The properties of clouds that may be observed by satellite instruments, such as optical thickness and cloud-top pressure, are only loosely related to the way clouds are represented in models of the ...atmosphere. One way to bridge this gap is through ‘‘instrument simulators,’’ diagnostic tools that map the model representation to synthetic observations so that differences can be interpreted as model error. But simulators may themselves be restricted by limited information or by internal assumptions. This paper considers the extent to which instrument simulators are able to capture essential differences between the Moderate Resolution Imaging Spectroradiometer (MODIS) and the International Satellite Cloud Climatology Project (ISCCP), two similar but independent estimates of cloud properties. The authors review the measurements and algorithms underlying these two cloud climatologies, introduce a MODIS simulator, and detail datasets developed for comparison with global models using ISCCP and MODIS simulators. In nature MODIS observes less midlevel cloudiness than ISCCP, consistent with the different methods used to determine cloud-top pressure; aspects of this difference are reproduced by the simulators. Differences in observed distributions of optical thickness, however, are not captured. The largest differences can be traced to different approaches to partly cloudy pixels, which MODIS excludes and ISCCP treats as homogeneous. These cover roughly 15% of the planet and account for most of the optically thinnest clouds. Instrument simulators cannot reproduce these differences because there is no way to synthesize partly cloudy pixels. Nonetheless, MODIS and ISCCP observations are consistent for all but the optically thinnest clouds, and models can be robustly evaluated using instrument simulators by integrating over the robust subset of observations.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND—Long noncoding RNAs (lncRNAs) have emerged as critical molecular regulators in various biological processes and diseases. Here we sought to identify and functionally characterize lncRNAs ...as potential mediators in abdominal aortic aneurysm (AAA) development.
METHODS—We profiled RNA transcript expression in two murine AAA models, Angiotensin II (ANGII) infusion in ApoE-/- mice (n=8) and porcine pancreatic elastase (PPE) instillation in C57BL/6 wildtype mice (n=12). The lncRNA H19 was identified as one of the most highly up-regulated transcripts in both mouse aneurysm models compared to sham-operated controls. This was confirmed by qRT-PCR and in situ hybridization.
RESULTS—Experimental knock-down of H19, utilizing site-specific antisense oligonucleotides (LNA-GapmeRs) in vivo, significantly limited aneurysm growth in both models. Upregulated H19 correlated with smooth muscle cell (SMC) content and SMC apoptosis in progressing aneurysms. Importantly, a similar pattern could be observed in human AAA tissue samples, and in a novel preclinical LDLR-/- Yucatan mini-pig aneurysm model. In vitro knock-down of H19 markedly decreased apoptotic rates of cultured human aortic SMCs, while overexpression of H19 had the opposite effect. Notably, H19-dependent apoptosis mechanisms in SMCs appeared to be independent of miR-675, which is embedded in the first exon of the H19 gene. A customized transcription factor array identified hypoxia-inducible factor 1-alpha (HIF1α) as the main downstream effector. Increased SMC apoptosis was associated with cytoplasmic interaction between H19 and HIF1α and sequential p53 stabilization. Additionally, H19 induced transcription of HIF1α via recruiting the transcription factor specificity protein 1 (Sp1) to the promoter region.
CONCLUSIONS—The lncRNA H19 is a novel regulator of SMC survival in AAA development and progression. Inhibition of H19 expression might serve as a novel molecular therapeutic target for aortic aneurysm disease.
A nondegrading, low-impedance interface between a solid electrolyte and cathode active materials remains a key challenge for the development of functional all-solid-state batteries (ASSBs). The ...widely employed thiophosphate-based solid electrolytes are not stable toward oxidation and suffer from growing interface resistance and thus rapid fading of capacity in a solid-state battery. In contrast, NASICON-type phosphates such as Li1+x Al x Ti2–x (PO4)3 and Li1+x Al x Ge2–x (PO4)3 are stable at high potentials, but their mechanical rigidity and high grain boundary resistance are thought to impede their application in bulk-type solid-state batteries. In this work, we present a comparative study of a LiNi0.8Co0.1Mn0.1O2 (NCM-811) cathode composite employing either β-Li3PS4 (LPS) or Li1.5Al0.5Ti1.5(PO4)3 (LATP) as a solid electrolyte. LPS is employed as a separator in both cases to assemble a functional ASSB. To avoid high-temperature processing of LATP, along with subsequent detrimental interfacial reactions with NCM materials, the ASSBs are constructed and operated in a hot-press setup at 150 °C. The cathode interfaces are investigated using in situ electrochemical impedance spectroscopy and X-ray photoelectron spectroscopy, which reveals that the interface resistance is strongly suppressed and the chemical state of the composite is unchanged during cycling when employed with LATP. The cell using LATP is reversibly charged and discharged for multiple cycles and outperforms a comparable cell using a thiophosphate composite electrode. The results indicate that LATP in the cathode composite represents an excellent candidate to overcome interfacial challenges in bulk-type solid-state batteries.
This paper describes a set of metrics for evaluating the simulation of clouds, radiation, and precipitation in the present‐day climate. As with the skill scores used to measure the accuracy of ...short‐term weather forecasts, these metrics are low‐order statistical measures of agreement with relevant, well‐observed physical quantities. The metrics encompass five statistical summaries computed for five physical quantities (longwave, shortwave, and net cloud radiative effect, projected cloud fraction, and surface precipitation rate) over the global climatological annual cycle. Agreement is measured against two independent observational data sets. The metrics are computed for the models that participated in the Coupled Model Intercomparison Project phase 3, which formed the basis for the Fourth Assessment of the IPCC. Model skill does not depend strongly on the data set used for verification, indicating that observational uncertainty does not limit the ability to assess model simulations of these fields. No individual model excels in all scores though the “IPCC mean model,” constructed by averaging the fields produced by all the CMIP models, performs particularly well across the board. This skill is due primarily to the individual model errors being distributed on both sides of the observations, and to a lesser degree to the models having greater skill at simulating large‐scale features than those near the grid scale. No measure of model skill considered here is a good predictor of the strength of cloud feedbacks under climate change. The model climatologies, observational data sets, and metric scores are available on‐line.
BACKGROUND:The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact of long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and ...functionally important endothelial lncRNAs.
METHODS:Epigenetically controlled lncRNAs in human umbilical vein endothelial cells were searched by exon-array analysis after knockdown of the histone demethylase JARID1B. Molecular mechanisms were investigated by RNA pulldown and immunoprecipitation, mass spectrometry, microarray, several knockdown approaches, CRISPR-Cas9, assay for transposase-accessible chromatin sequencing, and chromatin immunoprecipitation in human umbilical vein endothelial cells. Patient samples from lung and tumors were studied for MANTIS expression.
RESULTS:A search for epigenetically controlled endothelial lncRNAs yielded lncRNA n342419, here termed MANTIS, as the most strongly regulated lncRNA. Controlled by the histone demethylase JARID1B, MANTIS was downregulated in patients with idiopathic pulmonary arterial hypertension and in rats treated with monocrotaline, whereas it was upregulated in carotid arteries of Macaca fascicularis subjected to atherosclerosis regression diet, and in endothelial cells isolated from human glioblastoma patients. CRISPR/Cas9-mediated deletion or silencing of MANTIS with small interfering RNAs or GapmeRs inhibited angiogenic sprouting and alignment of endothelial cells in response to shear stress. Mechanistically, the nuclear-localized MANTIS lncRNA interacted with BRG1, the catalytic subunit of the switch/sucrose nonfermentable chromatin-remodeling complex. This interaction was required for nucleosome remodeling by keeping the ATPase function of BRG1 active. Thereby, the transcription of key endothelial genes such as SOX18, SMAD6, and COUP-TFII was regulated by ensuring efficient RNA polymerase II machinery binding.
CONCLUSION:MANTIS is a differentially regulated novel lncRNA facilitating endothelial angiogenic function.
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of end-stage kidney disease, primarily due to mutations in UMOD and MUC1. The lack of clinical ...recognition and the small size of cohorts have slowed the understanding of disease ontology and development of diagnostic algorithms. We analyzed two registries from Europe and the United States to define genetic and clinical characteristics of ADTKD-UMOD and ADTKD-MUC1 and develop a practical score to guide genetic testing. Our study encompassed 726 patients from 585 families with a presumptive diagnosis of ADTKD along with clinical, biochemical, genetic and radiologic data. Collectively, 106 different UMOD mutations were detected in 216/562 (38.4%) of families with ADTKD (303 patients), and 4 different MUC1 mutations in 72/205 (35.1%) of the families that are UMOD-negative (83 patients). The median kidney survival was significantly shorter in patients with ADTKD-MUC1 compared to ADTKD-UMOD (46 vs. 54 years, respectively), whereas the median gout-free survival was dramatically reduced in patients with ADTKD-UMOD compared to ADTKD-MUC1 (30 vs. 67 years, respectively). In contrast to patients with ADTKD-UMOD, patients with ADTKD-MUC1 had normal urinary excretion of uromodulin and distribution of uromodulin in tubular cells. A diagnostic algorithm based on a simple score coupled with urinary uromodulin measurements separated patients with ADTKD-UMOD from those with ADTKD-MUC1 with a sensitivity of 94.1%, a specificity of 74.3% and a positive predictive value of 84.2% for a UMOD mutation. Thus, ADTKD-UMOD is more frequently diagnosed than ADTKD-MUC1, ADTKD subtypes present with distinct clinical features, and a simple score coupled with urine uromodulin measurements may help prioritizing genetic testing.
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Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report ...the identification of the aging-regulated lncRNA Sarrah (ENSMUST00000140003) that is anti-apoptotic in cardiomyocytes. Importantly, loss of SARRAH (OXCT1-AS1) in human engineered heart tissue results in impaired contractile force development. SARRAH directly binds to the promoters of genes downregulated after SARRAH silencing via RNA-DNA triple helix formation and cardiomyocytes lacking the triple helix forming domain of Sarrah show an increase in apoptosis. One of the direct SARRAH targets is NRF2, and restoration of NRF2 levels after SARRAH silencing partially rescues the reduction in cell viability. Overexpression of Sarrah in mice shows better recovery of cardiac contractile function after AMI compared to control mice. In summary, we identified the anti-apoptotic evolutionary conserved lncRNA Sarrah, which is downregulated by aging, as a regulator of cardiomyocyte survival.
Thin film solid-state batteries are suitable model systems for the study of degradation phenomena in bulk solid-state batteries. As a necessary prerequisite for the construction of thin film ...batteries, high quality thin films of electrode materials and solid electrolytes have to be deposited. In this study, phosphate-based cathode (LiCoPO4) and solid electrolyte (Li1.5Al0.5Ti1.5(PO4)3) thin films were successfully deposited by pulsed laser deposition on silicon substrates. By temperature dependent grazing incidence X-ray diffraction measurements, the high quality of the deposited thin films was shown as well as crystallization temperatures were determined. Moreover, atomic force microscopy and scanning electron microscopy measurements were carried out for surface analysis, highlighting the surface smoothness of the films and unraveling the microstructure of the deposited LATP films, which contain grain boundaries. Further, a model interface composed of a thin layer of LiCoPO4 of varying thickness on top of Li1.5Al0.5Ti1.5(PO4)3 was used to corroborate information about changes in the chemical state of the materials as well as to track the inter-diffusion across the interface of all corresponding ionic species. This was done by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry depth profiling. While well-defined interfaces were observed for unheated interfaces, significant inter-diffusion of transition metal ions was observed between heated LATP and LCP films. Despite inter-diffusion, no changes in the chemical states were observed at the interface, excluding significant phase transformations to compounds with altered oxidation states. Although stable phosphate-based materials were chosen for, both, electrolyte and active material to diminish known instabilities of the interface in this study, the need for interfacial layers arises to suppress the inter-diffusion, which may affect lithium ion transport across the interface. This work provides detailed insight into the complex problems of interfacial stability in all-solid-state batteries.
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•Preparation of the solid electrolyte Li1.5Al0.5Ti1.5(PO4)3 and the cathode material LiCoPO4 as thin films by PLD.•Crystallization behavior of the thin films dependent on heat treatment is shown by GIXRD measurements.•Surface smoothing of LATP thin films by rapid annealing process shown by AFM measurements.•LiCoPO4 film growth dependent on underlying substrate.•Severe inter-diffusion of cobalt and titanium ions into adjacent films highlighted by ToF-SIMS measurements.
The Magnéli phase V6O11 was synthesized in gram amounts from a powder mixture of V6O11/V7O13 and vanadium metal, using the spark plasma sintering (SPS) technique. Its structure was determined with ...synchrotron X-ray powder diffraction data from a phase-pure sample synthesized by conventional solid-state synthesis. A special feature of Magnéli-type oxides is a combination of crystallographic shear and intrinsic disorder that leads to relatively low lattice thermal conductivities. SPS prepared V6O11 has a relatively low thermal conductivity of κ = 2.72 ± 0.06 W (m K)-1 while being a n-type conductor with an electrical conductivity of σ = 0.039 ± 0.005 (μΩ m)-1, a Seebeck coefficient of α = -(35 ± 2) μV K-1, which leads to a power factor of PF = 4.9 ± 0.8 × 10-5W (m K2)-1 at ∼600 K. Advances in the application of Magnéli phases are mostly hindered by synthetic and processing challenges, especially when metastable and nanostructured materials such as V6O11 are involved. This study gives insight into the complications of SPS-assisted synthesis of complex oxide materials, provides new information about the thermal and electrical properties of vanadium oxides at high temperatures, and supports the concept of reducing the thermal conductivity of materials with structural building blocks such as crystallographic shear (CS) planes.
Leukocytes follow the well-defined steps of rolling, spreading, and crawling prior to diapedesis through endothelial cells (ECs). We found increased expression of DLC-1 in stiffness-associated ...diseases like atherosclerosis and pulmonary arterial hypertension. Depletion of DLC-1 in ECs cultured on stiff substrates drastically reduced cell stiffness and mimicked leukocyte transmigration kinetics observed for ECs cultured on soft substrates. Mechanistic studies revealed that DLC-1-depleted ECs or ECs cultured on soft substrates failed to recruit the actin-adaptor proteins filamin B, α-actinin-4, and cortactin to clustered ICAM-1, thereby preventing the ICAM-1 adhesome formation and impairing leukocyte spreading. This was rescued by overexpressing DLC-1, resulting in ICAM-1 adhesome stabilization and leukocyte spreading. Our results reveal an essential role for substrate stiffness-regulated endothelial DLC-1, independent of its GAP domain, in locally stabilizing the ICAM-1 adhesome to promote leukocyte spreading, essential for efficient leukocyte transendothelial migration.
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•DLC-1 expression is stiffness related and determines local stiffness•The RhoGAP DLC-1 is crucial for the ICAM-1 adhesome•DLC-1 shows increased expression in stiffness-related diseases•DLC-1 regulates leukocyte spreading independent of its GAP domain
Leukocyte extravasation depends on local cellular and substrate stiffness. Schimmel et al. identified endothelial DLC-1 as a mediator to translate stiffness to leukocyte behavior. DLC-1 is crucial for the ICAM-1 adhesome, which allows leukocytes to switch from the rolling to the spreading and crawling phase, followed by diapedesis.
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