Abundance analysis for long-period variables II. RGB and AGB stars in the globular cluster 47\,Tuc

Asymptotic giant branch (AGB) stars play a key role in the enrichment of galaxies with heavy elements. Due to their large amplitude variability, the measurement of elemental abundances is a highly challenging task that has not been solved in a satisfactory way yet. Following our previous work we use hydrostatic and dynamical model atmospheres to simulate observed high-resolution near-infrared spectra of 12 variable and non-variable red giants in the globular cluster 47 Tuc. The 47 Tuc red giants are independently well-characterized in important parameters (mass, metallicity, luminosity). The principal aim was to compare synthetic spectra based on the dynamical models with observational spectra of 47 Tuc variables. Assuming that the abundances are unchanged on the upper giant branch in these low-mass stars, our goal is to estimate the impact of atmospheric dynamics on the abundance determination. We present new measurements of the C/O and 12C/13C ratio for 5 non-variable red giants in 47Tuc. The equivalent widths measured for our 7 variable stars strongly differ from the non-variable stars and cannot be reproduced by either hydrostatic or dynamical model atmospheres. Nevertheless, the dynamical models fit the observed spectra of long-period variables much better than any hydrostatic model. For some spectral features, the variations in the line intensities predicted by dynamical models over a pulsation cycle give similar values as a sequence of hydrostatic models with varying temperature and constant surface gravity.Comment: 16 pages, 12 figures; accepted for publication in A&

Autowaves in a dc complex plasma confined behind a de Laval nozzle

Experiments to explore stability conditions and topology of a dense microparticle cloud supported against gravity by a gas flow were carried out. By using a nozzle shaped glass insert within the glass tube of a dc discharge plasma chamber a weakly ionized gas flow through a de Laval nozzle was produced. The experiments were performed using neon gas at a pressure of 100 Pa and melamine-formaldehyde particles with a diameter of 3.43 {\mu}m. The capturing and stable global confining of the particles behind the nozzle in the plasma were demonstrated. The particles inside the cloud behaved as a single convection cell inhomogeneously structured along the nozzle axis in a tube-like manner. The pulsed acceleration localized in the very head of the cloud mediated by collective plasma-particle interactions and the resulting wave pattern were studied in detail.Comment: 6 pages, 4 figure

τBu₂SiF-Derivatized D₂-Receptor Ligands: The First SiFA-Containing Small Molecule Radiotracers for Target-Specific PET-Imaging

The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D-2-receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules such as receptor-ligands, is the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA-conjugates derivatized either directly at the benzoic acid ring system (SiFA-DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested their receptor affinities. We found D2-receptor affinities for all compounds in the nanomolar range (Ki(SiFA-DMFP) = 13.6 nM, Ki(SiFA-FP) = 33.0 nM, Ki(SiFA-DDMFP) = 62.7 nM and Ki(SiFA-M-FP) = 4.21 nM). The radiofluorination showed highest yields when 10 nmol of the precursors were reacted with F-18]fluoride/TBAHCO(3) in acetonitrile. After a reversed phased cartridge purification the desired products could be isolated as an injectable solution after only 10 min synthesis time with radiochemical yields (RCY) of more than 40% in the case of SiFA-DMFP resulting in specific activities >41 GBq/mu mol (>1,100 Ci/mmol). Furthermore, the radiolabeled products were shown to be stable in the injectable solutions, as well as in human plasma, for at least 90 min

A close halo of large transparent grains around extreme red giant stars

Intermediate-mass stars end their lives by ejecting the bulk of their envelope via a slow dense wind back into the interstellar medium, to form the next generation of stars and planets. Stellar pulsations are thought to elevate gas to an altitude cool enough for the condensation of dust, which is then accelerated by radiation pressure from starlight, entraining the gas and driving the wind. However accounting for the mass loss has been a problem due to the difficulty in observing tenuous gas and dust tens of milliarcseconds from the star, and there is accordingly no consensus on the way sufficient momentum is transferred from the starlight to the outflow. Here, we present spatially-resolved, multi-wavelength observations of circumstellar dust shells of three stars on the asymptotic giant branch of the HR diagram. When imaged in scattered light, dust shells were found at remarkably small radii (<~ 2 stellar radii) and with unexpectedly large grains (~300 nm radius). This proximity to the photosphere argues for dust species that are transparent to starlight and therefore resistant to sublimation by the intense radiation field. While transparency usually implies insufficient radiative pressure to drive a wind, the radiation field can accelerate these large grains via photon scattering rather than absorption - a plausible mass-loss mechanism for lower-amplitude pulsating stars.Comment: 13 pages, 1 table, 6 figure

Active surveillance inclusion criteria under scrutiny in magnetic resonance imaging-guided prostate biopsy : a multicenter cohort study

Background Although multiparametric magnetic resonance imaging (mpMRI) is recommended for primary risk stratification and follow-up in Active Surveillance (AS), it is not part of common AS inclusion criteria. The objective was to compare AS eligibility by systematic biopsy (SB) and combined MRI-targeted (MRI-TB) and SB within real-world data using current AS guidelines. Methods A retrospective multicenter study was conducted by a German prostate cancer (PCa) working group representing six tertiary referral centers and one outpatient practice. Men with PCa and at least one MRI-visible lesion according to Prostate Imaging Reporting and Data System (PI-RADS) v2 were included. Twenty different AS inclusion criteria of international guidelines were applied to calculate AS eligibility using either a SB or a combined MRI-TB and SB. Reasons for AS exclusion were assessed. Results Of 1941 patients with PCa, per guideline, 583–1112 patients with PCa in both MRI-TB and SB were available for analysis. Using SB, a median of 22.1% (range 6.4–72.4%) were eligible for AS. Using the combined approach, a median of 15% (range 1.7–68.3%) were eligible for AS. Addition of MRI-TB led to a 32.1% reduction of suitable patients. Besides Gleason Score upgrading, the maximum number of positive cores were the most frequent exclusion criterion. Variability in MRI and biopsy protocols potentially limit the results. Conclusions Only a moderate number of patients with PCa can be monitored by AS to defer active treatment using current guidelines for inclusion in a real-world setting. By an additional MRI-TB, this number is markedly reduced. These results underline the need for a contemporary adjustment of AS inclusion criteria

Synthesis and biological evaluation of novel MB327 analogs as resensitizers for desensitized nicotinic acetylcholine receptors after intoxication with nerve agents

Poisoning with organophosphorus compounds, which can lead to a cholinergic crisis due to the inhibition of acetylcholinesterase and the subsequent accumulation of acetylcholine (ACh) in the synaptic cleft, is a serious problem for which treatment options are currently insufficient. Our approach to broadening the therapeutic spectrum is to use agents that interact directly with desensitized nicotinic acetylcholine receptors (nAChRs) in order to induce functional recovery after ACh overstimulation. Although MB327, one of the most prominent compounds investigated in this context, has already shown positive properties in terms of muscle force recovery, this compound is not suitable for use as a therapeutic agent due to its insufficient potency. By means of in silico studies based on our recently presented allosteric binding pocket at the nAChR, i.e. the MB327-PAM-1 binding site, three promising MB327 analogs with a 4-aminopyridinium ion partial structure (PTM0056, PTM0062, and PTM0063) were identified. In this study, we present the synthesis and biological evaluation of a series of new analogs of the aforementioned compounds with a 4-aminopyridinium ion partial structure (PTM0064-PTM0072), as well as hydroxy-substituted analogs of MB327 (PTMD90–0012 and PTMD90–0015) designed to substitute entropically unfavorable water clusters identified during molecular dynamics simulations. The compounds were characterized in terms of their binding affinity towards the aforementioned binding site by applying the UNC0642 MS Binding Assays and in terms of their muscle force reactivation in rat diaphragm myography. More potent compounds were identified compared to MB327, as some of them showed a higher affinity towards MB327-PAM-1 and also a higher recovery of neuromuscular transmission at lower compound concentrations. To improve the treatment of organophosphate poisoning, direct targeting of nAChRs with appropriate compounds is a key step, and this study is an important contribution to this research

Azidobupramine, an Antidepressant-Derived Bifunctional Neurotransmitter Transporter Ligand Allowing Covalent Labeling and Attachment of Fluorophores

The aim of this study was to design, synthesize and validate a multifunctional antidepressant probe that is modified at two distinct positions. The purpose of these modifications was to allow covalent linkage of the probe to interaction partners, and decoration of probe-target complexes with fluorescent reporter molecules. The strategy for the design of such a probe (i.e., azidobupramine) was guided by the need for the introduction of additional functional groups, conveying the required properties while keeping the additional moieties as small as possible. This should minimize the risk of changing antidepressant-like properties of the new probe azidobupramine. To control for this, we evaluated the binding parameters of azidobupramine to known target sites such as the transporters for serotonin (SERT), norepinephrine (NET), and dopamine (DAT). The binding affinities of azidobupramine to SERT, NET, and DAT were in the range of structurally related and clinically active antidepressants. Furthermore, we successfully visualized azidobupramine-SERT complexes not only in SERT-enriched protein material but also in living cells stably overexpressing SERT. To our knowledge, azidobupramine is the first structural analogue of a tricyclic antidepressant that can be covalently linked to target structures and further attached to reporter molecules while preserving antidepressant-like properties and avoiding radioactive isotopes

Monoprophylaxis With Cephalosporins for Transrectal Prostate Biopsy After the Fluoroquinolone-Era: A Multi-Institutional Comparison of Severe Infectious Complications

BackgroundTo compare severe infectious complication rates after transrectal prostate biopsies between cephalosporins and fluoroquinolones for antibiotic monoprophylaxis.Material and MethodsIn the multi-institutional cohort, between November 2014 and July 2020 patients received either cefotaxime (single dose intravenously), cefpodoxime (multiple doses orally) or fluoroquinolones (multiple-doses orally or single dose intravenously) for transrectal prostate biopsy prophylaxis. Data were prospectively acquired and retrospectively analyzed. Severe infectious complications were evaluated within 30 days after biopsy. Logistic regression models predicted biopsy-related infectious complications according to antibiotic prophylaxis, application type and patient- and procedure-related risk factors.ResultsOf 793 patients, 132 (16.6%) received a single dose of intravenous cefotaxime and were compared to 119 (15%) who received multiple doses of oral cefpodoxime and 542 (68.3%) who received fluoroquinolones as monoprophylaxis. The overall incidence of severe infectious complications was 1.0% (n=8). No significant differences were observed between the three compared groups (0.8% vs. 0.8% vs. 1.1%, p=0.9). The overall rate of urosepsis was 0.3% and did not significantly differ between the three compared groups as well.ConclusionMonoprophylaxis with third generation cephalosporins was efficient in preventing severe infectious complications after prostate biopsy. Single intravenous dose of cefotaxime and multiday regimen of oral cefpodoxime showed a low incidence of infectious complications &lt;1%. No differences were observed in comparison to fluoroquinolones

The propagation of uncertainties in stellar population synthesis modeling III: model calibration, comparison, and evaluation

Stellar population synthesis (SPS) provides the link between the stellar and dust content of galaxies and their observed spectral energy distributions. In the present work we perform a comprehensive calibration of our own flexible SPS (FSPS) model against a suite of data. Several public SPS models are intercompared, including the models of Bruzual & Charlot (BC03), Maraston (M05) and FSPS. The relative strengths and weaknesses of these models are evaluated, with the following conclusions: 1) The FSPS and BC03 models compare favorably with MC data at all ages, whereas M05 colors are too red and the age-dependence is incorrect; 2) All models yield similar optical and near-IR colors for old metal-poor systems, and yet they all provide poor fits to the integrated J-K and V-K colors of both MW and M31 star clusters; 4) All models predict ugr colors too red, D4000 strengths too strong and Hdelta strengths too weak compared to massive red sequence galaxies, under the assumption that such galaxies are composed solely of old metal-rich stars; 5) FSPS and, to a lesser extent, BC03 can reproduce the optical and near-IR colors of post-starburst galaxies, while M05 cannot. Reasons for these discrepancies are explored. The failure at predicting the ugr colors, D4000, and Hdelta strengths can be explained by some combination of a minority population of metal-poor stars, young stars, blue straggler and/or blue horizontal branch stars, but not by appealing to inadequacies in either theoretical stellar atmospheres or canonical evolutionary phases (e.g., the main sequence turn-off). We emphasize that due to a lack of calibrating star cluster data in regions of the metallicity-age plane relevant for galaxies, all of these models continue to suffer from serious uncertainties that are difficult to quantify. (ABRIDGED)Comment: 26 pages, 16 figures, submitted to ApJ. The FSPS code can be downloaded at http://www.astro.princeton.edu/~cconroy/SPS