Structure and activity in assessing antioxidant activity in vitro and in vivo:a critical appraisal illustrated with the flavonoids

Structure–activity relationships are indispensable to identify the most optimal antioxidants. The advantages of in vitro over in vivo experiments for obtaining these relationships are, that the structure is better defined in vitro, since less metabolism takes place. It is also the case that the concentration, a parameter that is directly linked to activity, is more accurately controlled. Moreover, the reactions that occur in vivo, including feed-back mechanisms, are often too multi-faceted and diverse to be compensated for during the assessment of a single structure–activity relationship. Pitfalls of in vitro antioxidant research include: (i) by definition, antioxidants are not stable and substantial amounts of oxidation products are formed and (ii) during the scavenging of reactive species, reaction products of the antioxidants accumulate. Another problem is that the maintenance of a defined concentration of antioxidants is subject to processes such as oxidation and the formation of reaction products during the actual antioxidant reaction, as well as the compartmentalization of the antioxidant and the reactive species in the in vitro test system. So determinations of in vitro structure-activity relationships are subject to many competing variables and they should always be evaluated critically. (c) 2005 Published by Elsevier B.V.

Testing term structure estimation methods:evidence from the UK STRIPs market

Prices and yields of UK government zero-coupon bonds are used to test alternative yield curve estimation models. Zero-coupon bonds permit a more pure comparison, as the models are providing only the interpolation service and also not making estimation feasible. It is found that better yield curves estimates are obtained by fitting to the yield curve directly rather than fitting first to the discount function. A simple procedure to set the smoothness of the fitted curves is developed, and a positive relationship between oversmoothness and the fitting error is identified. A cubic spline function fitted directly to the yield curve provides the best overall balance of fitting error and smoothness, both along the yield curve and within local maturity regions.

The Team Climate Inventory (TCI): a psychometric test on a Taiwanese sample of work groups

Understanding the feasibility of applying the Team Climate Inventory (TCI) in non-Western cultures is essential for researchers attempting to understand the influence of culture on workers' perceived climate. This study describes the application of the TCI in such a setting using data from 203 administrators employed in a Taiwanese medical center. Reliability and factor analyses were performed to establish the feasibility and psychometric properties of the TCI Taiwan version. Reliabilities of both the four- and five-factor solutions exceeded .80. Factor analyses indicated a satisfactory four-factor structure, despite some variations in comparison with the U.K. version. The TCI Taiwan version is feasible and has acceptable psychometric properties. Further research is warranted regarding the degree to which disparities result from cultural differences and the specific nature of organizational systems in Chinese communities.

The design of environmental test rigs

Product reliability and its environmental performance have become critical elements within a product's specification and design. To obtain a high level of confidence in the reliability of the design it is customary to test the design under realistic conditions in a laboratory. The objective of the work is to examine the feasibility of designing mechanical test rigs which exhibit prescribed dynamical characteristics. The design is then attached to the rig and excitation is applied to the rig, which then transmits representative vibration levels into the product. The philosophical considerations made at the outset of the project are discussed as they form the basis for the resulting design methodologies. It is attempted to directly identify the parameters of a test rig from the spatial model derived during the system identification process. It is shown to be impossible to identify a feasible test rig design using this technique. A finite dimensional optimal design methodology is developed which identifies the parameters of a discrete spring/mass system which is dynamically similar to a point coordinate on a continuous structure. This design methodology is incorporated within another procedure which derives a structure comprising a continuous element and a discrete system. This methodology is used to obtain point coordinate similarity for two planes of motion, which is validated by experimental tests. A limitation of this approach is that it is impossible to achieve multi-coordinate similarity due to an interaction of the discrete system and the continuous element at points away from the coordinate of interest. During the work the importance of the continuous element is highlighted and a design methodology is developed for continuous structures. The design methodology is based upon distributed parameter optimal design techniques and allows an initial poor design estimate to be moved in a feasible direction towards an acceptable design solution. Cumulative damage theory is used to provide a quantitative method of assessing the quality of dynamic similarity. It is shown that the combination of modal analysis techniques and cumulative damage theory provides a feasible design synthesis methodology for representative test rigs.

Development of a neurotoxicity test-system, using human post-mitotic, astrocytic and neuronal cell lines in co-culture

Astrocytes are essential for neuronal function and survival, so both cell types were included in a human neurotoxicity test-system to assess the protective effects of astrocytes on neurons, compared with a culture of neurons alone. The human NT2.D1 cell line was differentiated to form either a co-culture of post-mitotic NT2.N neuronal (TUJ1, NF68 and NSE positive) and NT2.A astrocytic (GFAP positive) cells (∼2:1 NT2.A:NT2.N), or an NT2.N mono-culture. Cultures were exposed to human toxins, for 4 h at sub-cytotoxic concentrations, in order to compare levels of compromised cell function and thus evidence of an astrocytic protective effect. Functional endpoints examined included assays for cellular energy (ATP) and glutathione (GSH) levels, generation of hydrogen peroxide (H2O2) and caspase-3 activation. Generally, the NT2.N/A co-culture was more resistant to toxicity, maintaining superior ATP and GSH levels and sustaining smaller significant increases in H2O2 levels compared with neurons alone. However, the pure neuronal culture showed a significantly lower level of caspase activation. These data suggest that besides their support for neurons through maintenance of ATP and GSH and control of H2O2 levels, following exposure to some substances, astrocytes may promote an apoptotic mode of cell death. Thus, it appears the use of astrocytes in an in vitro predictive neurotoxicity test-system may be more relevant to human CNS structure and function than neuronal cells alone. © 2007 Elsevier Ltd. All rights reserved.

Network effects, network structure and consumer interaction in mobile telecommunications in Europe and Asia

This paper estimates the importance of (tariff-mediated) network effects and the impact of a consumer's social network on her choice of mobile phone provider. The study uses network data obtained from surveys of students in several European and Asian countries. We use the Quadratic Assignment Procedure, a non-parametric permutation test, to adjust for the particular error structure of network data. We find that respondents strongly coordinate their choice of mobile phone providers, but only if their provider induces network effects. This suggests that this coordination depends on network effects rather than on information contagion or pressure to conform to the social environment.

Differences between younger and older adults in the structure of suicidal intent and its correlates

OBJECTIVE: To analyze differences in the variables associated with severity of suicidal intent and in the main factors associated with intent when comparing younger and older adults. DESIGN: Observational, descriptive cross-sectional study. SETTING: Four general hospitals in Madrid, Spain. PARTICIPANTS: Eight hundred seventy suicide attempts by 793 subjects split into two groups: 18-54 year olds and subjects older than 55 years. MEASUREMENTS: The authors tested the factorial latent structure of suicidal intent through multigroup confirmatory factor analysis for categorical outcomes and performed statistical tests of invariance across age groups using the DIFFTEST procedure. Then, they tested a multiple indicators-multiple causes (MIMIC) model including different covariates regressed on the latent factor "intent" and performed two separate MIMIC models for younger and older adults to test for differential patterns. RESULTS: Older adults had higher suicidal intent than younger adults (z = 2.63, p = 0.009). The final model for the whole sample showed a relationship of intent with previous attempts, support, mood disorder, personality disorder, substance-related disorder, and schizophrenia and other psychotic disorders. The model showed an adequate fit (chi²[12] = 22.23, p = 0.035; comparative fit index = 0.986; Tucker-Lewis index = 0.980; root mean square error of approximation = 0.031; weighted root mean square residual = 0.727). All covariates had significant weights in the younger group, but in the older group, only previous attempts and mood disorders were significantly related to intent severity. CONCLUSIONS: The pattern of variables associated with suicidal intent varies with age. Recognition, and treatment of geriatric depression may be the most effective measure to prevent suicidal behavior in older adults.