1,721,244 research outputs found
Resampling approaches for the quantitative analysis of spatially distributed cells
Full text linkImage segmentation is a crucial step in various image analysis pipelines and constitutes one of the cutting-edge areas of digital pathology. The advent of quantitative analysis has enabled the evaluation of millions of individual cells in tissues, allowing for the combined assessment of morphological features, biomarker expression, and spatial context.
The recorded cells can be described as a point pattern process. However, the classical statistical approaches to point pattern processes prove unreliable in this context due to the presence of multiple irregularly-shaped interstitial cell-devoid spaces in the domain, which correspond to anatomical features (e.g. vessels, lipid vacuoles, glandular lumina) or tissue artefacts (e.g. tissue fractures), and whose coordinates are unknown. These interstitial spaces impede the accurate calculation of the domain area, resulting in biased clustering measurements. Moreover, the mistaken inclusion of empty regions of the domain can directly impact the results of hypothesis testing.
The literature currently lacks any introduced bias correction method to address interstitial cell- devoid spaces. To address this gap, we propose novel resampling methods for testing spatial randomness and evaluating relationships among different cell populations. Our methods obviate the need for domain area estimation and provide non-biased clustering measurements. We created the SpaceR software (https://github.com/GBertolazzi/SpaceR) to enhance the accessibility of our methodologies
The good and bad of targeting cancer-associated extracellular matrix
Full text linkThe maintenance of tissue homeostasis requires extracellular matrix (ECM) remodeling. Immune cells actively participate in regenerating damaged tissues contributing to ECM deposition and shaping. Dysregulated ECM deposition characterizes fibrotic diseases and cancer stromatogenesis, where a chronic inflammatory state sustains the ECM increase. In cancer, the ECM fosters several steps of tumor progression, providing pro-survival and proliferative signals, promoting tumor cell dissemination via collagen fibers or acting as a barrier to impede drug diffusion. Interfering with processes leading to chronic ECM deposition, as occurring in cancer, might allow the simultaneous targeting of both primary tumors and metastatic lesions. However, a note of caution comes from data showing that defective ECM deposition is associated with an exacerbated inflammatory and autoimmune phenotype and to lymphomagenesis. Immune cells display ITIM-inhibitory receptors recognizing collagens as counter ligands, which negatively regulate the immune response. This is in line with the idea that ECM components can provide homeostatic signals to immune cells to regulate and prevent unwanted activation, a concept particularly relevant in cancer where these mechanisms could be in place to keep infiltrating immune cells in a suppressive pro-tumoral state. In this context, the pharmacological targeting of myeloid cells, for which both direct and indirect roles in ECM deposition have been shown, can be a relevant option to this purpose
Common extracellular matrix regulation of myeloid cell activity in the bone marrow and tumor microenvironments
Full text linkThe complex interaction between cells undergoing transformation and the various stromal and immunological cell components of the tumor microenvironment (TME) crucially influences cancer progression and diversification, as well as endowing clinical and prognostic significance. The immunosuppression characterizing the TME depends on the recruitment and activation of different cell types including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Less considered is the non-cellular component of the TME. Here, we focus on the extracellular matrix (ECM) regulatory activities that, within the TME, actively contribute to many aspects of tumor progression, acting on both tumor and immune cells. Particularly, ECM-mediated regulation of tumor-associated immunosuppression occurs through the modulation of myeloid cell expansion, localization, and functional activities. Such regulation is not limited to the TME but occurs also within the bone marrow, wherein matricellular proteins contribute to the maintenance of specialized hematopoietic stem cell niches thereby regulating their homeostasis as well as the generation and expansion of myeloid cells under both physiological and pathological conditions. Highlighting the commonalities among ECM-myeloid cell interactions in bone marrow and TME, in this review we present a picture in which myeloid cells might sense and respond to ECM modifications, providing different ECM-myeloid cell interfaces that may be useful to define prognostic groups and to tailor therapeutic interventions
Development of a control-oriented power plant simulator for the molten salt fast reactor
Full text linkIn this paper, modelling and simulation of a control-oriented plant-dynamics tool for the molten salt fast reactor (MSFR) is presented. The objective was to develop a simulation tool aimed at investigating the plant response to standard control transients, in order to support the system design finalization and the definition of control strategies. The simulator was developed employing the well tested, flexible and open-source object-oriented Modelica language. A one-dimensional modelling approach was used for thermal-hydraulics and heat transfer. Standard and validated thermal-hydraulic Modelica libraries were employed for various plant components (tubes, pumps, turbines, etc.). An effort was spent in developing a new MSR library modelling the 1D flow of a liquid nuclear fuel, including an ad-hoc neutron-kinetics model which properly takes into consideration the motion of the Delayed Neutron Precursors along the fuel circuit and the consequent reactivity insertion due to the variation of the effective delayed fractions. An analytical steady-state 2-D model of the core and the fuel circuit was developed using MATLAB in order to validate the Decay Neutron Precursors model implemented in the plant simulator. The plant simulator was then employed to investigate the plant dynamics in response to three transients (variation of fuel flow rate, intermediate flow rate and turbine gas flow rate) that are relevant to control purposes. Simulation outcomes highlight the typical reactor-follows-turbine behavior of the MSFR, and they show the small influence of fuel and intermediate flow rate on the reactor power and their strong effects on the temperatures in their respective circuits. Starting from the insights on the reactor behavior gained from the analysis of its free dynamics, the plant simulator here developed will provide a valuable tool in support to the finalization of the design phase, the definition of control strategies and the identification of controlled operational procedures for reactor startup and shutdown
Dual role of the complement system in pre-eclampsia
No full textComplement is an important player of the inflammatory process associated with pre-eclampsia (PE) as suggested by the finding reported by several groups that complement activation products are present both in the circulation and at tissue level in PE patients. We now present data showing that activators of the classical and lectin pathways play a different role in inducing local changes in PE placentae.
Immunohistochemical analysis of placental tissue revealed deposition of C1q and MBL on endothelial cells and stroma in normal placentae, The distribution of C1q and MBL was essentially similar in PE placentae, but the staining intensity was definitely stronger. Failure to detect C1s excluded complement activation through the classical pathway, while the presence of C4 and C3 was compatible with the activation of the lectin pathway. Deposits of C9 in the basal plate enriched in fibrinoid material and in the subendothelium of vessels, particularly in those undergoing acute atherosis, were observed in PE placentae.
The pathogenic role of the lectin pathway of complement activation in PE was investigated using the CBA/J x DBA/2 mouse model of PE characterized by recurrent miscarriages. Pregnancy loss was found to be associated with an early localization of MBL-A, but not of MBL-C, at embryo implantation sites followed by deposition of C4, C3 and C9. C1q was also detected at the same sites in the absence of C1s ruling out its involvement in the classical pathway activation. To determine the contribution of MBL-A to embryo resorption, we generated female MBL-A -/- CBA/J mice that were mated to DBA/2 male mice. This mating combination resulted in a significant decrease in the miscarriage rate. Similar results were obtained treating MBL-A +/+ CBA/J female mice pregnant by DBA/2 male mice with Polyman2, a mannosylated molecule known to bind to MBL-A and to control brain ischemic injury.
We have previously shown that extravillous trophoblasts invading the decidua and surrounding remodelled spiral arteries synthesize C1q and that C1q-/- mice, like PE patients, fail to remodel these vessels. Data will be presented indicating that this pathological situation can be reversed by mating C1q +/+ male mice with C1q -/- female mice. Under this condition the vessels are to a large extent remodelled and are surrounded by trophoblasts expressing C1q
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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