Enhancing the catalytic repertoire of nucleic acids: a systematic study of linker length and rigidity

The incorporation of potentially catalytic groups in DNA is of interest for the in vitro selection of novel deoxyribozymes, A series of 10 C5-modified analogues of 2'-deoxyuridine triphosphate have been synthesised that possess side chains of differing flexibility and bearing a primary amino or imidazole functionality, For each series of nucleotide analogues differing degrees of flexibility of the C5 side chain was achieved through the use of alkynyl, alkenyl and alkyl moieties, The imidazole function was conjugated to these CS-amino-modified nucleotides using either imidazole 4-acetic acid or imidazole 4-acrylic acid (urocanic acid), The substrate properties of the nucleotides (fully replacing dTTP) with Taq polymerase during PCR have been investigated in order to evaluate their potential applications for in vitro selection experiments, 5-(3-Aminopropynyl)dUTP and 5-(E-3-aminopropenyl)dUTP and their imidazole 4-acetic acid- and urocanic acid-modified conjugates were found to be substrates, In contrast, C5-amino-modified dUTPs with alkane or Z-alkene linkers and their corresponding conjugates were not substrates, The incorporation of these analogues during PCR has been confirmed by inhibition of restriction enzyme digestion using XbaI and by mass spectrometry of the PCR products.

MOOCs: a systematic study of the published literature 2008-2012

Massive open online courses (MOOCs) are a recent addition to the range of online learning options. Since 2008, MOOCs have been run by a variety of public and elite universities, especially in North America. Many academics have taken interest in MOOCs recognising the potential to deliver education around the globe on an unprecedented scale; some of these academics are taking a research-oriented perspective and academic papers describing their research are starting to appear in the traditional media of peer reviewed publications. This paper presents a systematic review of the published MOOC literature (2008-2012): Forty-five peer reviewed papers are identified through journals, database searches, searching the Web, and chaining from known sources to form the base for this review. We believe this is the first effort to systematically review literature relating to MOOCs, a fairly recent but massively popular phenomenon with a global reach. The review categorises the literature into eight different areas of interest, introductory, concept, case studies, educational theory, technology, participant focussed, provider focussed, and other, while also providing quantitative analysis of publications according to publication type, year of publication, and contributors. Future research directions guided by gaps in the literature are explored.

Systematic study of the impact of fresh water fluxes on the glacial carbon cycle

During glacial periods, atmospheric CO2 concentration increases and decreases by around 15 ppm. At the same time, the climate changes gradually in Antarctica. Such climate changes can be simulated in models when the AMOC (Atlantic Meridional Oceanic Circulation) is weakened by adding fresh water to the North Atlantic. The impact on the carbon cycle is less straightforward, and previous studies give opposite results. Because the models and the fresh water fluxes were different in these studies, it prevents any direct comparison and hinders finding whether the discrepancies arise from using different models or different fresh water fluxes. In this study we use the CLIMBER-2 coupled climate carbon model to explore the impact of different fresh water fluxes. In both preindustrial and glacial states, the addition of fresh water and the resulting slow-down of the AMOC lead to an uptake of carbon by the ocean and a release by the terrestrial biosphere. The duration, shape and amplitude of the fresh water flux all have an impact on the change of atmospheric CO2 because they modulate the change of the AMOC. The maximum CO2 change linearly depends on the time integral of the AMOC change. The different duration, amplitude, and shape of the fresh water flux cannot explain the opposite evolution of ocean and vegetation carbon inventory in different models. The different CO2 evolution thus depends on the AMOC response to the addition of fresh water and the resulting climatic change, which are both model dependent. In CLIMBER-2, the rise of CO2 recorded in ice cores during abrupt events can be simulated under glacial conditions, especially when the sinking of brines in the Southern Ocean is taken into account. The addition of fresh water in the Southern Hemisphere leads to a decline of CO2, contrary to the addition of fresh water in the Northern Hemisphere.

Photocatalytic degradation of humic acid in saline waters. Part 1. Artificial seawater: influence of TiO2, temperature, pH, and air-flow

We report the first systematic study on the photocatalytic oxidation of humic acid (HA) in artificial seawater (ASW). TiO2 (Degussa P25) dispersions were used as the catalyst with irradiation from a medium-pressure mercury lamp. The optimum quantity of catalyst was found to be between 2 and 2.5 g l(-1); whiled the decomposition was fastest at low pH values (pH 4.5 in the range examined), and the optimum air-flow, using an immersion well reactor with a capacity of 400 ml, was 850 ml min(-1). Reactivity increased with air-flow up to this figure, above which foaming prevented operation of the reactor. Using pure. oxygen, an optimal flow rate was observed at 300 nil min(-1), above which reactivity remains essentially constant. Following treatment for 1 h, low-salinity water (2700 mg l(-1)) was completely mineralised, whereas ASW (46000 mg l(-1)) had traces of HA remaining. These effects are interpreted and kinetic data presented. To avoid problems of precipitation due to change of ionic strength humic substances were prepared directly in ASW, and the effects of ASW on catalyst suspension and precipitation have been taken into account. The Langmuir-Hinshelwood kinetic model has been shown to be followed only approximately for the catalytic oxidation of HA in ASW. The activation energy for the reaction derived from an Arrhenius treatment was 17 ( +/-0.6) kJ mol(-1). (C) 2003 Elsevier Science Ltd. All rights reserved.

The influence of carbon surface oxygen groups on Dubinin–Astakhov equation parameters calculated from CO2 adsorption isotherm

We present the results of a systematic study of the influence of carbon surface oxidation on Dubinin–Astakhov isotherm parameters obtained from the fitting of CO2 adsorption data. Using GCMC simulations of adsorption on realistic VPC models differing in porosity and containing the most frequently occurring carbon surface functionalities (carboxyls, hydroxyls and carbonyls) and their mixtures, it is concluded that the maximum adsorption calculated from the DA model is not strongly affected by the presence of oxygen groups. Unfortunately, the same cannot be said of the remaining two parameters of this model i.e. the heterogeneity parameter (n) and the characteristic energy of adsorption (E0). Since from the latter the pore diameters of carbons are usually calculated, by inverse-type relationships, it is concluded that they are questionable for carbons containing surface oxides, especially carboxyls.

Validation of three new measure-correlate-predict models for the long-term prospection of the wind resource

The estimation of the long-term wind resource at a prospective site based on a relatively short on-site measurement campaign is an indispensable task in the development of a commercial wind farm. The typical industry approach is based on the measure-correlate-predict �MCP� method where a relational model between the site wind velocity data and the data obtained from a suitable reference site is built from concurrent records. In a subsequent step, a long-term prediction for the prospective site is obtained from a combination of the relational model and the historic reference data. In the present paper, a systematic study is presented where three new MCP models, together with two published reference models �a simple linear regression and the variance ratio method�, have been evaluated based on concurrent synthetic wind speed time series for two sites, simulating the prospective and the reference site. The synthetic method has the advantage of generating time series with the desired statistical properties, including Weibull scale and shape factors, required to evaluate the five methods under all plausible conditions. In this work, first a systematic discussion of the statistical fundamentals behind MCP methods is provided and three new models, one based on a nonlinear regression and two �termed kernel methods� derived from the use of conditional probability density functions, are proposed. All models are evaluated by using five metrics under a wide range of values of the correlation coefficient, the Weibull scale, and the Weibull shape factor. Only one of all models, a kernel method based on bivariate Weibull probability functions, is capable of accurately predicting all performance metrics studied.

How do multilateral institutions influence individual perceptions of international affairs? Evidence from Europe and Asia

To date there has been no systematic study of the relationship between individuals’ opinions of different institutions and their perceptions of world affairs. This article tries to fill this gap by using a large cross-country data set comprising nine EU members and seven Asian nations and instrumental variable bivariate probit regression analysis. Controlling for a host of factors, the article shows that individuals’ confidence in multilateral institutions affects their perceptions of whether or not their country is being treated fairly in international affairs. This finding expands upon both theoretical work on multilateral institutions that has focused on state actors’ rationale for engaging in multilateral cooperation and empirical work that has treated confidence in multilateral institutions as a dependent variable. The article also shows that individuals’ confidence in different international organizations has undifferentiated effects on their perceptions of whether or not their country is being treated fairly in international affairs, though individuals more knowledgeable about international affairs exhibit slightly different attitudes. Finally, the article demonstrates significant differences in opinion across Europe and Asia.

Using experimental evolution to explore natural patterns between bacterial motility and resistance to bacteriophages

Resistance of bacteria to phages may be gained by alteration of surface proteins to which phages bind, a mechanism that is likely to be costly as these molecules typically have critical functions such as movement or nutrient uptake. To address this potential trade-off, we combine a systematic study of natural bacteria and phage populations with an experimental evolution approach. We compare motility, growth rate and susceptibility to local phages for 80 bacteria isolated from horse chestnut leaves and, contrary to expectation, find no negative association between resistance to phages and bacterial motility or growth rate. However, because correlational patterns (and their absence) are open to numerous interpretations, we test for any causal association between resistance to phages and bacterial motility using experimental evolution of a subset of bacteria in both the presence and absence of naturally associated phages. Again, we find no clear link between the acquisition of resistance and bacterial motility, suggesting that for these natural bacterial populations, phage-mediated selection is unlikely to shape bacterial motility, a key fitness trait for many bacteria in the phyllosphere. The agreement between the observed natural pattern and the experimental evolution results presented here demonstrates the power of this combined approach for testing evolutionary trade-offs.

Private industrial project management: a systems-based case study

The technique of linear responsibility analysis is used for a retrospective case study of a private industrial development consisting of an extension to existing buildings to provide a warehouse, services block and packing line. The organizational structure adopted on the project is analysed using concepts from systems theory which are included in Walker's theoretical model of the structure of building project organizations (Walker, 1981). This model proposes that the process of building provision can be viewed as systems and subsystems which are differentiated from each other at decision points. Further to this, the subsystems can be viewed as the interaction of managing system and operating system. Using Walker's model, a systematic analysis of the relationships between the contributors gives a quantitative assessment of the efficacy of the organizational structure used. The causes of the client's dissatisfaction with the outcome of the project were lack of integration and complexity of the managing system. However, there was a high level of satisfaction with the completed project and this is reflected by the way in which the organization structure corresponded to the model's propositions.

A conventionally managed project: a systems based case study

The technique of linear responsibility analysis is used for a retrospective case study of a private development consisting of an extension to an existing building to provide a wholesale butchery facility. The project used a conventionally organized management process. The organization structure adopted on the project is analysed using concepts from the systems theory, which are included in Walkers theoretical model of the structure of building project organizations. This model proposes that the process of building provision can be viewed as systems and sub-systems that are differentiated from each other at decision points. Further to this, the sub-systems can be viewed as the interaction of managing system and operating system. Using Walkers model, a systematic analysis of the relationships between the contributors gives a quantitative assessment of the efficiency of the organizational structure used. The project's organization structure diverged from the models propositions resulting in delay to the project's completion and cost overrun but the client was satisfied with the project functionally.

A project managed by a multi disciplinary practice: a systems based case study.

The technique of linear responsibility analysis is used for a retrospective case study of a private industrial development consisting of an engineering factory and offices. A multi-disciplinary professional practice was used to manage and design the project. The organizational structure adopted on the project is analysed using concepts from systems theory which are included in Walker's theoretical model of the structure of building project organizations (Walker, 1981). This model proposes that the process of buildings provision can be viewed as systems and sub-systems which are differentiated form each other at decision points. Further to this, the sub-systematic analysis of the relationship between the contributors gives a quantitative assessment of the efficiency of the organizational structure used. There was a high level of satisfaction with the completed project and this is reflected by the way in which the organization structure corresponded to the model's proposition. However, the project was subject to string environmental forces which the project organization was not capable of entirely overcoming.

Variance estimation for systematic sampling from deliberately ordered populations

The systematic sampling (SYS) design (Madow and Madow, 1944) is widely used by statistical offices due to its simplicity and efficiency (e.g., Iachan, 1982). But it suffers from a serious defect, namely, that it is impossible to unbiasedly estimate the sampling variance (Iachan, 1982) and usual variance estimators (Yates and Grundy, 1953) are inadequate and can overestimate the variance significantly (Särndal et al., 1992). We propose a novel variance estimator which is less biased and that can be implemented with any given population order. We will justify this estimator theoretically and with a Monte Carlo simulation study.

Genetic structure and systematic relationships within the Ophrys fuciflora aggregate (Orchidaceae: Orchidinae): high diversity in Kent and a wind-induced discontinuity bisecting the Adriatic

A recent phylogenetic study based on multiple datasets is used as the framework for a more detailed examination of one of the ten molecularly circumscribed groups identified, the Ophrys fuciflora aggregate. The group is highly morphologically variable, prone to phenotypic convergence, shows low levels of sequence divergence and contains an unusually large proportion of threatened taxa, including the rarest Ophrys species in the UK. The aims of this study were to (a) circumscribe minimum resolvable genetically distinct entities within the O. fuciflora aggregate, and (b) assess the likelihood of gene flow between genetically and geographically distinct entities at the species and population levels. Fifty-five accessions sampled in Europe and Asia Minor from the O. fuciflora aggregate were studied using the AFLP genetic fingerprinting technique to evaluate levels of infraspecific and interspecific genetic variation and to assess genetic relationships between UK populations of O. fuciflora s.s. in Kent and in their continental European and Mediterranean counterparts. The two genetically and geographically distinct groups recovered, one located in England and central Europe and one in south-eastern Europe, are incongruent with current species delimitation within the aggregate as a whole and also within O. fuciflora s.s. Genetic diversity is higher in Kent than in the rest of western and central Europe. Gene flow is more likely to occur between populations in closer geographical proximity than those that are morphologically more similar. Little if any gene flow occurs between populations located in the south-eastern Mediterranean and those dispersed throughout the remainder of the distribution, revealing a genetic discontinuity that runs north-south through the Adriatic. This discontinuity is also evident in other clades of Ophrys and is tentatively attributed to the long-term influence of prevailing winds on the long-distance distribution of pollinia and especially seeds. A cline of gene flow connects populations from Kent and central and southern Europe; these individuals should therefore be considered part of an extensive meta-population. Gene flow is also evident among populations from Kent, which appear to constitute a single metapopulation. They show some evidence of hybridization, and possibly also introgression, with O. apifera.

Strategies to prevent falls and fractures in hospitals and care homes and effect of cognitive impairment: systematic review and meta-analyses

OBJECTIVES: To evaluate the evidence for strategies to prevent falls or fractures in residents in care homes and hospital inpatients and to investigate the effect of dementia and cognitive impairment. DESIGN: Systematic review and meta-analyses of studies grouped by intervention and setting (hospital or care home). Meta-regression to investigate the effects of dementia and of study quality and design. DATA SOURCES: Medline, CINAHL, Embase, PsychInfo, Cochrane Database, Clinical Trials Register, and hand searching of references from reviews and guidelines to January 2005. RESULTS: 1207 references were identified, including 115 systematic reviews, expert reviews, or guidelines. Of the 92 full papers inspected, 43 were included. Meta-analysis for multifaceted interventions in hospital (13 studies) showed a rate ratio of 0.82 (95% confidence interval 0.68 to 0.997) for falls but no significant effect on the number of fallers or fractures. For hip protectors in care homes (11 studies) the rate ratio for hip fractures was 0.67 (0.46 to 0.98), but there was no significant effect on falls and not enough studies on fallers. For all other interventions (multifaceted interventions in care homes; removal of physical restraints in either setting; fall alarm devices in either setting; exercise in care homes; calcium/vitamin D in care homes; changes in the physical environment in either setting; medication review in hospital) meta-analysis was either unsuitable because of insufficient studies or showed no significant effect on falls, fallers, or fractures, despite strongly positive results in some individual studies. Meta-regression showed no significant association between effect size and prevalence of dementia or cognitive impairment. CONCLUSION: There is some evidence that multifaceted interventions in hospital reduce the number of falls and that use of hip protectors in care homes prevents hip fractures. There is insufficient evidence, however, for the effectiveness of other single interventions in hospitals or care homes or multifaceted interventions in care homes.