Molecular spintronics seeks to use single or few molecules as functional building blocks for spintronic applications, directly relying on molecular properties or properties of interfaces between molecules and inorganic electrodes. Spin-crossover molecules (SCMs) are one of the most promising classes of candidates for molecular spintronics due to their bistability deriving from the existence of two spin states that can be reversibly switched by temperature, light, electric fields, etc. Building devices based on single or few molecules would entail connecting the molecule(s) with solid surfaces and understanding the fundamental behavior of the resulting assemblies. Herein, the investigations of SCMs on solid surfaces, ranging from isolated single molecules (submonolayers) to ultrathin films (mainly in the sub-10 nm range) are summarized. The achievements, challenges and prospects in this field are highlighted.View less
Simultaneous visualization and concentration quantification of molecules in biological tissue is an important though challenging goal. The advantages of fluorescence lifetime imaging microscopy (FLIM) for visualization, and electron paramagnetic resonance (EPR) spectroscopy for quantification are complementary. Their combination in a multiplexed approach promises a successful but ambitious strategy because of spin label-mediated fluorescence quenching. Here, we solved this problem and present the molecular design of a dual label (DL) compound comprising a highly fluorescent dye together with an EPR spin probe, which also renders the fluorescence lifetime to be concentration sensitive. The DL can easily be coupled to the biomolecule of choice, enabling in vivo and in vitro applications. This novel approach paves the way for elegant studies ranging from fundamental biological investigations to preclinical drug research, as shown in proof-of-principle penetration experiments in human skin ex vivo.View less
Particle sorting is a fundamental method in various fields of medical and biological research. However, existing sorting applications are not capable for high-throughput sorting of large-size (>100 micrometers) particles. Here, we present a novel on-chip sorting method using traveling vortices generated by on-demand microjet flows, which locally exceed laminar flow condition, allowing for high-throughput sorting (5 kilohertz) with a record-wide sorting area of 520 micrometers. Using an activation system based on fluorescence detection, the method successfully sorted 160-micrometer microbeads and purified fossil pollen (maximum dimension around 170 micrometers) from lake sediments. Radiocarbon dates of sorting-derived fossil pollen concentrates proved accurate, demonstrating the method’s ability to enhance building chronologies for paleoenvironmental records from sedimentary archives. The method is capable to cover urgent needs for high-throughput large-particle sorting in genomics, metabolomics, and regenerative medicine and opens up new opportunities for the use of pollen and other microfossils in geochronology, paleoecology, and paleoclimatology.View less
The whole-genome sequence of the type strain Mycoplasma (Mesomycoplasma) hyorhinis DSM 25591 is reported and compared to the available sequences of the corresponding type strains from other strain collections to ascertain conformity. Knowledge of the identity of type strains is of importance for their application in standardized test systems.
Archaeological radiocarbon dating in coastal northern Hokkaido is challenged by the marine reservoir effect and the scarcity of materials with terrestrial carbon sources. This has contributed to gaps and general uncertainty in the timing of the region's culture-historical periods. The Late Holocene site of Hamanaka 2 on Rebun Island, featuring a stratified shell midden context with excellent preservation of organic remains, provides an ideal setting for addressing this issue. A Bayesian chronological model was deployed to study the timing of the site using a series of radiocarbon-dated macrobotanical samples. This resulted in narrowed-down estimated age-ranges in eight of thirteen phases examined, providing the site with a more accurate radiocarbon chronology than before. These temporal data were consequently integrated with local palaeoecological evidence, revealing synchrony between cultural chronology and human-induced landscape transformations. The study demonstrates that the technique should permit more efficient building of archaeological chronologies in similar maritime environments.View less
Musical Group Interaction (MGI) has been found to promote prosocial tendencies, including empathy, across various populations. However, experimental study is lacking in respect of effects of everyday forms of musical engagement on prosocial tendencies, as well as whether key aspects—such as physical co-presence of MGI participants—are necessary to enhance prosocial tendencies. We developed an experimental procedure in order to study online engagement with collaborative playlists and to investigate socio-cognitive components of prosocial tendencies expected to increase as a consequence of engagement. We aimed to determine whether mere perceived presence of a partner during playlist-making could elicit observable correlates of social processing implicated in both MGI and prosocial behaviors more generally and identify the potential roles of demographic, musical, and inter-individual differences. Preliminary results suggest that for younger individuals, some of the social processes involved in joint music-making and implicated in empathic processes are likely to be elicited even by an assumption of virtual co-presence. In addition, individual differences in styles of listening behavior may mediate the effects of mere perceived partner presence on recognition memory.View less
When predicting complex systems one typically relies on differential equation which can often be incomplete, missing unknown influences or higher order effects. By augmenting the equations with artificial neural networks we can compensate these deficiencies. We show that this can be used to predict paradigmatic, high-dimensional chaotic partial differential equations even when only short and incomplete datasets are available. The forecast horizon for these high dimensional systems is about an order of magnitude larger than the length of the training data.View less
Otto Warburg (1859–1938) had a great interest in tropical botany. He travelled in South-East Asia and the South Pacific between 1885 and 1889 and brought back a considerable collection of plant specimens from this expedition later donated to the Royal Botanical Museum in Berlin. Warburg published the first comprehensive monograph on the family Pandanaceae in 1900 in the third issue of Das Pflanzenreich established and edited by Adolf Engler (1844–1930). The aim of this article is to clarify the taxonomy, nomenclature and typification of Warburg's contributions to the Pandanaceae. Considerable parts of Warburg's original material was destroyed in Berlin during World War II but duplicates survived, shared by Engler and Warburg with Ugolino Martelli (1860–1934). Martelli was an expert on the family and he assembled a precious herbarium of Pandanaceae that was later donated to the Museo di Storia Naturale dell'Università degli Studi di Firenze. Warburg published 86 new names in Pandanaceae between 1898 and 1909 (five new sections, 69 new species, five new varieties, two new combinations and five replacement names). A complete review of the material extant in B and FI led to the conclusion that 38 names needed a nomenclatural act: 34 lectotypes, three neotypes and one epitype are designated here. Twenty new synonyms are also proposed. One Freycinetia name and six Pandanus names are considered as incertae sedis. A total of 21 names published by Warburg are accepted: 11 in Freycinetia and ten in Pandanus. In addition, four names published in Pandanus by Warburg serve as the basionyms of accepted names in the genus Benstonea.View less
The interplay between diet, intestinal microbiota and host is a major factor impacting health. A diet rich in unsaturated fatty acids has been reported to stimulate the growth of Bilophila wadsworthia by increasing the proportion of the sulfonated bile acid taurocholate (TC). The taurine-induced overgrowth of B. wadsworthia promoted the development of colitis in interleukin-10-deficient (IL-10-/-) mice. This study aimed to investigate whether intake of the sulfonates sulfoquinovosyl diacylglycerols (SQDG) with a dietary supplement or their degradation product sulfoquinovose (SQ), stimulate the growth of B. wadsworthia in a similar manner and, thereby, cause intestinal inflammation. Conventional IL-10-/- mice were fed a diet supplemented with the SQDG-rich cyanobacterium Arthrospira platensis (Spirulina). SQ or TC were orally applied to conventional IL-10-/- mice and gnotobiotic IL-10-/- mice harboring a simplified human intestinal microbiota with or without B. wadsworthia. Analyses of inflammatory parameters revealed that none of the sulfonates induced severe colitis, but both, Spirulina and TC, induced expression of pro-inflammatory cytokines in cecal mucosa. Cell numbers of B. wadsworthia decreased almost two orders of magnitude by Spirulina feeding but slightly increased in gnotobiotic SQ and conventional TC mice. Changes in microbiota composition were observed in feces as a result of Spirulina or TC feeding in conventional mice. In conclusion, the dietary sulfonates SQDG and their metabolite SQ did not elicit bacteria-induced intestinal inflammation in IL-10-/- mice and, thus, do not promote colitis.View less
The phrases, “essential businesses” and “essential jobs,” emerged at the beginning of the COVID-19 pandemic, raising questions about and reflecting concerns over which goods, services, and workers were necessary to prevent societal collapse. In an attempt to continue to probe “essentiality,” this article coins the term “essential crimes” to refer to those socially injurious acts and omissions that are part and parcel of a global neoliberal capitalist order, and that are, therefore, vital to keep the socioeconomic system running. In other words, if keeping humans alive in the midst of the COVID-19 pandemic required supermarkets and hospitals to remain open (“essential business and jobs”), maintaining the existing socioeconomic system and ensuring that the powerful remained powerful required harmful acts and omissions by states and corporations—what we refer to as “essential crimes.” This article sheds light on how the COVID-19 pandemic has helped illuminate just how essential these crimes and harms are to the perpetuation of the status quo by the powerful. In addition, this article encourages us to consider which punishments, if any, are vital to a well-ordered society, and it demands that we rethink whether prison is an “essential punishment” for ensuring public safety.View less
How do we choose when confronted with many alternatives? There is surprisingly little decision modelling work with large choice sets, despite their prevalence in everyday life. Even further, there is an apparent disconnect between research in small choice sets, supporting a process of gaze-driven evidence accumulation, and research in larger choice sets, arguing for models of optimal choice, satisficing, and hybrids of the two. Here, we bridge this divide by developing and comparing different versions of these models in a many-alternative value-based choice experiment with 9, 16, 25, or 36 alternatives. We find that human choices are best explained by models incorporating an active effect of gaze on subjective value. A gaze-driven, probabilistic version of satisficing generally provides slightly better fits to choices and response times, while the gaze-driven evidence accumulation and comparison model provides the best overall account of the data when also considering the empirical relation between gaze allocation and choice.View less
Focused beams of helium ions are a powerful tool for high-fidelity machining with spatial precision below 5 nm. Achieving such a high patterning precision over large areas and for different materials in a reproducible manner, however, is not trivial. Here, we introduce the Python toolbox FIB-o-mat for automated pattern creation and optimization, providing full flexibility to accomplish demanding patterning tasks. FIB-o-mat offers high-level pattern creation, enabling high-fidelity large-area patterning and systematic variations in geometry and raster settings. It also offers low-level beam path creation, providing full control over the beam movement and including sophisticated optimization tools. Three applications showcasing the potential of He ion beam nanofabrication for two-dimensional material systems and devices using FIB-o-mat are presented.View less
Drug penetration in human skin ex vivo following a modification of skin barrier permeability is systematically investigated by scanning transmission X-ray microscopy. Element-selective excitation is used in the O 1s regime for probing quantitatively the penetration of topically applied rapamycin in different formulations with a spatial resolution reaching <75 nm. The data were analyzed by a comparison of two methods: (i) two-photon energies employing the Beer–Lambert law and (ii) a singular value decomposition approach making use of the full spectral information in each pixel of the X-ray micrographs. The latter approach yields local drug concentrations more reliably and sensitively probed than the former. The present results from both approaches indicate that rapamycin is not observed within the stratum corneum of nontreated skin ex vivo, providing evidence for the observation that this high-molecular-weight drug inefficiently penetrates intact skin. However, rapamycin is observed to penetrate more efficiently the stratum corneum when modifications of the skin barrier are induced by the topical pretreatment with the serine protease trypsin for variable time periods ranging from 2 to 16 h. After the longest exposure time to serine protease, the drug is even found in the viable epidermis. High-resolution micrographs indicate that the lipophilic drug preferably associates with corneocytes, while signals found in the intercellular lipid compartment were less pronounced. This result is discussed in comparison to previous work obtained from low-molecular-weight lipophilic drugs as well as polymer nanocarriers, which were found to penetrate the intact stratum corneum exclusively via the lipid layers between the corneocytes. Also, the role of the tight junction barrier in the stratum granulosum is briefly discussed with respect to modifications of the skin barrier induced by enhanced serine protease activity, a phenomenon of clinical relevance in a range of inflammatory skin disorders.View less
We present the synthesis and characterization of the first non-classical Cl(I) polyinterhalide [NMe4][F(ClF)3] as well as the homologous polychloride [NPr3Me][Cl7]. Both salts were obtained from the reaction of the corresponding ammonium chlorides with ClF or Cl2, respectively. Quantum-chemical investigations predict an unexpected planar structure for the [F(ClF)3]− anion.
The intensity and frequency of storms are projected to increase in many regions of the world because of climate change. Storms can alter environmental conditions in many ecosystems. In lakes and reservoirs, storms can reduce epilimnetic temperatures from wind-induced mixing with colder hypolimnetic waters, direct precipitation to the lake's surface, and watershed runoff. We analyzed 18 long-term and high-frequency lake datasets from 11 countries to assess the magnitude of wind- vs. rainstorm-induced changes in epilimnetic temperature. We found small day-to-day epilimnetic temperature decreases in response to strong wind and heavy rain during stratified conditions. Day-to-day epilimnetic temperature decreased, on average, by 0.28°C during the strongest windstorms (storm mean daily wind speed among lakes: 6.7 ± 2.7 m s−1, 1 SD) and by 0.15°C after the heaviest rainstorms (storm mean daily rainfall: 21.3 ± 9.0 mm). The largest decreases in epilimnetic temperature were observed ≥2 d after sustained strong wind or heavy rain (top 5th percentile of wind and rain events for each lake) in shallow and medium-depth lakes. The smallest decreases occurred in deep lakes. Epilimnetic temperature change from windstorms, but not rainstorms, was negatively correlated with maximum lake depth. However, even the largest storm-induced mean epilimnetic temperature decreases were typically <2°C. Day-to-day temperature change, in the absence of storms, often exceeded storm-induced temperature changes. Because storm-induced temperature changes to lake surface waters were minimal, changes in other limnological variables (e.g., nutrient concentrations or light) from storms may have larger impacts on biological communities than temperature changes.View less
The glycocalyx, a thick layer of carbohydrates, surrounds the cell wall of most bacterial and parasitic pathogens. Recognition of these unique glycans by the human immune system results in destruction of the invaders. To elicit a protective immune response, polysaccharides either isolated from the bacterial cell surface or conjugated with a carrier protein, for T-cell help, are administered. Conjugate vaccines based on isolated carbohydrates currently protect millions of people against Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitides infections. Active pharmaceutical ingredients (APIs) are increasingly discovered by medicinal chemistry and synthetic in origin, rather than isolated from natural sources. Converting vaccines from biologicals to pharmaceuticals requires a fundamental understanding of how the human immune system recognizes carbohydrates and could now be realized. To illustrate the chemistry-based approach to vaccine discovery, I summarize efforts focusing on synthetic glycan-based medicinal chemistry to understand the mammalian antiglycan immune response and define glycan epitopes for novel synthetic glycoconjugate vaccines against Streptococcus pneumoniae, Clostridium difficile, Klebsiella pneumoniae, and other bacteria. The chemical tools described here help us gain fundamental insights into how the human system recognizes carbohydrates and drive the discovery of carbohydrate vaccines.View less
Integrating information on species-specific sensory perception with spatial activity provides a high-resolution understanding of how animals explore environments, yet frequently used exploration assays commonly ignore sensory acquisition as a measure for exploration. Echolocation is an active sensing system used by hundreds of mammal species, primarily bats. As echolocation call activity can be reliably quantified, bats present an excellent model system to investigate intraspecific variation in environmental cue sampling. Here, we developed an in situ roost-like novel environment assay for tree-roosting bats. We repeatedly tested 52 individuals of the migratory bat species, Pipistrellus nathusii, across 24 h, to examine the role of echolocation when crawling through a maze-type arena and test for consistent intraspecific variation in sensory-based exploration. We reveal a strong correlation between echolocation call activity and spatial activity. Moreover, we show that during the exploration of the maze, individuals consistently differed in spatial activity as well as echolocation call activity, given their spatial activity, a behavioral response we term ’acoustic exploration’. Acoustic exploration was correlated with other exploratory behaviors, but not with emergence latency. We here present a relevant new measure for exploration behavior and provide evidence for consistent (short-term) intra-specific variation in the level at which wild bats collect information from a novel environment.View less
Hintergrund Die Steuerungsinstrumente der Arzneimittelversorgung in der gesetzlichen Krankenversicherung (GKV) sind schon länger Bestandteil der gesundheitspolitischen Reformdebatte. Über die Jahre hat sich eine Gemengelage sehr verschiedener Werkzeuge herausgebildet, die zumeist auf eine Kontrolle der Arzneimittelausgaben zielen. Die Instrumente der regionalen Verordnungssteuerung fokussieren vor allem auf eine Verhaltenssteuerung des verordnenden Arztes. Zu erwähnen ist nicht zuletzt der verstärkte Einsatz von indikationsbezogenen Quoten, vorrangig Leitsubstanzen und/oder Generika/Biosimilars. Diese gibt es mittlerweile auch im Bereich des Humanen Immundefizienz-Virus (HIV), etwa die seit 2020 in Bayern und Berlin eingeführten Generikaquoten für HIV-Therapeutika.
Zielstellung Ziel des vorliegenden Beitrages ist es, auf Grundlage von GKV-Apothekenabrechnungsdaten das Potenzial sowie Grenzen von Generikaquotenlösungen in der HIV-Versorgung zu analysieren und Handlungsempfehlungen zu skizzieren.
Ergebnisse Es zeigte sich, dass das Quotenpotenzial für Generika im patentfreien Bereich in der HIV-Versorgung bereits weitgehend ausgeschöpft wird. Dieser Umstand ist vor allem darauf zurückzuführen, dass die HIV-Verordner den Austausch durch Verzicht auf Aut-idem-Kreuze auf dem Kassenrezept unterstützen.
Diskussion Das steuerungspolitische Optimum ist fast erreicht. Dies ist auf das geeignete Instrumentarium zurückzuführen, das aus dem Rahmenvertrag zur Arzneimittelversorgung und einer leitliniengerechten Wirkstoffverordnung durch den Arzt besteht – in Verbindung mit dem AMNOG(Arzneimittelmarktneuordnungsgesetz)-Verfahren und Festbeträgen. Leitlinienkonformität und (existierende) Eintablettenregime müssen beibehalten werden, damit die gute Versorgungsqualität gewährleistet bleibt.View less
The highly anionic synthetic pentasaccharide fondaparinux (FDPX) – representing the antithrombin binding sequence of heparin – is in clinical use as a potent anticoagulant. Contrary to the unfractionated heparin, FDPX lacks potent antidote completely reversing its anticoagulant activity, therefore it is of great importance to identify new structures exhibiting strong intermolecular interactions towards FDPX. The polycationic heptakis(6-amino-6-deoxy)-beta-cyclodextrin (NH2-β-CD) can serve as an excellent model compound to mimic these interactions between the oppositely charged oligosaccharides. Herein, extensive NMR spectroscopic and nano-electrospray ionization mass spectrometric (nESI-MS) studies were conducted to understand the molecular-level interactions in the FDPX - NH2-β-CD systems. NMR experiments were performed at pD 7.4 and 2.0. Job’s method of continuous variation and 1H NMR titration experiments suggested the formation of FDPX∙NH2-β-CD complex at pD 7.4, while the presence of multiple complexes was assumed at pD 2.0. Stability constants were determined by separate 1H NMR titrations, yielding log β11=3.65 ± 0.02 at pD 7.4, while log β11 ≥ 4.9 value suggested a high-affinity system at pD 2.0. 2D NOESY NMR studies indicated spatial proximities between the anomeric resonance α-l-iduronic acid residue and the cyclodextrin’s methylene unit in the proximity of the cationic amino function. Acidic degradation of FDPX was investigated by NMR and MS for the first time in detail confirming that desulfation occurs involving one to two sulfate moieties. The desulfation of FDPX was inhibited by the cationic cyclodextrin in the case of equimolar ratio at pD 2.0. This is the first report on the stabilizing effect of cyclodextrin complexation on heparin degradation.View less
When experiencing negative emotions, individuals often reach out for social support to help regulate their emotions. In times of an acute crisis, however, close friends might not be available, and physical closeness might be impossible. This functional magnetic resonance imaging (fMRI) study investigated the effect of social proximity on the effectiveness of social support for regulating emotions and the underlying neural mechanisms. Participants regulated their emotions in response to negative images either alone (intrapersonal regulation), or with help of a picture and supporting sentence provided by the best friend, or by a stranger (interpersonal regulation). Regulation success was enhanced for the support of friends compared to regulating alone or with the support of strangers. This effect was accompanied by the interplay of large-scale brain networks involved in processing emotions, social cognition, and cognitive control. Interpersonal regulation appeared to be implemented by lateral prefrontal regions. The amygdala showed increased activation for strangers. The activation profile of the social cognition network suggests a role in supporting empathic and mentalizing processes. The results highlight the power of social connectedness for boosting emotion regulation ability and the different neural networks that contribute to this effect.View less