Design, synthesis, and conformational analysis of a novel series of HIV protease inhibitors

A combination of structure-based design and both solution, and solid-phase synthesis were utilized to derive a potent (nM) series of HIV-1 protease inhibitors bearing a structurally novel backbone. Detailed structural analysis of several inhibitors prepared in this series has suggested that rigidification of the P1/P2 region of this class of molecules may result in compounds with improved potency.     

Philosophically Based Limitations to Freedom of Speech in Virtual Communities

This paper applies political philosophy to the question of freedom of speech in virtual communities. It takes as its starting point the philosophical justifications given for freedom of speech in (Greenawalt, in Computers, Ethics and Social Values, Prentice-Hall, 1995). For each of these justifications I discuss the types of speech to which they apply, and implications for virtual communities. The justifications imply several limitations to freedom of speech within a well-run virtual community. I give some examples in which the existence of virtual communities can be used to reflect on extant philosophical arguments and practices. By applying the list of steps for thinking about systems given in (Churchman, in The Systems Approach, New York: Dell Publishing Co., Inc., 1968), I obtain a classification framework for thinking about the merits and demerits of a particular speech act, and describe a justification for freedom of speech, missing from Greenawalt's list, that this classification helped me to identify. I give a summary of practical suggestions for administrators of virtual communities. Finally, I discuss why I consider the question of how to regulate speech in virtual communities matters, from a global perspective.     

When is a lifting movement too asymmetric to identify low-back loading by 2-D analysis?

In ergonomics research, two-dimensional (2-D) biomechanical models are often used to study the mechanical loading of the low back in lifting movements. When lifting movements are asymmetric, errors of unknown size may be introduced in a 2-D analysis. In the current study, an estimation of these errors was made by comparing the outcome of a 2-D analysis to the results of a recently developed and validated 3-D model. Four subjects made two repetitions of five lifting movements, differing in the amount of asymmetry. The results showed a significant underestimation of the peak torque by 20, 36 and 61% when the initial position of a box was rotated 30, 60 and 90 degrees with respect to the sagittal plane of the subject. The main cause of this underestimation was a pelvic twist, resulting in an erroneous projection of a pelvic marker on to the sagittal plane due to pelvic twist. It is suggested that from 30 degrees box rotation a 2-D analysis may easily lead to wrong conclusions when it is used to study asymmetric lifting.     

Development and utility of anti-PepT1 anti-peptide polyclonal antibodies

We have considered the access resistance (AR) of a single conducting channel placed in a membrane bathed by an electrolyte. The classical expression for AR is due to Hall, who modeled the electrolyte as an ohmic conducting homogeneous medium. This approach is discussed in the present paper and it is shown that it is not valid in all cases, but depends on the ion concentration in solution and the ratio between solution and channel resistivities. To get a new expression for AR, we have combined the use of one-dimensional Nernst-Planck and Poisson (NPP) equations for the mouth of the channel and three-dimensional NPP equations for the outside solution. The influence of ion gradients and the channel itself on AR tums out to be considerable in diluted solutions (and also in the case of small channels in any solution). This influence is weaker in concentrated solutions, for which AR is well described by Hall's expression.