Proposal for a 10-high-power-fields scoring method for the assessment of tumor budding in colorectal cancer

Although tumor budding is linked to adverse prognosis in colorectal cancer, it remains largely unreported in daily diagnostic work due to the absence of a standardized scoring method. Our aim was to assess the inter-observer agreement of a novel 10-high-power-fields method for assessment of tumor budding at the invasive front and to confirm the prognostic value of tumor budding in our setting of colorectal cancers. Whole tissue sections of 215 colorectal cancers with full clinico-pathological and follow-up information were stained with cytokeratin AE1/AE3 antibody. Presence of buds was scored across 10-high-power fields at the invasive front by two pathologists and two additional observers were asked to score 50 cases of tumor budding randomly selected from the larger cohort. The measurements were correlated to the patient and tumor characteristics. Inter-observer agreement and correlation between observers' scores were excellent (P<0.0001; intraclass correlation coefficient=0.96). A test subgroup of 65 patients (30%) was used to define a valid cutoff score for high-grade tumor budding and the remaining 70% of the patients were entered into the analysis. High-grade budding was defined as an average of ≥10 buds across 10-high-power fields. High-grade budding was associated with a higher tumor grade (P<0.0001), higher TNM stage (P=0.0003), vascular invasion (P<0.0001), infiltrating tumor border configuration (P<0.0001) and reduced survival (P<0.0001). Multivariate analysis confirmed its independent prognostic effect (P=0.007) when adjusting for TNM stage and adjuvant therapy. Using 10-high-power fields for evaluating tumor budding has independent prognostic value and shows excellent inter-observer agreement. Like the BRE and Gleason scores in breast and prostate cancers, respectively, tumor budding could be a basis for a prognostic score in colorectal cancer.

The STEREO/PLASTIC response to solar wind ions (Flight measurements and models)

The Plasma and Supra-Thermal Ion Composition (PLASTIC) instrument is one of four experiment packages on board of the two identical STEREO spacecraft A and B, which were successfully launched from Cape Canaveral on 26 October 2006. During the two years of the nominal STEREO mission, PLASTIC is providing us with the plasma characteristics of protons, alpha particles, and heavy ions. PLASTIC will also provide key diagnostic measurements in the form of the mass and charge state composition of heavy ions. Three measurements (E/qk, time of flight, ESSD) from the pulse height raw data are used to characterize the solar wind ions from the solar wind sector, and part of the suprathermal particles from the wide-angle partition with respect to mass, atomic number and charge state. In this paper, we present a new method for flight data analysis based on simulations of the PLASTIC response to solar wind ions. We present the response of the entrance system / energy analyzer in an analytical form. Based on stopping power theory, we use an analytical expression for the energy loss of the ions when they pass through a thin carbon foil. This allows us to model analytically the response of the time of flight mass spectrometer to solar wind ions. Thus we present a new version of the analytical response of the solid state detectors to solar wind ions. Various important parameters needed for our models were derived, based on calibration data and on the first flight measurements obtained from STEREO-A. We used information from each measured event that is registered in full resolution in the Pulse Height Analysis words and we derived a new algorithm for the analysis of both existing and future data sets of a similar nature which was tested and works well. This algorithm allows us to obtain, for each measured event, the mass, atomic number and charge state in the correct physical units. Finally, an important criterion was developed for filtering our Fe raw flight data set from the pulse height data without discriminating charge states.

Tracking individual membrane proteins and their biochemistry: The power of direct observation

The advent of single molecule fluorescence microscopy has allowed experimental molecular biophysics and biochemistry to transcend traditional ensemble measurements, where the behavior of individual proteins could not be precisely sampled. The recent explosion in popularity of new super-resolution and super-localization techniques coupled with technical advances in optical designs and fast highly sensitive cameras with single photon sensitivity and millisecond time resolution have made it possible to track key motions, reactions, and interactions of individual proteins with high temporal resolution and spatial resolution well beyond the diffraction limit. Within the purview of membrane proteins and ligand gated ion channels (LGICs), these outstanding advances in single molecule microscopy allow for the direct observation of discrete biochemical states and their fluctuation dynamics. Such observations are fundamentally important for understanding molecular-level mechanisms governing these systems. Examples reviewed here include the effects of allostery on the stoichiometry of ligand binding in the presence of fluorescent ligands; the observation of subdomain partitioning of membrane proteins due to microenvironment effects; and the use of single particle tracking experiments to elucidate characteristics of membrane protein diffusion and the direct measurement of thermodynamic properties, which govern the free energy landscape of protein dimerization. The review of such characteristic topics represents a snapshot of efforts to push the boundaries of fluorescence microscopy of membrane proteins to the absolute limit.

Characterization of the Abydos region through OSIRIS high-resolution images in support of CIVA measurements

Context. On 12 November 2014, the European mission Rosetta delivered the Philae lander on the nucleus of comet 67P /Churyumov-Gerasimenko (67P). After the first touchdown, the lander bounced three times before finally landing at a site named Abydos. Aims. We provide a morphologically detailed analysis of the Abydos landing site to support Philae's measurements and to give context for the interpretation of the images coming from the Comet Infrared and Visible Analyser (CIVA) camera system onboard the lander. Methods. We used images acquired by the OSIRIS Narrow Angle Camera (NAC) on 6 December 2014 to perform the analysis of the Abydos landing site, which provided the geomorphological map, the gravitational slope map, the size-frequency distribution of the boulders. We also computed the albedo and spectral reddening maps. Results. The morphological analysis of the region could suggest that Philae is located on a primordial terrain. The Abydos site is surrounded by two layered and fractured outcrops and presents a 0.02 km(2) talus deposit rich in boulders. The boulder size frequency distribution gives a cumulative power-law index of 4.0 + 0.3/0.4, which is correlated with gravitational events triggered by sublimation and /or thermal fracturing causing regressive erosion. The average value of the albedo is 5.8% at lambda(1) = 480.7 nm and 7.4% at lambda(2) = 649.2 nm, which is similar to the global albedos derived by OSIRIS and CIVA, respectively.