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Studies of the fragmentation of jets into charged particles in heavy-ion collisions can help in understanding the mechanism of jet quenching by the hot and dense QCD matter created in such collisions, the quark-gluon plasma. These proceedings present a measurement of the angular distribution of charged particles around the jet axis in root s(NN) = 5.02 TeV Pb+Pb and pp collisions, done using the ATLAS detector at the LHC. The measurement is performed inside jets reconstructed with the anti-k(t) algorithm with radius parameter R = 0.4, and is extended to regions outside the jet cone. Results are presented as a function of Pb+Pb collision centrality, and both jet and charged-particle transverse momenta.
Purpose The purpose of this paper is to enhance consistent partial least squares (PLSc) to yield consistent parameter estimates for population models whose indicator blocks contain a subset of correlated measurement errors. Design/methodology/approach Correction for attenuation as originally applied by PLSc is modified to include a priori assumptions on the structure of the measurement error correlations within blocks of indicators. To assess the efficacy of the modification, a Monte Carlo simulation is conducted. Findings In the presence of population measurement error correlation, estimated parameter bias is generally small for original and modified PLSc, with the latter outperforming the former for large sample sizes. In terms of the root mean squared error, the results are virtually identical for both original and modified PLSc. Only for relatively large sample sizes, high population measurement error correlation, and low population composite reliability are the increased standard errors associated with the modification outweighed by a smaller bias. These findings are regarded as initial evidence that original PLSc is comparatively robust with respect to misspecification of the structure of measurement error correlations within blocks of indicators. Originality/value Introducing and investigating a new approach to address measurement error correlation within blocks of indicators in PLSc, this paper contributes to the ongoing development and assessment of recent advancements in partial least squares path modeling.
Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10(+), but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-kappa B signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-kappa B activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.
Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events Aoccur during the first two years and hence we aimed to analyze the outcome of 2-year disease-free survivors. A total of 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, disease-free survival was 64% (60-68%) and overall survival was 74% (71-78%) at ten years; results were better in younger individuals and in women. Excess mortality was 14% (8-21%) in patients aged <45 years and 33% (13-53%) in patients aged >= 65 years. The main cause of death was relapse of the primary disease. Graft-versus-host disease (GvHD) before two years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GvHD disease prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at two years. However, the occurrence of late complications, including late relapses, infectious complications and secondary malignancies, highlights the importance of screening and monitoring of long-term survivors.
Zinc oxide nanoparticles (ZnO-NPs) are widely utilized, for example in manufacturing paints and in the cosmetic industry. In addition, there is raising interest in the application of NPs in stem cell research. However, cytotoxic, genotoxic and pro-inflammatory effects were shown for NPs. The aim of this study was to evaluate the impact of ZnO-NPs on cytokine secretion and differentiation properties of human adipose tissue-derived stromal cells (ASCs). Human ASCs were exposed to the subtoxic concentration of 0.2 mu g/mL ZnO-NPs for 24 h. After four weeks of cultivation, adipogenic and osteogenic differentiation procedures were performed. The multi-differentiation potential was confirmed histologically and using polymerase chain reaction (PCR). In addition, the gene expression of IL-6, IL-8, vascular endothelial growth factor (VEGF) and caspase 3 was analyzed. Over the course of four weeks after ZnO-NPs exposure, no significant differences were detected in the gene expression of IL-6, IL-8, VEGF and caspase 3 compared to non-exposed cells. The differentiation was also not affected by the ZnO-NPs. These findings underline the fact, that functionality of ASCs is likely to be unaffected by ZnO-NPs, despite a long-term disposition of NPs in the cells, supposing that the starting concentration was safely in the non-toxic range. This might provide important information for single-use nanomedical applications of ZnO-NPs.
Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells co-cultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi-based focal adhesion kinase silencing was performed. We showed that focal adhesion kinase is highly expressed in bone marrow infiltrates of mantle cell lymphoma and in mantle cell lymphoma cell lines. Stroma-mediated activation of focal adhesion kinase led to activation of multiple kinases (AKT, p42/44 and NF-kappa B), that are important for prosurvival and proliferation signaling. Interestingly, RNAi-based focal adhesion kinase silencing or inhibition with small molecule inhibitors (FAKi) resulted in blockage of targeted cell invasion and induced apoptosis by inactivation of multiple signaling cascades, including the classic and alternative NF-kappa B pathway. In addition, the combined treatment of ibrutinib and FAKi was highly synergistic, and ibrutinib resistance of mantle cell lymphoma could be overcome. These data demonstrate that focal adhesion kinase is important for stroma-mediated survival and drug resistance in mantle cell lymphoma, providing indications for a targeted therapeutic strategy.
In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP–2, BMP–7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP–2. In vitro, both scaffolds presented similar mechanical properties, rhBMP–2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP–2 mediated bone healing.
Many parts of sub-Saharan Africa (SSA) are prone to land use and land cover change (LULCC). In many cases, natural systems are converted into agricultural land to feed the growing population. However, despite climate change being a major focus nowadays, the impacts of these conversions on water resources, which are essential for agricultural production, is still often neglected, jeopardizing the sustainability of the socio-ecological system. This study investigates historic land use/land cover (LULC) patterns as well as potential future LULCC and its effect on water quantities in a complex tropical catchment in Tanzania. It then compares the results using two climate change scenarios. The Land Change Modeler (LCM) is used to analyze and to project LULC patterns until 2030 and the Soil and Water Assessment Tool (SWAT) is utilized to simulate the water balance under various LULC conditions. Results show decreasing low flows by 6–8% for the LULC scenarios, whereas high flows increase by up to 84% for the combined LULC and climate change scenarios. The effect of climate change is stronger compared to the effect of LULCC, but also contains higher uncertainties. The effects of LULCC are more distinct, although crop specific effects show diverging effects on water balance components. This study develops a methodology for quantifying the impact of land use and climate change and therefore contributes to the sustainable management of the investigated catchment, as it shows the impact of environmental change on hydrological extremes (low flow and floods) and determines hot spots, which are critical for environmental development.
Among the Microbacteriaceae the species of Subtercola and Agreia form closely associated clusters. Phylogenetic analysis demonstrated three major phylogenetic branches of these species. One of these branches contains the two psychrophilic species Subtercola frigoramans and Subtercola vilae, together with a larger number of isolates from various cold environments. Genomic evidence supports the separation of Agreia and Subtercola species. In order to gain insight into the ability of S. vilae to adapt to life in this extreme environment, we analyzed the genome with a particular focus on properties related to possible adaptation to a cold environment. General properties of the genome are presented, including carbon and energy metabolism, as well as secondary metabolite production. The repertoire of genes in the genome of S. vilae DB165\(^T\) linked to adaptations to the harsh conditions found in Llullaillaco Volcano Lake includes several mechanisms to transcribe proteins under low temperatures, such as a high number of tRNAs and cold shock proteins. In addition, S. vilae DB165\(^T\) is capable of producing a number of proteins to cope with oxidative stress, which is of particular relevance at low temperature environments, in which reactive oxygen species are more abundant. Most important, it obtains capacities to produce cryo-protectants, and to combat against ice crystal formation, it produces ice-binding proteins. Two new ice-binding proteins were identified which are unique to S. vilae DB165\(^T\). These results indicate that S. vilae has the capacity to employ different mechanisms to live under the extreme and cold conditions prevalent in Llullaillaco Volcano Lake.
For the understanding of the variable, transient and non-thermal universe, unbiased long-term monitoring is crucial. To constrain the emission mechanisms at the highest energies, it is important to characterize the very high energy emission and its correlation with observations at other wavelengths. At very high energies, only a limited number of instruments is available. This article reviews the current status of monitoring of the extra-galactic sky at TeV energies.
Even today, the automatic digitisation of scanned documents in general, but especially the automatic optical music recognition (OMR) of historical manuscripts, still remains an enormous challenge, since both handwritten musical symbols and text have to be identified. This paper focuses on the Medieval so-called square notation developed in the 11th–12th century, which is already composed of staff lines, staves, clefs, accidentals, and neumes that are roughly spoken connected single notes. The aim is to develop an algorithm that captures both the neumes, and in particular its melody, which can be used to reconstruct the original writing. Our pipeline is similar to the standard OMR approach and comprises a novel staff line and symbol detection algorithm based on deep Fully Convolutional Networks (FCN), which perform pixel-based predictions for either staff lines or symbols and their respective types. Then, the staff line detection combines the extracted lines to staves and yields an F\(_1\) -score of over 99% for both detecting lines and complete staves. For the music symbol detection, we choose a novel approach that skips the step to identify neumes and instead directly predicts note components (NCs) and their respective affiliation to a neume. Furthermore, the algorithm detects clefs and accidentals. Our algorithm predicts the symbol sequence of a staff with a diplomatic symbol accuracy rate (dSAR) of about 87%, which includes symbol type and location. If only the NCs without their respective connection to a neume, all clefs and accidentals are of interest, the algorithm reaches an harmonic symbol accuracy rate (hSAR) of approximately 90%. In general, the algorithm recognises a symbol in the manuscript with an F\(_1\) -score of over 96%.
Large-area remote sensing time-series offer unique features for the extensive investigation of our environment. Since various error sources in the acquisition chain of datasets exist, only properly validated results can be of value for research and downstream decision processes. This review presents an overview of validation approaches concerning temporally dense time-series of land surface geo-information products that cover the continental to global scale. Categorization according to utilized validation data revealed that product intercomparisons and comparison to reference data are the conventional validation methods. The reviewed studies are mainly based on optical sensors and orientated towards global coverage, with vegetation-related variables as the focus. Trends indicate an increase in remote sensing-based studies that feature long-term datasets of land surface variables. The hereby corresponding validation efforts show only minor methodological diversification in the past two decades. To sustain comprehensive and standardized validation efforts, the provision of spatiotemporally dense validation data in order to estimate actual differences between measurement and the true state has to be maintained. The promotion of novel approaches can, on the other hand, prove beneficial for various downstream applications, although typically only theoretical uncertainties are provided.
Fungi of the order Mucorales colonize all kinds of wet, organic materials and represent a permanent part of the human environment. They are economically important as fermenting agents of soybean products and producers of enzymes, but also as plant parasites and spoilage organisms. Several taxa cause life-threatening infections, predominantly in patients with impaired immunity. The order Mucorales has now been assigned to the phylum Mucoromycota and is comprised of 261 species in 55 genera. Of these accepted species, 38 have been reported to cause infections in humans, as a clinical entity known as mucormycosis. Due to molecular phylogenetic studies, the taxonomy of the order has changed widely during the last years. Characteristics such as homothallism, the shape of the suspensors, or the formation of sporangiola are shown to be not taxonomically relevant. Several genera including Absidia, Backusella, Circinella, Mucor, and Rhizomucor have been amended and their revisions are summarized in this review. Medically important species that have been affected by recent changes include Lichtheimia corymbifera, Mucor circinelloides, and Rhizopus microsporus. The species concept of Rhizopus arrhizus (syn. R. oryzae) is still a matter of debate. Currently, species identification of the Mucorales is best performed by sequencing of the internal transcribed spacer (ITS) region. Ecologically, the Mucorales represent a diverse group but for the majority of taxa, the ecological role and the geographic distribution remain unknown. Understanding the biology of these opportunistic fungal pathogens is a prerequisite for the prevention of infections, and, consequently, studies on the ecology of the Mucorales are urgently needed.
Synergy of chemo- and photodynamic therapies with C\(_{60}\) Fullerene-Doxorubicin nanocomplex
(2019)
A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C\(_{60}\) fullerene (C\(_{60}\)) were applied in 1:1 and 2:1 molar ratio, exploiting C\(_{60}\) both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox’s nuclear and C\(_{60}\)'s extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox's antiproliferative activity and C\(_{60}\)'s photoinduced pro-oxidant activity. When cells were treated with 2:1 C\(_{60}\)-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C\(_{60}\)-Dox enabled a nanomolar concentration of Dox and C\(_{60}\) to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC\(_{50}\) 16, 9 and 7 × 10\(^3\)-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C\(_{60}\)'s photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C\(_{60}\)-mediated Dox delivery and C\(_{60}\) photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C\(_{60}\)-Dox nanoformulation provides a promising synergetic approach for cancer treatment.
Advances in remote inventory and analysis of forest resources during the last decade have reached a level to be now considered as a crucial complement, if not a surrogate, to the long-existing field-based methods. This is mostly reflected in not only the use of multiple-band new active and passive remote sensing data for forest inventory, but also in the methodic and algorithmic developments and/or adoptions that aim at maximizing the predictive or calibration performances, thereby minimizing both random and systematic errors, in particular for multi-scale spatial domains. With this in mind, this editorial note wraps up the recently-published Remote Sensing special issue “Remote Sensing-Based Forest Inventories from Landscape to Global Scale”, which hosted a set of state-of-the-art experiments on remotely sensed inventory of forest resources conducted by a number of prominent researchers worldwide.
Dead wood comprises a vast amount of biological legacies that set the scene for ecological regeneration after wildfires, yet its removal is the most frequent management strategy worldwide. Soil-dwelling organisms are conspicuous, and they provide essential ecosystem functions, but their possible affection by different post-fire management strategies has so far been neglected. We analyzed the abundance, richness, and composition of belowground macroarthropod communities under two contrasting dead-wood management regimes after a large wildfire in the Sierra Nevada Natural and National Park (Southeast Spain). Two plots at different elevation were established, each containing three replicates of two experimental treatments: partial cut, where trees were cut and their branches lopped off and left over the ground, and salvage logging, where all the trees were cut, logs were piled, branches were mechanically masticated, and slash was spread on the ground. Ten years after the application of the treatments, soil cores were extracted from two types of microhabitat created by these treatments: bare-soil (in both treatments) and under-logs (in the partial cut treatment only). Soil macroarthropod assemblages were dominated by Hemiptera and Hymenoptera (mostly ants) and were more abundant and richer in the lowest plot. The differences between dead-wood treatments were most evident at the scale of management interventions: abundance and richness were lowest after salvage logging, even under similar microhabitats (bare-soil). However, there were no significant differences between microhabitat types on abundance and richness within the partial cut treatment. Higher abundance and richness in the partial cut treatment likely resulted from higher resource availability and higher plant diversity after natural regeneration. Our results suggest that belowground macroarthropod communities are sensitive to the manipulation of dead-wood legacies and that management through salvage logging could reduce soil macroarthropod recuperation compared to other treatments with less intense management even a decade after application.
Here, we present a small Iranian family, where the index patient received a diagnosis of restrictive cardiomyopathy (RCM) in combination with atrioventricular (AV) block. Genetic analysis revealed a novel homozygous missense mutation in the DES gene (c.364T > C; p.Y122H), which is absent in human population databases. The mutation is localized in the highly conserved coil-1 desmin subdomain. In silico, prediction tools indicate a deleterious effect of the desmin (DES) mutation p.Y122H. Consequently, we generated an expression plasmid encoding the mutant and wildtype desmin formed, and analyzed the filament formation in vitro in cardiomyocytes derived from induced pluripotent stem cells and HT-1080 cells. Confocal microscopy revealed a severe filament assembly defect of mutant desmin supporting the pathogenicity of the DES mutation, p.Y122H, whereas the wildtype desmin formed regular intermediate filaments. According to the guidelines of the American College of Medical Genetics and Genomics, we classified this mutation, therefore, as a novel pathogenic mutation. Our report could point to a recessive inheritance of the DES mutation, p.Y122H, which is important for the genetic counseling of similar families with restrictive cardiomyopathy caused by DES mutations.
The alarming increase in the magnitude and spatiotemporal patterns of changes in composition, structure and function of forest ecosystems during recent years calls for enhanced cross-border mitigation and adaption measures, which strongly entail intensified research to understand the underlying processes in the ecosystems as well as their dynamics. Remote sensing data and methods are nowadays the main complementary sources of synoptic, up-to-date and objective information to support field observations in forest ecology. In particular, analysis of three-dimensional (3D) remote sensing data is regarded as an appropriate complement, since they are hypothesized to resemble the 3D character of most forest attributes. Following their use in various small-scale forest structural analyses over the past two decades, these sources of data are now on their way to be integrated in novel applications in fields like citizen science, environmental impact assessment, forest fire analysis, and biodiversity assessment in remote areas. These and a number of other novel applications provide valuable material for the Forests special issue “3D Remote Sensing Applications in Forest Ecology: Composition, Structure and Function”, which shows the promising future of these technologies and improves our understanding of the potentials and challenges of 3D remote sensing in practical forest ecology worldwide.
Human health is known to be affected by the physical environment. Various environmental influences have been identified to benefit or challenge people's physical condition. Their heterogeneous distribution in space results in unequal burdens depending on the place of living. In addition, since societal groups tend to also show patterns of segregation, this leads to unequal exposures depending on social status. In this context, environmental justice research examines how certain social groups are more affected by such exposures. Yet, analyses of this per se spatial phenomenon are oftentimes criticized for using “essentially aspatial” data or methods which neglect local spatial patterns by aggregating environmental conditions over large areas. Recent technological and methodological developments in satellite remote sensing have proven to provide highly detailed information on environmental conditions. This narrative review therefore discusses known influences of the urban environment on human health and presents spatial data and applications for analyzing these influences. Furthermore, it is discussed how geographic data are used in general and in the interdisciplinary research field of environmental justice in particular. These considerations include the modifiable areal unit problem and ecological fallacy. In this review we argue that modern earth observation data can represent an important data source for research on environmental justice and health. Especially due to their high level of spatial detail and the provided large-area coverage, they allow for spatially continuous description of environmental characteristics. As a future perspective, ongoing earth observation missions, as well as processing architectures, ensure data availability and applicability of ’big earth data’ for future environmental justice analyses.
Estimating penetration-related X-band InSAR elevation bias: a study over the Greenland ice sheet
(2019)
Accelerating melt on the Greenland ice sheet leads to dramatic changes at a global scale. Especially in the last decades, not only the monitoring, but also the quantification of these changes has gained considerably in importance. In this context, Interferometric Synthetic Aperture Radar (InSAR) systems complement existing data sources by their capability to acquire 3D information at high spatial resolution over large areas independent of weather conditions and illumination. However, penetration of the SAR signals into the snow and ice surface leads to a bias in measured height, which has to be corrected to obtain accurate elevation data. Therefore, this study purposes an easy transferable pixel-based approach for X-band penetration-related elevation bias estimation based on single-pass interferometric coherence and backscatter intensity which was performed at two test sites on the Northern Greenland ice sheet. In particular, the penetration bias was estimated using a multiple linear regression model based on TanDEM-X InSAR data and IceBridge laser-altimeter measurements to correct TanDEM-X Digital Elevation Model (DEM) scenes. Validation efforts yielded good agreement between observations and estimations with a coefficient of determination of R\(^2\) = 68% and an RMSE of 0.68 m. Furthermore, the study demonstrates the benefits of X-band penetration bias estimation within the application context of ice sheet elevation change detection.