Corrigendum to "Discrimination of biomass burning smoke and clouds in MAIAC algorithm" published in Atmos. Chem. Phys., 12, 9679–9686, 2012

No abstract available

Discrimination of Biomass Burning Smoke and Clouds in MAIAC Algorithm

The multi-angle implementation of atmospheric correction (MAIAC) algorithm makes aerosol retrievals from MODIS data at 1 km resolution providing information about the fine scale aerosol variability. This information is required in different applications such as urban air quality analysis, aerosol source identification etc. The quality of high resolution aerosol data is directly linked to the quality of cloud mask, in particular detection of small (sub-pixel) and low clouds. This work continues research in this direction, describing a technique to detect small clouds and introducing the smoke test to discriminate the biomass burning smoke from the clouds. The smoke test relies on a relative increase of aerosol absorption at MODIS wavelength 0.412 micrometers as compared to 0.47-0.67 micrometers due to multiple scattering and enhanced absorption by organic carbon released during combustion. This general principle has been successfully used in the OMI detection of absorbing aerosols based on UV measurements. This paper provides the algorithm detail and illustrates its performance on two examples of wildfires in US Pacific North-West and in Georgia/Florida of 2007

Chemotherapy resistance and stemness in mitotically quiescent human breast cancer cells identified by fluorescent dye retention

Metastatic recurrence in breast cancer is a major cause of mortality and often occurs many years after removal of the primary tumour. This process is driven by the reactivation of disseminated tumour cells that are characterised by mitotic quiescence and chemotherapeutic resistance. The ability to reliably isolate and characterise this cancer cell population is critical to enable development of novel therapeutic strategies for prevention of breast cancer recurrence. Here we describe the identification and characterisation of a sub-population of slow-cycling tumour cells in the MCF-7 and MDA-MB-231 human breast cancer cell lines based on their ability to retain the lipophilic fluorescent dye Vybrant® DiD for up to six passages in culture. Vybrant® DiD-retaining (DiD+) cells displayed significantly increased aldehyde dehydrogenase activity and exhibited significantly reduced sensitivity to chemotherapeutic agents compared to their rapidly dividing, Vybrant® DiD-negative (DiD-) counterparts. In addition, DiD+ cells were exclusively capable of initiating population re-growth following withdrawal of chemotherapy. The DiD+ population displayed only partial overlap with the CD44+CD24-/low cell surface protein marker signature widely used to identify breast cancer stem cells, but was enriched for CD44+CD24+ cells. Real-time qPCR profiling revealed differential expression of epithelial-to-mesenchymal transition and stemness genes between DiD+ and DiD- populations. This is the first demonstration that both MCF-7 and MDA-MB-231 human breast cancer lines contain a latent therapy-resistant population of slow-cycling cells capable of initiating population regrowth post-chemotherapy. Our data support that label-retaining cells can serve as a model for identification of molecular mechanisms driving tumour cell quiescence and de novo chemoresistance and that further characterisation of this prospective tumour-reinitiating population could yield novel therapeutic targets for elimination of the cells responsible for breast cancer recurrence

Anti-angiogenic drugs: direct anti-cancer agents with mitochondrial mechanisms of action

Components of the mitochondrial electron transport chain have recently gained much interest as potential therapeutic targets. Since mitochondria are essential for the supply of energy that is required for both angiogenic and tumourigenic activity, targeting the mitochondria represents a promising potential therapeutic approach for treating cancer. Here we investigate the established anti-angiogenesis drugs combretastatin A4, thalidomide, OGT 2115 and tranilast that we hypothesise are able to exert a direct anti-cancer effect in the absence of vasculature by targeting the mitochondria. Drug cytotoxicity was measured using the MTT assay. Mitochondrial function was measured in intact isolated mitochondria using polarography, fluorimetry and enzymatic assays to measure mitochondrial oxygen consumption, membrane potential and complex I–IV activities respectively. Combretastatin A4, OGT 2115 and tranilast were both shown to decrease mitochondrial oxygen consumption. OGT 2115 and tranilast decreased mitochondrial membrane potential and reduced complex I activity while combretastatin A4 and thalidomide did not. OGT 2115 inhibited mitochondrial complex II–III activity while combretastatin A4, thalidomide and tranilast did not. Combretastatin A4, thalidomide and OGT 2115 induced bi-phasic concentration-dependent increases and decreases in mitochondrial complex IV activity while tranilast had no evident effect. These data demonstrate that combretastatin A4, thalidomide, OGT 2115 and tranilast are all mitochondrial modulators. OGT 2115 and tranilast are both mitochondrial inhibitors capable of eliciting concentration-dependent reductions in cell viability by decreasing mitochondrial membrane potential and oxygen consumption

Prospects for the Search for a Standard Model Higgs Boson in ATLAS using Vector Boson Fusion

The potential for the discovery of a Standard Model Higgs boson in the mass range m_H < 2 m_Z in the vector boson fusion mode has been studied for the ATLAS experiment at the LHC. The characteristic signatures of additional jets in the forward regions of the detector and of low jet activity in the central region allow for an efficient background rejection. Analyses for the H -> WW and H -> tau tau decay modes have been performed using a realistic simulation of the expected detector performance. The results obtained demonstrate the large discovery potential in the H -> WW decay channel and the sensitivity to Higgs boson decays into tau-pairs in the low-mass region around 120 GeV.Comment: 20 pages, 13 ps figures, uses EPJ style fil

Transcriptomic profiling reveals novel candidate genes and signalling programs in breast cancer quiescence and dormancy

Metastatic recurrence, the major cause of breast cancer mortality, is driven by reactivation of dormant disseminated tumour cells that are defined by mitotic quiescence and chemoresistance. The molecular mechanisms underpinning mitotic quiescence in cancer are poorly understood, severely limiting the development of novel therapies for removal of residual, metastasis-initiating tumour cells. Here, we present a molecular portrait of the quiescent breast cancer cell transcriptome across the four main breast cancer sub-types (luminal, HER2-enriched, basal-like and claudin-low) and identify a novel quiescence-associated 22-gene signature using an established lipophilic-dye (Vybrant® DiD) retention model and whole-transcriptomic profiling (mRNA-Seq). Using functional association network analysis, we elucidate the molecular interactors of these signature genes. We then go on to demonstrate that our novel 22-gene signature strongly correlates with low tumoural proliferative activity, and with dormant disease and late metastatic recurrence (≥5 years after primary tumour diagnosis) in metastatic breast cancer in multiple clinical cohorts. These genes may govern the formation and persistence of disseminated tumour cell populations responsible for breast cancer recurrence, and therefore represent prospective novel candidates to inform future development of therapeutic strategies to target disseminated tumour cells in breast cancer, eliminate minimal residual disease and prevent metastatic recurrence

ALIGNMENT OF HG-AR VAN-DER-WAALS MOLECULE PHOTOFRAGMENTS FOLLOWING PHOTODISSOCIATION

Published versio

Human Alpha Defensin 5 Expression in the Human Kidney and Urinary Tract

The mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects.Using RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection.DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility