No / Although Streptococcus agalactiae, the group B Streptococcus, is a leading cause of invasive neonatal disease worldwide the molecular basis of its virulence is still poorly understood. To investigate the role of lipoproteins in the physiology and interaction of this pathogen with host cells, we generated a mutant S. agalactiae strain (A909DeltaLgt) deficient in the Lgt enzyme and thus unable to lipidate lipoprotein precursors (pro-lipoproteins). The loss of pro-lipoprotein lipidation did not affect the viability of S. agalactiae or its growth in several different media, including cation-depleted media. The processing of two well-characterized lipoproteins, but not a non-lipoprotein, was clearly shown to be aberrant in A909DeltaLgt. The mutant strain was shown to be more sensitive to oxidative stress in vitro although the molecular basis of this increased sensitivity was not apparent. The inactivation of Lgt also resulted in changes to the bacterial cell envelope, as demonstrated by reduced retention of both the group B carbohydrate and the polysaccharide capsule and a statistically significant reduction (P=0.0079) in A909DeltaLgt adherence to human endothelial cells of fetal origin. These data confirm that failure to process lipoproteins correctly has pleiotropic effects that may be of significance to S. agalactiae colonization and pathogenesis.

The current Coronavirus disease 2019 (COVID-19) outbreak, caused by a virus called severe acute respiratory syndrome 2 (SARS-CoV-2), has become a global health emergency. Recent findings in case studies assert that the transmigration of SARS-CoV-2 to the nervous system implicates severe neurotropic pathologies, including the onset of the rare autoimmune disease called Guillain-Barré syndrome (GBS). GBS is recognized as several disorders characterized by immune-mediated polyradiculoneuropathy, which is typically preceded by an infection or other immune stimulation. The symptoms of GBS initially present as acute symmetrical ascending paresthesia, weakness, and paralysis. This meta-analysis serves to help understand the predisposing factors (such as gender, age, comorbidities) and the clinical features of COVID-19- induced GBS. Most patients affected were 40 years or older and comprised 78.2% of all the cases. Males comprised most of the cases (62.8%; n=76). The patient mortality was 9.1%, intensive care unit (ICU) admission was 46.6%, and the need for mechanical ventilation was 35.8%. It was found that concomitant GBS and COVID-19 patients most often presented with increased cerebral spinal fluid (CSF) protein levels (88%; n=106), hyporeflexia or areflexia (87.6%) (n=106), lower limb strength and sensation impairment (91.7%; n=111), upper limb strength and sensation impairment (83.5; n=101), and somatic sensation impairment (73.6%; n=89). It is postulated that COVID-19 triggers the onset of GBS through a “cytokine release storm” (CRS) that occurs in the early stages of the disease. The same cytokines and chemokines involved in this CRS caused by COVID-19 contribute to the onset of GBS. Predisposing factors which influence this concomitance include male gender and older age. Most of the reported symptoms included abnormal limb functions (including paresthesia, weakness, and paralysis) and absent or weak deep tendon reflexes. The most common variant of GBS observed was AIDP, and the most significant laboratory finding among patients was high CSF protein levels.

No description available.

Este trabalho propõe um método com base no planejamento estatístico de testes de confiabilidade para proporcionar um tratamento quantitativo aos dois primeiros níveis da abordagem de padrões baseados em metas (Goal-Based Standards). O uso do método é demonstrado em dois exemplos práticos, através da sua aplicação na meta de confiabilidade dos componentes do sistema de pós-tratamento de gases de exaustão, em motores a diesel de veículos automotivos e marítimos. Os fundamentos do trabalho incluem a teoria do planejamento estatístico de testes de confiabilidade, os princípios do GBS, tipos e características de metas de confiabilidade, a ferramenta de avaliação de segurança formal (FSA), e da análise do modo e efeito da falha (FMEA). A originalidade da contribuição do trabalho está na combinação das técnicas de planejamento de testes de confiabilidade com os princípios do GBS para quantificar o nível de atendimento das metas de confiabilidade. Dessa forma, é possível ajustar o programa de testes na verificação das metas de segurança, aumentando o conhecimento sobre o desempenho do sistema. O método é de simples aplicação permitindo a sua aplicação expedita e integrada aos processos de desenvolvimento de sistemas. / This research proposes a probabilistic method based on reliability test planning in order to provide a quantitative approach to the Tier I and II of the Goal-Based Standards (GBS). The use of the method is exhibited through its application in the reliability goal of the components of the exhaust gases post-treatment system in diesel engines for automotive and marine vehicles. The fundamentals of this work includes the theory of statistical design of reliability tests, the GBS principles, a brief description of the types and characteristics of reliability goals, the tool of Formal Safety Assessment (FSA) recommended for marítima projects, and the risk qualitative methodology based on Failure Mode Effect Analysis (FMEA). This theoretical framework was applied to two practical examples, one in the automotive industry and the other in the shipbuilding sector. The originality of this research lies in the combination of the reliability test planning techniques with the principles of GBS, in order to verify, from the whole project tests planning, the reliability goals of the basic components as a fundamental step in the assessment of system safety. The testing program can be adjusted to focus on verifying the safety goals, so that the level of knowledge about the product performance before it is delivered to the client. This work also offers the benefit of providing an easy method of system safety assessment, which allows a large number of companies to use it and to integrate it into their product development process.

Este trabalho propõe um método com base no planejamento estatístico de testes de confiabilidade para proporcionar um tratamento quantitativo aos dois primeiros níveis da abordagem de padrões baseados em metas (Goal-Based Standards). O uso do método é demonstrado em dois exemplos práticos, através da sua aplicação na meta de confiabilidade dos componentes do sistema de pós-tratamento de gases de exaustão, em motores a diesel de veículos automotivos e marítimos. Os fundamentos do trabalho incluem a teoria do planejamento estatístico de testes de confiabilidade, os princípios do GBS, tipos e características de metas de confiabilidade, a ferramenta de avaliação de segurança formal (FSA), e da análise do modo e efeito da falha (FMEA). A originalidade da contribuição do trabalho está na combinação das técnicas de planejamento de testes de confiabilidade com os princípios do GBS para quantificar o nível de atendimento das metas de confiabilidade. Dessa forma, é possível ajustar o programa de testes na verificação das metas de segurança, aumentando o conhecimento sobre o desempenho do sistema. O método é de simples aplicação permitindo a sua aplicação expedita e integrada aos processos de desenvolvimento de sistemas. / This research proposes a probabilistic method based on reliability test planning in order to provide a quantitative approach to the Tier I and II of the Goal-Based Standards (GBS). The use of the method is exhibited through its application in the reliability goal of the components of the exhaust gases post-treatment system in diesel engines for automotive and marine vehicles. The fundamentals of this work includes the theory of statistical design of reliability tests, the GBS principles, a brief description of the types and characteristics of reliability goals, the tool of Formal Safety Assessment (FSA) recommended for marítima projects, and the risk qualitative methodology based on Failure Mode Effect Analysis (FMEA). This theoretical framework was applied to two practical examples, one in the automotive industry and the other in the shipbuilding sector. The originality of this research lies in the combination of the reliability test planning techniques with the principles of GBS, in order to verify, from the whole project tests planning, the reliability goals of the basic components as a fundamental step in the assessment of system safety. The testing program can be adjusted to focus on verifying the safety goals, so that the level of knowledge about the product performance before it is delivered to the client. This work also offers the benefit of providing an easy method of system safety assessment, which allows a large number of companies to use it and to integrate it into their product development process.

Adaptive population shifts in response to climate change Ing. Michaela Horníková, Doctoral thesis Abstract Understanding of species' reactions to past climate and environmental changes is a hot topic in many fields of biology as it is relevant also for addressing species' future under the contemporary climate change. Using an emerging model species, the bank vole, I combine genomic phylogeographic data with information on known intraspecific functional variability and environmental niche modelling and aim to elucidate the particular role of intraspecific variation and ultimately selection in shaping the species' response to the climatic and environmental changes after the end of the last glaciation. Based on the mtDNA markers, bank voles exhibit a complex phylogeographic pattern suggesting population replacement events during the postglacial recolonization of Europe and thus possible involvement of selection in the process. An extensive dataset of more than 6000 SNPs was used to search for signs of population replacement in the bank vole genomic DNA and to investigate the species' postglacial recolonization history throughout its European distribution range. The genomic data revealed even more complex population history than previously detected with mtDNA markers, including not only admixture but also...

The purpose of the thesis was to investigate if integrity promoting care improves functions in demented patients over time. The Erikson (1982) theory of ”eight stages of man” was used as a basis for training of staff in a three-month intervention study (I-VI) at a nursing home ward. A collective living unit where staff had had support in the performance of the delivery of care was also evaluated and compared with a nursing home in a long-term study (VII). Patients, relatives, staff, and the environments were investigated. Cerebrospinal fluid concentrations of somatostatin increased, and reduction of distractability, anxiety and confusion was seen in the intervention group (I) in contrast to controls. In the collective living group (VII) EEG activities indicated a reduction of supposed dementia induced changes. Better motor and social ability, some improved intellectual ability, more alertness and reduced signs of depression were seen (I, II, VII). Patients expressed more autonomy (IV, VII) and initiatives (II-VII) and showed a lot of competence (V) in conversations. Five patients (V) showed patterns of behaviour which seemed to reflect life-long characteristics in spite of their severe dementia. The improvement in the patients' functions can be attributed to the physical environment and the integrity promoting care, since the medical treatment of the patients remained unchanged. In the thesis medical, psychological, and nursing sciences were connected in a complementary process. The results were congruent, and indicate that patients in the care of staff who had had training and support, declined less than controls. / <p>S. 1-61: sammanfattning, s. 63-184: 7 uppsatser</p> / digitalisering@umu

Superplastic deformation behaviour of AZ31 magnesium alloy having initial grain sizes 8, 11 and 17μm alloy was investigated at 673 K with initial strain rates ranging from 1x10-2 to 1x10-4 s-1. Mechanical data on fine grained AZ31 alloy with grain sizes 8 and 11 μm indicated a transition in deformation mechanisms. The strain rate sensitivity, m ~ 0.5 at low strain rates and m ~ 0.2 at high strain rates which suggest GBS and dislocation slip as the corresponding deformation mechanism. For coarse grained alloy having grain size 17 μm, m < 0.4 at low strain rates and ~ 0.2 at high strain rates, suggesting dislocation slip as the deformation mechanism. A superplastic maximum elongation of ~ 475% was observed for 8 μm alloy at low rate of deformation. At high strain rates, the deformation was non-superplastic for fine and coarse grained alloys. The contribution of GBS to total strain, ξ in the low strain rate regime was evaluated to be 50 – 60%, for both low and high elongation. EBSD studies indicated the maintenance of high fraction of high angle boundaries up to true strain of ~ 0.88 and a reduction in texture intensity. These observations show GBS as the dominant deformation mechanism for fine grained alloy. At higher strain rate, ξ was estimated to be 30%. Fraction of high angle boundaries was reduced and [0001] direction of grains was found to be rotated towards the tensile direction, suggesting dislocation slip. Based on mechanical data, flow localization and cavitation studies; the failure of the material during high rates of deformation was mainly due to flow localization. Extensive cavitation along with more uniform flow at a lower strain rate regime suggests the failure due to the cavity interlinkage and coalescence. The present GBS data are consistent with the previous relevant data in fine grained Mg based alloys in the low strain rate regime. The GBS data obtained in the dislocation regime in the present study are also in agreement with that of the previous investigations in fine grained Mg alloys.

No description available.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Estreptococos do grupo B (EGB), principalmente sorotipo III são a principal causa de pneumonia neonatal, sepse e meningite. O potencial de virulência das amostras de EGB pode determinar a colonização ou a infecção do hospedeiro. Como o pulmão constitui uns dos primeiros órgãos durante o processo de invasão sistêmica por EGB, nós decidimos investigar os mecanismos de adesão e invasão de amostras do sorotipo III (90356-líquor e 80340-vagina) com linhagem de células epiteliais do pulmão humano (A549). Desta forma, o principal objetivo deste estudo foi avaliar a capacidade de aderência e invasão de duas amostras de EGB sorotipo III com células de epiteliais pulmonares A549, a persistência bacteriana intracelular, a fusão com compartimentos acídicos, potencial citotóxico e indução de apoptose. As amostras mostraram capacidade de aderir e invadir o epitélio pulmonar A549, onde a amostra 90356-líquor isolada de paciente a que apresentou maior propriedade adesiva e invasiva que a amostra 80340-vagina (p<0,05). Ambas as cepas mostraram persistência intracelular sem replicação no interior do epitélio respiratório até 24h de incubação. Além disso, verificamos que os EGB são capazes de promover vacuolização celular permanecendo viáveis dentro de vacúolos acídicos, sugerindo a ocorrência de fusão lisossomo-fagossomo. A amostra 90356-líquor também mostrou maior citotoxidade quando comparada com a amostra 80340-vagina. A análise por citometria de fluxo demonstrou, pela primeira vez, que o EGB induz apoptose em epitélio respiratório, podendo representar um mecanismo importante para o desenvolvimento da lesão celular aguda e a patogênese bacteriana. / Group B streptococci (GBS), mainly serotype III, is a major cause of neonatal pneumonia, sepsis and meningitis. Virulence potential of GBS strains may determine the outcome of host colonization or infection. Because the lung constitutes a first step in GBS systemic invasion processes, we have investigates the adherence and invasion mechanisms of GBS-III isolates to human lung epithelial cell line (A549). Thus, the main objective of this study was to evaluate the ability of adhesion and invasion of GBS strains serotype III (90356-liquor and 80340-vagina) with A549 lung epithelial cells, intracellular bacterial persistence, fusion with acidic compartments, cytotoxic potential, and induction of apoptosis. The strains showed ability to adhere and invade the epithelial A549 cells; GBS 90356-liquor isolated from a patient showed a more efficient adherence and invasion properties than GBS-III 80340 isolated from vagina (P<0,05). Both strains showed persistent intracellular viability without replication into A549 cells up to 24h incubation. In addition, we found that GBS are able to promote cellular vacuolization and persisted viable inside acidic vacuoles, suggesting lysosome-phagosome fusion. The GBS 90356-líquor also showed higher cytotoxicity when compared with 80340-vagina strain. The present work describe for first time by flow cytometry that GBS induces apoptosis in respiratory epithelium and be an important mechanism for the development of acute cellular injury and bacterial pathogenesis.