Thèses sur le sujet « Resistance-to-time »

Housing is both a durable good and an investment vehicle, which makes it importantin people’s daily life aswell as for a nation’s economy. This thesis innovatively applies the Sharpe ratio on evaluating the performance of the US residentialhousing market within the time period from 2005:Q1 to 2019:Q3, andinvestigates how this performance would react upon macroeconomic shocks,including sudden changes in GDP growth rate and personal income growthrate, by establishing a vector auto-regression model with the lag order of four.The main results are that: (1)in the long run, direct residential investments are not significantly more profitable than treasury bills but not disappointing compared to the market portfolio of Dow Jones Industrial Average; (2)the performance of residential investments seem to slightly and positively co-move withGDP and personal income growth rate; (3)the long-term impacts that sudden GDP and personal income growths have on the performance seem inconspicuous and tend to mitigate within about three years and (4) limited evidence supports the hypothesis that current housing market performance can help predictfuture GDP growth rate. Based on housing’s two purpose of consumption andinvestment and the empirical results showing that direct investments on residentialproperties have similar risk-adjusted return level to short-term treasurybills, I suggest that financially feasible households purchase their own houseinstead of renting for a long time, and that speculative investors avoid puttingmoney in residential properties unless they have access to inside information.
Bostäder kan betraktas både som en hållbar vara och som ett investeringsinstrument.De är essentiella för människors vardag och har en viktig roll förett lands ekonomi. Denna avhandling använder innovativt Sharpe-förhållandet för att utvärdera hur den amerikanska bostadsmarknaden presterade under perioden2005: kvartal 1 till 2019: kvartal 3. Den försöker även undersöka om denna prestation påverkas av makroekonomiska chocker inklusive plötsligaförändringar i BNP-tillväxttakt och personliga inkomsttillväxthastighet. Detta görs genom att upprätta en vektor autoregression modell med en fördröjningsordningför fyra. De viktigaste resultaten är att: (1) på långsikt är direktabostadsinvesteringar inte betydligt mer lönsamma än statsskuldväxlar dock är det hellre inte en besvikelse jämfört med en marknadsportföljen av Dow JonesIndustrial Average; (2) Prestationen av bostadsinvesteringar verkar vara svagt och samverkar positivit både med BNP och tillväxttakten för personinkomst.(3) De långsiktiga effekterna av plötsliga tillväxter av BNP och personliga inkomster har på utvecklingen verkar vara vaga och tenderar att mildra inomcirka tre år och (4) begränsade bevis stöder hypotesen om att nuvarande bostadsmarknadsresultat kan bidra till att förutsäga framtida BNP-tillväxttakten.Baserat på bostädernas två syften inom konsumtion och investeringar, visar deempiriska resultaten att direkta investeringar i bostadsfastigheter har en liknande riskjusterad avkastningsnivå som kortfristiga statsskuldväxla. Därför föreslår jag att ekonomisk stabila hushåll borde köpa ett eget hus istället för att hyraunder en lång tid, och att spekulativa investerare borde undvika att satsa pengar inom bostadsfastigheter såvida de inte har tillgång till insider-information.

In previous work with mouse lines selected for resistance (R) and susceptibility (S) to fescue toxicosis, R mice had higher activities of Phase II liver enzymes glutathione S-transferase and uridine diphosphate glucuronosyl-transferase than S mice. Objectives of this study were: 1. to determine whether selection for toxicosis response had also caused divergence between lines in hepatic Phase I enzyme activity (as assessed by sleep time following sodium pentobarbital anesthesia), 2. to determine whether sleep time differences between lines were modulated by fescue toxins or enzyme inducers in the diet, and 3. to determine whether sleep time differences among individual mice were correlated with the impact of a toxin-containing diet on their post-weaning growth. In experiment 1, five dietary treatments were assigned to 24 male mice in each line: rodent food control, E+ (50% endophyte-infected fescue seed, 50% control), E+P (E+ with 1000 ppm phenobarbital), E- (50% endophyte-free fescue seed, 50% control), and E-P (E- with 1000 ppm phenobarbital). After four weeks on these diets, mice were challenged with a sleep time test. All mice were then switched to a pelleted rodent food diet. Each mouse then received a second sleep time test, a random 1/4 of the population after one, two, three, and four weeks on the standard diet. Results demonstrated that, regardless of dietary treatment, R mice had a shorter sleep time than S mice, suggesting higher activity of liver Phase I microsomal enzymes. Mice that were fed phenobarbital had significantly shorter sleep time than those whose diets did not include this microsomal enzyme inducer. Time interval between the first and second sleep time did not significantly impact the second sleep time, confirming line differences in the absence of toxins and inducers and with advancing age. In experiment 2, male and female R and S mice were fed an E- diet for 2 weeks, then an E+ diet for 2 weeks, followed by a pelleted rodent food diet for 2 weeks. Mice were then administered a sleep time test. Their growth rate response to fescue toxicosis was quantified as the proportional reduction in gain during two weeks on the E+ diet, compared to gain on E- during the previous two weeks. Sleep time was significantly influenced by line but not by sex or the line x sex interaction. As in Experiment 1, S mice slept longer than their R counterparts. The residual correlation between reduction in gain associated with the E+ diet and sleep time was only 0.04. Thus, under these experimental conditions an individual animal's Phase 1 enzyme activity did not predict how severely its growth rate would be depressed by a toxin-containing diet. Based upon these and previous studies, divergent selection for toxicosis response in mice was successful partially by causing divergence between lines both in Phase I and Phase II liver detoxification enzyme activities. If a heritable, practical, and economical criterion could be identified to quantify such differences in livestock species, then selection for toxicosis resistance might contribute to the solution of this important problem for American agriculture.
Master of Science

In this thesis, I combined observational studies with field and greenhouse experiments to examine selection on life history traits and variation in tolerance and resistance against herbivores in natural populations of the annual herb Arabidopsis thaliana in its native range. I investigated (1) phenotypic selection on flowering time and plant size, (2) the effects of timing of germination on plant fitness, (3) the effect of leaf damage on seed production, and (4) correlations between resistance against a specialist and a generalist insect herbivore. In all three study populations, flowering time was negatively related to plant fitness, but in only one of the populations, significant selection on flowering time was detected when controlling for size prior to the flowering season. The results show that correlations between flowering time and plant fecundity may be confounded by variation in plant size prior to the reproductive season. A field experiment detected conflicting selection on germination time: Early germination was associated with low seedling survival, but also with large leaf rosette before winter and high survival and fecundity among established plants. The results suggest that low survival among early germinating seeds is the main force opposing the evolution of earlier germination, and that the optimal timing of germination should vary in space and time as a function of the relative strength of selection acting during different life-history stages. Experimental leaf damage demonstrated that tolerance to damage was lowest among vegetative plants early in the season, and highest among flowering plants later in the season. Given similar damage levels, leaf herbivores feeding on plants before flowering should thus exert stronger selection on defence traits than those feeding on plants during flowering. Resistance against larval feeding by the specialist Plutella xylostella was negatively correlated with resistance against larval feeding by the generalist Mamestra brassicae and with resistance against oviposition by P. xylostella when variation in resistance was examined within and among two Swedish and two Italian A. thaliana populations. The results suggest that negative correlations between resistance against different herbivores and different life-history stages of herbivores may contribute to the maintenance of genetic variation in resistance.

UA Open Access Publishing Fund
Molecular diagnostics offers quick access to information but fails to operate at a speed required for clinical decision-making. Our novel methodology, droplet-on-thermocouple silhouette real-time polymerase chain reaction (DOTS qPCR), uses interfacial effects for droplet actuation, inhibition relief, and amplification sensing. DOTS qPCR has sample-to-answer times as short as 3 min 30 s. In infective endocarditis diagnosis, DOTS qPCR demonstrates reproducibility, differentiation of antibiotic susceptibility, subpicogram limit of detection, and thermocycling speeds of up to 28 s/cycle in the presence of tissue contaminants. Langmuir and Gibbs adsorption isotherms are used to describe the decreasing interfacial tension upon amplification. Moreover, a log-linear relationship with low threshold cycles is presented for real-time quantification by imaging the droplet-on-thermocouple silhouette with a smartphone. DOTS qPCR resolves several limitations of commercially available real-time PCR systems, which rely on fluorescence detection, have substantially higher threshold cycles, and require expensive optical components and extensive sample preparation. Due to the advantages of low threshold cycle detection, we anticipate extending this technology to biological research applications such as single cell, single nucleus, and single DNA molecule analyses. Our work is the first demonstrated use of interfacial effects for sensing reaction progress, and it will enable point-of-care molecular diagnosis of infections.

Abstract Background Many different variables are important to consider when creating resistancetraining programs. However the lifting speed that exercises are performed with has not beenstudied as extensively as many of the other factors. Some research has indicated that trainingwith specific lifting speeds results in improved strength or hypertrophy adaptations comparedto other lifting tempos, but more research is needed to reach better knowledge on what liftingspeeds are optimal for specific goals.Aim The aim of this study was to analyze the effect of various lifting speeds on differentfactors known to influence resistance training. The measured variables were muscle activity,maximum amount of repetitions performed and time under tension during bench press.Method Thirteen males performed bench press at their individual 6 RM. The exercise wasperformed to fatigue with three different lifting tempos (4 second repetitions, 6 secondrepetitions and repetitions intentionally performed as fast as possible). Number of repetitions performed and total time under tension for each test was recorded in seconds. Surfaceelectromyography (EMG) was used to register muscle activity of pectoralis major anddeltoideus anterior. Reference values were gathered using MVIC (Maximum voluntaryisometric contraction) tests.Results EMG amplitudes were higher in pectoralis major when a fast lifting speed (60.1 ± 7.3% of MVIC) was used compared to the medium (54.8 ± 10.2) and slow (54.3 ± 7.1)conditions. More repetition were performed with faster lifting speeds. The time under tensionwas longer for the slow and medium lifting tempos than for the fast lifting tempo.Conclusion The result from this study can be considered when designing resistance trainingprograms. Based on the increased performance and muscle activity associated with the fastlifting tempo, faster lifting speeds may be beneficial when the training goal is to increasestrength levels. It is difficult to draw any conclusions regarding the optimal lifting tempo forspecific training designed to increase hypertrophy, but the time under tension appears to belonger for slower lifting speeds.

Il rilevamento di gas tossici e pericolosi è sempre stato necessario per motivi di sicurezza. Negli ultimi anni, in particolare, l’attenzione per lo sviluppo di sistemi portatili e a basso costo per il rilevamento dei gas è aumentata notevolmente. Questa tesi presenta circuiti CMOS versatili, veloci, ad alta precisione e basso consumo per applicazioni portatili di rilevamento di gas. I sensori target sono i Metal Oxide Semiconductor (MOX). Questi sensori sono ampiamente utilizzati per la loro intrinseca compatibilità con le tecnologie MEMS integrate. Le tipologie di lettura scelte sono basate su un oscillatore controllato dalla resistenza del sensore stessa, in modo da ottenere una conversione resistenza-tempo. Ciò garantisce un ampio range dinamico, una buona precisione e la capacità di far fronte alle grandi variazioni di resistenza del sensore MOX. Quattro diversi prototipi sono stati sviluppati e testati con successo. Sono state anche eseguite misurazioni chimiche con un vero sensore SnO2 MOX, validando i risultati ottenuti. Le misure hanno mostrato come il sensore e l’interfaccia sia in grado di rilevare fino a 5ppm di CO in aria. Gli ASIC sono in grado di coprire 128 dB di DR a 4Hz di output data rate digitale, o 148 dB a 0.4Hz, garantendo un errore relativo percentuale sempre migliore dello 0,4% (SNDR> 48 dB). Le prestazioni target sono state raggiunte con aggressive strategie di progettazione e ottimizzazione a livello di sistema. È stata utilizzata una tecnologia CMOS a 130nm fornita da Infineon Technologies AG. La scelta di un nodo tecnologico così scalato (rispetto alle tipiche implementazioni in questo settore) ha consentito di ridurre ulteriormente i consumi fino a circa 450 μA. Inoltre, questo lavoro introduce la possibilità di utilizzare la stessa architettura basata su oscillatore per eseguire la lettura di sensori capacitivi. I risultati delle misurazioni con sensori capacitivi MEMS hanno mostrato 116 dB di DR, con un SNR di 74 dB a 10Hz di velocità di trasmissione dati digitale. Le architetture sviluppate in questa tesi sono compatibili con gli standard moderni nel settore del rilevamento del gas per dispositivi portatili.
Detection of toxic and dangerous gases has always been a need for safety purpose and, in recent years, portable and low-cost gas sensing systems are becoming of main interest. This thesis presents fast, high precision, low-power, versatile CMOS interface circuits for portable gas sensing applications. The target sensors are Metal Oxide Semiconductor (MOX) sensors which are widely used due to their inherent compatibility with integrated MEMS technologies. The chosen readout typologies are based on the time-domain Resistor-Controlled Oscillator. This guarantees wide dynamic range, good precision and the ability to cope with the large MOX sensor resistance variations. Four different prototypes have been successfully developed and tested. Chemical measurements with a real SnO2 MOX sensor have also been performed to validate the results, showing a minimum CO detection capability in ambient air of 5 ppm. The ASICs are able to cover 128 dB of DR at 4 Hz of digital output data rate, or 148 dB at 0.4 Hz, while providing a relative error always better than 0.4% (SNDR >48 dB). Target performances have been achieved with aggressive design strategies and system-level optimization, and using a scaled (compared to typical implementations in this field) 130nm CMOS technology provided by Infineon Technologies AG. Power consumption is about 450 μA. Moreover, this work introduces the possibility to use the same oscillator-based architecture to perform capacitive sensors readout. Measurement results with capacitive MEMS sensors have shown 116 dB of DR in CSENS mode, with an SNR of 74 dB at 10 Hz of digital output data rate. The architectures developed in this thesis are compatible with the modern standards in the portable gas sensing industry.

The aim of this thesis was to investigate roller ski characteristics; classical and freestyle roller skis’ rolling resistance coefficients (μR) and classical style roller skis’ static friction coefficients (μS), and to study the influence of different μR and μS on cross-country skiers’ performance and both physiological and biomechanical indices. The aim was also to study differences in skiing economy and efficiency between recreational skiers, female and male junior and senior elite cross-country skiers.The experiments showed that during a time period of 30 minutes of rolling on a treadmill (warm-up), μR decreased significantly (p<0.05) to about 60-65 % and 70-75 % of its initial value for freestyle and classical roller skis respectively. Also, there was a significant influence of normal force on μR, while different velocities and inclinations of the treadmill only resulted in small changes in μR.The study of the influence on physiological variables of a ~50 % change in μR showed that during submaximal steady rate exercise, external power, oxygen uptake, heart rate and blood lactate were significantly changed, while there were non-significant or only small changes to cycle rate, cycle length and ratings of perceived exertion. Incremental maximal tests showed that time to exhaustion was significantly changed and this occurred without a change in maximal power, maximal oxygen uptake, maximal heart rate and blood lactate, and that the influence on ratings of perceived exertion was non-significant or small.The study of classical style roller skis μS showed values that were five to eight times more than the values of μS reported from on-snow skiing with grip-waxed cross-country skis.The subsequent physiological and biomechanical experiments with different μS showed a significantly lower skiing economy (~14 % higher v̇O2), higher heart rate, lower propulsive forces coming from the legs and shorter time to exhaustion (~30 %) when using a different type of roller ski with a μS similar to on-snow skiing, while there was no difference between tests when using different pairs of roller skis with a (similar) higher μS.The part of the thesis which focused on skiing economy and efficiency as a function of skill, age and gender, showed that the elite cross-country skiers had better skiing economy and higher gross efficiency (5-18 %) compared with the recreational skiers, and the senior elite had better economy and higher efficiency (4-5 %) than their junior counterparts, while no differences could be found between the genders.
Syftet med denna avhandling var att undersöka fristils- och klassiska rullskidors rullmotståndskoefficienter (μR) och klassiska rullskidors statiska friktionskoefficienter (μS) samt effekter av olika μR och μS på längdskidåkares prestation vid rullskidåkning på rullande band. Syftet var även att undersöka s.k. åkekonomi och mekanisk verkningsgrad mellan motionärer och kvinnliga och manliga junior- och seniorlängdskidåkare på elitnivå.Experimenten visade att under en period av 30 minuters kontinuerligt rullande, på rullande band, så sjönk μR signifikant (p<0.05) till 60-65 % och 70-75 % av initiala värden, för fristils- respektive klassiska rullskidor. Undersökandet av olika normalkrafter, hastigheter och lutningars påverkan på μR resulterade i en signifikant, negativ korrelation för μR som funktion av normalkraft, medan olika hastigheter och lutningar endast medförde små förändringar av μR.Studien som undersökte fysiologiska effekter av olika μR visade, vid submaximala konstanta arbetsbelastningar, att yttre effekt, syreupptagning, hjärtfrekvens och blodlaktat förändrades signifikant vid ~50 % förändring av μR. Försökspersonernas frekvens och sträcka per frekvens samt skattning av upplevd ansträngning resulterade dock i mestadels icke signifikanta eller små förändringar. Protokollen med successivt ökande arbetsbelastning (maxtest) resulterade i signifikant förändrad tid till utmattning, vid ~50 % förändring av μR. Detta inträffade utan signifikant skillnad i maximal syreupptagning, hjärtfrekvens och blodlaktat, vilket även mestadels gällde för skattning av upplevd ansträngning.Experimenten som undersökte klassiska rullskidors μS visade att dessa erhöll värden som är fem till åtta gånger högre än vad som rapporterats från studier av μS på snö med fästvallade skidor.Den efterföljande studien som undersökte fysiologiska och biomekaniska influenser av olika μS visade, vid submaximala konstanta arbetsbelastningar, att åkekonomin försämrades (~14 % högre syreförbrukning), hjärtfrekvensen ökade, den framåtdrivande kraften från benen på rullskidorna minskade samt att det blev kortare tid till utmattning (~30 %), vid maxtest, när skidåkarna använde rullskidor med en μS i likhet med vad som rapporterats för skidåkning på snö. För arbetsförsöken med olika rullskidor av olika fabrikat med en högre, och likartad, μS förelåg ingen skillnad i de undersökta variablerna.Studien som undersökte åkekonomi och mekanisk verkningsgrad som funktion av prestationsnivå, ålder och kön, visade att elitskidåkarna hade bättre åkekonomi och verkningsgrad (5-18 %) i jämförelse med motionärerna, att seniorerna hade bättre åkekonomi och verkningsgrad (4-5 %) än juniorerna och att ingen skillnad kunde konstateras mellan könen.

Neutropenia febril (NF) constitui complicação frequente do tratamento quimioterápico do câncer e está associada a altas taxas de morbimortalidade. O reconhecimento dos principais fatores associados ao desenvolvimento de desfechos clínicos desfavoráveis na NF é fundamental, uma vez que estes podem ser utilizados como marcadores prognósticos ou alvos terapêuticos. Este estudo objetiva determinar os principais fatores associados com mortalidade, tempo de hospitalização, incidência de bacteremia por patógenos multirresistentes e incidência de choque séptico no início da febre em pacientes hospitalizados com NF secundária à quimioterapia citotóxica para o câncer. Na presente coorte prospectiva composta por 305 episódios consecutivos de NF (em 169 pacientes com câncer) realizada em um hospital terciário no período de outubro de 2009 a agosto de 2011, as seguintes questões de pesquisa foram avaliadas: impacto do tempo de início da antibioticoterapia na mortalidade em 28 dias; fatores relacionados com tempo de hospitalização; impacto dos fatores microbiológicos da bacteremia no desenvolvimento de choque séptico no início do episódio de NF; fatores de risco para bacteremia por patógenos multirresistentes; impacto da bacteremia por Staphylococcus coagulase-negativo na mortalidade em 28 dias. Em 5 publicações distintas, os seguintes resultados foram notados: o atraso do início da antibioticoterapia está associado a maiores taxas de mortalidade em 28 dias; neoplasia hematológica, regimes quimioterápicos de altas doses, duração da neutropenia e bacteremia por Gram-negativos multirresistentes estão associados com períodos prolongados de internação por NF; infecção de corrente sanguínea polimicrobiana, bacteremia por Escherichia coli e bacteremia por Streptococcus viridans estão associados a choque séptico no início do episódio de NF; idade avançada, duração da neutropenia e presença de cateter venoso central estão associados com bacteremia por patógenos multirresistentes; bacteremia por Staphylococcus coagulase-negativo está associada a menores taxas de mortalidade em 28 dias quando comparado à bacteremia por outros patógenos.
Febrile neutropenia (FN) is a common complication of cancer chemotherapy and is associated with high morbidity and mortality rates. Recognition of the main factors associated with the development of adverse clinical outcomes in FN is crucial, given that these factors can be used as prognostic markers or therapeutic targets. This study aims to determine the main factors associated with mortality, length of hospital stay, incidence of bacteremia by multidrug-resistant pathogens and incidence of septic shock at the onset of fever in hospitalized patients with FN secondary to cancer cytotoxic chemotherapy. In the present prospective cohort of 305 FN episodes (in 169 cancer patients) conducted at a tertiary hospital from October 2009 to August 2011, the following research questions were evaluated: impact of time to antibiotic administration on 28-day mortality; factors associated with length of hospital stay; impact of microbiological factors of bacteremia on the development of septic shock at the onset of FN; risk factors for bacteremia by multidrug-resistant pathogens; impact of coagulasenegative Staphylococcus bacteremia on 28-day mortality. In 5 distinct publications, the following results were noted: delay of antibiotic administration is associated with higher 28-day mortality rates; hematologic malignancy, high-dose chemotherapy regimens, duration of neutropenia and bacteremia by multidrug-resistant Gram-negative bacteria are associated with prolonged length of hospital stay; polymicrobial bloodstream infection, bacteremia by Escherichia coli, and bacteremia by viridans sreptococci are associated with septic shock at the onset of FN; advanced age, duration of neutropenia and presence of indwelling central venous catheters are associated with bacteremia by multidrug-resistant pathogens; coagulase-negative Staphylococcus bacteremia is associated with lower 28-day mortality rates compared with bacteremia by other pathogens.

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Introduction: There is strong evidence that obesity leads to an imbalance of the Autonomic Nervous System (ANS), especially in the increase of sympathetic modulation and a decrease in vagal tone, and that associated cardiovascular risk factors may increase the risk of developing cardiovascular diseases. Objective: To analyze the association between cardiovascular autonomic modulation and clinical variables, food consumption and level of physical activity in obese patients. Methodology: A cross-sectional study with 64 volunteers submitted to biochemical tests, accelerometry, 24-hour recall (R24H), and evaluation of cardiac autonomic modulation. For the analysis of heart rate variability (HRV), the R-R (iRR) intervals were captured in the sitting position for 10 minutes. Statistical analysis: Kolmogorov-Smirnov test; linear regression to identify the association between HRV data and BMI, CC, HOMA-IR, insulin, glycemia, MVPAS, TS, VET, macronutrient, SBP and PAD. The multiple linear regression between the indexes of the frequency domain and the adjusted variables CC, HOMA-IR, insulin, glycemia, MVPA, TS, VET, carbohydrate and lipids (p <0.05). Results: Of the 64 severe obese patients analyzed in the present study, 9 were male (14.06%) and 55 female (85.93%), with a mean age of 39.10 ± 7.74 years ( 27 to 58 years). For the anthropometric data evaluated, the mean BMI was 46.61 ± 6.86 kg / m2, with a more frequent degree of morbid obesity (60.93%). The mean WC was 118.83 ± 10.66 cm for men and women, with a higher risk for all males and 84.37% for females. Patients were insulinresistant (HOMA-IR 6.03 ± 4.10 mg / dl). In the MVPA analysis it was verified that the obese patients had a mean of 98.92 ± 41.00 min / week. In the frequency domain, the severely obese had a sympathetic predominance (LF 56.44 ± 20.31 un) and low parasympathetic modulation (HF 42.52 ± 19.18 un). From the Simple Linear Regression analysis, it was observed that the BMI, CC, VET, carbohydrate, lipid, protein, SBP and DBP were not associated with cardiovascular autonomic modulation (p> 0.05). However, a negative association between HOMA-IR and HF (p = 0.049), HOMA-IR and LF / HF variables was observed (p = 0.001). For insulin and glycemia, there was a negative association with the sympatho-vagal balance (p = 0.002 and p = 0.021, respectively). In the AF analysis, there was a negative association between MVPA and the sympathetic component (p = 0.042), and for TS there was a negative association with HF (p = 0.049) and LF / HF (p = 0.036) and LF p = 0.014). For multiple linear regression, CC and HOMAIR values were negatively and significantly associated with HF (p = 0.010). HOMA-IR and lipid values were negatively associated with LF / HF (p = 0.003 and p = 0.043, respectively). There were no associations between insulin, glycemia, MVPA, TS, VET and carbohydrate and cardiac autonomic modulation. Conclusion: The study reveals that, among cardiovascular risk factors, insulin resistance, glycemia, and sedentary time influence the cardiac autonomic modulation of the severely obese, increasing the risk for the occurrence of cardiovascular diseases
Introdução: Existem fortes evidências que a obesidade leva a um desequilíbrio do Sistema Nervoso Autônomo (SNA), sobretudo no aumento da modulação simpática e uma diminuição do tônus vagal e que os fatores de risco cardiovasculares associados podem aumentar o risco de desenvolvimento de doenças cardiovasculares. Objetivo:Analisar a associação entre a modulação autonômica cardiovascular e as variáveis clínicas, consumo alimentar e nível de atividade física em obesos graves.Metodologia: Estudo transversal realizado com 64 voluntários submetidos a exames bioquímicos, acelerometria, recordatório 24 horas (R24H) e avaliação da modulação autonômica cardíaca. Para a análise da variabilidade da frequência cardíaca (VFC), os intervalos R-R (iRR) foram captados na posição sentada durante 10 minutos. Análise estatística: Teste KolmogorovSmirnov; regressão linear simples para identificar a associação entre os dados de VFC e IMC, CC, HOMA-IR, insulina, glicemia, MVPAS, TS, VET, macronutriente, PAS e PAD. A regressão linear múltipla entre os índices do domínio da frequência e as variáveis ajustadas CC, HOMA-IR, insulina, glicemia, MVPA, TS, VET, carboidrato e lipídeos (p<0,05). Resultados: Dentre os 64 pacientes obesos graves analisados no presente estudo, 9 eram do sexo masculino (14,06%) e 55 do sexo feminino (85,93%), com média de idade de 39,10± 7,74 anos (27 a 58 anos). Para os dados antropométricos avaliados, o IMC médio de 46,61 ± 6,86 kg/m2 , com grau de obesidade mórbida mais frequente (60,93%). A CC média de 118,83 ± 10,66 cm para homens e mulheres, com maior risco para todos os homens e para 84,37% das mulheres. Os pacientes demonstraram ser insulinoresistentes (HOMA-IR 6,03 ± 4,10 mg/dl). Na análise do MVPA verificou-se que os obesos graves realizaram uma média de 98,92 ± 41,00min/semana. No domínio da frequência, os obesos graves apresentaram predomínio simpático (LF 56,44 ± 20,31 un) e baixa modulação parassimpática (HF 42,52 ± 19,18 un). A partir da análise de Regressão Linear Simples, foi observado que o IMC, CC, VET, carboidrato, lipídeo, proteína, PAS e PAD não foram associados à modulação autonômica cardiovascular (p>0,05). Porém, foi observado associação negativa entre as variáveis HOMA-IR e HF (p=0,049), HOMA-IR e LF/HF (p=<0,001). Para a insulina e glicemia houve associação negativa com o balanço simpato-vagal (p=0,002 e p=0,021, respectivamente). Na análise da AF, houve associação negativa entre MVPA e o componente simpático (p=0,042), e para o TS verificou-se associação negativa com HF (p=0,049) e LF/HF (p=0,036) e positiva com LF (p=0,014). Para a regressão linear múltipla, os valores de CC e HOMA-IR foram associados negativa e significativamente com HF (p=0,010). Os valores de HOMA-IR e lipídeos em porcentagem foram associados negativamente com a LF/HF (p=0,003 e p=0,043, respectivamente). Não foram observadas associações entre insulina, glicemia, MVPA, TS, VET e carboidrato e modulação autonômica cardíaca. Conclusão: O estudo revela que, dentre os fatores de risco cardiovasculares, a resistência à insulina, glicemia, e o tempo sedentário influenciam na modulação autonômica cardíaca dos obesos graves, aumentando o risco para a ocorrência de doenças cardiovasculares.

Pre-professional ballet dancers are at risk of injury to bone, particularly stress reactions and stress fractures. Low energy availability (LEA), high number of training hours, irregular menstruation, and subsequent poor bone health are factors that may increase this risk. Bone stress injuries (BSI) result in long periods of rehabilitation for young dancers, negatively affect career progression and may indicate poor bone or systemic health, which can affect quality of life in later years. Such injuries occur due to repeated load exposures below the fracture threshold of bone. Whilst the benefits of supplementary resistance training in ballet have been explored with aims to improve performance and reduce injury, there has been no specific focus on reducing bone-related injury. Conversely, resistance training incorporated into youth sports training may reduce risk of injury by up to 68%. Additionally, jumping and multidirectional loading exercises have been shown to improve bone health in adolescents and athlees respectively. High intensity, resistance and impact training (HiRIT) improves bone health in older persons who have low bone density. Thus, it is possible that HiRIT may improve bone density and reduce bone stress injuries in adolescent female ballet dancers. Before large scale testing is considered, the feasibility of HiRIT in an elite ballet setting must be tested. Methods Eighteen female adolescent dancers (baseline age 16.6 ±1.6yrs) training more than 12 hours per week from an elite training school in Brisbane, Queensland were recruited to participate in twice-weekly HiRIT for eight months. Participants completed exercise diaries to determine compliance and progress in the HiRIT. Ballet students and their teachers completed separate researcher-designed, Likert scale questionnaires to gauge satisfaction (perceived worth, enjoyment and benefits) with the HiRIT program. Student participants recalled the previous 12 months injuries pre- and postintervention, estimating days of complete rest and/or modified dance. Bone mass was estimated with dual energy X-ray absorptiometry (DXA) at study commencement and completion, along with trunk extensor strength (kg), simple anthropometrics (height, weight, lower limb girth), and double and single leg jump height (m). A calcium intake questionnaire (AusCal) and the Low Energy Availability in Females Questionnaire (LEAF-Q) were completed to determine menstrual irregularity and identify potential LEA. Exercise history and lower limb hypermobility was also determined. Adverse events were recorded. Recruitment, attendance, and loss to follow up were recorded as percentages. A paired t-test was used to analyse responses to student satisfaction questionnaires of HiRIT (acceptability) and a one sample t-test was used to determine teacher acceptance of HiRIT. A Wilcoxon Rank Signed Test determined differences in days rest and days modified due to injury. Mean percent change for other secondary outcomes was determined. Pearson and Spearman correlations of secondary outcomes were conducted to explore trends, depending on normality testing. COVID19 Note The intervention phase of this study was conducted in 2020 and halted by the unprecedented coronavirus pandemic. Dancers had completed one month of a planned 8- month HiRIT program. A framework for return to sport in a COVID19 environment has been released by the Australian Institute of Sport, detailing events leading to COVID19 arriving in Australia. During the pandemic, dancers were confined to their homes. Modified ballet training was continued via video conference, but it was not possible to continue HiRIT activities. No participants were confirmed to have contracted COVID19. Ballet training returned face to face after 9-11 weeks of isolation. The HiRIT program recommenced two weeks after returning from isolation and resuming normal training. Total HiRIT training time was reduced from 35 weeks to between 23 and 26 weeks. Results HiRIT was not feasible in terms of recruitment (36% of eligible female ballet students) or compliance (60.2 ±18.8) %, however loss to follow up was lower than the anticipated 30% (19%). The program was acceptable (scores ± 30/50) to ballet students (44.0 ± 4.2), p = 0.019, but not to their ballet teachers (22.6 ± 6.4), p = 0.6. Time lost (days of rest or modified training) due to injury was not reduced, nor was the incidence of BSI. No adverse events were recorded. Mean percent improvement in whole body bone mineral density (BMD) (3.63 ± 4.33) and bone mineral content (BMC) (5.11 ± 4.37), lumbar spine BMD (3.23 ± 2.62) and BMC (5.55 ± 3.59), and forearm and back extensor strength (22.16 ± 23.84) were observed. Conclusion HiRIT was not feasible in an elite ballet training institution, due to low recruitment numbers and low compliance. Numbers lost to follow up were low and no adverse events were recorded. Ballet students accepted HiRIT, however ballet teachers did not. There was no reduction in time loss injuries. Future controlled trials or longitudinal follow up are required to determine the clinical significance of bone and performance effects of HiRIT.
Thesis (Masters)
Master of Medical Research (MMedRes)
School of Pharmacy & Med Sci
Griffith Health
Full Text

The effect of the arbuscular mycorrhizal symbiosis at reducing the incidence of root diseases has received considerable attention. However, information on the role of mycorrhizae in reducing disease incidence of Fusarium root rot of beans (Phaseolus vulgaris), caused by the root pathogen Fusarium solani f. sp. phaseoli, is scarce. A study was undertaken to investigate how the arbuscular mycorrhizal fungus (AMF) Glomus intraradices affects disease development and population number of F. solani f. sp. phaseoli in the mycorhizosphere of bean plants growing in an experimental microcosm unit. This newly designed unit facilitated the spatial monitoring and quantification of both the symbiont and pathogen in different ecological soil regions of the mycorrhizosphere using compartmentation based on a physical segregation of roots, colonized or not by AMF (rhizosphere), AMF mycelium alone (mycosphere), or none (bulk soil). To study the interaction between both organisms, the experimental set-up consisted of a randomized complete block design using bean seedlings pre-colonized or not for 28 days by G. intraradices and infected or not for 6 days with F. solani f. sp. phaseoli. Monitoring of population number of the symbiont and the pathogen in bean plants and in the different mycorrhizosphere soil compartments was achieved with quantitative real-time PCR using specific molecular probes for each fungus, and with cultivation-dependant or morphological based methods. The results of this study indicated that non-mycorrhizal bean plants infected with the pathogen had typical root rot symptoms while infected plants that were pre-colonized by G. intraradices remained free of disease. The population number of F. solani f. sp. phaseoli was significantly reduced in the root system and in each of the mycorrhizosphere soil compartments of mycorrhizal infected plants. The mycorrhizosphere population of G. intraradices was not significantly modified, although the p

Context: Gilthead seabream (Sparus aurata) is a highly important farmed fish species specifically in the Mediterranean aquaculture industry. Infectious diseases present a significant threat to the sustainability of aquaculture with high economic losses due to mortalities, reduced productivity, and the necessity of additional treatments/vaccinations. Specific and sensitive methods for the detection of fish pathogens represent useful tools to investigate infection dynamics and enable early detection of the disease for better prevention. Selection and breeding for resistance against infectious diseases is also a highly valuable tool to help prevent or diminish disease outbreaks, and applying genomic information to the currently available advanced selection methods could accelerate the response to selection. The gram-negative bacteria Photobacterium damselae subsp. piscicida (Phdp) and the ectoparasite Sparicotyle chrisophrii (Sc) are two of the most important pathogens affecting seabream cultivation. Purpose of the study: The aims of this work are: (i) to investigate the genomic prediction of resistance to two highly problematic diseases in seabream through the application of 2b-RAD with the objective of achieving selective breeding goals and (ii) to design an effective assay for the detection and quantification of Phdp. Materials and methods: (i) 1233 and 1001 seabream individuals were challenged trough intramuscular injection with a virulent strain of Phdp and by co-habitation with naturally Sc-infected seabreams, respectively. Animals were monitored daily and data of dead/survived fish and number of parasites in the gills/body length were recorded. Genomic DNA was extracted from the finfish of all individuals and used to construct 2b-RAD libraries. Data were analyzed in order to find SNP based genotypes (GATK, SAMtools), perform Genome-Wide Association Studies, estimate breeding values (ASReml 4.0) and construct linkage-maps (Lep-Map v2). (ii) A primer set was designed from a partial sequence of the bamB gene (Primer3 web) considering two SNPs that discriminate between Phdp and its strictly correlated subspecies Phdd. The assay was tested for specificity/sensitivity on laboratory-generated samples as well as on previous experimentally infected seabream tissue samples. Results and discussion: (i) The reference catalogue contained 175,725 and 269,660 tags for the Phdp and the Sc challenge, respectively. The SNP detection process yielded genotypic data for 19,313 and 21,773 quality SNPs for Phdp and Sc, respectively, both grouped into 24 linkage groups (LG), which are consistent with the karyotype of this species. Genomic heritability for resistance to photobacteriosis was 0.31-0.33 and genomic heritability for tolerance to Sc was 0.11-0.22, suggesting potential to enhance both resistances through family-based selection. Estimated breeding values (EBV) using genomic (GBLUP) information presented 5-43% higher accuracy in comparison to those measured using the only pedigree information (PBLUP). GWAS revealed a quantitative trait locus (QTL) including 7 SNPs at LG17 which presented significant association with resistance to Phdp, while one SNP (LG17) was found affecting tolerance to Sc. (ii) The molecular method proposed for P. damselae diagnosis, with high specificity and sensitivity, proved to be suitable for detection, quantification and subspecies identification in one-step, overcoming the limitations of previous assays. Conclusions: The SNPs discovered through 2b-RAD genotyping could be used to implement new marker-assisted selection programs for the generation of more resistant fish, preventing important disease outbreaks in fish farms. In addition, the original molecular method proposed holds the potential to improve the current knowledge of Phdp infection dynamics and the development of better strategies to control this important fish disease.
Contesto: L’ orata (Sparus aurata) è una specie ittica molto importante per il settore dell'acquacoltura nel Mediterraneo. Le malattie infettive rappresentano una minaccia significativa per questo settore, provocando elevate perdite economiche dovute a mortalità, riduzione della produttività e la necessità di trattamenti / vaccinazioni aggiuntivi. Metodi specifici e sensibili per il rilevamento di patogeni rappresentano strumenti utili per studiare le dinamiche di infezione e consentirne una diagnosi precoce per una migliore prevenzione. La selezione per la resistenza alle malattie infettive rappresenta anch’essa uno strumento prezioso per aiutare a prevenire o ridurre i focolai di malattie; l'applicazione delle informazioni genomiche ai metodi di selezione avanzati attualmente disponibili, potrebbe accelerare la risposta alla selezione. Il batterio gram-negativo Photobacterium damselae subsp. piscicida (Phdp) e l'ectoparassita Sparicotyle chrysophrii (Sc) sono due importanti patogeni che colpiscono la coltivazione delle orate. Scopo dello studio: Gli obiettivi di questo lavoro sono: (i) studiare la previsione genomica della resistenza a due malattie altamente problematiche in orata attraverso l'applicazione di strumenti genomici innovativi (2b-RAD) e (ii) progettare un saggio efficace per il rilevamento e la quantificazione di Phdp. Materiali e metodi: (i) 1233 e 1001 individui di orata sono stati infettati sperimentalmente rispettivamente tramite iniezione intramuscolare con un ceppo virulento di Phdp e per co-abitazione con orate naturalmente infette da Sc. I pesci sono stati monitorati giornalmente. In questo contesto sono stati registrati dati quali numero morti / sopravvissuti, numero di parassiti nelle branchie / lunghezza. Il DNA genomico è stato estratto da tessuto di pinna da tutti gli individui e utilizzato per costruire le librerie 2b-RAD. I dati sono stati analizzati al fine di trovare i genotipi basati su SNPs (GATK, SAMtools), eseguire genome-wide association studies (GWAS), stimare i parametri genetici (ASReml 4.0) e costruire mappe di linkage (Lep-Map v2). (ii) Un set di primer è stato progettato su una porzione di sequenza del gene bamB (Primer3 web) considerando due SNP che discriminano tra Phdp e la specie a cui esso è strettamente correlato, Phdd. Il saggio è stato testato per specificità / sensibilità sia su campioni generati in laboratorio che su campioni di tessuto di orata precedentemente infettati sperimentalmente. Risultati e discussione: (i) Il catalogo di riferimento è risultato contenere rispettivamente 175.725 e 269.660 per gli esperimenti con Phdp e Sc. La SNP discovery ha prodotto dati genotipici per 19.313 e 21.773 SNP di alta qualità per Phdp e Sc, rispettivamente, entrambi raggruppati in 24 gruppi di linkage (LG), sono coerenti con il cariotipo di questa specie. L'ereditabilità genomica per la resistenza alla fotobatteriosi è risultata 0,31-0,33 mentre l'ereditabilità genomica per la tolleranza a Sc 0,11-0,22, suggerendo l’esistenza di un potenziale per migliorare entrambe le resistenze attraverso la selezione. Le stime dei valori riproduttivi (EBV) mediante informazioni genomiche (GBLUP) hanno presentato un'accuratezza del 5-43% superiore rispetto a quelle misurate utilizzando le sole informazioni del pedigree (PBLUP). La GWAS ha rivelato un quantitative trait locus (QTL) comprendente 7 SNPs nel LG17, avente un'associazione significativa con la resistenza al Phdp, mentre uno SNP (LG17) è stato riscontrato influenzare la tolleranza a Sc. (ii) Il metodo molecolare proposto per la diagnosi di P. damselae, con un'elevata specificità e sensibilità, si è dimostrato idoneo per l'individuazione, la quantificazione e l'identificazione delle due sottospecie in un unico step, superando i limiti delle analisi precedenti. Conclusioni: gli SNPs scoperti attraverso la genotipizzazione 2b-RAD potrebbero essere utilizzati per implementare nuovi programmi di selezione assistita da marcatori per la generazione di pesci più resistenti, prevenendo importanti epidemie in allevamenti ittici. Inoltre, l’innovativo metodo molecolare proposto potrebbe migliorare l'attuale conoscenza delle dinamiche dell'infezione da Phdp e lo sviluppo di migliori strategie per controllare questa importante malattia in orata.

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Thesis (M.S.)--University of South Florida, 2003.
Includes bibliographical references.
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ABSTRACT: Bacterial source tracking (BST) methods often involve the use of phenotypic or genotypic fingerprinting techniques to compare indicator bacteria such as Escherichia coli isolated from unknown sources against a library of fingerprints from indicator bacteria found in the feces of various known source animals. The predictive capability of a library is based in part on how well the library isolates reflect the true population diversity of indicator bacteria that can potentially impact a water body. The purpose of this study was to compare the behavior of E. coli population structures in the feces of humans, beef cattle and horses across different parameters. Ribotyping and antibiotic resistance analysis were used to "fingerprint", or subtype E. coli isolates. Significantly greater diversity was observed in the E. coli population of horses compared to the human or beef cattle sampled.
ABSTRACT: Subtype sharing between individuals from all host categories was infrequent, therefore the majority of E. coli subtypes were sampled from a single individual. The dominant E. coli populations of nine individuals (three per host source category) were monitored over time, which demonstrated that E. coli subtypes within a host individual vary on a monthly time frame, and an increase in the frequency of subtype sharing was noted between individuals within the same source group over time. The E. coli population of a single human that had just finished antibiotic treatment was studied on a daily basis for one month. The loss of an E. coli subtype with high antibiotic resistance was observed over time, however there was a single dominant E. coli subtype that was present at every sampling event during the entire month. Geographic distinctiveness of E. coli populations was investigated by sampling four herds located in different geographical regions. We observed that E.
ABSTRACT: coli populations are not geographically distinct, but are somewhat individual-specific, as most E. coli isolates had a subtype that was found in a single individual. This study defines factors that should be considered when constructing a successful BST library, and suggests that E. coli may not be the appropriate indicator organism for BST.
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Autoinducer 2 (AI-2) is a quorum sensing signal employed by bacteria to coordinate their response to environmental stresses. The objective of this study was to determine the relationship between presence of AI-2 molecules, exposure to sub-therapeutic tetracycline, the expression of genes associated with the conjugal transfer of antibiotic resistance plasmids, and the conjugal transfer of these plasmids in Escherichia coli. The studies showed that AI-2 activity increased in Tets E. coli in the presence of tetracycline (2 µg/mL) under both batch and continuous culture conditions. The presence of AI-2 molecules induced tetracycline tolerance development in Tets E. coli. The studies showed that the survival rates of Tets E. coli exposed to AI-2 molecules were significantly higher compared to the cells not exposed to AI-2 molecules or cells that were exposed to only LB (Lauria-Bertani) broth. Molecular analyses using real-time PCR indicate that the expression of at least one conjugation-associated gene (trbC) is increased 9-fold in cells exposed to AI-2 molecules in the presence of sub-therapeutic tetracycline compared to its negative controls. The transconjugation frequency of the plasmid RP4 carrying the tet(A) gene increased between 10-100 fold in the presence of AI-2 molecules. In companion studies, AI-2-like activity was detected in fish, tomatoes, cantaloupes, carrots and milk samples. Interestingly, ground beef and poultry meat contained substances that appear to inhibit AI-2 activity. Collectively, these results highlight the potential importance of bacterial quorum sensing signals such as AI-2 in the response of bacterial cells to environmental stimuli and the possible role of quorum sensing signals in the quality and safety of foods.

Current methods for measuring energy flow rate in a pipe use a variety of invasive sensors, including temperature sensors, turbine flow meters, and vortex shedding devices. These systems are costly to buy and install. A new approach that uses non-invasive sensors that are easy to install and less expensive has been developed. A thermal interrogation method using heat flux and temperature measurements is used. A transient thermal model, lumped capacitance method LCM, before and during activation of an external heater provides estimates of the fluid heat transfer coefficient h and fluid temperature. The major components of the system are a thin-foil thermocouple, a heat flux sensor (PHFS), and a heater. To minimize the thermal contact resistance R" between the thermocouple thickness and the pipe surface, two thermocouples, welded and parallel, were tested together in the same set-up. Values of heat transfer coefficient h, thermal contact resistance R", time constant �[BULLET], and the water temperature �[BULLET][BULLET], were determined by using a parameter estimation code which depends on the minimum root mean square RMS error between the analytical and experimental sensor temperature values. The time for processing data to get the parameter estimation values is from three to four minutes. The experiments were done over a range of flow rates (1.5 gallon/minute to 14.5 gallon/minute). A correlation between the heat transfer coefficient h and the flow rate Q was done for both the parallel and the welded thermocouples. Overall, the parallel thermocouple is better than the welded thermocouple. The parallel thermocouple gives small average thermal contact resistance average R"=0.00001 (m2.�[BULLET][BULLET]/W), and consistence values of water temperature and heat transfer coefficient h, with good repeatability and sensitivity. Consequently, a non-invasive energy flow rate meter or (BTU) meter can be used to estimate the flow rate and the fluid temperature in real life.
MS

This thesis has investigated the fire performance and design of light gauge cold-formed steel frame walls under realistic fires which occur in modern buildings. It examined the appropriateness of using the standard fire curve to represent the modern building fires in full scale laboratory tests and developed suitable realistic design fire curves. Experimental and numerical studies of light gauge steel frame walls using realistic fires led to the verification of existing fire design rules based on Australian and International standards and the development of simplified fire design rules. This research has significantly improved the understanding of fire severity in modern buildings and developed valuable fire design tools for light gauge steel frame walls used in these buildings.

L’objectif de cette thèse est de développer des solveurs numériques et des méthodologies afin d’améliorer le temps de calcul et la précision des simulations de tenue à la mer et de résistance ajoutée sur houle. Tout d’abord, une synthèse de l’algorithme du solver foamStar développé en interne est effectuée. A partir de cette analyse, une modification est proposée afin de pouvoir utiliser le "Multidimensional Universal Limiterfor Explicit Solution" (MULES) avec un schéma temporel backward d’ordre deux. Ensuite, plusieurs études successives sont réalisées afin de : vérifier l’implémentation du schéma backward ; définir une configuration numérique et des maillages efficaces pour la simulation de houle. Les cas d’étude sont : les tourbillons de Taylor-Green, la houle régulière non linéaire se propageant dans un domaine periodique, et enfin, la houle régulière générée avec des zones de relaxation et des configurations numériques proches de celles utilisées pour des applications navales. Dans la dernière partie de cette thèse, une étude préliminaire est réalisée en simulant un porte-conteneur avec une vitesse d’avance dans des houles régulières de face. Les recommandations définies tout au long de cette thèse sont également évaluées
The objective of the present thesis is to develop solvers and methodologies in order to improve the computational cost andthe accuracy with regard to the thematics of seakeeping and added resistance. First, a synthetic workflow of the algorithmof the in-house solver foamStar is proposed. From this analysis a modification is proposed in order to use the Multidimensional Universal Limiter for Explicit Solution (MULES) with a second-order backward time scheme. Then, successive studies are done in order to: verify the implementation of the backward scheme; define an efficient numerical set-up and adequate mesh structures for numerical wave simulations. The case studies are, Taylor-Green vortices, nonlinear regular wave propagating in a periodic domain, and finally, regular waves generated with relaxation zones considering numerical configurations close to what is used for naval applications. In the last part of this Thesis, a preliminary study is done simulating a containership with forward speed in head regular waves. The recommendations derived all along this thesis are also evaluated

碩士
國防醫學院
微生物及免疫學研究所
104
The entire genome of influenza A virus is composed of eight RNA segments which are separately recognized as different sequences with individual identification numbers on database. Current studies are therefore limited by such database architecture which allows mutation or polymorphism identification within only one segment at a time with no further extension potential to inter-segment evolution tracking. In order to perform whole genome analysis, we re-organized existing Influenza database by align all the protein sequences under the name of viral strain and consider the entire coding as a single item in the system. Consequently, virus can be grouped at given position of amino acid character and the rest proteome are also sorted into the same group so that further comprehensive analyses on other segments can be achieved. Moreover, multi-layer sub-grouping including date and area of isolation and host species can be performed as well in our Excel-based system. We have also developed an automated analysis algorism to quickly identify every polymorphic position on entire genome and map the individual correlation almost instantly on dynamic graph, with a time-lapse analysis capability to further dissect simple correlation or potential cause and effect relationships between the two variables. To the best of our knowledge, this is the first tool that allows genome-wide, cross-segment, time-lapse analysis tool to identify potential permissive mutations that confers Influenza Oseltamivir resistance which potentially will facilitate the investigation of novel hypothesis systematically and efficiently.

MSc (Med), Virology, Faculty of Health Sciences, University of the Witwatersrand
Introduction High resolution melting analysis (HRMA) accurately, rapidly and cost effectively detects single nucleotide polymorphisms by monitoring DNA dissociation kinetics. This technology was applied to HIV samples to assess whether it could be used to detect clinically relevant drug resistance mutations. Methods HRMA-PCR assays incorporating unlabeled probes were designed to genotype 12 mutation codons in the HIV-1 p66/p51 of engineered plasmids and 116 HIV-1 samples. Results HRMA correctly genotyped 63%-88% of the K103N, Y181C, M184V, Q151M and G190A mutations. Each assay had a 1.7%-3.4% discordance, most of which was due to the increased analytical sensitivity of HRMA (~5-20%). Only mutant K65R and V106M were correctly identified while the 41, 67, 70, 215 and 225 codons could not be genotyped. Assay modifications had some success in masking the affects of polymorphisms. Conclusion These assays can be used for genotyping selected major HIV-1 resistance mutations and should be further developed as a resistance surveillance tool.

Die Intensivierung des Rapsanbaus in den letzten Jahren hat zu einem verstärkten Aufkommen des bodenbürtigen Gefäßpathogens V. longisporum geführt. Die für den Pilz charakteristischen Mikrosklerotien können langjährig im Boden überdauern, akkumulieren und somit zur fortdauernden Bodenkontamination führen. Eine Infektion mit V. longisporum kann bereits im Herbst erfolgen, wenn durch Wurzelexsudate stimulierte Mikrosklerotien auskeimen und direkt die Wurzelepidermis der Rapspflanze penetrieren. Einer sowohl intra-als auch interzellulär gerichteten Ausbreitung bis zu den Gefäßelementen schließt sich eine langanhaltende Phase des Pilzes im Gefäßsystem an. In dieser latenten Phase zeigen sich keine auffälligen Symptome an der Pflanze, erst zum Ende der Pflanzenentwicklung zeigt sich halbseitige Stängelverbräunung und vorzeitige Abreife kann zu Ertragseinbußen führen. Der Pilz bleibt so lange auf die Gefäße beschränkt bis die Pflanze in die Seneszenzphase eintritt. Dann erfolgt eine Besiedelung der angrenzenden parenchymatischen Zellen und die Bildung von Mikrosklerotien. Mit Pflanzenresten können diese wieder in den Boden gelangen. Da derzeit keine adequaten Pflanzenschutzmittel zur Verfügung stehen, ist der Anbau resistenter Sorten eine wirkungsvolle Maßnahme die Verbreitung des Pilzes einzudämmen und der Anreicherung von Mikrosklerotien im Boden entgegenzuwirken. Im Rahmen dieser Arbeit wurde ein entscheidender Beitrag zur Züchtung neuer resistenter Genotypen geleistet. Phänotypisierungen zur Identifizierung resistenter B. napus-Linien (darunter auch DH-Linien) erfolgten unter kontrollierten Bedingungen im Gewächshaus in Göttingen. Darüber hinaus wurde die Resistenz ausgewählter B. napus-Linien in zwei aufeinander folgenden Jahren anhand von Feldversuchen in Göttingen, an verschiedenen Standorten in Norddeutschland und an einem Standort in Südschweden evaluiert. Eine Untersuchung der von 2004 bis 2009 im Gewächshaus getesteten B. napus Akzessionen wurde hinsichtlich der Häufigkeitsverteilungen der berechneten normierten AUDPC-Werte betrachtet. So konnte deutlich gezeigt werden, dass sich das Resistenzlevel in den aktuellsten Screenings deutlich verbessert hat im Vergleich zum Beginn der Screenings. Die Reproduzierbarkeit der Screenings wurde deutlich durch die Betrachtung der normierten AUDPC-Werte der Referenzsorten ‘Falcon’ und ‘Express’. So waren die normierten AUDPC-Werte der mittelgradig resistenten Referenzsorte ‘Express’ durchgängig niedriger im Vergleich zu der anfälligen Sorte ‘Falcon’, was für die Robustheit der Methodik spricht. Der Vergleich zwischen Gewächshaus- und Feldversuchen zeigte, dass eine geringe Korrelation zwischen den im Feld und Gewächshaus getesteten Akzessionen besteht und macht die Komplexität der Untersuchungen deutlich. Ein Screening von Genotypen kann jedoch nur schnell und in großem Umfang unter Gewächshaus-Bedingungen erfolgen. Die erweiterte Testung im Feld ist dann jedoch nötig, um die Resistenz unter zusätzlichem abiotischem Stress zu evaluieren. Neben der Bewertung des Befallsgrades (Befallshäufigkeit, Befallsstärke) mittels Stoppelbonitur wurde eine alternative Bewertungsmethode zur Evaluierung der Resistenz im Feld kultivierter Rapspflanzen gegenüber V. longisporum entwickelt. Die Entwicklung einer sensitiven real-time PCR (qPCR)-Methode zur Detektion von V. longisporum in Rapsstängeln beinhaltete die Bewertung zweier unterschiedlicher Primer, abzielend auf die internal transcribed spacer (ITS) Region bzw. auf die β-Tubulin-Region, die hinsichtlich ihrer Sensitivität und Spezifität analysiert wurden. Die hier getesteten ITS-Primer wiesen eine hohe Sensitivität gegenüber genomischer Pilz-DNA auf, jedoch wurde keine Spezifität gegenüber V. longisporum Isolaten festgestellt; vielmehr wurden V. dahliae Isolate und zwei weitere Verticillium Arten mit ITS-Primern detektiert. Das zweite getestete Primerpaar zeigte hingegen eine hohe Spezifität gegenüber V. longsiporum Isolaten, lediglich 3 von 15 getesteten V. longisporum Isolaten wurden nicht erfasst. Die Sensitivität dieser Primer war jedoch im Vergleich zu den ITS-Primern stark verringert. Die ITS-basierte qPCR Analyse führte zur Detektion des Pathogens noch vor der Symptomausbildung im Feld. So konnte in der Saison 2008/09 am Standort Göttingen gezeigt werden, dass frühe Infektionen bereits zu BBCH 65 auftraten und innerhalb weniger Wochen eine massive Besiedelung anfälliger Sorten erfolgte. Zudem konnte die pilzliche DNA-Konzentration in infizierten Rapsstängeln verschieden anfälliger Sorten quantifiziert und eine Korrelation zwischen der herkömmlichen Stoppelbonitur und dem Screening im Gewächshaus hinsichtlich der Einordnung der Resistenzniveaus hergestellt werden. Dies unterstützt die Verwendung der molekularen Methode als Alternative zur Stoppelbonitur. Neben der Verbesserung der Detektion von V. longisporum im Feld wurde die Pathogen-Wirt-Interaktion hinsichtlich der Ausbildung von Resistenzmechanismen charakterisiert. Dazu wurden zwei verschieden anfällige B. napus-Linien nach Inokulation mit V. longisporum sowohl auf histologischer als auch auf molekularbiologischer Ebene im Hypokotylbereich untersucht. Dieser Abschnitt, der den Bereich vom Wurzelhals bis zum Keimblattansatz markiert, konnte in vorangegangenen Untersuchungen als Schlüsselgewebe für die Ausbildung von Resistenzstrukturen identifiziert werden (Eynck et al., 2009). Anknüpfend an diese Untersuchungen wurden mittels Transmissionselektronenmikroskopie (TEM) genotypabhängige Resistenzstrukturen wie Gefäßverschlüsse und morphologische Veränderungen des Gefäßbereiches untersucht und begleitende qPCR-Messungen dokumentierten die Pathogenausbreitung. Diese ließen erkennen, dass der anfällige Genotyp im Vergleich zum resistenten Genotyp schneller besiedelt wird. Jedoch zeigten beide mit V. longisporum inokulierten Genotypen ähnliche ultrastrukturelle Veränderungen im vaskulären Bereich. So konnten Veränderungen an vaskulären Zellwänden wie elektronendichte Ablagerungen und Degradation primärer Zellwände im Bereich der Tüpfel beobachtet werden. Zudem konnte das Verschließen von Gefäßelementen mittels gelartiger Strukturen nachgewiesen werden. Unsere Untersuchungen lassen vermuten, dass der resistente Genotyp fähig ist Infektionen schneller zu erkennen und Resistenzmechanismen zielgerichteter und intensiver zu aktivieren. Da eine V. longisporum-Infektion in dem untersuchten resistenten Genotyp SEM 05-500256 u. a. zu einer verstärkten Bildung von Gefäßbarrieren im Hypokotylbereich führt (Eynck et al., 2009), wurde eine Beeinträchtigung des pflanzlichen Wassertransportes vermutet. Zur Klärung dieser Frage wurde der resistente Genotyp zusätzlich zu einer Infektion mit V. longisporum Trockenstressbedingungen (30% Feldkapazität) ausgesetzt und physiologische Parameter (Gaswechselmessungen), Befallswerte (AUDPC, Stauchung) und agronomische Parameter (Phänologisches Entwicklungsstadium, Anzahl Seitentriebe, Ertragsparameter) erfasst und im Vergleich zu der anfälligen Sorte ‘Falcon’ evaluiert. Weder die Befallsparameter noch die agronomischen Parameter zeigten eine Beeinträchtigung der Resistenz von SEM bei V. longisporum-Infektion in Kombination mit Trockenstress an.

International Atomic Energy Agency (IAEA) safeguards are one method of proliferation resistance which is applied at most nuclear facilities worldwide. IAEA safeguards act to prevent the diversion of nuclear materials from a facility through the deterrence of detection. However, even with IAEA safeguards present at a facility, the country where the facility is located may still attempt to proliferate nuclear material by exploiting weaknesses in the safeguards system. The IAEA's mission is to detect the diversion of nuclear materials as soon as possible and ideally before it can be weaponized. Modern IAEA safeguards utilize unattended monitoring systems (UMS) to perform nuclear material accountancy and maintain the continuity of knowledge with regards to the position of nuclear material at a facility. This research focuses on evaluating the reliability of unattended monitoring systems and integrating the probabilistic failure of these systems into the comprehensive probabilistic proliferation resistance model of a facility. To accomplish this, this research applies reliability engineering analysis methods to probabilistic proliferation resistance modeling. This approach is demonstrated through the analysis of a safeguards design for the Example Sodium Fast Reactor Fuel Cycle Facility (ESFR FCF). The ESFR FCF UMS were analyzed to demonstrate the analysis and design processes that an analyst or designer would go through when evaluating/designing the proliferation resistance component of a safeguards system. When comparing the mean time to failure (MTTF) for the system without redundancies versus one with redundancies, it is apparent that redundancies are necessary to achieve a design without routine failures. A reliability engineering approach to probabilistic safeguards system analysis and design can be used to reach meaningful conclusions regarding the proliferation resistance of a UMS. The methods developed in this research provide analysts and designers alike a process to follow to evaluate the reliability of a UMS.

Plants and microorganisms interact with each other constantly, with some interactions being mutually beneficial and others being detrimental to the plants. The features of the organisms involved in such interactions will determine the characteristics of individual pathosystems. Plants respond readily to pathogen attacks, regardless of the pathosystem; furthermore, variation in the resistance to pathogens within species is common and well documented in many plant species. The variability in pathogen resistance is at the core of genetic improvement programs for disease resistance. True resistance to pathogens in plants is a genetically determined and complex trait that can involve both constitutive and induced mechanisms at different levels of organization. The complexity of this phenomenon makes the study of compatible plant - pathogen interactions challenging, and typically, disease resistance studies focus on specific aspects of a pathosystem, such as field resistance, anatomical or physiological features of resistant plants, or molecular mechanisms of resistance. The Thuja sp. - Didymascella thujina (E.J. Durand) Maire interaction is an important pathosystem in western North America, which has been studied for more than five decades. Western redcedar (Thuja plicata Donn ex D. Don) is very susceptible to cedar leaf blight (D. thujina), a biotroph that affects the tree at all stages, although seedlings are the most sensitive to the pathogen. The characteristics of the Thuja sp. - D. thujina interaction, the wealth of information on the pathosystem and the excellent Thuja sp. genetic resources available from the British Columbia Ministry of Forests, Lands, Natural Resource Operations and Rural Development make this interaction an ideal system to advance the study of disease resistance mechanisms in conifers. This Doctoral project presents a comprehensive investigation of the constitutive and induced resistance mechanisms against D. thujina in T. plicata, Thuja standishii (Gord.) Carrière and a Thuja standishii x plicata hybrid at the phenotypic and gene expression levels, undertaken with the objective of exploring the resistance mechanisms against the biotroph in these conifers. The project also aimed to establish base knowledge for the future development of markers for marker-assisted breeding of T. plicata. The investigations included a combination of histological, chemical and next generation sequencing (NGS) methodologies. NGS data were analyzed, in addition to the traditional clustering analyses, with cutting edge machine learning methods, including grade of membership analysis, dynamic topic modelling and stability selection analysis. The studies were progressively more controlled to narrow the focus on the resistance mechanisms to D. thujina in Thuja sp. Histological characteristics related to D. thujina resistance in Thuja sp. were studied first, along with the relationship between climate of origin and disease resistance. The virulence of D. thujina was also documented early in this project. Chemical and gene expression constitutive and induced responses to D. thujina infection in T. plicata seedlings were studied next. T. plicata clonal lines were then comprehensively studied to shed light on the mechanisms behind known physiologically determined resistance. A holistic investigation of the resistance mechanisms to D. thujina in T. standishii, T. plicata and a T. standishii x plicata hybrid explored the possibility of a gene-for-gene resistance model. Thirty-five T. plicata families were screened during the four field seasons carried out between 2012 and 2015, totalling more than 1,400 seedlings scored for D. thujina severity. Thirteen of those families were used in the five studies performed during the program, along with two T. plicata seedling lines self-pollinated for five generations and three T. plicata clonal lines. One T. standishii clonal line, and one T. standishii x plicata clone were also investigated during the program. A total of 16 histological and anatomical characteristics were studied in more than 750 samples, and more than 270 foliar samples were analyzed for 60 chemical and nutritional compounds. Almost one million transcriptomic sequences in four individually assembled reference transcriptomes were examined during the program. The results of the project support the variability in the resistance to D. thujina in T. plicata, as well as the higher resistance to the pathogen in plants originating from cooler and wetter environments. The data collected also depicted the existence of age-related resistance in T. plicata, and confirmed the full resistance to the disease in T. standishii. Western redcedar plants resistant and susceptible to D. thujina showed constitutive differences at the phenotypic and gene expression levels. Resistant T. plicata seedlings had thicker cuticles, constitutively higher concentrations of sabinene, alpha-thujene, and higher levels of expression of NBS-LRR disease resistance proteins. Resistant clones of T. plicata and T. standishii had higher expression levels of bark storage proteins and of dirigent proteins. Plants from all ages, species and resistance classes studied that were infected with D. thujina showed the accumulation of aluminum in the foliage, and increased levels of sequences involved in cell wall reinforcement. Additional responses to D. thujina infection in T. plicata seedlings included the downregulation of some secondary metabolic pathways, whereas pathogenesis-related proteins were upregulated in clonal lines of T. plicata. The comprehensive approach used here to study the Thuja sp. - D. thujina pathosystem could be applied to other compatible plant-pathogen interactions.
Graduate
2020-08-31

As a social worker practising in long-term residential care for people living with dementia, I am alarmed by discourses in the media and health policy that construct persons living with dementia and their health care needs as a threatening “rising tide” or crisis. I am particularly concerned about the material effects such dominant discourses, and the values they uphold, might have on the collective provision of care and support for our elderly citizens in the present neoliberal economic and political context of health care. To better understand how dominant discourses about dementia work at this time when Canada’s population is aging and the number of persons living with dementia is anticipated to increase, I have rooted my thesis in poststructural methodology. My research method is a discourse analysis, which draws on Foucault’s archaeological and genealogical concepts, to examine two contemporary health policy documents related to dementia care – one national and one provincial. I also incorporate some poetic representation – or found poetry – to write up my findings. While deconstructing and disrupting taken for granted dominant crisis discourses on dementia in health policy, my research also makes space for alternative constructions to support discursive and health policy possibilities in solidarity with persons living with dementia so that they may thrive.
Graduate
0452
0680
0351
macsuz@shaw.ca