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Point mutations and deletions of mitochondrial DNA (mtDNA) accumulate in a variety of tissues during ageing in humans, monkeys and rodents. These mutations are unevenly distributed and can accumulate clonally in certain cells, causing a mosaic pattern of respiratory chain deficiency in tissues such as heart, skeletal muscle and brain. In terms of the ageing(More)
Dictionary-based modeling is a mechanism used in many practical compression schemes. In most implementations of dictionary-based compression the encoder operates on-line, incrementally inferring its dictionary of available phrases from previous parts of the message. An alternative approach is to use the full message to infer a complete dictionary in(More)
This doctoral dissertation presents a range of results concerning efficient algorithms and data structures for string processing, including several schemes contributing to sequential data compression. It comprises both theoretic results and practical implementations. We study the suffix tree data structure, presenting an efficient representation and several(More)
Mitochondrial DNA (mtDNA) copy number regulation is altered in several human mtDNA-mutation diseases and it is also important in a variety of normal physiological processes. Mitochondrial transcription factor A (TFAM) is essential for human mtDNA transcription and we demonstrate here that it is also a key regulator of mtDNA copy number. We initially(More)
A practical scheme for maintaining an index for a sliding window in optimal time and space, by use of a suffix tree, is presented. The index supports location of the longest matching substring in time proportional to the length of the match. The total time for build and update operations is proportional to the size of the input. The algorithm, which is(More)
Transcription factors involved in the specification and differentiation of neurons often continue to be expressed in the adult brain, but remarkably little is known about their late functions. Nurr1, one such transcription factor, is essential for early differentiation of midbrain dopamine (mDA) neurons but continues to be expressed into adulthood. In(More)
Regulation of mtDNA expression is critical for maintaining cellular energy homeostasis and may, in principle, occur at many different levels. The leucine-rich pentatricopeptide repeat containing (LRPPRC) protein regulates mitochondrial mRNA stability and an amino-acid substitution of this protein causes the French-Canadian type of Leigh syndrome (LSFC), a(More)
We discuss an intrinsic generalization of the suffix tree, designed to index a string of length n which has a natural partitioning into m multi-character substrings or words. This word suffix tree represents only the m suffixes that start at word boundaries. These boundaries are determined by delimiters, whose definition depends on the application. Since(More)
There is an intense debate concerning whether selection or demographics has been most important in shaping the sequence variation observed in modern human mitochondrial DNA (mtDNA). Purifying selection is thought to be important in shaping mtDNA sequence evolution, but the strength of this selection has been debated, mainly due to the threshold effect of(More)
Mitochondrial dysfunction is implicated in the pathophysiology of Parkinson's disease (PD), a common age-associated neurodegenerative disease characterized by intraneuronal inclusions (Lewy bodies) and progressive degeneration of the nigrostriatal dopamine (DA) system. It has recently been demonstrated that midbrain DA neurons of PD patients and elderly(More)