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Ein systematischer, wertorientierter Ansatz kann für verschiedene Anlageklassen Investitionsentscheidungen stark verbessern

High-resolution mapping of nitrogen oxide emissions in large US cities from TROPOMI retrievals of tropospheric nitrogen dioxide columns

Satellite-derived spatiotemporal patterns of nitrogen oxide (NOx) emissions can improve accuracy of emission inventories to better support air quality and climate research and policy studies. In this study, we develop a new method by coupling the chemical transport Model-Independent SATellite-derived Emission estimation Algorithm for Mixed-sources (MISATEAM) with a divergence method to map high-resolution NOx emissions across US cities using TROPOspheric Monitoring Instrument (TROPOMI) tropospheric nitrogen dioxide (NO2) retrievals. The accuracy of the coupled method is validated through application to synthetic NO2 observations from the NASA-Unified Weather Research and Forecasting (NU-WRF) model, with a horizontal spatial resolution of 4 km × 4 km for 33 large and mid-size US cities. Validation reveals excellent agreement between inferred and NU-WRF-provided emission magnitudes (R= 0.99, normalized mean bias, NMB = −0.01) and a consistent spatial pattern when comparing emissions for individual grid cells (R=0.88±0.06). We then develop a TROPOMI-based database reporting annual emissions for 39 US cities at a horizontal spatial resolution of 0.05° × 0.05° from 2018 to 2021. This database demonstrates a strong correlation (R= 0.90) with the National Emission Inventory (NEI) but reveals some bias (NMB = −0.24). There are noticeable differences in the spatial patterns of emissions in some cities. Our analysis suggests that uncertainties in TROPOMI-based emissions and potential misallocation of emissions and/or missing sources in bottom-up emission inventories both contribute to these differences.</p

Water woes: the institutional challenges in achieving SDG 6

Background: Sustainable Development Goal (SDG) 6 envisions a future where everyone has access to clean water and sanitation. Yet, as 2030 looms closer, the complexity of achieving this target becomes apparent, with issues far surpassing basic water infrastructure and utility challenges. The underlying problems lie in broader spheres such as governance, policymaking, and financing. Main body: The global landscape of water management is marked by complexities that transcend the operational troubles of water utilities. Financial sustainability is a monumental task. And while it is true that water utilities struggle with revenue generation, the broader picture reveals systemic challenges. The true cost of water provision often extends to ecosystem services such as watershed protection. Often, these services are not internalized in the revenue models of utilities but are typically subsidized by governments or simply not considered. Balancing affordability for users with cost recovery for service providers, however, is not just an arithmetic exercise. It is also a question of equitable policies. Non-revenue water (NRW), resulting from physical losses such as leaks, theft, and inaccurate [or lack of] metering, exacerbates existing financial strain. Annual NRW losses are estimated at an astonishing 126 billion cubic meters, costing roughly USD 39 billion. But at the most fundamental level of achieving SDG 6 is misgovernance. Effective water governance demands consistent policies, coherent collaboration among diverse stakeholders, and comprehensive strategies that cater to specific regional contexts. Current models often suffer from fragmented policies, inadequate public-private partnerships, and weak engagement mechanisms. A glaring gap exists between academic advancements in water management and their practical implementation in policymaking. Moreover, international cooperation, while vital, reveals an unequal landscape in knowledge exchange. Knowledge transfer is often skewed, favoring dominant nations while sidelining voices from the Global South. This emphasizes the need for an inclusive, equitable, and context-specific global cooperation model. Conclusion: The road to realizing SDG 6 is multifaceted, and while on-the-ground solutions are essential, the real success lies in addressing the foundational challenges. This requires innovative financial solutions, reimagining water governance structures, and ensuring all voices, especially from the Global South, are heard and integrated into global policies. As 2030 nears, it is the synergy of governance, finance, and technology that will ultimately make clean water and sanitation a reality for all

Water woes: the institutional challenges in achieving SDG 6

Background Sustainable Development Goal (SDG) 6 envisions a future where everyone has access to clean water and sanitation. Yet, as 2030 looms closer, the complexity of achieving this target becomes apparent, with issues far surpassing basic water infrastructure and utility challenges. The underlying problems lie in broader spheres such as governance, policymaking, and financing. Main body The global landscape of water management is marked by complexities that transcend the operational troubles of water utilities. Financial sustainability is a monumental task. And while it is true that water utilities struggle with revenue generation, the broader picture reveals systemic challenges. The true cost of water provision often extends to ecosystem services such as watershed protection. Often, these services are not internalized in the revenue models of utilities but are typically subsidized by governments or simply not considered. Balancing affordability for users with cost recovery for service providers, however, is not just an arithmetic exercise. It is also a question of equitable policies. Non-revenue water (NRW), resulting from physical losses such as leaks, theft, and inaccurate [or lack of] metering, exacerbates existing financial strain. Annual NRW losses are estimated at an astonishing 126 billion cubic meters, costing roughly USD 39 billion. But at the most fundamental level of achieving SDG 6 is misgovernance. Effective water governance demands consistent policies, coherent collaboration among diverse stakeholders, and comprehensive strategies that cater to specific regional contexts. Current models often suffer from fragmented policies, inadequate public-private partnerships, and weak engagement mechanisms. A glaring gap exists between academic advancements in water management and their practical implementation in policymaking. Moreover, international cooperation, while vital, reveals an unequal landscape in knowledge exchange. Knowledge transfer is often skewed, favoring dominant nations while sidelining voices from the Global South. This emphasizes the need for an inclusive, equitable, and context-specific global cooperation model. Conclusion The road to realizing SDG 6 is multifaceted, and while on-the-ground solutions are essential, the real success lies in addressing the foundational challenges. This requires innovative financial solutions, reimagining water governance structures, and ensuring all voices, especially from the Global South, are heard and integrated into global policies. As 2030 nears, it is the synergy of governance, finance, and technology that will ultimately make clean water and sanitation a reality for all

Using neural networks and evolutionary information in decoy discrimination for protein tertiary structure prediction

Background: We present a novel method of protein fold decoy discrimination using machine learning, more specifically using neural networks. Here, decoy discrimination is represented as a machine learning problem, where neural networks are used to learn the native-like features of protein structures using a set of positive and negative training examples. A set of native protein structures provides the positive training examples, while negative training examples are simulated decoy structures obtained by reversing the sequences of native structures. Various features are extracted from the training dataset of positive and negative examples and used as inputs to the neural networks.Results: Results have shown that the best performing neural network is the one that uses input information comprising of PSI-BLAST [1] profiles of residue pairs, pairwise distance and the relative solvent accessibilities of the residues. This neural network is the best among all methods tested in discriminating the native structure from a set of decoys for all decoy datasets tested. Conclusion: This method is demonstrated to be viable, and furthermore evolutionary information is successfully used in the neural networks to improve decoy discrimination

Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses.

Fibroblast-like cells of secondary lymphoid organs (SLO) are important for tissue architecture. In addition, they regulate lymphocyte compartmentalization through the secretion of chemokines, and participate in the orchestration of appropriate cell-cell interactions required for adaptive immunity. Here, we provide data demonstrating the functional importance of SLO fibroblasts during Notch-mediated lineage specification and immune response. Genetic ablation of the Notch ligand Delta-like (DL)1 identified splenic fibroblasts rather than hematopoietic or endothelial cells as niche cells, allowing Notch 2-driven differentiation of marginal zone B cells and of Esam(+) dendritic cells. Moreover, conditional inactivation of DL4 in lymph node fibroblasts resulted in impaired follicular helper T cell differentiation and, consequently, in reduced numbers of germinal center B cells and absence of high-affinity antibodies. Our data demonstrate previously unknown roles for DL ligand-expressing fibroblasts in SLO niches as drivers of multiple Notch-mediated immune differentiation processes

Sustained axon regeneration induced by co-deletion of PTEN and SOCS3

A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either phosphatase and tensin homologue (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signalling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around 2 weeks after the crush injury. Here we show that, remarkably, simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only results in the induction of many growth-related genes, but also allows RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as key for sustaining long-distance axon regeneration in adult CNS, a crucial step towards functional recovery

A designer hyper interleukin 11 (H11) is a biologically active cytokine

<p>Abstract</p> <p>Background</p> <p>Interleukin 11 (IL-11) is a pleiotropic cytokine with anti-apoptotic, anti-inflammatory and hematopoietic potential. The IL-11 activity is determined by the expression of the IL-11R receptor alpha (IL-11Rα) and the signal transducing subunit β (gp130) on the cell membrane. A recombinant soluble form of the IL-11Rα (sIL-11Rα) in combination with IL-11 acts as an agonist on cells expressing the gp130 molecule. We constructed a designer cytokine Hyper IL-11 (H11), which is exclusively composed of naturally existing components. It contains the full length sIL-11Rα connected with the mature IL-11 protein using their natural sequences only. Such a construct has two major advantages: (i) its components are as close as possible to the natural forms of both proteins and (ii) it lacks an artificial linker what should avoid induction of antibody production.</p> <p>Results</p> <p>The H11 construct was generated, the protein was produced in a baculovirus expression system and was then purified by using ion exchange chromatography. The H11 protein displayed activity in three independent bioassays, (i) it induced acute phase proteins production in HepG2 cells expressing IL-11, IL-11Rα and gp130, (ii) it stimulated the proliferation of B9 cells (cells expressing IL-11Rα and gp130) and (iii) proliferation of Baf/3-gp130 cells (cells not expressing IL-11 and IL-11Rα but gp130). Moreover, the preliminary data indicated that H11 was functionally distinct from Hyper-IL-6, a molecule which utilizes the same homodimer of signal transducing receptor (gp130).</p> <p>Conclusions</p> <p>The biologically active H11 may be potentially useful for treatment of thrombocytopenia, infertility, multiple sclerosis, cardiovascular diseases or inflammatory disorders.</p

Replicating viral vector platform exploits alarmin signals for potent CD8⁺ T cell-mediated tumour immunotherapy.

Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL &lt;sup&gt;eff&lt;/sup&gt; ) responses. Conversely, the induction of protective tumour-specific CTL &lt;sup&gt;eff&lt;/sup&gt; and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33. By triggering interleukin-33 signals, artLCMV elicits CTL &lt;sup&gt;eff&lt;/sup&gt; responses of higher magnitude and functionality than those induced by replication-deficient vectors. Superior anti-tumour efficacy of artLCMV immunotherapy depends on interleukin-33 signalling, and a massive CTL &lt;sup&gt;eff&lt;/sup&gt; influx triggers an inflammatory conversion of the tumour microenvironment. Our observations suggest that replicating viral delivery systems can release alarmins for improved anti-tumour efficacy. These mechanistic insights may outweigh safety concerns around replicating viral vectors in cancer immunotherapy

The Innofusion of Electronic Banking in Indonesia

Even though financial innovation plays an important role in the modern economy, surprisingly there have been few empirical literatures. In developing countries, electronic banking (e-banking), for example, received relatively little attention although has been deployed for years. Indonesia presents unique case of Asian tiger economies, especially after experiencing crisis, financial recession, and economic reform. This research address how e-banking being developed in Indonesia, how it diffused from time to time, what factors that drives and influences the e-banking implementation, how banks manage their e-banking, and what lessons can we learn from it. This study concludes by summarising the case of innofusion of electronic banking in Indonesia. Customers and competitors play an important role in influencing e-banking services adoption. There is also an indication that bigger and older banks are not as innovative and dynamic as their smaller and newer peers. Interestingly, the unavailability of legal protection does not discourage them to partner and cooperate with each other and probably true that it is only 'those' people who drive innovation among Indonesian banks