Genetic Investigations of Sporadic Inclusion Body Myositis and Myopathies with Structural Abnormalities and Protein Aggregates in Muscle

The application of whole-exome sequencing (WES) has not only dramatically accelerated the discovery of pathogenic genes of Mendelian diseases, but has also shown promising findings in complex diseases. This thesis focuses on exploring genetic risk factors for a large series of sporadic inclusion body myositis (sIBM) cases, and identifying disease-causing genes for several groups of patients with abnormal structure and/or protein aggregates in muscle. Both conventional and advanced techniques were applied. Based on the International IBM Genetics Consortium (IIBMGC), the largest sIBM cohort of blood and muscle tissue for DNA analysis was collected as the initial part of this thesis. Candidate gene studies were carried out and revealed a disease modifying effect of an intronic polymorphism in TOMM40, enhanced by the APOE ε3/ε3 genotype. Rare variants in SQSTM1 and VCP genes were identified in seven of 181 patients, indicating a mutational overlap with neurodegenerative diseases. Subsequently, a first whole-exome association study was performed on 181 sIBM patients and 510 controls. This reported statistical significance of several common variants located on chromosome 6p21, a region encompassing genes related to inflammation/infection. WES was performed on a group of 35 cases with tubular aggregates/cylindrical spirals, and detected rare variants in known/candidate genes. Disease-causing genes were identified in four families with protein aggregates in muscle also by WES. In one family identified with a novel homozygous deletion in SBF1 with a rare autosomal-recessive neuromuscular condition, functional analysis was carried out indicating a loss-of-function mechanism underlying the pathogenesis of the disease. The collection of a large series of sIBM patients through the IIBMGC has been shown here to reveal important genetic findings and will be a valuable resource for the future. WES proved to be important in sIBM and also to be an efficient method to investigate the genetics basis of rare complex muscle disorders

Quantum Phase Transition in Finite-Size Lipkin-Meshkov-Glick Model

Lipkin model of arbitrary particle-number N is studied in terms of exact differential-operator representation of spin-operators from which we obtain the low-lying energy spectrum with the instanton method of quantum tunneling. Our new observation is that the well known quantum phase transition can also occur in the finite-N model only if N is an odd-number. We furthermore demonstrate a new type of quantum phase transition characterized by level-crossing which is induced by the geometric phase interference and is marvelously periodic with respect to the coupling parameter. Finally the conventional quantum phase transition is understood intuitively from the tunneling formulation in the thermodynamic limit.Comment: 4 figure

Strain in epitaxial CoSi2 films on Si (111) and inference for pseudomorphic growth

The perpendicular x-ray strain of epitaxial CoSi2 films grown on Si(111) substrates at ~600 °C was measured at temperatures from 24 up to 650 °C. At 600 °C, the perpendicular x-ray strain is –0.86%, which is about the x-ray strain that a stress-free CoSi2 film on Si(111) would have at that temperature. This result shows that the stress in the epitaxial CoSi2 film is fully relaxed at the growth temperature. Strains in the film below the growth temperature are induced by the difference in the thermal expansion coefficient of CoSi2 and Si, alphaf–alphas=0.65×10^–5/°C. Within experimental error margins, the strain increases linearly with decreasing temperature at a rate of (1.3±0.1)×10^–5/C. The slope of the strain-temperature dependence, obtained by assuming that the density of misfit dislocations formed at the growth temperature remains unchanged, agrees with the measured slope if the unknown Poisson ratio of CoSi2 is assumed to be nuf=1/3. These observations support three rules postulated for epitaxial growth

Facilitated movement of inertial Brownian motors driven by a load under an asymmetric potential

Based on recent work [L. Machura, M. Kostur, P. Talkner, J. Luczka, and P. Hanggi, Phys. Rev. Lett. 98, 040601 (2007)], we extend the study of inertial Brownian motors to the case of an asymmetric potential. It is found that some transport phenomena appear in the presence of an asymmetric potential. Within tailored parameter regimes, there exists two optimal values of the load at which the mean velocity takes its maximum, which means that a load can facilitate the transport in the two parameter regimes. In addition, the phenomenon of multiple current reversals can be observed when the load is increased.Comment: 7 pages, 3 figure

Exotic quantum phase transitions in a Bose-Einstein condensate coupled to an optical cavity

A new extended Dicke model, which includes atom-atom interactions and a driving classical laser field, is established for a Bose-Einstein condensate inside an ultrahigh-finesse optical cavity. A feasible experimental setup with a strong atom-field coupling is proposed, where most parameters are easily controllable and thus the predicted second-order superradiant-normal phase transition may be detected by measuring the ground-state atomic population. More intriguingly, a novel second-order phase transition from the superradiant phase to the \textquotedblleft Mott" phase is also revealed. In addition, a rich and exotic phase diagram is presented.Comment: 4 pages; figures 1 and 3 are modified; topos are correcte