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Aberrant remodeling of trabecular meshwork (TM) extracellular matrix (ECM) may induce ocular hypertensive phenotypes in human TM (hTM) cells to cause ocular hypertension, via a yet unknown mechanism. Here, we show that, in the absence of exogenous transforming growth factor-beta2 (TGFβ2), compared with control matrices (VehMs), glucocorticoid-induced cell-derived matrices (GIMs) trigger non-Smad TGFβ2 signaling in hTM cells, correlated with overexpression/activity of structural ECM genes (fibronectin, collagen IV, collagen VI, myocilin), matricellular genes (connective tissue growth factor [CTGF], secreted protein, acidic and rich in cysteine), crosslinking genes/enzymes (lysyl oxidase, lysyl oxidase-like 2–4, tissue transglutaminase-2), and ECM turnover genes/enzymes (matrix metalloproteinases-MMP2,14 and their inhibitors-TIMP2). However, in the presence of exogenous TGFβ2, VehMs and GIMs activate Smad and non-Smad TGFβ2 signaling in hTM cells, associated with overexpression of α-smooth muscle actin (α-SMA), and differential upregulation of aforementioned ECM genes/proteins with new ones emerging (collagen-I, thrombospondin-I, plasminogen activator inhibitor, MMP1, 9, ADAMTS4, TIMP1); with GIM-TGFβ2-induced changes being mostly more pronounced. This suggests dual glaucomatous insults potentiate profibrotic signaling/phenotypes. Lastly, we demonstrate type I TGFβ receptor kinase inhibition abrogates VehM-/GIM- and/or TGFβ2-induced upregulation of α-SMA and CTGF. Collectively, pathological TM microenvironments are sufficient to elicit adverse cellular responses that may be ameliorated by targeting TGFβ2 pathway. [ABSTRACT FROM AUTHOR]

Global ionospheric products of vertical total electron content (VTEC) derived from GNSS measurements may have low accuracy over oceans and southern latitudes where there are not rich observations. Project Loon provides a great opportunity to enhance the measurements over those areas. In this contribution, a simulation of Project Loon based augmentation for global ionospheric modeling is performed by using the international reference ionosphere (IRI) which could simulate VTEC measurements for the balloons. The performance of the enhanced method based on simulation of Project Loon is investigated by comparing with VTEC maps from Ionosphere Associate Analysis Centers (IAACs) as well as IGS final GIMs. The comparison indicates that there is a better consistency between the VTEC maps by the enhanced method and IGS final GIMs. Also, obvious improvements of RMS maps in GIMs for the middle latitudes and southern latitudes are enabled by the augmentation of Project Loon. Additionally, JASON data are used to validate the specific improvement of the VTEC maps. The results show that the performance of VTEC maps is improved slightly, especially in southern latitudes. It is possible that the VTEC maps could be improved significantly by using real GPS measurements from balloons of Project Loon in the near future. [ABSTRACT FROM AUTHOR]

A large range of climate change impacts is expected during the twenty-first century in vulnerable regions such as West Africa, where local populations largely rely on livestock systems as their main food production and income source. As climate change threatens livestock systems in various ways, here we assess how regional livestock could be exposed to cumulated climate-related stressors in the future. Using the world's largest multi-model climate impacts simulations database ISIMIP, we find that a large part of West Africa will experience at least 5–6 cumulated multiple climate stressors before the 2030s, including amplified severe heat stress conditions and flood risks. Consequently, about 30% of the current total regional livestock could be exposed to these cumulated stressors, with sheep and goat as the most affected species. This paper brings new quantifications that may help policy makers to prioritize decisions that could prepare local populations to face multiple climate-related impacts. [ABSTRACT FROM AUTHOR]

Selecting appropriate global climate models (GCMs) is crucial for minimizing uncertainty in regional climate projections under future scenarios. Previous studies have predominantly assessed the modeling capability of GCMs for regional precipitation climatology and its long-term patterns based on annual and seasonal precipitation data. Building upon these, we primally evaluated the performance of five GCMs from phase 3b of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3b) in simulating precipitation concentration and its variations in the Southwest River Basin (SWRB) of China using the precipitation concentration index (PCI). The results indicate that: (1) The 5 GCMs generally capture the spatial distribution of annual average precipitation in the SWRB but significantly overestimate its magnitude, with a maximum regional average deviation of 207.80 mm. Furthermore, all models tend to overestimate the overall drying trend in the SWRB and show limited capability in simulating interdecadal variations of annual precipitation. (2) While the 5 GCMs reasonably simulate the spatial distribution of annual average PCI in the SWRB, they tend to overestimate its values, with a maximum regional average deviation of 1.54. Additionally, their simulation performance in capturing PCI trends and interdecadal variations is also limited. (3) The 5 GCMs tend to overestimate seasonal precipitation in the SWRB, with the best simulation performance for the distribution of autumn precipitation, followed by spring and summer, and the poorest for winter. Significant differences exist in the simulation performance of the models for seasonal precipitation proportions, which result in discrepancies in the models' representation of PCI. Moreover, the models' poor simulation performance of PCI trends is partly due to their inadequate modeling of trends in seasonal precipitation proportions. The findings will contribute to laying the foundation for meteorological hydrological research and water resource management in the SWRB. [ABSTRACT FROM AUTHOR]

Meiosis, recombination, and gametogenesis normally ensure that gametes combine randomly. But in exceptional cases, fertilization depends on the genetics of gametes from both females and males. A key question is whether their non-random union results from factors intrinsic to oocytes and sperm, or from their interactions with conditions in the reproductive tracts. To address this question, we used in vitro fertilization (IVF) with a mutant and wild-type allele of the A1cf (APOBEC1 complementation factor) gene in mice that are otherwise genetically identical. We observed strong distortion in favor of mutant heterozygotes showing that bias depends on the genetics of oocyte and sperm, and that any environmental input is modest. To search for the potential mechanism of the 'biased fertilization', we analyzed the existing transcriptome data and demonstrated that localization of A1cf transcripts and its candidate mRNA targets is restricted to the spermatids in which they originate, and that these transcripts are enriched for functions related to meiosis, fertilization, RNA stability, translation, and mitochondria. We propose that failure to sequester mRNA targets in A1cf mutant heterozygotes leads to functional differences among spermatids, thereby providing an opportunity for selection among haploid gametes. The study adds to the understanding of the gamete interaction at fertilization. Discovery that bias is evident with IVF provides a new venue for future explorations of preference among genetically distinct gametes at fertilization for A1cf and other genes that display significant departure of Mendelian inheritance. [ABSTRACT FROM AUTHOR]

Abstract Aberrant remodeling of trabecular meshwork (TM) extracellular matrix (ECM) may induce ocular hypertensive phenotypes in human TM (hTM) cells to cause ocular hypertension, via a yet unknown mechanism. Here, we show that, in the absence of exogenous transforming growth factor-beta2 (TGFβ2), compared with control matrices (VehMs), glucocorticoid-induced cell-derived matrices (GIMs) trigger non-Smad TGFβ2 signaling in hTM cells, correlated with overexpression/activity of structural ECM genes (fibronectin, collagen IV, collagen VI, myocilin), matricellular genes (connective tissue growth factor [CTGF], secreted protein, acidic and rich in cysteine), crosslinking genes/enzymes (lysyl oxidase, lysyl oxidase-like 2–4, tissue transglutaminase-2), and ECM turnover genes/enzymes (matrix metalloproteinases-MMP2,14 and their inhibitors-TIMP2). However, in the presence of exogenous TGFβ2, VehMs and GIMs activate Smad and non-Smad TGFβ2 signaling in hTM cells, associated with overexpression of α-smooth muscle actin (α-SMA), and differential upregulation of aforementioned ECM genes/proteins with new ones emerging (collagen-I, thrombospondin-I, plasminogen activator inhibitor, MMP1, 9, ADAMTS4, TIMP1); with GIM-TGFβ2-induced changes being mostly more pronounced. This suggests dual glaucomatous insults potentiate profibrotic signaling/phenotypes. Lastly, we demonstrate type I TGFβ receptor kinase inhibition abrogates VehM-/GIM- and/or TGFβ2-induced upregulation of α-SMA and CTGF. Collectively, pathological TM microenvironments are sufficient to elicit adverse cellular responses that may be ameliorated by targeting TGFβ2 pathway.

In this work, we demonstrate an one-dimensional cloak consisting of parallel-plated waveguide with two slabs of gradient index metamaterials attached to its metallic walls. In it objects are hidden without limitation of polarizations, and good performance is observed for a broadband of frequencies. The experiments at microwave frequencies are carried out, supporting the theoretical results very well. The essential principle behind the proposed cloaking device is based on mode conversion, which provides a new strategy to manipulate wave propagation. [ABSTRACT FROM AUTHOR]

Global estimation of thermospheric neutral density (TND) on various altitudes is important for geodetic and space weather applications. This is typically provided by models, however, the quality of these models is limited due to their imperfect structure and the sensitivity of their parameters to the calibration period. Here, we present an ensemble Kalman filter (EnKF)-based calibration and data assimilation (C/DA) technique that updates the model's states and simultaneously calibrates its key parameters. Its application is demonstrated using the TND estimates from on-board accelerometer measurements, e.g., those of the Gravity Recovery and Climate Experiment (GRACE) mission (at ∼ 410 km altitude), as observation, and the frequently used empirical model NRLMSISE-00. The C/DA is applied here to re-calibrate the model parameters including those controlling the influence of solar radiation and geomagnetic activity as well as those related to the calculation of exospheric temperature. The resulting model, called here 'C/DA-NRLMSISE-00', is then used to now-cast TNDs and individual neutral mass compositions for 3 h, where the model with calibrated parameters is run again during the assimilation period. C/DA-NRLMSISE-00 is also used to forecast the next 21 h, where no new observations are introduced. These forecasts are unique because they are available globally and on various altitudes (300–600 km). To introduce the impact of the thermosphere on estimating ionospheric parameters, the coupled physics-based model TIE-GCM is run by replacing the O2, O1, He and neutral temperature estimates of the C/DA-NRLMSISE-00. Then, the non-assimilated outputs of electron density (Ne) and total electron content (TEC) are validated against independent measurements. Assessing the forecasts of TNDs with those along the Swarm-A ( ∼ 467 km), -B ( ∼ 521 km), and -C ( ∼ 467 km) orbits shows that the root-mean-square error (RMSE) is considerably reduced by 51, 57 and 54%, respectively. We find improvement of 30.92% for forecasting Ne and 26.48% for TEC compared to the radio occulation and global ionosphere maps (GIM), respectively. The presented C/DA approach is recommended for the short-term global multi-level thermosphere and enhanced ionosphere forecasting applications. [ABSTRACT FROM AUTHOR]

Geometry images parameterise a mesh with a square domain and store the information in a single chart. A one-to-one correspondence between the 2D plane and the 3D model is convenient for processing 3D models. However, the parameterised vertices are not all located at the intersection of the gridlines the existing geometry images. Thus, errors are unavoidable when a 3D mesh is reconstructed from the chart. In this paper, we propose parameterise surface onto a novel geometry image that preserves the constraint of topological neighbourhood information at integer coordinate points on a 2D grid and ensures that the shape of the reconstructed 3D mesh does not change from supplemented image data. We find a collection of edges that opens the mesh into simply connected surface with a single boundary. The point distribution with approximate blue noise spectral characteristics is computed by capacity-constrained delaunay triangulation without retriangulation. We move the vertices to the constrained mesh intersection, adjust the degenerate triangles on a regular grid, and fill the blank part by performing a local affine transformation between each triangle in the mesh and image. Unlike other geometry images, the proposed method results in no error in the reconstructed surface model when floating-point data are stored in the image. High reconstruction accuracy is achieved when the xyz positions are in a 16-bit data format in each image channel because only rounding errors exist in the topology-preserving geometry images, there are no sampling errors. This method performs one-to-one mapping between the 3D surface mesh and the points in the 2D image, while foldovers do not appear in the 2D triangular mesh, maintaining the topological structure. This also shows the potential of using a 2D image processing algorithm to process 3D models. [ABSTRACT FROM AUTHOR]