Cílem této práce je uspořádat a obohatit teoretickou základnu řízení rizik v projektovém managementu, analyzovat a zhodnotit přístup k této problematice dle metodiky PMBOK a poskytnout základní praktický pohled na řízení rizik ve skutečných projektech z oblasti IS/ICT. Vlastní text je strukturován do sedmi kapitol, z nichž první poskytuje úvod a vymezení celé práce. Ve druhé kapitole je proveden úvod do oblasti řízení rizik v projektech a dále analyzován přístup a základní principy metodiky řízení projektu PMBOK. Ve třetí kapitole je uveden seznam projektových rizik, který byl vytvořen a popsán na základě průzkumu literatury, diskusí s odborníky a praktických zkušeností autora. Ve čtvrté kapitole, která obsahuje řadu nových teoretických pojmů, jsou poté popsány autorem identifikované různé způsoby řízení rizik projektu podle jeho základních charakteristik. Pátá kapitola se zaměřuje na posouzení metodiky PMBOK vzhledem ke všem zjištěným typům rizik a identifikovaným způsobům jejich řízení a pokouší se o její doplnění. V šesté kapitole jsou konečně využity všechny poznatky získané ve všech předchozích kapitolách a je provedena jejich aplikace na oblast IS/ICT, mimo jiné pomocí vzorového příkladu obsahujícího některé autorem navržené analytické nástroje. V sedmé kapitole je provedeno závěrečné zhodnocení.

Colony-Stimulating Factor (CSF-1) is required for the proliferation, differentiation and survival of cells of the mononuclear phagocyte lineage. Mice with a mutation in their CSF-1 gene demonstrate abnormal development in many organ systems and severe growth retardation. These defects can be corrected by administration of rh- CSF-1, and when similarly administered to wild-type mice, can increase organ and body weight, thus highlighting the importance of CSF-1 in postnatal growth. CSF-1 is known to be elevated in the circulation in the immediate postnatal period of both mice and humans. It remains to be seen whether CSF-1 deficiency underlies important clinical issues such as low birth weight, and whether there are any functionally important variations in expression or biology of CSF-1, or the alternative CSF-1R ligand IL-34 that contributes to variation in somatic growth between individuals. This thesis aimed to use the pig as a model for human innate immunity and disease based upon recent publications that highlighted the similarities in their immune systems. To investigate the effects of CSF-1 on postnatal growth the first aim was to characterise the CSF-1R system in pigs and produce reagents. Biologically active porcine CSF-1 and IL-34 were produced along with expression of full length functional porcine CSF-1R and production of anti-CSF-1R antibodies. A bioassay was developed and optimised to assess the biological activity of these proteins. The cross-species reactivity of a range of species CSF-1 and IL-34 proteins was investigated in-vitro using the bioassay and cell culture systems. Recombinant CSF-1 is known to have a short half-life. Since conjugation of proteins to the Fc region of immunoglobulins has been used extensively to improve circulating half-life; a porcine Fc CSF-1 fusion protein was generated by commercial partners, Pfizer Animal Health. The conjugated and un-conjugated CSF-1 proteins had identical activity in cell line and primary cell assays in-vitro. The in-vivo activity of porcine Fc CSF-1 was tested initially in the Csf1r-EGFP+ mouse reporter line and C57BL/6 mice. The Fc CSF-1 protein was more active than the native protein in promoting increased monocyte and tissue macrophage numbers, increasing body weight and inducing hepatosplenomegaly. Hepatic growth was associated with extensive macrophage infiltration and hepatocyte proliferation, identified by gene expression profiling as well as immunohistochemistry. Fc CSF-1 was then tested in neonatal pigs. They were found to have an immature immune system that develops with age. No postnatal surge of CSF-1 was detected. Fc CSF-1 administration increased blood monocyte and neutrophil numbers confirming that CSF-1 is not saturating at this time. Nevertheless, no influence on postnatal growth rate was identified. This is discussed in terms of the differences in placental architecture in the pig compared to human and mouse. This thesis demonstrates the effectiveness of porcine Fc CSF-1 in both mice and porcine and highlights the important role that CSF-1 and macrophages play in liver homeostasis. Fc CSF-1 is identified as candidate therapeutic agent in humans and companion animals for tissue regeneration, and a tool for the study of the role of macrophages in physiology and pathology.

Strategies for enterprise resource planning (ERP) system implementation success have been a focus of scholars since the 1990s. Researchers have demonstrated that ERP system implementation could cause both system failures and organization failures, affecting both operations and stakeholders. The theory of constraints was the conceptual framework for this single qualitative case study that explored ERP system critical success factors (CSFs) and strategies U.S. city governments use to successfully implement ERP systems. One city government in New Mexico with a successful ERP system served as the case study's population. Data were collected from semistructured interviews and relevant documents and then open coded and thematically analyzed. Triangulation was employed to increase the trustworthiness of interpretations. The primary themes that emerged from the analysis of this single case study revealed the importance of the city government adequately resourcing and staffing the organization, providing top management support, continuously communicating to clarify motivations for implementations, gaining concurrence, and maintaining a change management asset. Other city government end-users, managers, leaders, and vendors could benefit from results of this study by identifying and addressing the relevant principal CSFs, and then developing and deploying strategies for the implementation, control, and remediation phases to increase ERP systems' utility. City governments seeking to implement ERPs could effect social change by demonstrating fiscal stewardship of resources, adding fiscally efficient and efficacious operations directly supporting constituents, and increasing public confidence.

Background: Several neuropsychiatrie disorders have shown season of birth associations. Low cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-HIAA and the dopamine metabolite HVA have been associated with suicidal behaviour, impulsivity, and aggression. This thesis investigated associations between the season of birth, the CSF levels of three monoamine metabolites (including MHPG of norepinephrine), the scales of the diagnostic interview for borderline patients (DIB), and psychiatric diagnoses. Also, the methods of suicide were investigated in relation to the season of birth. Methods: We studied a clinical sample of 241 patients in Stockholm with mood, anxiety and adjustment disorders with respect to the CSF levels of monoamine metabolites in relation to the season of birth, and in relation to the DIB in an overlapping sample. We also analysed all completed suicides during the 42 years 1952- 1993inVästerbottenin northern Sweden (1466 cases) by multiple logistic regressions to relate suicide methods with season of birth, gender, age, urban-rural residence, marital status, year of suicide, and season of suicide. For the 20 years 1961- 1980 (693cases), psychiatric in-patient and out-patient records were also examined for any history of psychiatric contacts and psychiatric diagnoses. In two mutually independent samples, we investigated the DIB in relation to the season of birth. Results: In the Stockholm sample, those born during February to April had significantly lower CSF levels of 5-HIAA, and those born during October to January had significantly higher CSF levels of HVA, HVA/5-HIAA, and HVA/MHPG, as well as (non-significantly) higher levels of 5-HIAA. Those with an intermediate score of section II (impulse action patterns) of the DIB had significantly higher CSF levels of 5-HIAA and HVA, and they were significantly more likely to have been born during October to January. In the Västerbotten register, those born during February to April were significantly more likely to have preferred hanging rather than poisoning or petrol gases, and conversely for those born during October to January. These associations with suicide methods were found for the total sample and for those without any history of psychiatric contacts, but not for those with psychiatric contacts. Conclusions: Suicidal behaviour shows statistically significant variation according to the season of birth, most probably mediated by a variation in an independent trait of vulnerability to suicide based on neurodevelopmental parameters, particularly the serotonergic system. The suicidal process differs between those who seek psychiatric care compared to those who do not, reflecting differences in the diagnostic spectra and in the extent of mental illness. / <p>Härtill 6 delarbeten.</p>

The high performance organic light-emitting diodes (OLEDs) have been studied. First, we have fabricated a WOLED with AlF3 and m-MTDATA as a hybrid buffer layer. Results indicate that the turn-on voltage can be reduced to 3.1V, and the luminous efficiency can be improved to 14.7 cd/A when a hybrid buffer layer was used. Since the turn-on voltage decreases and the efficiency increases, the power consumption as well as lifespan are then improved. Moreover, the luminous efficiency of the hybrid buffer layer devices also immunes to drive voltage variations. Second, we studied the properties of transportation in OLEDs. The study presented the device of a WOLED with a combination of a graded hole transport layer (GH) structure and a gradually doped emissive layer (GE) structure as a double graded (DG) structure. The DG structure: ITO/MTDATA(15 nm/NPB(15 nm)/NPB:25% BAlq (15 nm)/NPB : 50% BAlq (15 nm)/BAlq:0.5% Rubrene (10 nm)/ BAlq : 1% Rubrene (10nm) /BAlq:1.5%Rubrene (10 nm) / Alq3 (20 nm)/ LiF (0.5 nm)/Al (200 nm) is beneficial for improving both electrical and optical performances. The luminous efficiency of the DG device is 11.8cd/A, which is larger than that of 7.9cd/A with the HJ device. This improvement is attributed to the discrete interface between hole transport layer and emissive layer can be eliminated, surplus holes can be suppressed, electron-hole pairs can obtain optimal transportation and recombination in the emissive layer, and quenching effects can be significantly suppressed. Moreover, the spectra were almost not changed with an increasing drive current. As the efficiency was improved, it is expected that the power consumption can be reduced as well. Third, high efficiency and brightness p-i-n OLEDs with a CsI-doped Alq3 layer as a n-ETL has been studied. The p-i-n WOLED with a 15 % CsI-doped Alq3 layer exhibits a luminous efficiency of 5.75 cd/A at a driving current of 20mA/cm2 as well as a maximum power efficiency of 4.67lm/W. This improved performance is attributed to the increased electron carriers of the n-ETL and the balance of electrons and holes in the recombination zone. The X-ray photoelectron spectroscopy (XPS) have shown that doping of CsI caused chemical reaction, attributing to the increase of carriers. Finally, we focus on the improvement of contrast ration (CR) of OLEDs. We successfully fabricated a conductive organic-metal light-absorbing layer with a high CR and low reflectance for use as a black cathode in an OLED. The black cathode that was fabricated using vacuum deposition has the advantages of low cost and simple fabrication. Moreover, the J-V characteristic of the black cathode device is almost identical to that of a conventional device. Additionally, the reflectance can be reduced from 66.2% to 11.3% and a small reflectance variation around 3.3% over the visible spectrum is appealed. At an ambient illumination of 250 lx, the CR can be increased from 4.2 to 10.8 at a brightness of 250 cd/m2.

Zwischen 1995 und 2001 wurden an der Medizinischen Tierklinik der Universität Leipzig Liquor cerebrospinalis (CSF)- und Serumproben von 59 Pferdepatienten gewonnen. Von diesen Patienten waren 16 neurologisch gesund, 33 litten an Bornascher Krankheit und 10 hatten andere neurologische Krankheiten (EMND, Spinale Ataxie, Nekrose des Kleinhirns, 2x Epilepsie, Faciale Lähmung, Enzephalitis, Narkolepsie, EHV-1 Enzephalomyelitis, Stringhalt). Fünf Pferde mit Bornascher Krankheit wurden zweimal in verschiedenen zeitlichen Abständen punktiert. In der CSF wurde die Zellzahl, die Zelldifferenzierung und die GEW-Konzentration analysiert. Mittels isoelektrischer Fokussierung, Nephelometrie und ELISA wurde die Konzentration des Albumins und der Immunglobuline G, A und M gemessen. Bei allen Patienten wurden die Altersverteilung, die Quotienten (Albumin und Immunglobuline), die Ig-Indizes und die intrathekale Synthese bzw. die Immunreaktion festgestellt. / Serum and cerebrospinal fluid (CSF) samples were collected from 59 patients at the Large Animal Clinic for Internal Medicine at the University of Leipzig from 1995 to 2001. Of these 59 patients, 16 were considered neurologically healthy, 33 were diagnosed as suffering from Borna Disease and 10 were afflicted with other neurological diseases (EMND, spinal ataxia, cerebellar necrosis, epilepsy (2), facial paralysis, encephalitis, narcolepsy, EHV-1 encephalomyelitis, stringhalt). Five of the horses diagnosed with Borna disease were tapped twice at different stages of the disease. A cell count, cell differentiation and total protein were analyzed in all CSF samples. The albumin, IgG, IgA and IgM concentrations were measured by means of isoelectric focusing, nephelometry and ELISA. The age, albumin and Ig quotients, Ig indexes, intrathecal syntheses and class reactions were established for all patients.

Los macrófagos son células fagocíticas pertenecientes al sistema inmunitario que participan tanto en la respuesta innata como en la adaptativa. En presencia de M-CSF, su estímulo mitogénico específico, proliferan, mientras que el tratamiento con estímulos activadores como el IFN-&#947; o el LPS hace que detengan su proliferación, se activen y pasen así a ejercer sus funciones específicas. En este contexto, existen dos tipos de citocinas con capacidad de activar al macrófago, las llamadas citocinas de tipo Th1 y las de tipo Th2. Las citocinas de tipo Th1 como el IFN-&#947; inducen en los macrófagos un patrón de activación llamado "clásico" cuya finalidad es provocar una respuesta de tipo proinflamatoria que acabará por eliminar la presencia de agentes patógenos. Por el contrario, las citocinas de tipo Th2 como la IL-4 inducen una activación "alternativa" en los macrófagos, cuya finalidad es la de llevar a cabo la reparación y remodelación tisular tras la respuesta proinflamatoria. En este estudio hemos observado, por primera vez, que la activación alternativa del macrófago cumple también la dicotomía proliferación/activación observada bajo estímulos clásicos e inhibe la proliferación del macrófago en el umbral entre las fases G1 y S del ciclo celular. En este sentido, hemos visto que tanto el IFN-&#947; como la IL-4 inducen un alargamiento en el tiempo de la cinética de activación de la MAPK ERK-1/2, encargada de regular la proliferación del macrófago en respuesta al M-CSF. Esta MAPK es regulada por la fosfatasa MKP-,1 quien se encarga de defosforilarla. Así, en presencia del M-CSF, MKP-1 se induce para regular a ERK-1/2 mientras que el IFN-&#947; y la IL-4 bloquean su expresión de forma dependiente de STAT. La inhibición directa de MKP-1 mediante tecnología de RNA de interferencia induce también un alargamiento de la actividad de ERK-1/2 y, en consecuencia, una parada de la proliferación, corroborando así los resultados obtenidos previamente. También hemos analizado el estado de activación de los complejos cdk2/cicE, encargados de la progresión del ciclo celular entre las fases G1 y S. Hemos visto que, mientras que el M-CSF induce la expresión de la ciclina E y, en consecuencia, la activación del complejo cdk2/cicE, tanto el IFN-&#947; como la IL-4 inhiben a ambos, explicando así el mecanismo utilizado por estas citocinas para mantener la parada en G1. Este bloqueo de la actividad cdk2/cicE es llevado a cabo gracias a la acción del inhibidor de cdk p21Waf1. Sin embargo, aunque ambas citocinas inducen la expresión de esta proteína, utilizando células knockout para p21Waf1 hemos demostrado que sólo la parada inducida por la IL-4 es dependiente de esta proteína, lo cual sugiere que el IFN-&#947; y la IL-4 utilizan vías de señalización distintas para ejercer funciones celulares similares. Por otro lado, hemos analizado también la implicación de la vía de las MAPK en la activación alternativa del macrófago. En este aspecto hemos demostrado que, aunque la expresión de los principales genes responsables de dicha activación es dependiente de STAT6, la acción de JNK1 ejerce un efecto sinérgico sobre su inducción, ya que la inhibición de esta quinasa resulta en una disminución de la expresión de dichos genes. El mecanismo mediante el cual JNK1 ejerce esta función no está aún del todo claro. Sin embargo, los resultados obtenidos mediante ensayos de inmunoprecipitacion de cromatina sugieren que JNK1 podría estar fosforilando a determinados cofactores en las zonas promotoras de algunos genes, colaborando así con la actividad del factor de transcripción STAT6. / Macrophages play a crucial role as regulators of immune response. They are originated from bone marrow stem cells and, in response of growth factors and particularly to macrophage colony-stimulating factor (M-CSF), they proliferate and differentiate. We have previously observed that activation of extracellularly regulated kinase (ERK) 1/2 is required for macrophage proliferation in response to growth factors. A short and early pattern of ERK activity correlated with the proliferative response. In contrast, slightly prolonged patterns of activity of these kinases were induced by signals that lead to macrophage activation and growth arrest. IFN-&#947; is the main endogenous Th1 type macrophage activator and IL-4 is the main Th2 type one. While M-CSF withdrawal arrested the cell cycle at early G1, treatment of macrophages with IFN-&#947; or IL-4 stopped the cell cycle later, at the G1/S boundary. IFN-&#947; and IL-4 induced the expression of the Cdk inhibitor p21Waf1. Using knockout mice and siRNA experiments, we found that p21Waf1 is required for IL-4- but not for IFN-&#947;-dependent inhibition of proliferation. Moreover, both IFN-&#947; and IL-4 elongate the activity pattern of the MAPK ERK-1/2 through the inhibition of the phosphatase MKP-1, which in fact results in a decrease of proliferation. Moreover, inhibition of MKP-1 expression using siRNA technology or synthetic inhibitors also led to elongated ERK activity and significant blockage of M-CSF-dependent proliferation. On the other hand, we have also analyzed the relationship between IL-4 and the MAPK pathway on the context of the alternative activation of macrophages. The IL-4 signaling pathway involves activation of STAT-6. However, IL-4 has also the capability to activate members of the MAPK family. In primary bone marrow-derived macrophages, we have observed strong activation of JNK-1 at early time points of IL-4 stimulation, whereas weak activation of ERK-1/2 and p38 were detected at a more delayed stage. By using selective inhibitors and knockout models, we have explored the contributions of MAPK activation to the macrophage response to IL-4. Our findings indicate that JNK-1 regulate IL-4-mediated expression of genes typically involved in alternative activation such as arginase 1.

Zugl.: Leipzig, Universiẗat, Diss., 2001.

O objetivo desta dissertação é propor um modelo estendido para operacionalização do Business Process Management (BPM), observando fatores culturais e interpessoais. Para atingir o objetivo, foram desenvolvidos três artigos. No primeiro artigo, foi realizada uma revisão da literatura explorando a relação entre os pressupostos culturais básicos das organizações e as novas tecnologias de gestão. Como resultado, a pesquisa apresenta um quadro que relaciona as novas tecnologias de gestão em função dos pressupostos culturais básicos, identificando as tecnologias de gestão que mais afetam ou são afetadas pela cultura organizacional, dando um novo panorama aos conceitos subjacentes às tecnologias de gestão, no qual BPM se enquadra. No segundo artigo, buscou-se identificar os Fatores Críticos de Sucesso (FCS) em uma iniciativa BPM através da revisão da literatura e observação participante em um estudo de caso. Entre os principais resultados deste artigo destaca-se: a identificação de novos FCS, antes não mencionados na literatura. No terceiro artigo, foi proposto um modelo estendido para operacionalização do BPM baseado nos novos FCS apresentados no artigo anterior, dentre eles está: a falta de uma estrutura de trabalho entre a área de TI e Equipe de Processos; através do estudo de diversas metodologias de implantação e as relações entre as áreas foi proposto um modelo estendido para solucionar o problema em questão. Além disso, verificou-se que as poucas soluções propostas pela literatura raramente são relacionadas à operacionalização e às adversidades na inter-relação entre as áreas em uma organização. Por fim, os resultados encontrados devem possibilitar pesquisas futuras na área de BPM. / The aim of this work is to propose an extended model for operating Business Process Management (BPM), observing cultural and interpersonal factors. To achieve the goal, it was developed three articles. In the first article, a literature review exploring the relationship between the basic cultural assumptions of organizations and new management technologies was held. As a result, the research presents a framework that relates the new management according to the basic cultural assumptions, identifying the management technologies that most affect or are affected by organizational culture, giving a new perspective to the concepts underlying management technologies, in which BPM fits. In the second article, we sought to identify the Critical Success Factors (CSF) in a BPM initiative through literature review and participant observation in a case study. The main results of this article stands out: the identification of new CSF, not previously mentioned in the literature. In the third article, we propose an extended model for implementation of BPM based on the new CSF presented in the previous article, among them are: the lack of a framework between the area of IT and Process Team; through the study of various implementation methodologies and the relationship between areas was proposed an extended model to solve the problem at hand. In addition, it was found that the few solutions proposed in the literature are rarely related to the implementation and the adversities in the interrelationship between the areas in an organization. Finally, the results should enable future research in the BPM area.

O objetivo desta dissertação é propor um modelo estendido para operacionalização do Business Process Management (BPM), observando fatores culturais e interpessoais. Para atingir o objetivo, foram desenvolvidos três artigos. No primeiro artigo, foi realizada uma revisão da literatura explorando a relação entre os pressupostos culturais básicos das organizações e as novas tecnologias de gestão. Como resultado, a pesquisa apresenta um quadro que relaciona as novas tecnologias de gestão em função dos pressupostos culturais básicos, identificando as tecnologias de gestão que mais afetam ou são afetadas pela cultura organizacional, dando um novo panorama aos conceitos subjacentes às tecnologias de gestão, no qual BPM se enquadra. No segundo artigo, buscou-se identificar os Fatores Críticos de Sucesso (FCS) em uma iniciativa BPM através da revisão da literatura e observação participante em um estudo de caso. Entre os principais resultados deste artigo destaca-se: a identificação de novos FCS, antes não mencionados na literatura. No terceiro artigo, foi proposto um modelo estendido para operacionalização do BPM baseado nos novos FCS apresentados no artigo anterior, dentre eles está: a falta de uma estrutura de trabalho entre a área de TI e Equipe de Processos; através do estudo de diversas metodologias de implantação e as relações entre as áreas foi proposto um modelo estendido para solucionar o problema em questão. Além disso, verificou-se que as poucas soluções propostas pela literatura raramente são relacionadas à operacionalização e às adversidades na inter-relação entre as áreas em uma organização. Por fim, os resultados encontrados devem possibilitar pesquisas futuras na área de BPM. / The aim of this work is to propose an extended model for operating Business Process Management (BPM), observing cultural and interpersonal factors. To achieve the goal, it was developed three articles. In the first article, a literature review exploring the relationship between the basic cultural assumptions of organizations and new management technologies was held. As a result, the research presents a framework that relates the new management according to the basic cultural assumptions, identifying the management technologies that most affect or are affected by organizational culture, giving a new perspective to the concepts underlying management technologies, in which BPM fits. In the second article, we sought to identify the Critical Success Factors (CSF) in a BPM initiative through literature review and participant observation in a case study. The main results of this article stands out: the identification of new CSF, not previously mentioned in the literature. In the third article, we propose an extended model for implementation of BPM based on the new CSF presented in the previous article, among them are: the lack of a framework between the area of IT and Process Team; through the study of various implementation methodologies and the relationship between areas was proposed an extended model to solve the problem at hand. In addition, it was found that the few solutions proposed in the literature are rarely related to the implementation and the adversities in the interrelationship between the areas in an organization. Finally, the results should enable future research in the BPM area.