Identification of kinetic triplets by results of derivatographic analysis

The method for identification of the triplet of kinetic parameters of a heterogeneous reaction using the data of the derivatographic analysis is proposed. This method is characterized by high accuracy and relative simplicity and it can be effectively realized using MS Excel software

Sphingosine Kinase 2 Modulates Retinal Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy.

Purpose Neovascularization is a major cause of blindness in various ocular diseases. Bioactive sphingosine 1-phosphate (S1P), synthesized by two sphingosine kinases (Sphk1, Sphk2), emerged as a key player in a multitude of cellular processes, including cell survival, proliferation, inflammation, migration, and angiogenesis. We investigated the role of Sphk2, S1P, and S1P receptors (S1PR) during retinal neovascularization using the oxygen-induced retinopathy mouse model (OIR). Methods Sphk2 overexpressing (tgSphk2) and Sphk2 knockout (Sphk2-/-) mice were used in the OIR model, exposed to 75% O2 over 5 days from postnatal day (P)7 to 12 to initiate vessel regression. After returning to room air, these mice developed a marked neovascularization. Retinae recovered from untreated and treated eyes at P7, P12, P14, and P17 were used for lectin-stained retinal whole mounts, mass spectrometry, and quantitative real-time PCR. Results tgSphk2 mice showed higher retinal S1P concentrations, accelerated retinal angiogenesis, and increased neovascularization. Expression of S1PR, vascular endothelial growth factor α (VEGFα), and angiopoietin 1 and 2 was differentially regulated during the course of OIR in the different genotypes. Sphk2-/- displayed a markedly reduced retinal angiogenesis and neovascularization as well as decreased VEGFα and angiopoietin expression. Conclusions Using genetic models of Sphk2 overexpression or deletion we demonstrate a strong impact of Sphk2/S1P on retinal vasculopathy and expression of vascular growth factors like VEGF and angiopoietin in the retina. Consequently, Sphk2, S1P, and S1PR may offer attractive novel therapeutic targets for ischemic retinopathies

Hotspots of uncertainty in land-use and land-cover change projections: a global-scale model comparison

Model-based global projections of future land use and land cover (LULC) change are frequently used in environmental assessments to study the impact of LULC change on environmental services and to provide decision support for policy. These projections are characterized by a high uncertainty in terms of quantity and allocation of projected changes, which can severely impact the results of environmental assessments. In this study, we identify hotspots of uncertainty, based on 43 simulations from 11 global-scale LULC change models representing a wide range of assumptions of future biophysical and socio-economic conditions. We attribute components of uncertainty to input data, model structure, scenario storyline and a residual term, based on a regression analysis and analysis of variance. From this diverse set of models and scenarios we find that the uncertainty varies, depending on the region and the LULC type under consideration. Hotspots of uncertainty appear mainly at the edges of globally important biomes (e.g. boreal and tropical forests). Our results indicate that an important source of uncertainty in forest and pasture areas originates from different input data applied in the models. Cropland, in contrast, is more consistent among the starting conditions, while variation in the projections gradually increases over time due to diverse scenario assumptions and different modeling approaches. Comparisons at the grid cell level indicate that disagreement is mainly related to LULC type definitions and the individual model allocation schemes. We conclude that improving the quality and consistency of observational data utilized in the modeling process as well as improving the allocation mechanisms of LULC change models remain important challenges. Current LULC representation in environmental assessments might miss the uncertainty arising from the diversity of LULC change modeling approaches and many studies ignore the uncertainty in LULC projections in assessments of LULC change impacts on climate, water resources or biodiversity

Overview of habitat history in subtropical oceanic island summit ecosystems

Summit ecosystems of oceanic islands constitute one of the most ephemeral and isolated ecosystems existing, harboring specific features that confer on their biota an outstanding distinctness. Summits are short-lived entities, being the last ecosystems to be constructed during the growth of the new oceanic island, and the first to vanish due either to island subsidence, island erosion, or both. Whereas their geological emergence/disappearance is controlled by the volcanic/erosion activity, Pleistocene glaciations in the past million years, by forcing the altitudinal shift of the timberline, have also likely created or destroyed summit ecosystems, enabling the appearance of alpine ecosystems during glacial maxima where they were not present in interglacial periods and vice versa. On the other hand, summit ecosystems constitute islands within islands, being more isolated from climatically similar ecosystems than the coastlines of the islands containing them. Thus summit biota, frequently displaying a high endemicity, may originate either through dispersal from other close summit ecosystems during peak periods, or from the colonization of the summits and later evolution to the new conditions from mid-altitude species of the same island. Conversely, if peak periods are absent, the disappearance of summit ecosystems implies the extinction or extirpation of their constitutive species. Current summit species have likely occupied a much larger area during glacial periods. Thus the summits may be classified as climatic refuges. This is especially the case if glacial periods were associated with much drier conditions on oceanic islands as is the case on continents

Cathepsin D and H2O2 stimulate degradation of thioredoxin-1: implication for endothelial cell apoptosis

Cathepsin D (CatD) is a lysosomal aspartic proteinase and plays an important role in the degradation of proteins and in apoptotic processes induced by oxidative stress, cytokines, and aging. All of these stimuli are potent inducers of endothelial cell apoptosis. Therefore, we investigated the role of CatD in endothelial cell apoptosis and determined the underlying mechanisms. Incubation with 100-500 microm H2O2 for 12 h induced apoptosis in endothelial cells. To determine a role for CatD, we co-incubated endothelial cells with the CatD inhibitor pepstatin A. Pepstatin A as well as genetic knock down of CatD abolished H2O2-induced apoptosis. In contrast, overexpression of CatD wild type but not a catalytically inactive mutant of CatD (CatDD295N) induced apoptosis under basal conditions. To gain insights into the underlying mechanisms, we investigated the effect of CatD on reactive oxygen species (ROS) formation. Indeed, knocking down CatD expression reduced H2O2-induced ROS formation and apoptosis. The major redox regulator in endothelial cells is thioredoxin-1 (Trx), which plays a crucial role in apoptosis inhibition. Thus, we hypothesized that CatD may alter Trx protein levels and thereby promote formation of ROS and apoptosis. Incubation with 100 microm H2O2 for 6 h decreased Trx protein levels, whereas Trx mRNA was not altered. H2O2-induced Trx degradation was inhibited by pepstatin A and genetic knock down of CatD but not by other protease inhibitors. Incubation of unstimulated cell lysates with recombinant CatD significantly reduced Trx protein levels in vitro, which was completely blocked by pepstatin A pre-incubation. Overexpression of CatD reduced Trx protein in cells. Moreover, H2O2 incubation led to a translocation of Trx to the lysosomes prior to the induction of apoptosis. Taken together, CatD induces apoptosis via degradation of Trx protein, which is an essential anti-apoptotic and reactive oxygen species scavenging protein in endothelial cells

Experimental Characterization of an Adaptive Supersonic Micro Turbine for Waste Heat Recovery Applications

Micro turbines (el) are commercially used as expansion machines in waste heat recovery (WHR) systems such as organic Rankine cycles (ORCs). These highly loaded turbines are generally designed for a specific parameter set, and their isentropic expansion efficiency significantly deteriorates when the mass flow rate of the WHR system deviates from the design point. However, in numerous industry processes that are potentially interesting for the implementation of a WHR process, the temperature, mass flow rate or both can fluctuate significantly, resulting in fluctuations in the WHR system as well. In such circumstances, the inlet pressure of the ORC turbine, and therefore the reversible cycle efficiency must be significantly reduced during these fluctuations. In this context, the authors developed an adaptive supersonic micro turbine for WHR applications. The variable geometry of the turbine nozzles enables an adjustment of the swallowing capacity in respect of the available mass flow rate in order to keep the upper cycle pressure constant. In this paper, an experimental test series of a WHR ORC test rig equipped with the developed adaptive supersonic micro turbine is analysed. The adaptive turbine is characterized concerning its off-design performance and the results are compared to a reference turbine with fixed geometry. To create a fair data basis for this comparison, a digital twin of the plant based on experimental data was built. In addition to the characterization of the turbine itself, the influence of the improved pressure ratio on the energy conversion chain of the entire ORC is analysed

Experimental Characterization of an Adaptive Supersonic Micro Turbine for Waste Heat Recovery Applications

Micro turbines (<100 kWel) are commercially used as expansion machines in waste heat recovery (WHR) systems such as organic Rankine cycles (ORCs). These highly loaded turbines are generally designed for a specific parameter set, and their isentropic expansion efficiency significantly deteriorates when the mass flow rate of the WHR system deviates from the design point. However, in numerous industry processes that are potentially interesting for the implementation of a WHR process, the temperature, mass flow rate or both can fluctuate significantly, resulting in fluctuations in the WHR system as well. In such circumstances, the inlet pressure of the ORC turbine, and therefore the reversible cycle efficiency must be significantly reduced during these fluctuations. In this context, the authors developed an adaptive supersonic micro turbine for WHR applications. The variable geometry of the turbine nozzles enables an adjustment of the swallowing capacity in respect of the available mass flow rate in order to keep the upper cycle pressure constant. In this paper, an experimental test series of a WHR ORC test rig equipped with the developed adaptive supersonic micro turbine is analysed. The adaptive turbine is characterized concerning its off-design performance and the results are compared to a reference turbine with fixed geometry. To create a fair data basis for this comparison, a digital twin of the plant based on experimental data was built. In addition to the characterization of the turbine itself, the influence of the improved pressure ratio on the energy conversion chain of the entire ORC is analysed

The consequences of soluble epoxide hydrolase deletion on tumorigenesis and metastasis in a mouse model of breast cancer

Epoxides and diols of polyunsaturated fatty acids (PUFAs) are bioactive and can influence processes such as tumor cell proliferation and angiogenesis. Studies with inhibitors of the soluble epoxide hydrolase (sEH) in animals overexpressing cytochrome P450 enzymes or following the systemic administration of specific epoxides revealed a markedly increased incidence of tumor metastases. To determine whether PUFA epoxides increased metastases in a model of spontaneous breast cancer, sEH-/- mice were crossed onto the polyoma middle T oncogene (PyMT) background. We found that the deletion of the sEH accelerated the growth of primary tumors and increased both the tumor macrophage count and angiogenesis. There were small differences in the epoxide/diol content of tumors, particularly in epoxyoctadecamonoenic acid versus dihydroxyoctadecenoic acid, and marked changes in the expression of proteins linked with cell proliferation and metabolism. However, there was no consequence of sEH inhibition on the formation of metastases in the lymph node or lung. Taken together, our results confirm previous reports of increased tumor growth in animals lacking sEH but fail to substantiate reports of enhanced lymph node or pulmonary metastases