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The existence of mammary stem cells (MaSCs) has been postulated from evidence that the mammary gland can be regenerated by transplantation of epithelial fragments in mice. Interest in MaSCs has been further stimulated by their potential role in breast tumorigenesis. However, the identity and purification of MaSCs has proved elusive owing to the lack of(More)
Elucidation of the cellular and molecular mechanisms that maintain mammary epithelial tissue integrity is of broad interest and paramount to the design of more effective treatments for breast cancer. Evidence from both in vitro and in vivo experiments suggests that mammary cell differentiation is a hierarchical process originating in an uncommitted stem(More)
A fundamental question in cancer biology is whether cells with tumorigenic potential are common or rare within human cancers. Studies on diverse cancers, including melanoma, have indicated that only rare human cancer cells (0.1-0.0001%) form tumours when transplanted into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, the(More)
Natural evolutionaryy systems exhibit a complexx mapping from genotype too phenotype. One propertyy of these mappings is neutrality, where manyy mutations doo not have ann appreciable effect onn the phenotype. Inn this case the mappingg from genotype too phenotype contains redundancy suchh that a phenotype is representedd byy manyy genotypes. Studies of RNA(More)
The inactivation of the p53 tumor suppressor pathway, which often occurs through mutations in TP53 (encoding tumor protein 53) is a common step in human cancer. However, in melanoma-a highly chemotherapy-resistant disease-TP53 mutations are rare, raising the possibility that this cancer uses alternative ways to overcome p53-mediated tumor suppression. Here(More)
In this paper, we investigate the global self-aggregation dynamics arising from local decision-based rewiring of an overlay network, used as an abstraction for an autonomic service-oriented architecture. We measure the ability of a selected set of local rules to foster self-organization of what is originally a random graph into a structured network.(More)
The identification and characterization of cancer stem cells might lead to more effective treatments for some cancers by focusing therapy on the most malignant cells. To achieve this goal it will be necessary to determine which cancers follow a cancer stem cell model and which do not, to address technical issues related to tumorigenesis assays, and to test(More)
Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from(More)
This paper shows how self-(*) mechanisms give rise to complex but predictable and therefore steerable global system behavior in a cooperative computing environment. The operation of and the interactions between a set of networked autonomic devices are simulated. These are used as access points to a number of services, have the ability to accept or delegate(More)