A First Step Towards Cost Functions for Quantum-dot Cellular Automata Designs

Quantum-dot cellular automata (QCA) is potentially a very attractive alternative to CMOS for future digital designs. Circuit designs in QCA have been extensively studied. However, how to properly evaluate the QCA circuits has not been carefully considered. To date, metrics and area-delay cost functions directly mapped from CMOS technology have been used to compare QCA designs, which is inappropriate due to the differences between these two technologies. In this paper, several cost metrics specifically aimed at QCA circuits are studied. It is found that delay, the number of QCA logic gates, and the number and type of crossovers, are important metrics that should be considered when comparing QCA designs. A family of new cost functions for QCA circuits is proposed. As fundamental components in QCA computing arithmetic, QCA adders are reviewed and evaluated with the proposed cost functions. By taking the new cost metrics into account, previous best adders become unattractive and it has been shown that different optimization goals lead to different “best” adders.

All-Cause Mortality up to and After Coronary Heart Disease and Stroke Events in European Middle-Aged Men The PRIME Study

Background and Purpose-The aim was to investigate prospectively the all-cause mortality risk up to and after coronary heart disease (CHD) and stroke events in European middle-aged men.

Methods-The study population comprised 10 424 men 50 to 59 years of age recruited between 1991 and 1994 in France (N=7855) and Northern Ireland (N=2747) within the Prospective Epidemiological Study of Myocardial Infarction. Incident CHD and stroke events and deaths from all causes were prospectively registered during the 10-year follow-up. In Cox's proportional hazards regression analysis, CHD and stroke events during follow-up were used as time-dependent covariates.

Results-A total of 769 CHD and 132 stroke events were adjudicated, and 569 deaths up to and 66 after CHD or stroke occurred during follow-up. After adjustment for study country and cardiovascular risk factors, the hazard ratios of all-cause mortality were 1.58 (95% confidence interval 1.18-2.12) after CHD and 3.13 (95% confidence interval 1.98-4.92) after stroke.

Conclusions-These findings support continuous efforts to promote both primary and secondary prevention of cardiovascular disease.

Parasite neuropeptide biology:Seeding rational drug target selection?

The rationale for identifying drug targets within helminth neuromuscular signalling systems is based on the premise that adequate nerve and muscle function is essential for many of the key behavioural determinants of helminth parasitism, including sensory perception/host location, invasion, locomotion/orientation, attachment, feeding and reproduction. This premise is validated by the tendency of current anthelmintics to act on classical neurotransmitter-gated ion channels present on helminth nerve and/or muscle, yielding therapeutic endpoints associated with paralysis and/or death. Supplementary to classical neurotransmitters, helminth nervous systems are peptide-rich and encompass associated biosynthetic and signal transduction components - putative drug targets that remain to be exploited by anthelmintic chemotherapy. At this time, no neuropeptide system-targeting lead compounds have been reported, and given that our basic knowledge of neuropeptide biology in parasitic helminths remains inadequate, the short-term prospects for such drugs remain poor. Here, we review current knowledge of neuropeptide signalling in Nematoda and Platyhelminthes, and highlight a suite of 19 protein families that yield deleterious phenotypes in helminth reverse genetics screens. We suggest that orthologues of some of these peptidergic signalling components represent appealing therapeutic targets in parasitic helminths.

Optimising drug solubilisation in amorphous polymer dispersions: rational selection of hot-melt extrusion processing parameters

The aim of this article was to construct a T–ϕ phase diagram for a model drug (FD) and amorphous polymer (Eudragit® EPO) and to use this information to understand the impact of how temperature–composition coordinates influenced the final properties of the extrudate. Defining process boundaries and understanding drug solubility in polymeric carriers is of utmost importance and will help in the successful manufacture of new delivery platforms for BCS class II drugs. Physically mixed felodipine (FD)–Eudragit® EPO (EPO) binary mixtures with pre-determined weight fractions were analysed using DSC to measure the endset of melting and glass transition temperature. Extrudates of 10 wt% FD–EPO were processed using temperatures (110°C, 126°C, 140°C and 150°C) selected from the temperature–composition (T–ϕ) phase diagrams and processing screw speed of 20, 100 and 200rpm. Extrudates were characterised using powder X-ray diffraction (PXRD), optical, polarised light and Raman microscopy. To ensure formation of a binary amorphous drug dispersion (ADD) at a specific composition, HME processing temperatures should at least be equal to, or exceed, the corresponding temperature value on the liquid–solid curve in a F–H T–ϕ phase diagram. If extruded between the spinodal and liquid–solid curve, the lack of thermodynamic forces to attain complete drug amorphisation may be compensated for through the use of an increased screw speed. Constructing F–H T–ϕ phase diagrams are valuable not only in the understanding drug–polymer miscibility behaviour but also in rationalising the selection of important processing parameters for HME to ensure miscibility of drug and polymer.

Nuclear translocation and functions of growth factor receptors

Cellular signal transduction in response to environmental signals involves a relay of precisely regulated signal amplifying and damping events. A prototypical signaling relay involves ligands binding to cell surface receptors and triggering the activation of downstream enzymes to ultimately affect the subcellular distribution and activity of DNA-binding proteins that regulate gene expression. These so-called signal transduction cascades have dominated our view of signaling for decades. More recently evidence has accumulated that components of these cascades can be multifunctional, in effect playing a conventional role for example as a cell surface receptor for a ligand whilst also having alternative functions for example as transcriptional regulators in the nucleus. This raises new challenges for researchers. What are the cues/triggers that determine which role such proteins play? What are the trafficking pathways which regulate the spatial distribution of such proteins so that they can perform nuclear functions and under what circumstances are these alternative functions most relevant?

Nuclear trafficking and functions of endocytic proteins implicated in oncogenesis

A subset of proteins predominantly associated with early endosomes or implicated in clathrin-mediated endocytosis can shuttle between the cytoplasm and the nucleus. Although the endocytic functions of these proteins have been extensively studied, much less effort has been expended in exploring their nuclear roles. Membrane trafficking proteins can affect signalling and proliferation and this can be achieved either at a nuclear or endocytic level. Furthermore, some proteins, such as Huntingtin interacting protein 1, are known as cancer biomarkers. This review will highlight the limits of our understanding of their nuclear functions and the relevance of this to signalling and oncogenesis.

Some Attempts in the Rational Design of Heterogeneous Catalysts Using Density Functional Theory Calculations

Heterogeneous catalysis is of great importance both industrially and academically. Rational design of heterogeneous catalysts is highly desirable, and the computational screening and design method is one of the most promising approaches for rational design of heterogeneous catalysts. Herein, we review some attempts towards the rational catalyst design using density functional theory from our group. Some general relationships and theories on the activity and selectivity are covered, such as the Brønsted–Evans–Polanyi relation, volcano curves/surfaces, chemical potentials, optimal adsorption energy window and energy descriptor of selectivity. Furthermore, the relations of these relationships and theories to the rational design are discussed, and some examples of computational screening and design method are given.