Maintenance of an intact genome and proper regulation of the genes within are crucial aspects for life. The work of this dissertation has implicated the Drosophila condensin II complex in both processes. Condensin II's ability to reconfigure chromosomes into spatially separated and discrete units is necessary to ensure proper meiotic segregation. When this "individualization" activity fails in a condensin II mutant, chromosomes remain entangled, and either cosegregate or become lost during cell division. This leads to the creation of aneuploid sperm. We have also implicated condensin II as a factor necessary to individualize interphase somatic chromosomes from one another. This is relevant in Drosophila because the association of homologous chromosomes is thought to facilitate gene regulation activity in trans. We speculate that condensin II individualization spatially distances aligned chromosomes from one another and prevents this trans-communication between allelic loci. This is supported first by an increase of homologous chromosome pairing in a condensin II mutant background. Secondly, loss of condensin II leads to elevated production from alleles that are known to depend on pairing for transcriptional activation. These meiotic and interphase condensin II roles support its necessity to Drosophila genome integrity and transcriptional regulation. Given the conservation of condensin from bacteria to humans, it is likely that equivalent or related roles exist in a variety of species.

Aicardi-Goutières Syndrome (AGS) is a single gene, autoimmune disorder, with variable onset in the first year of life. Its clinical features exhibit similarities to several autoimmune diseases and congenital viral infections. AGS can result from mutations in ADAR1, TREX1 and SAMHD1 as well as any of the three genes that encode the protein subunits of the RNase H2 enzyme. It is hypothesised that impairment of nucleic acid metabolism results in abnormal nucleic acid species within the cell. This in turn is thought to cause the aberrant immune response that leads to AGS. The RNase H2 complex contains the catalytic RNASEH2A subunit and the auxiliary RNASEH2B and RNASEH2C subunits, which are thought to provide structural support and facilitate interactions with additional cellular proteins. RNase H2 can cleave the RNA strand of an RNA:DNA hybrid as well as 5’ of a single ribonucleotide embedded in dsDNA. Therefore, RNase H2 may have roles in several cellular processes, including DNA replication and repair, transcription, and viral infection. The aim of this PhD project was to investigate the physiological functions of RNase H2. The localisation of the RNase H2 proteins was investigated using EGFP-tagging and fluorescent microscopy. The interaction between the PIP-box of RNASEH2B and PCNA was found to localise RNase H2 and not RNase H1 to nuclear replication foci during S-phase. This suggests that RNase H2 is the dominant RNase H activity during DNA replication. Stable cell lines expressing EGFP-RNASEH2B and an alternative isoform, EGFP-RNASEH2Balt, were generated and used to perform a protein-protein interaction screen by GFP-Trap and mass spectrometry. The results indicate putative physical interactions between RNASEH2B and other factors involved in DNA replication and repair. Further evidence for a role in DNA repair was revealed when mammalian RNase H2 null cells were treated with hydroxyurea. Low doses of hydroxyurea increased ribonucleotide incorporation into genomic DNA and impaired S-phase progression. In contrast to wild-type cells, RNase H2 null cell proliferation also failed to recover from this replicative stress after HU withdrawal. However, the ribonucleotide content of genomic DNA from these cells did return to pre-hydroxyurea treatment levels. This suggests that an alternative repair pathway exists in mammalian cells, which can remove ribonucleotides from DNA in the absence of RNase H2, but that this pathway is also harmful to the cells. There is evidence that TREX1 facilitates viral infection while SAMHD1 has been shown to restrict viral infection. Therefore, experiments were performed to investigate if RNase H2 could be a viral facilitator or restriction factor. Ribonucleotides can be incorporated into viral DNA, so RNase H2 could act as a restriction factor by nicking and damaging the pre-integration complex. However, RNase H2 could also function as a facilitator of infection by processing viral RNA:DNA hybrid by-products and thus prevent the host immune response. The data obtained during this PhD project provides further evidence that RNase H2 is involved in DNA replication and repair and has contributed to the understanding of the function of RNase H2 in the cell. However, it is still unknown how mutations in RNase H2 lead to the pathology of AGS.

No description available.

L'analyse des conditions physico-chimiques régnant dans le milieu interstellaire(ISM) nécessité de connaître les constantes de vitesse de collision inélastique qui ont lieu plus fréquemment dans l'ISM. Nous avons à cettefin calculées les surfaces d'énergie potentielles ainsi que les états liés descomplexes CS-H2, HCN-H2, HCN-He et C3-He. Nous avons déterminé pour la collision CS-H2 les sections efficaces et les taux d'excitation collisionnels pour les premiers niveaux rotationnels. Des observations récentes suggérentque l'excitation des modes de pliage des molécules triatomiques doit êtreprise en compte dans les modèles astrochimiques. Nous présentons doncdeux nouvelles approches théoriques permettant d'effectuer un traitementClose Coupling des collisions inélastiques d'un atome avec une molécule triatomique. Le couplage entre les mouvements de rotation et de pliage de la molécule est traité soit exactement dans le cadre de l'approximation du rigid bender (RBCC) ou de façon approximée en moyennant le potentiel d'interaction atome-molècule sur le mode de pliage de la molécule (RBAA). La méthode RBCC est appliquée à l'étude des collisions HCN-He et C3-He pour lesquelles les sections efficaces de transition entre niveaux rotationnels appartenant à des modes de pliage différents sont obtenues. Les résultats sont comparés avec ceux fournis par l'opproximation du rotateur rigide linéaire. Dans le cas de la collision HCN-He ils sont aussi comparés avec ceux obtenus en utilisant l'approche RBAA. Nous montrons que les sections efficaces de transitions entre des niveaux rotationels appartenant à des niveaux de bending différents doivent être calculées au niveau RBCC. / Tha analysis of the physico-chemical conditons taking place in the interstellar medium (ISM) requires to know the inclastic rate coefficents of the detected interstellar molecules in collisions with the moste common colliders int the ISM. We have comuted the four dimensional potential energy surfaces, and the bound levels for the CS-H2, HCN-H2, HCN-He and C3 -He complexes. For the collisions of Cs with H2, we also determined the rst inelastic cross section and rate coefficeients<; Several recent observations suggest that the vibrational excitation of triatomic molecules in the ISM at least in the bending motion needs to be considered in the collision mechanismes. We present a nex theorical method to treat atom-rigid bender ineslastic collisions at close the coupling level (RBCC). The coupling between rotation and bending is treated exactly within the rigid bender approximation and we obtain the cross section for the rotational transition between levels belonging to dierent bending levels. This approach is applied to the study of HCN-He and C3-He. The results are compared with those obtained whenconsidering the molecules to be linear rigid rotors. In the case of HCN-He,they are also compared with the cross sections determined using the interactionpotential averaged over the bending wavefunction. We demonstratethat the cross sections involving vibrational transitions should be computedusing the RBCC method. For HCN-He, the linear rigid approach is foundto offer a good description of pure rotational transitions while for C3-Hethis method is shown to overestimate the cross section for collision energieshigher than the first excited bending threshold.

The impact of H2 partial pressure (H2 pp) during the hydrotreating of heavy gas oil, derived from Athabasca bitumen, over commercial NiMo/¥ã-Al2O3 catalyst was studied in a micro-trickle bed reactor. The experimental conditions were varied as follows: temperature: 360 to 400¨¬C, pressure: 7 to 11 MPa, gas/oil ratio: 400 to 1270 mL/mL, H2 purity range of 0 to 100 vol. % (with the rest either CH4 or He), and LHSV range of 0.65 to 2 h-1. The two main objectives of the project were to study the nature of the dependence of H2 pp on temperature, pressure, gas/oil ratio, LHSV (Liquid Hourly Space Velocity), and H2 purity. The project was divided into three phases: in phase one the effect of H2 purity on hydrotreating of heavy gas oil (HGO) was studied, in phase two the nature of H2 pp dependency and the effect of H2 pp on hydrotreating of HGO was investigated, and in phase three kinetic studies were carried out using different kinetic models.<p> The objective of phase one was to study the effect of hydrogen purity on hydrotreating of HGO was studied in a trickle bed reactor over a commercial Ni−Mo/¥ã-alumina catalyst. Methane was used as a diluent for the hydrogen stream, and its effect on the catalyst performance was compared to that of helium, which is inert toward the catalyst. Furthermore, a deactivation study was conducted over a period of 66 days, during which the catalyst was subjected to H2 purities ranging from 75 to 95% (with the rest methane); no significant deterioration in the hydroprocessing activities of the catalyst was observed. Therefore, it was concluded that methane was inert toward a commercial Ni−Mo/¥ã-alumina catalyst. However, its presence resulted in hydrogen partial pressure reduction, which in turn led to a decrease in hydrodesulphurization (HDS), hydrodenitrogenation (HDN), hydrodearomatization (HDA) conversions. This reduction can be offset by increasing the total pressure of the system. HDS, HDN, HDA, and mild hydrocracking (MHC) conversions were studied. Also determined were cetane index, density, aniline point, diesel index, and fractional distribution of the products.<p> The main objective of phase two was to study the effects of H2 pp on hydrotreating conversions, feed vaporization, H2 dissolution, and H2 consumption were studied. The results show that HDN and HDA are significantly more affected by H2 partial pressure than HDS; with the HDN being the most affected. For instance as the inlet H2 partial pressure was increased from 4.6 to 8.9 MPa HDS, HDN, and HDA conversions increased for 94.9%, 55.1%, and 46.0% to 96.7%, 83.9%, and 58.0% , respectively. Moreover, it was observed that H2 dissolution and H2 consumption increased with increasing H2 pp. No clear trend was observed for the effect of H2 pp on feed vaporization.<p> In phase three the kinetics of HDS, HDN, and HDA were studied. The power law, multi-parameter, and Langmuir - Hinshelwood type models were used to fit the data. The prediction capacities of the resulting models were tested. It was determined that, while multi-parameter model yielded better prediction, L-H had an advantage in that it took a lesser number of experimental data to determine its parameters. Kinetic fitting of the data to a pseudo-first-order power law model suggested that conclusions on the effect of H2 pp on hydrotreating activities could be equally drawn from either inlet or outlet hydrogen partial pressure. However, from the catalyst deactivation standpoint, it is recommended that such conclusions are drawn from the outlet H2 partial pressure, since it is the reactor point with the lowest hydrogen partial pressure.

The impact of H2 partial pressure (H2 pp) during the hydrotreating of heavy gas oil, derived from Athabasca bitumen, over commercial NiMo/¥ã-Al2O3 catalyst was studied in a micro-trickle bed reactor. The experimental conditions were varied as follows: temperature: 360 to 400¨¬C, pressure: 7 to 11 MPa, gas/oil ratio: 400 to 1270 mL/mL, H2 purity range of 0 to 100 vol. % (with the rest either CH4 or He), and LHSV range of 0.65 to 2 h-1. The two main objectives of the project were to study the nature of the dependence of H2 pp on temperature, pressure, gas/oil ratio, LHSV (Liquid Hourly Space Velocity), and H2 purity. The project was divided into three phases: in phase one the effect of H2 purity on hydrotreating of heavy gas oil (HGO) was studied, in phase two the nature of H2 pp dependency and the effect of H2 pp on hydrotreating of HGO was investigated, and in phase three kinetic studies were carried out using different kinetic models.<p> The objective of phase one was to study the effect of hydrogen purity on hydrotreating of HGO was studied in a trickle bed reactor over a commercial Ni−Mo/¥ã-alumina catalyst. Methane was used as a diluent for the hydrogen stream, and its effect on the catalyst performance was compared to that of helium, which is inert toward the catalyst. Furthermore, a deactivation study was conducted over a period of 66 days, during which the catalyst was subjected to H2 purities ranging from 75 to 95% (with the rest methane); no significant deterioration in the hydroprocessing activities of the catalyst was observed. Therefore, it was concluded that methane was inert toward a commercial Ni−Mo/¥ã-alumina catalyst. However, its presence resulted in hydrogen partial pressure reduction, which in turn led to a decrease in hydrodesulphurization (HDS), hydrodenitrogenation (HDN), hydrodearomatization (HDA) conversions. This reduction can be offset by increasing the total pressure of the system. HDS, HDN, HDA, and mild hydrocracking (MHC) conversions were studied. Also determined were cetane index, density, aniline point, diesel index, and fractional distribution of the products.<p> The main objective of phase two was to study the effects of H2 pp on hydrotreating conversions, feed vaporization, H2 dissolution, and H2 consumption were studied. The results show that HDN and HDA are significantly more affected by H2 partial pressure than HDS; with the HDN being the most affected. For instance as the inlet H2 partial pressure was increased from 4.6 to 8.9 MPa HDS, HDN, and HDA conversions increased for 94.9%, 55.1%, and 46.0% to 96.7%, 83.9%, and 58.0% , respectively. Moreover, it was observed that H2 dissolution and H2 consumption increased with increasing H2 pp. No clear trend was observed for the effect of H2 pp on feed vaporization.<p> In phase three the kinetics of HDS, HDN, and HDA were studied. The power law, multi-parameter, and Langmuir - Hinshelwood type models were used to fit the data. The prediction capacities of the resulting models were tested. It was determined that, while multi-parameter model yielded better prediction, L-H had an advantage in that it took a lesser number of experimental data to determine its parameters. Kinetic fitting of the data to a pseudo-first-order power law model suggested that conclusions on the effect of H2 pp on hydrotreating activities could be equally drawn from either inlet or outlet hydrogen partial pressure. However, from the catalyst deactivation standpoint, it is recommended that such conclusions are drawn from the outlet H2 partial pressure, since it is the reactor point with the lowest hydrogen partial pressure.

The emission of polycyclic aromatic hydrocarbons (PAHs) from the diesel engine on a dynamometer by mixing ratio of the fuel (H2/O2 /diesel) was investigated. The engine was operated at a one load steady-state condition of 1,600 rpm with torque and power outputs of 145 Nm and 24.5 kW. In this condition, the measurement of the mixing ratio of the fuel (H2/O2 /diesel) was first recorded without any induction of H2/O2 mixture (Base) into the engine. Then, seven flow rate levels of H2/O2 mixture were used by 10 L/min, 20 L/min, 30 L/min, 40 L/min, 50 L/min, 60 L/min, and 70 L/min, respectively. The concentrations of total PAHs were 106.58, 101.89, 95.30, 90.70, 85.98, 82.35, 72.38, and 67.30 £gg/m3, respectively for Base (0 L/min), 10 L/min, 20 L/min, 30 L/min, 40 L/min, 50 L/min, 60 L/min, and 70 L/min of H2/O2 mixture. The emission factor of total PAHs were 6.00, 5.73, 5.36, 4.99, 4.84, 4.50, 4.07, and 3.78 mg/bhp-hr, respectively for Base (0 L/min), 10 L/min, 20 L/min, 30 L/min, 40 L/min, 50 L/min, 60 L/min, and 70 L/min of H2/O2 mixture. The removal rate of total PAHs were 4.4%, 10.6%, 14.9%, 19.3%, 22.7%, 32.1%, and 36.9%, respectively for 10 L/min, 20 L/min, 30 L/min, 40 L/min, 50 L/min, 60 L/min, and 70 L/min of H2/O2 mixture. This result showed using H2/O2 mixture significantly reduced emissions of PAHs. As the regulated harmful matters, using H2/O2 mixture, CO¡BCO2¡BTHC and PM decreased, whereas the NOx emission increased. The energy saving of the fuels (H2/O2 /diesel), the total oil equivalents combined by fuel consumption of diesel engine and electricity consumption of H2/O2 generator, were 2.42, 2.49, 2.50, 2.48, 2.51, 2.35, 2.18, and 2.17 for Base (0 L/min), 10 L/min, 20 L/min, 30 L/min, 40 L/min, 50 L/min, 60 L/min, and 70 L/min of H2/O2 mixture. The result showed that reduced saving energy of the fuel (H2/O2 /diesel) by 3.2% for 50 L/min, 9.8% for 60 L/min, and 10.4% for 70 L/min, respectively.

This research carries out all tests in diesel engine takes neat diesel and hydrogen+oxygen (H2/O2) which is used as an additive (H2/O2 mixture: 10 to 70 L/min, interval 10 L/min) in a stable state condition (engine was operated at one load steady-state condition of 1600 rpm with torque and power outputs of 145 Nm and 24.5 kW, respectively). Characteristics of carbonyls emissions from H2/O2 as an additive were investigated in a HDDE (heavy-duty diesel engine) and compared with those from neat diesel, contains the concentration, emission factor and elimination efficiency, whole of change tendency in order to help the understanding of diesel engine pollutant emissions, and appraises energy conservation of benefit which add to H2/O2. The regulated pollutants emission, using H2/O2 mixture (10 to 70 L/min), THC, CO, CO2 and PM emission all increased while H2/O2 showed signs of decrease; on the contrary, NOx emission increased while H2/O2 increased. Regarding Carbonyls emissions, the total carbonyls concentration of diesel engine take neat diesel was 3218.02 £gg/m3 and the emission factors for diesel engine take neat diesel were 180.882 mg/bhp-hr and 788.061 mg/L-fuel, respectively. When H2/O2 mixture was added, total carbonyls concentration of 3068.28, 3006.42, 2823.10, 2707.06, 2500.54, 2216.87 and 2178.27 mg/m3 were 10 L/min, 20 L/min, 30 L/min, 40 L/min, 50 L/min, 60 L/min and 70 L/min, respectively. The emission factor may be divided into mg/bhp-hr and mg/L-fuel; the emission factor of total carbonyls were 231.36¡B226.18¡B211.41¡B203.14¡B186.98¡B167.17 and 164.23 mg/bhp-hr, respectively; the emission factor of total carbonyls were 764.95¡B755.15¡B719.97¡B707.36¡B704.40¡B694.27 and 690.47 mg/L-fuel, respectively. Increases in H2/O2 can reduce total carbonyls emissions with an eliminating efficiency rate of 4.7, 6.6, 12.3, 15.9, 22.3, 31.1 and 32.3%, respectively. Energy conservation of appraisal increase H2/O2, diesel equivalent sun of fuel consumption of diesel engine and electricity consumption of H2/O2 generator, namely can distinguish that its energy consumption, whole consumes were 2.51, 2.58, 2.59, 2.57, 2.60, 2.43, 2.26 and 2.25, respectively. When compared with neat diesel, result showed in H2/O2 from 10 L/min to 40 L/min, diesel equivalent increased while H2/O2 showed increase; but in H2/O2 from 50 L/min to 70 L/min reflected in a gradual decrease in diesel equivalent, indicating that increases in H2/O2 can effectively achieve energy conservation. The result showed that energy conservation was 3.4%, 10.0% and 10.6% for 50 L/min, 60 L/min and 70 L/min, respectively. The result indicated H2/O2 was 60 L/min when energy conservation benefit was most remarkable, therefore this had the best energy conservation.

By exploiting the Projection Lemma, this thesis provides less conservative LMI-like conditions for mixed H2 and H_inf control of continuous-time systems than those appeared in the current literature. The same technique has been extended to problems with time-invariant polytopic uncertainties. Numerical examples are illustrated to show improvement of the proposed results. Finally, an attempt is made to apply the Projection Lemma to stability analysis and design of systems with time-varying polytopic uncertainties.

<p>The last years a TC-sensing module called HSS-440 has been developed at AppliedSensor. The sensor is used in hydrogen powered cars to detect H2-leakages. TC-sensing is a technique that uses small changes in thermal conductivity when H2 is present to determine concentrations. Today these small changes are estimated with a prediction model that uses several hundreds of parameters.</p><p>A sensor substrate from a new manufacturer is now introduced. This means an opportunity to look over the current solution. The task for this thesis is to investigate system properties and new solutions regarding a prediction model with minimal need for calibration.</p><p>System properties are investigated and relations for heat flow and influence of H2 are established. In the process an earlier not known nonlinearity are proved to exist. From this, a new open loop nonlinear greybox model is estimated and the nonlinearity are concluded to improve the model. The model is then closed with an earlier implemented PI-regulator and concluded to be useful for H2-predictions. The new model also utilizes 11 parameters instead of hundreds which is a big improvement.</p> / <p>Sista åren har en sensor, med beteckningen HSS-440, mätandes Termisk konduktivitet utvecklats på AppliedSensor. Sensorn används för att upptäcka läckage av H2-gas i vätgasdrivna bilar. Vid Termisk Konduktivitets mätning används små förändringar av den termiska konduktiviteten, då H2 är närvarande i det omgivande mediumet, som ett mått på koncentrationen. Idag änvänder prediktionsmodellen flera hundra parametrar för att skatta denna koncentration.</p><p>Nu introduceras ett sensorsubstrat från en ny tillverkare, vilket innebär ett bra tillfälle att se över den gamla lösningen. Syftet med examensarbetet är därför att undersöka nya systemegenskaper i och med introduktionen av det nya sensorsubstratet samt nya lösningar på en prediktionsmodel med ett minimalt behov av kalibrering.</p><p>Systemegenskaperna undersöks och samband för värmeflöden och H2's påverkan på systemet fastställs. Vid denna undersökning upptäcks en tidigare okänd olinjäritet. Utifrån detta bestämms en ny olinjär greybox modell där den nyfunna olinjäriteten bevisas förbättra modellen. Modellen sluts med en tidigare implementerade PI-regulator och bevisas vara användbar vid H2-prediktion. Den nya modellen använder även bara 11 parametrar istället för flera hundra vilket är en stor förbättring.</p>