Aus klinischen Studien ist bereits bekannt, dass die aus der Christrose (Helleborus purpurascens) isolierte makrozyklische Substanz MCS-18 in der Lage ist, eine pathologisch aktivierte Immunreaktion wie die rheumatoide Arthritis zu unterdrücken. In der vorliegenden Arbeit stand die Untersuchung der immunmodulatorischen Wirkung von MCS-18 auf dendritische Zellen (DZ) im Vordergrund. Um eine potente Immunantwort zu induzieren, müssen DZ reifen. Hier konnte in vitro gezeigt werden, dass MCS-18 in der Lage ist, die Expression der typischen Reifungsmarker wie CD80, CD86 und vor allem CD83 zu unterdrücken. Darüber hinaus konnte in vitro eine konzentrationsabhängige Reduktion der DZ- T-Zell - Clusterbildung und eine Blockade der DZ-vermittelten T-Zell Stimulation nachgewiesen werden. Im weiteren Verlauf der Arbeit konnte zusätzlich eine dosisabhängige Reduktion der DZ-unabhängigen, anti-CD3/anti-CD28-vermittelten T-Zell Stimulation gezeigt werden. Ferner konnte eine konzentrationsabhängig reduzierte CCR7 -Expression auf der Oberfläche behandelter DZ und daraus resultierend eine eingeschränkte Migrationsfähigkeit der DZ entlang eines CCL19-Gradienten nachgewiesen werden. In vivo besitzt MCS-18 das Potential, die der EAE (ein Mausmodell der humanen Multiplen Sklerose) assoziierten Paralysesymptome sowohl bei prophylaktischer als auch bei einer realen Verhältnisse am nächsten kommenden therapeutischen Gabe zu reduzieren. Selbst bei der Induktion einer zweiten EAE konnte ein lang anhaltender immunsupprimierender Effekt von MCS-18 festgestellt werden. Am bedeutendsten für eine potentielle spätere therapeutische Anwendung am Menschen ist jedoch die Tatsache, dass MCS-18 auch oral verabreicht wirksam bleibt. Histologisch konnte bei mit MCS-18 behandelten Mäusen eine stark reduzierte Infiltration des Gehirns und Rückenmarks mit CD45+ Leukozyten nachgewiesen werden. Zusammengefasst zeigen sowohl die in vitro als auch die in vivo gewonnenen Daten das große therapeutische Potential von MCS-18 für die Therapie von autoimmunen oder anderen immunbedingten Erkrankungen auf.

The aim of this study is to investigate how explicit CSR values are implemented in the organizational culture of companies through MCS. The focus is on which elements of MCS affect the tacit CSR values of employees, so that employee and corporate values can be aligned. Additionally, the role that shared values play on corporate social behavior is explored. To answer the research question both primary and secondary data were collected and analyzed by conducting multiple case studies. The primary data was collected through qualitative, semi-structured interviews. Secondary data was collected from the case companies’ official reports, codes of conduct and statements. A model was created to create a visualization of the concepts used in the theoretical framework. This study found that companies from nine different industries utilize MCS to align CSR values in their organization, and realize green marketing behavior. Shared values are created through four MCS; a belief system, a diagnostic control system, a boundary system and an interactive control system. These are the building blocks upon which positive corporate social behavior is grounded on. This study’s results provide managers tools to affect their company’s corporate social behavior. Additionally, on a broader level, this study indicates that green marketing and greenwashing behavior can be viewed as choices that companies can deliberately make. Managers can affect the corporate social behavior of their company and are therefore responsible for the path they choose regarding CSR.

This paper is concerned with the use of management control systems (MCSs) within high growth firms (HGFs) to support rapid growth. Considering that a lack of MCSs has been identified as a major cause of failure among start-ups, as well as that MCSs have been claimed to enable firms to grow more during their early years, this is a highly interesting topic for scholars as well as entrepreneurs. However, despite the exceptional opportunity that HGFs provide in examining this topic, there is a lack of contemporary research on how HGFs use MCSs to support their growth. To fill this gap a multiple case study was conducted, investigating how Simons’ (1995) levers of control were used to support growth within 12 different HGFs. Through drawing upon data from interviews with 19 different key people it was then found that MCSs support growth in various ways. Different boundary systems were found to increase chances of firm survival and provide a platform for growth. Additionally, the use of interactive systems was identified as a potential characteristic of HGFs. Moreover, the research questions former assumptions on the importance of forecasting.

Submitted by Lucelia Lucena (lucelia.lucena@ufpe.br) on 2015-03-09T19:29:39Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO Luíz Vieira e Silva Filho.pdf: 2176053 bytes, checksum: 4882a96e67804421bca22e07debc49da (MD5) / Made available in DSpace on 2015-03-09T19:29:39Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO Luíz Vieira e Silva Filho.pdf: 2176053 bytes, checksum: 4882a96e67804421bca22e07debc49da (MD5) Previous issue date: 2014-02-17 / Sistemas de Múltiplos Classificadores (Multiple Classifiers Systems - MCS) se baseiam na ideia de que combinar a opinião de vários especialistas pode produzir melhores resultados do que quando se usa apenas um especialista. Diversas técnicas de MCS foram desenvolvidas, apresentando pontos fortes e fracos, a depender do contexto em que são aplicadas. Este trabalho propõe uma arquitetura para MCS que visa potencializar a complementaridade entre essas técnicas, possuindo dois objetivos principais: i) a combinação de métodos de amostragem tradicionais, visando a geração de classificadores de melhor desempenho que componham um pool de classificadores; ii) a aplicação de um algoritmo de poda para remover do pool aqueles classificadores incompetentes para lidar com o problema em questão, considerando os critérios de seleção adotados. A arquitetura proposta foi avaliada em uma aplicação de credit-scoring. Os métodos de amostragem usados foram o Bagging e o Random Subspace com classificadores-base sendo árvores-de-decisão, construídas com base no algoritmo CART. Para o processamento da poda foi usado o algoritmo Orientation Ordering, e para combinação das saídas dos classificadores do ensemble adotou-se o método Majority Vote. Os experimentos realizados mostraram que a arquitetura proposta alcançou taxas de acerto similares ou superiores às atingidas pelos métodos apresentados na literatura. Esses resultados ainda foram obtidos com ensembles cujos tamanhos eram da ordemde 20% dos pools originais gerados na fase de treinamento.

Abstract Small businesses are numerous in any country. However, we have very limited knowledge regarding their management accounting (MA) and management control systems (MCS). Traditionally, it has been stated that small firms do not need and use MCS due to their simple structures and poor resources. On the other hand, a few studies on high technology firms have shown that these firms have developed their MCS and are also utilizing sophisticated management accounting practices and information. The aim of this study is to analyse small firms' use of MCS practices as well as to examine the role of MCS practices and information of small firms in a contingency theoretical framework. Furthermore, the study is not only focusing on small, rapidly growing firms but also on traditional, more stable small firms, all employing from 10 to 49 persons. Based on the survey responses of 183 managing directors of small Finnish firms, the study describes the diffusion and penetration of MCS practices and information among small firms. Two theoretical models are constructed linking the use of MCS with strategy, perceived environmental uncertainty (PEU), use of diversified management team and financial performance of small firms. Tests are made by using structural equation modeling (SEM). The results suggest that small firms do use a wide range of MCS practices and information. The main results also indicate that the use of a more diversified management team seems to increase the use of MCS practices and information. The use of more advanced practices is related to small firms which have been more profitable or which have had lower growth rates in sales. In addition, the use of MCS seems to be associated with small firms' strategies, both realized and intended. The pursued strategy seems to drive small firms' profitability and growth in net sales. However, such an association was not found between the intended strategy and financial performance after two years. The use of MCS seems to have only a few positive effects on small firm's financial performance. Nevertheless, more use of advanced dimensions of MCS seems to predict significant improvements for longer-term growth in net sales.

Class of 2015 Abstract / Objectives: To determine if using three-factor prothrombin complex concentrate (PCC) immediately prior to heart transplantation reduces blood product transfusions in patients bridged to heart transplantation by mechanical circulatory support (MCS) devices who are treated with warfarin. Methods: This study retrospectively reviewed patients that either received PCC or received usual care (i.e. fresh frozen plasma – FFP) prior to heart transplantation. Outcomes that were evaluated included packed red blood cell (RBC), FFP, platelet and cryoprecipitate transfusions intra and five days post-operatively, Cell Saver autologous blood volume administered intra-operatively, chest tube output for the five days post-operatively, and thromboembolic events post-operatively. Results: There were 24 patients included in the study, 12 from each group. The PCC group showed significantly less intra-operative RBC transfusion (2.60 ± 1.49 units vs. 5.09 ± 2.42 units, p=0.018), Cell Saver autologous blood usage (2.60 ± 1.49 units vs. 4.02 ± 1.55 units, p=0.032), and FFP transfusion (2.14 ± 2.30 units vs. 10.94 ± 5.96 units, p=0.0005) than the usual care group. There was no difference in amount of vitamin K given, change in INR, platelets administered, cryoprecipitate administered, chest tube output, or thromboembolic events between the groups. The average dose of PCC was 31 units/kg IV; repeat doses were given to 2 patients. Conclusions: We propose that the use of PCC prior to heart transplant surgery for patients on MCS devices anticoagulated with warfarin may result in the reduction for the need of RBC’s, autologous blood use and FFP during surgery.

The purpose of this study was to find what appropriate Management Control Systems exist that can help fast-growing start-ups to achieve a controlled and healthy growth. We also studied how the control systems can be used together, and balanced between each other. To find appropriate control systems, we conducted a literature review of important factors for implementing management control, that ended with a tentative framework of control systems. After that, we conducted a multiple case study including several fast-growing technology start-ups to see how they use the collection of control systems in our tentative control framework, and analyzed what effect they have on the organization’s activities and how they balance between them. After the case study, a cross-case analysis was conducted were differences and similarities between the cases were analyzed and related to the theoretical concepts from the literature review. This led to conclusions regarding how start-ups tend to use and balance the control systems, which in turn led to the finalized control framework for fast-growing start-ups. The framework provides a set of control systems that start-ups can use that are relevant for supporting growth and managing the most common challenges that fast-growing start-ups face. By using different levers of control, the control systems complement each other and create a dynamic tension, which increases performance. For start-ups that are in a product development phase, the balance of the control systems is mostly on growth and innovation, which supports exploration of opportunities. However, there is still a little focus on control and efficiency to keep the organization focused. For start-ups with an already developed and commercialized product, the balance of control systems is more towards the middle. The most focus is put on growth and efficiency, with a little less emphasis on innovation and control. This is a way to keep an even balance between exploration of opportunities and exploitation of current resources.

Cancer is the second leading cause of death and is responsible for approximately 9.6 million deaths worldwide in 2018. Among all oncological diseases, lung cancer claims the highest mortality (male: 23.5%; female: 22%) and the second most new cases (male: 13%; female: 12%) in the US. Approximately 40% of newly diagnosed lung cancer patients are in the advanced stage IV, for which platinum-based chemotherapy is the first-line treatment, either by itself or in combination with surgery or radiotherapy. Cisplatin, the first-generation platinum-based anticancer chemotherapeutic agent, has the highest potency against lung cancer but carries many severe adverse effects. Cisplatin also induces drug resistance during long-term chemotherapy. Many more platinum complexes have been investigated as better alternatives, which led to the approval of carboplatin and oxaliplatin by Food and Drug Administration (FDA). In addition, miriplatin suspended in iodolipds (lipiodolization) was approved in Japan for the treatment of hepatocellular carcinoma (HCC) in 2009. Miriplatin has the same non-leaving group as oxaliplatin but different leaving groups of two myristate chains, which make it highly lipophilic. Several characteristics of solid tumors in lung cancer constitute a physiochemical barrier to the homogenous distribution and deep penetration of chemotherapy agents. Nanocarriers provide a promising platform to overcome the physiochemical barrier and to reduce the systemic toxicity of anticancer chemotherapy. In this study, miriplatin is formulated with various lipid-based nanocarriers including micelles and solid lipid nanoparticles (SLNs) thanks to its highly lipophilic structure. The goal of this thesis is to develop and evaluate miriplatin-loaded nano formulations against lung cancer. Miriplatin-loaded formulations were prepared by different methods, including thin film hydration and several scale-up methods including chloroform dripping, chloroform injection, chloroform evaporation, co-solvent evaporation, chloroform slow evaporation and co-solvent slow evaporation. Between the two types of nano formulations under this study, micelles were much smaller (~10 nm in diameter) and more homogeneous (PDI < 0.3), while SLNs were bigger (~ 100 nm in diameter) and more heterogeneous (PDI ~0.8). A quantification method of miriplatin was established using inductively coupled plasma-optical emission spectrometry (ICP-OES). The quantification of platinum recovery from different miriplatin-loaded nano formulations was facilitated by digestion with 70% nitric acid and heating. The co-solvent slow evaporation method to prepare miriplatin-loaded nano formulations improved the platinum recovery prominently from 10% to 70%. Thus, co-solvent slow evaporation has been established as a pharmaceutically viable scale-up method to prepare nano formulations of miriplatin. Miriplatin-loaded nano formulations of different compositions were negatively stained with uranyl acetate and then imaged by transmission electron microscopy (TEM), which showed the formulations’ size and morphology that were consistent with the size and PDI data from dynamic light scattering studies by the Malvern Zetasizer. In the TEM studies, micelles showed a morphology of spherical dots at around 10 nm in diameter while SLNs showed both spherical and rod structures with a size distribution from 50 to 150 nm. A three-dimensional multicellular spheroid (3D MCS) model of A549-iRFP cells was used for in vitro evaluation of the nano formulations’ activity against lung cancer. A549-iRFP cells were engineered from the common lung cancer cell line A549 to stably express the near-infrared fluorescent protein (iRFP). The viability of A549-iRFP 3D MCS after exposure to cisplatin or nano formulations was similar to A549 3D MCS. The anticancer activity of miriplatin-loaded nano formulations against 3D MCS was positively associated with the platinum recovery as quantified by ICP-OES. The miriplatin-loaded nano formulations that had been prepared by the co-solvent slow evaporation method showed substantial anticancer activities against A549 3D MCS and A549-iRFP 3D MCS, which were comparable to cisplatin. Taken together, miriplatin-loaded nano formulations were successfully prepared by co-solvent slow evaporation. The formulations were developed to carry favorable physiochemical properties to enhance the activities of platinum drugs against lung cancer.

Purpose- This study aims to explore how management control systems are used to manage their corporate social responsibility strategies in organizations. This paper dives into how sustainability managers use existing controls in planning, executing, measuring, and reporting on their CSR. The challenges they face in implementing their CSR strategies with these control systems are also covered.  Methodology- The research was conducted using a qualitative research approach and a multiple case study strategy. The multiple case study involved three companies within a CSR network in Sweden. Secondary data from sustainability reports, internal financial control (IFC) reports were used together with seven semi-structured interviews.  Findings- Control systems monitor influence and steer the employee's behavior and actions towards achieving organizational goals. The thesis provides practical insights into how sustainability managers from the studied companies use management control systems. The findings indicate that companies use similar clusters of management controls in planning, executing, measuring and reporting on their corporate social responsibility. However, there are differences in how the same management controls are used. The author identified a different type of control which is mostly not included in discussing when discussing MCS.

Syftet med denna studie är att undersöka hur ett företag använder ekonomistyrning för att bidra till ekonomisk, social och miljömässig hållbarhet. Studien baseras på en analysmodell kallad Management Control System (MCS), som utgår från teoretiska ramverk inom ekonomistyrningssystemet och särskilt främjar ekonomisk hållbarhet. För att undersöka företagets arbete med sociala och miljömässiga aspekter tillämpas alla dessa dimensioner på MCS. I en kvalitativ fallstudie av företaget Hedern Fastigheter genomfördes semistrukturerade intervjuer med anställda från olika arbetsområden. Resultaten visar att företaget använder sina styrverktyg på olika sätt för att främja olika aspekter av hållbarhet. Slutsatser dras kring att miljömässiga dimensionen inom verksamheten ges mindre fokus än de finansiella och sociala dimensionerna på grund av implementeringsmognad och prioritering av ekonomisk lönsamhet, vilket resulterar i minskad belysning av vissa hållbarhetsaspekter. Studien visar att varje hållbarhetsdimension erhåller olika uppmärksamhet beroende på hur integrerade de anses vara i styrverktygen. Slutligen framkommer det att ekonomisk lönsamhet är central i verksamheten men ger upphov till vissa indirekta sociala och miljömässiga hållbarheter.