Learning by building digital libraries

The implications of using digital library software in educational contexts, for both students and software developers, are discussed using two case studies of students building digital libraries

Thermodynamic and structural properties of zinc/copper alloys

The thesis, entitled as above, is concerned with the measurement of thermodynamic properties of zinc copper alloys in the liquid and solid states, and with the interpretation of these in terms of alloy structure. A conventional dew-point technique was used to determine, initially, the vapour pressure of the zinc component at a number of temperatures and, from these values, partial and integral thermodynamic functions were calculated. For evaluation of the vapour pressures, the equations of Kubaschewski and Evans, relating the vapour pressure of pure zinc, in solid and liquid otates,to temperature were used as a basis. The results of other workers were recalculated, wherever possible, to the same basis for comparison. In general, the present results show fair agreement with previous work but with certain differences. For liquid alloys, for instance, a change from negative to positive deviation +0. from ideality is shown by the thermodynamic activity of the zinc as high zinc contents are approached. Previously, the results of other workers have indicated negative deviation over the whole compositional range. Also, characteristic minima and maxima were obtained in the curves when Deltas-x zn values from the present work on liquid and solid alloys were plotted against composition. One of these minima, viz. that occurring at 0.43 NZn in the solid alloys, is considered difficult to explain and probably spurious. Otherwise, the minima occur at compositions corresponding approximately to the centre of the beta and r-phase fields and are associated with the critical electron/atom ratios (1.48 and 1.615 respectively) required, by electron theory for the formation of the appropriate electron compounds. The peak positive value (i.e. highest maximum) in the DeltaS-x zn curve for liquid alloys, which occurs at 0.68 Nzn, has analogies in at least two other binary systems, viz. Zn/Sb and Cd/Sb. This positive value of excess entropy is considered to be associated with an increased vibrational contribution to entropy, and linked with the previously reported defect structure of the delta-phase. Quantitative application of quasi-chemical theory to the partial and integral thermodynamic functions was attempted but, after comparison with other systems, reasons are advanced for the limited applicability. However, qualitative application, particularly when integral properties are considered, is possible. The partial thermodynamic functions of the second component, i.e. copper, were calculated from the Gibbs-Duhem relationship, and thus integral properties obtained. For the liquid alloys, both of the partial and the integral functions are compared and the conclusion drawn that, in certain compositional regions there is build up of "excess" enthalpy (stored probably as vibrational energy) which is released again to allow the "minimum" value to he attained at fixed compositions. Two of these fixed compositions co-incide approximately with the critical electron/atom ratios necessary, according to electron theory, for the formation of the beta and r-phases in solid alloys, but it is postulated that the true "critical" compositions are those corresponding to the maximum build-up of excess enthalpy. In addition, the variation of the partial properties in the region of those critical compositions suggests that the release of the excess enthalpy is accompanied by a redistribution of the vibrational energy between the two components of the solution. Because of the close approximation of the compositions, at which the minimal values occur, to the centres of the solid beta, -r and -phase fields, a fourth minimum, corresponding to the unexplored delta-phase field region is predicted. Also, the existence of these minima, in plots referring to liquid alloys, is taken as an indication of the extent to which "solid" structures persist above liquidus temperatures. The above postulations and the link with electron theory are less clearly applicable to the solid alloys, but sufficient similarity exists to suggest that complete analogy may be established by further study

Actinoid pnictides--II : Heat capacities of UAs2 and USb2 from 5 to 750 K and antiferromagnetic transitions

The heat capacities of uranium diarsenide (UAs2) and uranium diantimonide (USb2), with tetragonal structures of the anti-Cu2Sb-type, have been measured by adiabatic-shield calorimetry from 5 to about 750 K. Lambda-type transitions with maxima at 272.2 and 202.5 K for UAs2 and USb2, respectively, are related to maxima in the magnetic susceptibilities at 277 and 203 K, occasioned by transitions from antiferro- to paramagnetism in the compounds. Values of the heat capacities (Cp), entropies [S[deg](T) - S[deg](0)], and Gibbs energy functions -{[G[deg](T) - H[deg](o)]/T} at 298.15 K in cal K-1 mole-1 are 19.12, 29.41 and 15.05 for UAs2 and 19.16, 33.81 and 18.39 for USb2. Tentative resolutions of the cooperative magnetic heat capacities of UAs2 and USb2 lead to the magnetic entropies [Delta]S(mag) = 0.99 and 1.70 cal K-1 mole-1, respectively. The values for both are significantly lower than the spin-only magnetic entropy value R ln 3 = 2.18 cal K-1 mole-1.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22763/1/0000318.pd

An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans

Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is ∼1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462×10−26, Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13–0.26, p = 2.4×10−28, Fisher's exact), suggesting a protective effect. This SNP is polymorphic in the African population (minor allele frequency [MAF] 0.09 in the Yoruba population), but is very rare in other groups (MAF = 0.002 in 530 Caucasians genotyped for this study). Markers associated with RA in populations of European ancestry (rs3087243 [+60C/T] and rs231775 [+49A/G]) were not replicated in African Americans. We found no confounding of association for rs231778 after stratifying for the HLA-DRB1 shared epitope, presence of anti-cyclic citrullinated peptide antibody, or degree of admixture from the European population. An African ancestry-specific genetic variant of CTLA4 appears to be associated with protection from RA in African Americans. This finding may explain, in part, the relatively low prevalence of RA in black African populations

A theory-based educational intervention targeting nurses' attitudes and knowledge concerning cancer-related pain management: A study protocol of a quasi-experimental design

<p>Abstract</p> <p>Background</p> <p>Pain is one of the most frequent problems among patients diagnosed with cancer. Despite the availability of effective pharmacological treatments, this group of patients often receives less than optimal treatment. Research into nurses' pain management highlights certain factors, such as lack of knowledge and attitudes and inadequate procedures for systematic pain assessment, as common barriers to effective pain management. However, educational interventions targeting nurses' pain management have shown promise. As cancer-related pain is also known to have a negative effect on vital aspects of the patient's life, as well as being commonly associated with problems such as sleep, fatigue, depression and anxiety, further development of knowledge within this area is warranted.</p> <p>Methods/design</p> <p>A quasi-experimental study design will be used to investigate whether the implementation of guidelines for systematic daily pain assessments following a theory-based educational intervention will result in an improvement in knowledge and attitude among nurses. A further aim is to investigate whether the intervention that targets nurses' behaviour will improve hospital patients' perception of pain. Data regarding nurses' knowledge and attitudes to pain (primary outcome), patient perception regarding pain (secondary outcome), together with socio-demographic variables, will be collected at baseline and at four weeks and 12 weeks following the intervention.</p> <p>Discussion</p> <p>Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential complex intervention." To be able to change and improve clinical practice thus requires multiple points of attack appropriate to meet complex challenges. Consequently, we expect the theory-based intervention used in our quasi-experimental study to improve care as well as quality of life for this group of patients and we also envisage that evidence-based guidelines targeting this patient group's pain will be implemented more widely.</p> <p>Trial Registration Number</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01313234">NCT01313234</a></p

Cellular Phenotype-Dependent and -Independent Effects of Vitamin C on the Renewal and Gene Expression of Mouse Embryonic Fibroblasts

Vitamin C has been shown to delay the cellular senescence and was considered a candidate for chemoprevention and cancer therapy. To understand the reported contrasting roles of vitamin C: growth-promoting in the primary cells and growth-inhibiting in cancer cells, primary mouse embryonic fibroblasts (MEF) and their isogenic spontaneously immortalized fibroblasts with unlimited cell division potential were used as the model pair. We used microarray gene expression profiling to show that the immortalized MEF possess human cancer gene expression fingerprints including a pattern of up-regulation of inflammatory response-related genes. Using the MEF model, we found that a physiological treatment level of vitamin C (10−5 M), but not other unrelated antioxidants, enhanced cell growth. The growth-promoting effect was associated with a pattern of enhanced expression of cell cycle- and cell division-related genes in both primary and immortalized cells. In the immortalized MEF, physiological treatment levels of vitamin C also enhanced the expression of immortalization-associated genes including a down-regulation of genes in the extracellular matrix functional category. In contrast, confocal immunofluorescence imaging of the primary MEF suggested an increase in collagen IV protein upon vitamin C treatment. Similar to the cancer cells, the growth-inhibitory effect of the redox-active form of vitamin C was preferentially observed in immortalized MEF. All effects of vitamin C required its intracellular presence since the transporter-deficient SVCT2−/− MEF did not respond to vitamin C. SVCT2−/− MEF divided and became immortalized readily indicating little dependence on vitamin C for the cell division. Immortalized SVCT2−/− MEF required higher concentration of vitamin C for the growth inhibition compared to the immortalized wildtype MEF suggesting an intracellular vitamin C toxicity. The relevance of our observation in aging and human cancer prevention was discussed

Exploring the symbiotic pangenome of the nitrogen-fixing bacterium Sinorhizobium meliloti

<p>Abstract</p> <p>Background</p> <p><it>Sinorhizobium meliloti </it>is a model system for the studies of symbiotic nitrogen fixation. An extensive polymorphism at the genetic and phenotypic level is present in natural populations of this species, especially in relation with symbiotic promotion of plant growth. AK83 and BL225C are two nodule-isolated strains with diverse symbiotic phenotypes; BL225C is more efficient in promoting growth of the <it>Medicago sativa </it>plants than strain AK83. In order to investigate the genetic determinants of the phenotypic diversification of <it>S. meliloti </it>strains AK83 and BL225C, we sequenced the complete genomes for these two strains.</p> <p>Results</p> <p>With sizes of 7.14 Mbp and 6.97 Mbp, respectively, the genomes of AK83 and BL225C are larger than the laboratory strain Rm1021. The core genome of Rm1021, AK83, BL225C strains included 5124 orthologous groups, while the accessory genome was composed by 2700 orthologous groups. While Rm1021 and BL225C have only three replicons (Chromosome, pSymA and pSymB), AK83 has also two plasmids, 260 and 70 Kbp long. We found 65 interesting orthologous groups of genes that were present only in the accessory genome, consequently responsible for phenotypic diversity and putatively involved in plant-bacterium interaction. Notably, the symbiosis inefficient AK83 lacked several genes required for microaerophilic growth inside nodules, while several genes for accessory functions related to competition, plant invasion and bacteroid tropism were identified only in AK83 and BL225C strains. Presence and extent of polymorphism in regulons of transcription factors involved in symbiotic interaction were also analyzed. Our results indicate that regulons are flexible, with a large number of accessory genes, suggesting that regulons polymorphism could also be a key determinant in the variability of symbiotic performances among the analyzed strains.</p> <p>Conclusions</p> <p>In conclusions, the extended comparative genomics approach revealed a variable subset of genes and regulons that may contribute to the symbiotic diversity.</p

Exercise and manual physiotherapy arthritis research trial (EMPART): a multicentre randomised controlled trial

BACKGROUND: Osteoarthritis (OA) of the hip is a major cause of functional disability and reduced quality of life. Management options aim to reduce pain and improve or maintain physical functioning. Current evidence indicates that therapeutic exercise has a beneficial but short-term effect on pain and disability, with poor long-term benefit. The optimal content, duration and type of exercise are yet to be ascertained. There has been little scientific investigation into the effectiveness of manual therapy in hip OA. Only one randomized controlled trial (RCT) found greater improvements in patient-perceived improvement and physical function with manual therapy, compared to exercise therapy. METHODS AND DESIGN: An assessor-blind multicentre RCT will be undertaken to compare the effect of a combination of manual therapy and exercise therapy, exercise therapy only, and a waiting-list control on physical function in hip OA. One hundred and fifty people with a diagnosis of hip OA will be recruited and randomly allocated to one of 3 groups: exercise therapy, exercise therapy with manual therapy and a waiting-list control. Subjects in the intervention groups will attend physiotherapy for 6-8 sessions over 8 weeks. Those in the control group will remain on the waiting list until after this time and will then be re-randomised to one of the two intervention groups. Outcome measures will include physical function (WOMAC), pain severity (numerical rating scale), patient perceived change (7-point Likert scale), quality of life (SF-36), mood (hospital anxiety and depression scale), patient satisfaction, physical activity (IPAQ) and physical measures of range of motion, 50-foot walk and repeated sit-to stand tests. DISCUSSION: This RCT will compare the effectiveness of the addition of manual therapy to exercise therapy to exercise therapy only and a waiting-list control in hip OA. A high quality methodology will be used in keeping with CONSORT guidelines. The results will contribute to the evidence base regarding the clinical efficacy for physiotherapy interventions in hip OA

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Metabolic constituents of grapevine and grape-derived products

The numerous uses of the grapevine fruit, especially for wine and beverages, have made it one of the most important plants worldwide. The phytochemistry of grapevine is rich in a wide range of compounds. Many of them are renowned for their numerous medicinal uses. The production of grapevine metabolites is highly conditioned by many factors like environment or pathogen attack. Some grapevine phytoalexins have gained a great deal of attention due to their antimicrobial activities, being also involved in the induction of resistance in grapevine against those pathogens. Meanwhile grapevine biotechnology is still evolving, thanks to the technological advance of modern science, and biotechnologists are making huge efforts to produce grapevine cultivars of desired characteristics. In this paper, important metabolites from grapevine and grape derived products like wine will be reviewed with their health promoting effects and their role against certain stress factors in grapevine physiology