Automated design of self-stabilization

Self-stabilization is a property of a distributed system such that, regardless of the legitimacy of its current state, the system behavior shall eventually reach a legitimate state and shall remain legitimate thereafter. The elegance of self-stabilization stems from the fact that it distinguishes distributed systems by a strong fault tolerance property against arbitrary state perturbations. The difficulty of designing and reasoning about self-stabilization has been witnessed by many researchers; most of the existing techniques for the verification and design of self-stabilization are either brute-force, or adopt manual approaches non-amenable to automation. In this dissertation, we first investigate the possibility of automatically designing self-stabilization through global state space exploration. In particular, we develop a set of heuristics for automating the addition of recovery actions to distributed protocols on various network topologies. Our heuristics equally exploit the computational power of a single workstation and the available parallelism on computer clusters. We obtain existing and new stabilizing solutions for classical protocols like maximal matching, ring coloring, mutual exclusion, leader election and agreement. Second, we consider a foundation for local reasoning about self-stabilization; i.e., study the global behavior of the distributed system by exploring the state space of just one of its components. It turns out that local reasoning about deadlocks and livelocks is possible for an interesting class of protocols whose proof of stabilization is otherwise complex. In particular, we provide necessary and sufficient conditions – verifiable in the local state space of every process – for global deadlock- and livelock-freedom of protocols on ring topologies. Local reasoning potentially circumvents two fundamental problems that complicate the automated design and verification of distributed protocols: (1) state explosion and (2) partial state information. Moreover, local proofs of convergence are independent of the number of processes in the network, thereby enabling our assertions about deadlocks and livelocks to apply on rings of arbitrary sizes without worrying about state explosion.

DESIGN AND DEVELOPMENT OF BODIPY-BASED FLUORESCENT PROBES FOR SENSING AND IMAGING OF CYANIDE, Zn (II) IONS, LYSOSOMAL pH AND CANCER CELLS

BODIPY (4,4-Difluoro-3a,4a-diaza-s-indacene) dyes have gained lots of attention in application of fluorescence sensing and imaging in recent years because they possess many distinctive and desirable properties such as high extinction coefficient, narrow absorption and emission bands, high quantum yield and low photobleaching effect. However, most of BODIPY-based fluorescent probes have very poor solubilities in aqueous solution, emit less than 650 nm fluorescence that can cause cell and tissue photodamages compared with bio-desirable near infrared (650-900 nm) light. These undesirable properties extremely limit the applications of BODIPY-based fluorescent probes in sensing and imaging applications. In order to overcome these drawbacks, we have developed a very effective strategy to prepare a series of neutral highly water- soluble BODIPY dyes by enhancing the water solubilities of BODIPY dyes via incorporation of tri(ethylene glycol)methyl ether (TEG) and branched oligo(ethylene glycol)methyl ether (BEG) residues onto BODIPY dyes at 1,7-, 2,6-, 3,5-, 4- and meso- positions. We also have effectively tuned absorptions and emissions of BOIDPY dyes to red, deep red and near infrared regions via significant extension of π-conjugation of BODIPY dyes by condensation reactions of aromatic aldehydes with 2,6-diformyl BODIPY dyes at 1,3,5,7-positions. Based on the foundation that we built for enhancing water solubility and tuning wavelength, we have designed and developed a series of water-soluble, BODIPY-based fluorescent probes for sensitive and selective sensing and imaging of cyanide, Zn (II) ions, lysosomal pH and cancer cells. We have developed three BODIPY-based fluorescent probes for sensing of cyanide ions by incorporating indolium moieties onto the 6-position of TEG- or BEG-modified BOIDPY dyes. Two of them are highly water-soluble. These fluorescent probes showed selective and fast ratiometric fluorescent responses to cyanide ions with a dramatic fluorescence color change from red to green accompanying a significant increase in fluorescent intensity. The detection limit was measured as 0.5 mM of cyanide ions. We also have prepared three highly water-soluble fluorescent probes for sensing of Zn (II) ions by introducing dipicoylamine (DPA, Zn ion chelator) onto 2- and/or 6-positions of BEG-modified BODIPY dyes. These probes showed selective and sensitive responses to Zn (II) ion in the range from 0.5 mM to 24 mM in aqueous solution at pH 7.0. Particularly, one of the probes displayed ratiometric responses to Zn (II) ions with fluorescence quenching at 661 nm and fluorescence enhancement at 521 nm. This probe has been successfully applied to the detection of intracellular Zn (II) ions inside the living cells. Then, we have further developed three acidotropic, near infrared emissive BODIPY- based fluorescent probes for detection of lysosomal pH by incorporating piperazine moiety at 3,5-positions of TEG- or BEG-modified BODIPY dyes as parts of conjugation. The probes have low auto-fluorescence at physiological neutral condition while their fluorescence intensities will significant increase at 715 nm when pH shift to acidic condition. These three probes have been successfully applied to the in vitro imaging of lysosomes inside two types of living cells. At the end, we have synthesized one water- soluble, near infrared emissive cancer cell targetable BODIPY-based fluorescent polymer bearing cancer homing peptide (cRGD) residues for cancer cell imaging applications. This polymer exhibited excellent water-solubility, near infrared emission (712 nm), good biocompatibility. It also showed low nonspecific interactions to normal endothelial cells and can effectively detect breast tumor cells.