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Mit einer am Fraunhofer-Institut für Bauphysik IBP durchgeführten Analyse wurde untersucht, inwieweit vorhandene Heizsysteme zur Vermeidung von sommerlicher Überhitzung beitragen können. Das Potenzial von ursprünglich reinen Heiz-Übergabesystemen zum Kühlen kann mit einer hygrothermischen Gebäudesimulation untersucht werden. Diese Metadaten wurden zur Verfügung gestellt von der Literaturdatenbank RSWB®plus

The intensity and frequency of extreme weather events in Europe are one of the most dangerous consequences of a warming climate. Some regions suffer more under heat waves and droughts, while others are experiencing extreme rainfalls. Thus, for example, a severe flood in July 2021 in several European countries caused widespread damages particularly in Belgium and Germany.Which extreme weather events are to be expected in the future? How can the damage of irretrievable historical sites be avoided or, at least, limited or dealt with? All these questions are addressed in the three-year research project KERES, which is funded by the German Federal Ministry of Education and Research (BMBF) and is coordinated by the Fraunhofer ISC together with the Fraunhofer EU Office in Brussels.As first step the regional relevance of future extreme weather events in Germany will be investigated. This information will be further used to estimate the potential damages to buildings and outdoor facilities. The precautionary and responsive measures to manage potential or acute damage situations will be investigated as well. The designed methodologies will be tested for five case studies including World Heritage Sites (historical buildings and historical gardens) in Germany.The major tools of KERES include building component and indoor climate simulations and high-resolution urban climate models. The necessary input will be taken from the most recent ensemble of regional climate change projections of the EURO-CORDEX Initiative (www.euro-cordex.net). As a result, an ontology-based information system will be designed for managing the expected damage situations.We will present first results from the KERES project. The discussion will be focused on how to access and visualize the robustness of projected changes of extreme weather events in a way oriented to individual cultural heritage sites.

International audience; The pharmaceutical industry has a pervasive need for chiral specific molecules with optimal affinity for their biological targets. However, the mass production of such compounds is currently limited by conventional chemical routes, that are costly and have an environmental impact. Here, we propose an easy access to obtain new tetrahydroquinolines, a motif found in many bioactive compounds, that is rapid and cost effective. Starting from simple raw materials, the procedure uses a proline-catalyzed Mannich reaction followed by the addition of BF3.OEt2, which generates a highly electrophilic aza-ortho-quinone methide intermediate capable of reacting with different nucleophiles to form the diversely functionalized tetrahydroquinoline. Moreover, this enantioselective one-pot process provides access for the first time to tetrahydroquinolines with a cis-2,3 and trans-3,4 configuration. As proof of concept, we demonstrate that a three-step reaction sequence, from simple and inexpensive starting compounds and catalysts, can generate a BD2-selective BET bromodomain inhibitor with anti-inflammatory effect.

Neben der Neuinstallation von Klimaanlagen in Bestandsgebäuden ist die Möglichkeit, eine vorhandene Wärmepumpe im reversiblen Betrieb auch zum Kühlen einzusetzen, interessant. In diesem Fall kann für die Kühlung das gleiche System verwendet werden, das bereits zum Heizen installiert ist. Für eine Abschätzung inwiefern diese Technologie zur Vermeidung sommerlicher Überhitzung geeignet ist, wird am Fraunhofer-Institut für Bauphysik IBP eine Potenzialanalyse durchgeführt.

Der Beitrag stellt eine Studie des Fraunhofer-Instituts für Bauphysik (IBP) vor, welche die Verwendbarkeit bestehender Heizkörper und Fußbodenheizungen für die Raumkühlung bei sommerlicher Hitze untersucht. Zur Beurteilung der Tauglichkeit dieser Kühlmethode führte das Fraunhofer IBP eine Parameterstudie durch. Der Beitrag erläutert die zugrunde liegenden Laboruntersuchungen und die Validierung der Labormessergebnisse durch Simulation des Raumklimas anhand der Gebäudesimulationssoftware WUFI Plus. Die dargelegten Ergebnisse zeigen, dass es möglich ist, bestehende Heiz-Übergabesysteme auch zum Kühlen zu verwenden, um den thermischen Komfort zu verbessern. Das Potenzial der betrachteten Systeme zur Vermeidung von Überhitzung wird als vielversprechend bewertet. Zugleich werden die Aspekte aufgezeigt, welche für eine vollumfängliche Beurteilung dieser Kühltechnologie noch zu untersuchen sind, um die Systemtechnik und Steuerungsverfahren zu optimieren. Diese Metadaten wurden zur Verfügung gestellt von der Literaturdatenbank RSWB®plus

Natural cannabidiol ((-)-CBD) and its derivatives have increased interest for medicinal applications due to their broad biological activity spectrum, including targeting of the cannabinoid receptors type 1 (CB

Background/aim Endothelin causes vasoconstriction via the endothelin-A receptor (ET-A) in the intrahepatic circulation in cirrhosis and its increase leads to portal hypertension. The aim of the study was to investigate the acute effect of a selective ET-A antagonist in patients with portal hypertension and cirrhosis. Methods Proof-of-concept study with two different substudies: (a) local intrahepatic administration of the ET-A antagonist BQ 123 and (b) systemic oral administration of the ET-A antagonist Ambrisentan. Portal pressure was determined by hepatic venous pressure gradient (HVPG, both substudies) and hepatic arterial blood flow (HABF) by intra-arterial Doppler measurements (substudy 1) before and under the ET-A antagonist. Systemic haemodynamic parameters were measured in substudy 2. Results Twelve patients (Child-Pugh [CP] B/C n = 7/5) were included in substudy 1 and 14 patients (CP A/B/C n = 4/6/4) in substudy 2. The relative decrease in HVPG was -12.5% (IQR: -40% to 0%; P = .05) in substudy 1 and -5.0% (IQR: -11.5% to 0%; P = .01) in substudy 2. Substudy 1 revealed higher decrease in HVPG in CP B patients. HABF increased significantly and patients without portal pressure decrease showed a higher increase of HABF. Substudy 2 showed a slight decrease in the mean arterial pressure without changes of other systemic haemodynamic parameters. Conclusion Administration of a selective ET-A antagonist decreases the portal pressure in cirrhotic patients. This decrease was higher in CP B patients and the non-responders showed a higher increase in hepatic arterial flow. Selective ET-A antagonists might be a future treatment option in patients with portal hypertension.

Introduction: Preclinical studies have shown that calcium seems to be the active component of the anti-craving drug acamprosate (Ca2+ bis-acetyl-homotaurinate). Clinical effects in humans have also indicated an association between increased calcium plasma concentration due to acamprosate treatment and better outcome relating to time to relapse and cumulative abstinence. In contrast, low calcium concentration in alcohol-dependent patients was related with craving for alcohol. The main goal of the trial was to investigate whether an oral calcium administration is able to affect craving, withdrawal, and relapse risk in alcohol-dependent patients. Methods: We conducted a single-blind, randomized, monocentric, controlled clinical two-arm trial in alcohol-dependent patients (Clinical Trials Registration: DRKS00011293). A total of 55 alcohol-dependent subjects received calcium carbonate (800 mg + 5 μg vitamin D) versus sodium bicarbonate (1,000 mg) daily during the 14 days of inpatient alcohol-withdrawal treatment. Results: Based on an intention-to-treat protocol, withdrawal intensity (assessed with CIWA-Ar) in the calcium carbonate group attenuated faster than in the sodium bicarbonate subgroup. Alcohol craving (assessed with OCDS) in the calcium carbonate subgroup was also significantly reduced versus the sodium bicarbonate subgroup. Conclusion: Our data support earlier findings and show that treatment with calcium carbonate during alcohol withdrawal reduces symptoms of alcohol withdrawal as well as alcohol craving in a controlled clinical pilot study. Mode of actions will need to be determined to allow the further development of pharmacological interventions beyond Ca2+ bis-acetyl-homotaurinate.

T-705 (favipiravir) is a fluorinated hydroxypyrazine carboxamide that exhibits antiviral activities against a variety of RNA viruses. Given the lack of potent agents to combat these infections caused by a large number of high-impact pathogens, significant emphasis has been put on studies of the antiviral properties of T-705 and its mechanism of action. T-705 acts as a nucleobase analogue; it is therefore metabolized to the corresponding ribonucleoside triphosphate intracellularly. Herein we report a reliable synthesis of T-705-ribonucleoside as well as its 5'-monophosphate. Moreover, we disclose detailed studies on the remarkable lability of the heterocycle when attached to ribose under very mild conditions, as typically applied in biochemical studies.

Numerical urban climate models have the potential to be commonly used tools in urban development processes in practice. With integrated modules for building and envelope simulation these complex models allow the assessment of measures in the building sector on the urban climate, e.g. for mitigation of urban heat island effects or preparing for the effects of climate change. However, the currently existing models do not fulfil the requirements that arise in the field of urban planning, as they lack for example functionality, user-friendliness, are hard to integrate in the municipalities’ technical equipment or are not freely available. The German research and development project Urban Climate under Change (2016-2019) developed and validated a new innovative urban climate model called PALM-4U. Aim of the research was to create a model that meets the requirements of users in science as well as practitioners in engineering offices and urban administrations. Therefore, technical features and operational functionalities which the model has to meet to support users in their daily work have been assessed in a first project phase. In total more than 200 requirements were collected which are summed up in the so called “User and Requirements Catalogue”. They served as the basis for testing and evaluating the model’s real-world applicability. To ensure that these complex requirements are met, the whole project follows a transdisciplinary approach integrating science (model development and data assimilation) and practice (user requirements, testing and evaluation) applying a living lab approach: Stakeholders from participating cities and companies took part in on-site workshops, introducing the model with practical use-cases. Afterwards, participants were given tasks covering different features of the model’s applications, which they tested in personal use. The model fulfils the majority of the tested requirements and the users appreciated the model’s concept and functionality. But further development is necessary to provide the practitioners a tool that is applicable in their daily work: Preparation of input data, a user-friendly graphical user-interface, enhanced interfaces to other software and planning tools, use cases that were prepared from experts as well as guidelines and tools for result assessment and interpretation were main suggestions for improvement..

Climate change is among the most important societal challenges of our time. The IPCC special report “Global Warming of 1.5 °C” (IPCC 2018) has shown that even a warming of 1.5 °C compared to pre-industrial levels will have a significant impact on society. Climate change-related risks and impacts are increasing steadily. Many of these risks and impacts will hit urban areas in particular, regardless of their size, location and economic and social circumstances. Key issues include rising temperatures (especially the urban heat island effect) and related issues such as heat stress and increased air pollution, longer dry periods in combination with rising water stress, extreme weather events such as heavy rains, river flooding, and, in coastal areas, sea-level rise. The combined effects of these events are already causing health problems and even death, as well as serious economic damage (Smith et al., 2014). It is expected that these challenges will become even more severe in the coming decades and will require additional efforts.

New two-story wood-construction classrooms where added to an existing heavy-weight construction school building in the year 2006. The glass façade of some classrooms is south oriented. The building design meets the local thermal protection requirement of 2006, but the indoor temperature rises above thermal comfort conditions in the classrooms. As usual in Germany, no active cooling device is and shall be used. Measurements during holidays with close to none internal loads in addition to measurements during regular school occupancy documented the overheating. The measurement results were used to verify a baseline hygrothermal building simulation model that represents the status quo. Various passive measures with regards to construction, design and operation to improve the thermal comfort were assessed. Among them are ventilation strategies and solar protection foil on the glass façade. Furthermore, the already installed temporary sunscreen devices and mechanical night ventilation system coupled to mechanically openable skylights above the classroom doors and within the gravel covered flat roof were investigated with different operating strategies. This paper presents the required steps to improve the simulation model with the measured data in an iterative process. Measures to improve building performance, achieve thermal comfort, and protect overheating are identified.

Natural cannabidiol ((-)-CBD) and its derivatives have increased interest for medicinal applications due to their broad biological activity spectrum, including targeting of the cannabinoid receptors type 1 (CB1R) and type 2 (CB2R). Herein, we synthesized the (+)-enantiomer of CBD and its derivative (+)-CBD hydroxypentylester ((+)-CBD-HPE) that showed enhanced CB1R and CB2R binding and functional activities compared to their respective (-) enantiomers. (+)-CBD-HPE Ki values for CB1R and CB2R were 3.1 ± 1.1 and 0.8 ± 0.1 nM respectively acting as CB1R antagonist and CB2R agonist. We further tested the capacity of (+)-CBD-HPE to prevent hyperglycemia and its complications in a mouse model. (+)-CBD-HPE significantly reduced streptozotocin (STZ)-induced hyperglycemia and glucose intolerance by preserving pancreatic beta cell mass. (+)-CBD-HPE significantly reduced activation of NF-κB by phosphorylation by 15% compared to STZ-vehicle mice, and CD3+ T cell infiltration into the islets was avoided. Consequently, (+)-CBD-HPE prevented STZ-induced apoptosis in islets. STZ induced inflammation and kidney damage, visualized by a significant increase in plasma proinflammatory cytokines, creatinine, and BUN. Treatment with (+)-CBD-HPE significantly reduced 2.5-fold plasma IFN-γ and increased 3-fold IL-5 levels compared to STZ-treated mice, without altering IL-18. (+)-CBD-HPE also significantly reduced creatinine and BUN levels to those comparable to healthy controls. At the macroscopy level, (+)-CBD-HPE prevented STZ-induced lesions in the kidney and voided renal fibrosis and CD3+ T cell infiltration. Thus, (+)-enantiomers of CBD, particularly (+)-CBD-HPE, have a promising potential due to their pharmacological profile and synthesis, potentially to be used for metabolic and immune-related disorders.

In the 1790s, the influx and presence of French emigres was an enduring issue in all parts of the Habsburg monarchy. This chapter conceptualises the exile period as a mutual challenge for both the emigres and the host society and investigates their interactions and interrelation on several levels. Analysing legislation, it identifies three stages of policies towards emigration reflecting different mobility patterns of emigres as well as changing attitudes towards them in the reception country and vice versa. The broad spectrum of everyday relations reveals the productive interplay of interests between emigres and hosts, as the former offered prestige and cultural skills, while the latter provided support and sociability. The final section discusses perspectives on the lasting integration of emigres into the host society.

We here disclose chemical synthesis of ribonucleoside 5'-monophosphate (RMP), -diphosphate (RDP), and -triphosphate (RTP) and cycloSal-, Di PPro-, and Tri PPPro nucleotide prodrugs of the antiviral pseudobase T-1105. Moreover, we include one nucleoside diphosphate prodrug of the chemically less stable T-705. We demonstrate efficient T-1105-RDP and -RTP release from the Di PPro and Tri PPPro compounds by esterase activation. Using crude enzyme extracts, we saw rapid phosphorylation of T-1105-RDP into T-1105-RTP. In sharp contrast, phosphorylation of T-1105-RMP was not seen, indicating a yet unrecognized bottleneck in T-1105's metabolic activation. Accordingly, Di PPro and Tri PPPro compounds displayed improved cell culture activity against influenza A and B virus, which they retained in a mutant cell line incapable of activating the nucleobase parent. T-1105-RTP had a strong inhibitory effect against isolated influenza polymerase, and Di PPro-T-1105-RDP showed 4-fold higher potency in suppressing one-cycle viral RNA synthesis versus T-1105. Hence, our T-1105-RDP and -RTP prodrugs improve antiviral potency and achieve efficient metabolic bypass.

An efficient synthetic access to two amino-oxazoline compound libraries was developed employing the branching cascades approach. A common precursor, that is, chromonylidene β-ketoester was transformed into two different ring-systems, that is, the pyridine and the benzopyrane substituted hydroxyphenones. In further two steps, the ketone moiety in two ring-systems was transformed into an amino-oxazoline ring. The functional groups on the two amino-oxazoline scaffolds were exploited further to generate, a compound collection of ca. 600 amino-oxazolines which are being exposed to various biological screenings within the European Lead Factory consortium.

Itaconic acid, a renewable feedstock obtained by fermentation of carbohydrates, is used as a key substrate to produce aliphatic unsaturated polyesters as well as polynorbornenes. Renewable unsatura...

Epoxides derived from 1,4-cyclohexadiene (CHD), the latter produced from renewable resources via self-metathesis of plant oil derivatives, are applied as key substrates in ring-opening copolymerizations to produce aliphatic polycarbonates and polyesters. Renewable, unsaturated polycarbonates are prepared by the ring-opening copolymerization of epoxide/CO2; these are catalysed by di-zinc/magnesium complexes previously reported by Williams et al. or by using chromium(III) or cobalt(III) salen complexes. Renewable, unsaturated polyesters, with glass transition temperatures up to 128 °C, were obtained by the ring-opening copolymerization of epoxide/phthalic anhydride. The relative rates of these copolymerizations were monitored using in situ attenuated total reflectance infra-red (ATR-IR) spectroscopy. The polymers were fully characterized using spectroscopy (nuclear magnetic resonance, infra-red), mass spectrometry (matrix assisted laser desorption ionization), and by thermal methods (differential scanning calorimetry and thermogravimetric analysis).

With further increasing temperatures during warm summers, cooling of buildings is becoming more popular even in moderate middle or northern European climate zones. Techniques that allow fast conditioning of rooms with intermittent usage, like conference rooms or certain types of residential rooms, promise high potentials for energy savings. Combining heat pumps, that can be used both in cooling and heating modes, with floor and wall heating systems can be a suitable technology. In many cases houses have a conventional heating system with radiators and the question arise if the oil or gas based heating system can be replaced by a heat pump. Mixed systems combining e.g.gas and a heatpump are also possible. For summertime cooling, the same system that is already installed for heating can be used and the radiators allow comparatively fast reaction times in theory. However, the system comes with potential shortcomings: Cooled surfaces increase the risk of condensation and mold growth significantly while higher surface temperatures decrease cooling power of the system. Also, the system’s reaction times have to be tested in realistic conditions. For a first prove of the system’s applicability a study with combined measurements and hygrothermal building simulations was performed. In a test chamber measurements of a system were conducted under controlled conditions. A simulation model in the hygrothermal whole building software WUFI® Plus was developed and validated with the measurements. The research shows that the simulation model is able to represent the effects on indoor climate as well as condensation reliably.

The preparation of a novel class of e-caprolactone (CL) monomers, modified at the β-position of the ester function, is described. The efficient thia-Michael addition to cyclohex-2-en-1-one and subsequent Baeyer–Villiger oxidation provided the regioselectively modified CL monomers. To enable a sustainable Baeyer–Villiger oxidation, several reaction procedures were investigated. In order to test a controlled ring-opening polymerization of the prepared monomers, the kinetics were studied and the monomer to initiator ratios were varied in order to prepare poly(e-caprolactone)s with different molecular weights and different side groups.

Here, we describe the use of biochemically derived fatty acid derivatives (ω- and ω-1 hydroxy fatty acid methyl esters) as starting materials for renewable polyesters and polyamides. The required long-chain monomers were obtained by chemical derivatization of biochemically derived fatty acids. Thus, a long chain diester and a ω-amino fatty acid methyl ester were synthesized and used to prepare polyester PE 32–34:32–34 and polyamide PA 16. The polyester was prepared by transesterification using 5 mol% of the catalyst tin(II) 2-ethylhexanoate (Sn(Oct)2), leading to an average molecular weight of Mn = 7.4 kDa and a melting point of 109 °C. PA 16 was prepared by amidation using TBD as catalyst and resulting in an average molecular weight of Mn = 20.3 kDa and a melting point of 166 °C.

An efficient and environmentally benign strategy for the oxyfunctionalization of fatty acid methyl esters (FAMEs) employing molecular oxygen as an oxidizing agent is described. Keto-fatty acid esters were directly synthesized by co-catalyst-free Wacker oxidations employing oxygen as a sole re-oxidant. Amine functionalization of the thus obtained keto-fatty acid esters was achieved by reductive amination. The prepared renewable AB-type monomers were studied in homopolymerizations as well as in copolymerization reactions with hexamethylendimethylamine and dimethyl adipate to modify the properties of conventional Nylon 6,6. The obtained (co)-polymers were characterized by SEC, NMR and DSC analysis as well as water uptake tests.