Two-dimensional distribution of Gi2α in the plasma membrane: a critical evaluation by immunocytochemistry

AbstractCaveolae have been postulated as a center for signal transduction, because many signaling molecules are concentrated in caveolin-rich fractions. We took Gi2α as an example and examined whether it is constitutively concentrated in caveolae. First, the behavior of caveolin and Gi2α in density-equilibrium ultracentrifugation was reexamined. By collecting fractions efficiently, caveolin and Gi2α were found to distribute differently. Secondly, by novel immunocytochemical methods it was found that the labeling density of Gi2α was 2.29 times higher in caveolae than in the non-caveolar plasma membrane. The results indicate that the concentration of Gi2α in caveolae is lower than deduced from most biochemical studies

Report on the method for determining the location of the polar vortex boundary region

To determine the boundary region of the polar vortex objectively using the PV distribution on isentropic surfaces, the equivalent latitude(Eql) of the polar vortex boundary was calculated using a slightly modified form of the technique of E.R. Nash et al.(J. Geophys. Res., 101D, 9471, 1996). Using the NCEP/NCAR reanal- ysis data, the Eql of the polar vortex boundary region in the winter of 1999/2000 was calculated, and compared with the ozone mixing ratio in the lower stratosphere over Eureka observatory(80°N , 86°W ). The results indicate that this method determines the boundary region of the polar vortex well

Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic β cells: a simulation study

To clarify the mechanisms underlying the pancreatic β-cell response to varying glucose concentrations ([G]), electrophysiological findings were integrated into a mathematical cell model. The Ca2+ dynamics of the endoplasmic reticulum (ER) were also improved. The model was validated by demonstrating quiescent potential, burst–interburst electrical events accompanied by Ca2+ transients, and continuous firing of action potentials over [G] ranges of 0–6, 7–18, and >19 mM, respectively. These responses to glucose were completely reversible. The action potential, input impedance, and Ca2+ transients were in good agreement with experimental measurements. The ionic mechanisms underlying the burst–interburst rhythm were investigated by lead potential analysis, which quantified the contributions of individual current components. This analysis demonstrated that slow potential changes during the interburst period were attributable to modifications of ion channels or transporters by intracellular ions and/or metabolites to different degrees depending on [G]. The predominant role of adenosine triphosphate–sensitive K+ current in switching on and off the repetitive firing of action potentials at 8 mM [G] was taken over at a higher [G] by Ca2+- or Na+-dependent currents, which were generated by the plasma membrane Ca2+ pump, Na+/K+ pump, Na+/Ca2+ exchanger, and TRPM channel. Accumulation and release of Ca2+ by the ER also had a strong influence on the slow electrical rhythm. We conclude that the present mathematical model is useful for quantifying the role of individual functional components in the whole cell responses based on experimental findings

The significance of extended lymphadenectomy for colorectal cancer with isolated synchronous extraregional lymph node metastasis

SummaryBackground/ObjectiveThe significance of extended lymphadenectomy for colorectal cancer with extraregional lymph node metastasis, such as para-aortic lymph node metastasis, has not been established. The purpose of this study was to evaluate the significance of extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis.MethodsBetween July 2004 and December 2013, 16 patients with synchronous extraregional lymph node metastasis without other organ metastases underwent curative resection and extended lymphadenectomy (R0 group). The clinical characteristics and survival outcomes of the R0 group were compared with those of 12 patients with extraregional lymph node metastasis who underwent palliative surgery (control group).ResultsIn the R0 group, the 5-year cancer-specific survival (CSS) rate was 70.3% and the 5-year relapse-free survival (RFS) rate was 60.5%. The 5-year CSS differed significantly between the R0 and control groups (70.3% vs. 12.5%; p = 0.0003). Univariate analyses revealed that the total numbers of metastatic lymph nodes and metastatic regional lymph nodes present were significantly associated with RFS (p = 0.019 for both).ConclusionFindings from our study suggest that extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis might be effective in carefully selected patients

Rethinking business models for innovation

One of the major challenges confronted by those in charge of technological innovation involves anticipating the value creation model sufficiently early on,in a highly uncertain context both as far as the technology itself is concerned and the potential market. Today, in many industrial sectors, the innovation boundaries have moved towards projects that are more and more exploratory and fuzzy. The simple optimisation of linear processes of the "stage-gate" type is no longer sufficient to build sustainable competitive advantages. The notion of Business Models, when applied to innovation, enables us to describe how a company creates value through innovation, generally within a business ecosystem, and how the value will be distributed between the actors involved. The authors of this book believe that the notions of Business Modelling and value creation are key to all the dimensions of successful innovation, whether technology, marketing, organisational or economically based. Rethinking Business Models for Innovation: this title describes the relationship between thinking, modelling, and also field-testing. The book is based on a series of nine recent cases of innovation involving company managers, often assisted by researchers (the co-authors of each chapter), and how they built and formalised their Business Models and then tested their strategies. After having discovered the variety of the cases, the reader will understand that every innovation situation generates specific questions about Business Models. However, we feel that we can identify three key issues that arise, more or less, in each of these projects. The chapters in this book build on these issues: the identification of sources of value and revenue models (the notion of value creation), the position of the company in the value-network or ecosystem (the sharing of value) and finally the evolution of Business MoDdels over time (the sustainability and the competitiveness of the company). The last chapter goes over all the contributions, exploring the notion of value in the Business Model approach.business model ; innovation ; value ; entrepreneurial project

: Lessons from entrepreneurial projects

International audienceOne of the major challenges confronted by those in charge of technological innovation involves anticipating the value creation model sufficiently early on,in a highly uncertain context both as far as the technology itself is concerned and the potential market. Today, in many industrial sectors, the innovation boundaries have moved towards projects that are more and more exploratory and fuzzy. The simple optimisation of linear processes of the "stage-gate" type is no longer sufficient to build sustainable competitive advantages. The notion of Business Models, when applied to innovation, enables us to describe how a company creates value through innovation, generally within a business ecosystem, and how the value will be distributed between the actors involved. The authors of this book believe that the notions of Business Modelling and value creation are key to all the dimensions of successful innovation, whether technology, marketing, organisational or economically based. Rethinking Business Models for Innovation: this title describes the relationship between thinking, modelling, and also field-testing. The book is based on a series of nine recent cases of innovation involving company managers, often assisted by researchers (the co-authors of each chapter), and how they built and formalised their Business Models and then tested their strategies. After having discovered the variety of the cases, the reader will understand that every innovation situation generates specific questions about Business Models. However, we feel that we can identify three key issues that arise, more or less, in each of these projects. The chapters in this book build on these issues: the identification of sources of value and revenue models (the notion of value creation), the position of the company in the value-network or ecosystem (the sharing of value) and finally the evolution of Business MoDdels over time (the sustainability and the competitiveness of the company). The last chapter goes over all the contributions, exploring the notion of value in the Business Model approach.L'innovation technologique, qu'elle soit conduite par des start-ups ou par de grandes entreprises, n'est plus une condition suffisante de la création de valeur. Créer de la valeur sur des marchés nouveaux nécessite le plus souvent de repenser l'organisation de l'entreprise, sa façon de faire des affaires, ses partenariats stratégiques, autrement dit, son business model. Cet ouvrage se veut un guide pour les porteurs de projets d'innovation en leur fournissant des outils de compréhension et d'analyse de la dimension stratégique de leur projet. Les études de cas présentées sont le fruit d'une collaboration étroite entre les porteurs de chacun des projets et des chercheurs en management de l'innovation reconnus. Au travers de ces cas, trois grandes problématiques sont abordées : l'identification des sources de valeur chez les clients potentiels, la position que l'entreprise pourra prendre dans son écosystème et enfin l'évolution des business models dans le temps. Sur chacun des cas, le lecteur aura accès à une compréhension fine des problèmes stratégiques posés par l'innovation ainsi que des outils de management mis en œuvre pour aider à réfléchir et à agir. (http://www.rethinkingbusinessmodel.net/

First Data Release of the Hyper Suprime-Cam Subaru Strategic Program

The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is a three-layered imaging survey aimed at addressing some of the most outstanding questions in astronomy today, including the nature of dark matter and dark energy. The survey has been awarded 300 nights of observing time at the Subaru Telescope and it started in March 2014. This paper presents the first public data release of HSC-SSP. This release includes data taken in the first 1.7 years of observations (61.5 nights) and each of the Wide, Deep, and UltraDeep layers covers about 108, 26, and 4 square degrees down to depths of i~26.4, ~26.5, and ~27.0 mag, respectively (5sigma for point sources). All the layers are observed in five broad bands (grizy), and the Deep and UltraDeep layers are observed in narrow bands as well. We achieve an impressive image quality of 0.6 arcsec in the i-band in the Wide layer. We show that we achieve 1-2 per cent PSF photometry (rms) both internally and externally (against Pan-STARRS1), and ~10 mas and 40 mas internal and external astrometric accuracy, respectively. Both the calibrated images and catalogs are made available to the community through dedicated user interfaces and database servers. In addition to the pipeline products, we also provide value-added products such as photometric redshifts and a collection of public spectroscopic redshifts. Detailed descriptions of all the data can be found online. The data release website is https://hsc-release.mtk.nao.ac.jp/.Comment: 34 pages, 20 figures, 7 tables, moderate revision, accepted for publication in PAS

膀胱癌における抗クローディン4細胞外ドメイン中和抗体の化学療法増感効果

Bladder cancer displays an aggressive phenotype in the muscle-invasive phase, and is associated with a high mortality rate. Therefore, novel molecular therapeutic targets are needed to improve patient survival. A monoclonal antibody against the extracellular domain of the claudin-4 (CLDN4) tight junction protein was established by immunizing rats with a plasmid vector encoding human CLDN4. A hybridoma clone, producing a rat monoclonal antibody recognizing CLDN4 (clone 4D3), was obtained. Immunohistochemistry by using the 4D3 antibody showed that CLDN4 expression was associated with local invasion, nodal metastasis, distant metastasis, and advanced stage in 86 cases of bladder cancer. The 4D3 antibody inhibited growth, invasion, and survival, associated with abrogation of the intratumoral microenvironment; lowered concentrations of epidermal growth factor and vascular endothelial growth factor were found in three-dimensional cultures of T24 and RT4 cells. In combination with cisplatin therapy, 4D3 enhanced cisplatin cytotoxicity by increasing cellular permeability, leading to increased intracellular cisplatin concentrations. In mouse models of subcutaneous tumors and lung metastasis, 4D3 enhanced tumor growth inhibition, alone and with concurrent cisplatin treatment. The anti-tumor activity of the newly established 4D3 antibody suggests that it may be a powerful tool in CLDN4-targeting therapy, and in combination with chemotherapy.博士（医学）・甲第649号・平成28年3月15日Copyright © 2015 Elsevier Ireland Ltd. All rights reserved