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Dynamical Systems on Generalised Klein Bottles
Get PDFWe propose a high-dimensional generalisation of the standard Klein bottle extending beyond those considered previously. We address the problem of generating continuous scalar fields (distributions) and dynamical systems (flows) on such state spaces, which can provide a rich source of examples for future investigations. We consider a class of high-dimensional dynamical systems that model distributed information processing within the human cortex, which may be capable of exhibiting some Klein bottle symmetries. We deploy topological data analytic methods in order to analyse their resulting dynamical behaviour and suggesting future challenges
The Peregrine Ion Trap Mass Spectrometer (PITMS): Results from a CLPS-delivered Mass Spectrometer
Get PDFThe Peregrine Ion Trap Mass Spectrometer (PITMS) was a mass spectrometer designed to measure lunar gases. PITMS flew on the first flight of Astrobotic’s Peregrine lander via the Commercial Lunar Payload Services (CLPS) program in 2024 January. After launch, the lander suffered a propulsion system anomaly that prevented the mission from reaching the Moon, but PITMS collected 80 high-quality spectra while in cislunar space. PITMS observed abundant outgassing products from the Peregrine lander, including water, MON-25 oxidizer from the propulsion system leak, and traces of combustion products. PITMS data help constrain the nature of the propulsion system failure: oxidizer molecular ratios show that the leak released molecules rapidly enough for them to fully dissociate, and the high observed abundances imply that the oxidizer traveled within the lander surfaces rather than jetting into space. The amount of water offgassed by the spacecraft is substantially more than other planetary spacecraft, so the PITMS results suggest that instruments flying in the CLPS paradigm need to consider lander cleanliness. Though not successful in measuring the native lunar exosphere, the PITMS results showcase the capabilities of a mass spectrometer on board a lunar lander, along with lessons in pragmatism and flexibility that would enable such an instrument to ultimately be successful in the CLPS initiative
Phänomik‐basierte Entdeckung neuer orthosterischer Cholinkinase Inhibitoren
Get PDFCholinkinase alpha (CHKA) ist ein zentraler Signalgeber innerhalb des Zellstoffwechsels, der mit Krebs und der Immunregulation in Verbindung gebracht wird. Die zelluläre und klinische Bewertung von CHKA als Zielstruktur für Wirkstoffe wurde bisher durch Herausforderungen bei der Entwicklung von arzneimittelähnlichen Cholinkinasehemmstoffen behindert. In der vorliegenden Studie zeigen wir mihilfe eines integrierten phänomischen Ansatzes, dass CHKA ein unerwartetes Off‐Target von Histonmethyltransferasehemmstoffen ist. Wir identifizieren CHKA als direkte Proteinzielstruktur der Aminochinazoline UNC0638 und UNC0737 durch eine Kombination von chemoproteomischen, biochemischen, zellulären und metabolischen Analysen. Diese Entdeckung erklärt möglicherweise die zuvor berichteten Diskrepanzen, die für unterschiedliche G9a/GLP‐Hemmstoffgerüste in zellulären Versuchen beobachtet wurden. Unter Verwendung von primären menschlichen Zellmodellsystemen weisen wir nach, dass die pharmakologische Beeinflussung von CHKA die IgG‐Freisetzung und die B‐Zell‐Reifung beeinträchtigt, im Einklang mit der These, dass der Cholin‐Stoffwechsel eine wichtige Rolle bei der Signalgebung des Immunsystems spielt. Die Kristallstrukturen von UNC0638 und UNC0737 im Komplex mit CHKA offenbaren einen unerwarteten Bindungsmodus und deuten darauf hin, dass diese Hemmstoffe als attraktive Ausgangspunkte für die Entwicklung selektiver chemischer Sonden zur weiteren Erforschung der biologischen Rolle von CHKA im Krebs‐ und Immunstoffwechsel genutzt werden können
Uncovering hidden protein modifications with native top-down mass spectrometry
No full textProtein modifications drive dynamic cellular processes by modulating biomolecular
interactions, yet capturing these modifications within their native structural context remains a
significant challenge. Native top-down mass spectrometry (nTDMS) promises to preserve the
critical link between modifications and interactions. However, current methods often fail to
detect uncharacterized or low-abundance modifications, limiting insights into proteoform
diversity. To address this gap, we introduce precisION, an interactive end-to-end software
package that leverages a robust, data-driven fragment-level open search to detect, localize,
and quantify “hidden” modifications within intact protein complexes. Applying precisION to
four therapeutically relevant targets—PDE6, ACE2, osteopontin (SPP1), and a GABA
transporter (GAT1)—here we discover undocumented phosphorylation, glycosylation, and
lipidation, and resolve previously uninterpretable density in an electron cryo-microscopy map
of GAT1. As an open-source software package, precisION offers an intuitive means for
interpreting complex protein fragmentation data. This tool will empower the community to
unlock the potential of nTDMS, advancing integrative structural biology, molecular pathology,
and drug development
Characteristics of suicide prevention apps: a content analysis of apps available in Canada and the UK
Get PDFObjectives: We aimed to examine the characteristics, features and content of suicide prevention mobile apps available in app stores in Canada and the UK. Design: Suicide prevention apps were identified from Apple and Android app stores between March and April 2023. Apps were screened against predefined inclusion criteria, and duplicate apps were removed. Data were then extracted based on descriptive (eg, genre, app developer), security (eg, password protection) and design features (eg, personalisation options). Content of apps was assessed using the Essential Features Framework. Extracted data were analysed using a content analysis approach including narrative frequencies and descriptive statistics. Data sources: Apple and Android app stores between March and April 2023. Eligibility criteria: Identified apps were eligible for inclusion if they were: (a) free, (b) developed in the English language, (c) could be downloaded on an Apple or Android device in England or Canada, (d) the focus of the app was suicide prevention and (e) the target users of the app were individuals experiencing suicide-related thoughts and/or behaviours. Data extraction and synthesis: Apps were assessed on basic descriptive data (eg, name, genre, developer of the app), alongside security (eg, whether password protection was available) and design features (eg, whether the app could be personalised). App content was examined using the Essential Features Framework. Results: 52 suicide prevention apps were included within the review. Most were tailored for the general population and were in English language only. One app had the option to increase app accessibility by offering content presented using sign language. Many apps allowed some form of personalisation by adding text content, however most did not facilitate further customisation such as the ability to upload photo and audio content. All identified apps included content from at least one of the domains of the Essential Features Framework. The most commonly included domains were sources of suicide prevention support, and information about suicide. The domain least frequently included was screening tools followed by wellness content. No identified apps had the ability to be linked to patient medical records. Conclusions: The findings of this research present implications for the development of future suicide prevention apps. Development of a co-produced suicide prevention app which is accessible, allows for personalisation and can be integrated into clinical care may present an opportunity to enhance suicide prevention support for individuals experiencing suicidal thoughts and behaviours
Reasoning to Justify Eating Animals Varies With Age
Get PDFThe present study examined the justifications used by children, adolescents, and adults to justify eating animals. Children (n = 100, Mage = 9.82, SD = 0.77, female n = 49) as compared to adolescents (n = 76, Mage = 14.0, SD = 1.62, female n = 36) and adults (n = 113, Mage = 44.1, SD = 14.4, female n = 54) were more ambivalent or opposed to eating animals, and they showed a distinct reasoning pattern. Children relied less on arguments about meat eating being natural or with to humane slaughter practices. These findings align with recent theoretical perspectives that reasoning may be used to counter cognitive dissonance arising from knowledge of food production systems
High-temperature surface state in Kondo insulator U<sub>3</sub>Bi<sub>4</sub>Ni<sub>3</sub>
Get PDFThe resurgence of interest in Kondo insulators has been driven by two major mysteries: the presence of metallic surface states and the observation of quantum oscillations. To further explore these mysteries, it is crucial to investigate another similar system beyond the two existing ones, SmB6 and YbB12. Here, we address this by reporting on a Kondo insulator, U3Bi4Ni3. Our transport measurements reveal that a surface state emerges below 250 kelvin and dominates transport properties below 150 kelvin, which is well above the temperature scale of SmB6 and YbB12. At low temperatures, the surface conductivity is about one order of magnitude higher than the bulk. The robustness of the surface state indicates that it is inherently protected. The similarities and differences between U3Bi4Ni3 and the other two Kondo insulators will provide valuable insights into the nature of metallic surface states in Kondo insulators and their interplay with strong electron correlations