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OBJECTIVE To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. DESIGN Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key(More)
  • Serena Nik-Zainal, Ludmil B. Alexandrov, David C. Wedge, Peter Van Loo, Christopher D. Greenman, Keiran Raine +47 others
  • 2012
All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of(More)
  • Serena Nik-Zainal, Peter Van Loo, David C. Wedge, Ludmil B. Alexandrov, Christopher D. Greenman, King Wai Lau +43 others
  • 2012
Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast(More)
Two methods are described for using the jellyfish green fluorescent protein (GFP) as a reporter gene for ion channel expression. GFP fluorescence can be used to identify the transfected cells, and to estimate the relative levels of ion channel expression, in cotransfection experiments. A GFP-NMDAR1 chimera can be constructed that produces a functional,(More)
  • Okunola Jeyifous, Clarissa L Waites, Christian G Specht, Sho Fujisawa, Manja Schubert, Eric I Lin +6 others
  • 2009
Synaptic plasticity is dependent on the differential sorting, delivery and retention of neurotransmitter receptors, but the mechanisms underlying these processes are poorly understood. We found that differential sorting of glutamate receptor subtypes began in the endoplasmic reticulum of rat hippocampal neurons. As AMPA receptors (AMPARs) were trafficked to(More)
Variability of the North Atlantic Oscillation and the Tropical Atlantic dominate the climate of the North Atlantic sector, the underlying ocean and surrounding continents on interannual to decadal time scales. Here we review these phenomena, their climatic impacts and our present state of understanding of their underlying cause.
Insulin-like growth factor 1 (IGF-1) rapidly potentiates N and L calcium channel currents in cerebellar granule neurons by an unknown mechanism. Here, we show that the L channel alpha1C subunit is tyrosine phosphorylated in response to IGF-1. Moreover, expression of kinase-dead c-Src in neurons or acute block of Src family kinases with a cell-permeable(More)
The genetics of renal cancer is dominated by inactivation of the VHL tumour suppressor gene in clear cell carcinoma (ccRCC), the commonest histological subtype. A recent large-scale screen of ∼3,500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX (also known as KDM6A), JARID1C (also known as KDM5C) and SETD2(More)
BACKGROUND Three patients who received visceral-organ transplants from a single donor on the same day died of a febrile illness 4 to 6 weeks after transplantation. Culture, polymerase-chain-reaction (PCR) and serologic assays, and oligonucleotide microarray analysis for a wide range of infectious agents were not informative. METHODS We evaluated RNA(More)
  • Elizabeth P. Murchison, Ole B. Schulz-Trieglaff, Zemin Ning, Ludmil B. Alexandrov, Markus J. Bauer, Beiyuan Fu +50 others
  • 2012
The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the(More)