit beabsichtigte meine Arbeit, die funktionelle Beteiligung des CB1 Rezeptors, einer Hauptkomponente des neuronalen Endocannabinoid-Systems (ECS), an der Ausbildung von verschiedenen Verhaltensphänotypen mit Hilfe von konditionalen Mausmutanten, denen der CB1 Rezeptor auf verschiedenen neuronalen Unterpopulationen fehlt, aufzuschlüsseln und zu untersuchen. Verschiedene Verhaltensmodelle wurden hierzu getestet. Dabei lag der Fokus dieser Arbeit auf der CB1f/f;D1-Cre Mauslinie, welche der CB1 Rezeptor auf den D1 Rezeptor exprimierenden Neuronen des Striatums fehlt. Ich konnte zeigen, dass der Verlust des CB1 Rezeptors auf diesen Neuronen keinen Einfluss auf basale neurologische Funktionen, Gewicht, Bewegung, Exploration, Sozialverhalten, Angst und Stressbewältigung der Tiere hat, jedoch eine Beteiligung an der Entwicklung von Suchtverhalten gegeben ist. Bei Betrachtung des Kokain-induzierten Suchtverhaltens zeigten die konditionalen Mausmutanten eine reduzierte Suchtanfälligkeit sowohl im Vergleich zu Tieren mit einem totalen CB1 Rezeptor Verlust in allen Körperzellen, als auch zu genetisch unveränderten Kontrollmäusen beider Linien.rnDes Weiteren zeigen die Ergebnisse dieser Studie eine große, aber gegensätzliche Beteiligung des ECS bei der Regulation von Exploration in Abhängigkeit des Verlustes des CB1 Rezeptors auf GABAergen Neuronen des Vorderhirns und kortikalen glutamatergen Neuronen, jedoch nicht auf striatalen Neuronen alleine. Zusätzlich war ich in der Lage, die Wichtigkeit des genetischen Hintergrunds von Mauslinien nicht nur auf die Ausbildung von spezifischen Verhaltensphänotypen, sondern auch auf die Genexpression zu zeigen.rnIn dem zweiten Teil dieser Arbeit, in dem ich mich auf die Funktion von Gliazellen konzentrierte, wurden ebenfalls Mausmutanten in verschiedenen Verhaltensmodellen getestet. Ein genetisches Auslöschen des NG2 Glykoproteins in Gliazellen sorgt in den Knock-out Mäusen für ein schlechteres Hörvermögen und ein reduziertes Depressionsverhalten im Vergleich zu ihren Wildtyp-Kontrollmäusen. Interessanterweise zeigten diese Tiere auch eine reduzierte Empfänglichkeit bei chemisch induzierten epileptischen Krämpfen, was eine Rolle des NG2 Glykoproteins bei der Kontrolle der glutamatergen Homöostase vorschlägt, die wahrscheinlich durch Strukturänderungen der Neuron-Glia-Synapse verursacht wird. rn

The Blue Dog Coalition: Impact of a Single-Issue Caucus from the 104th to the 110th Congress

The Blue Dog Coalition is an informal organization of legislators within the House of Representatives that strives to influence policy on fiscal responsibility, attract the attention of the electorate, They are a group that elicits wide range of reactions covering the length of the political spectrum, but despite this, their claims of special defense of fiscal conservatism within the Democratic Party have gone relatively undocumented by the academic community.This project has integrated a party literature with a caucus literature, in the attempt of building a novel framework for research. Work on polarization, the significance of parties, the purpose and history of caucuses all have been fused in such away that the Blue Dogs have created an opportunity to test broad congressional questions on a caucus-microcosm scale. Three important questions have emerged from the many possible avenues of exploration on the topic: How does admission into the Blue Dog Coalition effect voting behavior - measured by interest, ideology, and party unityscores? How does party leadership delegate prestigious committee assignments, a traditional indicator of partisan favor and influence, towards Blue Dogs? Can we use the Blue Dog Coalition as an indicator of fiscal conservatism? To each of these questions, a number of interesting results emerged. Blue Dogs, in the 104th scored higher in conservative interest group scores, more towards the center in ideological methods, and lower in party unity Dogs began to behave closer to their Democratic counterparts. In addition, membership on these select committees rose from a very small number to greater proportional parity within the Democratic Party. Perhaps most interesting, the Blue Dog Coalition does behave as a significant, independent predictor effect on NTU scores, a variable used to demonstrate fiscal conservatism. This research has shown, first and foremost, that it is useful and practical to applyold arguments within the party literature to a smaller, caucus level of analysis that is relatively untouched by the political science field. For the Blue Dogs, specifically, we have tested the validity of their claims in an attempt to reach broader questions ofdemocratic responsibility and electoral clarity. This work, and other work I have drawn upon, has barely scratched the surface on Blue Dog Democrats and other caucuses of comparable influence and popularity, and there remains a wealth of research material onthis caucus alone to be explored by scholars in the field of congressional politics.

Visual exploration in Parkinson's disease and Parkinson's disease dementia

Parkinson's disease, typically thought of as a movement disorder, is increasingly recognized as causing cognitive impairment and dementia. Eye movement abnormalities are also described, including impairment of rapid eye movements (saccades) and the fixations interspersed between them. Such movements are under the influence of cortical and subcortical networks commonly targeted by the neurodegeneration seen in Parkinson's disease and, as such, may provide a marker for cognitive decline. This study examined the error rates and visual exploration strategies of subjects with Parkinson's disease, with and without cognitive impairment, whilst performing a battery of visuo-cognitive tasks. Error rates were significantly higher in those Parkinson's disease groups with either mild cognitive impairment (P = 0.001) or dementia (P < 0.001), than in cognitively normal subjects with Parkinson's disease. When compared with cognitively normal subjects with Parkinson's disease, exploration strategy, as measured by a number of eye tracking variables, was least efficient in the dementia group but was also affected in those subjects with Parkinson's disease with mild cognitive impairment. When compared with control subjects and cognitively normal subjects with Parkinson's disease, saccade amplitudes were significantly reduced in the groups with mild cognitive impairment or dementia. Fixation duration was longer in all Parkinson's disease groups compared with healthy control subjects but was longest for cognitively impaired Parkinson's disease groups. The strongest predictor of average fixation duration was disease severity. Analysing only data from the most complex task, with the highest error rates, both cognitive impairment and disease severity contributed to a predictive model for fixation duration [F(2,76) = 12.52, P ≤ 0.001], but medication dose did not (r = 0.18, n = 78, P = 0.098, not significant). This study highlights the potential use of exploration strategy measures as a marker of cognitive decline in Parkinson's disease and reveals the efficiency by which fixations and saccades are deployed in the build-up to a cognitive response, rather than merely focusing on the outcome itself. The prolongation of fixation duration, present to a small but significant degree even in cognitively normal subjects with Parkinson's disease, suggests a disease-specific impact on the networks directing visual exploration, although the study also highlights the multi-factorial nature of changes in exploration and the significant impact of cognitive decline on efficiency of visual search.

Anatomic pathways of peripancreatic fluid draining to mediastinum in recurrent acute pancreatitis: visible human project and CT study

BACKGROUND In past reports, researchers have seldom attached importance to achievements in transforming digital anatomy to radiological diagnosis. However, investigators have been able to illustrate communication relationships in the retroperitoneal space by drawing potential routes in computerized tomography (CT) images or a virtual anatomical atlas. We established a new imaging anatomy research method for comparisons of the communication relationships of the retroperitoneal space in combination with the Visible Human Project and CT images. Specifically, the anatomic pathways of peripancreatic fluid extension to the mediastinum that may potentially transform into fistulas were studied. METHODS We explored potential pathways to the mediastinum based on American and Chinese Visible Human Project datasets. These drainage pathways to the mediastinum were confirmed or corrected in CT images of 51 patients with recurrent acute pancreatitis in 2011. We also investigated whether additional routes to the mediastinum were displayed in CT images that were not in Visible Human Project images. PRINCIPAL FINDINGS All hypothesized routes to the mediastinum displayed in Visible Human Project images, except for routes from the retromesenteric plane to the bilateral retrorenal plane across the bilateral fascial trifurcation and further to the retrocrural space via the aortic hiatus, were confirmed in CT images. In addition, route 13 via the narrow space between the left costal and crural diaphragm into the retrocrural space was demonstrated for the first time in CT images. CONCLUSION This type of exploration model related to imaging anatomy may be used to support research on the communication relationships of abdominal spaces, mediastinal spaces, cervical fascial spaces and other areas of the body.

The Role of Artefacts in the Process of Replication

This paper investigates the role of artefacts for the replication or routines in organizations. Drawing on data of a large franchise organization in the UK, we show that actors' engagement with a portfolio of different primary (e.g. software, tools) and secondary (e.g. manuals) artefacts that are part of the business format, gives rise to five artefact enabled practices of replication (activity scoping, time patterning, practical enquiry, use in practice and contextual enquiry). Importantly, these practices of replication enable three different types of franchisee agency (iterational, practical evaluative and projective agency) that support but partly also challenge replication in terms of the similarity of organizational routines across units. Our findings have several theoretical contributions for the growing literature on replication as well as materiality and artefacts in organizations.

Challenges for the comprehensive management of cloud services in a PaaS framework

The 4CaaSt project aims at developing a PaaS framework that enables flexible definition, marketing, deployment and management of Cloud-based services and applications. The major innovations proposed by 4CaaSt are the blueprint and its lifecycle management, a one stop shop for Cloud services and a PaaS level resource management featuring elasticity. 4CaaSt also provides a portfolio of ready to use Cloud native services and Cloud-aware immigrant technologies.

4CaaSt: Comprehensive management of Cloud services through a PaaS

The 4CaaSt project aims at developing a PaaS framework that enables flexible definition, marketing, deployment and management of Cloud-based services and applications. The major innovations proposed by 4CaaSt are the blueprint and its management and lifecycle, a one stop shop for Cloud services and the management of resources in the PaaS level (including elasticity). 4CaaSt also provides a portfolio of ready to use Cloud native services and Cloud- aware immigrant technologies.

An Analysis Of The Recommended Knowledge For The Software Project Management Discipline

According to the PMBOK (Project Management Body of Knowledge), project management is “the application of knowledge, skills, tools, and techniques to project activities to meet the project requirements” [1]. Project Management has proven to be one of the most important disciplines at the moment of determining the success of any project [2][3][4]. Given that many of the activities covered by this discipline can be said that are “horizontal” for any kind of domain, the importance of acknowledge the concepts and practices becomes even more obvious. The specific case of the projects that fall in the domain of Software Engineering are not the exception about the great influence of Project Management for their success. The critical role that this discipline plays in the industry has come to numbers. A report by McKinsey & Co [4] shows that the establishment of programs for the teaching of critical skills of project management can improve the performance of the project in time and costs. As an example of the above, the reports exposes: “One defense organization used these programs to train several waves of project managers and leaders who together administered a portfolio of more than 1,000 capital projects ranging in Project management size from $100,000 to $500 million. Managers who successfully completed the training were able to cut costs on most projects by between 20 and 35 percent. Over time, the organization expects savings of about 15 percent of its entire baseline spending”. In a white paper by the PMI (Project Management Institute) about the value of project management [5], it is stated that: “Leading organizations across sectors and geographic borders have been steadily embracing project management as a way to control spending and improve project results”. According to the research made by the PMI for the paper, after the economical crisis “Executives discovered that adhering to project management methods and strategies reduced risks, cut costs and improved success rates—all vital to surviving the economic crisis”. In every elite company, a proper execution of the project management discipline has become a must. Several members of the software industry have putted effort into achieving ways of assuring high quality results from projects; many standards, best practices, methodologies and other resources have been produced by experts from different fields of expertise. In the industry and the academic community, there is a continuous research on how to teach better software engineering together with project management [4][6]. For the general practices of Project Management the PMI produced a guide of the required knowledge that any project manager should have in their toolbox to lead any kind of project, this guide is called the PMBOK. On the side of best practices 10 and required knowledge for the Software Engineering discipline, the IEEE (Institute of Electrical and Electronics Engineers) developed the SWEBOK (Software Engineering Body of Knowledge) in collaboration with software industry experts and academic researchers, introducing into the guide many of the needed knowledge for a 5-year expertise software engineer [7]. The SWEBOK also covers management from the perspective of a software project. This thesis is developed to provide guidance to practitioners and members of the academic community about project management applied to software engineering. The way used in this thesis to get useful information for practitioners is to take an industry-approved guide for software engineering professionals such as the SWEBOK, and compare the content to what is found in the PMBOK. After comparing the contents of the SWEBOK and the PMBOK, what is found missing in the SWEBOK is used to give recommendations on how to enrich project management skills for a software engineering professional. Recommendations for members of the academic community on the other hand, are given taking into account the GSwE2009 (Graduated Software Engineering 2009) standard [8]. GSwE2009 is often used as a main reference for software engineering master programs [9]. The standard is mostly based on the content of the SWEBOK, plus some contents that are considered to reinforce the education of software engineering. Given the similarities between the SWEBOK and the GSwE2009, the results of comparing SWEBOK and PMBOK are also considered valid to enrich what the GSwE2009 proposes. So in the end the recommendations for practitioners end up being also useful for the academic community and their strategies to teach project management in the context of software engineering.

Increasing the quality of seismic interpretation

Euan Macrae was funded by a NERC Open CASE PhD award (NE/F013728/1) with Midland Valley Exploration Ltd. as the industry partner. We thank the 763 geoscientists for their participation, and in particular, the reference experts who gave their time freely to the project. Marian Scott (University of Glasgow, UK) is thanked for assisting with the statistical analysis. Four reviewers are thanked for their constructive comments which improved the manuscript.

The evolutionary impact of invasive species

Since the Age of Exploration began, there has been a drastic breaching of biogeographic barriers that previously had isolated the continental biotas for millions of years. We explore the nature of these recent biotic exchanges and their consequences on evolutionary processes. The direct evidence of evolutionary consequences of the biotic rearrangements is of variable quality, but the results of trajectories are becoming clear as the number of studies increases. There are examples of invasive species altering the evolutionary pathway of native species by competitive exclusion, niche displacement, hybridization, introgression, predation, and ultimately extinction. Invaders themselves evolve in response to their interactions with natives, as well as in response to the new abiotic environment. Flexibility in behavior, and mutualistic interactions, can aid in the success of invaders in their new environment.

Building International CSR on Solid Foundations: Location and Network Aspects of Nonmarket Environments in Europe and Non-Europe Markets. ACES Working Papers, 2011

Multinational companies' (MNCs) corporate social responsibility (CSR) programs frequently comprise a portfolio of disconnected country-level programs or, alternatively, consist of blanket corporate policies that apply in the same way across the geographies where the company operates. Yet, the international nonmarket environment in which CSR programs operate is neither a completely fragmented nor a perfectly homogeneous one. Building on the concept of stakeholder-issue-networks, we develop a model that explicitly takes into consideration the role of geography in the characterization of a firm's nonmarket environment. This allows us to develop a taxonomy of nonmarket environments on the basis of their geographic spread and their degree of cross-border connectedness. We then explore the strategic and organizational implications that different ideal types of (cross-border) nonmarket environments have for the development of international CSR policies.

Petrophysical measurement of ODP Leg 122 and 123 samples (Tables 1, 2)

The capillary-pressure characteristics of 22 samples of lithified post-Paleozoic Indian-Ocean carbonates were compared to published data from older carbonate rocks (lower Paleozoic Hunton Group of Texas and Oklahoma). The Indian-Ocean samples are considerably more porous than are the Paleozoic samples, yet all of the Indian-Ocean samples fit readily into a descriptive petrofacies scheme previously established for the Hunton Group. The Indian-Ocean samples may be assigned to four petrophysical facies (petrofacies) based on the shapes of their capillary-pressure curves, their pore-throat-size distributions, their estimated recovery efficiency values (for nonwetting fluids), and the visual characteristics of their pore systems, as observed with a scanning-electron microscope. Petrofacies assignments for the Indian-Ocean samples are as follows. Petrofacies I includes six samples collected from the coarse basal portions of event deposits (primarily turbidites). These samples have large throats, leptokurtic throat-size distributions, low- to moderate recovery efficiency values, concave cumulative-intrusion capillary-pressure curves, and high porosity values. Petrofacies II includes two sedimentologically dissimilar samples that have medium-size throats, platykurtic throat-size distributions, moderate- to-high recovery efficiency values, gently sloping cumulative-intrusion capillary-pressure curves, and high porosity values. Petrofacies III includes two polymictic sandstones and a skeletal packstone that have small throats, polymodal throat-size distributions, moderate recovery efficiency values, gently sloping cumulative-intrusion capillary-pressure curves, and high porosity values. Petrofacies IV includes 11 samples, mostly recrystallized neritic carbonates, that have small throats, leptokurtic throat-size distributions, high recovery efficiency values, convex cumulative-intrusion capillary-pressure curves, and low porosity values. Comparison of petrofacies assignment to core-, thin-section-, and smear-slide data, and to inferred depositional setting, suggests that pore systems in most samples from Holes 765C and 766A result from primary depositional features, whereas pore systems in samples from Hole 761C and one sample from Hole 765C have been strongly influenced by diagenetic processes. For Hole 761C, prediction of petrophysical parameters should be most successful if based on diagenetic facies patterns. By contrast, the distribution of favorable reservoir facies and of permeability barriers in less highly altered rocks collected from Holes 765C and 766A is related to depositional patterns. Recovery efficiency is inversely related to both porosity and median throat size for the present data set. This relationship is similar to that observed for carbonates of the lower Paleozoic Hunton Group and the Ordovician Ellenburger dolomite, but opposite of that observed for some other ancient carbonates. The coarse deposits of the massive basal units of turbidites are petrophysically distinct and form a coherent petrophysical group (Petrofacies I) with substantial reservoir potential. Two samples assigned to Petrofacies I have extremely large throats (median throat size at least 4 ?m, and at least six times that of any other sample) and therefore high permeability values. These two samples come from thin, coarse turbidites that lack or have poorly developed fine divisions and are interpreted to have been deposited on channeled suprafan lobes in a proximal mid-fan setting. The restriction of extremely high permeability values to a single depositional facies suggests that careful facies mapping of deep-sea fans in a deliberate search for such coarse turbidites could dramatically enhance the success of exploration for aquifers or hydrocarbon reservoirs. Such reservoirs should have substantial vertical heterogeneity. They should have high lateral permeability values but low vertical permeability values, and reservoir sections should include numerous thin units having widely differing petrophysical characteristics.

Kirkman's science of railways.

[v. 1] The locomotive -- [v. 1 portfolio] Locomotive portfolio -- [v. 2] Engineers' and firemen's handbook -- [v. 3] Locomotive appliances -- [v. 3 suppl.] Supplement to volume Locomotive appliances -- [v. 4] Electricity applied to railways -- [v. 5] Cars, their construction and handling -- [v. 5 suppl. 2] Cars, their construction and handling : supplement --[v. 5 portfolio 1] Supplement to Kirkman's Science of railways : cars, their construction and handling -- [v. 5 portfolio 2] Portfolio of cars -- [v. 6-7] The air brake -- [v. 6-7 portfolio 1] Air brake portfolio : Westinghouse diagrammatic & sectional views air brake & air signal instruction charts -- [v. 6-7 portfolio 2] Air brake portfolio : New York diagrammatic and sectional views air brake instruction charts -- [v. 7 suppl. 1] Westinghouse universal common standard U.C. two-cylinder brake equipment with U-12 universal valve -- [v. 7 suppl. 2] Auxiliary devices governor -- [v. 8] Operating trains -- [v. 9-10] Shops and shop practice.