Subcellular protein expression models for microsatellite instability in colorectal adenocarcinoma tissue images

Background New bioimaging techniques capable of visualising the co-location of numerous proteins within individual cells have been proposed to study tumour heterogeneity of neighbouring cells within the same tissue specimen. These techniques have highlighted the need to better understand the interplay between proteins in terms of their colocalisation. Results We recently proposed a cellular-level model of the healthy and cancerous colonic crypt microenvironments. Here, we extend the model to include detailed models of protein expression to generate synthetic multiplex fluorescence data. As a first step, we present models for various cell organelles learned from real immunofluorescence data from the Human Protein Atlas. Comparison between the distribution of various features obtained from the real and synthetic organelles has shown very good agreement. This has included both features that have been used as part of the model input and ones that have not been explicitly considered. We then develop models for six proteins which are important colorectal cancer biomarkers and are associated with microsatellite instability, namely MLH1, PMS2, MSH2, MSH6, P53 and PTEN. The protein models include their complex expression patterns and which cell phenotypes express them. The models have been validated by comparing distributions of real and synthesised parameters and by application of frameworks for analysing multiplex immunofluorescence image data. Conclusions The six proteins have been chosen as a case study to illustrate how the model can be used to generate synthetic multiplex immunofluorescence data. Further proteins could be included within the model in a similar manner to enable the study of a larger set of proteins of interest and their interactions. To the best of our knowledge, this is the first model for expression of multiple proteins in anatomically intact tissue, rather than within cells in culture.QNRF grant NPRP 5-1345-1-228. BBSRC and University of Warwick Institute of Advanced Study

On the suitability of baked clay for archaeomagnetic studies as deduced from detailed rock-magnetic studies

Extensive rock-magnetic investigations have been carried out on baked clays from four kilns (two from Bulgaria and two from Switzerland) found in archaeological sites of different age. Knowledge of the magnetic characteristics of the grains responsible for the archaeomagnetic signal enables us to determine which baked clays have the stablest magnetization and why this is so. This is important in directional studies, but even more so in painstaking palaeointensity studies that require a very careful evaluation of the suitability of the burnt clay material. The proposed rock-magnetic experiments enable the identification of the carriers responsible for the remanence and an adequate interpretation of the experimental results connected with the palaeointensity evaluation. The experimental methods employed are illustrated with the particular results obtained from each of the four kilns studied. The preliminary elucidation of the magnetic mineralogy of the archaeological samples helps first by obtaining a more reliable palaeointensity result, and secondly by explaining some of the discrepancies in the palaeodirectional results. Examples of successful and failed palaeointensity experiments are given in relation to the magnetic properties previously established for each oven. The burnt-clay materials in this present study satisfy the essential condition of carrying a thermoremanence. In spite of that, it is shown that there are many factors that can produce undesirable magnetic properties and thus restrict the suitability of these materials for archaeomagnetic analysis. The most important factors influencing the magnetic behaviour during magneto-diagnostic experiments are: the degree of heating in antiquity, the initial composition of the unbaked material and the burial conditions. The large difference in heating temperatures within a particular archaeological feature is a major cause of variation in magnetic behaviour amongst individual specimens, and so preventing a successful pre-selection of specimens for palaeointensity experiments. Nevertheless, the study has shown a very good coincidence between the determined rock-magnetic characteristics and the success rate in palaeointensity evaluatio

A model of the spatial tumour heterogeneity in colorectal adenocarcinoma tissue

Background There have been great advancements in the field of digital pathology. The surge in development of analytical methods for such data makes it crucial to develop benchmark synthetic datasets for objectively validating and comparing these methods. In addition, developing a spatial model of the tumour microenvironment can aid our understanding of the underpinning laws of tumour heterogeneity. Results We propose a model of the healthy and cancerous colonic crypt microenvironment. Our model is designed to generate synthetic histology image data with parameters that allow control over cancer grade, cellularity, cell overlap ratio, image resolution, and objective level. Conclusions To the best of our knowledge, ours is the first model to simulate histology image data at sub-cellular level for healthy and cancerous colon tissue, where the cells have different compartments and are organised to mimic the microenvironment of tissue in situ rather than dispersed cells in a cultured environment. Qualitative and quantitative validation has been performed on the model results demonstrating good similarity to the real data. The simulated data could be used to validate techniques such as image restoration, cell and crypt segmentation, and cancer grading.BBSRC and University of Warwick Institute of Advanced Study. QNRF grant NPRP 5-1345-1-228

Extended and revised archaeomagnetic database and secular variation curves from Bulgaria for the last eight millennia

International audienceThe efforts of geophysicists to describe geomagnetic field behaviour in the past lead to creation of different geomagnetic field models. On the other hand, the established regional palaeosecular variations of geomagnetic elements are increasingly used for dating purposes in archaeology. Both of these goals can be achieved if sufficient amounts of long archaeomagnetic data sets exist for different geographical regions. The accumulation of archaeomagnetic determinations began at the middle of the last century, parallel with the progressive development of experimental methodology and acceptance criteria. The presence of great number of old determinations requires their critical assessment. The important question about the reliability of the associated dating intervals should be also re-assessed. All this requires the continuous refinement and extension of the accumulated databases. This paper presents the last synthesis of Bulgarian archaeomagnetic database and the local palaeosecular variation curves obtained using a statistical treatment based on Bayesian approach (RenCurve software). The rock-magnetic characteristics of the newly included, non-published results are summarized

Estimating cardiac active tension from wall motion—An inverse problem of cardiac biomechanics

The contraction of the human heart is a complex process as a consequence of the interaction of internal and external forces. In current clinical routine, the resulting deformation can be imaged during an entire heart beat. However, the active tension development cannot be measured in vivo but may provide valuable diagnostic information. In this work, we present a novel numerical method for solving an inverse problem of cardiac biomechanics—estimating the dynamic active tension field, provided the motion of the myocardial wall is known. This ill‐posed non‐linear problem is solved using second order Tikhonov regularization in space and time. We conducted a sensitivity analysis by varying the fiber orientation in the range of measurement accuracy. To achieve RMSE 0.95). The results obtained with non‐matching input data are promising and indicate directions for further improvement of the method. In future, this method will be extended to estimate the active tension field based on motion data from clinical images, which could provide important insights in terms of a new diagnostic tool for the identification and treatment of diseased heart tissue

Superconducting BSCCO Ceramics as Additive to the Zinc Electrode Mass in the Rechargeable Nickel-Zinc Batteries

The electronic conductivity of the main component of the zinc electrode in the rechargeable zinc-nickel battery – ZnO,  is rather poor and this is the main reason for the electrochemical heterogeneity of the anode mass and the loss of active surface area during charge/discharge cycling with a corresponding negative effect on the electrode characteristics In the present work, the possibility of application of superconductive cuprate Bi-Pb-Sr-Ca-Cu-O (BSCCO) ceramic as a multifunctional conductive additive to the zinc electrode mass is studied. Powder samples of the BSCCO ceramic Bi1,7Pb0,3Sr2Ca2Cu3Ox are produced by two-stage solid-state synthesis and they are physicochemically characterized. The XRD patterns and SEM observation reveal a well crystallized single phase of superconducting 2212 BSCCO system with average crystallite size 5-10 µm. The chemical stability of BSCCO ceramics in highly alkaline medium of the Ni-Zn battery is confirmed by structural and morphological analysis (XRD, SEM and EDX) of the samples before and after prolong exposure (96 h) to 7M KOH. The electrochemical tests are carried out by a specially designed prismatic alkaline Ni-Zn battery cell with conventional sintered type nickel electrodes and pasted zinc electrode with active electrode mass based on ZnO (88 wt.%) and addition of BSCCO powder or acetylene black as conductive additives. The study show that the zinc electrode with BSCCO superconducting ceramic additive exhibits very good cycleability, remarkable capacity stability and much higher discharge capacity at prolong charge/discharge cycling in comparison to the  zinc electrode with the “classic” carbon conductive additive. It is suggested that the addition of BSCCO ceramics improves not only conductivity of the electrode mass and reduces the gas evolution but also stabilizes porosity structure. The results obtained prove the possibility of application of superconducting BSCCO ceramics as a multifunctional additive to the active mass of the zinc electrodes for alkaline battery systems

Catalytic VOCs elimination over copper and cerium oxide modified mesoporous SBA-15 silica

[EN] Copper and cerium oxide bi-component materials with different Cu/Ce ratio were prepared using ordered SBA-15 silica as a support and compared with their bulk analogs. The samples were characterized by nitrogen physisorption, XRD, UV-Vis, FTIR, XPS, Raman spectroscopy and TPR with hydrogen. Cyclohexanol conversion was used as a catalytic test to obtain more information for the surface properties of the supported materials. The catalytic properties of the samples were studied in VOCs oxidation using toluene and ethyl acetate as probe molecules. A strong effect of mesoporous silica support and samples composition on the formation of catalytic sites was established. (C) 2012 Elsevier B.V. All rights reserved.Financial support of Bulgarian Academy of Science and National Scientific Fond of Ministry of Education Projects DTK 02/64 and ДНTC/Киtай 01/8, financial support from DGICYT in Spain (Project CTQ-2009-14495) and bilateral project Bulgarian-Spain Inter-academic Exchange Agreement (Project 2009BG0002) are acknowledged.Tsoncheva, T.; Issa, G.; Blasco Lanzuela, T.; Dimitrov, M.; Popova, M.; Hernández Morejudo, S.; Kovacheva, D.... (2013). Catalytic VOCs elimination over copper and cerium oxide modified mesoporous SBA-15 silica. Applied Catalysis A General. 453:1-12. https://doi.org/10.1016/j.apcata.2012.12.007S11245

Epsilon iron oxide: Origin of the high coercivity stable low Curie temperature magnetic phase found in heated archeological materials

The identification of epsilon iron oxide (-Fe2O3) as the low Curie temperature high coercivity stable phase (HCSLT) carrying the remanence in heated archeological samples has been achieved in samples from two archeological sites that exhibited the clearest evidence of the presence of the HCSLT. This uncommon iron oxide has been detected by Confocal Raman Spectroscopy (CRS) and characterized by rock magnetic measurements. Large numbers of -Fe2O3 microaggregates (in CO) or isolated clusters (in HEL) could be recognized, distributed over the whole sample, and embedded within the ceramic matrix, along with hematite and pseudobrookite and with minor amounts of anatase, rutile, and maghemite. Curie temperature estimates of around 170 degrees C for CO and 190 degrees C for HEL are lower than for pure, synthetic -Fe2O3 (227 degrees C). This, together with structural differences between the Raman spectra of the archeologically derived and synthetic samples, is likely due to Ti substitution in the -Fe2O3 crystal lattice. The -Fe2O3--Fe2O3--Fe2O3 transformation series has been recognized in heated archeological samples, which may have implications in terms of their thermal history and in the factors that govern the formation of -Fe2O3

Magneto-Optical and Multiferroic Properties of Transition-Metal (Fe, Co, or Ni)-Doped ZnO Layers Deposited by ALD

ZnO doped with transition metals (Co, Fe, or Ni) that have non-compensated electron spins attracts particular interest as it can induce various magnetic phenomena and behaviors. The advanced atomic layer deposition (ALD) technique makes it possible to obtain very thin layers of doped ZnO with controllable thicknesses and compositions that are compatible with the main microelectronic technologies, which further boosts the interest. The present study provides an extended analysis of the magneto optical MO Kerr effect and the dielectric properties of (Co, Fe, or Ni)-doped ZnO films prepared by ALD. The structural, magneto optical, and dielectric properties were considered in relation to the technological details of the ALD process and the corresponding dopant effects. All doped samples show a strong MO Kerr behavior with a substantial magnetization response and very high values of the Kerr polarization angle, especially in the case of ZnO/Fe. In addition, the results give evidence that Fe-doped ZnO also demonstrates a ferroelectric behavior. In this context, the observed rich and versatile physical nature and functionality open up new prospects for the application of these nanostructured materials in advanced electronic, spintronic, and optical devices