Potential of low-temperature aquifer thermal energy storage (LT-ATES) in Germany

More than 30% of Germany’s final energy consumption currently results from thermal energy for heating and cooling in the building sector. One possibility to achieve significant greenhouse gas emission savings in space heating and cooling is the application of aquifer thermal energy storage (ATES) systems. Hence, this study maps the spatial technical potential of shallow low-temperature ATES systems in Germany. Important criteria for efficient ATES operation considered in this assessment encompass suitable hydrogeological conditions, such as aquifer productivity and groundwater flow velocity, and balanced space heating and cooling demands. The latter is approximated by the ratio of heating and cooling degree days, which is incorporated as a time-dependent criterion to also evaluate the impact of climate change on the ATES potential. The hydrogeological and climatic criteria are combined within a spatial analysis revealing that, regarding the upcoming decades, about 54% of the investigated German area are very well or well suitable for ATES applications, largely concentrating on three regions: the North German Basin, the Upper Rhine Graben and the South German Molasse Basin. Considering time-dependent climatic conditions, the very well or well suitable areas will increase by 13% for the time period 2071–2100. This is mostly caused by a large relative area increase of the very well suitable regions due to an increasing cooling demand in the future. The sensitivity of the very well and well suitable regions to the criteria weightings is relatively low. Accounting for existing water protection zones shows a reduction of the country-wide share of very well or well suitable areas by around 11%. Nevertheless, the newly created potential map reveals a huge potential for shallow low-temperature ATES systems in Germany

Localization of Small Leakages in Water Distribution Networks using Concept Drift Explanation Methods

Facing climate change the already limited availability of drinking water will decrease in the future rendering drinking water an increasingly scarce resource. Considerable amounts of it are lost through leakages in water transportation and distribution networks. Leakage detection and localization are challenging problems due to the complex interactions and changing demands in water distribution networks. Especially small leakages are hard to pinpoint yet their localization is vital to avoid water loss over long periods of time. While there exist different approaches to solving the tasks of leakage detection and localization, they are relying on various information about the system, e.g. real-time demand measurements and the precise network topology, which is an unrealistic assumption in many real-world scenarios. In contrast, this work attempts leakage localization using pressure measurements only. For this purpose, first, leakages in the water distribution network are modeled employing Bayesian networks, and the system dynamics are analyzed. We then show how the problem is connected to and can be considered through the lens of concept drift. In particular, we argue that model-based explanations of concept drift are a promising tool for localizing leakages given limited information about the network. The methodology is experimentally evaluated using realistic benchmark scenarios

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Feline low-grade alimentary lymphoma: an emerging entity and a potential animal model for human disease

Background: Low-grade alimentary lymphoma (LGAL) is characterised by the infiltration of neoplastic T-lymphocytes, typically in the small intestine. The incidence of LGAL has increased over the last ten years and it is now the most frequent digestive neoplasia in cats and comprises 60 to 75% of gastrointestinal lymphoma cases. Given that LGAL shares common clinical, paraclinical and ultrasonographic features with inflammatory bowel diseases, establishing a diagnosis is challenging. A review was designed to summarise current knowledge of the pathogenesis, diagnosis, prognosis and treatment of feline LGAL. Electronic searches of PubMed and Science Direct were carried out without date or language restrictions. Results: A total of 176 peer-reviewed documents were identified and most of which were published in the last twenty years. 130 studies were found from the veterinary literature and 46 from the human medicine literature. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. The pathophysiology of feline LGAL still needs to be elucidated, not least the putative roles of infectious agents, environmental factors as well as genetic events. The most common therapeutic strategy is combination treatment with prednisolone and chlorambucil, and prolonged remission can often be achieved. Developments in immunohistochemical analysis and clonality testing have improved the confidence of clinicians in obtaining a correct diagnosis between LGAL and IBD. The condition shares similarities with some diseases in humans, especially human indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Conclusions: The pathophysiology of feline LGAL still needs to be elucidated and prospective studies as well as standardisation of therapeutic strategies are needed. A combination of conventional histopathology and immunohistochemistry remains the current gold-standard test, but clinicians should be cautious about reclassifying cats previously diagnosed with IBD to lymphoma on the basis of clonality testing. Importantly, feline LGAL could be considered to be a potential animal model for indolent digestive T-cell lymphoproliferative disorder, a rare condition in human medicine

Substrate profiling of anion methyltransferases for promiscuous synthesis of S-adenosylmethionine analogs from haloalkanes

Schülke KH, Ospina Sánchez F, Hörnschemeyer K, Gergel S, Hammer S. Substrate profiling of anion methyltransferases for promiscuous synthesis of S-adenosylmethionine analogs from haloalkanes. ChemBioChem . 2022;23(4): e202100632.Biocatalytic alkylation reactions can be performed with high chemo-, regio- and stereoselectivity using S -adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) and SAM analogs. Currently, however, this methodology is limited in application due to the rather laborious protocols to access SAM analogs. It has recently been shown that halide methyltransferases (HMTs) enable synthesis and recycling of SAM analogs with readily available haloalkanes as starting material. Here we expand this work by using substrate profiling of the anion MT enzyme family to explore promiscuous SAM analog synthesis. Our study shows that anion MTs are in general very promiscuous with respect to the alkyl chain as well as the halide leaving group. Substrate profiling further suggests that promiscuous anion MTs cluster in sequence space. Next to iodoalkanes, cheaper, less toxic and more available bromoalkanes have been converted and several haloalkanes bearing short alkyl groups, alkyl rings, and functional groups such as alkene, alkyne and aromatic moieties are accepted as substrates. Further, we applied the SAM analogs as electrophiles in enzyme-catalyzed regioselective pyrazole allylation with 3-bromopropene as starting material. © 2021 Wiley-VCH GmbH

Heat vs. Health: Home Office under a Changing Climate

Stressors are especially widespread in urban agglomerations. Common themes of built environment interventions that support health and well-being are blue and green infrastructure, indoor and outdoor air quality, thermal comfort, access to natural lighting, and acoustics. Given the current megatrends of increasing summer temperatures and the high popularity of home offices, we aimed at modeling thermal comfort changes of people working at home in three Austrian cities (Vienna, Innsbruck, and Graz) during the next decades until 2090. We present findings based on (I) an inter-disciplinary literature search and (II) indoor and outdoor climate simulations for actual and future climate scenarios. Based on the results, we discuss the potential impacts for work and human health and well-being, and we suggest a framework for the home office in “post-COVID-19 Austria” that integrates social, ecological, and economic aspects. The results of our study indicate that, in future climate scenarios, overheating of the interior can no longer be prevented without active cooling measures and nature-based solutions. Recommendations on the adjustment of behavior under climate change, including greening, adequate ventilation, and cooling techniques, are thus urgently needed for employees who are working from home in order to maintain physical and mental health and wellbeing

Direct Quantification of Cytochromes P450 and Drug Transporters-A Rapid, Targeted Mass Spectrometry-Based Immunoassay Panel for Tissues and Cell Culture Lysates

The quantification of drug metabolizing enzymes and transporters has recently been revolutionized on the basis of targeted proteomic approaches. Isotope-labeled peptides are used as standards for the quantification of the corresponding proteins in enzymatically fragmented samples. However, hurdles in these approaches are low throughput and tedious sample prefractionation steps prior to mass spectrometry (MS) readout. We have developed an assay platform using sensitive and selective immunoprecipitation coupled with mass spectrometric readout allowing the quantification of proteins directly from whole cell lysates using less than 20,000 cells per analysis. Peptide group-specific antibodies (triple X proteomics antibodies) enable the enrichment of proteotypic peptides sharing a common terminus. These antibodies were employed to establish a MS-based immunoassay panel for the quantification of 14 cytochrome P450 (P450) enzymes and nine transporters. We analyzed the P450 enzyme and transporter levels in genotyped liver tissue homogenates and microsomes, and in samples from a time course induction experiment in human hepatocytes addressing different induction pathways. For the analysis of P450 enzymes and transporters only a minute amount of sample is required and no prefractionation is necessary, thus the assay platform bears the potential to bridge cell culture model experiments and results from whole organ tissue studies