Tumour-stroma crosstalk in the development of squamous cell carcinoma.

Squamous cell carcinoma (SCC) represents one of the most frequently diagnosed tumours and contributes significant mortality worldwide. Recent deep sequencing of cancer genomes has identified common mutations in SCC arising across different tissues highlighting perturbation of squamous differentiation as a key event. At the same time significant data have been accumulating to show that common tumour-stroma interactions capable of driving disease progression are also evident when comparing SCC arising in different tissues. We and others have shown altered matrix composition surrounding SCC can promote tumour development. This review focuses on some of the emerging data with particular emphasis on SCC of head and neck and skin with discussion on the potential tumour suppressive properties of a normal microenvironment. Such data indicate that regardless of the extent and type of somatic mutation it is in fact the tumour context that defines metastatic progression

Pro-Inflammatory Chemokines and Cytokines Dominate the Blister Fluid Molecular Signature in Patients with Epidermolysis Bullosa and Affect Leukocyte and Stem Cell Migration.

Hereditary epidermolysis bullosa (EB) is associated with skin blistering and the development of chronic nonhealing wounds. Although clinical studies have shown that cell-based therapies improve wound healing, the recruitment of therapeutic cells to blistering skin and to more advanced skin lesions remains a challenge. Here, we analyzed cytokines and chemokines in blister fluids of patients affected by dystrophic, junctional, and simplex EB. Our analysis revealed high levels of CXCR1, CXCR2, CCR2, and CCR4 ligands, particularly dominant in dystrophic and junctional EB. In vitro migration assays demonstrated the preferential recruitment of CCR4+ lymphocytes and CXCR1+, CXCR2+, and CCR2+ myeloid cells toward EB-derived blister fluids. Immunophenotyping of skin-infiltrating leukocytes confirmed substantial infiltration of EB-affected skin with resting (CD45RA+) and activated (CD45RO+) T cells and CXCR2+ CD11b+ cells, many of which were identified as CD16b+ neutrophils. Our studies also showed that abundance of CXCR2 ligand in blister fluids also creates a favorable milieu for the recruitment of the CXCR2+ stem cells, as validated by in vitro and in-matrix migration assays. Collectively, this study identified several chemotactic pathways that control the recruitment of leukocytes to the EB-associated skin lesions. These chemotactic axes could be explored for the refinement of the cutaneous homing of the therapeutic stem cells. © 2017 The Author

Design and development of an event related potential measurement system.

Event-related potentials have been found to be a useful indicator of brain states and brain abnormality. The contingent negative variation, P300 and bereitschafts potential are well researched event-related potentials of particular interest. Many factors have to be considered in the design of measurement systems to record multiple channels of these signals accurately. The correlation between channels must be high and channel noise and distortion must be minimal, whilst the system as a whole must meet the requirements of the medical safety standards. For further research there was found to be a requirement for a dedicated thirty-two channel ERP measurement system that met these criteria. This has been achieved in a PC based system that utilises simultaneous sampling of all channels, and filters that extend to very low frequencies. Software control of the system enables user adjustment of recording parameters and paradigm implementation. Data processing using high level software enables digital signal processing techniques to be applied for further noise removal and signal analysis. The system has been tested using synthetically generated signals and by limited recording of the three ERPs. The results prove that the system is a suitable tool for high accuracy, multi-channel recording of ERPs

Guide to electric and natural gas utilities in South Carolina

This report is intended to serve as a customer-focused guide to South Carolina's retail electricity and natural gas distribution utilities, based on the most current publicly-available data. The following data are included in this report: customer, revenue, sales, and average price, green power customer, revenue, sales, and average price, net metering customer and purchases, automatic meter reading and advanced metering Infrastructure and demand-side management programs

Saving Energy, Saving Money : How South Carolina's Electric and Natural Gas Utilities Are Using Demand-Side Management to Help Customers Reduce Their Energy Bills

Demand-side management ("DSM") is a strategy that electric and natural gas utilities employ to decrease or defer demand for their energy services. South Carolina's three large investor-owned electric utilities (Duke Energy Carolinas, Progress Energy Carolinas, and South Carolina Electric & Gas Company) and state-owned Santee Cooper all offered a broad range of DSM programs in 2011

Mutation signature analysis identifies increased mutation caused by tobacco smoke associated DNA adducts in larynx squamous cell carcinoma compared with oral cavity and oropharynx.

Squamous cell carcinomas of the head and neck (HNSCC) arise from mucosal keratinocytes of the upper aero-digestive tract. Despite a common cell of origin and similar driver-gene mutations which divert cell fate from differentiation to proliferation, HNSCC are considered a heterogeneous group of tumors categorized by site of origin within the aero-digestive mucosa, and the presence or absence of HPV infection. Tobacco use is a major driver of carcinogenesis in HNSCC and is a poor prognosticator that has previously been associated with poor immune cell infiltration and higher mutation numbers. Here, we study patterns of mutations in HNSCC that are derived from the specific nucleotide changes and their surrounding nucleotide context (also known as mutation signatures). We identify that mutations linked to DNA adducts associated with tobacco smoke exposure are predominantly found in the larynx. Presence of this class of mutation, termed COSMIC signature 4, is responsible for the increased burden of mutation in this anatomical sub-site. In addition, we show that another mutation pattern, COSMIC signature 5, is positively associated with age in HNSCC from non-smokers and that larynx SCC from non-smokers have a greater number of signature 5 mutations compared with other HNSCC sub-sites. Immunohistochemistry demonstrates a significantly lower Ki-67 proliferation index in size matched larynx SCC compared with oral cavity SCC and oropharynx SCC. Collectively, these observations support a model where larynx SCC are characterized by slower growth and increased susceptibility to mutations from tobacco carcinogen DNA adducts