Polymer-drug conjugates: current status and future trends

Polymer conjugates are nano-sized, multicomponent constructs already in the clinic as anticancer compounds, both as single agents or as elements of combinations. They have the potential to improve pharmacological therapy of a variety of solid tumors. Polymer-drug conjugation promotes passive tumor targeting by the enhanced permeability and retention (EPR) effect and allows for lysosomotropic drug delivery following endocytic capture. In the first part of this review, we analyze the promising results arising from clinical trials of polymer-bound chemotherapy. The experience gained on these studies provides the basis for the development of a more sophisticated second-generation of polymer conjugates. However, many challenges still lay ahead providing scope to develop and refine this field. The "technology platform'' of polymer therapeutics allows the development of both new and exciting polymeric materials, the incorporation of novel bioactive agents and combinations thereof to address recent advances in drug therapy. The rational design of polymer drug conjugates is expected to realize the true potential of these "nanomedicines".

A new organization for a perceptron-based branch predictor and its FPGA implementation

An unaltered rearrangement of the original computation of a neural based predictor at the algorithmic level is introduced as a new organization. Its FPGA implementation generates circuits that are 1.7 faster than a direct implementation of the original algorithm. This faster clock rate allows to implement predictors with longer history lengths using the nearly the same hardware budget.

An ontological modelling of user requirements for personalised information provision

The knowledge economy offers opportunity to a broad and diverse community of information systems users to efficiently gain information and know-how for improving qualifications and enhancing productivity in the work place. Such demand will continue and users will frequently require optimised and personalised information content. The advancement of information technology and the wide dissemination of information endorse individual users when constructing new knowledge from their experience in the real-world context. However, a design of personalised information provision is challenging because users’ requirements and information provision specifications are complex in their representation. The existing methods are not able to effectively support this analysis process. This paper presents a mechanism which can holistically facilitate customisation of information provision based on individual users’ goals, level of knowledge and cognitive styles preferences. An ontology model with embedded norms represents the domain knowledge of information provision in a specific context where users’ needs can be articulated and represented in a user profile. These formal requirements can then be transformed onto information provision specifications which are used to discover suitable information content from repositories and pedagogically organise the selected content to meet the users’ needs. The method is provided with adaptability which enables an appropriate response to changes in users’ requirements during the process of acquiring knowledge and skills.

Nitrogen fluxes from the landscape are controlled by net anthropogenic nitrogen inputs and by climate

The flux of nitrogen (N) to coastal marine ecosystems is strongly correlated with the “net anthropogenic nitrogen inputs” (NANI) to the landscape across 154 watersheds, ranging in size from 16 km2 to 279 000 km2, in the US and Europe. When NANI values are greater than 1070 kg N km−2 yr−1, an average of 25% of the NANI is exported from those watersheds in rivers. Our analysis suggests a possible threshold at lower NANI levels, with a smaller fraction exported when NANI values are below 1070 kg N km−2 yr−1. Synthetic fertilizer is the largest component of NANI in many watersheds, but other inputs also contribute substantially to the N fluxes; in some regions, atmospheric deposition of N is the major component. The flux of N to coastal areas is controlled in part by climate, and a higher percentage of NANI is exported in rivers, from watersheds that have higher freshwater discharge.

How often does direct real estate increase the risk-adjusted performance of the US mixed-asset portfolio?

The “case for real estate” in the mixed-asset portfolio is a topic of continuing interest to practitioners and academics. The argument is typically made by comparing efficient frontiers of portfolio with real estate to those that exclude real estate. However, most investors will have held inefficient portfolios. Thus, when analysing the real estate’s place in the mixed-asset portfolio it seems illogical to do so by comparing the difference in risk-adjusted performance between efficient portfolios, which few if any investor would have held. The approach adopted here, therefore, is to compare the risk-adjusted performance of a number of mixed-asset portfolios without real estate (which may or not be efficient) with a very large number of mixed-asset portfolios that include real estate (which again may or may not be efficient), to see the proportion of the time when there is an increase in risk-adjusted performance, significant or otherwise using appraisal-based and de-smoothed annual data from 1952-2003. So to the question how often does the addition of private real estate lead to increases the risk-adjusted performance compared with mixed-asset portfolios without real estate the answer is almost all the time. However, significant increases are harder to find. Additionally, a significant increase in risk-adjusted performance can come from either reductions in portfolio risk or increases in return depending on the investors’ initial portfolio structure. In other words, simply adding real estate to a mixed-asset portfolio is not enough to ensure significant increases in performance as the results are dependent on the percentage added and the proper reallocation of the initial portfolio mix in the expanded portfolio.

Peripersonal space: a multisensory interface for body-object interactions

Research in the last four decades has brought a considerable advance in our understanding of how the brain synthesizes information arising from different sensory modalities. Indeed, many cortical and subcortical areas, beyond those traditionally considered to be ‘associative,’ have been shown to be involved in multisensory interaction and integration (Ghazanfar and Schroeder 2006). Visuo-tactile interaction is of particular interest, because of the prominent role played by vision in guiding our actions and anticipating their tactile consequences in everyday life. In this chapter, we focus on the functional role that visuo-tactile processing may play in driving two types of body-object interactions: avoidance and approach. We will first review some basic features of visuo-tactile interactions, as revealed by electrophysiological studies in monkeys. These will prove to be relevant for interpreting the subsequent evidence arising from human studies. A crucial point that will be stressed is that these visuo-tactile mechanisms have not only sensory, but also motor-related activity that qualifies them as multisensory-motor interfaces. Evidence will then be presented for the existence of functionally homologous processing in the human brain, both from neuropsychological research in brain-damaged patients and in healthy participants. The final part of the chapter will focus on some recent studies in humans showing that the human motor system is provided with a multisensory interface that allows for continuous monitoring of the space near the body (i.e., peripersonal space). We further demonstrate that multisensory processing can be modulated on-line as a consequence of interacting with objects. This indicates that, far from being passive, the monitoring of peripersonal space is an active process subserving actions between our body and objects located in the space around us.