Feature-based Groundwater Hydrograph Clustering Using Unsupervised Self-Organizing Map-Ensembles

Hydrograph clustering helps to identify dynamic patterns within aquifers systems, an important foundation of characterizing groundwater systems and their influences, which is necessary to effectively manage groundwater resources. We develope an unsupervised modeling approach to characterize and cluster hydrographs on regional scale according to their dynamics. We apply feature-based clustering to improve the exploitation of heterogeneous datasets, explore the usefulness of existing features and propose new features specifically useful to describe groundwater hydrographs. The clustering itself is based on a powerful combination of Self-Organizing Maps with a modified DS2L-Algorithm, which automatically derives the cluster number but also allows to influence the level of detail of the clustering. We further develop a framework that combines these methods with ensemble modeling, internal cluster validation indices, resampling and consensus voting to finally obtain a robust clustering result and remove arbitrariness from the feature selection process. Further we propose a measure to sort hydrographs within clusters, useful for both interpretability and visualization. We test the framework with weekly data from the Upper Rhine Graben System, using more than 1800 hydrographs from a period of 30 years (1986-2016). The results show that our approach is adaptively capable of identifying homogeneous groups of hydrograph dynamics. The resulting clusters show both spatially known and unknown patterns, some of which correspond clearly to external controlling factors, such as intensive groundwater management in the northern part of the test area. This framework is easily transferable to other regions and, by adapting the describing features, also to other time series-clustering applications.

     

Synthesis of Light Hydrocarbons from Biogas and Hydrogen: Investigation of a Fe-Mn-K/MgO Catalyst

Fischer-Tropsch synthesis of the CO₂ in biogas aims at producing light hydrocarbons and increasing its calorific value for feeding into the grid. Fe catalysts with Mn and K as promoters are supposed to yield high amounts of light hydrocarbons. Using a Fe-Mn-K/MgO catalyst, a parameter screening and long-term experiments were carried out. The catalyst shows, within the examined range, the highest selectivity to C₂–C₄ hydrocarbons at 450 °C, 8 bar(a), and a gas hourly space velocity of 350 h⁻¹. Calcination of the catalyst resulted in a significant drop of activity and an almost complete loss of selectivity to hydrocarbons. Admixture of steam to the reactant gas lowers the tendency to carbon deposition but also promotes the water-gas shift reaction and results in lower yields of hydrocarbons.     

Exploring design trade-offs for achieving social inclusion in multi-tiered design problems

ABSTRACT

The digital age of the future is ‘not out there to be discovered’, but it needs to be ‘designed’. The design challenge has to address questions about how we want to live, work, and learn (as individuals and as communities) and what we value and appreciate, e.g.: reflecting on quality of life and creating inclusive societies. An overriding design trade-off for the digital age is whether new developments will increase the digital divide or will create more inclusive societies. Sustaining inclusive societies means allowing people of all ages and all abilities to exploit information technologies for personally meaningful activities. Meta-design fosters the design of socio-technical environments that end-user developers can modify and evolve at use time to improve their quality of life and favour their inclusion in the society. This paper describes three case studies in the domain of assistive technologies in which end users themselves cannot act as end-user developers, but someone else (e.g.: a caregiver or a clinician) must accept this role requiring multi-tiered architectures. The design trade-offs and requirements for meta-design identified in the context of the case studies and other researchers’ projects are described to inform the development of future socio-technical environments focused on social inclusion.     

ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

Engineering egress data considering pedestrians with reduced mobility

To quantify the evacuation process, evacuation practitioners use engineering egress data describing the occupant movement characteristics. These data are typically based to young and fit populations. However, the movement abilities of occupants who might be involved in evacuations are becoming more variable—with the building populations of today typically including increasing numbers of individuals: with impairments or who are otherwise elderly or generally less mobile. Thus, there will be an increasing proportion of building occupants with reduced ability to egress. For safe evacuation, there is therefore a need to provide valid engineering egress data considering pedestrians with disabilities. Gwynne and Boyce recently compiled a series of data sets related to the evacuation process to support practitioner activities in the chapter Engineering Data in the SFPE Handbook of Fire Protection Engineering. This paper supplements these data sets by providing information on and presenting data obtained from additional research related to the premovement and horizontal movement of participants with physical‐, cognitive‐, or age‐related disabilities. The aim is to provide an overview of currently available data sets related to, and key factors affecting the egress performance of, mixed ability populations which could be used to guide fire safety engineering decisions in the context of building design.     

Epos – an instrument for the assessment of the ethical position in software development

Digital technology becomes more powerful, intelligent, pervasive and ubiquitous. Ethical aspects of this development have not yet drawn the appropriate attention of researchers and engineers. This paper presents an instrument that aims at measuring the individual ethical position with regard to the design and development of computer software. The development of the Epos tool was based on two data collections. The data of the first survey (n₁ = 147 participants) were used to select items and to determine the factorial structure of the questionnaire. Results show that the Epos instrument reliably assesses peoples’ ethical opinion with respect to five central components: (1) regulation, (2) data privacy, (3) domain specific knowledge, (4) societal responsibility and (5) company responsibility. In the second survey, we determined the stability of the instruments factor structure by assessing a sample of n₂?=?196 participants. A confirmatory factor analysis (CFA) supported the initial factor structure. Next steps and further implications are discussed regarding the final version of the questionnaire.     

Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.