Simultaneous determination of the lactone and carboxylate forms of irintecan (CPT-11) and its actie metabolite SN-38 by high-performance liquid chromatography: Application to plasma pharmacokinetic studies in the rat.

Irinotecan (CPT-11) and its main metabolite SN-38 are potent anticancer derivatives of camptothecin (CPT), with active lactone and inactive carboxylate forms coexisting. A simple and sensitive HPLC method using the ion-pairing reagent tetrabutylammonium hydrogen sulfate (TBAHS) was developed to simultaneously determine all four analytes in rat plasma samples. Camptothecin (CPT) was used as internal standard. The mobile phase was 0.1 M potassium dihydrogen phosphate containing 0.01 M TBAHS (pH 6.4)–acetonitrile (75:25, v/v). Separation of the compounds was carried out on a Hypersil C18 column, monitored at 540 nm (excitation wavelength at 380 nm). All four compounds gave linear response as a function of concentration over 0.01–10 μM. The limit of quantitation in rat plasma was 0.01, 0.008, 0.005 and 0.005 μM for CPT-11 lactone, CPT-11 carboxylate, SN-38 lactone and SN-38 carboxylate, respectively. The method was successfully used in the study on the effect of coadministered thalidomide on the plasma pharmacokinetics of CPT-11 and SN-38 in rats. Coadministered thalidomide (100 mg/kg body weight by intraperitoneal injection) significantly increased the AUC_0–10h values of CPT-11 lactone and CPT-11 carboxylate by 32.6% and 30.3 %, respectively, (P < 0.01), but decreased the values by 19.2% and 32.4% for SN-38 lactone and carboxylate, respectively, (P < 0.05). Accordingly, the value of total body clearance (CL) of CPT-11 lactone was significantly lower in combination group compared to the control (1.329 versus 1.837 L/h/kg, P = 0.0002). Plasma t_1/2β values for SN-38 lactone and carboxylate were significantly (P < 0.01) smaller in rats with coadministered thalidomide, as compared to rats receiving CPT-11 alone. Further studies are needed to explore the underlying mechanisms for the observed kinetic interaction between CPT-11 and thalidomide.

Simultaneous state and input estimation with application to a two-link robotic system

This paper addresses the problem of estimating simultaneously the state and input of a nonlinear system with application to a two link robotic manipulator - the Pendubot. The system nonlinearity comprises a Lipschitz function with respect to the state, and a nonlinear term which is a function of both the state and input. It is shown that under some conditions, an observer can be designed to estimate simultaneously the system’s state and input. Simulation and experimental results, obtained around the inverted equilibrium position, are presented to demonstrate the validity of the approach.

Interpreting the public interest : A survey of professional accountants

The accounting profession, like all professions, has a commitment to advance the interests of the general community, as well as those they are contractually bound to serve. Providing services altruistically, at times without compensation, is a salient feature of the public interest ideal. A review of the literature indicates that the profession has abandoned its public interest role so that serving self-interest now appears to have primacy ( Bédard 2001 ; Canning and O'Dwyer 2001 ; Parker 1994 ; Saravanamuthu 2004 ). The aim of this paper is to examine members' interpretation of the public interest ideal and to elicit their perceptions on issues arising from the literature. The results of a survey to members of CPA Australia indicate that members can iterate the formal definition of the public interest, but their application of the public interest in conflict of interest situations is inconsistent with this definition.

Interpreting risk allocation mechanism in public-private partnership projects : an empirical study in a transaction cost economics perspective

Risk allocation in public-private partnership (PPP) projects is currently claimed as capability driven. While lacking theoretical support, the claim is often 'violated' by current industrial practice. There is thus a need for formal mechanisms to interpret why a particular risk is retained by government in one project while transferred to private partners in another. From the viewpoint of transaction cost economics (TCE), integrated with the resource-based view (RBV) of organizational capabilities, this paper proposed a theoretical framework for understanding risk allocation practice in PPP projects. The theories underlying the major constructs and their links were articulated. Data gathered from an industry-wide survey were used to test the framework. The results of multiple linear regression (MLR) generally support the proposed framework. It has been found that partners' risk management routine, mechanism, commitment, cooperation history, and uncertainties associated with project risk management could serve to determine the risk allocation strategies adopted in a PPP project. This theoretical framework thus provides both government and private agencies with a logical and complete understanding of the process of selecting the allocation strategy for a particular risk in PPP projects. Moreover, it could be utilized to steer the risk allocation strategy by controlling certain critical determinants identified in the study. Study limitations and future research directions have also been set out.

Object focused simultaneous estimation of optical flow and state dynamics

The framework of differential optical flow has been built upon to enhance the performance of motion estimation from optical flow. By coupling optical flow and object state parameters, an effective procedure for object tracking is implemented with the dasiaSimultaneous Estimation of Optical Flow and Object Statepsila (SEOS) technique. The SEOS method utilizes dynamic object parameter information when calculating optical flow for tracking a moving object within a video stream. Optical flow estimation for the SEOS method requires minimization of an error functional containing object physical parameter data. The convergence of an energy functional to a feasible or optimal solution set is not guaranteed. Convergence criteria is often assumed and not shown explicitly. Convergence of the SEOS method for both the Jacobi and Gauss-Seidel numerical resolution methods is evaluated.

The impact of ownership structure on corporate debt policy : two stage least square simultaneous model approach for post crisis period : evidence from Kuala Lumpur Stock Exchange

Ownership concentration as a governance mechanism has received considerable attention among academician, practitioners as well as policy makers because large-block shareholders are increasingly active in their demands that corporations adopt effective governance mechanisms to control managerial decisions, which include corporate debt policy. Earlier study on the agency model of the firm widely recognizes that the managerial ownership and external debt play an important role in mitigating agency conflicts and enhancing firm value. They also found that increase in the external monitors, for example the institutional investors, can actually play a useful role in limiting agency problems in the firm. This paper, using 100 Composite Index companies from Brusa Malaysia between 1998 to 2002 explores the impact of institutional holdings on managerial ownership and debt policy in an integrated framework by using a simultaneous equations estimation procedure (2SLS). The findings show that there is a significant impact of institutional ownership which serves effective control mechanism on managerial ownership and corporate debt policy as hypothesized. Findings of such evidence suggest that institutional holding thus have played an important role in managers' strategic management decision and reduce agency conflict. In addition, corporate debt policy too is governed by managerial ownership and exhibited a negative relation.

Simultaneous presentation of measured and calculated environmental results

Continuous measurement of internal and external environmental parameters is critical to our understanding of how buildings perform. Yet, the quantity and variety of time-series data can be quite overwhelming as well as onerous to decipher and present. In addition to this, is the fact that several of the collected data are useless in their raw format unless processed through algorithms to obtain identifiable and meaningful results.
These circumstances challenge the conventional way we present accumulated data and their processed outputs in order to get a better understanding of how and why the environmental performance occurred. It would be ideal if all of the collected and processed data could be presented in a simultaneous, yet, useful format. It is exactly the intention of this paper to suggest and present such a process as well as its format.
An example case study is provided where several parameters (air velocity, mean radiant temperature, humidity and air temperature) are measured periodically to calculate a time-series of internal comfort performance. However, external conditions of solar radiation and solar position as well as air temperature drive the interior building surface temperatures and help to explain the end result of internal comfort.
A program has been written to present the various sets of data graphically, in an integrated manner, animated as a function of time. The animation shows solar position, a cursor scanning weather data, the changing infra-red image and a representation of the resulting internal comfort performance throughout the
monitored period.

Simultaneous neuroprotection and blockade of inflammation reverses autoimmune encephalomyelitis

In multiple sclerosis, the immune system attacks the white matter of the brain and spinal cord, leading to disability and/or paralysis. Myelin, oligodendrocytes and neurons are lost due to the release by immune cells of cytotoxic cytokines, autoantibodies and toxic amounts of the excitatory neurotransmitter glutamate. Experimental autoimmune encephalomyelitis (EAE) is an animal model that exhibits the clinical and pathological features of multiple sclerosis. Current therapies that suppress either the inflammation or glutamate excitotoxicity are partially effective when administered at an early stage of EAE, but cannot block advanced disease. In a multi-faceted approach to combat EAE, we blocked inflammation with an anti-MAdCAM-1 (mucosal addressin cell adhesion molecule-1) monoclonal antibody and simultaneously protected oligodendrocytes and neurons against glutamate-mediated damage with the -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate antagonist 2,3-dihydroxy-6-nitro-7- sulfamoylbenzo(f)quinoxaline (NBQX) and the neuroprotector glycine–proline–glutamic acid (GPE; N-terminal tripeptide of insulin-like growth factor). Remarkably, administration at an advanced stage of unremitting EAE of either a combination of NBQX and GPE, or preferably all three latter reagents, resulted in amelioration of disease and repair of the CNS, as assessed by increased oligodendrocyte survival and remyelination, and corresponding decreased paralysis, inflammation, CNS apoptosis and axonal damage. Each treatment reduced the expression of nitric oxide and a large panel of proinflammatory and immunoregulatory cytokines, in particular IL-6 which plays a critical role in mediating EAE. Mice displayed discernible improvements in all physical features examined. Disease was suppressed for 5 weeks, but relapsed when treatment was suspended, suggesting treatment must be maintained to be effective. The above approaches, which allow CNS repair by inhibiting inflammation and/or simultaneously protect neurons and oligodendrocytes from damage, could thus be effective therapies for multiple sclerosis.

On the simultaneous estimation of optical flow and object state

This thesis focuses on the enhancement of differential optical flow techniques. The framwork of differential optical flow has been built upon to improve object motion estimation within a video stream or image sequence. This augmentation comes in the form of a combined optical flow and object state estimation method (SEOS)

Simultaneous removal of ammonia and phosphate from wastewater by precipitation of struvite using magnesia

A thorough investigation of conditions required for the precipitation of magnesium ammonium phosphate hexahydrate using magnesia as the source of magnesium was carried out and two computer models were used to make predictions as to optimum conditions for production of suitable crystal size and structure for a successful process. A process was developed and a bench scale model operated for a number of high ammonia wastes. Removal of ammonia was affected to levels of up to 97% with 94% ammonia removal being achievable consistently.

Interpreting and modeling baggage handling systems as a system of systems

The topic of systems of systems has been one of the most challenging areas in science and engineering due to its multidisciplinary scope and inherent complexity. Despite all attempts carried out so far in both academia and industry, real world applications are far remote. The purpose of this paper is to modify and adopt a recently developed modeling paradigm for system of systems and then employ it to model a generic baggage handling system of an airport complex. In a top-down design approach, we start modeling process by definition of some modeling goals that guide us in selection of some high level attributes. Then functional attributes are defined which act as ties between high level attributes (the first level of abstraction) and low level metrics/measurements. Since the most challenging issues in developing models for system of systems are identification and representation of dependencies amongst constituent entities, a machine learning technique is adopted for addressing these issues.

Simultaneous volatility transmission and spillover effects

Simultaneous volatility models are developed and shown to be separate from multivariate GARCH estimators. An example is provided that allows for simultaneous and unidirectional volatility and volume of trade effects. These effects are tested using intraday data from the Australian cash index and index futures markets. Overnight volatility spillover effects from the United States S&P500 index futures markets are tested using alternative estimates of this US market volatility. The simultaneous volatility model proves to be robust to alternative specifications of returns equations and to misspecification of the direction of volatility causality.