Cellular uptake and biological activity of synthetic hammerhead ribozymes

Glioblastoma Multiforme (GBM) is a highly malignant form of brain cancer for which there is no effective cure. The over-expression of a number of genes, including the epidermal growth factor receptor (EGFr), has been implicated as a causative factor of tumourigenesis. Ribozymes are a class of ribonucleic acid that possess enzymatic properties. They can inhibit gene-expression in a highly sequence specific manner by catalysing the trans-cleavage of target RNA. The potential use of synthetic hammerhead ribozymes as novel anti-brain tumour agents was investigated in this study. The successful use of synthetic, exogenously administered ribozymes for such applications will require chemical modifications that improve biological stability and a fundamental understanding of cellular uptake mechanisms. Chimeric 2'-O-methylated hammerhead ribozymes proved to be significantly more stable (>4000-fold) in serum than unmodified RNA ribozymes and exhibited high in vitro catalytic activity. The cellular association of an internally [32P]-labelled 2'-O-methylated chimeric ribozyme in U87-MG human glioma cells was temperature-, energy- and pH-dependent and involved an active process that could be competed with a variety of polyanions. Indications are that the predominant mechanism of uptake is by adsorptive and / or receptor mediated endocytosis. Twenty 2'-O-methylated chimeric ribozymes were designed to cleave various sites along the EGFr mRNA. In vitro, 18 ribozymes exhibited high activity in cleaving a complementary short substrate. Using LipofectAMINETM as a delivery agent, the efficacy of these ribozymes was evaluated in the A431 cell line, which expresses amplified levels of EGFr. Studies revealed that although the ribozymes were taken up by the cells and remained stable over a period of 4 days, no significant reduction in either EGFr expression or cell proliferation was evident. The presence of telomerase, a ribonucleoprotein responsible for telomere elongation, has been strongly associated with tumour progression. The biological activity of a 2'-O-methylated ribozyme targeted against the RNA component of telomerase was determined. The ribozyme exhibited specific dose-dependent inhibition of telomerase activity in U87-MG cell lysates with an IC50 of –4μM. When 4μM ribozyme was delivered to intact U87-MG cells, complexed to LipofectAMINETM, telomerase activity was significantly reduced to 74.5±4.17% of the untreated control. Free ribozyme showed no significant inhibitory effect demonstrating the importance of an appropriate delivery system for optimum delivery of exogenously administered ribozymes.

Consumer responses to really new products: examining the impacts of learning strategies and presentation formats on product comprehension and attitude formation

Mental simulations and analogies have been identified as powerful learning tools for RNPs. Furthermore, visuals in advertising have recently been conceptualized as meaningful sources of information as opposed to peripheral cues and thus may help consumers learn about RNPs. The study of visual attention may also contribute to understanding the links between conceptual and perceptual analyses when learning for a RNP. Two conceptual models are developed. the first model consists of causal relationships between the attributes of advertising stimuli for RNPs and consumer responses, as well as mediating influences. The second model focuses on the role of visual attention in product comprehension as a response to advertising stimuli. Two experiments are conducted: a Web-Experiment and an eye-tracking experiment. The first experiment (858 subjects) examines the effect of learning strategies (mental simulation vs. analogy vs. no analogy/no mental simulation) and presentation formats (words vs. pictures) on individual responses. The mediating role of emotions is assessed. The second experiment investigates the effect of learning strategies and presentation formats on product comprehension, along with the role of attention (17 subjects). The findings from experiment 1 indicate that learning strategies and presentation formats can either enhance or undermine the effect of advertising stimuli on individual responses. Moreover, the nature of the product (i.e. hedonic vs. utilitarian vs. hybrid) should be considered when designing communications for RNPs. The mediating role of emotions is verified. Experiment 2 suggests that an increase in attention to the message may either reflect enhanced comprehension or confusion.

Breaking down barriers:teenage girls’ perceptions of engineering as a study and career choice

Background: Stereotypically perceived to be an ‘all male’ occupation, engineering has for many years failed to attract high numbers of young women [1,2]. The reasons for this are varied, but tend to focus on misconceptions of the profession as being more suitable for men. In seeking to investigate this issue a participatory research approach was adopted [3] in which two 17 year-old female high school students interviewed twenty high school girls. Questions focused on the girls’ perceptions of engineering as a study and career choice. The findings were recorded and analysed using qualitative techniques. The study identified three distinctive ‘influences’ as being pivotal to girls’ perceptions of engineering; pedagogical; social; and, familial. Pedagogical Influences: Pedagogical influences tended to focus on science and maths. In discussing science, the majority of the girls identified biology and chemistry as more ‘realistic’ whilst physics was perceived to more suitable for boys. The personality of the teacher, and how a particular subject is taught, proved to be important influences shaping opinions. Social Influences: Societal influences were reflected in the girls’ career choice with the majority considering medical or social science related careers. Although all of the girls believed engineering to be ‘male dominated’, none believed that a woman should not be engineer. Familial Influences: Parental influence was identified as key to career and study choice; only two of the girls had discussed engineering with their parents of which only one was being actively encouraged to pursue a career in engineering. Discussion: The study found that one of the most significant barriers to engineering is a lack of awareness. Engineering did not register in the girls’ lives, it was not taught in school, and only one had met a female engineer. Building on the study findings, the discussion considers how engineering could be made more attractive to young women. Whilst misconceptions about what an engineer is need to be addressed, other more fundamental pedagogical barriers, such as the need to make physics more attractive to girls and the need to develop the curriculum so as to meet the learning needs of 21st Century students are discussed. By drawing attention to the issues around gender and the barriers to engineering, this paper contributes to current debates in this area – in doing so it provides food for thought about policy and practice in engineering and engineering education.

Decreased NADPH oxidase expression and antioxidant activity in cachectic skeletal muscle

Background - Cancer cachexia is the progressive loss of skeletal muscle protein that contributes significantly to cancer morbidity and mortality. Evidence of antioxidant attenuation and the presence of oxidised proteins in patients with cancer cachexia indicate a role for oxidative stress. The level of oxidative stress in tissues is determined by an imbalance between reactive oxygen species production and antioxidant activity. This study aimed to investigate the superoxide generating NADPH oxidase (NOX) enzyme and antioxidant enzyme systems in murine adenocarcinoma tumour-bearing cachectic mice. Methods - Superoxide levels, mRNA levels of NOX enzyme subunits and the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidise (GPx) and catalase was measured in the skeletal muscle of mice with cancer and cancer cachexia. Protein expression levels of NOX enzyme subunits and antioxidant enzyme activity was also measured in the same muscle samples. Results - Superoxide levels increased 1.4-fold in the muscle of mice with cancer cachexia, and this was associated with a decrease in mRNA of NOX enzyme subunits, NOX2, p40phox and p67phox along with the antioxidant enzymes SOD1, SOD2 and GPx. Cancer cachexia was also associated with a 1.3-fold decrease in SOD1 and 2.0-fold decrease in GPx enzyme activity. Conclusion - Despite increased superoxide levels in cachectic skeletal muscle, NOX enzyme subunits, NOX2, p40phox and p67phox, were downregulated along with the expression and activity of the antioxidant enzymes. Therefore, the increased superoxide levels in cachectic skeletal muscle may be attributed to the reduction in the activity of endogenous antioxidant enzymes.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder

Background: The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Method: Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. Results: BD individuals scored significantly higher on these spectrum measures than healthy individuals (p < 0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p < 0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p < 0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p < 0.02) and neutral faces (p < 0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BD individuals. Limitations: Small sample size of predominantly medicated BD individuals. Conclusion: This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD.

Postgraduate study and managers' subsequent work experience:an exploratory evaluation

Drawing on an exploratory qualitative study, this article considers the link between business school teaching at graduate level and subsequent work behaviour and experiences of former students. It evaluates the student experience some time after graduation. The findings of the retrospective evaluation point to the value of classroom peer discussion, the testing of ideas against prior work experience and the opportunity to make sense of organisational issues by setting them into broader context. The importance of andragogical approaches to teaching is discussed as well as the implications of the study findings for teaching quality enhancement. © 2009 Taylor & Francis.

Technology-Enhanced Learning: Review and Prospects

This paper is a reflection on the history and future of technology-enhanced learning. Over the last century various new technologies were introduced in education. Often, educational revolutions were proclaimed. Unfortunately, most of these new technologies failed to meet the high expectations. This paper reviews the rise and fall of various "revolutionary" learning technologies and analyses what went wrong. Three main driving factors are identified that influence the educational system: 1) educational practice, 2) educational research, and 3) educational technology. The role and position of these factors is elaborated and critically reviewed. Today, again many promising new technologies are being put in place for learning: gaming, social web, and mobile technologies, for example. Inevitably, these are once again proclaimed by its supporters to revolutionise teaching and learning. The paper concludes with identifying a number of relevant factors that substantiate a favourable future outlook of technology-enhanced learning.

Muscle motion and EMG activity in vibration treatment

The aim of this study is to highlight the relationship between muscle motion, generated by whole body vibration, and the correspondent electromyographic (EMG) activity and to suggest a new method to customize the stimulation frequency. Simultaneous recordings of EMG and tri-axial accelerations of quadriceps rectus femoris from fifteen subjects undergoing vibration treatments were collected. Vibrations were delivered via a sinusoidal oscillating platform at different frequencies (10-45 Hz). Muscle motion was estimated by processing the accelerometer data. Large EMG motion artifacts were removed using sharp notch filters centred at the vibration frequency and its superior harmonics. EMG-RMS values were computed and analyzed before and after artifact suppression to assess muscular activity. Muscles acceleration amplitude increased with frequency. Muscle displacements revealed a mechanical resonant-like behaviour of the muscle. Resonance frequencies and dumping factors depended on subject. Moreover, RMS of artifact-free EMG was found well correlated (R 2 = 0.82) to the actual muscle displacement, while the maximum of the EMG response was found related to the mechanical resonance frequency of muscle. Results showed that maximum muscular activity was found in correspondence to the mechanical resonance of the muscle itself. Assuming the hypothesis that muscle activation is proportional to muscle displacement, treatment optimization (i.e. to choose the best stimulation frequency) could be obtained by simply monitoring local acceleration (resonance), leading to a more effective muscle stimulation. Motion artifact produced an overestimation of muscle activity, therefore its removal was essential. © 2009 IPEM.

Correspondence between muscle motion and EMG activity during whole body vibration

The aim of this study is to highlight the relation between muscle motion and electromyographyc activity during whole body vibration. This treatment is accounted for eliciting a reflex muscle activity in response to vibratory stimulation. Simultaneous recordings from quadriceps Rectus Femoris EMG and 3D muscle accelerations on fifteen subjects undergoing vibration treatments were collected. In our study vibrations were delivered via a sinusoidal oscillating platform at different frequencies (10-45 Hz), with a constant amplitude. Muscle motion was estimated by processing accelerometer data. Displacements revealed a mechanical resonant-like behaviour of the muscle; resonance frequencies and dumping factors depended on subject. Large EMG motion artifacts were removed using sharp notch filters centred at the vibration frequency and its superior harmonics. RMS values of artifact-free EMG were found correlated to the actual muscle displacement. The results were in accordance to the hypothesis of a proprioceptive response during vibration treatment. Nevertheless, motion artifacts produced an overestimation of muscle activity, therefore its removal was essential. © 2009 Springer Berlin Heidelberg.

French linguistics research and teaching in UK and Irish HE institutions

Introduction: The research and teaching of French linguistics in UK higher education (HE) institutions have a venerable history; a number of universities have traditionally offered philology or history of the language courses, which complement literary study. A deeper understanding of the way that the phonology, syntax and semantics of the French language have evolved gives students linguistic insights that dovetail with their study of the Roman de Renart, Rabelais, Racine or the nouveau roman. There was, in the past, some coverage of contemporary French phonetics but little on sociolinguistic issues. More recently, new areas of research and teaching have been developed, with a particular focus on contemporary spoken French and on sociolinguistics. Well supported by funding councils, UK researchers are also making an important contribution in other areas: phonetics and phonology, syntax, pragmatics and second-language acquisition. A fair proportion of French linguistics research occurs outside French sections in psychology or applied linguistics departments. In addition, the UK plays a particular role in bringing together European and North American intellectual traditions and methodologies and in promoting the internationalisation of French linguistics research through the strength of its subject associations, and that of the Journal of French Language Studies. The following sections treat each of these areas in turn. History of the French Language There is a long and distinguished tradition in Britain of teaching and research on the history of the French language, particularly, but by no means exclusively, at the universities of Cambridge, Manchester and Oxford.

Is pregnancy a teachable moment for diet and physical activity behaviour change? An interpretative phenomenological analysis of the experiences of women during their first pregnancy

OBJECTIVES: Pregnancy may provide a 'teachable moment' for positive health behaviour change, as a time when women are both motivated towards health and in regular contact with health care professionals. This study aimed to investigate whether women's experiences of pregnancy indicate that they would be receptive to behaviour change during this period. DESIGN: Qualitative interview study. METHODS: Using interpretative phenomenological analysis, this study details how seven women made decisions about their physical activity and dietary behaviour during their first pregnancy. RESULTS: Two women had required fertility treatment to conceive. Their behaviour was driven by anxiety and a drive to minimize potential risks to the pregnancy. This included detailed information seeking and strict adherence to diet and physical activity recommendations. However, the majority of women described behaviour change as 'automatic', adopting a new lifestyle immediately upon discovering their pregnancy. Diet and physical activity were influenced by what these women perceived to be normal or acceptable during pregnancy (largely based on observations of others) and internal drivers, including bodily signals and a desire to retain some of their pre-pregnancy self-identity. More reasoned assessments regarding benefits for them and their baby were less prevalent and influential. CONCLUSIONS: Findings suggest that for women who conceived relatively easily, diet and physical activity behaviour during pregnancy is primarily based upon a combination of automatic judgements, physical sensations, and perceptions of what pregnant women are supposed to do. Health professionals and other credible sources appear to exert less influence. As such, pregnancy alone may not create a 'teachable moment'. Statement of contribution What is already known on this subject? Significant life events can be cues to action with relation to health behaviour change. However, much of the empirical research in this area has focused on negative health experiences such as receiving a false-positive screening result and hospitalization, and in relation to unequivocally negative behaviours such as smoking. It is often suggested that pregnancy, as a major life event, is a 'teachable moment' (TM) for lifestyle behaviour change due to an increase in motivation towards health and regular contact with health professionals. However, there is limited evidence for the utility of the TM model in predicting or promoting behaviour change. What does this study add? Two groups of women emerged from our study: the women who had experienced difficulties in conceiving and had received fertility treatment, and those who had conceived without intervention. The former group's experience of pregnancy was characterized by a sense of vulnerability and anxiety over sustaining the pregnancy which influenced every choice they made about their diet and physical activity. For the latter group, decisions about diet and physical activity were made immediately upon discovering their pregnancy, based upon a combination of automatic judgements, physical sensations, and perceptions of what is normal or 'good' for pregnancy. Among women with relatively trouble-free conception and pregnancy experiences, the necessary conditions may not be present to create a 'teachable moment'. This is due to a combination of a reliance on non-reflective decision-making, perception of low risk, and little change in affective response or self-concept.

Assessing the effectiveness of two-year banking and insurance technology programs of junior colleges in Taiwan, R.O.C.: An application of the Context Input Process Product (CIPP) evaluation model

The purpose of this descriptive study was to evaluate the banking and insurance technology curriculum at ten junior colleges in Taiwan. The study focused on curriculum, curriculum materials, instruction, support services, student achievement and job performance. Data was collected from a diverse sample of faculty, students, alumni, and employers. ^ Questionnaires on the evaluation of curriculum at technical junior colleges were developed for use in this specific case. Data were collected from the sample described above and analyzed utilizing ANOVA, T-Tests and crosstabulations. Findings are presented which indicate that there is room for improvement in terms of meeting individual students' needs. ^ Using Stufflebeam's CIPP model for curriculum evaluation it was determined that the curriculum was adequate in terms of the knowledge and skills imparted to students. However, students were dissatisfied with the rigidity of the curriculum and the lack of opportunity to satisfy the individual needs of students. Employers were satisfied with both the academic preparation of students and their on the job performance. ^ In sum, the curriculum of the two-year banking and insurance technology programs of junior college in Taiwan was shown to have served adequately preparing a work force to enter businesses. It is now time to look toward the future and adapt the curriculum and instruction for the future needs of the ever evolving high-tech society. ^

Electrocardiogram breathing: A study of electrocardiogram derived respiration plus multiresolution wavelet analysis of heartbeat interval variability in sleep study patients

This dissertation presents a unique research opportunity by using recordings which provide electrocardiogram (ECG) plus a reference breathing signal (RBS). ECG derived breathing (EDR) is measured and correlated against RBS. Standard deviations of multiresolution wavelet analysis coefficients (SDMW) are obtained from heart rate and classified using RBS. Prior works by others used select patients for sleep apnea scoring with EDR but no RBS. Another prior work classified select heart disease patients with SDMW but no RBS. This study used randomly chosen sleep disorder patient recordings; central and obstructive apneas, with and without heart disease.^ Implementation required creating an application because existing systems were limited in power and scope. A review survey was created to choose a development environment. The survey is presented as a learning tool and teaching resource. Development objectives were rapid development using limited resources (manpower and money). Open Source resources were used exclusively for implementation. ^ Results show: (1) Three groups of patients exist in the study. Grouping RBS correlations shows a response with either ECG interval or amplitude variation. A third group exists where neither ECG intervals nor amplitude variation correlate with breathing. (2) Previous work done by other groups analyzed SDMW. Similar results were found in this study but some subjects had higher SDMW, attributed to a large number of apneas, arousals and/or disconnects. SDMW does not need RBS to show apneic conditions exist within ECG recordings. (3) Results in this study support the assertion that autonomic nervous system variation was measured with SDMW. Measurements using RBS are not corrupted due to breathing even though respiration overlaps the same frequency band.^ Overall, this work becomes an Open Source resource which can be reused, modified and/or expanded. It might fast track additional research. In the future the system could also be used for public domain data. Prerecorded data exist in similar formats in public databases which could provide additional research opportunities. ^

The effect of osteoporosis education on calcium intake and physical activity in a group of community-dwelling Black older adults

The unprecedented increase in the number of older adults is expected to increase the burden of osteoporosis on the individual and society. Blacks have been understudied in osteoporosis prevention education research. Although the risk of osteoporosis is low in this population, its consequences are significant. This study employs a two-group experimental design (experimental and wait-list control groups) to evaluate the effect of an osteoporosis education on two osteoporosis prevention behaviors (OPBs)—calcium intake (CI) and physical activity (PA), in a group of community-dwelling Black older adults, 50 years and older resident in South Florida. A final sample of 110 (mean age 70.15 years), 90% female and 10% male completed a battery of questionnaires at two assessment periods. The experimental group participated in six weekly education program sessions immediately following baseline assessment, and the wait-list control group received the education following end of program assessment by all participants. The weekly educational sessions were conducted in social settings (church or senior center) employing constructs of the Revised Health Belief Model. The sessions focused on improving CI; osteoporosis knowledge (OKT), self-efficacy (SE), health beliefs (HB) and PA. Findings revealed significantly greater increase in reported CI ( M = 556 mg, Wilks’ λ = .47, F (1,108)=122.97, p< .001, η2=.53), OKT (p< .001), and SE (p< .001) among participants in the experimental compared to the wait-list control group. There was no significant difference between the two groups for PA and most of the HB subscales. OKT and SE were the best predictors of CI, while perceived barrier was a predominant factor predicting PA. Over the study period, a change in SE was the only variable related to changes in both OPBs. Attrition rate was lower than expected, which can be attributed to the settings utilized for the study. These findings support the importance of utilizing a familiar social setting. These results suggested the effectiveness of a program offered in multiple short sessions among this underserved minority population to improve OKT and SE resulting in a change in OPBs (increase in CI). However, there is need to explore alternative strategies to improve PA in this population group.

Television Watching, Diet Quality, and Physical Activity and Diabetes among Three Ethnicities in the United States

Diabetes is a world-wide epidemic associated with multiple environmental factors. Prolonged television viewing (TV) time has been related to increased risk of obesity and type 2 diabetes in several studies. TV viewing has been positively associated with cardiovascular disease risk factors, lower energy expenditure, over-eating high-calorie and high-fat foods. The objective of this study was to assess the associations of hours of TV viewing with dietary quality, obesity and physical activity for three ethnic minorities with and without type 2 diabetes. Diet quality and physical activity were inversely related to prolonged TV viewing. African Americans and participants with type 2 diabetes were more likely to watch more than 4 hours of TV per day as compared to their counterparts. Diet quality was inversely associated with physical activity level. Future studies are needed to establish the risk factors of prolonged TV watching in adult populations for the development of diabetes or diabetes-related complications. Although strategies to reduce TV watching have been proven effective among children, few trials have been conducted in adults. Intervention trials aimed at reducing TV viewing targeting people with type 2 diabetes may be beneficial to improve dietary quality and physical activity, which may reduce diabetes complications.