AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
The relation between flux and fluctuation is fundamental to complex physical systems that support and transport flows. A recently obtained law predicts monotonous enhancement of fluctuation as the average flux is increased, which in principle is valid but only for large systems. For realistic complex systems of small sizes, this law breaks down when both the average flux and fluctuation become large. Here we demonstrate the failure of this law in small systems using real data and model complex networked systems, derive analytically a modified flux-fluctuation law, and validate it through computations of a large number of complex networked systems. Our law is more general in that its predictions agree with numerics and it reduces naturally to the previous law in the limit of large system size, leading to new insights into the flow dynamics in small-size complex systems with significant implications for the statistical and scaling behaviors of small systems, a topic of great recent interest.
An outstanding and fundamental problem in contemporary physics is to include and probe the many-body effect in the study of relativistic quantum manifestations of classical chaos. We address this problem using graphene systems described by the Hubbard Hamiltonian in the setting of resonant tunneling. Such a system consists of two symmetric potential wells separated by a potential barrier, and the geometric shape of the whole domain can be chosen to generate integrable or chaotic dynamics in the classical limit. Employing a standard mean-field approach to calculating a large number of eigenenergies and eigenstates, we uncover a class of localized states with near-zero tunneling in the integrable systems. These states are not the edge states typically seen in graphene systems, and as such they are the consequence of many-body interactions. The physical origin of the non-edge-state type of localized states can be understood by the one-dimensional relativistic quantum tunneling dynamics through the solutions of the Dirac equation with appropriate boundary conditions. We demonstrate that, when the geometry of the system is modified to one with chaos, the localized states are effectively removed, implying that in realistic situations where many-body interactions are present, classical chaos is capable of facilitating greatly quantum tunneling. This result, besides its fundamental importance, can be useful for the development of nanoscale devices such as graphene-based resonant-tunneling diodes.
Dynamical systems based on the minority game (MG) have been a paradigm for gaining significant insights into a variety of social and biological behaviors. Recently, a grouping phenomenon has been unveiled in MG systems of multiple resources (strategies) in which the strategies spontaneously break into an even number of groups, each exhibiting an identical oscillation pattern in the attendance of game players. Here we report our finding of spontaneous breakup of resources into three groups, each exhibiting period-three oscillations. An analysis is developed to understand the emergence of the striking phenomenon of triple grouping and period-three oscillations. In the presence of random disturbances, the triple-group/period-three state becomes transient, and we obtain explicit formula for the average transient lifetime using two methods of approximation. Our finding indicates that, period-three oscillation, regarded as one of the most fundamental behaviors in smooth nonlinear dynamical systems, can also occur in much more complex, evolutionary-game dynamical systems. Our result also provides a plausible insight for the occurrence of triple grouping observed, for example, in the U.S. housing market.