Potential synergy effects and conflicts, so-called interactions, between a climate action that aims to mitigate the climate impact and five targets of the Sustainable Development Goals are identified in this study. The climate action is Conscious material choices for the frame, and the materials assessed are climate improved concrete and domestic wood. Standard concrete is used as the business as usual scenario. A pre-school building is used as an example building to demonstrate the difference in the climate impact of a frame made from the two materials assessed in the study. Life cycle assessments (LCA) of the frames shows that the domestic wood frame has a lower climate impact than the climate improved concrete frame.Two methods are used in this study. The first method is making an LCA for transportation of the materials assessed to see the environmental impact, and there is one scenario for each material where the transportation method is by a truck and one that is by train. The second method used for the study is a goal interaction scoring-method from “A draft framework for understanding SDG interactions” by Nilsson et al. (2016) that gives the interactions a score based on specific criteria. The scores are visualised in a colour coordinated matrix. The interactions generate synergies if the sums of the scores in the matrix are positive and will likely help accomplish the target. If the sums of the scores in the matrix are negative, it indicates that there are conflicts that could endanger the possibilities to reach the target.LCA of the transport scenarios shows that when the transportation distance is long, the climate impact is lowest when transporting as much as possible of the materials by train. Transporting the domestic wood for the frame by train (for longer distances) has a lower climate impact than transporting the climate improved concrete. For shorter distances, there is not a significant difference between transportation by truck or by train. The climate improved concrete gets score 0, meaning that there are neither positive nor negative interactions for the chosen material for the frame. The domestic wood gets the score +8, which indicates that there are synergies. Both the climate improved concrete and the domestic wood should not interfere with the accomplishment of the Sustainable Development Goal’s targets. However, the domestic wood for the frame generates more synergies and by choosing the domestic wooden frame for a building using a train as a transportation of the material when possible has the lowest environmental impact of the assessed materials for the frame. / <p>2020-06-08</p>

The master’s thesis aims to evaluate the existence of the financial synergistic effect concerning consolidating companies in the construction industry area. For this purpose three appropriate financial indicators, which are to be calculated separately for the parent company and the concern, will be proposed. The subsequent comparison of these values will enable us to determine if the positive financial synergistic effects were achieved in the researched area.

En France, le cancer de la prostate est le premier cancer par son incidence ainsi que la troisième cause de mortalité pour cette pathologie. La progression de la maladie est dépendante des androgènes. Ainsi l’un des traitements majeurs du cancer de la prostate est la déprivation androgénique : le blocage de la production ou de l’action des androgènes conduit à inhiber la croissance tumorale. La plupart des patients répondent à cette thérapie, cependant l’évolution de la pathologie vers un stade d’insensibilité à la castration est inévitable, ce qui est associé à un mauvais pronostic. Au cours de la progression du cancer de la prostate, la voie de signalisation des androgènes demeure active grâce au récepteur des androgènes. Ce récepteur est une cible idéale afin de traiter et de bloquer la progression tumorale. Une telle inhibition du récepteur des androgènes peut être faite par l’utilisation d’un anti-androgènes de seconde génération : l’Enzalutamide. Cette molécule perturbe l’interaction entre le récepteur des androgènes et son ligand, elle peut bloquer la translocation nucléaire du récepteur activé mais elle empêche aussi son interaction avec l’ADN. Bien que l’utilisation de l’Enzalutamide ait contribué à améliorer la survie des patients, son utilisation conduit à l’émergence d’une résistance à l’Enzalutamide, ce qui constitue un défi thérapeutique considérable.L’objectif principal de mes travaux de thèse est d’identifier de nouvelles protéines afin d’améliorer les effets thérapeutiques de l’Enzalutamide ou de surmonter la résistance à ce médicament. Ainsi dans notre étude, nous avons supposé que le traitement à l’Enzalutamide induit l’activation de voies de signalisation spécifiques, pouvant être impliquées soit dans le mécanisme d’action du médicament ou dans la résistance à ce dernier. Cette hypothèse nous a conduit à l’identification des protéines MAPKs p38, qui sont activées lors d’un traitement avec l’Enzalutamide. Nos résultats démontrent que la combinaison d’Enzalutamide et d’inhibiteur de la MAPK p38 a un effet antitumoral significatif aussi bien in vitro que in vivo. Le mécanisme d’action de cet effet cytotoxique et synergique reste à l’étude. Ces données permettraient d’approfondir la compréhension des mécanismes de résistance lors d’un traitement à l’Enzalutamide et contribuer à la potentialisation de l’effet thérapeutique de cet antiandrogènes. / In France, prostate cancer is the most frequently diagnosed male cancer and its progression is tightly associated with the androgen signals. One of the major treatments for prostate cancer is androgen deprivation therapy which is based on blocking the production or action of the androgens to induce a tumor growth inhibition. Most patients respond to this therapy, however they still reach a castration-resistant stage which is associated with a poor prognosis. Since the progression till this late cancer stage is still driven by the androgen signaling pathway, the second-line therapy is focused on targeting the active androgen receptor by using a second-generation anti-androgens: the Enzalutamide. This molecule disrupts the interaction between the androgen receptor and its ligand, it can block the nuclear translocation of the receptor and it also prevents the receptor interaction with DNA. Although Enzalutamide treatment has enhance the patient survival, some drug resistance still arises which is a considerable therapeutic challenge.The main objective of my thesis is to identify new proteins in order to improve the therapeutic effects of Enzalutamide or to overcome resistance to this drug. Thus, in our study, we assumed that Enzalutamide treatment induces the activation of specific signaling pathways which may be involved in the cancer cell response to the treatment. This hypothesis led us to identify the MAPKs p38 proteins, which are activated during treatment with Enzalutamide. Our results show that the combination of Enzalutamide and p38 inhibitor has a significant antitumor effect both in vitro and in vivo. The mechanism of action of this cytotoxic and synergistic effect remains under study. These data would allow a better understanding of the Enzalutamide resistance mechanisms and contribute to the enhancement of the therapeutic effect of this anti-androgen.

The Out-of-home advertising media are far more expansive than they used to be, and the shape and format of these media globally, as well as in South Africa, have changed considerably over the past few decades. Until rather recently, the out-ofhome advertising media landscape consisted primarily of outdoor advertising or billboards; but these days, this has expanded to include other platforms, such as transit advertising media, street and retail furniture advertising media, and a wide variety of alternative out-of-home advertising media types. This proliferation of out-of-home advertising media, the scant research on out-of-home advertising media planning and the number of obstacles in the South African advertising- and media industry have emphasised the need for a clear understanding of the changing nature of out-of-home advertising media and the planning and integration thereof. No previous study has addressed the integration of different out-of-home advertising media platforms as part of an integrated marketing communication plan. Very little has been published on how out-of-home advertising media planning across platforms should actually be done, even more so in a developing country such as South Africa. It was therefore necessary to investigate this further, in order to propose a framework for guiding the planning and integration of out-of-home advertising media; and one that can be applied in the South African environment. The main aim of this study was to explore how experienced out-of-home advertising media specialists plan and integrate different out-of-home advertising media platforms, as part of an overall integrated marketing communication plan. This, together with an extensive investigation into the relevant literature, was then used to develop a framework for the planning and integration of out-of-home advertising media in South Africa. Purposive sampling was used to select ten out-of-home media specialists from within prominent media-only agencies, and out-of-home advertising media-specialist agencies in South Africa. The specialists selected were responsible for planning out-of-home advertising media strategies of several of the largest advertisers in South Africa. These advertisers included Coca Cola, Unilever, Brandhouse, Cadbury, Pantene, Pfizer, Vodacom, Cell C, MTN, Spar, Shoprite, KFC, ABSA, Standard Bank Nedbank, Visa, Sony, Virgin Active, Adidas, Green Cross, Kulula airlines, NuMetro and Eskom. In-depth interviews with these specialists were conducted, using a basic guiding framework or interview guide. Qualitative thematic analysis was applied to the transcribed interviews using the software program, ATLAS.ti. The qualitative findings revealed nine themes, related to three theoretical constructs, namely: the alignment of the out-of-home advertising media campaign with the overall integrated marketing communication plan; the planning of out-of-home advertising media; and the evaluation and research of out-of-home advertising media It was recommended that specialists who understand the requirements of coordination and integration on several levels should do the planning of out-of-home advertising media. These are firstly, the alignment between the out-of-home advertising campaign and the overall integrated marketing communication plan objectives; secondly, the co-ordination between the message strategy and an out-ofhome advertising media plan; and thirdly, the integration between different platforms and formats used in the out-of-home advertising media mix. To optimally achieve integration on all these different levels required vertical integration and communication between all the role-players involved: the advertisers, the advertising agency, the media agency and the out-of-home media specialists. Effective integrated out-of-home advertising media campaigns can no longer be treated as mere add-ons; they should be part of the planning right from the start. / Thesis (DCom)--University of Pretoria, 2012. / Marketing Management / DCom / Unrestricted

Málková, H.: Multiplication of shape as a means of constructing reality. [Diplom thesis] Prague 2017 - Charles University, Faculty of Education, Department of Art Education, 123 pages. The diploma thesis focuses on the theme of creation of systems, structures and constructions in visual reality. The theoretical part is aimed at the possibilities of multiplication, its growth into space or a plane, while regarding creation of plastic arts by selected artists from the field of fine arts. The practical part introduces author's conception of the topic by the means of photographic medium. Structure is a crucial phenomena in possible understanding of visual reality. It has prerequisites for development of transcendental thinking. We can discover it throughout the whole universe as its unifying element. The findings from the theoretical part are used as basis for didactic activities. The didactic part presents the realized art assignments, which are a part of the implementation of the research. The thesis brings findings and conclusions within the framework of the results of creation and teaching of the topic of spatial composition of multiplied form within a coherent object. KEY WORDS: construction, structure, movement, shape, space, material variability, racionality, photography, object creation,...

Basal Ganglia are evolutionarily conserved brain nuclei involved in several physiologically important animal behaviors like motor control and reward learning. Striatum, which is the input nuclei of basal ganglia, integrates inputs from several neurons, like cortical and thalamic glutamatergic input and local GABAergic inputs. Several neuromodulators, such as dopamine, accetylcholine and serotonin modulate the functional properties of striatal neurons. Aberrations in the intracellular signaling of these neurons lead to several debilitating neurodegenerative diseases, like Parkinson’s disease. In order to understand these aberrations we should first identify the role of different molecular players in the normal physiology. The long term goal of this research is to understand the molecular mechanisms responsible for the integration of different neuromodulatory signals by striatal medium spiny neurons (MSN). This signal integration is known to play important role in learning. This is manifested via changes in the synaptic weights between different neurons. The group of synpases taken into consideration for the current work is the corticostriatal one, which are synapses between the cortical projection neurons and MSNs. One of the molecular processes of considerable interest is the interaction between dopaminergic and cholinergic inputs. In this thesis I have investigated the interactions between the biochemical cascades triggered by dopaminergic, cholinergic (ACh) and glutamatergic inputs to the striatal MSN. The dopamine induced signaling increases the levels of cAMP in the striatonigral MSNs. The sources of dopamine and acetylcholine are dopaminergic neurons (DAN) from midbrain and tonically active cholinergic interneurons (TAN) of striatum, respectively. A sub-second burst activity in DAN along with a simultaneous pause in TAN is a characteristic effect elicited by a salient stimulus. This, in turn, leads to a dopamine peak and, possibly, an acetylcholine (ACh) dip in striatum. I have looked into the possibility of sensing this ACh dip and the dopamine peak at striatonigral MSNs. These neurons express D1 dopamine receptor (D1R) coupled to Golf and M4 Muscarinic receptor (M4R) coupled to Gi/o . These receptors are expressed significantly in the dendritic spines of these neurons where the Adenylate Cyclase 5 (AC5) is a point of convergence for these two signals. Golf stimulates the production of cAMP by AC5 whereas Gi/o inhibits the Golf mediated cAMP production. I have performed a kinetic-modeling exercise to explore how dopamine and ACh interacts with each other via these receptors and what are the effects on the downstream signaling events. The results of model simulation suggest that the striatonigral MSNs are able to sense the ACh dip via M4R. They integrate the dip with the dopamine peak to activate AC5 synergistically. We also found that the ACh tone may act as a potential noise filter against noisy dopamine signals. The parameters for the G-protein GTPase activity indicate towards an important role of GTPase Activating Proteins (GAPs), like RGS, in this process. Besides this we also hypothesize that M4R may have therapeutic potential. / <p>QC 20140325</p>

AbstractTitle:Football coaches’ awareness and implementation of team dynamicsObjectives: This research aims to explore, based on the in-depth interviews with Czech male football coaches, how the football coaches work with team dynamics and its principles, during recruitment/transfers, training process, and specific situations, and potentially ascertain what are the obstacles for the team dynamics principles implementation.Methods:The primary method used in this research is the qualitative method of semistructured in-depth interviews. Research is focused on the population of male Czech football coaches with at least half a year of experience. The research sample consists of 7 respondents. The data are proceeded according to GDPR and anonymized. For the data interpretation, the interpretative phenomenological analysis (IPA) is used. Results:The respondents are aware of team cohesion, climate, and synergy and understand the importance of team dynamics in general. If it is possible, the coaches look at the players' psychological characteristics and consider them in relation to the rest of the team and even their potential behavior. The coaches’ behavior and interventions differ based on the situation. However, they tend not to intervene much, and they also don't use almost any analytical tools in terms of team dynamics. That can be caused by many factors such as they perceived the team dynamics as part of psychology, which according to this research, might be perceived as a tool for problem treatment, not as a preventive tool. There are also some structural barriers such as unclear club concept, unclear competency among the responsible, not enough emphasis on team dynamics during the licenses education and players’ agents pressure, as well as language barrier, which seems to prevent successful implementation of foreign players. The respondents tend to rationalize some of the problems. Keywords:cohesion, team climate, synergy, competencies, recruitment, training process, leadership styles, systematical obstacles, barriers

Les agents pharmacologiques ciblant la dynamique des microtubules (MTs) sont très utilisés en chimiothérapie des cancers agressifs. Le paclitaxel (PTX) est utilisé depuis des décennies et donne de bons résultats pour le traitement des tumeurs solides. Plusieurs inconvénients, notamment ses effets secondaires et la résistance de certains cancers limitent cependant l'efficacité de ce médicament. Dans le but d'identifier de nouveaux composés pharmacologiques qui sensibilisent les cellules au PTX, nous avons recherché, parmi une collection de 8000 molécules, celles capables de sensibiliser des cellules cancéreuses à une dose non toxique de PTX. Nous avons ainsi sélectionné un composé de la famille des carbazoles : Carba1. Dans les cellules, l’association carba1/PTX a un effet cytotoxique supérieur à la somme des effets de carba1 et de PTX, quand ces molécules sont appliquées séparément, indiquant un effet synergique. De plus, des analyses approfondies de différents phénotypes ont permis de montrer que l'administration de carba1 avait pour conséquence d'amplifier des effets du PTX.À fortes doses, carba1 entraine un blocage des cellules en prométaphase mais n’altère pas le réseau microtubulaire, ni en interphase ni en mitose. En revanche, in vitro, carba1 cible la tubuline en se fixant sur le site colchicine, provoquant un retard et une diminution de la polymérisation des MTs. En plus de la tubuline, des études génétiques réalisées sur la levure suggèrent que carba1 a d'autres cibles dont CENP-E, kinésine essentielle à l’alignement des chromosomes au cours de la mitose.Des études menées sur un modèle de cancer mammaire murin agressif (allogreffes) ont révélé que carba1 seul et carba1/PTX ne présentaient aucune toxicité. De plus, les effets anti-tumoraux et anti-métastatiques de la combinaison carba1/PTX sur ces modèles se sont montrés encourageants, bien que des mises au point, notamment sur la posologie sont encore à prévoir. Carba1 est une molécule nouvelle, avec des applications jusque-là inconnues. C’est pourquoi une déclaration d’invention, en vue d'un dépôt de brevet, a été soumise au CNRS. / Microtubules (MTs) targeting agents are a powerful weapon in the war against aggressive cancers. Paclitaxel (PTX) has been used successfully for the treatment of solid tumors for decades. Several features, including side-effects and resistance of some cancers make this drug not always effective. With the aim to identify new chemical compounds that sensitize cells to paclitaxel we screened a library of 8,000 compounds, to select those not toxic for cell cultures when applied alone, that become toxic when applied in combination with a non-toxic dose of paclitaxel. This lead to the selection of a carbazole derivative: carba1. In cells, the carba1/PTX combination has a greater cytotoxic effect than the addition of the effects of each drug assayed separately, indicating a synergistic effect. In addition, in-depth phenotypic analyzes indicate that the administration of carba1 amplify the effects of PTX.High doses of carba1 induce a cell blockade in prometaphase, but do not alter the MT network in interphase or mitosis. In contrast, in vitro, carba1 targets the tubulin colchicine binding site, causing a delay and a decrease in MT polymerization. Genetic studies conducted on yeast indicated other potential additional targets including CENP-E, an essential kinesin for chromosome alignment during mitosis.Studies conducted on a preclinical mouse model of aggressive breast cancer (orthotopic grafts) revealed that carba1 alone and carba1/PTX showed no toxicity. In addition, the anti-tumor and anti-metastatic effects of the carba1/PTX combination on these models have been encouraging, but an optimization of the posology is still needed. Carba1 is a new molecule, with previously unknown applications. This is why a declaration of invention, with a view to filing a patent, has been submitted to the CNRS.

<p>  </p> <p>Falls mostly occur when people are walking. Investigations of control of gait stability have focused primarily on the single stance phase. My dissertation focused on the double support phase of gait because (1) responses to perturbations occur during the double support (2) the portion of the gait cycle spent in double support is increased with old age, and, more importantly, (3) since both feet can push off the ground simultaneously, there are more kinetic degrees of freedom (DoF) and therefore greater control authority over body motion during this phase. However, how these kinetic DoFs are coordinated during the double support phase is not fully understood. Thus, the goal of this dissertation was to identify the inter-leg coordination to stabilize whole-body motion and quantify how the inter-leg coordination is affected by intrinsic and extrinsic factors. Specifically, Study 1 focused on healthy aging (an intrinsic factor) and varying task demands (an extrinsic factor that changed while curb ascent versus curb descent). Study 2 investigated another extrinsic factor of future uncertain environmental demands (fixed versus uncertain foot targeting demand for the step after descending a curb). Using the uncontrolled manifold analysis, I identified ground reaction variable (GRV) synergies, i.e., synergistic covariations between the ground reaction forces and moments under the two feet that stabilize whole-body linear and angular motions. Furthermore, I found that GRV synergies were modulated by extrinsic factors: GRV synergies were sensitive to current fixed environmental demands (Study 1), whereas they were robust to future environmental demands on foot placement (Study 2). Lastly, I found that GRV synergies were not changed by the intrinsic factor of age, despite the physiological declines with aging (Study 1). The absence of an age effect on GRV synergies indicates that older adults have the preserved ability to exploit the control authority during the double support phase to maintain stability while negotiating a curb. The work extends the current body of literature on gait stability mechanisms and improves our understanding of changes in stability control as a function of different environmental demands.</p>

Marketing aimed towards children under the age of 12 is prohibited in Sweden. Packaging design has a crucial role from a marketing perspective as it might be the only way to reach this target group. The purpose of this study is to analyze how graphic design and visual communication differs when it is aimed to children and adults. This essay also examines how media characters are used in marketing of health products targeted towards children and adults to create synergies. The use of media characters in packaging design results in two different types of synergies. The first type is the synergy between two brands when the collaboration benefits them by mutually increasing their legitimacy. The other type of synergy occurs when marketing of a product is designed to simultaneously reach two different target groups: children and adults.