A benchmark experiment on (208)Pb shows that polarized proton inelastic scattering at very forward angles including 0° is a powerful tool for high-resolution studies of electric dipole (E1) and spin magnetic dipole (M1) modes in nuclei over a broad excitation energy range to test up-to-date nuclear models. The extracted E1 polarizability leads to a neutron skin thickness r(skin) = 0.156(-0.021)(+0.025) fm in (208)Pb derived within a mean-field model [Phys. Rev. C 81, 051303 (2010)], thereby constraining the symmetry energy and its density dependence relevant to the description of neutron stars.

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Inelastic scattering from12 C has been measured at the extremely forward angles including 0• using 386 MeV α particles to study the α-cluster states around Ex ∼ 10 MeV, especially the 2 + state predicted by the α-cluster model. We have analyzed the (α,α ′ ) cross-section data using both the peak-fitting and the multipole decomposition techniques. A 2 + state at Ex = 9.84 ± 0.06 MeV with a width of 1.01 ± 0.15 MeV is found to be submerged in the broad 0 + state at Ex = 9.93 ± 0.03 MeV with a width of 2.71 ± 0.08 MeV. This 2 + state may be interpreted as the 2 + excitation of the Hoyle state and the α-condensate state.

Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets. Seven GLA-forming cell lines were derived from adenocarcinoma among the 8 lines. A neuroendocrine adenocarcinoma cell line PC-3 formed asymmetric GLA with ductal structures on the NCPs and rapidly growing asymmetric tumors that metastasized to lymph nodes in immunocompromised mice. In contrast, another adenocarcinoma cell line DU-145 formed spheroids in vitro and spheroid-like tumors in vivo that did not metastasize to lymph nodes until day 50 after transplantation. Culture in the 3D nanoenvironment and in a defined stem cell medium enabled the neuroendocrine adenocarcinoma cells to form slowly growing large organoids that expressed multiple stem cell markers, neuroendocrine markers, intercellular adhesion molecules, and oncogenes in vitro. In contrast, the more commonly used 2D serum-contained environment reduced intercellular adhesion and induced mesenchymal transition and promoted rapid growth of the cells. In addition, the 3D stemness nanoenvironment promoted secretion of HSP90 and EpCAM-exosomes, a marker of CSC phenotype, from the neuroendocrine organoids. These findings indicate that the NCP-based 3D environment enables cells to form stem cell tumoroids with multipotency and model more accurately the in vivo tumor status at the levels of morphology and gene expression.

BackgroundSmall caliber vascular prostheses are not clinically available because synthetic vascular prostheses lack endothelial cells which modulate platelet activation, leukocyte adhesion, thrombosis, and the regulation of vasomotor tone by the production of vasoactive substances. We developed a novel method to create scaffold-free tubular tissue from multicellular spheroids (MCS) using a “Bio-3D printer”-based system. This system enables the creation of pre-designed three-dimensional structures using a computer controlled robotics system. With this system, we created a tubular structure and studied its biological features.Methods and ResultsUsing a “Bio-3D printer,” we made scaffold-free tubular tissues (inner diameter of 1.5 mm) from a total of 500 MCSs (2.5× 104 cells per one MCS) composed of human umbilical vein endothelial cells (40%), human aortic smooth muscle cells (10%), and normal human dermal fibroblasts (50%). The tubular tissues were cultured in a perfusion system and implanted into the abdominal aortas of F344 nude rats. We assessed the flow by ultrasonography and performed histological examinations on the second (n = 5) and fifth (n = 5) day after implantation. All grafts were patent and remodeling of the tubular tissues (enlargement of the lumen area and thinning of the wall) was observed. A layer of endothelial cells was confirmed five days after implantation.ConclusionsThe scaffold-free tubular tissues made of MCS using a Bio-3D printer underwent remodeling and endothelialization. Further studies are warranted to elucidate the underlying mechanism of endothelialization and its function, as well as the long-term results.

Alexithymia is a personal trait characterized by a reduced ability to identify and describe one's own feelings and is known to contribute to a variety of physical and behavioural disorders. To elucidate the pathogenesis of stress-related disorders and the normal functions of emotion, it is important to investigate the neurobiology of alexithymia. Although several neurological models of alexithymia have been proposed, there is very little direct evidence for the neural correlates of alexithymia. Using PET, we studied brain activity in subjects with alexithymia when viewing a range of emotional face expressions. Twelve alexithymic and 12 non-alexithymic volunteers (all right-handed males) were selected from 247 applicants on the basis of the 20-item Toronto Alexithymia Scale (TAS-20). Regional cerebral blood flow (rCBF) was measured with H(2)(15)O-PET while the subjects looked at angry, sad and happy faces with varying emotional intensity, as well as neutral faces. Brain response in the subjects with alexithymia significantly differed from that in the subjects without alexithymia. The alexithymics exhibited lower rCBF in the inferior and middle frontal cortex, orbitofrontal cortex, inferior parietal cortex and occipital cortex in the right hemisphere than the non-alexithymics. Additionally, the alexithymics showed higher rCBF in the superior frontal cortex, inferior parietal cortex and cerebellum in the left hemisphere when compared with the non-alexithymics. A covariance analysis revealed that rCBF in the inferior and superior frontal cortex, orbitofrontal cortex and parietal cortex in the right hemisphere correlated negatively with individual TAS-20 scores when viewing angry and sad facial expressions, and that no rCBF correlated positively with TAS-20 scores. Moreover, the anterior cingulate cortex and insula were less activated in the alexithymics' response to angry faces than their response to neutral faces. These results suggest that people with alexithymia process facial expressions differently from people without alexithymia, and that this difference may account for the disorder of affect regulation and consequent peculiar behaviour in people with alexithymia.

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