銀行保險通路近年來成為壽險公司主要保險通路之一，因此壽險公司在銀行保險通路所承擔的風險逐漸加重。近年來金融市場處在一個低利環境下，儲蓄型商品（例如：利率變動型年金）為銀行定存商品替代品之一，故，儲蓄型商品逐漸成為銀行保險通路吸引銀行客戶的主力商品。因此可知，壽險公司對銀行保險通路，尤其是，儲蓄型商品之風險管理日漸重要。主管機關為了確保壽險公司清償能力，近年來針對儲蓄性商品制定相關策略，希望藉由限制儲蓄型商品之銷售比例，加強壽險公司之風險管理，防止壽險公司因為銷售過多儲蓄型商品而造成財務負擔。 本研究以商品組合互補效果的概念達到風險管理，其中儲蓄型商品以利率變動型年金作代表；傳統型商品以傷害保險與定期壽險作代表。本研究使用現金流量分析法，透過壓力測試和敏感度分析，嘗試在不同情境下，尋找一個規律，並簡易設算銀行保險通路下主力商品之最適銷售比例。 模擬結果發現，傳統型商品可有效彌補儲蓄型商品帶來的風險；而銷售比例之訂定，應該依照壽險公司在不同壓力測試、可控制之利差之下，設算出最適可銷售比例；只要壽險公司將其資本額大小、預計總保費收入、預計銷售商品、宣告利率策略及各項利率關係在不同情境下作設算，即可求出在不發生盈餘虧損下，商品組合之最適銷售比例。 另外本研究也發現，傷害保險與利率變動型年金保險之替代效果，比定期壽險與利率變動型年金保險佳，因此可作為商品組合搭配之參考。 本研究貢獻在於透過簡易的測試，設算出實際數值，可望提供壽險公司在資產負債管理方面的新思維。 / In recent year, baccasurance has become one of the major channels for life insurance companies. Therefore, adding up the risk the baccasurance channel imposes, life insurance companies has undertaken heavier risks. Due to the fact that the interest rate has been comparably low for the last ten years, more and more consumers choose to buy deposit insurance (EX：interest sensitive annuity ) the substitute for periodic deposit. As the vital product in baccasurance channel, managing the risk of deposit insurance become more and more important. This study adopted the idea of mixing products to achieve complementary effect, so that the risks might be better managed. Interest Sensitive Annuity was chosen to represent deposit-oriented products, and Injury Insurance and Periodical Annuity Life Insurance to represent traditional commodities. The method used for analysis was Cash Flow Test, in which stress test and sensitivity analysis were included, through which the researcher attempted to induce a rule from various situations and compute out the optimum ratio of the major products on the bancassurance channel. The simulation result showed that traditional insurance products are able to compensate the deposit-oriented insurance, and the maximum percentage this product accounts for should be computed abiding by to controllable interest gain under various kinds of stress tests, for which the companies need to take into account its capital size, total premium, products being promoted, declared interest rate, and interest rates to help simulate all kinds of situations. It is possible to compute out the optimum ratio for the products when the goal surplus more than or equals to zero. In addition, it was also found that injury insurance is a better substitute for interest sensitive annuity insurance than term life insurance. It is suggested that insurance companies to carefully gauge the respective proportion for Periodical Annuity Life Insurance, Injury Insurance, and Interest Sensitive Annuity Insurance. Finally, it is hoped that the numerical number tested out by the current study provides insurance companies a new insight in asset liability management.

<p>Rapid development in CMOS technology has resulted in its suitability for the implementation of readout front-end systems in terms of high integration density, and low power consumption yet at the same time posing many challenges for analog circuits design like readout front-end. One of the significant challenges is the low noise design for high speed front-end systems, while at the same time minimizing the power consumption as much as possible.</p><p>A high speed, low noise, low power, and programmable readout front-end system is designed and implemented for an X-ray detector in CMOS 0.18 m technology in this thesis work. The front-end system has a peaking time of 10 ns, which is the highest speed ever reported in the published work. The front-end system is designed to achieve low noise in terms of ENC, and a low power consumption of 2.9 mW. The detector capacitance is the most dominating parameter to low noise, which in turn is directly related to the power consumption. In this thesis work an ENC of 435 electrons is achieved for a detector capacitance of 5 pF and an ENC of 320 electrons for a detector capacitance of 3 pF. Based on the comparison to related published work, a performance improvement of at least two times is achieved taking peaking time, power, ENC, and detector capacitance all into consideration. The output pulse after amplification has peak amplitude of 300 mV for a maximum injected charge of 40000 electrons from the detector.</p><p>The readout front-end system noise performance is strongly dependent on the input MOSFET type, size, and biasing. In this work a PMOS has been selected and optimized as the input device due to its smaller 1/f noise and high gain as compare to NMOS when biased at same currents. The architecture designed in this work consists of a folded cascode CSA with extra cascode in first stage, a pole-zero cancellation circuit to eliminate undershoot, a shaper amplifier, and integrators using Gm-C filter technique. All of these components are optimized for low power while meeting the noise requirements. The whole front-end system is programmed for peaking times of 10, 20, and 40 ns. The programmability is achieved by switching different capacitors and resistors values for all the poles and zeros in the front-end, and by switching parallel transconductance in the Gm-C filters. Finally fine tuning of all the capacitance, resistance, and transconductance values is done to achieve required performance.</p>

<p>Physico-chemical characterisation of structure and stability of liposomes intended for drug delivery is the central issue in this thesis. In addition, targeted liposomes to be used in boron neutron capture therapy (BNCT) were developed.</p><p>Lysolipids and fatty acids are products formed upon hydrolysis of PC-lipids. The aggregate structure formed upon mixing lysolipids, fatty acids and EPC were characterised by means of cryo-TEM. A relatively monodisperse population of unilamellar liposomes was detected in mixtures containing equimolar concentration of the three components. </p><p>The interactions between alternative steric stabilisers (PEO-PPO-PEO copolymers) and conventional PC-and pH-sensitive PE-liposomes were investigated. Whereas the PE-liposomes could be stabilised by the PEO-PPO-PEO copolymers, the PC-liposomes showed an enhanced permeability concomitant with the PEO-PPO-PEO adsorption.</p><p>Permeability effects induced by different PEG-stabilisers on EPC liposomes were shown to be dependent on the length of the PEG chain but also on the linkage used to connect the PEG polymer with the hydrophobic membrane anchor.</p><p>An efficient drug delivery requires, in most cases, an accumulation of the drug in the cell cytoplasm. The mechanism behind cytosolic drug delivery from pH-sensitive liposomes was investigated. The results suggest that a destabilisation of the endosome membrane, due to an incorporation of non-lamellar forming lipids, may allow the drug to be released. </p><p>Furthermore, sterically stabilised liposomes intended for targeted BNCT have been characterised and optimised concerning loading and retention of boronated drugs. </p>

<p>A beam of 250A MeV ¹⁷O ions was scattered from argon and xenon targets. The large excess of fast neutrons compared with statistical model calculations that was observed earlier for xenon, was confirmed and found for argon as well. Analysis and calculations show that a considerable fraction of these neutrons can be interpreted as coming from direct knock-out reactions.</p><p>The angular distributions do not support the suggestion of using fast heavy ion scattering as a probe for the study of the neutron skin in nuclei. While the basic idea that a heavy projectile tends to sample the neutron wave function near the surface of the nucleus is sound, the measured neutron distribution is not as distinct as suggested by the previous experiment. This makes it difficult to distinguish direct reactions from other channels, such as semi-direct decay of giant resonances.</p><p>The improvements in the experimental methods have made the concept of using the CELSIUS storage and cooler ring as an internal magnetic spectrometer attractive for other of experiments presently being prepared.</p>

Nanoparticles were synthesized and modified for target drug delivery. The research involved the aqueous synthesis of near infrared (NIR) sensitive Au-Au₂S nanoparticles. An anti-cancer drug (<i>cis-platin</i>) was subsequently adsorbed onto the Au-Au₂S nanoparticle surface via the 11-mercaptoundecanoic acid layers. The results showed that the degree of adsorption of cis-platin onto Au-Au₂S nanoparticles was controlled by the pH value of solution, and the rate of drug release was sensitive to NIR irradiation. The results of the synthesis, drug-release properties and nanoparticle-cell interactions will be discussed. / Singapore-MIT Alliance (SMA)

Physico-chemical characterisation of structure and stability of liposomes intended for drug delivery is the central issue in this thesis. In addition, targeted liposomes to be used in boron neutron capture therapy (BNCT) were developed. Lysolipids and fatty acids are products formed upon hydrolysis of PC-lipids. The aggregate structure formed upon mixing lysolipids, fatty acids and EPC were characterised by means of cryo-TEM. A relatively monodisperse population of unilamellar liposomes was detected in mixtures containing equimolar concentration of the three components. The interactions between alternative steric stabilisers (PEO-PPO-PEO copolymers) and conventional PC-and pH-sensitive PE-liposomes were investigated. Whereas the PE-liposomes could be stabilised by the PEO-PPO-PEO copolymers, the PC-liposomes showed an enhanced permeability concomitant with the PEO-PPO-PEO adsorption. Permeability effects induced by different PEG-stabilisers on EPC liposomes were shown to be dependent on the length of the PEG chain but also on the linkage used to connect the PEG polymer with the hydrophobic membrane anchor. An efficient drug delivery requires, in most cases, an accumulation of the drug in the cell cytoplasm. The mechanism behind cytosolic drug delivery from pH-sensitive liposomes was investigated. The results suggest that a destabilisation of the endosome membrane, due to an incorporation of non-lamellar forming lipids, may allow the drug to be released. Furthermore, sterically stabilised liposomes intended for targeted BNCT have been characterised and optimised concerning loading and retention of boronated drugs.

A beam of 250A MeV 17O ions was scattered from argon and xenon targets. The large excess of fast neutrons compared with statistical model calculations that was observed earlier for xenon, was confirmed and found for argon as well. Analysis and calculations show that a considerable fraction of these neutrons can be interpreted as coming from direct knock-out reactions. The angular distributions do not support the suggestion of using fast heavy ion scattering as a probe for the study of the neutron skin in nuclei. While the basic idea that a heavy projectile tends to sample the neutron wave function near the surface of the nucleus is sound, the measured neutron distribution is not as distinct as suggested by the previous experiment. This makes it difficult to distinguish direct reactions from other channels, such as semi-direct decay of giant resonances. The improvements in the experimental methods have made the concept of using the CELSIUS storage and cooler ring as an internal magnetic spectrometer attractive for other of experiments presently being prepared.

Establishing process-structure-property relationships is an important objective in the paradigm of materials design in order to reduce the time and cost needed to develop new materials. A method to link phase field (process-structure relations) and microstructure-sensitive finite element (structure-property relations) modeling is demonstrated for subsolvus polycrystalline IN100. A three-dimensional (3D) experimental dataset obtained by orientation imaging microscopy performed on serial sections is utilized to calibrate a phase field model and to calculate inputs for a finite element analysis. Simulated annealing of the dataset realized through phase field modeling results in a range of coarsened microstructures with varying grain size distributions that are each input into the finite element model. A rate dependent crystal plasticity constitutive model that captures the first order effects of grain size, precipitate size, and precipitate volume fraction on the mechanical response of IN100 at 650°C is used to simulate stress-strain behavior of the coarsened polycrystals. Model limitations and ideas for future work are discussed.

The KATP channels play an important role in the membrane excitability and vascular tone regulation. Previous studies indicate that the function of KATP channels is disrupted in oxidative stress seen in a variety of cardiovascular diseases, while the underlying mechanism remains unclear. Here, we demonstrate S-glutathionylation to be a modulation mechanism underlying the oxidant-mediated vascular KATP channel inhibition, the molecular basis for the channel inhibition and the alleviation of the channel inhibition by vasoactive intestinal peptide (VIP). We found that an exposure of isolated mesenteric rings to H2O2 impaired the KATP channel-mediated vascular dilation. In whole-cell recordings and inside-out patches, micromolar H2O2 or diamide caused a strong inhibition of the vascular KATP channel (Kir6.1/SUR2B) in the presence, but not in the absence, of glutathione (GSH), indicating S-glutathionylation. By co-expressions of Kir6.1 or Kir6.2 with SUR2B subunits, we found that the oxidant sensitivity of the KATP channel relied on the Kir6.1 subunit. Systematic mutational analysis revealed three cysteine residues (Cys43, Cys120 and Cys176) to be important. Among them, Cys176 was prominent, contributing to >80% oxidant sensitivity. Biochemical pull-down assay with biotinylated glutathione ethyl ester (BioGEE) showed that mutations of Cys176 impaired the oxidant-induced incorporation of GSH to the Kir6.1 subunit. Simulation modeling of Kir6.1 S-glutathionylation revealed that after incorporation to residue 176, the GSH moiety occupied a space between slide helix and two transmembrane helices. This prevented the necessary conformational change of the inner helix for channel gating, and retained the channel in its closed state. VIP is a potent vasodilator, and is shown to have protective role against oxidative stress. We found that the channel was strongly augmented by VIP and the channel activation relied on PKA phosphorylation. These results therefore indicate that 1) the vascular KATP channel is strongly inhibited in oxidative stress, 2) S-glutathionylation underlies the oxidant-mediated KATP channel inhibition, 3) Cys176 in the Kir6.1 subunit is the major site for S-glutathionylation, and 4) the Kir6.1/SUR2B channel is activated in a PKA-dependent manner by VIP that has been previously shown to alleviate oxidative stress.

Rapid development in CMOS technology has resulted in its suitability for the implementation of readout front-end systems in terms of high integration density, and low power consumption yet at the same time posing many challenges for analog circuits design like readout front-end. One of the significant challenges is the low noise design for high speed front-end systems, while at the same time minimizing the power consumption as much as possible. A high speed, low noise, low power, and programmable readout front-end system is designed and implemented for an X-ray detector in CMOS 0.18 m technology in this thesis work. The front-end system has a peaking time of 10 ns, which is the highest speed ever reported in the published work. The front-end system is designed to achieve low noise in terms of ENC, and a low power consumption of 2.9 mW. The detector capacitance is the most dominating parameter to low noise, which in turn is directly related to the power consumption. In this thesis work an ENC of 435 electrons is achieved for a detector capacitance of 5 pF and an ENC of 320 electrons for a detector capacitance of 3 pF. Based on the comparison to related published work, a performance improvement of at least two times is achieved taking peaking time, power, ENC, and detector capacitance all into consideration. The output pulse after amplification has peak amplitude of 300 mV for a maximum injected charge of 40000 electrons from the detector. The readout front-end system noise performance is strongly dependent on the input MOSFET type, size, and biasing. In this work a PMOS has been selected and optimized as the input device due to its smaller 1/f noise and high gain as compare to NMOS when biased at same currents. The architecture designed in this work consists of a folded cascode CSA with extra cascode in first stage, a pole-zero cancellation circuit to eliminate undershoot, a shaper amplifier, and integrators using Gm-C filter technique. All of these components are optimized for low power while meeting the noise requirements. The whole front-end system is programmed for peaking times of 10, 20, and 40 ns. The programmability is achieved by switching different capacitors and resistors values for all the poles and zeros in the front-end, and by switching parallel transconductance in the Gm-C filters. Finally fine tuning of all the capacitance, resistance, and transconductance values is done to achieve required performance.