METHYLENE BLUE AS LIGHT AND REACTIVE OXYGEN SPECIES SENSITIVE LIGAND: APPICABILITY IN HYBRID DRUG AND MATERIAL SYNTHESIS

Methylene blue (MB) with a 10-N-carbamoyl linkage was discovered and developed as a multifunctional far-red (660 nm) photocleavable ligand capable of rendering a series of MB conjugated compounds with off-to-on fluorescence switch properties through the controlled release of MB. The released MB was successfully demonstrated to be an effective photosensitizer, imaging probe, and therapeutic agent. The complete release of MB was achieved with a cumulative light dose of 15 J/cm2. The photosensitivity was demonstrated to be dependent on the type of chemical bond at 10-N of the phenothiazine ring which links MB to a side group. Specifically, the urea bond-based derivatives could undergo a complete photolysis, while those with carbamate bond showed negligible photolysis. The released MB was subsequently utilized as fluorescent imaging dye, and photosensitizer demonstrated through the significant reduction in cell viability compare to un-irradiated samples (16.1 ± 16.7 % and 72.8±0.33 %, respectively). The 10-N carbamoyl linkage MB was also reported to be a hydroxyl radical triggered cleavable ligand. Probed by this platform, hemoproteins were demonstrated to be a much more efficient Fenton’s catalyst than commonly used inorganic Fe(II) salts. The applicability of this ligand was demonstrated through the capability of being triggered by elevated reactive oxygen species levels at diseased tissue, with malaria-parasitized erythrocytes as an in vitro model. The conjugation between antimalarial agent primaquine (PQ), and MB moiety, was suggested to be preferentially activated by malaria parasite. Subsequently, the hybrid drug MB-PQ successfully demonstrated a relatively low IC50 (\u3c30 \u3enM) towards malaria, and 2-5 times higher selectivity index compare to the parent compounds. The applicability of MB ligand was also utilized in the synthesis of liposome-forming material for drug delivery purposes. The MB conjugated phospholipid demonstrated the capability to form stimuli-responsive liposome. Specifically, upon irradiating with UV light or the treatment with ROS, the liposome structure was disrupted leading to the release of the payload

On the elastoplastic stability of a plate under shear forces, taking into account its real bending form

Using the theory of elastoplastic processes and the modified elastic solution method we investigate the stability outside elastic limit problem of a plate under shear forces, taking into account its real bending form after the loss of stability. An expression for determining the critical force is obtained and numerical calculations with various ratio of thickness have been fulfilled, from the results one can see the convergence of the modified elastic solution method

Non-linear analysis of laminated composite doubly curved shallow shells

This paper deals with governing equations and approximate analytical solutions based on some wellknown assumptions to the non-linear buckling and vibration problems of laminated composite doubly curved shallow shells. Obtained results will be presented by analytical expressions of the lower critical load, the postbuckling load-deflection curve and the fundamental frequency of non-linear free vibration of the shell

Improving Items and Contexts Understanding with Descriptive Graph for Conversational Recommendation

State-of-the-art methods on conversational recommender systems (CRS) leverage external knowledge to enhance both items' and contextual words' representations to achieve high quality recommendations and responses generation. However, the representations of the items and words are usually modeled in two separated semantic spaces, which leads to misalignment issue between them. Consequently, this will cause the CRS to only achieve a sub-optimal ranking performance, especially when there is a lack of sufficient information from the user's input. To address limitations of previous works, we propose a new CRS framework KLEVER, which jointly models items and their associated contextual words in the same semantic space. Particularly, we construct an item descriptive graph from the rich items' textual features, such as item description and categories. Based on the constructed descriptive graph, KLEVER jointly learns the embeddings of the words and items, towards enhancing both recommender and dialog generation modules. Extensive experiments on benchmarking CRS dataset demonstrate that KLEVER achieves superior performance, especially when the information from the users' responses is lacking.Comment: 14 pages, 3 figures, 9 table

Risk Management in Viet Nam Tourism Industry under the Impact of a Two Factor Model during and after the Global Crisis

Over past few years, the global financial crisis shows certain influence on emerging financial markets including Viet nam. Therefore, this study chooses an analytical approach to give some systematic opinions on how much some certain determinants such as income tax and leverage, affect the level of market risk in listed tourism companies. First, it calculates equity and asset beta values in three (3) different scenarios of changing tax rates and changing the level of financial leverage. Second, under 3 different scenarios of changing tax rates (20%, 25% and 28%), we recognized that there is not large disperse in equity beta values, estimated at 0,753 for current leverage situation. Third, by changing tax rates in 3 scenarios (25%, 20% and 28%), we recognized both equity and asset beta mean values have positive relationship with the increasing level of tax rate. Last but not least, this paper covers some ideas and policy suggestions. 

Risk Management in Viet Nam Tourism Industry Under the Impact of a Two Factor Model During and After the Global Crisis

Over past few years, the global financial crisis shows certain influence on emerging financial markets including Viet nam. Therefore, this study chooses an analytical approach to give some systematic opinions on how much some certain determinants such as income tax and leverage, affect the level of market risk in listed tourism companies.First, it calculates equity and asset beta values in three different scenarios of changing tax rates and changing the level of financial leverage. Second, under 3 different scenarios of changing tax rates (20%, 25% and 28%), we recognized that there is not large disperse in equity beta values, estimated at 0,753 for current leverage situation.Third, by changing tax rates in 3 scenarios (25%, 20% and 28%), we recognized both equity and asset beta mean values have positive relationship with the increasing level of tax rate.Last but not least, this paper covers some ideas and policy suggestions

Non-linear buckling analysis of functionally graded shallow spherical shells

In the present paper the non-linear buckling analysis of functionally graded spherical shells subjected to external pressure is investigated. The material properties are graded in the thickness direction according to the power-law distribution in terms of volume fractions of the constituents of the material. In the formulation of governing equations geometric non-linearity in all strain-displacement relations of the shell is considered. Using Bubnov-Galerkin's method to solve the problem an approximated analytical expression of non-linear buckling loads of functionally graded spherical shells is obtained, that allows easily to investigate stability behaviors of the shell

Elasto-plastic stability of thin plates subjected to complex loading process

Analyzing an elastic-plastic stability problem, the complex loading process acted on the body has an essential influence on the values of critical loads. For clearing up this effect, in the present paper the general elasto-plastic process theory, theory of process with average curvature and the simple loading process theory are applied into the consideration of the mentioned problem. A numerical comparison is given

Caractérisation de certains gènes polycétones synthases chez Aspergillus Ochraceus NRRL 3174 producteur d'ochratoxine A et d'acide pénicillique

Le champignon Aspergillus ochraceus est connu comme producteur de plusieurs polycétones dont les mycotoxines ochratoxines et acide pénicillique. L'étude de la diversité des gènes de polycétones synthases (PKS) chez Aspergillus ochraceus NRRL 3174 a été abordée en utilisant quatre couples d'amorces dégénérées dessinés pour cibler le domaine ketosynthase (3) et le domaine acyltransferase (1). 10 PKS différentes de type I ont été identifiées. Elles sont distribuées dans les trois groupes principaux de PKS : PKS réduite, partiellement réduite et non réduite. Le gène AoLC35-12 est responsable de la production d'ochratoxine A chez A. ochraceus. Le gène aomsas de type 6-methylsalicylique synthase intervient dans la biosynthèse d'acide pénicillique, de patuline, d'asperlactone, d'isoasperlactone, de melleine, d'hydroxymelleine et d'ochratoxine A. Ce gène a été totalement séquencé. Deux couples d'amorces spécifiques ont été synthétisés à partir du gène AoLC35-12. Avec le couple AoOTAL/AoOTAR, uniquement A. ochraceus est détecté par méthode PCR. Avec l'autre couple d'amorces, AoLC35-12L/AoLC35-12R, il est possible de détecter à la fois les producteurs d'ochratoxine A et les producteurs de citrinine. Des amorces spécifiques ont également été développées pour la détection rapide d'A. carbonarius, de P. verrucosum et de P. citrinum. ABSTRACT : Aspergillus ochraceus is known to produce many polyketides including ochratoxins and penicillic acid. The diversity of polyketide synthase (PKS) genes in A. ochraceus NRRL 3174 was investigated by using four degenerate primer pairs targeting ketosynthase domain (3) and acyltransferase domain (1). 10 different type I PKS were identified, and were classed into three main PKS groups: reduced, partially reduced and non reduced. AoLC35-12 gene was found to be involved in OTA biosynthesis. A PKS gene of 6-methylsalicyclic acid synthase type, aomsas, was found to be involved in the biosynthesis of penicillic acid, patulin, asperlactone, isoasperlactone, mellein, hydroxymellein, and ochratoxin A. This gene was completely sequenced. In order to detect ochratoxin A and citrinin producers by using PCR method, two specific primer pairs were generated from AoLC35-12 gene. AoOTAL/AoOTAR can detect only A. ochraceus while AoLC35-12L/AoLC35-12R can detect either ochratoxin A or citrinin producer fungi. Specific primers were also developed to detect A. carbonarius, P. verrucosum and P. citrinum

iPS細胞はin vitroデングウイルス感染実験に用いられる樹状細胞の由来として有用である

The lack of an appropriate model has been a serious concern in dengue research pertinent to immune response and vaccine development. It remains a matter of impediment in dengue virus (DENV) studies when it comes to an in vitro model, which requires adequate quantity of dendritic cells (DC) with uniform characters. Other sources of DC, mostly monocyte derived DC (moDC), have been used despite their limitations such as quantity, proliferation, and donor dependent characters. Recent development of human iPS cells with consistent proliferation for long, stable, functional characteristics and desired HLA background has certainly offered added advantages. Therefore, we hypothesised that iPS derived cells would be a reliable alternative to the traditional DCs to be used with an in vitro DENV system. To develop a DENV infection and T cell activation model, we utilised iPS cells (HLA-A*24) as the source of DC. iPS-ML-DC was prepared and DENV infectivity was assessed apart from the major surface markers expression and cytokine production potential. Our iPS-ML-DC had major DC markers expression, DENV infection efficiency and cytokine production properties similar to that of moDC. Moreover, DENV infected iPS-ML-DC demonstrated the ability to activate HLA-matched T cell (but not mismatched) in vitro as evidenced by significantly higher proportion of IFN-γ+ CD69+ T cells compared to non-infected iPS-ML-DC. This affirmed the antigen-specific T cell activation by iPS-ML-DC as a function of antigen presenting cells. To conclude, maturation potential, DENV infection efficiency and T cell activation ability collectively suggest that iPS-ML-DC serves as an attractive option of DC for use in DENV studies in vitro.長崎大学学位論文 学位記番号:博(医歯薬)甲第1094号 学位授与年月日:平成30年9月5日Author: Dao Huy Manh, Shusaku Mizukami, Shyam Prakash Dumre, Muhareva Raekiansyah, Satoru Senju, Yasuharu Nishimura, Juntra Karbwang, Nguyen Tien Huy, Kouichi Morita, Kenji HirayamaCitation: Journal of General Virology, 99(9), pp.1239-1247; 2018Nagasaki University (長崎大学)課程博