Expression of ATM, p53, and the MRE11-Rad50-NBS1 complex in myoepithelial cells from benign and malignant proliferations of the breast

Aims: To analyse the expression of proteins involved in DNA double strand break detection and repair in the luminal and myoepithelial compartments of benign breast lesions and malignant breast tumours with myoepithelial differentiation. Methods: Expression of the ataxia telangiectasia (ATM) and p53 proteins was immunohistochemically evaluated in 18 benign and malignant myoepithelial tumours of the breast. Fifteen benign breast lesions with prominent myoepithelial compartment were also evaluated for these proteins, in addition to those in the MRE11-Rad50-NBS1 (MRN) complex, and the expression profiles were compared with those seen in eight independent non-cancer (normal breast) samples and in the surrounding normal tissues of the benign and malignant tumours examined. Results: ATM expression was higher in the myoepithelial compartment of three of 15 benign breast lesions and lower in the luminal compartment of eight of these lesions compared with that found in the corresponding normal tissue compartments. Malignant myoepithelial tumours overexpressed ATM in one of 18 cases. p53 was consistently negative in benign lesions and was overexpressed in eight of 18 malignant tumours. In benign breast lesions, expression of the MRN complex was significantly more reduced in myoepithelial cells (up to 73%) than in luminal cells (up to 40%) (p = 0.0005). Conclusions: Malignant myoepithelial tumours rarely overexpress ATM but are frequently positive for p53. In benign breast lesions, expression of the MRN complex was more frequently reduced in the myoepithelial than in the luminal epithelial compartment, suggesting different DNA repair capabilities in these two cell types.

The role of drinking restraint in alcohol dependence: validation of the temptation and restraint inventory in an alcohol dependent sample

Objective: The Temptation and Restraint Inventory (TRI) is commonly used to measure drinking restraint in relation to problem drinking behavior. However, as yet the TRI has not been validated in a clinical group with alcohol dependence. Method: Male (n = 111) and female (n = 57) inpatients with DSM-IV diagnosed alcohol dependence completed the TRI and measures of problem drinking severity, including the Alcohol Dependence Scale and the quantity, frequency and week total of alcohol consumed. Results: The factor structure of the TRI was replicated in the alcohol dependent sample. Cognitive Emotional Preoccupation (CEP), one of the two higher order factors of the TRI, demonstrated sound predictive power toward all dependence severity indices. The other higher order factor, Cognitive Behavioral Control (CBC), was related to frequency of drinking. There was limited support for the CEP/CBC interactional model of drinking restraint. Conclusions: Although the construct validity of the TRI was sound, the measure appears more useful in understanding the development, maintenance and severity of alcohol-related problems in nondependent drinkers. The TRI may show promise in detecting either continuous drinking or heavy episodic type dependent drinkers.

Alcohol-responsive genes in the frontal cortex and nucleus accumbens of human alcoholics

The molecular processes underlying alcohol dependence are not fully understood. Many characteristic behaviours result from neuroadaptations in the mesocorticolimbic system. In addition, alcoholism is associated with a distinct neuropathology. To elucidate the molecular basis of these features, we compared the RNA expression profile of the nucleus accumbens and prefrontal cortex of human brain from matched individual alcoholic and control cases using cDNA microarrays. Approximately 6% of genes with a marked alcohol response were common to the two brain regions. Alcohol-responsive genes were grouped into 11 functional categories. Predominant alcohol-responsive genes in the prefrontal cortex were those encoding DNA-binding proteins including transcription factors and repair proteins. There was also a down-regulation of genes encoding mitochondrial proteins, which could result in disrupted mitochondrial function and energy production leading to oxidative stress. Other alcohol-responsive genes in the prefrontal cortex were associated with neuroprotection/apoptosis. In contrast, in the nucleus accumbens, alcohol-responsive genes were associated with vesicle formation and regulation of cell architecture, which suggests a neuroadaptation to chronic alcohol exposure at the level of synaptic structure and function. Our data are in keeping with the previously reported alcoholism-related pathology characteristic of the prefrontal cortex, but suggest a persistent decrease in neurotransmission and changes in plasticity in the nucleus accumbens of the alcoholic.

The use of non-verbal repair strategies by children with autism

This study examined possible links between the occurrence of prosodic changes to vocalizations and gestures and the use of problem behaviors by children with autism when attempting to repair communication breakdowns. The repair strategies of six children with autism aged 2-5 years and with fewer than 10 words or signs were analyzed. Mother-child dyads were videotaped at home interacting in naturally occurring contexts. Videotapes were analyzed and coded for communication breakdowns and repair attempts made by the child. Repairs were further analyzed according to the type of repair strategy used, changes in prosidy, and whether the repair mode involved problematic or non-problematic behavior. In most situations, this group of children attempted to repair breakdowns in communication that occurred while interacting with their mothers. Most children used both nonproblematic and problematic behaviors and were less likely to use augmentations as a repair strategy than repetitions and substitutions. Some repetitions and some augmentations involved the use of gestures or vocalizations with increased emphasis or prosidy. Possible links between repair strategies involving increased prosidy and the use of problem behaviors are discussed together with the implications and significance of these finding in relation to early intervention for children with significant communication impairments. (C) 2004 Elsevier Ltd. All rights reserved.

Legume nodulation: successful symbiosis through short- and long-distance signalling

Nodulation in legumes provides a major conduit of available nitrogen into the biosphere. The development of nitrogen-fixing nodules results from a symbiotic interaction between soil bacteria, commonly called rhizobia, and legume plants. Molecular genetic analysis in both model and agriculturally important legume species has resulted in the identification of a variety of genes that are essential for the establishment, maintenance and regulation of this symbiosis. Autoregulation of nodulation (AON) is a major internal process by which nodule numbers are controlled through prior nodulation events. Characterisation of AON-deficient mutants has revealed a novel systemic signal transduction pathway controlled by a receptor-like kinase. This review reports our present level of understanding on the short- and long-distance signalling networks controlling early nodulation events and AON.

Never-married childless women in Australia: Health and social circumstances in older age

A growing proportion of women reach older age without having married or having children. Assumptions that these older women are lonely, impoverished, and high users of social and health services are based on little evidence. This paper uses data from the Older cohort of the Australian Longitudinal Study on Women's Health to describe self-reported demographics, physical and emotional health, and use of services among 10,108 women aged 73-78, of whom 2.7% are never-married and childless. The most striking characteristic of this group is their high levels of education, which are associated with fewer reported financial difficulties and higher rates of private health insurance. There are few differences in self-reported physical or emotional health or use of health services between these and other groups of older women. Compared with older married women with children, they make higher use of formal services such as home maintenance and meal services, and are also more likely to provide volunteer services and belong to social groups. Overall, there is no evidence to suggest that these women are a problem group. Rather, it seems that their life experiences and opportunities prepare them for a successful and productive older age. (c) 2005 Elsevier Ltd. All rights reserved.

Stoichiometric and kinetic characterisation of Nitrobacter in mixed culture by decoupling the growth and energy generation processes

The growth, maintenance and lysis processes of Nitrobacter were characterised. A Nitrobacter culture was enriched in a sequencing batch reactor (SBR). Fluorescent in situ hybridisation showed that Nitrobacter constituted 73% of the bacterial population. Batch tests were carried out to measure the oxygen uptake rate and/or nitrite consumption rate when both nitrite and CO2 were in excess, and in the absence of either of these two substrates. The results obtained, along with the SBR performance data, allowed the determination of the maintenance coefficient and in situ cell lysis rate of Nitrobacter. Nitrobacter spends a significant amount of energy for maintenance, which varies considerably with the specific growth rate. At maximum growth, Nitrobacter consume nitrite at a rate of 0.042 mgN/mgCOD(biomass)center dot h for maintenance purposes, which increases more than threefold to 0.143 mgN/mgCOD(biomass)center dot h in the absence of growth. In the SBR, where Nitrobacter grew at 40% of its maximum growth rate, a maintenance coefficient of 0.113 mgN/mgCOD center dot h was found, resulting in 42% of the total amount of nitrite being consumed for maintenance. The above three maintenance coefficient values obtained at different growth rates appear to support the maintenance model proposed in Pirt (1982). The in situ lysis rate of Nitrobacter was determined to be 0.07/day under aerobic conditions at 22 C and pH 7.3. Further, the maximum specific growth rate of Nitrobacter was estimated to be 0.02/h (0.48/day). The affinity constant of Nitrobacter with respect to nitrite was determined to be 1.50 mgNO(2)(-)-N/L, independent of the presence or absence of CO2. (c) 2006 Wiley Periodicals, Inc.

Comparative susceptibility of indigenous and improved pig breeds to Classical swine fever virus infection: Practical and epidemiological implications in a subsistence-based, developing country setting

This study investigated the comparative susceptibility of indigenous Moo Laat and improved Large White/Landrace pig breeds to infection with classical swine fever virus (CSFV) under controlled conditions in the Lao People's Democratic Republic (Lao PDR). The Moo Laat (ML) and Large White/Landrace crossbreed (LWC) pigs were inoculated with a standard challenge strain designated Lao/Kham225 (infectivity titre of 10(2.75) TCID50/ml). The results demonstrated that both the native breed and an improved pig breed are fully susceptible to CSFV infection and the mortality rate is high. LWC pigs demonstrated lower (or shorter) survival times (50% survival time: 11 days), earlier and higher pyrexia and earlier onset of viraemia compared to ML pigs (50% survival time: 18 days). In the context of village-based pig production, the longer time from infection to death in native ML pigs means that incubating or early sick pigs are likely to be sold once an outbreak of CSF is recognized in a village. This increased longevity probably contributes to the maintenance and spread of disease in a population where generally the contact rate is low.

Using HLT for acquiring, retrieving and publishing knowledge in AKT:position paper

AKT is a major research project applying a variety of technologies to knowledge management. Knowledge is a dynamic, ubiquitous resource, which is to be found equally in an expert's head, under terabytes of data, or explicitly stated in manuals. AKT will extend knowledge management technologies to exploit the potential of the semantic web, covering the use of knowledge over its entire lifecycle, from acquisition to maintenance and deletion. In this paper we discuss how HLT will be used in AKT and how the use of HLT will affect different areas of KM, such as knowledge acquisition, retrieval and publishing.

Reconstructing the past? Low German and the creating of regional identity in public language display

This article deals with language contact between a dominant standard language -German - and a lesser-used variety - Low German - in a situation in which the minoritised language is threatened by language shift and language loss. It analyses the application of Low German in forms of public language display and the selfpresentation of the community in tourism brochures, focusing on bilingual linguistic practices on the one hand and on underlying discourses on the other. It reveals that top-down and bottom-up approaches to implementing Low German in public language display show a remarkable homogeneity, thus creating a regional 'brand'. The article asks whether a raised level of visibility will in itself guarantee better chances for linguistic maintenance and survival of the threatened language. © 2011 Taylor & Francis.

Bilingualism and educational achievement:a study of young bilinguals in Birmingham schools and colleges

This study aimed firstly to investigate current patterns of language use amongst young bilinguals in Birmingham and secondly to examine the relationship between this language use and educational achievement. The research then focussed on various practices, customs and attitudes which would favour the attrition or survival of minority languages in the British situation. The data necessary to address this question was provided by a sample of three hundred and seventy-four 16-19 year olds, studying in Birmingham schools and colleges during the period 1987-1990 and drawn from the main linguistic minority communities in Birmingham. The research methods chosen were both quantitative and qualitative. The study found evidence of ethnolinguistic vitality amongst many of the linguistic minority communities in Birmingham: a number of practices and a range of attitudes indicate that linguistic diversity may continue and that a stable diglossic situation may develop in some instances, particularly where demographical and religious factors lead to closeness of association. Where language attrition is occurring it is often because of the move from a less prestigious minority language or dialect to a more prestigious minority language in addition to pressures from English. The educational experience of the sample indicates that literacy and formal language study are of key importance if personal bilingualism is to be experienced as an asset; high levels of oral proficiency in the L1 and L2 do not, on their own, necessarily correlate with positive educational benefit. The intervening variable associated with educational achievement appears to be the formal language learning process and literacy. A number of attitudes and practices, including the very close associations maintained with some of the countries of origin of the families, were seen to aid or hinder first language maintenance and second language acquisition.

The appraisal and management of multi-storey dwelling blocks using large concrete panel systems

This exploratory study is concerned with the integrated appraisal of multi-storey dwelling blocks which incorporate large concrete panel systems (LPS). The first step was to look at U.K. multi-storey dwelling stock in general, and under the management of Birmingham City Council in particular. The information has been taken from the databases of three departments in the City of Birmingham, and rearranged in a new database using a suite of PC software called `PROXIMA' for clarity and analysis. One hundred of their stock were built large concrete panel system. Thirteen LPS blocks were chosen for the purpose of this study as case-studies depending mainly on the height and age factors of the block. A new integrated appraisal technique has been created for the LPS dwelling blocks, which takes into account the most physical and social factors affecting the condition and acceptability of these blocks. This appraisal technique is built up in a hierarchical form moving from the general approach to particular elements (a tree model). It comprises two main approaches; physical and social. In the physical approach, the building is viewed as a series of manageable elements and sub-elements to cover every single physical or environmental factor of the block, in which the condition of the block is analysed. A quality score system has been developed which depends mainly on the qualitative and quantitative conditions of each category in the appraisal tree model, and leads to physical ranking order of the study blocks. In the social appraisal approach, the residents' satisfaction and attitude toward their multi-storey dwelling block was analysed in relation to: a. biographical and housing related characteristics; and b. social, physical and environmental factors associated with this sort of dwelling, block and estate in general.The random sample consisted of 268 residents living in the 13 case study blocks. Data collected was analysed using frequency counts, percentages, means, standard deviations, Kendall's tue, r-correlation coefficients, t-test, analysis of variance (ANOVA) and multiple regression analysis. The analysis showed a marginally positive satisfaction and attitude towards living in the block. The five most significant factors associated with the residents' satisfaction and attitude in descending order were: the estate, in general; the service categories in the block, including heating system and lift services; vandalism; the neighbours; and the security system of the block. An important attribute of this method, is that it is relatively inexpensive to implement, especially when compared to alternatives adopted by some local authorities and the BRE. It is designed to save time, money and effort, to aid decision making, and to provide ranked priority to the multi-storey dwelling stock, in addition to many other advantages. A series of solution options to the problems of the block was sought for selection and testing before implementation. The traditional solutions have usually resulted in either demolition or costly physical maintenance and social improvement of the blocks. However, a new solution has now emerged, which is particularly suited to structurally sound units. The solution of `re-cycling' might incorporate the reuse of an entire block or part of it, by removing panels, slabs and so forth from the upper floors in order to reconstruct them as low-rise accommodations.

Evaluating and developing project-based learning:an empirical approach to evaluating CDIO

As a global profession, engineering is integral to the maintenance and further development of society. Indeed, contemporary social problems requiring engineering solutions are not only a consequence of natural and ‘manmade’ disasters (such as the Japanese earthquake or the oil leakage in the Gulf of Mexico) but also encapsulate 21st Century dilemmas around sustainability, poverty and pollution [2,6,7]. Given the complexity of such problems and the constant need for innovation, the demand for engineering education to provide a ready supply of suitably qualified engineering graduates, able to make innovative decisions has never been higher [3,5]. Bearing this in mind, and taking account problems of attrition in engineering education [1,6,4] innovation in the way in which the curriculum is developed and delivered is crucial. CDIO [Conceive, Design, Implement, Operate] provides a potentially ground-breaking solution to such dilemmas. Aimed at equipping students with practical engineering skills supported by the necessary theoretical background, CDIO could potentially change the way engineering is perceived and experienced within higher education. Aston University introduced CDIO into its Mechanical Engineering and Design programmes in October 2011. From its induction, engineering education researchers have ‘shadowed’ the staff responsible for developing and teaching the programme. Utilising an Action Research Design, and adopting a mixed methodological research design, the researchers have worked closely with the teaching team to critically reflect on the processes involved in introducing CDIO into the curriculum. Concurrently, research has been conducted to capture students’ perspectives of CDIO. In evaluating the introduction of CDIO at Aston, the researchers have developed a distinctive research strategy with which to evaluate CDIO. It is the emergent findings from this research that form the basis of this paper. Although early-on in its development CDIO is making a significant difference to engineering education at the University. The paper draws attention to pedagogical, practical and professional issues – discussing each one in turn and in doing so critically analysing the value of CDIO from academic, student and industrial perspectives. The paper concludes by noting that whilst CDIO represents a forwardthinking approach to engineering education, the need for constant innovation in learning and teaching should not be forgotten. Indeed, engineering education needs to put itself at the forefront of pedagogic practice. Providing all-rounded engineers, ready to take on the challenges of the 21st Century!

Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia

Context: Genetic, neuroimaging, and molecular neurobiological evidence support the hypothesis that the disconnectivity syndrome in schizophrenia (SZ) could arise from failures of saltatory conduction and abnormalities at the nodes of Ranvier (NOR) interface where myelin and axons interact. Objective: To identify abnormalities in the expression of oligodendroglial genes and proteins that participate in the formation, maintenance, and integrity of the NOR in SZ. Design: The messenger RNA (mRNA) expression levels of multiple NOR genes were quantified in 2 independent postmortem brain cohorts of individuals with SZ, and generalizability to protein expression was confirmed. The effect of the ANK3 genotype on the mRNA expression level was tested in postmortem human brain. Case-control analysis tested the association of the ANK3 genotype with SZ. The ANK3 genotype's influence on cognitive task performance and functional magnetic resonance imaging activation was tested in 2 independent cohorts of healthy individuals. Setting: Research hospital. Patients: Postmortem samples from patients with SZ and healthy controls were used for the brain expression study (n=46) and the case-control analysis (n=272). Healthy white men and women participated in the cognitive (n=513) and neuroimaging (n=52) studies. Main Outcome Measures: The mRNA and protein levels in postmortem brain samples, genetic association with schizophrenia, cognitive performance, and blood oxygenation level-dependent functional magnetic resonance imaging. Results: The mRNA expression of multiple NOR genes was decreased in schizophrenia. The ANK3 rs9804190 C allele was associated with lower ANK3 mRNA expression levels, higher risk for SZ in the case-control cohort, and poorer working memory and executive function performance and increased prefrontal activation during a working memory task in healthy individuals. Conclusions: These results point to abnormalities in the expression of genes and protein associated with the integrity of the NOR and suggest them as substrates for the disconnectivity syndrome in SZ. The association of ANK3 with lower brain mRNA expression levels implicates a molecular mechanism for its genetic, clinical, and cognitive associations with SZ. ©2012 American Medical Association. All rights reserved.

Total productive maintenance implementation in the newspaper printing industry:an action research approach

The objective of Total Productive Maintenance (TPM) is to maximise plant and equipment effectiveness, to create a sense of ownership for operators, and promote continuous improvement through small group activities involving production, engineering and maintenance personnel. This paper describes and analyses a case study of TPM implementation at a newspaper printing house in Singapore. However, rather than adopting more conventional implementation methods such as employing consultants or through a project using external training, a unique approach was adopted based on Action Research using a spiral of cycles of planning, acting observing and reflecting. An Action Research team of company personnel was specially formed to undertake the necessary fieldwork. The team subsequently assisted with administering the resulting action plan. The main sources of maintenance and operational data were from interviews with shop floor workers, participative observation and reviews conducted with members of the team. Content analysis using appropriate statistical techniques was used to test the significance of changes in performance between the start and completion of the TPM programme. The paper identifies the characteristics associated with the Action Research method when used to implement TPM and discusses the applicability of the approach in related industries and processes.