Excited-State Half-Lives in

The known I^{π}=8_{1}^{+}, E_{x}=2129-keV isomer in the semimagic nucleus ^{130}Cd_{82} was populated in the projectile fission of a ^{238}U beam at the Radioactive Isotope Beam Factory at RIKEN. The high counting statistics of the accumulated data allowed us to determine the excitation energy, E_{x}=2001.2(7) keV, and half-life, T_{1/2}=57(3) ns, of the I^{π}=6_{1}^{+} state based on γγ coincidence information. Furthermore, the half-life of the 8_{1}^{+} state, T_{1/2}=224(4) ns, was remeasured with high precision. The new experimental information, combined with available data for ^{134}Sn and large-scale shell model calculations, allowed us to extract proton and neutron effective charges for ^{132}Sn, a doubly magic nucleus far-off stability. A comparison to analogous information for ^{100}Sn provides first reliable information regarding the isospin dependence of the isoscalar and isovector effective charges in heavy nuclei.

Microbial dysbiosis in a mouse model of atopic dermatitis mimics shifts in human microbiome and correlates with the key pro-inflammatory cytokines IL-4, IL-33 and TSLP.

BACKGROUND: Cutaneous bacterial dysbiosis is a characteristic hallmark of atopic dermatitis (AD), and it decisively influences the severity of the disease. Despite this, frequently used murine models of AD have not been characterized regarding the changes in skin microbiome communities. OBJECTIVE: To analyse the skin microbiome of two frequently used murine models for AD for assessing their applicability in translational research. METHODS: AD was induced in mice by topical application of calcipotriol or oxazolone. Following comparable elicitation of AD-like dermatitis, including IgE induction, the skin microbial communities were analysed and compared with human AD. RESULTS: We detected critical differences in the microbiota composition of diseased skin. In contrast to calcipotriol treatment, application of oxazolone induced significant changes in the cutaneous microbiota and a drastic drop of bacterial richness. Furthermore, an expansion of Staphylococci, particularly S. xylosus, was observed in the oxazolone group, also displaying positive correlations with AD key markers including pH, TEWL, IL-4, TSLP and IL-33. CONCLUSIONS: In this article, we show that (a) the model of choice to investigate AD needs to be characterized for the cutaneous microbiota if applicable and (b) the oxazolone-mediated mixed Th1-Th2 immune response triggers microbiota-induced alterations which share similarities to dysbiosis in human AD and represents therefore a suitable model for translational research on AD if alterations of the microbiome are in the focus of the investigation.

Improved Value for the Gamow-Teller Strength of the

A record number of ^{100}Sn nuclei was detected and new isotopic species toward the proton dripline were discovered at the RIKEN Nishina Center. Decay spectroscopy was performed with the high-efficiency detector arrays WAS3ABi and EURICA. Both the half-life and the ß-decay end point energy of ^{100}Sn were measured more precisely than the literature values. The value and the uncertainty of the resulting strength for the pure 0^{+}→1^{+} Gamow-Teller decay was improved to B_{GT}=4.4_{-0.7}^{+0.9}. A discrimination between different model calculations was possible for the first time, and the level scheme of ^{100}In is investigated further.

[Histopathological research laboratories in translational research : Conception and integration into the infrastructure of pathological institutes]. / Histopathologische Forschungslabors in der translationalen Forschung : Konzeption sowie Integration in die Infrastruktur pathologischer Institute.

A systematic review of histopathology from experimental animal systems is an essential part of up-to-date biomedical research. Pathologists at university hospitals are especially and increasingly challenged by these specialized and time-consuming duties. This article presents and analyzes a new laboratory structure of comparative experimental pathology-jointly lead by veterinary and human pathologists-which might solve this problem. The focus is on the establishment and full integration of this laboratory structure into a local, regional, and nationwide biomedical research cluster. A detailed comparison with an established structure of routine histopathology laboratories discusses merits and benefits as well as disadvantages.

Superallowed Gamow-Teller decay of the doubly magic nucleus 100Sn.

The shell structure of atomic nuclei is associated with 'magic numbers' and originates in the nearly independent motion of neutrons and protons in a mean potential generated by all nucleons. During ß(+)-decay, a proton transforms into a neutron in a previously not fully occupied orbital, emitting a positron-neutrino pair with either parallel or antiparallel spins, in a Gamow-Teller or Fermi transition, respectively. The transition probability, or strength, of a Gamow-Teller transition depends sensitively on the underlying shell structure and is usually distributed among many states in the neighbouring nucleus. Here we report measurements of the half-life and decay energy for the decay of (100)Sn, the heaviest doubly magic nucleus with equal numbers of protons and neutrons. In the ß-decay of (100)Sn, a large fraction of the strength is observable because of the large decay energy. We determine the largest Gamow-Teller strength so far measured in allowed nuclear ß-decay, establishing the 'superallowed' nature of this Gamow-Teller transition. The large strength and the low-energy states in the daughter nucleus, (100)In, are well reproduced by modern, large-scale shell model calculations.

New Isotopes and Proton Emitters-Crossing the Drip Line in the Vicinity of

Several new isotopes, ^{96}In, ^{94}Cd, ^{92}Ag, and ^{90}Pd, have been identified at the RIKEN Nishina Center. The study of proton drip-line nuclei in the vicinity of ^{100}Sn led to the discovery of new proton emitters ^{93}Ag and ^{89}Rh with half-lives in the submicrosecond range. The systematics of the half-lives of odd-Z nuclei with T_{z}=-1/2 toward ^{99}Sn shows a stabilizing effect of the Z=50 shell closure. Production cross sections for nuclei in the vicinity of ^{100}Sn measured at different energies and target thicknesses were compared to the cross sections calculated by epax taking into account contributions of secondary reactions in the primary target.

ß-Decay Half-Lives of 110 Neutron-Rich Nuclei across the N=82 Shell Gap: Implications for the Mechanism and Universality of the Astrophysical r Process.

The ß-decay half-lives of 110 neutron-rich isotopes of the elements from _{37}Rb to _{50}Sn were measured at the Radioactive Isotope Beam Factory. The 40 new half-lives follow robust systematics and highlight the persistence of shell effects. The new data have direct implications for r-process calculations and reinforce the notion that the second (A≈130) and the rare-earth-element (A≈160) abundance peaks may result from the freeze-out of an (n,γ)⇄(γ,n) equilibrium. In such an equilibrium, the new half-lives are important factors determining the abundance of rare-earth elements, and allow for a more reliable discussion of the r process universality. It is anticipated that universality may not extend to the elements Sn, Sb, I, and Cs, making the detection of these elements in metal-poor stars of the utmost importance to determine the exact conditions of individual r-process events.

Yrast 6⁺ seniority isomers of (136,138)Sn.

Delayed γ-ray cascades, originating from the decay of (6⁺) isomeric states, in the very neutron-rich, semimagic isotopes (136,138)Sn have been observed following the projectile fission of a ²³8U beam at RIBF, RIKEN. The wave functions of these isomeric states are proposed to be predominantly a fully aligned pair of f(7/2) neutrons. Shell-model calculations, performed using a realistic effective interaction, reproduce well the energies of the excited states of these nuclei and the measured transition rates, with the exception of the B(E2;6⁺→4⁺) rate of ¹³6Sn, which deviates from a simple seniority scheme. Empirically reducing the νf(7/2)(2) orbit matrix elements produces a 41⁺ state with almost equal seniority 2 and 4 components, correctly reproducing the experimental B(E2;6⁺→4⁺) rate of ¹³6Sn. These data provide a key benchmark for shell-model interactions far from stability.

Monopole-driven shell evolution below the doubly magic nucleus 132Sn explored with the long-lived isomer in 126Pd.

A new isomer with a half-life of 23.0(8) ms has been identified at 2406 keV in (126)Pd and is proposed to have a spin and parity of 10(+) with a maximally aligned configuration comprising two neutron holes in the 1h(11/2) orbit. In addition to an internal-decay branch through a hindered electric octupole transition, ß decay from the long-lived isomer was observed to populate excited states at high spins in (126)Ag. The smaller energy difference between the 10(+) and 7(-) isomers in (126)Pd than in the heavier N=80 isotones can be interpreted as being ascribed to the monopole shift of the 1h(11/2) neutron orbit. The effects of the monopole interaction on the evolution of single-neutron energies below (132)Sn are discussed in terms of the central and tensor forces.

1p3/2 proton-hole state in 132Sn and the shell structure along N = 82.

A low-lying state in 131In82, the one-proton hole nucleus with respect to double magic 132Sn, was observed by its γ decay to the Iπ=1/2- ß-emitting isomer. We identify the new state at an excitation energy of Ex=1353 keV, which was populated both in the ß decay of 131Cd83 and after ß-delayed neutron emission from 132Cd84, as the previously unknown πp3/2 single-hole state with respect to the 132Sn core. Exploiting this crucial new experimental information, shell-model calculations were performed to study the structure of experimentally inaccessible N=82 isotones below 132Sn. The results evidence a surprising absence of proton subshell closures along the chain of N=82 isotones. The consequences of this finding for the evolution of the N=82 shell gap along the r-process path are discussed.

Isomers in 128Pd and 126Pd: evidence for a robust shell closure at the neutron magic number 82 in exotic palladium isotopes.

The level structures of the very neutron-rich nuclei 128Pd and 126Pd have been investigated for the first time. In the r-process waiting-point nucleus 128Pd, a new isomer with a half-life of 5.8(8) µs is proposed to have a spin and parity of 8(+) and is associated with a maximally aligned configuration arising from the g(9/2) proton subshell with seniority υ=2. For 126Pd, two new isomers have been identified with half-lives of 0.33(4) and 0.44(3) µs. The yrast 2(+) energy is much higher in 128Pd than in 126Pd, while the level sequence below the 8(+) isomer in 128Pd is similar to that in the N=82 isotone 130Cd. The electric quadrupole transition that depopulates the 8(+) isomer in 128Pd is more hindered than the corresponding transition in 130Cd, as expected in the seniority scheme for a semimagic, spherical nucleus. These experimental findings indicate that the shell closure at the neutron number N=82 is fairly robust in the neutron-rich Pd isotopes.

Well developed deformation in 42Si.

Excited states in (38,40,42) Si nuclei have been studied via in-beam γ-ray spectroscopy with multinucleon removal reactions. Intense radioactive beams of ^{40}S and (44)S provided at the new facility of the RIKEN Radioactive Isotope Beam Factory enabled γ-γ coincidence measurements. A prominent γ line observed with an energy of 742(8) keV in (42) Si confirms the 2(+) state reported in an earlier study. Among the γ lines observed in coincidence with the 2^{+} → 0+ transition, the most probable candidate for the transition from the yrast 4(+) state was identified, leading to a 4(1)+) energy of 2173(14) keV. The energy ratio of 2.93(5) between the 2(1)+ and 4(1)(+) states indicates well-developed deformation in (42) Si at N = 28 and Z = 14. Also for 38,40)Si energy ratios with values of 2.09(5) and 2.56(5) were obtained. Together with the ratio for (42)Si, the results show a rapid deformation development of Si isotopes from N = 24 to N = 28.

Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids.

The development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis.

Multi-Scale Investigation of Human Renal Tissue in Three Dimensions.

Histopathology as a diagnostic mainstay for tissue evaluation is strictly a 2D technology. Combining and supplementing this technology with 3D imaging has been proposed as one future avenue towards refining comprehensive tissue analysis. To this end, we have developed a laboratory-based X-ray method allowing for the investigation of tissue samples in three dimensions with isotropic volume information. To assess the potential of our method for micro-morphology evaluation, we selected several kidney regions from three patients with cystic kidney disease, obstructive nephropathy and diabetic glomerulopathy. Tissue specimens were processed using our in-house-developed X-ray eosin stain and investigated with a commercial microCT and our in-house-built NanoCT. The microCT system provided overview scans with voxel sizes of [Formula: see text] and the NanoCT was employed for higher resolutions including voxel sizes from [Formula: see text] to 210 nm. We present a methodology allowing for a precise micro-morphologic investigation in three dimensions which is compatible with conventional histology. Advantages of our methodology are its versatility with respect to multi-scale investigations, being laboratory-based, allowing for non-destructive imaging and providing isotropic volume information. We believe, that after future developmental work this method might contribute to advanced multi-modal tissue diagnostics.

Structural evolution in the neutron-rich nuclei ¹°6Zr and ¹°8Zr.

The low-lying states in ¹°6Zr and ¹°8Zr have been investigated by means of ß-γ and isomer spectroscopy at the radioactive isotope beam factory (RIBF), respectively. A new isomer with a half-life of 620 ± 150 ns has been identified in ¹°8Zr. For the sequence of even-even Zr isotopes, the excitation energies of the first 2⁺ states reach a minimum at N = 64 and gradually increase as the neutron number increases up to N = 68, suggesting a deformed subshell closure at N = 64. The deformed ground state of ¹°8Zr indicates that a spherical subshell gap predicted at N = 70 is not large enough to change the ground state of ¹°8Zr to the spherical shape. The possibility of a tetrahedral shape isomer in ¹°8Zr is also discussed.

ß-decay half-lives of very neutron-rich Kr to Tc isotopes on the boundary of the r-process path: an indication of fast r-matter flow.

The ß-decay half-lives of 38 neutron-rich isotopes from (36)Kr to (43)Tc have been measured; the half-lives of (100)Kr, (103-105)Sr, (106-108)Y, (108-110)Zr, (111,112)Nb, (112-115)Mo, and (116,117)Tc are reported here. The results when compared with previous standard models indicate an overestimation in the predicted half-lives by a factor of 2 or more in the A≈110 region. A revised model based on the second generation gross theory of ß decay better predicts the measured half-lives and suggests a more rapid flow of the rapid neutron-capture process (r-matter flow) through this region than previously predicted.

Thrombus Histology of Basilar Artery Occlusions : Are There Differences to the Anterior Circulation?

BACKGROUND: For patients with acute vessel occlusions of the anterior circulation histopathology of retrieved cerebral thrombi has been reported to be associated to stroke etiology. Due to the relatively small incidence of posterior circulation stroke, exclusive histopathologic analyses are missing for this subgroup. The aim of the study was to investigate thrombus histology for patients with basilar artery occlusions and uncover differences to anterior circulation clots with respect to underlying etiology. METHODS: A total of 59 basilar thrombi were collected during intracranial mechanical recanalization and quantitatively analyzed in terms of their relative fractions of the main constituents, e.g. fibrin/platelets (F/P), red (RBC) and white blood cells (WBC). Data were compared to histopathological analyses of 122 thrombi of the anterior circulation with respect to underlying pathogenesis. RESULTS: The composition of basilar thrombi differed significantly to thrombi of the anterior circulation with an overall higher RBC amount (median fraction in % (interquartile range):0.48 (0.37-0.69) vs. 0.37 (0.28-0.50), p < 0.001) and lower F/P count (0.45 (0.21-0.58) vs. 0.57 (0.44-0.66), p < 0.001). Basilar thrombi composition did not differ between the different etiological stroke subgroups. CONCLUSION: The results depict a differing thrombus composition of basilar thrombi in comparison to anterior circulation clots with an overall higher amount of RBC. This may reflect different pathophysiologic processes between anterior and posterior circulation thrombogenesis, e.g. a larger proportion of appositional thrombus growth in the posterior circulation.

Characterization of 22 Canine Pancreatic Carcinomas and Review of Literature.

Pancreatic carcinomas are rare in dogs and clinical signs are mostly non-specific. The literature on clinically and pathologically characterized canine exocrine pancreatic tumours is limited to 76 cases reported since 1963. This retrospective study analysed formalin-fixed samples of pancreatic carcinomas from 22 dogs, obtained during elective exploratory surgery (n = 16) or if the dog was humanely destroyed (n = 6). Tumours were diagnosed according to the World Health Organization classification of tumours of the pancreas of domestic animals. In seven cases, blood samples taken during or shortly before surgery were analysed for concentrations of alpha-amylase, 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester lipase (DGGR lipase), C-reactive protein (CRP), alanine aminotransferase, glutamate dehydrogenase, alkaline phosphatase (ALP), canine trypsin-like immunoreactivity (cTLI) and canine pancreatic lipase immunoreactivity (cPLI). Neutrophil and lymphocyte numbers were determined as part of a complete blood count. Clinical signs were non-specific and included vomiting, inappetence and diarrhoea. Acinar carcinomas were most common (19/22) and observed growth patterns included: solid (n = 14), acinar (n = 5), clear cell (n = 3), mucinous (n = 2), trabecular (n = 1) or rosette-like (n = 1), occurring as a single pattern or in combination. Ductal carcinomas were identified in three cases. Pancreatitis was a common additional histological finding; five dogs had mild and nine dogs had severe pancreatitis. cPLI, DGGR lipase, cTLI and CRP were elevated in 5/5 acinar carcinomas. All liver enzymes were elevated in three of these five animals and ALP was increased in 4/5 dogs. Two dogs with ductal pancreatic carcinomas showed normal cPLI concentrations. One had increased CRP, liver enzymes and leucocytosis with neutrophilia, the other had elevated DGGR lipase and cTLI concentrations. Clinical findings in canine pancreatic carcinomas were non-specific and simultaneous inflammation can mask the detection of the underlying neoplasm in clinical examination and laboratory testing.

Primary Solid and Cystic Tumours of the Exocrine Pancreas in Cats.

Tumours of the exocrine pancreas are rare in cats and few cases are described in the literature. Cystic tumours of the pancreas are not included in the World Health Organization (WHO) international histological classification of tumours of domestic animals. The aim of this study was to characterize the pathology of primary epithelial tumours of the feline exocrine pancreas, with emphasis on cystic tumours. We reviewed tumours of the exocrine pancreas in 70 cats, including complete tumours or the entire pancreas (n = 18) and excisional biopsy samples of pancreatic tumours (n = 52). Macroscopically, the tumours were grouped as solid (n = 45) or cystic (n = 25). Solid tumours were subdivided into adenomas (n = 5) and carcinomas (n = 40) and cystic neoplasms into adenomas (n = 15), carcinomas (n = 7) and cases with diverse growth patterns (n = 3). All five grossly solid adenomas had acinar morphology, while the macroscopically solid carcinomas showed acinar (n = 17), tubular (n = 14) or mixed (n = 9) growth microscopically. Cystic adenomas had acinar (n = 2), tubular (n = 12) or mixed (n = 1) growth, while cystic carcinomas had exclusively tubular growth (n = 7). Three cases with cystic lesions showed diverse histopathological growth patterns. The clinical outcome was available in 57 cases. The majority of cats with carcinomas died or were humanely destroyed during or shortly after surgery (n = 32). However, 2/7 animals with cystic carcinomas showed longer survival times. Cats with cystic adenomas had survival times of up to 5 years. The results of this study show that cystic pancreatic tumours should be considered a differential diagnosis in cats with cystic intra-abdominal masses, even though these are not yet described in the WHO classification. Based on the relatively long survival times of cats with cystic adenomas, complete resection with subsequent histopathological examination is recommended.

Apparent Diffusion Coefficient (ADC) predicts therapy response in pancreatic ductal adenocarcinoma.

Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system. Multi-parametric non-invasive imaging was used for therapy response monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours after treatment onset. Histopathological analyses showed increased apoptosis and matrix remodeling at this time point. Our findings suggest the ADC parameter as an early predictor of therapy response in PDAC.