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Although the route to generate microRNAs (miRNAs) is often depicted as a linear series of sequential and constitutive cleavages, we now appreciate multiple alternative pathways as well as diverse strategies to modulate their processing and function. Here, we identify an unusually profound regulatory role of conserved loop sequences in vertebrate pre-mir-144, which are essential for its cleavage by the Dicer RNase III enzyme in human and zebrafish models. Our data indicate that pre-mir-144 dicing is positively regulated via its terminal loop, and involves the ILF3 complex (NF90 and its partner NF45/ILF2). We provide further evidence that this regulatory switch involves reshaping of the pre-mir-144 apical loop into a structure that is appropriate for Dicer cleavage. In light of our recent findings that mir-144 promotes the nuclear biogenesis of its neighbor mir-451, these data extend the complex hierarchy of nuclear and cytoplasmic regulatory events that can control the maturation of clustered miRNAs.

The article critically examines Ivan Szelenyi’s reception of Max Weber’s sociology of rule, which he did in his essay under the title «Weber’s theory of domination and post-communist capitalism» in Theory & Society 2016, 45 (1): 1-24. The criticism exclusively concerns Ivan Szelenyi’s rendering of Weber’s sociology of rule, for example his comments on Weber’s concepts of power and domination. I refer directly to passages in Szelenyi where he deviates incorrectly from Weber’s sociology of rule (such as in his depiction of power and domination according to Weber). Even someone who is not familiar with Szelenyi’s text will benefit from my criticism insofar as it presents a correct, comprehensive account of Weber’s sociology of rule with its central concepts.

OBJECTIVE Morning glory disc anomaly (MGDA), a congenital abnormality of the optic nerve, may be associated with moyamoya arteriopathy, a cerebrovascular abnormality. In this study, the authors aimed to define the temporal evolution of cerebrovascular arteriopathy in patients with MGDA to characterize a rational strategy for screening and management over time. METHODS The records of pediatric neurosurgical patients at two academic institutions were retrospectively reviewed to identify cases of cerebral arteriopathy and MGDA, including radiographic and clinical records documenting patient outcomes of medical and surgical management. RESULTS Thirteen cases of moyamoya syndrome (MMS) associated with MGDA were identified in 13 children aged 0.6–17 years. The pattern of arteriopathy resembled that of non-MGDA MMS, with predominantly anterior circulation involvement. The arteriopathy lateralized with the MGDA, although 3 patients also had contralateral involvement. The overall group was followed for a median of 3.2 years. Radiological biomarkers of cerebral ischemia were applied to guide surgical decisions, and more than half of the patients (7 of 13) had evidence of stroke or progression on serial imaging. Nine patients underwent revascularization surgery, and 4 were managed medically. CONCLUSIONS Cerebral arteriopathy observed in association with MGDA resembles MMS seen in patients without MGDA and is dynamic, with progression observed over months to years and an associated risk of cerebral ischemia that indicates a role for surgical revascularization. Radiological biomarkers may augment clinical data to identify candidates for revascularization surgery.

Objectives The therapeutic antibody infliximab (IFX) has improved the life quality of numerous autoinflammatory disease patients. However, IFX can trigger the generation of anti-drug antibodies (ADA), whose optimal evaluation and management are currently subject of controversial discussions. We present two novel surface plasmon resonance (SPR) biosensor assays for therapeutic drug monitoring of IFX and characterization of ADA and investigated the diagnostic value of ADA binding properties. Methods IFX and ADA were quantified via developed SPR biosensor assays (IFXmon and ADAmon, respectively) and diagnostics-approved ELISA in sera from inflammatory bowel disease patients. Pre-analytic ADA enrichment with magnetic beads enabled analytical drug tolerance of the ADAmon assay. The dissociation ratio (DissR) as an index for ADA:IFX binding stability was calculated from the SPR sensorgrams of ADA quantification runs. Results IFX levels determined by IFXmon assay and ELISA showed high agreement, whereas ADA quantification concordance between ADAmon assay and ELISA was poor. In patients, DissR was predominantly constant over time and differed significantly between therapy outcomes. A DissR cut-off of 1.524 indicated undetectable IFX levels with 71.4% sensitivity and 88.9% specificity. Additionally, the SPR reference surface was exploited as serum-individual negative control to check result plausibility within multi-sample run sequences. Conclusions Overall, both SPR biosensor assays exhibited reliable quantitative performance with accuracies superior to their ELISA counterparts and precision inferior to ELISA only for ADAmon. DissR presented itself as promising ADA binding parameter and could contribute to both earlier and more tailored therapeutic decisions.

Global amphibian population decline is a major concern. Therefore, conservation centers have become increasingly needed for population sustainability breeding programs. This need makes proper nutrition programs while in human care imperative. The specific nutritional focus of this current research was to analyze vitamin A, vitamin E, and carotenoid (apocarotenoid, β-carotene, β-carotene ester, β-cryptoxanthin, lutein, lutein ester, zeaxanthin, and zeaxanthin ester) concentrations in the liver of 66 free-range marine toads (Rhinella marina) over a two-month period after entering human management. Toads were fed supplemented crickets randomly assigned to one of two diets: Diet 1 consisted of brown house crickets (Acheta domestica) gut loaded with Mazuri® Cricket Diet 5M38 and small amounts of sweet potato and carrots; Diet 2 consisted of an identical diet with the gut loaded crickets additionally dusted with Repashy® Superfoods Vitamin A Plus. Ten toads were euthanized prior to human management on Day 0 to assess baseline liver nutrients. Seven toads consuming each of the two diets (14 toads total) were euthanized on Days 9, 15, 32, and 62. Regardless of diet treatment, there were decreases (p < 0.05) in all the analyzed nutrient concentrations over the 62-day human management period. The results from this study indicate that higher dietary vitamin A, vitamin E, and carotenoid content may be needed and/or the cricket gut loading and dusting techniques used to feed the amphibians food source insects may be inadequate.

Conventional epilepsy surgery performed by microsurgical dissection typically requires large cranial working windows created with high-speed drills and lengthy incisions. In the past few decades, minimally invasive techniques have been developed with smaller incisions, comparable efficacy, shorter hospitalizations, and better safety profiles. These minimally invasive alternatives utilize stereotactic, ultrasonic, radiotherapeutic, and endoscopic techniques. Although not able to completely replace conventional surgery for all etiologies of epilepsy, these minimally invasive techniques have revolutionized modern epilepsy surgery and have been an invaluable asset to the neurosurgeon's repertoire. The endoscope has allowed for surgeons to have adequate visualization during resective and disconnective epilepsy surgeries using keyhole or miniature craniotomies. Modern stereotactic techniques such as laser interstitial thermal therapy and radiofrequency ablation can be used as viable alternatives for mesial temporal lobe epilepsy and can destroy lesional tissue deep areas without the approach-related morbidity of microsurgery such as with hypothalamic hamartomas. These stereotactic techniques do not preclude future surgery in the settings of treatment failure and have been used successfully after failed conventional surgery. Multiple ablation corridors can be performed in a single procedure that can be used for lesioning of large targets or to simplify treating multifocal epilepsies. These stereotactic techniques have even been used successfully to perform disconnective procedures such as hemispherotomies and corpus callosotomies. In patients unable to tolerate surgery, stereotactic radiosurgery is a minimally invasive option that can result in improved seizure control with minimal procedural risks. Advances in minimally invasive neurosurgery provide viable treatment options for drug-resistant epilepsy with quicker recovery, less injury to functional brain, and for patients that may otherwise not choose conventional surgery.

A new formal synthesis gave kibdelomycin with 2.8% yield over 19 steps, featuring a general method for introduction of a 3-(α-aminoalkyl) linkage into glycosides, and the first N-glycosylation of 3-acyltetramic acids.

The University of Minnesota Grape Breeding Program has developed cold-hardy wine grape cultivars that have facilitated the establishment of an economically important grape industry for the Midwest region. In recent years, the program has renewed efforts to breed cold-hardy table grapes. Table grapes might require postharvest storage if they are to be transported or stored for any period of time. Rachis dehydration, berry splitting, and decay can affect the postharvest quality of table grapes. In this study, we evaluated these postharvest traits in six released cultivars and nine advanced selections in the breeding program. For two growing seasons, we used industry standard packaging to assess postharvest traits (rachis dehydration, berry splitting, decay, and overall acceptability) at 2, 4, and 6 weeks of cold storage at 2.2 °C. The growing season had a significant effect on postharvest traits; therefore, the two were examined separately. There were significant differences in postharvest storage times for all traits, except berry splitting in 2020. Mean rachis dehydration reached unacceptable values (>3) after 4 weeks of postharvest storage in 2019 and after 6 weeks in 2020. All other trait means remained acceptable for many cultivars even after 6 weeks of postharvest storage. Advanced selections performed at and above the level of released cultivars, suggesting that selections will perform well in cold-hardy regions. The data collected regarding fruit quality and postharvest storage for two seasons will help to inform and improve breeding of cold-hardy grape cultivars.

The annual Virtual Hospital Diabetes Meeting was hosted by Diabetes Technology Society on April 1 and April 2, 2022. This meeting brought together experts in diabetes technology to discuss various new developments in the field of managing diabetes in hospitalized patients. Meeting topics included (1) digital health and the hospital, (2) blood glucose targets, (3) software for inpatient diabetes, (4) surgery, (5) transitions, (6) coronavirus disease and diabetes in the hospital, (7) drugs for diabetes, (8) continuous glucose monitoring, (9) quality improvement, (10) diabetes care and educatinon, and (11) uniting people, process, and technology to achieve optimal glycemic management. This meeting covered new technology that will enable better care of people with diabetes if they are hospitalized.

To introduce this special issue of Modern Africa, the editors review Eritrea’s current condition and consider its historical roots: they place this Horn of Africa state in a broader historical context, one where neither relevant comparative cases nor past precedents are limited to its region. Hopes that were once invested in Eritrea as a model developmental state have now, thirty years since its independence, been thoroughly disappointed. The human rights violations and persistent underdevelopment that make an Eritrean transition necessary are very real: equally real are the risks and dangers that would be involved in any such transition. Recent cases of failed transition are discussed here: so too are the possible routes Eritrea might take to a “developmental democracy.” This issue’s various contributions are then introduced and summarised.

Myocardial inflammation and edema are major pathological features in myocarditis. Myocardial tissue water content and myocardial edema can be quantified via T2 mapping. Thus, cardiac magnetic resonance (CMR) is the noninvasive gold standard for diagnosing myocarditis. Several studies showed an impact of short-term volume changes on T2 relaxation time. Plasma volume status (PVS) is a good surrogate parameter to quantify a patient’s volume status, and it is simple to use. The aim of this study was to determine the effect of PVS on the diagnostic value of T2 relaxation time in myocardial inflammation. Between April 2017 and December 2022, patients who were indicated for cardiac CMR were included in our prospective clinical registry. Patients with myocardial inflammation and those with unremarkable findings were analyzed in the present study. A blood sample was drawn, and PVS was calculated. Patients were separated into PVS tertiles to explore a possible nonlinear dose–response relationship. Logistic regression analysis was used to determine whether T2 is an independent predictor of myocardial inflammation. A total of 700 patients (47.43% female) were eligible for analysis. Of these, 551 patients were healthy (78.7%), while 149 (21.3%) showed signs of myocardial inflammation. The T2 relaxation time was elevated in patients with myocardial inflammation (40 ms [IQR 37–42 ms] vs. 38.0 ms [IQR 36–39 ms], p < 0.001). PVS showed no difference between the groups (−12.94 [IQR −18.4–−7.28] vs.−12.19 [IQR −18.93–−5.87], p = 0.384). T2 showed a clear dose–response relationship with PVS, with increasing T2 values along the PVS tertiles. In spite of this, T2 was found to be an independent marker of myocardial inflammation in logistic regression (OR T2 1.3 [95% CI 1.21–1.39], p < 0.001), even after adjusting for PVS (OR T2 [adj. PVS] 1.31 [95% CI 1.22–1.40], p < 0.001). Despite a dose–response relationship between T2 and the volume status, T2 was found to be an independent indicator of myocardial inflammation.

Accreting protoplanets are windows into planet formation processes, and high-contrast differential imaging is an effective way to identify them. We report results from the Giant Accreting Protoplanet Survey (GAPlanetS), which collected Hα differential imagery of 14 transitional disk host stars with the Magellan Adaptive Optics System. To address the twin challenges of morphological complexity and point-spread function instability, GAPlanetS required novel approaches for frame selection and optimization of the Karhounen–Loéve Image Processing algorithm pyKLIP. We detect one new candidate, CS Cha “c,” at a separation of 68 mas and a modest Δmag of 2.3. We recover the HD 142527 B and HD 100453 B accreting stellar companions in several epochs, and the protoplanet PDS 70 c in 2017 imagery, extending its astrometric record by nine months. Though we cannot rule out scattered light structure, we also recover LkCa 15 “b,” at Hα; its presence inside the disk cavity, absence in Continuum imagery, and consistency with a forward-modeled point source suggest that it remains a viable protoplanet candidate. Through targeted optimization, we tentatively recover PDS 70 c at two additional epochs and PDS 70 b in one epoch. Despite numerous previously reported companion candidates around GAplanetS targets, we recover no additional point sources. Our moderate Hα contrasts do not preclude most protoplanets, and we report limiting Hα contrasts at unrecovered candidate locations. We find an overall detection rate of ∼36 − 22 + 26 % , considerably higher than most direct imaging surveys, speaking to both GAPlanetS’s highly targeted nature and the promise of Hα differential imaging for protoplanet identification.

The impact of former COVID-19 infection on the performance of athletes is not fully understood. We aimed to identify differences in athletes with and without former COVID-19 infections. Competitive athletes who presented for preparticipation screening between April 2020 and October 2021 were included in this study, stratified for former COVID-19 infection, and compared. Overall, 1200 athletes (mean age 21.9 ± 11.6 years; 34.3% females) were included in this study from April 2020 to October 2021. Among these, 158 (13.1%) athletes previously had COVID-19 infection. Athletes with COVID-19 infection were older (23.4 ± 7.1 vs. 21.7 ± 12.1 years, p < 0.001) and more often of male sex (87.7% vs. 64.0%, p < 0.001). While systolic/diastolic blood pressure at rest was comparable between both groups, maximum systolic (190.0 [170.0/210.0] vs. 180.0 [160.0/205.0] mmHg, p = 0.007) and diastolic blood pressure (70.0 [65.0/75.0] vs. 70.0 [60.0/75.0] mmHg, p = 0.012) during the exercise test and frequency of exercise hypertension (54.2% vs. 37.8%, p < 0.001) were higher in athletes with COVID-19 infection. While former COVID-19 infection was not independently associated with higher blood pressure at rest and maximum blood pressure during exercise, former COVID-19 infection was related to exercise hypertension (OR 2.13 [95%CI 1.39–3.28], p < 0.001). VO2 peak was lower in athletes with compared to those without COVID-19 infection (43.4 [38.3/48.0] vs. 45.3 [39.1/50.6] mL/min/kg, p = 0.010). SARS-CoV-2 infection affected VO2 peak negatively (OR 0.94 [95%CI 0.91–0.97], p < 0.0019). In conclusion, former COVID-19 infection in athletes was accompanied by a higher frequency of exercise hypertension and reduced VO2 peak.

The path to European climate neutrality by 2050 will require comprehensive changes in all areas of life. For large industries such as steelworks, this results in the need for climate-friendly technologies. However, the age structure of existing steelworks makes transitional solutions such as carbon capture, utilization and storage (CCUS) necessary as short-term measures. Hence, a purposeful option is the integration of technical syntheses such as methanation into the overall process. This work summarizes hydrogen-intensified methanation experiments with synthetic steel gases in the novel additively manufactured reactor ‘ADDmeth1’. The studies include steady-state operating points at various reactor loads. Blast furnace gas (BFG), basic oxygen furnace gas (BOFG) and three mixtures of these two gases serve as carbon sources. The methanation achieved methane yields of 93.5% for BFG and 95.0% for BOFG in the one-stage once-through setup. The results suggest a kinetic limitation in the case of BFG methanation, while an equilibrium limitation is likely for BOFG. There is a smooth transition in all respects between the two extreme cases. The reaction channel inlet temperature ϑin showed a large influence on the reactor ignition behavior. By falling below the threshold value, a blow-off occurred during experimental operation. By means of a simulation model, practical operating maps were created which characterize permissible operating ranges for ϑin as a function of the gas composition and the reactor load.

Polazište. Akutno oštećenje bubrega (AOB) kod novorođenčeta često je povezano s perinatalnom hipoksijom/asfiksijom. Još uvijek nema jedinstvenog stajališta u odnosu na kriterije AOB, što je teško postići bez dobrog biokemijskog markera oštećenja bubrega. Serumski cistatin-C (cistatin-C) pokazao se kao obećavajući marker glomerulne filtracije (GFR) kod odraslih i veće djece, no ipak još nije validiran kod novorođenčadi. Rana ocjena bubrežne funkcije važna je i za otkrivanje povećanog rizika bubrežnog oštećenja kod nedostašćadi (SFD), što je dokazano povezano sa smanjenim brojem nefrona. Ultrazvučno utvrđene mjere bubrega pokazale su se kao dobar pokazatelj broja nefrona. Ciljevi. Svrha našeg istraživanja bila je utvrditi normalne referentne vrijednosti cistatina-C kod novorođenčadi prilikom rođenja i u dobi od 3 dana te ih usporediti s kreatininom, Schwartzovim izračunanim klirensom i različitim formulama za izračun GFR na bazi cistatina-C kod donošene eutrofične i hipotrofične novorođenčadi kao i kakva je vrijednost cistatina-C u pupkovnoj krvi kao pokazatelja AOB nakon perinatalne hipoksije/asfiksije u usporedbi s kreatininom. Ispitanici i metode. U istraživanje je uključeno ukupno 150 donošene novorođenčadi: 50 u skupini nakon perinatalne hipoksije/asfiksije (AS), 50 u skupini nedostaščadi (SFD) i 50 u kontrolnoj skupini eutrofične novorođenčadi (KS). Kod svih smo obavili antropometrijska mjerenja, mjerili smo krvni tlak i bilježili diurezu prva 3 dana nakon rođenja. Određivali smo vrijednosti cistatina-C i kreatinina u pupkovnoj krvi (cistC-umb i kreat-umb) i 3 dana nakon rođenja (cistC-3 i kreat-3) te u odnosu na normalnost distribucije rezultata koristili odgovarajuće parametrijske i neparametrijske metode z usporedbu između skupina. S multivarijatnom analizom utvrđivali smo mogući utjecaj spola, porođajne težine (PT), porođajne dužine (PD), gestacijske dobi (GS), bilirubina (Bil), hemoglobina (Hb) i stanja hidracije na vrijednosti cistatina-C i kreatinina. Analizirali smo i moguće prenatalne i perinatalne rizične čimbenike za perinatalnu hipoksiju/asfiksiju i s metodom linearne regresije utvrđivali njihov utjecaj na vrijednosti cistatina-C i kreatinina kod novorođenčeta. Perinatalna hipoksija/asfiksija definirana je laboratorijski i klinički (Apgar ocena, pH i BE pupkovne krvi, klinički znaci ometanog djelovanja raznih organa). Povezanost između vrijednosti cistatina-C odn. kreatinina i čimbenici koji određuju težinu hipoksije/asfiksije provjerena je s Pearsonovim korelacijskim testom i linearnom regresijom. Dijagnostička učinkovitost testiranih pokazatelja bubrežne funkcije u povezanosti s perinatalnom hipoksijom/asfiksijom ocijenjena je s konstruiranjem ROC krivulje i analizom AUC površine te računanjem senzitivnosti i specifičnosti pojedinog testa. Kod sve novorođenčadi je u dobi od 48 do 72 sati napravljena ultrazvučna (UZ) pretraga zbog isključivanja anomalija. U skupini SFD i KS obavljena su i UZ mjerenja volumena bubrega: 2DUZ mjerenje i izračun volumena po formuli za elipsu (Vol-f-T) te 3DUZ volumetrija (3Dvol-T). Povezanost dobivenih ukupnih volumena bubrega s oba ispitivana pokazatelja GFR provjeravana je s Pearsonovim korelacijskim testom. Do sada poznate normative GFR za novorođenčad uspoređivala sam sa Schwartzovim izračunanim klirensom (GFK) i 3 formule na bazi cistatina-C (GFC): varijantu 1 (100/cistatin-C); varijantu 2 (74.835/cistatin-C1/0.75) i novu konstruiranu varijantu 3, koja uzima u obzir ukupni volumen bubrega i tjelesnu površinu ((Vol-T/BSA)/cistatin-C)/1.73). Rezultati. Prosječna vrijednost cistC-umb u KS iznosi 1.39 ± 0.19 mg/l; u skupini AS 2.12 ± 0.53 mg/l; a u skupini SFD 1.48 ± 0.30 mg/l. Razlika između skupina AS i KS je statistički značajna (p < 0.001), a između SFD i KS nema razlike. Tri dana nakon rođe prosječne se vrijednosti cistC-3 snize statistički značajno samo u skupini AS (-38 %), u SFD i KS je sniženje minimalno (-8 % i -6 %). Razlika između AS i KS ostaja statistički značajna i nakon 3 dana (p < 0.001). Prosječna vrijednost kreat-umb u KS iznosi 62.74 ± 12.84 μmol/l; u skupini AS 72.60 ± 15.55 μmol/l; a u skupini SFD 67.08 ± 17.62 μmol/l. Razlika između skupina AS i KS je statistički značajna (p = 0.001), a između SFD i KS nema razlike. Pad vrijednosti kreatinina u prva 3 dana nakon rođenja ne razlikuje se statistički značajno između skupina AS, SFD i KS (-33 %, -27 % i -34 %). Povezanost između vrijednosti cistatina-C odnosno kreatinina i drugih varijabli od interesa provjerena je linearnom regresijom, konstruiranjem bločnog regresijskog modela. Pokazalo se da vrijednosti cistatina-C ne ovise od GS, vrijednosti hemoglobina i bilirubina te stanja hidracije, a naznačen je utjecaj spola i PT (skupina AS i KS). Utjecaj spomenutih varijabli na vrijednosti cistatina-C i kreatinina zavisi od broja uključenih. Kada radimo izračun zajedno sa skupinom SFD (n = 150) gubi se utjecaj PT na cistC-3 i spola na vrijednosti cistC-umb, a pokazuje se utjecaj hemoglobina na cistC-umb. Ostaje vidljiv utjecaj arterijske hipertenzije sa znacima gestoze na vrijednost cistatina-C, a promenljivo kreatinina u odnosu na maternalne čimbenike. Na vrijednost kreatinina utječe također paritet, promenljivo spol i PT. S čimbenicima koji određuju težinu hipoksije/asfiksije najviše se povezuje cistC-umb, što objašnjava najveći udio varijance (48.9 %), slijede cistC-3 (30.8 %), kreat-3 (26.2 %) i kreat-umb (22.2 %). I ROC krivulja prikazuje (AS u usporedbi s KS), da je AUC površina najveća za cistC-umb; slijede cistC-3, kreat-umb i kreat-3 (0.918; 0.698; 0.692; 0.660). Najuravnoteženiji cut-off za cistC-umb utvrđen je kod 1.67 mg/l (senzitivnost 84.0 %, specifičnost 90.0 %) odn. kod 1.69 mg/l (senzitivnost 82.0 %, specifičnost 94.0 %). Odmah nakon rođenja samo 3Dvol-T korelira statistički značajno s cistC-umb, a Vol-f-T ne korelira niti s cistC umb, niti s kreat-umb. 3 dana nakon rođenja bolje korelira s oba volumena kreat-3, a cistC-3 pokazuje bolju korelaciju s relat volumenom 3Dvol-T u odnosu na ponderalni indeks (PI) i tjelesnu površinu (BSA). Redukcija 3Dvol-T/BSA za 10 % vodi u povišenje vrijednosti cistC-umb za 9.3 %. Izračunane vrijednosti GFR u KS iz pupkovne krvi i 3 dana nakon rođenja su sljedeće (ml/min/1.73m2 ): GFK1 (31.53 ± 7.64); GFK3 (41.18 ± 13.17); GFC1-v1 (73.09 ± 9.93); GFC1-v2 (49.47 ± 8.97); GFC1-v3 (42.48 ± 12.36); GFC3-v1 (76.45 ± 11.74); GFC3-v2 (52.59 ± 10.77); GFC3-v3 (44.35 ± 12.55). Vrijednosti izračunane GFC-v3 najbliže su referentnoj GFR na bazi inulinskog klirensa (IK) i također su u okviru normalnih vrijednosti kreatininskog klirensa (KK) za donošenu novorođenčad. Zaključak. U skladu s rezultatima našeg istraživanja u prva 3 dana nakon rođenja cistatin- C je bolji pokazatelj GFR u usporedbi s kreatininom. Cistatin-C-umb je za razliku od kreatinina-umb dosta bolji prediktor AOB povezane s perinatalnom hipoksijom/asfiksijom., Background. The aim of this study was to clarify the reference values of serum cystatin C (cysC) as a marker of glomerular filtration rate (GFR) in full-term newborns, appropriate and small for gestational age (SFD), and in neonates after perinatal hypoxia/asphyxia (AS) in comparison with creatinine (Cr), Schwartz's formula and 3 different cystatin-C based equations. Patients and methods. 150 full-term newborns were enrolled, comprised of 3 groups (AS, SFD and control). CysC and Cr were measured in serum samples from the umbilical cord at birth (cysC-umb and Cr-umb) and from a peripheral vein 3 days later (cysC-3 and Cr-3). Kidney volume measurements by ultrasound were made. Results. At birth, the mean level of cysC in normal term babies was found to be 1.39 ± 0.19 mg/l, in AS group 2.12 ± 0.53 mg/l and in SFD group 1.48 ± 0.30 mg/l; not significantly decreased in controls but in SFD and AS group after 3 days of life. Cr levels, determined simultaneously at birth were 62.74 ± 12.84 μmol/l in control, 72.60 ± 15.55 μmol/l in AS and 67.08 ± 17.62 μmol/l in SFD group. After 3 days Cr levels significantly decreased in all three groups. The ROC curve analysis, comparing AS versus control, showed AUC for cysC-umb, cysC-3, Cr-umb and Cr-3 (0.918; 0.698; 0.692; 0.660). The highest diagnostic accuracy was achieved with a chosen cut-off for cysC-umb of 1.67 mg/l (sensitivity of 84.0%, specificity of 90.0%) or 1.69 mg/l (sensitivity of 82.0%, specificity of 94.0%). A new constructed cys-C based formula which requires kidney volume and body surface area for calculations is a reliable marker of GFR comparingly with the neonatal referential clearance values. Conclusions. Our results indicate CysC is more sensitive marker of GFR than Cr in the newborns.

The use of bacteriophage, viruses that specifically infect bacteria, as antibiotics has become an area of great interest in recent years as the effectiveness of conventional antibiotics recedes. The detection of phage interactions with specific bacteria in a rapid and quantitative way is key for identifying phage of interest for novel antimicrobials. Outer membrane vesicles (OMVs) derived from gram-negative bacteria can be used to make supported lipid bilayers (SLBs) and thereforein vitromembrane models that contain naturally occurring components of the bacterial outer membrane. In this study, we usedEscherichia coliOMV derived SLBs and use both fluorescent imaging and surface sensitive techniques to show their interactions with T4 phage. We also integrate these bilayers with microelectrode arrays (MEAs) functionalised with the conducting polymer PEDOT:PSS and show that the pore forming interactions of the phage with the SLBs can be monitored using electrical impedance spectroscopy. To highlight our ability to detect specific phage interactions, we also generate SLBs using OMVs derived fromCitrobacter rodentium, which is resistant to T4 phage infection, and identify their lack of interaction with phage. The work presented here shows how interactions occurring between phage and these complex SLB systems can be monitored using a range of experimental techniques. We believe this approach can be used to identify phage against bacterial strains of interest, as well as more generally to monitor any pore forming structure (such as defensins) interacting with bacterial outer membranes, and thus aid in the development of next generation antimicrobials.

Since the 2000s, digital ecosystems have been affecting markets—Facebook and Uber being prominent examples. Looking at the agrisector, however, there is not yet a winner-takes-all solution in place. Instead, numerous digital agriplatforms have emerged, many of which have already failed. In the context of this study, it was revealed that reasons for such failures can be manifold, with one key challenge being the orchestration of platform content. Because, however, publicly available knowledge on this regard is limited, we decided to introduce a methodology for the evaluation of digital agriecosystem services, enabling providers to optimize their existing offering and to prioritize new services prior to implementation. By deploying our methodology to digital agriecosystems with two different application focuses (DairyChainEnergy—data agriecosystem on energy management for dairy farmers, and NEVONEX—IoT agriecosystem comprising digital services for agrimachinery), its applicability was proven. Providers of digital agriecosystems will benefit from applying this new methodology because they receive a structured decision-making process, which takes the most relevant success criteria (e.g., customer benefit, technical feasibility, and resilience) into account. Hence, a resulting prioritization of digital agriservices will guide providers in making the right implementation choices in order to successfully generate network effects on their digital agriecosystems.

Introduction The transition to metabolically unhealthy obesity (MUO) is driven by the limited expandability of adipose tissue (AT). Familial Partial Lipodystrophy type 2 (FPLD2) is an alternative model for AT dysfunction that is suitable for comparison with obesity. While MUO is associated with low-grade systemic inflammation, studies of inflammation in FPLD2 have yielded inconsistent results. Consequently, comparison of inflammation markers between FPLD2 and obesity is of great interest to better understand the pathophysiological defects of FPLD2. Objective To compare the levels of inflammatory biomarkers between a population of patients with FPLD2 due to the same ‘Reunionese’ LMNA variant and a population of patients with obesity (OB group). Methods Adiponectin, leptin, IL-6, TNF-α and MCP-1 plasma levels were measured by enzyme-linked immuno assays for 60 subjects with FPLD2 and for 60 subjects with obesity. The populations were closely matched for age, sex, and diabetic status. Results Metabolic outcomes were similar between the two populations. Adiponectinemia and leptinemia were lower in the FPLD2 group than in the OB group (p Conclusions Insulin-resistant patients with FPLD2 and obesity share common complications related to AT dysfunction. Inflammatory biomarker analyses demonstrated that MCP-1 levels and adiponectin levels differ between patients with FPLD2 and patients with obesity. These two AT pathologies thus appear to have different inflammatory profiles.

In multiple sclerosis, an inflammatory attack results in myelin loss, which can be partially reversed by remyelination. Recent studies suggest that mature oligodendrocytes could contribute to remyelination by generating new myelin. Here, we show that in a mouse model of cortical multiple sclerosis pathology, surviving oligodendrocytes can indeed extend new proximal processes but rarely generate new myelin internodes. Furthermore, drugs that boost myelin recovery by targeting oligodendrocyte precursor cells did not enhance this alternate mode of myelin regeneration. These data indicate that the contribution of surviving oligodendrocytes to myelin recovery in the inflamed mammalian CNS is minor and inhibited by distinct remyelination brakes.

We describe here 11 consecutive patients with recurrence of high-grade glioma treated with regorafenib at our university medical center. The majority of patients had MGMT promoter methylation (9/11 cases). Regorafenib was given as 2nd line systemic treatment in 6/11 patients and 3rd or higher line treatment in 5/11 patients. The median number of applied cycles was 2 with dosage reductions in 5/11. Response to treatment was observed in 4/11 (PR in 1/11, and SD in 3/11). Median overall survival for the cohort was 16.1 months, median progression-free survival 9.0 months, and median time to treatment failure 3.3 months. Side effects of any CTCAE grade were noted in all patients, hereby 6/11 with CTCAE °III-IV reactions. High-grade side effects were of dermatologic, cardiovascular, and hematologic nature. A mean treatment delay of 57.5 days (range 23–119) was noted between tumor board recommendation and treatment initiation due to the application process for off-label use in this indication. In conclusion, treatment with regorafenib in relapsed high-grade glioma is a feasible treatment option but has to be considered carefully due to the significant side effect profile.

— Cecropia is a group of fast-growing pioneer trees that are important in forest regeneration and a common ant-plant mutualism in the Neotropics. To investigate the evolution of mutualism between Cecropia and associated ants, a phylogenetic framework is necessary. Cecropia species are difficult to distinguish morphologically and conventional genetic markers are insufficiently variable to resolve the phylogenetic relationships among species. Our study aimed to compare the phylogenetic utility of restriction site associated DNA (RAD) sequencing to prior work based on commonly sequenced gene regions. RAD sequence data resolved and supported species-level relationships better than previous studies. We identified a deeply divergent non-myrmecophytic clade including C. sciadophylla and African Musanga. Results from geographically widespread and morphologically heterogenous C. obtusifolia and C. angustifolia suggest that current synonymy has lumped phylogenetically divergent lineages. Reconstruction of ant associations on the highly supported Cecropia phylogeny inferred equal probability of the ancestor of Cecropia being myrmecophytic or not. More intensive genetic study is needed to refine species concepts in Cecropia.

Zusammenfassung Die Maßnahmen zur Eindämmung der Corona-Pandemie haben vielerorts Proteste nach sich gezogen – insbesondere in Sachsen. Betroffene Kommunen und Akteure der politischen Bildung sind geneigt, diesen Protesten durch verschiedene Formate für Dialog und Verständigung Rechnung zu tragen. Der vorliegende Artikel vollzieht diese Versuche anhand einiger Beispiele verschiedener Formate nach, die systematisch begleitet und evaluiert wurden. Die daraus resultierenden Erkenntnisse werden in das breitere Bild der Bürgerbeteiligung eingeordnet und Handlungsoptionen aufgezeigt. Zudem wird dargelegt, auf welche Abwege deliberative Formate in der pandemischen Lage unter dem Eindruck von Verschwörungsmythen sowie zunehmender Radikalisierung geraten können und welche Fehler es zu vermeiden gilt.

Purpose. Rewetting solutions and eye sprays are getting more popular recently and are available in many different compositions. They promise to help against symptoms of dry eyes. This study tries to determine if the eye drops EvoTears, which contains lipids, helps better against symptoms of dry eyes as the liposomal eye spray LipoNit. Material and Methods. Both preparations were tested on a total of 23 subjects (11 female, 12 male, age 33 years ± 13.8 years, 23 – 60 years). In a single-blinded, balanced, rand- omized and prospective cross- over study, according to the ethical principles of the Declaration of Helsinki, the subjective sensation as well as objective findings of dry eye were de- termined and evaluated in each case before dispensing and after a one-week application of the respective preparation. For the subjective determination the OSDI questionnaire was used. Objectively, lipid layer thickness was determined and evaluated using Polaris device (BON), as well as tear meniscus height and noninvasive tear film break-up using Oculus Keratograph. After one week of application of the respective preparations, the subjective and objective findings before and after application were compared. Furthermore, in an additional questionnaire, each subject was able to assign points for the simplicity of application as well as points for the subjective improvement of dry eyes of both preparations. Results. The difference of the findings in both products in between the week of usage were 0 in all four findings (OSDI, NIKBUT, meniscus height, lipid layer thickness). This means that both of the investigated Liquids have more or less the same impact on dry eyes. Further, this study statistically proves that EvoTears significantly reduces the OSDI Score after using (p-value 0,0403). There is a tendency that Evo- Tears also improves the thickness of the lipid layer, although it is almost statistically significant (p-value 0,0708). All the other findings were statistically not significant. Most of the participants felt the handling of LipoNit much easier com- pared to EvoTears. However, EvoTears had a slightly bigger impact on subjective feeling. Conclusion. In this study, EvoTears and LipoNit were found to have similar effects on dry eye. A statistically significant difference existed only in the OSDI questionnaire (decrease OSDI score) in combination with EvoTears. In principle, the results obtained could be attributed to the short applica- tion period of one week, the small number of subjects or a non-compliance. In addition, only participants with moderate dry eyes were examined. Despite all this, the subjective dry eye symptoms decreased with both agents. Keywords Rewetting solution, ophthalmic sprays, dry eyes, EvoTears, LipoNit, OSDI questionnaire

Most hops are produced in Europe; therefore, it is alarming that the citrus bark cracking viroid (CBCVd), the causal agent of the severe hop stunt disease, was detected in different nonadjacent hop growing countries. It is still unclear how the initial infection occurred since CBCVd is typically found in citrus and not in hops. To extent data for a viroid risk assessment, potential hosts were tested for the presence of viroids in grocery stores in the hop producing areas of Slovenia and Germany. Samples positive for hop-pathogenic viroids were further used for infection studies. The surveys covered CBCVd, hop stunt viroid (HSVd), citrus exocortis viroid (CEVd), citrus dwarfing viroid (CDVd), citrus viroid V (CVdV), and citrus bent leaf viroid (CBLVd). The results show that all tested viroids can be found in fruits sold in grocery stores, thus there is a risk of introducing CBCVd, HSVd, and other viroids into the hop growing regions via imported fruits and their remains. Furthermore, the transmission study reveals that CBCVd and HSVd infected citrus fruits can be infectious, irrespective of whether in the form of RNA inoculum, injected sap, or fruit peel in the soil. Finally, the phylogenetic analysis showed that the sequence diversity within viroid samples is high and that CBCVd and HSVd sequence variants can be found, which are almost identical to variants confirmed in hop. We assumed that fruit imports contribute to international viroid spreading and inappropriate handling like fruit waste deposition to agricultural lands is a serious risk factor.

Introduction Je propose dans cet article de prendre au sérieux la désignation de Heidegger par Foucault comme « le philosophe essentiel ». Cependant, contrairement à de nombreuses lectures qui considèrent, à l’instar de Dreyfus, que l’adjectif « essentiel » justifie de lire Foucault comme un prolongement de Heidegger, je défends l’idée que le qualificatif « essentiel » peut être compris au sens d’un contre-poids ou d’un défi essentiel. Rien, dans ce que Foucault dit ou écrit, ne suggère de pr...

BackgroundNative T1 has become a pivotal parameter of tissue composition that is assessed by cardiac magnetic resonance (CMR). It characterizes diseased myocardium and can be used for prognosis estimation. Recent publications have shown that native T1 is influenced by short-term fluctuations of volume status due to hydration or hemodialysis.MethodsPatients from a prospective BioCVI all-comers clinical CMR registry were included, and native T1 and plasma volume status (PVS) were determined according to Hakim’s formula as surrogate markers of patient volume status. The primary endpoint was defined as combined endpoint of cardiovascular death or hospitalization for heart failure events, the secondary endpoint was defined as all-cause mortality.ResultsA total of 2,047 patients were included since April 2017 [median (IQR); age 63 (52–72) years, 33% female]. There was a significant although weak influence of PVS on native T1 (β = 0.11, p −13%) showed significantly higher values for tissue markers than non-volume-overloaded patients [PVS ≤ −13%; median (IQR); native T1 1,130 (1,095–1,170) vs. 1,123 (1,086–1,166) ms, p p ConclusionDespite a weak effect of PVS on native T1, its predictive power was not affected in a large, all-comers cohort.

Background Cardiovascular magnetic resonance (CMR) plays a pivotal role in diagnosing myocardial inflammation. In addition to late gadolinium enhancement (LGE), native T1 and T2 mapping as well as extracellular volume (ECV) are essential tools for tissue characterization. However, the differentiation of cardiac sarcoidosis (CS) from myocarditis of other etiology can be challenging. Positron-emission tomography-computed tomography (PET-CT) regularly shows the highest Fluordesoxyglucose (FDG) uptake in LGE positive regions. It was therefore the aim of this study to investigate, whether native T1, T2, and ECV measurements within LGE regions can improve the differentiation of CS and myocarditis compared with using global native T1, T2, and ECV values alone. Methods PET/CT confirmed CS patients and myocarditis patients (both acute and chronic) from a prospective registry were compared with respect to regional native T1, T2, and ECV. Acute and chronic myocarditis were defined based on the 2013 European Society of Cardiology position paper on myocarditis. All parametric measures and ECV were acquired in standard fashion on three short-axis slices according to the ConSept study for global values and within PET-CT positive regions of LGE. Results Between 2017 and 2020, 33 patients with CS and 73 chronic and 35 acute myocarditis patients were identified. The mean ECV (± SD) in LGE regions of CS patients was higher than in myocarditis patients (CS vs. acute and chronic, respectively: 0.65 ± 0.12 vs. 0.45 ± 0.13 and 0.47 ± 0.1; p Conclusion This is the first study to show that the calculation of regional ECV within LGE-positive regions may help to differentiate CS from myocarditis. Further studies are warranted to corroborate these findings.

Recent experimental and empirical observations have demonstrated that stochasticity plays a critical role in car following (CF) dynamics. To reproduce the observations, quite a few stochastic CF models have been proposed. However, while calibrating the deterministic CF models is well investigated, studies on how to calibrate the stochastic models are lacking. Motivated by this fact, this paper aims to address this fundamental research gap. Firstly, the CF experiment under the same driving environment is conducted and analyzed. Based on the experimental results, we test two previous calibration methods, i.e., the method to minimize the Multiple Runs Mean (MRMean) error and the method of maximum likelihood estimation (MLE). Deficiencies of the two methods have been identified. Next, we propose a new method to minimize the Multiple Runs Minimum (MRMin) error. Calibration based on the experimental data and the synthetic data demonstrates that the new method outperforms the two previous methods. Furthermore, the mechanisms of different methods are explored from the perspective of error analysis. The analysis indicates that the new method can be regarded as a nested optimization model. The method separates the aleatoric errors caused by stochasticity from the epistemic error caused by parameters, and it is able to deal with the two kinds of errors effectively. Finally, we find that under the calibration framework of stochastic CF models, the calibrated parameter set using spacing as MoP may not always outperform that using velocity as MoP. These findings are expected to enhance the understanding of the role of stochasticity in CF dynamics where the new calibration framework for stochastic CF models is established., 34 pages, 13 figures, 17 tables

BackgroundThe non-pharmaceutical measures in the first Covid-19 winter season significantly impacted respiratory pathogens such as RSV, influenza, or metapneumovirus, which cause respiratory infections, especially in infants and young children. This longitudinal prospective study aimed to determine how less strict measures affect the pathogen profile in the second winter season.MethodsFrom September 2021 till the end of March 2022, 678 children (0–36 months) admitted to Vienna's largest pediatric center with an acute respiratory infection were enrolled in this study. The researchers performed nasal swabs and tested them by multiplex PCR for 23 respiratory pathogens, chronicled clinical features and treatment, and analyzed the effect of lockdown on the pathogen prevalence.ResultsThe 815 smears of 678 children revealed the most common pathogens to be rhino-/enterovirus (38.5%), RSV (26.7%), and metapneumovirus (7.2%). The lockdown interrupted the early RSV onset in September [RR 0.367, CI (0.184–0.767), p = 0.003], while no effects on the other pathogens were found. Metapneumovirus started circulating in January. Influenza was only sporadically detected. The hospitalization rate was significantly higher than last season due to RSV [OR 4.089, 95%CI (1.414–11.827), p-adj = 0.05].ConclusionWith more flexible non-pharmaceutical measures, children aged 0–36 months started presenting again with viral pathogens, such as RSV and metapneumovirus. RSV, associated with a high hospitalization rate, had a very early onset with an abrupt interruption due to the only lockdown.

Accreting planetary-mass companions offer an unprecedented window into substellar formation pathways and planetary accretion physics. However, accretion rate diagnostics are not well calibrated in this regime. Plausible (but unconfirmed) theoretical arguments suggest that different physical processes dominate at planetary vs. stellar masses, challenging the validity of extrapolating T Tauri-derived scaling relationships to planets and brown dwarfs. Observationally, accretion rate estimates for substellar objects show a scatter of more than five orders of magnitude around the canonical object mass-mass accretion rate relation. This spread probably results from a combination of selection effects, invalid scaling relations in certain mass regimes, heterogeneous diagnostics probing different parts of the accretion flow, and true physical effects such as accretion variability and age or surface density variation. I will present our group's efforts to disentangle systematics from true physical effects and to develop methods for reliably estimating mass accretion rates for substellar objects. These efforts include the assembly of the Comprehensive Archive of Substellar and Planetary Accretion Rates (CASPAR) Database and new simulation tools to understand the origins (physical and observational) of observed deviations in accretion rates among objects with similar physical properties. I will highlight preliminary results from observational campaigns on Keck, SOAR, and APO designed to create new empirical accretion templates and scaling relations for low mass objects. I will also outline the unique potential of JWST to inform the physics of accretion onto planets and brown dwarfs. The ultimate goal of these efforts is to establish robust accretion diagnostics for substellar objects, which are needed in order to derive accurate accretion rates for protoplanets and to make inferences about formation pathways for bound and isolated planetary-mass companions., {"references":["Betti, S. K., K. B. Follette, K. Ward-Duong, Y. Aoyama, G. -D. Marleau, J. Bary, C. Robinson, et al. \"Near-Infrared Accretion Signatures from the Circumbinary Planetary-Mass Companion Delorme 1 (AB)b.\" The Astrophysical Journal 935 (August 1, 2022): L18. https://doi.org/10.3847/2041-8213/ac85ef.","Aoyama, Yuhiko, Gabriel-Dominique Marleau, Masahiro Ikoma, and Christoph Mordasini. \"Comparison of Planetary Hα-Emission Models: A New Correlation with Accretion Luminosity.\" The Astrophysical Journal 917 (August 1, 2021): L30. https://doi.org/10.3847/2041-8213/ac19bd.","Aoyama, Yuhiko, Masahiro Ikoma, and Takayuki Tanigawa. \"Theoretical Model of Hydrogen Line Emission from Accreting Gas Giants.\" The Astrophysical Journal 866 (October 1, 2018): 84. https://doi.org/10.3847/1538-4357/aadc11.","Marleau, G.-D., Y. Aoyama, R. Kuiper, K. Follette, N. J. Turner, G. Cugno, C. F. Manara, et al. \"Accreting Protoplanets: Spectral Signatures and Magnitude of Gas and Dust Extinction at H α.\" Astronomy & Astrophysics, Volume 657, Id.A38, 31 Pp. 657 (January 2022): A38. https://doi.org/10.1051/0004-6361/202037494.","Hartmann, Lee, Gregory Herczeg, and Nuria Calvet. \"Accretion onto Pre-Main-Sequence Stars.\" Annual Review of Astronomy and Astrophysics, Vol. 54, p.135-180 54 (September 2016): 135. https://doi.org/10.1146/annurev-astro-081915-023347."]}

Hochmontane bis subalpine Lebensräume prägen das Frankenthal als Teil des Réserve Naturelle Nationale Frankenthal-Missheimle (Dep. Haut-Rhin, Frankreich). Auf 40 ha Fläche wurden 2011 und 2012 insgesamt 187 Schwebfliegenarten und damit 84 % der aktuell aus den Vogesen bekannten Arten nachgewiesen, wobei für zehn Arten der derzeitige Artstatus klärungsbedürftig ist. Der Methodenvergleich von Malaise-Fallen und selektiven Handfängen zeigt, dass die Kombination beider Methoden zur Gesamterfassung einen wesentlichen Beitrag geleistet hat. Der zusätzliche Einsatz von Malaise-Fallen ist in potenziell sehr artenreichen Gebieten fachlich sinnvoll.

Im Rahmen dieser Dissertation wurden Naturstoffe mit dem zentralen Motiv einer 3-Acyltetramsäure synthetisiert und derivatisiert. Vertreter dieser Klasse sind durch cytotoxische, antibiotische, antivirale oder herbizide Eigenschaften ins Blickfeld der Forschung gerückt. Durch deren Synthesen wird der Zugang zum Wirkstoff an sich, als auch zur Aufstellung von Struktur-Aktivitäts-Beziehungen geebenet. Eine anschließende Derivatisierung ermöglicht die Funktionalisierung oder Simplifizierung der ursprünglichen Struktur unter Wirkerhalt oder sogar Wirkstei¬gerung. Das erste Projekt beschäftigte sich mit der Darstellung des makrocyclischen Naturstoffs Macrocidin Z (4), wobei eine 3-Acyltetramsäure Teil des Ringssystems ist. Die Erstsynthese bestätigte die Strukturannahme und Stereokonfiguration der Substanz, die zusammen mit vier neuen Macrooxazolen aus dem Pilz Phoma macrostoma isoliert wurde. Als Startmaterial wurde die von L-Tyrosin abgeleitete 3-H2-Tetramsäure 2 gewählt. Nach diastereoselektiver Einführung einer Methylgruppe in 6-Heptensäure unter Gebrauch eines Evans-Auxiliars, wurde sie und die Tetramsäure 2 nach dem Yoshii-Yoda-Protokoll in zwei Schritten zur 3-Acyltetramsäure verknüpft. Mittels Ringschlussmetathese unter Verwendung eines Grubbs-Katalysators wurde der Makrocyclus mit hoher E-Selektivität geschlossen. Entschützung lieferte schließlich in 30% Gesamtausbeute über sechs Stufen Macrocidin Z (4). Neben der bereits bekannten herbiziden Aktivität konnte eine Biofilminhibition und sogar eine Induktion des Biofilmabbaus nachgewiesen werden. Die Ergebnisse aus den Bioaktivitätsstudien ermutigten zu weiteren Arbeiten am Strukturmotiv der Macrocidine. Es wurden divers funktionalisierte Derivate von Macrocidin Z (4) und des ähnlich aufgebauten Naturstoffs Macrocidin A dargestellt und auf verschiedene biologische Aktivitäten getestet. Zunächst gelang durch Hydrierung und Entschützung von Boc-Macrocidin Z 3 die Synthese des Dihydroanalogons 5 in 99% Ausbeute über zwei Stufen. Durch Anwendung der Synthese von 3-Enoyltetramsäuren mittels Ketenylidentriphenylphosphoran und anschließender Ringschlussmetathese sowie Entschützung wurde das doppelt ungesättigte Derivat 1 generiert. Weitere Derivatisierungen sollten ausgehend vom Schlüsselintermediats 6 erfolgen. Dessen Darstellung erfolgte in Analogie zur Synthese von Macrocidin Z (4) durch Acylierung der 6-Heptensäure an die Tetramsäure 2, Umlagerung zur 3-Acyltetramsäure sowie Aufbau des Makrocylcus durch Ringschlussmetathese in 54% über drei Stufen. Anschließend konnte durch Claisen-Umlagerung eine Ringkontraktion in 56% erzielt werden (→ 8) sowie eine Dibromierung in quanti¬tativer Ausbeute (→ 9). Außerdem wurde das zentrale Intermediat 6 durch Sharpless-Dihydroxylierung in den Diol (6’S,7’S)-10 sowie durch eine regioselektive Reaktion mit NBS und H2O in das anti-Bromohydrin (6’S,7’R)-11 überführt. Letzteres reagierte unter basischen Bedingungen zum Epoxid (6’R,7’R)-13. Bei allen Reaktionen konnte eine Stereoinduktion durch den Ring beobachtet werden, jedoch konnte nicht für alle Derivate die absolute Stereokonfiguration bestimmt werden. Im dritten Projekt wurde die formale Totalsynthese von Kibdelomycin (25) sowie die Derivatisierung einzelner Fragmente behandelt. Die Darstellung sollte konvergent erfolgen, wobei das Molekül in drei Bausteine unterteilt wurde. Das Zuckerfragment A, die Amykitanose, wurde ausgehend von L-Rhamnose (16) gebildet. Nach Schützung der anomeren Position und des syn-Diols wurde das Stereozentrum an 4-Position durch Oxidation und diastereoselektiver Reduktion invertiert. Es folgten die selektive Einführung der Acetyl- und Methylgruppe. Nach Aktivierung der anomeren Position kann in einer Au-katalysierten Reaktion gemäß Yang et al. das Glykosid mit einer 4-O-Alkyltetramsäure zum Zielmolekül 17 in einer Gesamtausbeute von 11% über 13 Stufen gekuppelt werden. In Analogie konnten die 3-Acyltetramsäuren 14 und 15 in elf Stufen dargestellt werden. Dabei wurde zum einen die erste direkte N-Glykosylierung mit einer 3-Acyltetramsäure entwickelt und zum anderen ein weiterer Zugang zur Amykitanose A und Kibdelomycin (25) ermöglicht. Das Decalinfragment wurde ausgehend vom Iodid 18 und dem Thioester 19 synthetisiert. Eine Fukuyama-Kupplung ermöglichte deren Verknüpfung zum Keton. CBS-Reduktion, α-Hydroxylierung mit dem Vedejs-Reagenz, eine orthogonale Schutzgruppenstrategie und HWE-Olefinierung lieferten den acyclischen Vorläufer 20. Durch eine Auxiliar-gesteuerte IMDA, Wittig-Olefinierung und Formation eines Acylcyanids wurde der Baustein 21 in 10% über 17 Stufen erhalten. Startmaterial für die Synthese der N-acylierten Amycolose 24 war D Mannose (23). Schlüsselschritte waren die Desoxygenierung an 2- und 6-Position und die stereoselektive Grignard-Reaktion zur Einführung eine C2-Einheit. Die Bildung des Amins mit anschließender Kupplung mit dem Pyrrol E komplettierten die Synthese der N-acylierten Amycolose (24) in einer Gesamt-ausbeute von 10% über 13 Stufen. Die Schlüsselschritte wurden bei der Darstellung eines Derivates 22 ausgehend von L-Rhamnose (16) übernommen, wobei zudem eine Strategie zur selektiven Schützung und Integration eines Linkers zum Pyrrol entwickelt wurde. Über diese Route können sämtliche Zucker als Ausgangsmaterial zu Derivatsynthese genutzt werden. Die drei Fragmente 17, 21 und 24 können in Anlehnung an die Erstsynthese zu Kibdelomycin (25) verknüpft werden.

Supplementary Material 1

Die Riesen-Wollbiene (Anthidium septemspinosum) wurde aktuell an 16 Fundorten in der Oberrheinebene zwischen Munchhausen und Erstein gefunden. Die Art besiedelt hier Feuchtwiesen und trockene Kiesflächen, oftmals angrenzend an wechselfeuchtes Grünland und Grünland angrenzend an eine Siedlung. Die Hauptflug- und Beobachtungszeit der Art liegt Anfang Juli bis Mitte August etwa zur Blütezeit des Weidenblättrigen Alants (Inula salicina). Aufgrund des anhaltenden Rückgangs geeigneter Lebensräume und des kleinen und isolierten besiedelten Areals halten wir die Art für hochgradig bedroht. Auf die große und auffällige Wildbiene sollte bei dem Besuch von Feuchtwiesen besonders geachtet werden.

Auch 2013 konnten wieder neue Naturschutzgebiete im Regierungsbezirk Karlsruhe ausgewiesen werden: Das NSG „Streuobstwiesen Kleingemünd“ ist geprägt durch einen teilweise sehr alten, 16 Hektar großen Obstbaumbestand mit einem reichen Angebot an Baumhöhlen und mulmigen Stammabschnitten sowie das Fehlen intensiver Nutzungen. Sie zeichnen sich durch das Vorkommen einer vom Aussterben bedrohten Insektenart – des Körnerbocks Megopis scabricornis – und weiterer in Baden-Württemberg gefährdeter Tierarten aus, darunter der Wendehals (Jynx torquilla), der Kleine Abendsegler (Nyctalus leisleri), das Große Mausohr (Myotis myotis), die Breitflügel-Fledermaus (Eptesicus serotinus) sowie die Sumpfschrecke (Stethophyma grossum). Damit erfüllt das Gebiet die naturschutzfachlichen Kriterien eines landesweit bedeutsamen Naturschutzgebietes. Über die aktuellen Artvorkommen hinaus hat das Gebiet überregionale Bedeutung als Trittsteinbiotop für wandernde Arten und für Arten, deren Verbreitungsareal sich aktuell auf Grund des Klimawandels verschiebt. Seine Gefährdung liegt im Wegfall oder der Intensivierung der Mahd und der Zunahme privater Nutzungen. Das NSG „Sauersbosch, Pfrimmersbach- und Märzenbachtal“ blickt auf eine bewegte Kulturgeschichte zurück und ist eng mit der Gründung der Zisterzienserinnen- Abtei des Klosters Lichtental im Jahr 1245 verbunden. Drei Bachtäler prägen das Gebiet, die überregional bedeutende Lebensräume, Pflanzen- und Tierarten aufweisen. Herausragend sind die großflächigen Grünlandbiotope in sehr gutem Zustand. Diese sind ausgebildet als Borstgrasrasen, Pfeifengras-Wiesen und Magerwiesen bzw. -weiden mittlerer Standorte sowie die verschiedenen Offenlandbiotope feuchter bis nasser Standorte, insbesondere Nasswiesen, Kleinseggenriede basenarmer Standorte und Waldsimsen- Sümpfe. Als Besonderheit kommt die Stein-Zwenke (Brachypodium sylvestre) als dealpine Art im Gebiet häufig vor. 25 Brutvogel-, sieben Fledermaus-, 71 Wildbienen-, 23 Heuschrecken- und 31 Tagfalter- und Widderchen- Arten zeichnen das Gebiet aus. Faunistisch bedeutend sind insbesondere die Fledermäuse mit der Bechstein-Fledermaus (Myotis bechsteinii), die Tagfalter mit dem letzten Vorkommen des Goldenen Scheckenfalters (Euphydryas aurinia) im Regierungsbezirk Karlsruhe und die Baumsaft-Schwebfliege Brachyopa bimaculosa, die weltweit erstmals aus dem Gebiet beschrieben wurde. Das Gebiet hat eine sehr große Bedeutung für die Bewahrung der Artenvielfalt und Lebensräume in sehr hoher Qualität und ist ein Musterbeispiel für die Schönheit und Eigenart einer durch Wiesen geprägten Kulturlandschaft.

Die Lösslandschaft des Kaiserstuhls ist geprägt von Terrassen und Böschungen. Die vorliegende Untersuchung versucht, anhand der Kulturgeschichte die Anfänge der Terrassierung zu klären. Diese reichen wahrscheinlich in die fränkische Zeit zurück, markiert durch die erstmalige urkundliche Erwähnung des Weinbaus im Jahr 769 n. Chr. Mit Hilfe des digitalen Geländemodells konnte berechnet werden, dass rund 322 ha historische Terrassen heute mit Wald und rund 29 ha mit Magerrasen bewachsen sind. Die Terrassenlandschaft war früher wesentlich ausgedehnter als heute, wenngleich rund 73 % aller heute bewaldeten Terrassen überwiegend auf klimatisch begünstigten, südlichen und westlichen Hanglagen angelegt wurden. Anhand der kulturgeschichtlichen Daten und dem Alter der Bäume konnte gezeigt werden, dass die Nutzungsaufgabe und Wiederbewaldung mit verschiedenen Kriegsereignissen und dem daraus abgeleiteten Mangel an Arbeitskräften zusammenhängen dürfte. Auf den Terrassen hat sich ein Wald entwickelt, in dem 16 Baumarten erfasst werden konnten. Die Rotbuche dominiert die Bestände. Neben der Robinie sind Esche und Bergahorn besonders häufig, welche auch die meisten Exemplare mit großem Brusthöhendurchmesser stellen. Nach einem zu erwartenden starken Rückgang der Esche durch das Eschentriebsterben ist künftig mit einer weiteren Zunahme der Rotbuche zu rechnen. Der Kaiserstuhl ist ein herausragendes Beispiel für eine terrassierte Kulturlandschaft in Baden-Württemberg.

Supplementary Material 2

During the third all-sky survey (eRASS3), eROSITA, the soft X-ray instrument aboard Spectrum-Roentgen-Gamma, detected a new hard X-ray transient, eRASSt J040515.6-745202, in the direction of the Magellanic Bridge. We arranged follow-up observations and searched for archival data to reveal the nature of the transient. Using X-ray observations with XMM-Newton, NICER, and Swift, we investigated the temporal and spectral behaviour of the source for over about 10 days. The X-ray light curve obtained from the XMM-Newton observation with an 28 ks exposure revealed a type-I X-ray burst with a peak bolometric luminosity of at least 1.4e37 erg/s. The burst energetics are consistent with a location of the burster at the distance of the Magellanic Bridge. The relatively long exponential decay time of the burst of 70 s indicates that it ignited in a H-rich environment. The non-detection of the source during the other eROSITA surveys, twelve and six months before and six months after eRASS3, suggests that the burst was discovered during a moderate outburst which reached 2.6e36 erg/s in persistent emission. During the NICER observations, the source showed alternating flux states with the high level at a similar brightness as during the XMM-Newton observation. This behaviour is likely caused by dips as also seen during the last hour of the XMM-Newton observation. Evidence for a recurrence of the dips with a period of 21.8 hr suggests eRASSt J040515.6-745202 is a low-mass X-ray binary (LMXB) system with an accretion disk seen nearly edge on. We identify a multi-wavelength counterpart to the X-ray source in UVW1 and g, r, i, and z images obtained by the optical/UV monitor on XMM-Newton and the Dark Energy Camera at the Cerro Tololo Inter-American Observatory. (abbreviated), Comment: Accepted for publication in Astronomy & Astrophysics. 10 pages, 13 figures

Gemäß dem bayerischen LehrplanPLUS soll schon in der Grundschule „ein Verständnis für den Wahrscheinlichkeitsbegriff angebahnt“ werden (Bayerisches Staatsministerium für Bildung und Kultus, Wissenschaft und Kunst, 2014, S. 109). Bereits bei recht einfach zu verstehenden Aufgabenstellungen zur Wahrscheinlichkeit werden jedoch auch von älteren Schüler*innen oder Erwachsenen noch Antworten gegeben, die mathematisch nicht korrekt sind, sondern auf Intuitionen, mentalen Vorstellungen oder Ansätzen beruhen, die im jeweiligen Kontext mathematisch nicht tragfähig sind (z. B. Falk, 1979; Fishbein, 1997; Lecoutre, 1992; Rolfes & Fahse, 2019). Im Folgenden werden diese als intuitive Vorstellungen bezeichnet.