Les théories actuelles suggèrent que l'efficacité de traduction (nombre de protéines produitespar ARN messager ; notion spécifique à chaque à gène) reste constante lorsque le taux decroissance varie. Néanmoins, une efficacité de traduction constante est incompatible avec lafaible corrélation observée, à l’échelle du génome, entre l’évolution en fonction du taux decroissance de la concentration des ARN messagers et des protéines pour lesquelles ils codent.Pour faire face à ce paradoxe, nous avons développé un modèle mathématique de la traductionbasé sur les connaissances actuelles de ce processus au niveau moléculaire. L’exploration despropriétés du modèle nous a amené à conduire des expériences de transcriptomique, de PCRquantitative et de Live Cell Array (LCA) dont l’analyse a montré que l'efficacité de traductiondiminue jusqu'à 4 fois entre faible et fort taux de croissance chez la bactérie modèle Bacillussubtilis. Notre modèle a révélé que la chute de l’efficacité de traduction repose sur une chutede la concentration des ribosomes libres. Pour étudier les conséquences de la chute desribosomes libres sur la production des protéines, nous avons rationnellement défini à partir dumodèle mathématique des constructions génétiques combinant des promoteurs, naturel ousynthétique, et différentes régions d'initiation de la traduction (TIRs) contrôlant l’expressiondu gène gfp. En utilisant ces constructions génétiques, nous avons montré que la productiondes protéines est non-linéaire en fonction de la concentration en ribosomes libres. Uneproduction non-linéaire entraine des efficacités de traduction différentielles des ARNmessagers en fonction de leurs TIRs. Ce mécanisme de régulation général des protéinesparticipe à la perte de corrélation entre la concentration des ARN messagers et des protéinescorrespondantes et nous a amené à revisiter la Physiologie Moléculaire Bactérienne. / Current theories suggest that translation efficiency (i.e. number of proteins produced permRNA) remains invariant with increasing growth rate, which is inconsistent with the scanty correlation between mRNAs and cognate proteins abundances at the genome-scale level. We tackled this apparent paradox using a systems biology approach. We developed a knowledgebased, nonlinear mathematical model of translation. The in-depth analysis of the model led us to reassess experimentally, using high-throughput and genome-wide technologies, each measurable RNA entity at different growth rates. In contrast to the current knowledge, the total mRNA abundance was not constant but linearly increased with respect to the growth rate. A model-driven integration of genome-wide and molecular experimental datasets demonstrated that the drop in abundance of a constitutively expressed protein with increasing growth rate is not only due to the dilution but also to an unexpected up to 4-fold decrease of translation efficiency. Our model revealed that this drop relies on a drastic decrease in free (untranslating) ribosomes, a non-measurable entity. Using a set of 18 Bacillus subtilis strains combining 9 synthetic translation initiation regions (TIRs) and 2 constitutive promoters, we show that TIRs together with free ribosome abundance strongly contribute to a nonlinear modulation of single proteins as a function of the growth rate. The nonlinearity accounted for the loss of correlation between mRNAs and cognate proteins abundances. Altogether, our results evidenced a unique, hard-coded and global growth-rate-dependent regulation of single bacterial proteins without dedicated regulators.

Thesis (BSc. Agriculture (Animal Production)) -- University of Limpopo, 2019 / An experiment was conducted to determine the effect of bovine colostrum feeding period after hatching on performance and carcass characteristics of male Ross 308 broiler chickens. The experiment was based on 0, 12, 24, 36, 48 and 72 hours of liquid bovine colostrum feeding after hatching of broiler chickens. The experiment commenced with 180 male Ross 308 broiler chicks with an initial live weight of 42 ± 2g per bird and was carried out for six weeks. The chicks were randomly assigned to six treatments with three replications, resulting in 18-floor pens with 10 chicks per replicate. A complete randomized design was used in this experiment. Data was analysed using the General Linear Model (GLM) procedures of the Statistical Analysis of system, Version 9.3.1 software program. Where there were significant differences, mean separation was done using the Turkey test at the 5% level of significance. A quadratic regression model was used to determine the optimum productivity of the experiment while a linear model was used to determine the relationships between bovine colostrum feeding period and responses in the variables measured. Feed intake during Week 1, growth rate during Week 3 and feed conversion ratio (FCR) during Weeks 2 and 3 of the growing period of male Ross 308 broiler chickens were not affected (p>0.05) by bovine colostrum feeding periods after hatching. Similarly, bovine colostrum feeding had no effect (p>0.05) on diet dry matter (DM), neutral detergent fibre (NDF), acid detergent fibre (ADF) and ash digestibilities in male Ross 308 broiler chickens aged 14 to 21 days. Bovine colostrum feeding period after hatching had no effect (p>0.05) on nitrogen retention (N-retention) in male broiler chickens aged one to 21 days. Similarly, gut organ digesta pH, length and weight of male Ross 308 broiler chickens aged 21 days were not improved (p>0.05) by bovine colostrum feeding after hatching. However, bovine colostrum feeding improved (p<0.05) feed intake during Weeks 2 and 3 of the growing period of male Ross 308 broiler chickens. Similarly, bovine colostrum feeding after hatching improved (p<0.05) crude protein (CP) digestibility in male broiler chickens aged 14 to 21 days. Metabolisable energy (ME) intake of male Ross 308 broiler chickens aged one to 21 days was improved (p<0.05) by bovine colostrum feeding period after hatching. Similarly, growth rate of male broiler v chickens during Weeks 1 and 2 was improved (p<0.05) by colostrum feeding after hatching. Feed conversion ratio of male broiler chickens during Week 1 was improved (p<0.05) by bovine colostrum feeding period after hatching. Bovine colostrum feeding after hatching improved (p<0.05) live weight of male Ross 308 broiler chickens at the ages of 7, 14 and 21 days. Nitrogen retention and FCR of male Ross 308 broiler chickens aged 22 to 42 days were not affected (p>0.05) by bovine colostrum feeding after hatching. In addition, live weights of male Ross 308 broiler chickens aged 35 and 42 days were not affected (p>0.05) by bovine colostrum feeding period after hatching. Similarly, bovine colostrum feeding had no effect (p>0.05) on gut organ digesta pH, large intestine lengths, breast and drumstick weights and breast meat juiciness of male Ross 308 broiler chickens aged 42 days. However, bovine colostrum feeding improved (p<0.05) feed intake and growth rate of male Ross 308 broiler chickens aged 22 to 42 days. Live weights of male Ross 308 broiler chickens aged 28 days were improved (p<0.05) by bovine colostrum feeding period after hatching. Similarly, bovine colostrum feeding after hatching did not affect (p<0.05) diet DM, CP, NDF, ADF and ash digestibilities in male Ross 308 broiler chickens aged 35 to 42 days. Metabolisable energy intake of male broiler chickens aged 22 to 42 days was improved (p<0.05) by bovine colostrum feeding period after hatching. Similarly, GIT, small intestine and caecum lengths and crop, proventriculus, gizzard, small intestine, caecum, large intestine, carcass and thigh weights of male Ross 308 broiler chickens aged 42 days were improved (p<0.05) by bovine colostrum feeding after hatching. Bovine colostrum feeding after hatching improved (p<0.05) breast meat tenderness, flavour and shear force of male Ross 308 broiler chickens aged 42 days. It is concluded that reasons for differing responses to bovine colostrum feeding periods of up to 72 hours after hatching are not clear. Therefore, further studies in which longer bovine colostrum feeding periods are used after hatching are recommended. / National Research Foundation (NRF)

Orientador: Cláudia Pio Ferreira / Abstract: This thesis presents two manuscripts previously sent to publication in scientific journals. In the first manuscript, a delay differential equation model is developed to study the dynamics of two Aedes aegypti mosquito populations: infected by the intracellular bacteria Wolbachia and non-infected (wild) individuals. All the steady states of the system are determined, namely extinction of both populations, extinction of the infected population and persistence of the non-infected one, and coexistence. Their local stability is analyzed, including Hopf bifurcation, which promotes periodic solutions around the nontrivial equilibrium points. Finally, one investigates the global asymptotic stability of the trivial solution. In the second manuscript, after rearing soybean looper Chrysodeixis includens in laboratory conditions, thermal requirements for this insect-pest are estimated, from linear and nonlinear regression models, as well as the intrinsic growth rate. This parameter depends on the life-history traits and can provide a measure of population viability of the species. / Doutor

Thesis (M.Sc. (Animal Production)) --University of Limpopo, 2019 / Two experiments were conducted to determine the effect of dietary threonine level on production performance and carcass characteristics of Ross 308 broiler chickens. In each experiment the diets were isocaloric and isonitrogenous but with different dietary threonine levels.The first part of the study determined the effect of dietary threonine level on feed intake, growth rate, mortality and carcass characteristics of Ross 308 broiler chickens aged between Day 1-21. A total of 150 unsexed day-old chicks were used in a complete randomized design having 5 treatments (6.4, 7.5, 8, 8.5 and 9g of threonine/kg DM feed), replicated three times and having ten chickens per replicate. The second part of the study determined the effect of dietary threonine level on feed intake, digestibility, growth rate, mortality and carcass characteristics of male Ross 308 broiler chickens aged between Day 22-42. Seventy-five male chickens were used in a complete randomized design having 5 treatments (6.4, 7.5, 8, 8.5 and 9g of threonine/kg DM feed), replicated three times and having five chickens per replicate. A quadratic regression model was used to determine the optimal productivity of the chickens while a General Linear Model (GLM) procedures for the statistical analysis of variance was used to detect dietary treatment effects. Where there were significant differences (P<0.05), Turkey’s honestly significant difference test (HSD) was used for mean separation. The chickens were slaughtered at the ages of 21 and 42 days for Experiments 1 and 2, respectively, following ethical standards as recommended by the University of Limpopo Animal Research Ethics Committee (AREC/12/2017: PG). Two chickens per replicate for both studies were slaughtered for the determination of carcass characteristics (carcass and organ weights, gut organ digesta pH and gastro-intestinal length measurements). Dietary threonine levels used in this experiment affected (P<0.05) feed intake, growth rate, live weight, metabolisable energy (ME) intake, nitrogen retention, feed conversion ratio and gut organ weights and lengths of unsexed Ross 308 broiler chickens aged 21 days. Dietary threonine level did not affect (P>0.05) diet digestibility. Feed conversion ratio, pH of the proventriculus digesta, gut intestine length and caecum length of unsexed broiler chickens were optimized at different dietary threonine levels of 9.6, 8.5, 6.6 and 8.4 g/kg DM, respectively. Dietary threonine levels had an effect (P<0.05) on feed intake, diet digestibility, metabolizable energy, live weight, proventriculus pH values, GIT length, gut organ and carcass organ weights of male Ross 308 broiler chickens between 22 to 42 days of age. Proventriculus and large intestine weights were optimized at different dietary threonine levels of 7.5 and 9.1 g/kg DM feed, respectively. Dietary threonine level did not affect (P>0.05) growth rate, feed conversion ratio of male Ross 308 broiler chickens between 22 to 42 days of age. It is concluded that dietary threonine levels used in this study affected production performance of younger broilers (Day 1-21) more than that of older birds (Day 22-42). However, production variables were optimized at different dietary threonine levels. This has implication on diet formulation for the chickens and no linear response could be established / National Research Foundation (NRF), and the Department of Agriculture, Forestry and Fisheries (DAFF)

An extended open system such as traffic flow is said to be convectively unstable if perturbations of the stationary state grow but propagate in only one direction, so they eventually leave the system. By means of data analysis, simulations, and analytical calculations, we give evidence that this concept is relevant for instabilities of congested traffic flow. We analyze detector data from several hundred traffic jams and propose estimates for the linear growth rate, the wavelength, the propagation velocity, and the severity of the associated bottleneck that can be evaluated semi-automatically. Scatter plots of these quantities reveal systematic dependencies. On the theoretical side, we derive, for a wide class of microscopic and macroscopic traffic models, analytical criteria for convective and absolute linear instabilities. Based on the relative positions of the stability limits in the fundamental diagram, we divide these models into five stability classes which uniquely determine the set of possible elementary spatiotemporal patterns in open systems with a bottleneck. Only two classes, both dominated by convective instabilities, are compatible wiqth observations. By means of approximate solutions of convectively unstable systems with sustained localized noise, we show that the observed spatiotemporal phenomena can also be described analytically. The parameters of the analytical expressions can be inferred from observations, and also (analytically) derived from the model equations.

Rolling contact fatigue is a problem encountered with many machine elements.In the current report a numerical study has been performed in order to predictthe crack path and crack propagation cycles of a surface initiated rolling contactfatigue crack. The implementation of the contact problem is based on theasperity point load mechanism for rolling contact fatigue. The practical studiedproblem is gear contact. Different loading types and models are studied andcompared to an experimental spall profile. Good agreement has been observedconsidering short crack lengths with a distributed loading model using normalloads on the asperity and for the cylindrical contact and a tangential load on theasperity. Several different crack propagation criteria have been implemented inorder to verify the validity of the dominant mode I crack propagation assumption.Some general characteristics of rolling contact fatigue cracks have beenhighlighted. A quantitative parameter study of the implemented model hasbeen performed. / Utmattning med rullande kontakter är ett ofta förekommande problem för många maskinelement. I den aktuella rapporten utfördes en numerisk studieför att förutsäga sprickvägen hos utmattningssprickor som initierats i ytan vidrullande kontakter. Implementeringen av kontaktproblemet bygger på asperitpunktlastmekanismen för rullande kontakter. Studien av kontaktproblemetär tillämpad till kugghjul. Olika belastningstyper och modeller studeradesoch jämfördes med profilen hos en experimentell spall. Bra överensstämmelseobserverades för korta spricklängder när en modell med fördelad belastninganvänds för en belastningstyp där en normalbelastning agerar på asperiten ochvid cylindriska kontakten och en tangentialbelastning införs på asperiten. Olikakriterier för spricktillväxt implementerades för att verifiera giltigheten av antagandetatt mode I spricktillväxt är dominant. Några generella kännetecken avutmattningssprickor med rullande kontakter framhävdes. En kvantitativ parameterstudie för den implementerade modellen utfördes.

Root exploitation of enriched soil microsites was examined for the tussock grasses Agropyron desertorum and Agropyron spicatum and the shrub Artemisia tridentata. Two mechanisms of exploitation of the microsites were examined: root proliferation and changes in nutrient uptake capacity. One day after nutrient solution was applied to small soil patches, the mean relative growth rate of Agropyron desertorum roots in enriched patches was two to four times greater than for roots of the same plants in soil patches treated with distilled water. This rapid and striking root proliferation occurred in response to N-P-K enrichment as well as to P or N enrichment alone. Agropyron spicatum showed no tendency to proliferate roots in enriched soil patches during the two-week experiments. The shrub Artemisia tridentata proliferated roots within one day of initial solution injection in the N-enrichment experiment, but root proliferation of this species was more gradual and less consistent in other experiments. The ability of Agropyron desertorum partly explain its to proliferate superior ability roots to rapidly may exploit soil nutrients compared to Agropyron spicatum in Great Basin rangelands of North America. Changes in nutrient uptake capacity in enriched soil patches were also studied for each species. rapid changes in uptake capacity of plant roots Large and from the field were observed after creation of nutrient-rich patches in the soil. Phosphate uptake of excised roots from enriched soil patches was roots of control patches as much as 80% greater than for treated with distilled water. These increases in uptake capacity took place within one week of patch treatment for all three species. A follow-up experiment showed increases within three days of patch treatment. These results showing rapid physiological plasticity in roots exploiting nutrient patches have important implications for nutrient belowground competition among plants.

It has been shown that fish of both marine and limnetic origin display increased growth at intermediate salinities. Furthermore, it has been shown that fish in the brackish water Baltic Sea are smaller compared to their conspecifics in the Atlantic, where salinities are higher. Also, it has been suggested that fish produce more eggs at the edges of their distribution range as a response to inferior environmental conditions. In this study, I investigated if there is a trade-off in energy investment between somatic and gonad growth in relation to salinity. To do this, I performed a growth experiment and a literature review. In the growth experiment, juvenile turbot were reared in salinities of 6, 10.5, 15 and 30 ‰. I found that turbot juveniles from Gotland grew equally well in all salinities investigated. In the literature review, data from the Baltic Sea was tested against data from the North and Black Seas. Data of turbot total energy investment (somatic and gonad growth) was analyzed. I found that energy content at age differed significantly between the populations investigated with lower energy content for the Baltic Sea populations. Also, growth rate in relation to energy content (size) was analyzed for the different populations, but no difference for growth rate in relation to energy content occurred. The result of the analysis of growth rate indicates that the change in allocated energy is the same, regardless of population, and thus that fish from the Baltic Sea display growth rates similar to those of other populations. It was also established that energy investment in gonads increased along with decreasing salinities. The smaller size of turbot in the Baltic Sea is therefore probably the result of a difference in size at maturity, possibly because less energy is allocated to somatic growth and more energy to start producing eggs. It is probably also the consequence of that the Baltic Sea turbot, post sexual maturity, continue to invest more energy in egg production.

Die Entwicklung der neuen Systemtherapien führte in den letzten Jahren zu einer bedeutenden Verbesserung des Langzeitüberlebens bei Patienten mit metastasiertem Melanom. Die verschiedenen Therapieoptionen mit ihren entsprechenden jeweiligen Toxizitäten sowie die Unterschiede im Therapieansprechen auf die differenten Therapieformen machen es erforderlich, anhand von prädiktiven Faktoren und Biomarkern Therapieentscheidungen zu treffen, um individuell die beste Therapie für den Patienten auszuwählen. Die Tumorwachstumskinetik wird dabei immer wieder als relevanter Faktor genannt. Ihr genauer Einfluss sowie die genaue Definition einer schnellen Tumorkinetik ist jedoch bis heute nicht klar definiert. Diese Arbeit soll dazu beitragen, die prognostische Wertigkeit der Metastasenwachstumsrate (MGR) als prädiktiven Marker vor dem Start einer Systemtherapie zu untersuchen. Konkret soll die Hypothese geprüft werden, ob eine schnelle MGR vor Therapiebeginn einen negativen Einfluss auf das Therapieansprechen sowie das klinische Outcome hat. Vor diesem Hintergrund wurde retrospektiv ein Patientenkollektiv von insgesamt 115 Patienten, aufgeteilt in drei Kohorten (Monotherapie mit PD-1-Antikörpern: n = 33, Kombinationstherapie mit PD-1- und CTLA-4-Antikörpern: n = 34, zielgerichtete Therapie mit BRAF- +/- MEK-Inhibitoren: n = 48), untersucht. Die Erhebung der Dresdner Daten war dabei Teil eines Verbundprojekts mit 12 teilnehmenden Kliniken, sodass zusätzlich zur Dresdner Auswertung für die Monotherapie aus PD-1-Antikörpern auch eine multizentrische Gesamtanalyse der Daten stattfinden konnte. Für die Datenerhebung wurden alle Patienten in Betracht gezogen, die seit Zulassung der einzelnen Therapieformen aufgrund eines kutanen, uvealen, mucosalen oder okkulten Melanoms im Stadium IIIB oder höher am Universitätsklinikum Dresden mit einer entsprechenden Systemtherapie behandelt wurden und eine messbare Metastasierung (CT/MRT/PET-CT) im Baseline-Staging sowie einem Pre-Baseline-Staging aufwiesen. Bei fehlenden Follow-Up-Daten sowie einer adjuvanten Therapiesituation wurden die Patienten aus der Datenerhebung ausgeschlossen. Die MGR wurde für den Zeitraum zwischen Pre-Baseline-Staging und dem Baseline-Staging bestimmt. Mittels Kaplan-Meier-Überlebenskurven sowie univariater und multivariater Cox-Regression wurde der prognostische Einfluss der MGR analysiert. Die Untersuchung des Einflusses der MGR auf das Therapieansprechen erfolgte mithilfe des Fisher-Tests und des Mann-Whitney-U-Tests. In der Dresdner Studie war eine hohe MGR (>3,9 mm/Monat) mit einem signifikant schlechteren progressionsfreien Überleben (PFS) für Patienten unter einer zielgerichteten Therapie verbunden. Zusätzlich zeigten diese Patienten ein signifikant schlechteres Ansprechen auf die Therapie mit BRAF- und MEK-Inhibitoren, im Vergleich zu Patienten, die eine MGR < 3,9 mm/Monat aufwiesen. Für das Gesamtüberleben (OS) zeigte sich trotz geringer Fallzahl sowohl in der Kohorte der zielgerichteten Therapie als auch in der Kohorte der kombinierten Immuntherapie mit Ipilimumab und Nivolumab ein Trend zu einem kürzeren OS, wenn eine hohe MGR vorlag. Dieser Trend konnte für die kombinierte Immuntherapie zusätzlich auch für das PFS festgestellt werden. Für die PD-1-Antikörper-Monotherapie konnte anhand der Dresdner Daten kein signifikanter Unterschied für das OS und PFS zwischen Patienten mit niedriger und hoher MGR festgestellt werden. In der Gesamtbetrachtung stellt die MGR einen prognostischen Marker für Patienten unter einer zielgerichteten Therapie mit BRAF- und MEK-Inhibitoren sowie in Zusammenschau mit den Ergebnissen der Gesamtstudie auch für Patienten unter einer PD-1-Antikörper-Monotherapie dar. Zusätzlich ergaben sich innerhalb dieser Arbeit Hinweise darauf, dass dies auch für die Immunkombinationstherapie mit Ipilimumab und Nivolumab zutrifft. Um die prognostische Wertigkeit der MGR für die unterschiedlichen Systemtherapien gleichermaßen beurteilen zu können, sind weitere Untersuchungen an größeren Patientenkollektiven notwendig. / The development of new system therapies has resulted in an important improvement in the long term survival of patients with a metastatic melanoma. Different therapy options with their respective individual toxicity, as well as differences in the reactions to different forms of therapy, require therapeutic decisions on the basis of predictive factors and bio markers in order to choose individually the best therapy for the patient. Tumor growth kinetics is often considered to be a relevant factor. Its specific influence as well as the exact definition of fast tumor kinetics has, however, not yet been clearly defined. This paper is supposed to support the examination of the prognostic value of the metastatic growth rate (MGR) as a predictive marker before a system therapy is introduced. The hypothesis that a fast MGR before a therapy begins has a negative influence on the therapy response and the clinical outcome has to be examined. On the basis of this hypothesis a patient collective of 115 patients in total, divided into three cohorts (mono therapy with PD-1-antibodies: n=33, combination therapy of PD-1- and CTLA-4-antibodies: n=34, target-orientated therapy with BRAF- t/- MEK inhibitors: n=48) was examined retrospectively. The collection of the Dresden data was part of a cooperative project of 12 participating clinics resulting in a multi-centric overall analysis of the data in addition to the Dresden evaluation of the mono therapy of PD1-antibodies. For the collection of the data those patients were considered who had been treated at Dresden university hospital since the approval of their individual form of therapy with a respective system therapy because of a cutaneous, uveal, mucosal or occult melanoma stage IIIB or higher and who showed a measurable metastasis (CT/MRT/PET-CT) in baseline staging as well as in pre-baseline staging. Patients without any follow-up data and an adjuvant therapy were excluded from the collection of data. The MGR was fixed for the timespan between pre-baseline staging and baseline staging. The prognostic influence of the MGR was analysed by means of the Kaplan-Meier-survival curve as well as univariate and multivariate cox regression. The study of the influence of MGR on the therapy response was based on the Fisher-Tests and the Mann-Whitney-U-Tests. The Dresden study showed the correlation between a high MGR (>3,9 mm/month) and a significantly worse progression free survival (PFS) for patients having a target-orientated therapy. Additionally, those patients showed a significantly weaker reaction to the therapy with BRAF - and MEK-inhibitors in comparison to patients who had an MGR < 3,9mm/month. Considering the overall survival (OS) of those with a fast MGR a trend to a shorter OS could be established, in spite of low case numbers in the cohort of the target-orientated therapy as well as in the cohort of the combined immune therapy with Ipilimumab and Nivolumab. This trend could be found for the combined immune therapy as well as for the PFS. Referring to the anti-PD1- mono therapy no significant difference could be found for the OS and the PFS between patients with faster and slower MGR. In the overall view the MGR proves to be a prognostic marker for patients having a target-orientated therapy with BRAF- and MEK-inhibitors and, also looking at the results of the overall study, for patients having a PD-1- antibody mono therapy. Additionally, this study revealed a significant indication that this also applies to the immune combination therapy of Ipilimumab and Nivolumab. Further studies with larger collectives of patients are necessary to be able to likewise judge the different prognostic valency of the MGR for the different system therapies.

No description available.