A quick and reproducible surface-enhanced Raman scattering (SERS)-based immunoassay technique, using hollow gold nanospheres (HGNs) and magnetic beads, has been developed. Here, HGNs show strong enhancement effects from individual particles because hot spots can be localized on the pinholes in the hollow particle structure. Thus, HGNs can be used for highly reproducible immunoanalysis of cancer markers. Magnetic beads were used as supporting substrates for the formation of the immunocomplex. This SERS-based immunoassay technique overcomes the problem of slow immunoreaction caused by the diffusion-limited kinetics on a solid substrate because all of the reactions occur in solution. For the validation of our SERS immunoassay, a well-known lung cancer marker, carcinoembryonic antigen (CEA), was used as a target marker. According to our experimental results, the limit of detection (LOD) was determined to be 1-10 pg/mL, this value being about 100-1000 times more sensitive than the LOD of enzyme-linked immunosorbent assay. Furthermore, the assay time took less than 1 h, including washing and optical detection steps.

Surface-enhanced Raman scattering (SERS) imaging has been used for the targeting and imaging of specific cancer markers in live cells. For this purpose, Au/Ag core-shell nanoparticles, conjugated with monoclonal antibodies, were prepared. The procedures to label live cells with those bimetallic nanoprobes have been developed and used for highly sensitive SERS imaging of live cells. In the present study, live HEK293 cells expressing PLCgamma1 have been used as the optical imaging target. Our results demonstrate the potential feasibility of SERS imaging technology for the highly sensitive imaging of cancer biomarkers in live cells.

Aims/hypothesis The relative lack of successful pancreatic differentiation of human embryonic stem cells (hESCs) may suggest that directed differentiation of hESCs into definitive endoderm and subsequent commitment towards a pancreatic fate are not readily achieved. The aim of this study was to investigate whether sequential exposure of hESCs to epigenetic signals that mimic in vivo pancreatic development can efficiently generate pancreatic endodermal cells, and whether these cells can be further matured and reverse hyperglycaemia upon transplantation. Materials and methods The hESCs were sequentially treated with serum, activin and retinoic acid (RA) during embryoid body formation. The patterns of gene expression and protein production associated with embryonic germ layers and pancreatic endoderm were analysed by RT-PCR and immunostaining. The developmental competence and function of hESC-derived PDX1-positive cells were evaluated after in vivo transplantation. Results Sequential treatment with serum, activin and RA highly upregulated the expression of the genes encoding forkhead box protein A2 (FOXA2), SRY-box containing gene 17 (SOX17), pancreatic and duodenal homeobox 1 (PDX1) and homeobox HB9 (HLXB9). The population of pancreatic endodermal cells that produced PDX1 was significantly increased at the expense of ectodermal differentiation, and a subset of the PDX1-positive cells also produced FOXA2, caudal-type homeobox transcription factor 2 (CDX2), and nestin (NES). After transplantation, the PDX1-positive cells further differentiated into mature cell types producing insulin and glucagon, resulting in amelioration of hyperglycaemia and weight loss in streptozotocin-treated diabetic mice. Conclusions/interpretation Our strategy allows the progressive differentiation of hESCs into pancreatic endoderm capable of generating mature pancreatic cell types that function in vivo. These findings may establish the basis of further investigations for the purification of transplantable islet progenitors derived from hESCs.

Keloids are benign skin tumors characterized by collagen accumulation and hyperproliferation of fibroblasts. To find an effective therapy for keloids, we explored the pharmacological potential of (-)-epigallocatechin-3-gallate (EGCG), a widely investigated tumor-preventive agent. When applied to normal and keloid fibroblasts (KFs) in vitro, proliferation and migration of KFs were more strongly suppressed by EGCG than normal fibroblast proliferation and migration (IC(50): 54.4 microM (keloid fibroblast (KF)) versus 63.0 microM (NF)). The level of Smad2/3, signal transducer and activator of transcription-3 (STAT3), and p38 phosphorylation is more enhanced in KFs, and EGCG inhibited phosphorylation of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated protein kinase 1/2 (ERK1/2), and STAT3 (Tyr705 and Ser727). To evaluate the contribution of these pathways to keloid pathology, we treated KFs with specific inhibitors for PI3K, ERK1/2, or STAT3. Although a PI3K inhibitor significantly suppressed proliferation, PI3K and MEK/ERK inhibitors had a minor effect on migration and collagen production. However, a JAK2/STAT3 inhibitor and a STAT3 siRNA strongly suppressed proliferation, migration, and collagen production by KFs. We also found that treatment with EGCG suppressed growth and collagen production in the in vivo keloid model. This study demonstrates that EGCG suppresses the pathological characteristics of keloids through inhibition of the STAT3-signaling pathway. We propose that EGCG has potential in the treatment and prevention of keloids.

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In the field of knowledge acquisition, dissemination, and utilization/impact, few studies have examined the appropriateness of rational actor theories as a theoretical framework. Rather, the rational actor perspective has been simply taken for granted as a relevant analytical tool for explaining the use of information in policymaking. This article singles out one major set of assumptions imbedded in rational actor theories, those dealing with information acquisition and processing in individual decisionmaking, and empirically examines to what extent the assumptions are realistic. It then puts forward an organizational interest and a communications perspective as alternative explanations for information processing in individual and organizational decisionmaking. The findings of this article show that decisionmakers' behavior does not conform to the assumptions put forward by the rational actor theorists. Instead, the organizational interest perspective is far more promising in accounting for the actual behavior of individuals in processing information in making policy decisions.

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