Electrically Switchable Photonic Molecule Laser

We have studied the coherent intercavity coupling of the evanescent fields of the whispering gallery modes of two terahertz quantum-cascade lasers implemented as microdisk cavities. The electrically pumped single-mode operating microcavities allow to electrically control the coherent mode coupling for proximity distances of the cavities up to 30-40 \mu\m. The optical emission of the strongest coupled photonic molecule can be perfectly switched by the electrical modulation of only one of the coupled microdisks. The threshold characteristics of the strongest coupled photonic molecule demonstrates the linear dependence of the gain of a quantum-cascade laser on the applied electric field.Comment: 4 pages, 4 figure

Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism

Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor

Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism

Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor. [Image: see text

Protectiveness of NAM-based hazard assessment: which testing scope is required?

Hazard assessment (HA) requires toxicity tests to allow deriving protective points of departure (PoDs) for risk assessment irrespective of a compound's mode of action (MoA). The scope of in vitro test batteries (ivTB) thereby necessitated for systemic toxicity is still unclear. We explored the protectiveness regarding systemic toxicity of an ivTB with a scope, which was guided by previous findings from rodent studies, where examining six main targets, including liver and kidney, was sufficient to predict the guideline scope-based PoD with high probability. The ivTB comprises human in vitro models representing liver, kidney, lung and the neuronal system covering transcriptome, mitochondrial dysfunction and neuronal outgrowth. Additionally, 32 CALUX®- and 10 HepG2 BAC-GFP reporters cover a broad range of disturbance mechanisms. Eight compounds were chosen for causing adverse effects such as immunotoxicity or anemia in vivo, i.e., effects not directly covered by assays in the ivTB. PoDs derived from the ivTB and from oral repeated dose studies in rodents were extrapolated to maximum unbound plasma concentrations for comparison. The ivTB-based PoDs were one to five orders of magnitude lower than in vivo PoDs for six of eight compounds, implying that they were protective. The extent of in vitro response varied across test compounds. Especially for hematotoxic substances, the ivTB showed either no response or only cytotoxicity. Assays better capturing this type of hazard would be needed to complement the ivTB. This study highlights the potentially broad applicability of ivTBs for deriving protective PoDs of compounds with unknown MoA.Toxicolog

Accessible Web Maps for Visually Impaired Users: Recommendations and Example Solutions

Due to advances in information and communication technology, web maps are an increasingly important means of communication. While paper maps provide solutions that are accessible to the visually impaired, the use of web maps is still difficult for these users. This is true even though technology opens up new possibilities for developing accessible web maps. But, what must be considered when creating web maps suitable for the visually impaired? This paper presents recommendations, including example solutions based on the results obtained in two projects: AccessibleMap and senTour. In both projects mixed methods were used: literature and internet review, questionnaires, and analysis of similar systems. All work was done in close cooperation with organizations that represent the interests of the target group. The findings underline that web maps accessible to visually impaired users must support different interaction modes and assistive technology. A carefully designed user interface, an easy-to-read map picture, and the provision of a verbal description of the map content are important. Further, additional aspects should be considered to enable these users to fully benefit from web maps. This refers to the need to widen the concept of accessibility, encompassing among others usability, the importance of building up these users’ digital and spatial competencies, and to leverage the advantages that result from the application of the participatory design approach.

Accessible Web Maps for Visually Impaired Users: Recommendations and Example Solutions

Due to advances in information and communication technology, web maps are an increasingly important means of communication. While paper maps provide solutions that are accessible to the visually impaired, the use of web maps is still difficult for these users. This is true even though technology opens up new possibilities for developing accessible web maps. But, what must be considered when creating web maps suitable for the visually impaired? This paper presents recommendations, including example solutions based on the results obtained in two projects: AccessibleMap and senTour. In both projects mixed methods were used: literature and internet review, questionnaires, and analysis of similar systems. All work was done in close cooperation with organizations that represent the interests of the target group. The findings underline that web maps accessible to visually impaired users must support different interaction modes and assistive technology. A carefully designed user interface, an easy-to-read map picture, and the provision of a verbal description of the map content are important. Further, additional aspects should be considered to enable these users to fully benefit from web maps. This refers to the need to widen the concept of accessibility, encompassing among others usability, the importance of building up these users’ digital and spatial competencies, and to leverage the advantages that result from the application of the participatory design approach.

Accessible Web Map Prototyp

<p>This short video clip presents the accessible web map prototype and main developed features. By this video  an impression of the accessible web map pilot and its functionalities is given.</p