Electron Transfer-oxy Radical Mechanism for Anti-cancer Agents: 9-anilinoacridines

A possible mode of action involving electron transfer is advanced for the 9- anilinoacridines. The mechanism entails formation of toxic oxy radicals which destroy the neoplasm. Cyclic voltammetry was performed on iminium type ions derived by protonation of the acridines. Reductions were generally reversible with potentials of about - 0.60 V. Involvement of quinoidal metabolites is also a possibility. The relationship of electrochemical behavior to structure and physiological activity is addressed

Anti-cancer Action of Metal Complexes: Electron Transfer and Oxidative Stress?

Evidence is presented in support of an electron transfer mechanism for various metal complexes possessing anti-neoplastic properties. Cyclic voltammetry was performed on several metallocenes, bis(acetato)bis(imidazole)Cu(II), and coordination compounds (Cu or Fe) of the anti-tumor agents, bipyridine, phenanthroline, hydroxyurea, diethyldithiocarbamate, and α, α1-bis(8-hydroxyquinolin-7-yl)-4-methoxytoluene. The favorable reduction potentials ranged from +0.5 to -0.5 V. Electrochemical behavior is correlated in some cases with structure and physiological activity. Relevant literature data are discussed

2D bipedal walking with knees and feet: A hybrid control approach

In this paper, we consider an anthropomorphically-inspired hybrid model of a bipedal robot with locking knees and feet in order to develop a control law that results in human-like walking. The presence of feet results in periods of full actuation and periods of underactuation during the course of a step. Properties of each of these phases of walking are utilized in order to achieve a stable walking gait. In particular, we will show that using controlled symmetries in the fully-actuated domains coupled with ¿partial¿ controlled symmetries and local ankle control laws in the underactuated domains yields stable walking; this result is possible due to the amount of time which the biped spends in the fully-actuated domains. The paper concludes with simulation results along with a comparison of these results to human walking data

3D bipedal walking with knees and feet: A hybrid geometric approach

Motivated by the goal of obtaining more-anthropomorphic walking in bipedal robots, this paper considers a hybrid model of a 3D hipped biped with feet and locking knees. The main observation of this paper is that functional Routhian Reduction can be used to extend two-dimensional walking to three dimensions-even in the presence of periods of underactuation-by decoupling the sagittal and coronal dynamics of the 3D biped. Specifically, we assume the existence of a control law that yields stable walking for the 2D sagittal component of the 3D biped. The main result of the paper is that utilizing this controller together with “reduction control laws” yields walking in three dimensions. This result is supported through simulation

Charge Transfer-oxy Radical Mechanism for Anti-cancer Agents

The proposal is advanced that anti-cancer drugs generally function by charge transfer resulting in formation of toxic oxy radicals which destroy the neoplasm. Electrochemical studies were performed with some of the main types of agents: iminium ions (adenine iminium from alkylating species, iminium metabolite of 6-mercaptopurine, nitidine, other polynuclear iminiums) and metal complexes (Pt(II)diaquodiammine-guanosine, copper salicylaldoximes). Reduction potentials ranged from -0.4 to -1.2 V. Literature data for quinones are presented and radiation is discussed. Based on the theoretical framework, a rationale is offered for the carcinogen-anti-cancer paradox and the role of antioxidants

Motivation Matters: Understanding the Antidepressant Mechanism of Physical Activity among Young Adults

International Journal of Exercise Science 17(5): 861-873, 2024. A negative association between physical activity and depressive symptoms is consistently reported within scientific literature and physical self-concept has been suggested to mediate this pathway. However, for whom these associations are strongest remains poorly understood, and little is known about how other psychosocial factors might be implicated. Consequently, we examined how various exercise motivations, specifically appearance, physical health, and mental health, might moderate the indirect effect of physical activity on depressive symptoms through physical self-concept. Canadian young adults (N = 496, Mage = 20.36, SD = 1.87) completed an online questionnaire. Mediation and moderated-mediation models were tested using PROCESS macro in RStudio. A significant indirect effect (ß = -0.18, CI [-0.005, -0.003]) of physical activity on depressive symptoms through physical self-concept was found. Exercise motivations moderated the association between physical activity and physical self-concept, such that the association was stronger when individuals were motivated by physical health. Thus, the effect of physical activity on depressive symptoms varied according to physical self-concept and physical health-exercise motivations. We conclude that motivation should be considered when developing and delivering physical activity prevention efforts for depressive symptoms

System Identification and Control of Valkyrie through SVA--Based Regressor Computation

This paper demonstrates simultaneous identification and control of the humanoid robot, Valkyrie, utilizing Spatial Vector Algebra (SVA). In particular, the inertia, Coriolis-centrifugal and gravity terms for the dynamics of a robot are computed using spatial inertia tensors. With the assumption that the link lengths or the distance between the joint axes are accurately known, it will be shown that inertial properties of a robot can be directly evaluated from the inertia tensor. An algorithm is proposed to evaluate the regressor, yielding a run time of O(n^2). The efficiency of this algorithm yields a means for online system identification via the SVA--based regressor and, as a byproduct, a method for accurate model-based control. Experimental validation of the proposed method is provided through its implementation in three case studies: offline identification of a double pendulum and a 4-DOF robotic leg, and online identification and control of a 4-DOF robotic arm

Binding interface change and cryptic variation in the evolution of protein-protein interactions

Background:Physical interactions between proteins are essential for almost all biological functions and systems. To understand the evolution of function it is therefore important to understand the evolution of molecular interactions. Of key importance is the evolution of binding specificity, the set of interactions made by a protein, since change in specificity can lead to “rewiring” of interaction networks. Unfortunately, the interfaces through which proteins interact are complex, typically containing many amino-acid residues that collectively must contribute to binding specificity as well as binding affinity, structural integrity of the interface and solubility in the unbound state. Results: In order to study the relationship between interface composition and binding specificity, we make use of paralogous pairs of yeast proteins. Immediately after duplication these paralogues will have identical sequences and protein products that make an identical set of interactions. As the sequences diverge, we can correlate amino-acid change in the interface with any change in the specificity of binding. We show that change in interface regions correlates only weakly with change in specificity, and many variants in interfaces are functionally equivalent. We show that many of the residue replacements within interfaces are silent with respect to their contribution to binding specificity. Conclusions: We conclude that such functionally-equivalent change has the potential to contribute to evolutionary plasticity in interfaces by creating cryptic variation, which in turn may provide the raw material for functional innovation and coevolution.BBSRCWellcome Trust Institutional Strategic Support Awar