BackgroundLower urinary tract symptoms (LUTS) are a costly and pervasive medical problem for millions of aging men. Recent studies have showed that peri-urethral tissue fibrosis is an untreated ...pathobiology contributing to LUTS. Fibrosis results from excessive extracellular matrix deposition which increases transition zone and peri-urethral tissue stiffness and compromises prostatic urethral flexibility and compliance, producing urinary obstructive symptoms. Inflammatory cells, including neutrophils, macrophages, and T-lymphocytes, secrete a medley of pro-fibrotic proteins into the prostatic microenvironment, including IFNγ, TNFα, CXC-type chemokines, and interleukins, all of which have been implicated in inflammation-mediated fibrosis. Among these, IL-4 and IL-13 are of particular interest because they share a common signaling axis that, as shown here for the first time, promotes the expression and maintenance of IL-4, IL-13, their cognate receptors, and ECM components by prostate fibroblasts, even in the absence of immune cells. Based on studies presented here, we hypothesize that the IL-4/IL-13 axis promotes prostate fibroblast activation to ECM-secreting cells.MethodsN1 or SFT1 immortalized prostate stromal fibroblasts were cultured and treated, short- or long-term, with pro-fibrotic proteins including IL-4, IL-13, TGF-β, TNF-α, IFNγ, with or without prior pre-treatment with antagonists or inhibitors. Protein expression was assessed by immunohistochemistry, immunofluorescence, ELISA, immunoblot, or Sircoll assays. Transcript expression levels were determined by qRT-PCR. Intact cells were counted using WST assays.ResultsIL-4Rα, IL-13Rα1, and collagen are concurrently up-regulated in human peri-urethral prostate tissues from men with LUTS. IL-4 and IL-13 induce their own expression as well as that of their cognate receptors, IL-4Rα and IL-13Rα1. Low concentrations of IL-4 or IL-13 act as cytokines to promote prostate fibroblast proliferation, but higher (>40ng/ml) concentrations repress cellular proliferation. Both IL-4 and IL-13 robustly and specifically promote collagen transcript and protein expression by prostate stromal fibroblasts in a JAK/STAT-dependent manner. Moreover, IL-4 and IL-13-mediated JAK/STAT signaling is coupled to activation of the IL-4Rα receptor.ConclusionsTaken together, these studies show that IL-4 and IL-13 signal through the IL-4Rα receptor to activate JAK/STAT signaling, thereby promoting their own expression, that of their cognate receptors, and collagens. These finding suggest that the IL-4/IL-13 signaling axis is a powerful, but therapeutically targetable, pro-fibrotic mechanism in the lower urinary tract.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Regional‐scale groundwater quality degradation from nonpoint source pollution threatens the long‐term sustainability of major alluvial aquifer‐aquitard systems worldwide. Models are needed to ...simulate regionally upscaled transport processes in heterogeneous geology that produces non‐Fickian (anomalous) transport. In this investigation, we show the impact of nonhorizontal and nonvertical mean flow direction on non‐Fickian transport within a 3D, kilometer‐scale, typical alluvial aquifer‐aquitard system. Notably, vertical anisotropy in K and seasonal pumping and recharge can fundamentally change hydraulic gradients and shift the mean flow direction between mostly horizontal and mostly vertical flow. Detailed 3D flow and transport simulations under varying mean flow directions indicate that alterations to hydraulic gradients which control the mean flow direction can lead to increasingly non‐Fickian transport. Under mostly horizontal flow, diffusion and slow advection dominant low‐K facies slow mass transfer rates from low‐K material, and preferential flow along connected high‐K networks causes increased spatial spreading along the mean flow direction. Conversely, predominantly vertical flow caused by spatially distributed pumping and recharge shifts mass transfer processes in low‐K material from diffusion and slow advection dominant to advection dominant, resulting in vertically oriented particle trajectories that compactly migrate through high‐K and low‐K facies alike, and increasingly Fickian transport. Thus, mean flow direction transience driven by vertical anisotropy in K and seasonal pumping and recharge can create oscillating transport patterns, that range from persistently non‐Fickian to more Fickian. Results illustrate the regional‐scale hydrogeologic factors that explain why upscaled transport models fail to capture non‐Fickian effects resulting from mean flow direction transience
Plain Language Summary
Regional‐scale groundwater quality degradation from nonpoint source pollution threatens long‐term aquifer sustainability and demands accurate contaminant transport models. These models must effectively represent non‐Fickian (i.e., anomalous) transport, which is widely observed in nature, and characterized by non‐Gaussian travel time and spatial spreading of subsurface plumes. In this research, we simulate groundwater flow and contaminant transport in a geostatistical representation of a regional‐scale alluvial aquifer‐aquitard system. We vary the vertical and horizontal hydraulic gradients, and thus, the mean direction of fluid flow and the hydraulic forcings on different sediments that control mass transfer processes. Results demonstrate that as the mean flow direction is increasingly parallel to the direction of laterally extensive aquifer stratigraphy, increasingly non‐Fickian transport is observed. These results suggest that strong vertical anisotropy in hydraulic conductivity and seasonal pumping and recharge can create strong vertical gradients and increasingly vertical flow that lead to more compact plumes, and when fields are fallow, ambient horizontal hydraulic gradients produce more non‐Fickian transport. These findings have important implications for efforts to upscale transport, explain why some boundary conditions remain difficult to solve with existing methods, and reveal the hydrogeologic parameters that may be used to improve existing transport modeling in regional aquifer‐aquitard systems
Key Points
Mean flow direction modulates anomalous transport in a heterogeneous alluvial aquifer‐aquitard
Transport is more non‐Fickian under horizontal flow with diffusion dominant facies
Strong vertical gradients can switch low‐K facies from diffusion to advection dominant
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
As a result of the study, fundamentally new results were obtained that allow creating intelligent decision support systems for the classification of medical risk. A bioimpedance analysis model has ...been created based on multifrequency bioimpedance measurement, which allows decomposition of the biomaterial impedance into structural elements. On the basis of the proposed model, descriptors were formed, intended for classifiers executed on trained neural networks. To obtain descriptors, multifrequency sounding of the biomaterial was carried out, on the basis of which Cole's graphs were constructed. Using iterative algorithms and these graphs, Voit models of biomaterial impedance were obtained. The parameters of these models are used as descriptors for the trained classifiers. In modern healthcare, the task of long-term monitoring of a person's condition is almost always associated with either his hospitalization, which is unacceptable both for the working-age population and in some cases for sick people, or with the rent of expensive monitoring systems for a period not exceeding, as a rule, 24 x hours, which is not always enough for diagnostic tasks.
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•A new design of the SAW UV is proposed, in which the sensitive element is located outside the acoustic channel and does not affect the propagation of SAW, which makes it possible to ...use such a sensor wireless in the frequency range 2400–2483 MHz, where wireless sensors have compact antennas.•It It is proposed to connect the impedance sensitive to UV radiation not to reflective, but to the transceiver IDT, which made it possible to increase the sensitivity of the sensor to 8000 ppm/(μW/cm2).•New sensor design allowed us to obtain 8000 ppm/μW cm2 sensitivity, measure UV radiation intensity from some units μW/cm2 to 4 mW/cm2 and to reduce the response time.•The theoretical and experimental studies of reflection coefficient UV dependence can also be used for the development of passive wireless UV radiation sensors.
An investigation of impedance-loaded surface acoustic waves (SAW) UV sensor is presented in this paper. New sensor design allowed us to obtain 8000 ppm/μW·cm2 sensitivity, measure UV radiation intensity from some units μW/cm2 to 4 mW/cm2 and to reduce the response time. The photosensitive film is located outside the acoustic channel in our design of the sensor, which makes it possible to avoids SAW damping by the surface of the film. The theoretical and experimental studies of reflection coefficient UV dependence can also be used for the development of passive wireless UV radiation sensors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Plasmon-induced chemical reactions (PICRs) have recently become promising approaches for highly efficient light-chemical energy conversion. However, an in-depth understanding of their mechanisms at ...the nanoscale still remains challenging. Here, we present an in-situ investigation by tip-enhanced Raman spectroscopy (TERS) imaging of the plasmon-induced 4+4-cycloaddition polymerization within anthracene-based monomer monolayers physisorbed on Au(111), and complement the experimental results with density functional theory (DFT) calculations. This two-dimensional (2D) polymerization can be flexibly triggered and manipulated by the hot carriers, and be monitored simultaneously by TERS in real time and space. TERS imaging provides direct evidence for covalent bond formation with ca. 3.7 nm spatial resolution under ambient conditions. Combined with DFT calculations, the TERS results demonstrate that the lateral polymerization on Au(111) occurs by a hot electron tunneling mechanism, and crosslinks form via a self-stimulating growth mechanism. We show that TERS is promising to be plasmon-induced nanolithography for organic 2D materials.
Obtaining the desired characteristics of products having complex geometry from compositions comprising powdered dissimilar materials used in the formation of consumable patterns allows the scope of ...application of specific precision casting methods to be extended. It is established that, when forming compacts having complex configurations using a mixture of wax and water-soluble components, it is impossible to achieve the distribution of properties in the volume of the final product, which determines the change in the geometry of compacts as a result of the elastic response of compacted material. The issue associated with the elastic response of such compacted material can be solved in an experiment, establishing the influence of the initial packing and compacting parameters of wax elements on the stress-strain state of the compact. In the paper, the research results represented as experimental polynomial dependences of stress on deformation in compacted bodies with various initial packing options, deformable plastic and elastic elements, are presented. The means of controlling the dimensional and geometric parameters of the final compacts from wax model materials obtained in the process of uniaxial compaction by regulating its stress-strain state are presented.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The article describes the worked on numerical technique for forming alternative coalitions of experts relating to solving weakly formalized problems and the results of verification of the proposed ...method by the example of the studying the attributes of violators in the field of physical protection of critical information infrastructure objects. The proposed methodology for conducting preliminary examination on the basis of the worked on numerical method for identifying coalitions of experts allows to perform the procedure for forming an agreed group of experts and obtaining preliminary estimates of the significance of the attributes of a violator during a single survey of experts, that significantly saves time and reduces the complexity of the expertise of objects. Using the worked on numerical method, the main and two alternative coalitions were identified. Taking into account the alternative opinion of experts allowed 31 experts to be identified as agreed upon, which more precisely determines the results of the expertise.
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