Influence of block versus random monomer distribution on the cellular uptake of hydrophilic copolymers

The use of polymers has revolutionized the field of drug delivery in the past two decades. Properties such as polymer size, charge, hydrophilicity, or branching have all been shown to play an important role in the cellular internalization of polymeric systems. In contrast, the fundamental impact of monomer distribution on the resulting biological properties of copolymers remains poorly studied and is always only investigated for biologically active self-assembling polymeric systems. Here, we explore the fundamental influence of monomer distribution on the cellular uptake of nonaggregating and biologically passive copolymers. Reversible addition–fragmentation chain-transfer (RAFT) polymerization was used to prepare precisely defined copolymers of three hydrophilic acrylamide monomers. The cellular internalization of block copolymers was compared with the uptake of a random copolymer where monomers are statistically distributed along the chain. The results demonstrate that monomer distribution in itself has a negligible impact on copolymer uptake

A Gaussian-Mixture based stochastic framework for the interpretation of spatial heterogeneity in multimodal fields

We provide theoretical formulations enabling characterization of spatial distributions of variables (such as, e.g., conductivity/permeability, porosity, vadose zone hydraulic parameters, and reaction rates) that are typical of hydrogeological and/or geochemical scenarios associated with randomly heterogeneous geomaterials and are organized on various scales of heterogeneity. Our approach and ensuing formulations embed the joint assessment of the probability distribution of a target variable and its associated spatial increments, DY, taken between locations separated by any given distance (or lag). The spatial distribution of Y is interpreted through a bimodal Gaussian mixture model. The modes of the latter correspond to an indicator random field which is in turn related to the occurrence of different processes and/or geomaterials within the domain of observation. The distribution of each component of the mixture is governed by a given length scale driving the strength of its spatial correlation. Our model embeds within a unique theoretical framework the main traits arising in a stochastic analysis of these systems. These include (i) a slight to moderate asymmetry in the distribution of Y and (ii) the occurrence of a dominant peak and secondary peaks in the distribution of DY whose importance changes with lag together with the moments of the distribution. This causes the probability distribution of increments to scale with lag in way that is consistent with observed experimental patterns. We analyze the main features of the modeling and parameter estimation framework through a set of synthetic scenarios. We then consider two experimental datasets associated with different processes and observation scales. We start with an original dataset comprising microscale reaction rate maps taken at various observation times. These are evaluated from AFM imaging of the surface of a calcite crystal in contact with a fluid and subject to dissolution. Such recent high resolution imaging techniques are key to enhance our knowledge of the processes driving the reaction. The second dataset is a well established collection of Darcy-scale air-permeability data acquired by Tidwell and Wilson (1999) [Water Resour Res, 35, 3375-3387] on a block of volcanic tuff through minipermeameters associated with various measurement scales

Stochastic Assessment of Dissolution at Fluid-Mineral Interfaces

Chemical weathering associated with dissolution/precipitation at interfaces between minerals and flowing fluids is key for the evolution of geologic systems, including groundwater contamination and storage capacity. Relying on Atomic Force Microscopy (AFM) yields reaction rates at nanoscale resolutions. Challenges limiting our ability to quantify heterogeneity associated with these processes include establishing reliable platforms allowing AFM imaging of real-time and in situ absolute material fluxes across mineral surfaces under continuous flow conditions to complement typically acquired surface topography images. We provide an experimental workflow and heterogeneous absolute rates at the nanoscale across the surface of a calcite crystal under dissolution. These high-quality experimental observations are then interpreted through a stochastic approach. The latter is geared to embed diverse kinetic modes driving the degree of spatial heterogeneity of the reaction and corresponding to different mechanistic processes documented across the crystal surface.Quantification of basic processes underpinning precipitation/dissolution at mineral/fluid interfaces is key for realistic assessment of chemical weathering rates driving rock morphology, subsurface storage capacity and contamination. We provide direct observation of the complex mechanistic processes acting at nanoscales through an original experimental platform relying on Atomic Force Microscopy imaging to evaluate absolute material fluxes associated with dissolution of a mineral subject to reaction under continuous flow conditions. Dissolution is characterized at very high spatial resolutions (similar to 10 nm). This enables observing in real-time and in situ mechanistic processes driving system evolution. The ensuing rich data set of absolute reaction rates displays a marked degree of spatial heterogeneity. The latter is then interpreted within a stochastic framework to yield a detailed mechanistic appraisal of mineral dissolution.A platform to evaluate absolute nanoscale topographic measurements of a crystal sample subject to dissolution/precipitation is designed The associated spatially heterogeneous fields of absolute material fluxes across the surface are evaluated Reaction rates are described through a stochastic framework encapsulating behaviors of surface features driving dissolution processe

Iron availability in tissue microenvironmen t: The key role of ferroportin

Body iron levels are regulated by hepcidin, a liver‐derived peptide that exerts its function by controlling the presence of ferroportin (FPN), the sole cellular iron exporter, on the cell surface. Hepcidin binding leads to FPN internalization and degradation, thereby inhibiting iron release, in particular from iron‐absorbing duodenal cells and macrophages involved in iron recycling. Disruption in this regulatory mechanism results in a variety of disorders associated with iron-deficiency or overload. In recent years, increasing evidence has emerged to indicate that, in addition to its role in systemic iron metabolism, FPN may play an important function in local iron control, such that its dysregulation may lead to tissue damage despite unaltered systemic iron homeostasis. In this review, we focus on recent discoveries to discuss the role of FPN‐mediated iron export in the microenvironment under both physiological and pathological conditions

Process Modeling of Mineral Dissolution From Nano-Scale Surface Topography Observations

We present an innovative approach that combines a unique real-time data set documenting absolute dissolution rates of a calcite crystal with an original reactive transport model tailored to the analysis of the dynamics of nano-scale mineral dissolution processes. Providing robust and physically based fundamental understanding on the kinetics of mineral dissolution is at the core of various geo-engineered strategies to quantify chemical weathering patterns across diverse spatial and temporal scales. Here, we rely on data obtained through Atomic Force Microscopy. We provide a mathematical framework to describe three-dimensional dynamics of the mineral surface topography, and show convergence of the numerical approach for vertical grid spacing down to sub-nm resolution.We focus on some fundamental aspects related to modeling of mechanisms underpinning chemical weathering of minerals. The latter is a ubiquitously active phenomenon driving the Earth system evolution. It underpins a variety of physico-chemical processes that are at the core of various geo-engineered strategies for sustainable development, including the assessment of the role of underground storage of carbon dioxide or geothermal energy in environmental stewardship. Here, we propose an innovative approach that combines for the first time a reactive transport model with a unique real-time data set documenting absolute calcite dissolution rates. Experimental observations correspond to high-resolution (i.e., horizontal and vertical resolution of 19.5 and similar to 0.1 nm, respectively) in-situ Atomic Force Microscopy data obtained across a calcite sample subject to dissolution. Our original reactive transport model is designed to assist quantitative appraisal of the ensuing mineral surface topography. To combine these two powerful techniques, we provide a mathematical framework for the representation of the evolution (in space and time) of the mineral surface topography, and document the robustness of the numerical approach through a convergence analysis for vertical grid spacing down to sub-nm resolution.We propose a novel combination of an original reactive transport model with a unique data set documenting absolute calcite dissolution rates We provide a sound mathematical framework to describe three-dimensional dynamics of mineral surface topography We document convergence of the numerical approach for vertical grid spacing down to sub-nm resolutio

THE INFLUENCE OF THERMAL BRIDGES ON REFRACTORY LININGS

In this study we analyze the influence of thermal bridges caused by the presence of anchoring systems. The engineering, especially heat transfer calculation, allow the preventive definition of the most suitable insulating linings. Thanks to the thermography, it is possible to determine which are the parameters that actually influence the heat transfer process, thus to work with not only theoretical values but also actual ones. Corrective actions together with general considerations are illustrated in this study, supported by drawings, pictures and thermo graphics scans

Local iron homeostasis in the breast ductal carcinoma microenvironment

Abstract BACKGROUND: While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. METHODS: Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. RESULTS: We confirm previous results by showing that breast cancer epithelial cells present an 'iron-utilization phenotype' with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an 'iron-donor' phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. CONCLUSIONS: The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context.info:eu-repo/semantics/publishedVersio