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Abstract A process for the production of tens to hundreds of GBq amounts of zirconium-88 (88Zr) using proton beams on yttrium was developed. For this purpose, yttrium metal targets (≈20 g) were irradiated in a ~16 to 34 MeV proton beam at a beam current of 100–200 µA at the Los Alamos Isotope Production Facility (IPF). The 88Zr radionuclide was produced and separated from the yttrium targets using hydroxamate resin with an elution yield of 94(5)% (1σ). Liquid DCl solution in D2O was selected as a suitable 88Zr sample matrix due to the high neutron transmission of deuterium compared to hydrogen and an even distribution of 88Zr in the sample matrix. The separated 88Zr was dissolved in DCl and 8 µL of the obtained solution was transferred to a tungsten sample can with a 1.2 mm diameter hole using a syringe and automated filling station inside a hot cell. Neutron transmission of the obtained 88Zr sample was measured at the Device for Indirect Capture Experiments on Radionuclides (DICER).

Abstract 1D spin-wave conduits are envisioned as nanoscale components of magnonics-based logic and computing schemes for future generation electronics. À-la-carte methods of versatile control of the local magnetization dynamics in such nanochannels are highly desired for efficient steering of the spin waves in magnonic devices. Here, we present a study of localized dynamical modes in 1- $$\upmu$$ μ m -wide permalloy conduits probed by microresonator ferromagnetic resonance technique. We clearly observe the lowest-energy edge mode in the microstrip after its edges were finely trimmed by means of focused Ne $$^+$$ + ion irradiation. Furthermore, after milling the microstrip along its long axis by focused ion beams, creating consecutively $$\sim$$ ∼ 50 and $$\sim$$ ∼ 100 nm gaps, additional resonances emerge and are attributed to modes localized at the inner edges of the separated strips. To visualize the mode distribution, spatially resolved Brillouin light scattering microscopy was used showing an excellent agreement with the ferromagnetic resonance data and confirming the mode localization at the outer/inner edges of the strips depending on the magnitude of the applied magnetic field. Micromagnetic simulations confirm that the lowest-energy modes are localized within $$\sim$$ ∼ 15-nm-wide regions at the edges of the strips and their frequencies can be tuned in a wide range (up to 5 GHz) by changing the magnetostatic coupling (i.e., spatial separation) between the microstrips.

Abstract The ferromagnetic resonance of a disordered A2 Fe60Al40 ferromagnetic stripe, of dimensions 5 µm × 1 µm × 32 nm, has been observed in two vastly differing surroundings: in the first case, the ferromagnetic region was surrounded by ordered B2 Fe60Al40, and in the second case it was free standing, adhering only to the oxide substrate. The embedded ferromagnet possesses a periodic magnetic domain structure, which transforms to a single domain structure in the freestanding case. The two cases differ in their dynamic response, for instance, the resonance field for the uniform (k = 0) mode at ~ 14 GHz excitation displays a shift from 209 to 194 mT, respectively for the embedded and freestanding cases, with the external magnetic field applied along the long axis. The resonant behavior of a microscopic ferromagnet can thus be finely tailored via control of its near-interfacial surrounding.

Abstract Listeria monocytogenes is a food-borne pathogen that can grow at very low temperatures close to the freezing point of food and other matrices. Maintaining cytoplasmic membrane fluidity by changing its lipid composition is indispensable for growth at low temperatures. Its dominant adaptation is to shorten the fatty acid chain length and, in some strains, increase in addition the menaquinone content. To date, incorporation of exogenous fatty acid was not reported for Listeria monocytogenes. In this study, the membrane fluidity grown under low-temperature conditions was affected by exogenous fatty acids incorporated into the membrane phospholipids of the bacterium. Listeria monocytogenes incorporated exogenous fatty acids due to their availability irrespective of their melting points. Incorporation was demonstrated by supplementation of the growth medium with polysorbate 60, polysorbate 80, and food lipid extracts, resulting in a corresponding modification of the membrane fatty acid profile. Incorporated exogenous fatty acids had a clear impact on the fitness of the Listeria monocytogenes strains, which was demonstrated by analyses of the membrane fluidity, resistance to freeze-thaw stress, and growth rates. The fatty acid content of the growth medium or the food matrix affects the membrane fluidity and thus proliferation and persistence of Listeria monocytogenes in food under low-temperature conditions.

Abstract Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease which affects primarily the joints. Peptides of several proteins have shown an effect in some experimental animal models of RA. We investigated arthritis development in male DBA/1 mice which were injected with bovine collagen II (bCII) and human fibrinogen (hFib) on days 0 and 21, leading to stable and reproducible disease induction in 100% of immunized mice (FIA-CIA). In a second study, two bCII—derived peptides were given three times in the course of 6 weeks after FIA-CIA induction to test for impact on arthritis. Mice were scored weekly for arthritis and anti-citrullinated peptide antibodies (ACPAs) were determined in the sera taken on days 0, 14, 35, 56 and 84. Histology of the hind paws was performed at the end of the experiment. Intravenous administration of peptide 90578, a novel fructosylated peptide derived from the immunodominant T cell epitope of bCII, at a dosage of 1 mg/kg resulted in significant beneficial effects on clinical outcome parameters and on the arthritis histology scores which was sustained over 12 weeks. Survival tended to be improved in peptide 90578-treated mice. Intravenous administration of pure soluble peptide 90578 without adjuvants is a promising approach to treat RA, with treatment starting at a time when ACPAs are already present. The results complement existing data on peptide “vaccination” of healthy animals, or on treatment using recombinant peptide expressing virus or complex biological compounds.

Genome-wide association (GWA) studies have identified 19 independent common risk loci for endometriosis. Most of the GWA variants are non-coding and the genes responsible for the association signals have not been identified. Herein, we aimed to assess the potential role of protein-modifying variants in endometriosis using exome-array genotyping in 7164 cases and 21005 controls, and a replication set of 1840 cases and 129016 controls of European ancestry. Results in the discovery sample identified significant evidence for association with coding variants in single-variant (rs1801232-CUBN) and gene-level (CIITA and PARP4) meta-analyses, but these did not survive replication. In the combined analysis, there was genome-wide significant evidence for rs13394619 (P = 2.3 × 10-9) in GREB1 at 2p25.1 - a locus previously identified in a GWA meta-analysis of European and Japanese samples. Despite sufficient power, our results did not identify any protein-modifying variants (MAF > 0.01) with moderate or large effect sizes in endometriosis, although these variants may exist in non-European populations or in high-risk families. The results suggest continued discovery efforts should focus on genotyping large numbers of surgically-confirmed endometriosis cases and controls, and/or sequencing high-risk families to identify novel rare variants to provide greater insights into the molecular pathogenesis of the disease.

Abstract Comparison studies using histopathology as standard of reference enable a validation of the diagnostic performance of imaging methods. This study analysed (1) the impact of different image-histopathology co-registration pathways, (2) the impact of the applied data analysis method and (3) intraindividually compared multiparametric magnet resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET) by using the different approaches. Ten patients with primary PCa who underwent mpMRI and [18F]PSMA-1007 PET/CT followed by prostatectomy were prospectively enrolled. We demonstrate that the choice of the intermediate registration step [(1) via ex-vivo CT or (2) mpMRI] does not significantly affect the performance of the registration framework. Comparison of analysis methods revealed that methods using high spatial resolutions e.g. quadrant-based slice-by-slice analysis are beneficial for a differentiated analysis of performance, compared to methods with a lower resolution (segment-based analysis with 6 or 18 segments and lesions-based analysis). Furthermore, PSMA-PET outperformed mpMRI for intraprostatic PCa detection in terms of sensitivity (median %: 83–85 vs. 60–69, p

Abstract A new method has been developed for the isolation of 223,224,225Ra, in high yield and purity, from a proton irradiated 232Th matrix. Herein we report an all-aqueous process using multiple solid-supported adsorption steps including a citrate chelation method developed to remove >99.9% of the barium contaminants by activity from the final radium product. A procedure involving the use of three columns in succession was developed, and the separation of 223,224,225Ra from the thorium matrix was obtained with an overall recovery yield of 91 ± 3%, average radiochemical purity of 99.9%, and production yields that correspond to physical yields based on previously measured excitation functions.