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Multidrug resistance (MDR) in tumors and pathogens remains a major problem in the efficacious treatment of patients by reduction of therapy options and subsequent treatment failure. Various mechanisms are described to be involved in the development of MDR with overexpression of ATP-binding cassette (ABC) transporters reflecting the most extensively studied. These membrane transporters translocate a wide variety of substrates utilizing energy from ATP hydrolysis leading to decreased intracellular drug accumulation and impaired drug efficacy. One treatment strategy might be inhibition of transporter-mediated efflux by small molecules. Isocoumarins and 3,4-dihydroisocoumarins are a large group of natural products derived from various sources with great structural and functional variety, but have so far not been in the focus as potential MDR reversing agents. Thus, three natural products and nine novel 3,4-dihydroisocoumarins were designed and analyzed regarding cytotoxicity induction and inhibition of human ABC transporters P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) in a variety of human cancer cell lines as well as the yeast ABC transporter Pdr5 in Saccharomyces cerevisiae. Dual inhibitors of P-gp and BCRP and inhibitors of Pdr5 were identified, and distinct structure-activity relationships for transporter inhibition were revealed. The strongest inhibitor of P-gp and BCRP, which inhibited the transporters up to 80 to 90% compared to the respective positive controls, demonstrated the ability to reverse chemotherapy resistance in resistant cancer cell lines up to 5.6-fold. In the case of Pdr5, inhibitors were identified that prevented substrate transport and/or ATPase activity with IC50 values in the low micromolar range. However, cell toxicity was not observed. Molecular docking of the test compounds to P-gp revealed that differences in inhibition capacity were based on different binding affinities to the transporter. Thus, these small molecules provide novel lead structures for further optimization.
Water shortage and a rising water demand are prevalent issues on the political agenda worldwide. Available water resources must not only be provided to ensure a domestic and drinking water supply for a steadily increasing population but also for the growing industrial and agricultural sectors. This work outlines how the use of the innovative vacuum multi‐effect membrane distillation contributes to improve the water management efficiency in the following key industry sectors: desalination, drinking water and beverage industry, pharmaceutical, agro and chemical as well as oil and gas industry.
Resilience in relation to flood risk management (FRM) is not a new concept, yet parts of the FRM community are still struggling to apply it. The main challenge this study addresses is the question as to whether parts of the FRM community should still adopt, or rather “leap‐frog,” resilience. The main purpose is to evaluate whether resilience is a still on‐going trend or, already subsiding. Research suggests that resilience is an on‐going trend that connects research and policy and has gained international recognition as expressed by international guidelines and bodies promoting its research but also its operationalization. Academic literature in the area of FRM also shows a significant continuing development. Resilience enables to analyze dynamics and transformations of riverine areas, or coastal zones in connection to an integrated social‐environmental system approach with more emphasis and conceptual basis than previous concepts. Resilience is more than a short‐lived notion and it appears that FRM researchers cannot avoid addressing it. Resilience often is a convergence of ideas and mainstreaming of efforts, which in many venues is absolutely necessary and can help, for example, to decrease silo‐thinking. But as academics, we have a mandate to remain skeptical and remain on the look‐out for novel ideas, too.
This article is categorized under:
Engineering Water > Planning Water
Life cycle assessment is a crucial tool in evaluating systems performances for sustainability and decision-making. This paper provided environmental impact of integrating renewable energy systems to the utility-grid based on a baseline optimized energy production data from “HOMER” for renewable systems modelling of a site in northern Nigeria. The ultimate goal was to ascertain the best hybrid option(s) in sustaining the environment. Different assumptions and scenarios were modelled and simulated using Ganzleitlichen Bilanz (GaBi). Uncertainty analysis was ensured to the impact data based on pedigree-matrix and Excel-program, as well as overall policy relevance. The results of the impact categories revealed first scenario (i.e., conventional path-based) with the highest impacts on global warming potential (GWP), acidification potential (AP), human toxicity potential (HTP), and abiotic depletion potential (ADP fossils). The lowest impacts arise in
the renewable-based scenarios for all the considered categories except the Ozone-layer depletion potential Category where the highest contribution falls in the third scenario (i.e., photovoltaic (PV)/biomass-biogas system) although all values being infinitesimal. In quantitative terms, the reduction in the GWP from the highest being the first scenario to the lowest being the fourth scenario (i.e., wind/biomass-biogas system) was 96.5%. Hence, with the outstanding contributions of the hybrid renewable systems, adopting them especially the lowest impact scenarios with expansions is relevant for environmental sustainability.
This contribution deals with the topic of the consistent further development of a wheel hub motor for battery electric vehicles (BEV) based on the principle of an outer rotor switched reluctance machine (SRM). The research work presented in this paper was founded by the ERDF.NRW program, Investment for Growth and Employment and the European Regional Development Fund. The R&D project was named Switched - Reluctance fo(u)r wheel (SR4Wheel). Based on the experience made by first prototype Evolution 0 (EVO 0), developed in the Laboratory for Automation Engineering, Power Electronics and Electrical Drives of the Cologne University of Applied Sciences (CUAS), the test results of EVO 1, as well as the redesign, EVO 2 is presented in this paper.
The prototype EVO 0, a first proof of concept leads to several optimizations and lessons learned for the predecessor model EVO 1. The overall target of developing such a gearless outer rotor wheel hub motor is the full integration of the complete machine including its power electronics into the given space between the original friction brake and the rim. Furthermore, due to the additional integration of the power electronics, great opportunities in terms of new vehicle design as well as retrofitting capabilities of already existing vehicle platforms can be achieved. Thereby, further drive train assembly space like the engine compartment is no longer necessary. The SRM does not require magnets for torque production which leads to independence from the changeable commodity prices on the rare earth element markets. This paper presents the developing process, testing, and verification of the innovative drive train concept starting with the final CAD of EVO 1. During the testing and verification process a machine characteristic mapping is performed on a drive train test bench and subsequently the results of a finite element analysis (FEA) are plausibility checked by the test bench results. The process continues with energy conversion test scenarios of the project demonstrator vehicle on a roller test bench focused on noise vibrationharshness (NVH) behavior and efficiency. As a conclusion, the gained knowledge by evaluating two EVO 1 prototypes on the rear axle of the test vehicle, and the design for the front axle drive train EVO 2 will be presented. As a major task on the front axle, the limited space due to the large disc brake can be identified and solved.
The quantification of greenhouse gas emissions from aquatic ecosystems requires knowledge about the spatial and temporal dynamics of free gas in sediments. Freezing the sediment in situ offers a promising method for obtaining gas‐bearing sediment samples, unaffected by changes in hydrostatic pressure and sample temperature during core withdrawal and subsequent analysis. This article presents a novel freeze coring technique to preserve the in situ stratigraphy and gas bubble characteristics. Nondestructive X‐ray computed tomography (CT) scans were used to identify and characterize coring disturbances of gravity and freeze cores associated with gassy sediment, as well as the effect of the freezing process on the gas bubble characteristics. Real‐time X‐ray CT scans were conducted to visualize the progression of the freezing process. Additional experiments were conducted to determine the freezing rate to assess the probability of sediment particle/bubble migration, and gas bubble nucleation at the phase transition of pore water to ice. The performance of the freeze coring technique was evaluated under field conditions in Olsberg and Urft Reservoir (Germany). The results demonstrate the capability of the freeze coring technique for the preservation of gas‐bearing sediments and the analysis of gas bubble distribution pattern in both reservoirs. Nevertheless, the obtained cores showed that nearly all gravity and freeze cores show some degree of coring disturbances.
Metallic tubular micro-components play an important role in a broad range of products,
from industrial microsystem technology, such as medical engineering, electronics and optoelectronics, to sensor technology or microfluidics. The demand for such components is increasing, and forming processes can present a number of advantages for industrial manufacturing. These include, for example, a high productivity, enhanced shaping possibilities, applicability of a wide spectrum of materials and the possibility to produce parts with a high stiffness and strength. However, certain difficulties arise as a result of scaling down conventional tube forming processes to the microscale. These include not only the influence of the known size effects on material and friction behavior, but also constraints in the feasible miniaturization of forming tools. Extensive research work has been conducted over the past few years on micro-tube forming techniques, which deal with the development of novel and optimized processes, to counteract these restrictions. This paper reviews the relevant advances in micro-tube fabrication and shaping. A particular focus is enhancement in forming possibilities, accuracy and obtained component characteristics, presented in the reviewed research work. Furthermore, achievements in severe plastic deformation for micro-tube generation and in micro-tube testing methods are discussed.
Anaerobic digestion plants have the potential to produce biogas on demand to help balance renewable energy production and energy demand by consumers. A proportional integral (PI) controller is constructed and tuned with a novel tuning method to control biogas production in an optimal manner. In this approach, the proportional part of the controller is a function of the feeding rate and system's degree of stability. To estimate the degree of stability, a simulation‐based soft sensor is developed. By means of the PI controller, the requirement for gas storage capacity of the digester is reduced by approximately 30 % compared to a constant, continuous feeding regime of the digester.
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.
Ecosystems provide a wide range of goods, services or ecosystem services (ES) to society. Estimating the impact of land use and land cover (LULC) changes on ES values (ESV) is an important tool to support decision making. This study used remote sensing and GIS tools to analyze LULC change and transitions from 2001 to 2016 and assess its impact on ESV in a tropical forested landscape in the southern plains of Nepal. The total ESV of the landscape for the year 2016 is estimated at USD 1264 million year−1. As forests are the dominant land cover class and have high ES value per hectare, they have the highest contribution in total ESV. However, as a result of LULC change (loss of forests, water bodies, and agricultural land), the total ESV of the landscape has declined by USD 11 million year−1. Major reductions come from the loss in values of climate regulation, water supply, provision of raw materials and food production. To halt the ongoing loss of ES and maintain the supply and balance of different ES in the landscape, it is important to properly monitor, manage and utilize ecosystems. We believe this study will inform policymakers, environmental managers, and the general public on the ongoing changes and contribute to developing effective land use policy in the region.