Pathogenic and therapeutic aspects of intrathecal immune responses in multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The target antigen of the intrathecal immune response has not been identified, and the immune response in MS may also hold neuroprotective potential. MS patients display an increased frequency of T cells that recognize CSF IgG. Work in this thesis shows that these T cells recognize idiotopes, which are mutated fragments on the IgG variable regions. We show that idiotope specific T cells from the blood and CSF of MS patients recognize several epitopes on self-IgG, that autologous B cells may present their own idiotope to T cells, and that idiotope specific T cells are able to induce apoptosis of oligodendrocytes. Idiotope-driven T-B cell collaboration has been shown to cause severe autoimmunity in animal models, and we postulate that a similar mechanism may contribute to the immune mediated tissue destruction in MS brains. As a model for neuroprotective immune responses in MS, we have investigated the mechanism of action of glatiramer acetate (GA), a widely used MS treatment. GA was shown to shift the phenotype of GA reactive T cells from the CSF from pro-inflammatory to anti-inflammatory

The northern sector of the last British ice sheet : maximum extent and demise

Strongly divided opinion has led to competing, apparently contradictory, views on the timing, extent, flow configuration and decay mechanism of the last British Ice Sheet. We review the existing literature and reconcile some of these differences using remarkable new sea-bed imagery. This bathymetric data provides unprecedented empirical evidence of confluence and subsequent separation of the last British and Fennoscandian Ice Sheets. Critically, it also allows a viable pattern of ice-sheet disintegration to be proposed for the first time. Covering the continental shelf around the northern United Kingdom, extensive echosounder data reveals striking geomorphic evidence – in the form of tunnel valleys and moraines – relating to the former British and Fennoscandian Ice Sheets. The pattern of tunnel valleys in the northern North Sea Basin and the presence of large moraines on the West Shetland Shelf, coupled with stratigraphic evidence from the Witch Ground Basin, all suggest that at its maximum extent a grounded ice sheet flowed from SE to NW across the northern North Sea Basin, terminating at the continental-shelf edge. The zone of confluence between the British and much larger Fennoscandian Ice Sheets was probably across the northern Orkney Islands, with fast-flowing ice in the Fair Isle Channel focusing sediment delivery to the Rona and Foula Wedges. This period of maximum confluent glaciation (c. 30–25 ka BP) was followed by a remarkable period of large-scale ice-sheet re-organisation. We present evidence suggesting that as sea level rose, a large marine embayment opened in the northern North Sea Basin, as far south as the Witch Ground Basin, forcing the two ice sheets to decouple rapidly along a north–south axis east of Shetland. As a result, both ice sheets rapidly adjusted to new quasi-stable margin positions forming a second distinct set of moraines (c. 24–18 ka BP). The lobate overprinted morphology of these moraines on the mid-shelf west of Orkney and Shetland indicates that the re-organisation of the British Ice Sheet was extremely dynamic — probably dominated by a series of internally forced readvances. Critically, much of the ice in the low-lying North Sea Basin may have disintegrated catastrophically as decoupling progressed in response to rising sea levels. Final-stage deglaciation was marked by near-shore ice streaming and increasing topographic control on ice-flow direction. Punctuated retreat of the British Ice Sheet continued until c. 16 ka BP when, following the North Atlantic iceberg-discharge event (Heinrich-1), ice was situated at the present-day coastline in NW Scotlan

On the energy stability of high-order finite volume schemes for initial-boundary value problems

We examine the energy stability of high-order finite volume schemes approximating linear hyperbolic initial- boundary value problems. In particular, we consider schemes obtained by the k-exact method and the spectral volume method using the central numerical flux. To determine the stability of the schemes we use the energy method, and investigate the resulting terms. Finally, we compute numerical results verifying the accuracy of the schemes.Masteroppgave i anvendt og beregningsorientert matematikkMAB399MAMN-MA

TEMPERATURE RECORDINGS IN NEONATES

Summary The purposes of this ex post facto research study were to answer the following questions: 1. What is the length of time required for glass thermometers to register the temperature in neonates at the rectal and axillary sites? 2. Do significant differences exist between simultaneous axillary and rectal temperature recordings in neonates? 3. What is the relationship between axillary and rectal temperature recordings at specified time intervals in neonates? A sample of 30, full-term neonates was obtained from the Newborn Nursery of a large teaching hospital in the Middle Atlantic region. All participants were over 24 hours of age and weighed greater than 2,500 grams. Each subject had simultaneous axillary and rectal temperature recordings made at one minute intervals over a 12 minute period. Data analysis was performed which determined thermometer placement time, mean, range and standard deviation of temperature recordings, level of significance for the differences between axillary and rectal sites, and the correlation between rectal and axillary temperature recordings. Conclusions On the basis of the data analysis, the data from this study supported the two stated hypotheses: 1. Significant differences exist between simul- taneous axillary and rectal temperature recordings in neo- nates (p \u3c .01). 2. There is a direct and positive correlation between axillary and rectal temperature recordings at specified time intervals in neonates (p \u3c .01). The following conclusions were also drawn from these data: 1. The maximum placement time for rectal thermometers to register the neonate\u27s temperatures was eight minutes. The optimum placement time for rectal thermometers was four minutes. 2. The maximum placement time for axillary ther- mometers to register the neonate\u27s temperatures was 12 minutes. The optimum placement time for axillary thermometers was eight minutes. 3. The mean rectal maximum temperature in neonates was 99.05 plus or minus .49 degrees Fahrenheit. The mean rectal optimum temperature was 98.88 plus or minus .51 degrees Fahrenheit. 84 4. The mean axillary maximum and optimum temperatures in neonates were 98.87 plus or minus .47 degrees Fahrenheit and 98.7 plus or minus .48 degrees Fahrenheit, respectively. 5. The mean difference between maximum rectal and axillary recordings was 0.18 degrees Fahrenheit. The mean difference between optimum rectal and axillary recordings was 0.19 degrees Fahrenheit. Implications for Nursing As a result of this study, the following implications for nursing practice are implied: 1. A longer thermometer placement time for determining rectal and axillary temperature recordings in neonates may be indicated. 2. Although significant differences between simul- taneous axillary and rectal temperature recordings exist in neonates (p\u3c.01), the small difference (i.e., 0.18 degrees Fahrenheit for maximum temperatures and 0.19 degrees Fahrenheit for optimum temperatures) between the two sites may not greatly influence nursing care of neonates. 3. In a constant environmental temperature,axillary and rectal temperature recordings may be used interchangeably in neonates (based on #2, above). Recommendations for Further Study It is recommended that this study be replicated: 1. Using a larger sample size of neonates to retest this study\u27s hypotheses. 2. Comparing axillary and rectal temperature recordings of a clinical glass thermometer with an electronic thermometer. 3. Specifically determine if gender, age, race, or weight influence thermometer placement time in neonates. 4. Comparing neonatal temperatures in varying environmental temperatures

The International Bathymetric Chart of the Arctic Ocean (IBCAO) Version 3.0

[1] The International Bathymetric Chart of the Arctic Ocean (IBCAO) released its first gridded bathymetric compilation in 1999. The IBCAO bathymetric portrayals have since supported a wide range of Arctic science activities, for example, by providing constraint for ocean circulation models and the means to define and formulate hypotheses about the geologic origin of Arctic undersea features. IBCAO Version 3.0 represents the largest improvement since 1999 taking advantage of new data sets collected by the circum-Arctic nations, opportunistic data collected from fishing vessels, data acquired from US Navy submarines and from research ships of various nations. Built using an improved gridding algorithm, this new grid is on a 500 meter spacing, revealing much greater details of the Arctic seafloor than IBCAO Version 1.0 (2.5 km) and Version 2.0 (2.0 km). The area covered by multibeam surveys has increased from ∼6% in Version 2.0 to ∼11% in Version 3.0

Impact of Enhanced Spatial Resolution in Energy System Modeling: Investigating the Impact of Bidding Zone Disaggregation and Cost-Effective Grid Expansion in the North Sea

Rask handling er nødvendig for a bekjempe effektene av klimaendingene. ˚ A˚ omstille det fossilbaserte energisystemet til et fornybart energibasert system, er avgjørende for a senke utslipp. Den europeiske unionen har satt et m ˚ al for medlem- ˚ slandene sine om a redusere klimagassutslippene med 55% sammenlignet med ˚ nivaene fra 1990 innen 2030[1]. For ˚ a oppn ˚ a dette trenger de mange nye og forny- ˚ bare energikilder, slik som 60 GW planlagt offshore vindkraft i Nordsjøen. Norge pa sin side har som m ˚ al˚ a tildele omr ˚ ader med en samlet kapasitet p ˚ a 30 GW off- ˚ shore vindkraft innen 2040[2]. Energisystem modellering kan bli benyttet for a utforske utfall av lav-utslipp energi ˚ system scenarioer. I denne masteroppgaven ble det opprettet fem ulike scenarier for energisystemmodellen GENeSYS-MOD. Disse er basert pa gradual develop- ˚ ment openENTRANCE-scenariet: en base case, Danmark disaggregert, offshoresone til NO2, offshore-sone koblet til NO2 og DK1, offshore-sone koblet til NO2, DK1 og UK. Disse scenariene ble utforsket for a besvare de følgende forskn- ˚ ingsspørsmalene: ˚ Forskningsspørsmal 1: ˚ Om a disaggregere Danmark har en signifikant be- ˚ tydning pa energisystemet eller om det er neglisjerbart? ˚ Forskningsspørsmal 2: ˚ Hva er den mest kostnadseffektive strategien for nettutvidelse fra det norske offshore vindomradet til nabolandene rundt Nordsjøen? ˚ Resultatene angaende forskningsspørsm ˚ al 1 understreket betydningen av op- ˚ pdeling, da det avdekket en flaskehals i det danske energisystemet som resulterte i en 25% forskjell i installert kapasitet mellom de to scenarioene. Den oppdelte scenarien hadde den laveste totale kapasiteten. Resultatene angaende forskningsspørsm ˚ al 2 viste en tydelig trend som favoris- ˚ erte en sammenkoblet struktur for strømnett i Nordsjøen. Strategien for nettutvidelse, som involverte tilkobling til NO2, DK1 og UK, resulterte i den mest kostnadseffektive løsningen og førte til den mest betydelige kapasitetsutvidelsen av offshore vind i NordsjøenUrgent actions are needed in order to combat the effects of climate change. Transforming the fossil-based energy system over to a renewable energy source-based system is integral to lowering emissions. The European Union has set a target for their member countries to reduce greenhouse gas emissions by 55% compared to 1990 levels by the year 2030 [1]. To achieve this they need a lot of new and renewable energy sources, like the planned 60 GW offshore wind power in the North Sea. Norway on their part aims to allocate areas with a combined offshore wind capacity of 30 GW by 2040 [2]. Energy system models can be utilized in order to explore the outcomes of lowcarbon energy system scenarios. In this thesis, five different scenarios were created for the open-source energy system model, GENeSYS-MOD. These were all based on the gradual development openENTRANCE scenario. A base case, Denmark disaggregated, offshore node connected to NO2, offshore node connected to NO2 and DK1, offshore node connected to NO2, DK1, and UK. These scenarios were studied in order to answer the following research questions: Research question 1: To investigate whether the disaggregation of Denmark into bidding zones has a meaningful impact on the energy system or if it is negligible. Research question 2: What is the cost-effective grid expansion strategy from the Norwegian offshore wind area to the neighboring countries around the North Sea? Results regarding research question 1 highlighted the significance of disaggregation, as it uncovered a bottleneck in the Danish energy system, resulting in a 21.9% difference in installed capacities in Denmark between the two scenarios. The disaggregated scenario had the least total capacity of 63.2 GW in 2050. Results regarding research question 2 showed a clear trend that favored a meshed grid structure in the North Sea. The grid expansion, which connected to NO2, DK1, and UK, resulted in the most cost-effective solution and produced the most significant capacity expansion of offshore wind in the North Sea

Linguistic and auditory temporal processing in children with specific language impairment

TEMA: diversos estudos sugerem a associação do distúrbio específico de linguagem (DEL) ao déficit no processamento auditivo. Pesquisas fornecem evidência de que a discriminação de estímulos breves estaria comprometida em crianças com DEL. Este déficit levaria a dificuldades em desenvolver habilidades fonológicas necessárias para mapear fonemas e decodificar e codificar palavras e frases efetiva e automaticamente. Entretanto, a correlação entre processamento temporal (PT)e distúrbios de linguagem tem recebido pouca atenção. OBJETIVO: analisar a correlação entre duas as áreas: PT (teste de padrão de freqüência - TPF) e Processamento Lingüístico (complexidade sintática). MÉTODO: Dezesseis crianças com desenvolvimento típico de linguagem (8;9 ± 1;1) e sete crianças diagnosticadas com DEL (8;1 ± 1;2) e participaram de TPF e Testes de Compreensão de Complexidade Sintática (TCCS). RESULTADOS: A porcentagem de acerto no TCCS decresceu com o aumento da complexidade sintática (p < 0,01). Na comparação inter-grupos, a diferença no desempenho no TCCS foi estatisticamente significante (p = 0,02). Como esperado, crianças com DEL apresentaram desempenho no TPF fora dos valores de referência.No grupo DEL, as correlações entre os resultados do TPF e do TCCS foram positivas e maiores para frases de alta complexidade sintática (r = 0,97) do que para frases com baixa complexidade sintática (r = 0,51). CONCLUSÃO: Resultados sugerem que o TPF está correlacionado positivamente com habilidades de complexidade sintática. O baixo desempenho no TPF pode servir de um indicativo adicional sobre déficits em processamento lingüístico complexo.Estudos futuros devem considerar, além do aumento da amostra,a análise do efeito do treinamento auditivo temporal de freqüência no desempenho em tarefas de compreensão sintática de alta complexidade.BACKGROUND: several studies suggest the association of specific language impairment (SLI) to deficits in auditory processing.It has been evidenced that children with SLI present deficit in brief stimuli discrimination. Such deficit would lead to difficulties in developing phonological abilities necessary to map phonemes and to effectively and automatically code and decode words and sentences. However, the correlation between temporal processing (TP) and specific deficits in language disorders - such as syntactic comprehension abilities - has received little or no attention. AIM: to analyze the correlation between: TP (through the Frequency Pattern Test - FPT) and Syntactic Complexity Comprehension (through a Sentence Comprehension Task). METHOD: Sixteen children with typical language development (8;9 ± 1;1 years) and seven children with SLI (8;1 ± 1;2 years) participated on the study. RESULTS: Accuracy of both groups decreased with the increase on syntactic complexity (both p < 0.01). On the between groups comparison, performance difference on the Test of Syntactic Complexity Comprehension (TSCC) was statistically significant (p = 0.02).As expected, children with SLI presented FPT performance outside reference values. On the SLI group, correlations between TSCC and FPT were positive and higher for high syntactic complexity (r = 0.97) than for low syntactic complexity (r = 0.51). CONCLUSION: Results suggest that FPT is positively correlated to syntactic complexity comprehension abilities.The low performance on FPT could serve as an additional indicator of deficits in complex linguistic processing. Future studies should consider, besides the increase of the sample, longitudinal studies that investigate the effect of frequency pattern auditory training on performance in high syntactic complexity comprehension tasks