PD-0462: Towards dosimetric tracking with adaptive VMAT?

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Scanning tunneling microscopy and spectroscopy at low temperatures of the (110) surface of Te doped GaAs single crystals

We have performed voltage dependent imaging and spatially resolved spectroscopy on the (110) surface of Te doped GaAs single crystals with a low temperature scanning tunneling microscope (STM). A large fraction of the observed defects are identified as Te dopant atoms which can be observed down to the fifth subsurface layer. For negative sample voltages, the dopant atoms are surrounded by Friedel charge density oscillations. Spatially resolved spectroscopy above the dopant atoms and above defect free areas of the GaAs (110) surface reveals the presence of conductance peaks inside the semiconductor band gap. The appearance of the peaks can be linked to charges residing on states which are localized within the tunnel junction area. We show that these localized states can be present on the doped GaAs surface as well as at the STM tip apex.Comment: 8 pages, 8 figures, accepted for publication in PR

Implications of rising temperatures for gametophyte performance of two kelp species from Arctic waters

The aim of this study was to determine the temperature effects on photosynthesis, growth and reproduction in gametophytes of Alaria esculenta (Linnaeus) Greville and Saccharina latissima (Linnaeus) C. E. Lane, C. Mayes, Druehl et G. W. Saunders from the Artic waters. After 24 days of culture, no gametophytes of either species survived at 20 degrees C. Most growth parameters were greater at 10-15 degrees C than at 5 degrees C. Length and width were similar for both species, but area was greater for A. esculenta and cell number was greater for S. latissima. Female gametophytes were larger than male gametophytes in width and area, but the opposite was observed in cell number. In A. esculenta, but not for S. latissima, the percentage of female gametophytes decreased with increasing temperature. Alaria esculenta female gametophytes produced more sporophytes at 5 degrees C than at 10 degrees C, with no sporophytes at 15 degrees C. In S. latissima, all female gametophytes produced sporophytes at both 5 degrees C and 10 degrees C, with a small percentage of sporophytes at 15 degrees C. Saccharina latissima still had a measurable F v/F m at 20 degrees C, while the F v/F m of A. esculenta was zero at this temperature. Maximum relative electron transport rate (rETR(max)) and non-photochemical quenching (NPQ) were constant in the male and female gametophytes of A. esculenta and the male gametophytes of S. latissima at temperatures between 5 degrees C and 15 degrees C. Photosynthesis was saturated at a higher irradiance in A. esculenta than in S. latissima

Increased chromosomal radiosensitivity in asymptomatic carriers of a heterozygous BRCA1 mutation

Background: Breast cancer risk increases drastically in individuals carrying a germline BRCA1 mutation. The exposure to ionizing radiation for diagnostic or therapeutic purposes of BRCA1 mutation carriers is counterintuitive, since BRCA1 is active in the DNA damage response pathway. The aim of this study was to investigate whether healthy BRCA1 mutations carriers demonstrate an increased radiosensitivity compared with healthy individuals. Methods: We defined a novel radiosensitivity indicator (RIND) based on two endpoints measured by the G2 micronucleus assay, reflecting defects in DNA repair and G2 arrest capacity after exposure to doses of 2 or 4 Gy. We investigated if a correlation between the RIND score and nonsense-mediated decay (NMD) could be established. Results: We found significantly increased radiosensitivity in the cohort of healthy BRCA1 mutation carriers compared with healthy controls. In addition, our analysis showed a significantly different distribution over the RIND scores (p = 0.034, Fisher’s exact test) for healthy BRCA1 mutation carriers compared with non-carriers: 72 % of mutation carriers showed a radiosensitive phenotype (RIND score 1–4), whereas 72 % of the healthy volunteers showed no radiosensitivity (RIND score 0). Furthermore, 28 % of BRCA1 mutation carriers had a RIND score of 3 or 4 (not observed in control subjects). The radiosensitive phenotype was similar for relatives within several families, but not for unrelated individuals carrying the same mutation. The median RIND score was higher in patients with a mutation leading to a premature termination codon (PTC) located in the central part of the gene than in patients with a germline mutation in the 5′ end of the gene. Conclusions: We show that BRCA1 mutations are associated with a radiosensitive phenotype related to a compromised DNA repair and G2 arrest capacity after exposure to either 2 or 4 Gy. Our study confirms that haploinsufficiency is the mechanism involved in radiosensitivity in patients with a PTC allele, but it suggests that further research is needed to evaluate alternative mechanisms for mutations not subjected to NMD

Assessment of Microbial Diversity in Biofilms Recovered from Endotracheal Tubes Using Culture Dependent and Independent Approaches

Ventilator-associated pneumonia (VAP) is a common nosocomial infection in mechanically ventilated patients. Biofilm formation is one of the mechanisms through which the endotracheal tube (ET) facilitates bacterial contamination of the lower airways. In the present study, we analyzed the composition of the ET biofilm flora by means of culture dependent and culture independent (16 S rRNA gene clone libraries and pyrosequencing) approaches. Overall, the microbial diversity was high and members of different phylogenetic lineages were detected (Actinobacteria, beta-Proteobacteria, Candida spp., Clostridia, epsilon-Proteobacteria, Firmicutes, Fusobacteria and gamma-Proteobacteria). Culture dependent analysis, based on the use of selective growth media and conventional microbiological tests, resulted in the identification of typical aerobic nosocomial pathogens which are known to play a role in the development of VAP, e.g. Staphylococcus aureus and Pseudomonas aeruginosa. Other opportunistic pathogens were also identified, including Staphylococcus epidermidis and Kocuria varians. In general, there was little correlation between the results obtained by sequencing 16 S rRNA gene clone libraries and by cultivation. Pyrosequencing of PCR amplified 16 S rRNA genes of four selected samples resulted in the identification of a much wider variety of bacteria. The results from the pyrosequencing analysis suggest that these four samples were dominated by members of the normal oral flora such as Prevotella spp., Peptostreptococcus spp. and lactic acid bacteria. A combination of methods is recommended to obtain a complete picture of the microbial diversity of the ET biofilm

Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics

RATIONALE: Atherosclerotic lesions are known for their cellular heterogeneity, yet the molecular complexity within the cells of human plaques has not been fully assessed. OBJECTIVE: Using single-cell transcriptomics and chromatin accessibility, we gained a better understanding of the pathophysiology underlying human atherosclerosis. METHODS AND RESULTS: We performed single-cell RNA and single-cell ATAC sequencing on human carotid atherosclerotic plaques to define the cells at play and determine their transcriptomic and epigenomic characteristics. We identified 14 distinct cell populations including endothelial cells, smooth muscle cells, mast cells, B cells, myeloid cells, and T cells and identified multiple cellular activation states and suggested cellular interconversions. Within the endothelial cell population, we defined subsets with angiogenic capacity plus clear signs of endothelial to mesenchymal transition. CD4+ and CD8+ T cells showed activation-based subclasses, each with a gradual decline from a cytotoxic to a more quiescent phenotype. Myeloid cells included 2 populations of proinflammatory macrophages showing IL (interleukin) 1B or TNF (tumor necrosis factor) expression as well as a foam cell-like population expressing TREM2 (triggering receptor expressed on myeloid cells 2) and displaying a fibrosis-promoting phenotype. ATACseq data identified specific transcription factors associated with the myeloid subpopulation and T cell cytokine profiles underlying mutual activation between both cell types. Finally, cardiovascular disease susceptibility genes identified using public genome-wide association studies data were particularly enriched in lesional macrophages, endothelial, and smooth muscle cells. CONCLUSIONS: This study provides a transcriptome-based cellular landscape of human atherosclerotic plaques and highlights cellular plasticity and intercellular communication at the site of disease. This detailed definition of cell communities at play in atherosclerosis will facilitate cell-based mapping of novel interventional targets with direct functional relevance for the treatment of human diseas