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Achieving urban water security is a major challenge for many countries. While several studies have assessed water security at a regional level, many studies have also emphasized the lack of assessment of water security and application of measures to achieve it at the urban level.
Recent studies that have focused on measuring urban water security are not holistic, and there is still no agreed-upon understanding of how to operationalize and identify an assessment framework to measure the current state and dynamics of water security. At present, there is also no clearly defined and widely endorsed definition of urban water security. To address this challenge, this study provides a systematic approach to better understand urban water security, with a working definition and an assessment framework to be applied in peri-urban and urban areas. The proposed working definition of urban water security is based on the United Nations (UN) sustainable development goal on water and sanitation and the human rights on water and sanitation. It captures issues of urban-level technical, environmental, and socio-economic indicators that emphasize credibility, legitimacy, and salience.
The assessment framework depends on four main dimensions to achieve urban water security: Drinking water and human beings, ecosystem, climate change and water-related hazards, and socio-economic factors (DECS). The framework further enables the analysis of relationships and trade-off between urbanization and water security, as well as between DECS indicators. Applying this framework will help governments, policy-makers, and water stakeholders to target scant resources more eff ectively and sustainably. The study reveals that achieving urban water security requires a holistic and integrated approach with collaborative stakeholders to provide a meaningful way to improve understanding and managing urban water security.
Stable recombinant mammalian cells are of growing importance in pharmaceutical biotechnology production scenarios for biologics such as monoclonal antibodies, growth and blood factors, cytokines and subunit vaccines. However, the establishment of recombinant producer cells using classical stable transfection of plasmid DNA is hampered by low stable gene transfer efficiencies. Consequently, subsequent selection of transgenic cells and the screening of clonal cell populations are time- and thus cost-intensive. To overcome these limitations, expression cassettes were embedded into transposon-derived donor vectors. Upon the co-transfection with transposase-encoding constructs, elevated vector copy numbers stably integrated into the genomes of the host cells are readily achieved facilitating under stringent selection pressure the establishment of cell pools characterized by sustained and high-yield recombinant protein production. Here, we discuss some aspects of transposon vector technologies, which render these vectors promising candidates for their further utilization in the production of biologics.
In this paper we describe traffic sign recognition with neural networks in the frequency domain. Traffic signs exist in all countries to regulate the traffic of vehicles and pedestrians. Each country has its own set of traffic signs that are more or less similar. They consist of a set of abstract forms, symbols, numbers and letters, which are combined into different signs. Automatic traffic sign recognition is important for driver assistance systems and for autonomous driving. Traffic sign recognition is a subtype of image recognition. The traffic signs are usually recorded by a camera and must be recognized in real time, i.e. assigned to a class. We use neural networks for traffic sign recognition. The special feature of our method is that the traffic sign recognition does not take place in the spatial domain but in the frequency domain. This has advantages because it is possible to significantly reduce the number of neurons and thus the computing effort of the neural network compared to a conventional neural network.
Despite intensive research over the last three decades, it has not yet been possible to bring an effective vaccine against human immunodeficiency virus (HIV) and the resulting acquired immunodeficiency syndrome (AIDS) to market. Virus-like particles (VLP) are a promising approach for efficient and effective vaccination and could play an important role in the fight against HIV. For example, HEK293 (human embryo kidney) cells can be used to produce virus-like particles. In this context, given the quality-by-design (QbD) concept for manufacturing, a digital twin is of great importance for the production of HIV-Gag-formed VLPs. In this work, a dynamic metabolic model for the production of HIV-Gag VLPs was developed and validated. The model can represent the VLP production as well as the consumption or formation of all important substrates and metabolites. Thus, in combination with already described process analytical technology (PAT) methods, the final step towards the implementation of a digital twin for process development and design, as well as process automation, was completed.
Abstract
Due to their pronounced bioactivity and limited availability from natural resources, metabolites of the soft coral Pseudopterogorgia elisabethae, such as erogorgiaene and the pseudopterosines, represent important target molecules for chemical synthesis. We have now developed a particularly short and efficient route towards these marine diterpenes exploiting an operationally convenient enantioselective cobalt‐catalyzed hydrovinylation as the chirogenic step. Other noteworthy C−C bond forming transformations include diastereoselective Lewis acid‐mediated cyclizations, a Suzuki coupling and a carbonyl ene reaction. Starting from 4‐methyl‐styrene the anti‐tubercular agent (+)‐erogorgiaene (>98 % ee) was prepared in only 7 steps with 46 % overall yield. In addition, the synthesis of the pseudopterosin A aglycone was achieved in 12 steps with 30 % overall yield and, surprisingly, was found to exhibit a similar anti‐inflammatory activity (inhibition of LPS‐induced NF‐κB activation) as a natural mixture of pseudopterosins A−D or iso‐pseudopterosin A, prepared by β‐D‐xylosylation of the synthetic aglycone.
Thioredoxin (Trx) overexpression is known to be a cause of chemotherapy resistance in various tumor entities. However, Trx effects on resistance are complex and depend strictly on tissue type. In the present study, we analyzed the impact of the Trx system on intrinsic chemoresistance of human glioblastoma multiforme (GBM) cells to cytostatic drugs. Resistance of GBM cell lines and primary cells to drugs and signaling inhibitors was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Impact of Trx inhibition on apoptosis was investigated by proteome profiling of a subset of proteins and annexin V apoptosis assays. Trx-interacting protein (TXNIP) was overexpressed by transfection and protein expression was determined by immunoblotting. Pharmacological inhibition of Trx by 1-methyl-2-imidazolyl-disulfide (PX-12) reduced viability of three GBM cell lines, induced expression of active caspase-3, and reduced phosphorylation of AKT-kinase and expression of β-catenin. Sensitivity to cisplatin could be restored by both PX-12 and recombinant expression of the upstream Trx inhibitor TXNIP, respectively.
In addition, PX-12 also sensitized primary human GBM cells to temozolomide. Combined inhibition of Trx and the phosphatidylinositide 3-kinase (PI3K) pathway resulted in massive cell death. We conclude that the Trx system and the PI3K pathway act as a sequential cascade and could potentially present a new drug target.
AbstractThis paper discusses the comparison of two methods to achieve thermal comfort utilising air conditioning (AC) system in a small indoor space – adaptive control and fuzzy control. Thermal comfort indoors is performed to provide comfortability individually or for a group of people. Due to the small indoor space which usually a bit cramped, crowded and less airy, the ambience can be very uncomfortable either for doing sedentary or active work, thus the AC system can be very useful to provide thermal comfort. Both methods can be utilised depending on how thermal comfort is viewed and how the level of thermal comfort is decided. Every method has its own advantage and limitations, and will be covered in this paper as well.
This paper documents the design, implementation and evaluation of the Unfolding Space Glove—an open source sensory substitution device. It transmits the relative position and distance of nearby objects as vibratory stimuli to the back of the hand and thus enables blind people to haptically explore the depth of their surrounding space, assisting with navigation tasks such as object recognition and wayfinding. The prototype requires no external hardware, is highly portable, operates in all lighting conditions, and provides continuous and immediate feedback—all while being visually unobtrusive. Both blind (n = 8) and blindfolded sighted participants (n = 6) completed structured training and obstacle courses with both the prototype and a white long cane to allow performance comparisons to be drawn between them. The subjects quickly learned how to use the glove and successfully completed all of the trials, though still being slower with it than with the cane. Qualitative interviews revealed a high level of usability and user experience. Overall, the results indicate the general processability of spatial information through sensory substitution using haptic, vibrotactile interfaces. Further research would be required to evaluate the prototype’s capabilities after extensive training and to derive a fully functional navigation aid from its features.
We examine the impact of the existence on an explicit deposit insurance (DI) scheme and its design features on bilateral cross‐border deposits (CBD) in a gravity model setting. We find that both the absolute quality of a country's DI and its relative quality vis‐à‐vis other countries' DI generally affect depositor behavior. However, during systemic banking crises, cross‐border depositors primarily seek countries with the best DI schemes. Similarly, during the 2008–2009 great financial crisis, the emergency actions taken by the governments, which supply and maintain these safe havens, have led to substantial relocations of CBD. (JEL F34, G18)
This study aimed to simulate the sector-coupled energy system of Germany in 2030 with the restriction on CO2 emission levels and to observe how the system evolves with decreasing emissions. Moreover, the study presented an analysis of the interconnection between electricity, heat and hydrogen and how technologies providing flexibility will react when restricting CO2 emissions levels. This investigation has not yet been carried out with the technologies under consideration in this study. It shows how the energy system behaves under different set boundaries of CO2 emissions and how the costs and technologies change with different emission levels. The study results show that the installed capacities of renewable technologies constantly increase with higher limitations on emissions. However, their usage rates decreases with low CO2 emission levels in response to higher curtailed energy. The sector-coupled technologies behave differently in this regard. Heat pumps show similar behaviour, while the electrolysers usage rate increases with more renewable energy penetration. The system flexibility is not primarily driven by the hydrogen sector, but in low CO2 emission level scenarios, the flexibility shifts towards the heating sector and electrical batteries.