The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Defocusing image to pattern contact holes using attenuated phase shift masks

The patterning of contact holes by selecting out-of-focus image plane (defocus) using attenuated phase shift masks (APSM) has been studied. Defocus is found to enhance the image modulation at low partial coherence for contact holes with negative local average of mask function. Semi-dense holes up to 130 nm in 8% APSM have been printed by 0.5 μm defocus at a partial coherence of 0.31 using KrF scanner with highest numerical aperture of 0.68. However, these holes were closed with in-focus imaging. Defocus is also found to be beneficial for patterning the pitches that have extensive side lobes with in-focus imaging.     

THERMODYNAMICS OF ASPHALTENE PRECIPITATION AND DISSOLUTION INVESTIGATION OF TEMPERATURE AND SOLVENT EFFECTS

Petroleum asphaltenes have been precipitated in solvent mixtures of n-heptane and toluene at various temperatures, likewise n-heptane asphaltenes have been dissolved in under similar conditions. This give added evidence to apparent hysteresis phenomenon between the two processes. The Asphaltenes have been characterized showing that although data is scattered convergence to certain structural parameters as incipient flocculation is approached. The asphaltenes are seen to consist of an associating and a non-associating part. The solubility of asphaltenes has been correlated/modelled using the Flory-Huggins equation using two different terms for the Flory parameter. A process for evaluation of best choice of solubility parameter and molar volume for the asphaltenes is proposed. Dissolution processes are seen to be best fitted by the equations. Based on these findings the asphaltenes are proposed to be formed by a colloidal and a true solution part.     

Adaptive motion control using neural network approximations

In this paper, we present a new adaptive technique for tracking control of mechanical systems in the presence of friction and periodic disturbances. Radial Basis Functions (RBFs) are used to compensate for the effects of nonlinearly occurring parameters in the friction and periodic disturbance model. Theoretical analysis, such as stability and transient performance, is provided. Furthermore, the performance of the adaptive RBF controller and its non-adaptive counterpart are compared.     

Fast internal dynamics in polyelectrolyte gels measured by dynamic light scattering

Summary Dynamic light scattering was used to investigate the dynamics of sodium poly(styrene sulfonate) and fully neutralized poly(acrylic acid) gels as a function of the degree of swelling and weight ratio of cross-linking agent. It was shown that the collective diffusion coefficient increases with increasing degree of swelling and that the diffusion coefficient shows stronger concentration dependence than predicted by scaling arguments. For gel samples measured at the swelling equilibrium, the diffusion coefficient increases with increasing gel concentration for both gel systems.     

Topology preservation of template-based 6-subiteration reduction operations

Generally, a reduction operation (e.g., thinning and shrinking) on 3D binary images can be represented as a set of reduction templates where every object voxel of the image satisfying any template is turned to a background voxel. Generally, it is rather difficult, error-prone and time-consuming for verifying the topological soundness of a 3D parallel reduction operation. This paper proposes sufficient conditions of time complexity O(n) for verifying the topological soundness of 3D parallel 6-subiteration reduction operations of n templates where such a kind of 3D reduction operations is performed alternatively from the six orthogonal directions to turn object voxels to background voxels. By such sufficient conditions, the topology soundness of a 3D 6-subiteration parallel reduction operation can be verified by checking each and every of its templates.     

Control of discrete time nonlinear systems with a time-varying structure

In this paper, we present a control methodology for a class of discrete time nonlinear systems that depend on a possibly exogenous scheduling variable. This class of systems consists of an interpolation of nonlinear dynamic equations in strict feedback form, and it may represent systems with a time-varying nonlinear structure. Moreover, this class of systems is able to represent some cases of gain scheduling control, Takagi-Sugeno fuzzy systems, as well as input-output realizations of nonlinear systems which are approximated via localized linearizations. We present two control theorems, one using what we call a “global” approach (akin to traditional backstepping), and a “local” approach, our main result, where backstepping is again used but the control law is an interpolation of local control terms. An aircraft wing rock regulation problem with varying angle of attack is used to illustrate and compare the two approaches.     

Stability robustness of networked control systems with respect to packet loss

This paper is concerned with stability analysis of discrete-time networked control systems over a communication channel subject to packet loss whose behavior is modeled by an i.i.d Bernoulli process with a packet dropping probability bounded by a constant. A necessary and sufficient condition for stability is obtained. A packet dropping margin is introduced as a measure of stability robustness of a system against packet dropping, and a formula for it is derived. A design method is proposed for achieving a large margin subject to a constraint that the system has a set of prescribed nominal closed-loop poles.     

Decentralized adaptive coordinated control of multiple robot arms without using a force sensor

This paper presents a distributed adaptive coordinated control method for multiple robot arms grasping a common object. The cases of rigid contact and rolling contact are analyzed. In the proposed controller, the dynamic parameters of both object and robot arms are estimated adaptively. The desired motions of the robot arms are generated by an estimated object reference model. The control method requires only the measurements of the positions and velocities of the object and robot arms, but not the measurements of forces and moments at contact points. The asymptotic convergence of trajectory is proven by the Lyapunov-like Lemma. Experiments involving two robot arms handling a common object are shown.