Roughness of the plasma membrane as an independent morphological parameter to study RBCs: A quantitative atomic force microscopy investigation

AbstractA novel approach to the study of RBCs based on the collection of three-dimensional high-resolution AFM images and on the measure of the surface roughness of their plasma membrane is presented. The dependence of the roughness from several parameters of the imaging was investigated and a general rule for a trustful analysis and comparison has been suggested. The roughness of RBCs is a morphology-related parameter which has been shown to be characteristic of the single cells composing a sample, but independent of the overall geometric shape (discocyte or spherocyte) of the erythrocytes, thus providing extra-information with respect to a conventional morphology study. The use of the average roughness value as a label of a whole sample was tested on different kinds of samples. Analyzed data revealed that the quantitative roughness value does not change after treatment of RBCs with various commonly used fixation and staining methods while a drastic decrease occurs when studying cells with membrane–skeletal alteration both naturally occurring or artificially induced by chemical treatments. The present method provides a quantitative and powerful tool for a novel approach to the study of erythrocytes structure through an ultrastructural morphological analysis with the potential to give information, in a non-invasive way, on the RBCs function

Mapping of physiological and trace elements with X-PEEM

We present chemical mapping of all physiologically relevant elements at the subcellular level, as well as the trace element Gd. A broad energy range (60-1200 eV) is fundamental to investigate all the elements in the same microscopic locations. Concentrated elements ($>$100 ppm) can be simply mapped by image ratio, while dilute species must be treated with great care to avoid artifacts. We propose a new method to obtain location maps of trace elements

RAPID GROWTH OF CHARGED PARTICLE MULTIPLICITY IN HIGH-ENERGY e+ e- ANNIHILATIONS

Hadron production by e+e− annihilation has been studied for c.m. energies W between 13 and 31.6 GeV. As a function of 1n W the charged particle multiplicity grows faster at high energy than at lower energies. This is correlated with a rise in the plateau of the rapidity distribution. The cross section sdσ/dx is found to scale within ±30% for x > 0.2 and 5 W 31.6 GeV

Argumentation in Foreign Policy Settings

This is a study of argumentation in three different kinds of high level, confidential, foreign policy settings: a collegial setting, a bureaucratic setting, and a bargaining setting. The causal and value assertions of the participants were coded using the detailed records of these three settings. The data show to be inadequate a defense/ attack model of argumentation in which the participants support their own arguments to make them resistant to attack, while attacking the weak spots in others'stated positions. In fact, there are few assertions which are supported by specific evidence, almost no mutually supported causal arguments, and the assertions which were attacked were no less emphasized than the assertions which were not attacked. More in accord with the data is the novel-arguments approach in which the key factor in persuasive argumentation is the development of arguments which others have not already taken into account.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67391/2/10.1177_002200277702100410.pd

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes