448 research outputs found

    Production Technology and Competitiveness In the Hungarian Manufacturing Industry

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    Following the big transformations of the 1990s, enterprise structure and technological level seem to have become stabilised in Hungary. Under these circumstances it is especially interesting to identify the elements responsible for competitiveness in general, and the role technology plays in development in particular, according to managers experienced in production and marketing. This empirical study – based on in-depth interviews and field research – summarises characteristics of the technological level in the sectors examined, role of technology and labour in production, effects of foreign direct investment, relations between competition and firm-level factors determining competitiveness, and concludes by summing up those most frequently mentioned proposals that should be incorporated into economic policy according to managers. Main findings indicate that more qualified, more intensive and cheaper labour can be substituted for high technology. The competitiveness of an enterprise is not determined by technology alone, but rather by a combination of technology, the parameters of available labour and the costs of investment increasing productivity. The insufficiency of inter-company relations, together with a shortage of available assets necessary for investment constitute the major threat undermining the competitiveness of enterprises in present-day Hungary

    Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase

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    The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His–1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C–H bonds. Prolyl 4-hydroxylase (P4H) is an α-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His–1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change

    Near-infrared rechargeable glass-based composites for green persistent luminescence

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    The fabrication of Yb3+, Tm3+ co-doped oxyfluorophosphate glass-based composites, with green persistent luminescence after being charged with near-infrared light, is demonstrated. The mechanism responsible for the green afterglow after near-infrared illumination is unveiled. The composite is prepared using a modified melting process to limit the evaporation of fluorine during melting. Intense (blue and ultraviolet) up-conversion emission is obtained by optimizing the Yb2O3 and Tm2O3 concentrations. A heat treatment promotes volume precipitation of Yb3+, Tm3+ co-doped CaF2 crystals. Although the intensity of the blue up-conversion emission from the Tm3+ 1G4 level is lower in the highly Yb3+-concentrated glass-ceramic due to reverse energy transfer from Tm3+ to Yb3+, the heat treatment leads to an increase of the intensity of the emissions around 346 nm, 361 nm nm and 450 nm coming from the Tm3+ 1I6 and 1D2 levels. By combining the Yb3+ and Tm3+ ions with SrAl2O4:Eu2+,Dy3+crystals, green afterglow can be obtained after charging with near-infrared light.publishedVersionPeer reviewe

    Evaluation of a standard provision versus an autonomy promotive exercise referral programme: rationale and study design

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    Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials. Recent empirical evidence in health care and physical activity promotion contexts provides a foundation for testing the utility of a Self Determination Theory (SDT) -based exercise referral consultation. Methods/Design Design: An exploratory cluster randomised controlled trial comparing standard provision exercise on prescription with a Self Determination Theory-based (SDT) exercise on prescription intervention. Participants: 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008. The 13 exercise on prescription sites in Birmingham were randomised to current practice (n=7) or to the SDT-based intervention (n=6). Outcomes measured at 3 and 6-months: Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall; physical health: blood pressure and weight; health status measured using the Dartmouth CO-OP charts; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score; motivation and processes of change: perceptions of autonomy support from the advisor, satisfaction of the needs for competence, autonomy, and relatedness via physical activity, and motivational regulations for exercise. Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a standard programme and will test the underlying SDT-based process model (perceived autonomy support, need satisfaction, motivation regulations, outcomes) via structural equation modelling. Trial registration The trial is registered as Current Controlled trials ISRCTN07682833

    Novel HTS Strategy Identifies TRAIL-Sensitizing Compounds Acting Specifically Through the Caspase-8 Apoptotic Axis

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    Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is potentially a very important therapeutic as it shows selectivity for inducing apoptosis in cancer cells whilst normal cells are refractory. TRAIL binding to its cognate receptors, Death Receptors-4 and -5, leads to recruitment of caspase-8 and classical activation of downstream effector caspases, leading to apoptosis. As with many drugs however, TRAIL's usefulness is limited by resistance, either innate or acquired. We describe here the development of a novel 384-well high-throughput screening (HTS) strategy for identifying potential TRAIL-sensitizing agents that act solely in a caspase-8 dependent manner. By utilizing a TRAIL resistant cell line lacking caspase-8 (NB7) compared to the same cells reconstituted with the wild-type protein, or with a catalytically inactive point mutant of caspase-8, we are able to identify compounds that act specifically through the caspase-8 axis, rather than through general toxicity. In addition, false positive hits can easily be “weeded out” in this assay due to their activity in cells lacking caspase-8-inducible activity. Screening of the library of pharmacologically active compounds (LOPAC) was performed as both proof-of-concept and to discover potential unknown TRAIL sensitizers whose mechanism is caspase-8 mediated. We identified known TRAIL sensitizers from the library and identified new compounds that appear to sensitize specifically through caspase-8. In sum, we demonstrate proof-of-concept and discovery of novel compounds with a screening strategy optimized for the detection of caspase-8 pathway-specific TRAIL sensitizers. This screen was performed in the 384-well format, but could easily be further miniaturized, allows easy identification of artifactual false positives, and is highly scalable to accommodate diverse libraries

    Walking ability during daily life in patients with osteoarthritis of the knee or the hip and lumbar spinal stenosis: a cross sectional study

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    <p>Abstract</p> <p>Background</p> <p>Degenerative musculoskeletal disorders are among the most frequent diseases occurring in adulthood, often impairing patients' functional mobility and physical activity. The aim of the present study was to investigate and compare the impact of three frequent degenerative musculoskeletal disorders -- knee osteoarthritis (knee OA), hip osteoarthritis (hip OA) and lumbar spinal stenosis (LSS) -- on patients' walking ability.</p> <p>Methods</p> <p>The study included 120 participants, with 30 in each patient group and 30 healthy control individuals. A uniaxial accelerometer, the StepWatchℱ Activity Monitor (Orthocare Innovations, Seattle, Washington, USA), was used to determine the volume (number of gait cycles per day) and intensity (gait cycles per minute) of walking ability. Non-parametric testing was used for all statistical analyses.</p> <p>Results</p> <p>Both the volume and the intensity of walking ability were significantly lower among the patients in comparison with the healthy control individuals (p < 0.001). Patients with LSS spent 0.4 (IQR 2.8) min/day doing moderately intense walking (>50 gait cycles/min), which was significantly lower in comparison with patients with knee and hip OA at 2.5 (IQR 4.4) and 3.4 (IQR 16.1) min/day, respectively (p < 0.001). No correlations between demographic or anthropometric data and walking ability were found. No technical problems or measuring errors occurred with any of the measurements.</p> <p>Conclusions</p> <p>Patients with degenerative musculoskeletal disorders suffer limitations in their walking ability. Objective assessment of walking ability appeared to be an easy and feasible tool for measuring such limitations as it provides baseline data and objective information that are more precise than the patients' own subjective estimates. In everyday practice, objective activity assessment can provide feedback for clinicians regarding patients' performance during everyday life and the extent to which this confirms the results of clinical investigations. The method can also be used as a way of encouraging patients to develop a more active lifestyle.</p

    A genome-wide search for genes involved in type 2 diabetes in a recently genetically isolated population from the Netherlands

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    Multiple genes, interacting with the environment, contribute to the susceptibility to type 2 diabetes. We performed a genome-wide search to localize type 2 diabetes susceptibility genes in a recently genetically isolated population in the Netherlands. We identified 79 nuclear families with type 2 diabetes who were related within 13 generations and performed a 770-marker genome-wide scan search for shared founder alleles. Twenty-six markers yielded a logarithm of odds (LOD) score >0.59 (nominal P 1.17 (nominal P < 0.01). The strongest evidence for a type 2 diabetes locus was at marker D18S63 on chromosome 18p (LOD 2.3, P = 0.0006). This region was investigated further using additional markers. For one of these markers (D18S1105), we found a significant association with type 2 diabetes (odds ratio 6.7 [95% CI 1.5-30.7], P = 0.005 for the 97-bp allele, assuming a dominant model), which increased when limiting the analysis to patients with high BMI (12.25 [2.1-71], P = 0.003). A locus on chromosome 18p in patients with high BMI was suggested earlier by Parker et al. Our study is the first to confirm this locus

    The evolution of the student as a customer in Australian higher education: a policy perspective

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    In 2014, the Australian Federal Government attempted to de-regulate higher education fees so as to allow universities to set their own tuition fees. The associated public debate offer critical insights into how the identity of a student as a ‘customer’ of higher education is understood and deployed when developing higher education policy. This paper uses the 2014 Australian higher education reforms as a lens through which to further scholarly research into the student-as-customer metaphor and to see how it is influenced by the perceptions and understandings of policy actors external to the higher education sector. These include politicians, special interest groups, the students and their parents and prospective employers. This study reveals that the public/private nexus—both of funding and benefit— problematizes traditional conceptualisations of students and others as higher education customers. In turn, this restricts the ability or desire of policy actors to describe how the student functions as a customer as a consequence of market reform. This inability compromises the development of effective and sustainable higher education polic

    Physical activity of Estonian family doctors and their counselling for a healthy lifestyle: a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>Physical activity offers major health benefits and counselling for it should be integrated into the medical consultation. Based on the literature, the personal health behaviour of the physician (including physical activity) is associated with his/her approach to counselling patients. Our hypothesis is that family doctors (FD) in Estonia are physically active and their recommendation to counsel patients with chronic diseases to use physical activity is high. The study was also interested in how FDs value physical activity among other important determinants of a healthy lifestyle, e.g. nutrition, non-consumption of alcohol, and non-smoking.</p> <p>Methods</p> <p>Physicians on the electronic list were contacted by e-mail and sent a questionnaire. The first part assessed physical activity by the International Physical Activity Questionnaire (IPAQ) short form. Self-reported physical activity during one week was calculated as total physical activity in minutes per week (MET min/week). The second part of the questionnaire included questions about the counselling of patients with chronic disease concerning their physical activity and a healthy lifestyle. The study focused on female FDs because 95% of the FDs in Estonia are women and to avoid bias related to gender.</p> <p>Results</p> <p>198 female FDs completed the questionnaire. 92% reported that they exercised over the past 7 days to a moderate or high level of physical activity. Analysis revealed no statistically significant relationship between the level of physical activity and general characteristics (age, living area, body mass index [BMI], time spent sitting). FDs reported that patients with heart problems, diabetes, and obesity seek their advice on physical activity more often than patients with depression. Over 94% of the FDs claimed that they counsel their patients with chronic diseases about exercising. According to the FDs' reports, the most important topic in counselling patients for a healthy lifestyle was physical activity.</p> <p>Conclusion</p> <p>This study showed that female FDs are physically active. The level of physical activity is not related to their age, BMI, living area, or time spent sitting. Also, FDs reported that promotion of physical activity is part of their everyday work.</p
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