Targeting the cell cycle machinery for the treatment of cardiovascular disease

Cardiovascular disease represents a major clinical problem affecting a significant proportion of the world's population and remains the main cause of death in the UK. The majority of therapies currently available for the treatment of cardiovascular disease do not cure the problem but merely treat the symptoms. Furthermore, many cardioactive drugs have serious side effects and have narrow therapeutic windows that can limit their usefulness in the clinic. Thus, the development of more selective and highly effective therapeutic strategies that could cure specific cardiovascular diseases would be of enormous benefit both to the patient and to those countries where healthcare systems are responsible for an increasing number of patients. In this review, we discuss the evidence that suggests that targeting the cell cycle machinery in cardiovascular cells provides a novel strategy for the treatment of certain cardiovascular diseases. Those cell cycle molecules that are important for regulating terminal differentiation of cardiac myocytes and whether they can be targeted to reinitiate cell division and myocardial repair will be discussed as will the molecules that control vascular smooth muscle cell (VSMC) and endothelial cell proliferation in disorders such as atherosclerosis and restenosis. The main approaches currently used to target the cell cycle machinery in cardiovascular disease have employed gene therapy techniques. We will overview the different methods and routes of gene delivery to the cardiovascular system and describe possible future drug therapies for these disorders. Although the majority of the published data comes from animal studies, there are several instances where potential therapies have moved into the clinical setting with promising results.

The relationship between phonological awareness and word reading accuracy in Oriya and English: A Study of Oriya-speaking fifth-graders

This study investigated the relationships between phonological awareness and reading in Oriya and English. Oriya is the official language of Orissa, an eastern state of India. The writing system is an alphasyllabary. Ninety-nine fifth grade children (mean age 9 years 7 months) were assessed on measures of phonological awareness, word reading and pseudo-word reading in both languages. Forty-eight of the children attended Oriya-medium schools where they received literacy instruction in Oriya from grade 1 and learned English from grade 2. Fifty-one children attended English-medium schools where they received literacy instruction in English from grade 1 and in Oriya from grade 2. The results showed that phonological awareness in Oriya contributed significantly to reading Oriya and English words and pseudo-words for the children in the Oriya-medium schools. However, it only contributed to Oriya pseudo-word reading and English word reading for children in the English-medium schools. Phonological awareness in English contributed to English word and pseudo-word reading for both groups. Further analyses investigated the contribution of awareness of large phonological units (syllable, onsets and rimes) and small phonological units (phonemes) to reading in each language. The data suggest that cross-language transfer and facilitation of phonological awareness to word reading is not symmetrical across languages and may depend both on the characteristics of the different orthographies of the languages being learned and whether the first literacy language is also the first spoken language.

Reprogramming the cell cycle machinery to treat cardiovascular disease

Coronary artery disease is one of the most common heart pathologies. Restriction of blood flow to the heart by atherosclerotic lesions, leading to angina pectoris and myocardial infarction, damages the heart, resulting in impaired cardiac function. Damaged myocardium is replaced by scar tissue since surviving cardiomyocytes are unable to proliferate to replace lost heart tissue. Although narrowing of the coronary arteries can be treated successfully using coronary revascularisation procedures, re-occlusion of the treated vessels remains a significant clinical problem. Cell cycle control mechanisms are key in both the impaired cardiac repair by surviving cardiomyocytes and re-narrowing of treated vessels by maladaptive proliferation of vascular smooth muscle cells. Strategies targeting the cell cycle machinery in the heart and vasculature offer promise both for the improvement of cardiac repair following MI and the prevention of restenosis and bypass graft failure following revascularisation procedures.

Multivariable cluster analysis for high-speed industrial machinery

The overall operation and internal complexity of a particular production machinery can be depicted in terms of clusters of multidimensional points which describe the process states, the value in each point dimension representing a measured variable from the machinery. The paper describes a new cluster analysis technique for use with manufacturing processes, to illustrate how machine behaviour can be categorised and how regions of good and poor machine behaviour can be identified. The cluster algorithm presented is the novel mean-tracking algorithm, capable of locating N-dimensional clusters in a large data space in which a considerable amount of noise is present. Implementation of the algorithm on a real-world high-speed machinery application is described, with clusters being formed from machinery data to indicate machinery error regions and error-free regions. This analysis is seen to provide a promising step ahead in the field of multivariable control of manufacturing systems.