Stereoselective Total Synthesis of (−)‐Thallusin for Bioactivity Profiling

Chemical mediators are key compounds for controlling symbiotic interactions in the environment. Here, we disclose a fully stereoselective total synthesis of the algae differentiation factor (−)‐thallusin that utilizes sophisticated 6‐ endo ‐cyclization chemistry and effective late‐stage sp 2 –sp 2 ‐couplings using non‐toxic reagents. An EC 50 of 4.8 pM was determined by quantitative phenotype profiling in the green seaweed Ulva mutabilis (Chlorophyte), underscoring this potent mediator‘s enormous, pan‐species bioactivity produced by symbiotic bacteria. SAR investigations indicate that (−)‐thallusin triggers at least two different pathways in Ulva that may be separated by chemical editing of the mediator compound structure

Macroalgal–bacterial interactions: identification and role of thallusin in morphogenesis of the seaweed Ulva (Chlorophyta)

Macroalgal microbiomes have core functions related to biofilm formation, growth, and morphogenesis of seaweeds. In particular, the growth and development of the sea lettuce Ulva spp. (Chlorophyta) depend on bacteria releasing morphogenetic compounds. Under axenic conditions, the macroalga Ulva mutabilis develops a callus-like phenotype with cell wall protrusions. However, co-culturing with Roseovarius sp. (MS2) and Maribacter sp. (MS6), which produce various stimulatory chemical mediators, completely recovers morphogenesis. This ecological reconstruction forms a tripartite community which can be further studied for its role in cross-kingdom interactions. Hence, our study sought to identify algal growth- and morphogenesis-promoting factors (AGMPFs) capable of phenocopying the activity of Maribacter spp. We performed bioassay-guided solid-phase extraction in water samples collected from U. mutabilis aquaculture systems. We uncovered novel ecophysiological functions of thallusin, a sesquiterpenoid morphogen, identified for the first time in algal aquaculture. Thallusin, released by Maribacter sp., induced rhizoid and cell wall formation at a concentration of 11 pmol l-1. We demonstrated that gametes acquired the iron complex of thallusin, thereby linking morphogenetic processes with intracellular iron homeostasis. Understanding macroalgae-bacteria interactions permits further elucidation of the evolution of multicellularity and cellular differentiation, and development of new applications in microbiome-mediated aquaculture systems.FCT: UID/Multi/04326/2019; UIDB/04326/2020; CCMAR/ID/16/2018; CEECINST/00114/2018. German Research Foundation (DFG) CRC1127; European Union (EU) 642575; ASSEMBLE 227799; COST Action 'Phycomorph' FA1406.info:eu-repo/semantics/publishedVersio

Stereoselektive Totalsynthese von (−)‐Thallusin zur Bioaktivitätsprofilierung

Chemische Mediatoren sind Schlüsselverbindungen zur Kontrolle von Symbiosen in unserer Umwelt. Hier berichten wir über eine völlig stereoselektive Totalsynthese des Algendifferenzierungsfaktors (−)‐Thallusin, die sich durchdachter 6‐ endo ‐Zyklisierungschemie und effektiver sp 2 –sp 2 ‐Kupplungen mittels Zinn‐freier Reagenzien auf späten Stufen bedient. Durch quantitative phänotypische Profilierung wurde für die weit verbreitete Grünalge Ulva mutabilis (Chlorophyta) ein EC 50 ‐Wert von 4.8 pM ermittelt, was die enorme artenübergreifende Bioaktivität dieses von symbiotischen Bakterien produzierten Mediators aufzeigt. SAR‐Untersuchungen weisen darauf hin, dass (−)‐Thallusin mindestens zwei unterschiedliche Signalwege in Ulva auslöst, die durch chemische Editierung der Mediatorstruktur separiert werden können

Incidence of Revision Surgery After Decompression With vs Without Fusion Among Patients With Degenerative Lumbar Spinal Stenosis.

Importance Only limited data derived from large prospective cohort studies exist on the incidence of revision surgery among patients who undergo operations for degenerative lumbar spinal stenosis (DLSS). Objective To assess the cumulative incidence of revision surgery after 2 types of index operations-decompression alone or decompression with fusion-among patients with DLSS. Design, Setting, and Participants This cohort study analyzed data from a multicenter, prospective cohort study, the Lumbar Stenosis Outcome Study, which included patients aged 50 years or older with DLSS at 8 spine surgery and rheumatology units in Switzerland between December 2010 and December 2015. The follow-up period was 3 years. Data for this study were analyzed between October and November 2021. Exposures All patients underwent either decompression surgery alone or decompression with fusion surgery for DLSS. Main Outcomes and Measures The primary outcome was the cumulative incidence of revision operations. Secondary outcomes included changes in the following patient-reported outcome measures: Spinal Stenosis Measure (SSM) symptom severity (higher scores indicate more pain) and physical function (higher scores indicate more disability) subscale scores and the EuroQol Health-Related Quality of Life 5-Dimension 3-Level questionnaire (EQ-5D-3L) summary index score (lower scores indicate worse quality of life). Results A total of 328 patients (165 [50.3%] men; median age, 73.0 years [IQR, 66.0-78.0 years]) were included in the analysis. Of these, 256 (78.0%) underwent decompression alone and 72 (22.0%) underwent decompression with fusion. The cumulative incidence of revisions after 3 years of follow-up was 11.3% (95% CI, 7.4%-15.1%) for the decompression alone group and 13.9% (95% CI, 5.5%-21.5%) for the fusion group (log-rank P = .60). There was no significant difference in the need for revision between the 2 groups over time (unadjusted absolute risk difference, 2.6% [95% CI, -6.3% to 11.4%]; adjusted absolute risk difference, 3.9% [95% CI, -5.2% to 17.0%]; adjusted hazard ratio, 1.40 [95% CI, 0.63-3.13]). The number of revisions was significantly associated with higher SSM symptom severity scores (β, 0.171; 95% CI, 0.047-0.295; P = .007) and lower EQ-5D-3L summary index scores (β, -0.061; 95% CI, -0.105 to -0.017; P = .007) but not with higher SSM physical function scores (β, 0.068; 95% CI, -0.036 to 0.172; P = .20). The type of index operation was not significantly associated with the corresponding outcomes. Conclusions and Relevance This cohort study showed no significant association between the type of index operation for DLSS-decompression alone or fusion-and the need for revision surgery or the outcomes of pain, disability, and quality of life among patients after 3 years. Number of revision operations was associated with more pain and worse quality of life

In search of the authentic nation: landscape and national identity in Canada and Switzerland

While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration

Evaluation of vardenafil for the treatment of subjective tinnitus: a controlled pilot study

<p>Abstract</p> <p>Background</p> <p>Vardenafil (Levitra^®) represents a potent and highly selective phosphodiesterase type 5 (PDE5) inhibitor, which is established for treatment of various diseases. There are several unpublished reports from patients stating that vardenafil has a considerable therapeutic effect on their concomitant tinnitus. This pilot study was conducted to specifically assess the effect of vardenafil in patients with chronic tinnitus.</p> <p>Methods</p> <p>This trial was based on a prospective, randomized, double-blind, placebo-controlled, parallel group design. Fourty-two consecutive subjects with mon- or binaural chronic tinnitus received 10 mg vardenafil (N = 21) or matching placebo tablets (N = 21) administered orally twice a day over a period of 12 weeks. Clinical examination and data acquisition took place at each visit: at baseline, after 4 weeks, after 12 weeks (end of treatment with study medication), and at non-medicated follow-up after 16 weeks. Assessment of clinical effectiveness was based on a standardized tinnitus questionnaire (TQ), the Short Form 36 health survey (SF-36), audiometric measurements (mode, pitch and loudness of tinnitus; auditory thresholds) and biomarkers of oxidative stress in patients' blood (malondialdehyde, protein carbonyl, homocysteine and total antioxidative status). Therapeutic efficacy was evaluated by comparison of subjective and objective parameters with baseline data between both treatment groups (ANCOVA).</p> <p>Results</p> <p>Vardenafil had no superior efficacy over placebo in the treatment of chronic tinnitus during this study. The primary efficacy criterion 'TQ total score' failed to demonstrate significant improvement compared to placebo. Subjective reports of TQ subscales and general quality of life areas (SF-36), objective audiometric examinations as well as investigated biomarkers for oxidative stress did not reveal any significant treatment effects. The safety profile was favorable and consistent with that in other vardenafil studies.</p> <p>Conclusion</p> <p>Although hypoxia and ischemia play a special role in the pathogenesis of tinnitus, the PDE5-inhibitor-induced increase of nitric oxide-mediated vasodilatation exerted no specific influence on tinnitus symptomatology. Considering the unclear risk of rarely associated hearing impairment, systemic application of vardenafil or other PDE5 inhibitors prove to be not appropriate for therapy of chronic tinnitus.</p

Electroosmotic flow reversal outside glass nanopores.

We report observations of a striking reversal in the direction of electroosmotic flow (EOF) outside a conical glass nanopore as a function of salt concentration. At high ionic strengths (>100 mM), we observe EOF in the expected direction as predicted by classical electrokinetic theory, while at low salt concentrations (<1 mM) the direction of the flow is reversed. The critical crossover salt concentration depends on the pore diameter. Finite-element simulations indicate a competition between the EOF generated from the inner and outer walls of the pore, which drives flows in opposite directions. We have developed a simple analytical model which reveals that, as the salt concentration is reduced, the flow rates inside the pore are geometrically constrained, whereas there is no such limit for flows outside the pore. This model captures all of the essential physics of the system and explains the observed data, highlighting the key role the external environment plays in determining the overall electroosmotic behavior

Sicherung von Dämmen, Deichen und Stauanlagen : Handbuch für Theorie und Praxis ; Vol. V - 2015

Die Universität Siegen beschäftigt sich seit über 15 Jahren wissenschaftlich und im Bereich der anwendungsorientierten Forschung mit diesem Thema und hat dazu mittlerweile fünf Symposien durchgeführt. Mit der Veröffentlichung soll die langjährige Tradition als etablierte wissenschaftliche Plattform mit einem Wissensaustausch auf europäischer Ebene fortgesetzt werden. Die Bearbeitung dieser Thematik erfolgt auf der Basis der bewährten Kooperation zwischen Geotechnik und Wasserbau an der Universität Siegen. Aktuelle Ereignisse, wie z.B. die aus England oder Australien im Februar des Jahres 2014, machen uns aber auch deutlich, dass ein absoluter Schutz gegen Extremereignisse nicht möglich ist. Sie zeigen aber auch, dass dort wo technischer Hochwasserschutz konsequent umgesetzt wurde Schäden vermieden werden konnten. Wir sind nach den Ereignissen in den vergangenen Jahren aufgefordert wissenschaftlich noch leistungsfähigere und duktilere Systeme zu entwickeln. Weiter ist die Wissenschaft in der Pflicht, die Zivile Sicherheit im Hochwasser-schutz permanent zu bewerten, zu bearbeiten und ganzheitliche-interdisziplinäre und länderübergreifende Lösungen für die Zivilgesellschaft einzufordern

Design of a dual species atom interferometer for space

Atom interferometers have a multitude of proposed applications in space including precise measurements of the Earth's gravitational field, in navigation & ranging, and in fundamental physics such as tests of the weak equivalence principle (WEP) and gravitational wave detection. While atom interferometers are realized routinely in ground-based laboratories, current efforts aim at the development of a space compatible design optimized with respect to dimensions, weight, power consumption, mechanical robustness and radiation hardness. In this paper, we present a design of a high-sensitivity differential dual species $^{85}$Rb/$^{87}$Rb atom interferometer for space, including physics package, laser system, electronics and software. The physics package comprises the atom source consisting of dispensers and a 2D magneto-optical trap (MOT), the science chamber with a 3D-MOT, a magnetic trap based on an atom chip and an optical dipole trap (ODT) used for Bose-Einstein condensate (BEC) creation and interferometry, the detection unit, the vacuum system for $10^{-11}$ mbar ultra-high vacuum generation, and the high-suppression factor magnetic shielding as well as the thermal control system. The laser system is based on a hybrid approach using fiber-based telecom components and high-power laser diode technology and includes all laser sources for 2D-MOT, 3D-MOT, ODT, interferometry and detection. Manipulation and switching of the laser beams is carried out on an optical bench using Zerodur bonding technology. The instrument consists of 9 units with an overall mass of 221 kg, an average power consumption of 608 W (819 W peak), and a volume of 470 liters which would well fit on a satellite to be launched with a Soyuz rocket, as system studies have shown.Comment: 30 pages, 23 figures, accepted for publication in Experimental Astronom