An Update of the Rules for Pyranoside Sulfonate Displacement

The original 1967 Richardson–Hough rules for predicting SN2 displacement viability in carbohydrate sulfonate derivatives with external nucleophiles have now been updated. Not only do the original rules still hold, but the newly updated rules rationalize why O-triflates (trifluoromethanesulfonate esters) frequently allow many seemingly “disallowed” pyranosidic nucleophilic substitutions to proceed. The new guidelines, which are based on three decades of experimental evidence, allow the feasibility of many pyranosidic O-triflate SN2 displacements to be gauged beforehand.

A Novel Bradykinin-Related Dodecapeptide (RVALPPGFTPLR) from the Skin Secretion of the Fujian Large-Headed Frog (Limnonectes fujianensis) Exhibiting Unusual Structural and Functional Features

Bradykinin-related peptides (BRPs) are significant components of the defensive skin secretions of many anuran amphibians, and these secretions represent the source of the most diverse spectrum of such peptides so far encountered in nature. Of the many families of bioactive peptides that have been identified from this source, the BRPs uniquely appear to represent homologues of counterparts that have specific distributions and receptor targets within discrete vertebrate taxa, ranging from fishes through mammals. Their broad spectra of actions, including pain and inflammation induction and smooth muscle effects, make these peptides ideal weapons in predator deterrence. Here, we describe a novel 12-mer BRP (RVALPPGFTPLR-RVAL-(L1, T6, L8)-bradykinin) from the skin secretion of the Fujian large-headed frog (Limnonectes fujianensis). The C-terminal 9 residues of this BRP (-LPPGFTPLR) exhibit three amino acid substitutions (L/R at Position 1, T/S at Position 6 and L/F at Position 8) when compared to canonical mammalian bradykinin (BK), but are identical to the kinin sequence present within the cloned kininogen-2 from the Chinese soft-shelled turtle (Pelodiscus sinensis) and differ from that encoded by kininogen-2 of the Tibetan ground tit (Pseudopodoces humilis) at just a single site (F/L at Position 8). These data would imply that the novel BRP is an amphibian defensive agent against predation by sympatric turtles and also that the primary structure of the avian BK, ornithokinin (RPPGFTPLR), is not invariant within this taxon. Synthetic RVAL-(L1, T6, L8)-bradykinin was found to be an antagonist of BK-induced rat tail artery smooth muscle relaxation acting via the B2-receptor.

Multiphysics Simulation of Thermal Plasma Produced by Lightning Strike on Aircraft Structures

A novel numerical technique is proposed to model thermal plasma of microseconds/milliseconds time-scale effect. Modelling thermal plasma due to lightning strike will allow the estimation of electric current density, plasma pressure, and heat flux at the surface of the aircraft structure. These input data can then be used for better estimation of the mechanical/thermal induced damage on the aircraft structures for better protection systems design. Thermal plasma generated during laser cutting, electric (laser) welding and other plasma processing techniques have been the focus of many researchers. Thermal plasma is a gaseous state that consists from a mixture of electrons, ions, and natural particles. Thermal plasma can be assumed to be in local thermodynamic equilibrium, which means the electrons and the heavy species have equal temperature. Different numerical techniques have been developed using a coupled Navier Stokes – Heat transfer – Electromagnetic equations based on the assumption that the thermal plasma is a single laminar gas flow. These previous efforts focused on generating thermal plasma of time-scale in the range of seconds. Lighting strike on aircraft structures generates thermal plasma of time-scale of milliseconds/microseconds, which makes the previous physics used not applicable. The difficulty comes from the Navier-Stokes equations as the fluid is simulated under shock load, this introducing significant changes in the density and temperature of the fluid.

The statistical significance of randomized controlled trial results is frequently fragile: A case for a Fragility Index

Objectives

A P-value <0.05 is one metric used to evaluate the results of a randomized controlled trial (RCT). We wondered how often statistically significant results in RCTs may be lost with small changes in the numbers of outcomes.

Study Design and Setting

A review of RCTs in high-impact medical journals that reported a statistically significant result for at least one dichotomous or time-to-event outcome in the abstract. In the group with the smallest number of events, we changed the status of patients without an event to an event until the P-value exceeded 0.05. We labeled this number the Fragility Index; smaller numbers indicated a more fragile result.

Results

The 399 eligible trials had a median sample size of 682 patients (range: 15-112,604) and a median of 112 events (range: 8-5,142); 53% reported a P-value <0.01. The median Fragility Index was 8 (range: 0-109); 25% had a Fragility Index of 3 or less. In 53% of trials, the Fragility Index was less than the number of patients lost to follow-up.

Conclusion

The statistically significant results of many RCTs hinge on small numbers of events. The Fragility Index complements the P-value and helps identify less robust results. 

Energy conserving schemes for the simulation of musical instrument contact dynamics

Collisions are an innate part of the function of many musical instruments. Due to the nonlinear nature of contact forces, special care has to be taken in the construction of numerical schemes for simulation and sound synthesis. Finite difference schemes and other time-stepping algorithms used for musical instrument modelling purposes are normally arrived at by discretising a Newtonian description of the system. However because impact forces are non-analytic functions of the phase space variables, algorithm stability can rarely be established this way. This paper presents a systematic approach to deriving energy conserving schemes for frictionless impact modelling. The proposed numerical formulations follow from discretising Hamilton׳s equations of motion, generally leading to an implicit system of nonlinear equations that can be solved with Newton׳s method. The approach is first outlined for point mass collisions and then extended to distributed settings, such as vibrating strings and beams colliding with rigid obstacles. Stability and other relevant properties of the proposed approach are discussed and further demonstrated with simulation examples. The methodology is exemplified through a case study on tanpura string vibration, with the results confirming the main findings of previous studies on the role of the bridge in sound generation with this type of string instrument.

Falls prevention and support:: translating research, integrating services and promoting the contribution of service users for quality and innovative programmes of care

Falls are a significant threat to the safety, health and independence of older citizens. Despite the substantial evidence that is available around effective falls prevention programmes and interventions, their translation into falls reduction programmes and policies has yet to be fully realised. While hip fracture rates are decreasing, the number and incidence of fall-related hospital admissions among older people continue to rise. Given the demographic trends that highlight increasing numbers of older people in the UK, which is broadly reflected internationally, there is a financial and social imperative to minimise the rate of falls and associated injuries. Falling is closely aligned to growing older (Slips, Trips and Falls Update: From Acute and Community Hospitals and Mental Health Units in England and Wales, Department of Health, HMSO, London, 2010). According to the World Health Organization, around 30% of older people aged over 65 and 50% of those over 80 will fall each year (Falls Fact Sheet Number 344, WHO, Geneva, 2010). Falls happen as a result of many reasons and can have harmful consequences, including loss of mobility and independence, confidence and in many cases even death (Cochrane Database Syst Rev 15, 2009, 146; Slips, Trips and Falls Update: From Acute and Community Hospitals and Mental Health Units in England and Wales, Department of Health, HMSO, London, 2010; Falling Standards, Broken Promises: Report of the National
Audit of Falls and Bone Health in Older People 2010, Health Care Quality
Improvement Partnership, London, 2011). What is neither fair nor correct is the
common belief by old and young alike that falls are just another inconvenience to put up with. The available evidence justifiably supports the view that well-organised services, based upon national standards and expert guidance, can prevent future falls among older people and reduce death and disability from fractures. This paper will draw from the UK, as an exemplar for policy and practice, to discuss the strategic direction of falls prevention programmes for older people and the partnerships that need to exist between researchers, service providers and users of services to translate evidence to the clinical setting. Second, it will propose some mechanisms for disseminating evidence to healthcare professionals and other stakeholders, to improve the quality and capacity of the clinical workforce.

European Recommendations for Primary Prevention of Congenital Anomalies: A Joined Effort of EUROCAT and EUROPLAN Projects to Facilitate Inclusion of This Topic in the National Rare Disease Plans

Congenital anomalies (CA) are the paradigm example of rare diseases liable to primary prevention actions due to the multifactorial etiology of many of them, involving a number of environmental factors together with genetic predispositions. Yet despite the preventive potential, lack of attention to an integrated preventive strategy has led to the prevalence of CA remaining relatively stable in recent decades. The 2 European projects, EUROCAT and EUROPLAN, have joined efforts to provide the first science-based and comprehensive set of recommendations for the primary prevention of CA in the European Union. The resulting EUROCAT-EUROPLAN 'Recommendations on Policies to Be Considered for the Primary Prevention of Congenital Anomalies in National Plans and Strategies on Rare Diseases' were issued in 2012 and endorsed by EUCERD (European Union Committee of Experts on Rare Diseases) in 2013. The recommendations exploit interdisciplinary expertise encompassing drugs, diet, lifestyles, maternal health status, and the environment. The recommendations include evidence-based actions aimed at reducing risk factors and at increasing protective factors and behaviors at both individual and population level. Moreover, consideration is given to topics specifically related to CA (e.g. folate status, teratogens) as well as of broad public health impact (e.g. obesity, smoking) which call for specific attention to their relevance in the pre- and periconceptional period. The recommendations, reported entirely in this paper, are a comprehensive tool to implement primary prevention into national policies on rare diseases in Europe.

Electron recombination, photoionization, and scattering via many-electron compound resonances

Highly excited eigenstates of atoms and ions with open f shell are chaotic superpositions of thousands, or even millions, of Hartree-Fock determinant states. The interaction between dielectronic and multielectronic configurations leads to the broadening of dielectronic recombination resonances and relative enhancement of photon emission due to opening of thousands of radiative decay channels. The radiative yield is close to 100% for electron energy <1 eV and rapidly decreases for higher energies due to opening of many autoionization channels. The same mechanism predicts suppression of photoionization and relative enhancement of the Raman scattering. Results of our calculations of the recombination rate are in agreement with the experimental data for W20+ and Au25+.

The organizational ecology of ethnic cleavages: The nonlinear effects of ethnic diversity on party system fragmentation

The conventional wisdom regarding party system fragmentation assumes that the effects of electoral systems and social cleavages are linear. However, recent work applying organizational ecology theories to the study of party systems has challenged the degree to which electoral system effects are linear. This paper applies such concepts to the study of social cleavages. Drawing from theories of organizational ecology and the experience of many ethnically diverse African party systems, I argue that the effects of ethnic diversity are nonlinear, with party system fragmentation increasing until reaching moderate levels of diversity before declining as diversity reaches extreme values. Examining this argument cross-nationally, the results show that accounting for nonlinearity in ethnic diversity effects significantly improves model fit.

Effects of Elodea nuttallii on temperate freshwater plants, microalgae and invertebrates: small differences between invaded and uninvaded areas

The invasive aquatic plant species Elodea nuttallii could pose a considerable risk to European freshwater ecosystems based on its current distribution, rate of spread and potential for high biomass. However, little research has been conducted on the impacts of this species on native biota. This study takes an ecosystem-wide approach and examines the impact of E. nuttallii on selected physicochemical parameters (dissolved oxygen and pH), algae, invertebrate and macrophyte communities. Elodea nuttallii had small but significant impacts on plant, invertebrate and algal species. The richness of algal periphyton was lower on E. nuttallii than on native macrophytes. The taxonomic composition of invertebrate communities associated with E. nuttallii differed from that associated with similar native plant species, but did not differ in terms of total biomass or species richness. Macrophyte species richness and total cover were positively correlated with percentage cover of E. nuttallii. Not all macrophyte species responded in the same way to E. nuttallii invasion; cover of the low-growing species, Elodea canadensis and charophytes were negatively correlated with E. nuttallii cover, whilst floating-rooted plants were positively correlated with E. nuttallii cover. All observed differences in the macrophyte community were small relative to other factors such as nutrient levels, inter-annual variation and differences between sites. Despite this, the observed negative association between E. nuttallii and charophytes is a key concern due to the rarity and endangered status of many charophyte species.

New insights on postglacial colonization in western Europe: the phylogeography of the Leisler’s bat (Nyctalus leisleri)

Despite recent advances in the understanding of the interplay between a dynamic physical environment and phylogeography in Europe, the origins of contemporary Irish biota remain uncertain. Current thinking is that Ireland was colonized post-glacially from southern European refugia, following the end of the last glacial maximum(LGM), some 20 000 years BP. The Leisler’s bat (Nyctalus leisleri), one of the few native Irish mammal species, is widely distributed throughout Europe but, with the exception of Ireland, is generally rare and considered vulnerable. We investigate the origins and phylogeographic relationships of Irish populations in relation to those across Europe, including the closely related species N. azoreum. We use a combination of approaches, including mitochondrial and nuclear DNA markers, in addition to approximate Bayesian computation and palaeo-climatic species distribution modelling. Molecular analyses revealed two distinct and diverse European mitochondrialDNAlineages,which probably diverged in separate glacial refugia. Awestern lineage, restricted to Ireland, Britain and the Azores, comprises Irish and British N. leisleri and N. azoreum specimens; an eastern lineage is distributed throughout mainland Europe. Palaeo-climatic projections indicate suitable habitats during the LGM, including known glacial refugia, in addition to potential novel cryptic refugia along the western fringe of Europe. These results may be applicable to populations of many species.

Efficient Structure Learning of Bayesian Networks using Constraints

This paper addresses the problem of learning Bayesian network structures from data based on score functions that are decomposable. It describes properties that strongly reduce the time and memory costs of many known methods without losing global optimality guarantees. These properties are derived for different score criteria such as Minimum Description Length (or Bayesian Information Criterion), Akaike Information Criterion and Bayesian Dirichlet Criterion. Then a branch-and-bound algorithm is presented that integrates structural constraints with data in a way to guarantee global optimality. As an example, structural constraints are used to map the problem of structure learning in Dynamic Bayesian networks into a corresponding augmented Bayesian network. Finally, we show empirically the benefits of using the properties with state-of-the-art methods and with the new algorithm, which is able to handle larger data sets than before.

Losses of bioactive polyacetylenes during minimal processing of carrots

Vegetables of the Apiaceae plant family such as carrots, parsnip, celery and parsley,contain in minor quantities, a group of bioactive aliphatic C17-polyacetylenes (falcarinol,falcarindiol, falcarindiol-3- acetate). Recent studies have highlighted important biologicalfunctions in vitro and in vivo (animal studies) although the beneficial effect in humannutrition attributable to an increased in polyacetylenes diet are yet to be confirmed(Lund, 1990).Carrots not only contain relatively high polyacetylene content but also form a significantpart of many countries dietary habits. Carrots are also present in some ready-to-eat foodssuch as chilled freshly prepared salads, as part of the increasingly popular minimallyprocessed foods. Whereas the effect of conventional processing (boiling, vacuum processing) on the levels of polyacetylenes has been relatively well studied, the effect of minimal mechanical operations such as “peeling”, “mechanical cutting” and “chlorine washing” remains unknown.

Intensity Enhancement of O VI Ultraviolet Emission Lines in Solar Spectra due to Opacity

Opacity is a property of many plasmas. It is normally expected that if an emission line in a plasma becomes optically thick, then its intensity ratio to that of another transition that remains optically thin should decrease. However, radiative transfer calculations undertaken both by ourselves and others predict that under certain conditions the intensity ratio of an optically thick to an optically thin line can show an increase over the optically thin value, indicating an enhancement in the former. These conditions include the geometry of the emitting plasma and its orientation to the observer. A similar effect can take place between lines of differing optical depths. While previous observational studies have focused on stellar point sources, here we investigate the spatially resolved solar atmosphere using measurements of the I(1032 Å)/I(1038 Å) intensity ratio of O VI in several regions obtained with the Solar Ultraviolet Measurements of Emitted Radiation instrument on board the Solar and Heliospheric Observatory satellite. We find several I(1032 Å)/I(1038 Å) ratios observed on the disk to be significantly larger than the optically thin value of 2.0, providing the first detection (to our knowledge) of intensity enhancement in the ratio arising from opacity effects in the solar atmosphere. The agreement between observation and theory is excellent and confirms that the O VI emission originates from a slab-like geometry in the solar atmosphere, rather than from cylindrical structures.

The imprint of the geographical, evolutionary and ecological context on species-area relationships

Species-area relationships (SAR) are fundamental in the understanding of biodiversity patterns and of critical importance for predicting species extinction risk worldwide. Despite the enormous attention given to SAR in the form of many individual analyses, little attempt has been made to synthesize these studies. We conducted a quantitative meta-analysis of 794 SAR, comprising a wide span of organisms, habitats and locations. We identified factors reflecting both pattern-based and dynamic approaches to SAR and tested whether these factors leave significant imprints on the slope and strength of SAR. Our analysis revealed that SAR are significantly affected by variables characterizing the sampling scheme, the spatial scale, and the types of organisms or habitats involved. We found that steeper SAR are generated at lower latitudes and by larger organisms. SAR varied significantly between nested and independent sampling schemes and between major ecosystem types, but not generally between the terrestrial and the aquatic realm. Both the fit and the slope of the SAR were scale-dependent. We conclude that factors dynamically regulating species richness at different spatial scales strongly affect the shape of SAR. We highlight important consequences of this systematic variation in SAR for ecological theory, conservation management and extinction risk predictions.