1,460 research outputs found

    The management of de-cumulation risks in a defined contribution environment

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    The aim of the paper is to lay the theoretical foundations for the construction of a flexible tool that can be used by pensioners to find optimal investment and consumption choices in the distribution phase of a defined contribution pension scheme. The investment/consumption plan is adopted until the time of compulsory annuitization, taking into account the possibility of earlier death. The effect of the bequest motive and the desire to buy a higher annuity than the one purchasable at retirement are included in the objective function. The mathematical tools provided by dynamic programming techniques are applied to find closed form solutions: numer-ical examples are also presented. In the model, the trade-off between the different desires of the individual regarding consumption and final annuity can be dealt with by choosing appropriate weights for these factors in the setting of the problem. Conclusions are twofold. Firstly, we find that there is a natural time-varying target for the size of the fund, which acts as a sort of safety level for the needs of the pensioner. Secondly, the personal preferences of the pensioner can be translated into optimal choices, which in turn affect the distribution of the consumption path and of the final annuity

    Simulations of a lattice model of two-headed linear amphiphiles: influence of amphiphile asymmetry

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    Using a 2D lattice model, we conduct Monte Carlo simulations of micellar aggregation of linear-chain amphiphiles having two solvophilic head groups. In the context of this simple model, we quantify how the amphiphile architecture influences the critical micelle concentration (CMC), with a particular focus on the role of the asymmetry of the amphiphile structure. Accordingly, we study all possible arrangements of the head groups along amphiphile chains of fixed length N=12N=12 and 16 molecular units. This set of idealized amphiphile architectures approximates many cases of symmetric and asymmetric gemini surfactants, double-headed surfactants and boloform surfactants. Consistent with earlier results, we find that the number of spacer units ss separating the heads has a significant influence on the CMC, with the CMC increasing with ss for s<N/2s<N/2. In comparison, the influence of the asymmetry of the chain architecture on the CMC is much weaker, as is also found experimentally.Comment: 30 pages, 17 fgure

    Modulation of P-glycoprotein by zosuquidar trihydrochloride.

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    P-glycoprotein (P-gp), a major contributor in multidrug resistance (MDR), is a cell surface drug efflux pump restricting the intracellular accumulation of many agents used in cancer chemotherapy leading to treatment failure. Over-expression of P-gp is a significant indicator of poor outcome in cancer including acute myelogenous leukaemia (AML). In addition to its primary drug efflux role, P-gp over-expression may also exert a protective influence on a cell's ability to undergo apoptosis in response to certain stimuli. A wide range of P-gp inhibitors have been developed for clinical use in an attempt to modulate the MDR phenotype. Zosuquidar Trihydrochloride (Z.3HCL) is a potent and specific third generation P-gp inhibitor and functions in a non competitive manner. Z.3HCL was the subject of three phase I clinical trials: two on patients with solid tumours and one on 16 patients with AML. Functional and expression assays were conducted on CD56+ NK cells isolated from patients enrolled on these studies. Safety and efficacy data were also analysed, where available. Z.3HCL was also implemented in a number of in vitro assays investigating P-gp expression and function in malignant cells isolated from patients with haematological malignancies: 48 with AML, 75 with CLL, and 16 with MM. Apoptosis assays, utilising normal, patient, and cultured cells were undertaken to investigate the putative role of P-gp in apoptotic modulation. In the solid tumour trials, in vitro assays showed that Z.3HCL infusion was associated with rapid inhibition of P-gp mediated efflux in CD56+ NK cells in 85.2% patients studied. Of the patients enrolled on the AML trial, 11 achieved a complete remission and one a partial remission, with a median survival of 559 (range 38-906) days. Non-haematologic grade 3 and 4 toxicities were observed in four patients. The in vitro assays showed that Z.3HCL infusion was associated with rapid inhibition of P-gp mediated efflux in CD56+ NK cells in all 16 patients, and in CD33+ cells from 6/10 patients. The median IC50 for daunorubicin (DNR) using a MTT assay, decreased significantly between Z.3HCL modulated and unmodulated cells (153 and 247 ng/mL respectively, P=0.01). In vitro studies showed that 38.2% of samples from AML patients, 61.3% from CLL and 41.2% from MM over-expressed P-gp. Drug sensitisation studies on AML cells showed significantly increased drug sensitivity in P-gp positive co- incubated with Z.3HCL and DNR, which was not observed for P-gp negative cells or for co-incubation with cytarabine. Further studies in CLL patients showed that P-gp function and expression did not correlate with other prognostic indicators such as Binet stage, ZAP-70 expression or lgVH mutation status. The intermediately P-gp expressing cell line CEMv showed a significant resistance to ionising radiation compared with CEM cells. Apoptosis assays demonstrated that modulating P-gp with Z.3HCL was able to increase significantly the apoptotic sensitivity above baseline in the highly P-gp expressing CEM-VLB10o cells, an effect not seen in the P-gp negative parent CEM cells

    Identification of Photorhabdus asymbiotica in cases of human infection

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    Simulations of a lattice model of two-headed linear amphiphiles: influence of amphiphile asymmetry

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    Using a 2D lattice model, we conduct Monte Carlo simulations of micellar aggregation of linear-chain amphiphiles having two solvophilic head groups. In the context of this simple model, we quantify how the amphiphile architecture influences the critical micelle concentration (CMC), with a particular focus on the role of the asymmetry of the amphiphile structure. Accordingly, we study all possible arrangements of the head groups along amphiphile chains of fixed length N=12N=12 and 16 molecular units. This set of idealized amphiphile architectures approximates many cases of symmetric and asymmetric gemini surfactants, double-headed surfactants and boloform surfactants. Consistent with earlier results, we find that the number of spacer units ss separating the heads has a significant influence on the CMC, with the CMC increasing with ss for s<N/2s<N/2. In comparison, the influence of the asymmetry of the chain architecture on the CMC is much weaker, as is also found experimentally.Comment: 30 pages, 17 fgure

    Rumah Sakit Kanker di Malang Selatan

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    Rumah Sakit Kanker di Malang Selatan ini merupakan fasilitas kesehatan yang dikhususkan untuk penderita kanker. Rumah Sakit ini merawat dan mengobati kanker yang sudah mengalami tahap lanjut. Perawatan yang diberikan dari rumah sakit ini bersifat paliatif dan kuratif. Dimana dengan perawatan ini dapat memperbaiki pola hidup penderita sehingga penderita dapat memperpanjang umur hidup maupun dapat menikmati masa-masa akhir hidup penderita. Oleh karena itu proyek yang berada di kabupaten Bantur ini menggunakan pendekatan sistem arsitektur yang memperhatikan sirkulasi, zoning dan spatial agar dapat mewujudkan bangunan yang mampu mempermudah kegiatan perawatan. Pendalaman utilitas udara dipilih untuk memaksimalkan pengobatan pada pasien
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