Toluene dioxygenase-catalyzed cis-dihydroxylation of benzo[b]thiophenes and benzo[b]furans: synthesis of benzo[b]thiophene 2,3-oxide

Enzymatic cis-dihydroxylation of benzo[b]thiophene, benzo[b]furan and several methyl substituted derivatives was found to occur in both the carbocyclic and heterocyclic rings. Relative and absolute configurations and enantiopurities of the resulting dihydrodiols were determined. Hydrogenation of the alkene bond in carbocyclic cis-dihydrodiols and ring-opening epimerization/reduction reactions of heterocyclic cis/trans-dihydrodiols were also studied. The relatively stable heterocyclic dihydrodiols of benzo[b]thiophene and benzo[b]furan showed a strong preference for the trans configuration in aqueous solutions. The 2,3-dihydrodiol metabolite of benzo[b]thiophene was utilized as a precursor in the chemoenzymatic synthesis of the unstable arene oxide, benzo[b]thiophene 2,3-oxide.

Long-term consequences of pain in human neonates

The low tactile threshold in preterm infants when they are in the neonatal intensive care unit (NICU), while their physiological systems are unstable and immature, potentially renders them more vulnerable to the effects of repeated invasive procedures. There is a small but growing literature on pain and tactile responsivity following procedural pain in the NICU, or early surgery. Long-term effects of repeated pain in the neonatal period on neurodevelopment await further research. However, there are multiple sources of stress in the NICU, which contribute to inducing high overall 'allostatic load', therefore determining specific effects of neonatal pain in human infants is challenging.

Stomatal proxy record of CO2 concentrations from the last termination suggests an important role for CO2 at climate change transitions

A new stomatal proxy-based record of CO₂ concentrations ([CO₂]), based on Betula nana (dwarf birch) leaves from the Hässeldala Port sedimentary sequence in south-eastern Sweden, is presented. The record is of high chronological resolution and spans most of Greenland Interstadial 1 (GI-1a to 1c, Allerød pollen zone), Greenland Stadial 1 (GS-1, Younger Dryas pollen zone) and the very beginning of the Holocene (Preboreal pollen zone). The record clearly demonstrates that i) [CO₂] were significantly higher than usually reported for the Last Termination and ii) the overall pattern of CO₂ evolution through the studied time period is fairly dynamic, with significant abrupt fluctuations in [CO₂] when the climate moved from interstadial to stadial state and vice versa. A new loss-on-ignition chemical record (used here as a proxy for temperature) lends independent support to the Hässeldala Port [CO₂] record. The large-amplitude fluctuations around the climate change transitions may indicate unstable climates and that " tipping-point" situations were involved in Last Termination climate evolution. The scenario presented here is in contrast to [CO₂] records reconstructed from air bubbles trapped in ice, which indicate lower concentrations and a gradual, linear increase of [CO₂] through time. The prevalent explanation for the main climate forcer during the Last Termination being ocean circulation patterns needs to re-examined, and a larger role for atmospheric [CO₂] considered.

Rapid succession of plant associations on the small ocean island of Mauritius at the onset of the Holocene

The island of Mauritius offers the opportunity to study the poorly understood vegetation response to climate change on a small tropical oceanic island. A high-resolution pollen record from a 10 m long peat core from Kanaka Crater (560 m elevation, Mauritius, Indian Ocean) shows that vegetation shifted from a stable open wet forest Last Glacial state to a stable closed-stratified-tall-forest Holocene state. An ecological threshold was crossed at ∼11.5 cal ka BP, propelling the forest ecosystem into an unstable period lasting ∼4000 years. The shift between the two steady states involves a cascade of four abrupt (<150 years) forest transitions in which different tree species dominated the vegetation for a quasi-stable period of respectively ∼1900, ∼1100 and ∼900 years. We interpret the first forest transition as climate-driven, reflecting the response of a small low topography oceanic island where significant spatial biome migration is impossible. The three subsequent forest transitions are not evidently linked to climate events, and are suggested to be driven by internal forest dynamics. The cascade of four consecutive events of species turnover occurred at a remarkably fast rate compared to changes during the preceding and following periods, and might therefore be considered as a composite tipping point in the ecosystem. We hypothesize that wet gallery forest, spatially and temporally stabilized by the drainage system, served as a long lasting reservoir of biodiversity and facilitated a rapid exchange of species with the montane forests to allow for a rapid cascade of plant associations.

Limbal stem cells of the corneal epithelium

Stem cells have certain unique characteristics, which include longevity, high capacity of self-renewal with a long cell cycle time and a short S-phase duration, increased potential for error-free proliferation, and poor differentiation. The ocular surface is made up of two distinct types of epithelial cells, constituting the conjunctival and the corneal epithelia. Although anatomically continuous with each other at the corneoscleral limbus, the two cell phenotypes represent quite distinct subpopulations. Stem cells for the cornea reside at the corneoscleral limbus. The limbal palisades of Vogt and the interpalisade rete ridges are believed to be repositories of stem cells. The microenvironment of the limbus is considered to be important in maintaining the stemness of stem cells. Limbal stem cells also act as a 'barrier' to conjunctival epithelial cells and normally prevent them from migrating on to the corneal surface. Under certain conditions, however, the limbal stem cells may be partially or totally depleted, resulting in varying degrees of stem cell deficiency with resulting abnormalities in the corneal surface. Such deficiency of limbal stem cells leads to 'conjunctivalization' of the cornea with vascularization, appearance of goblet cells, and an irregular and unstable epithelium. This results in ocular discomfort and reduced vision. Partial stem cell deficiency can be managed by removing the abnormal epithelium and allowing the denuded cornea, especially the visual axis, to resurface with cells derived from the remaining intact limbal epithelium. In total stem cell deficiency, autologous limbus from the opposite normal eye or homologous limbus from living related or cadaveric donors can be transplanted on to the affected eye. With the latter option, systemic immunosuppression is required. Amniotic membrane transplantation is a useful adjunct to the above procedures in some instances. Copyright (C) 2000 Elsevier Science Inc.

Direct, positive feedbacks produce instability in models of interrelationships among soil structure, plants and arbuscular mycorrhizal fungi

Current conceptual models of reciprocal interactions linking soil structure, plants and arbuscular mycorrhizal fungi emphasise positive feedbacks among the components of the system. However, dynamical systems with high dimensionality and several positive feedbacks (i.e. mutualism) are prone to instability. Further, organisms such as arbuscular mycorrhizal fungi (AMF) are obligate biotrophs of plants and are considered major biological agents in soil aggregate stabilization. With these considerations in mind, we developed dynamical models of soil ecosystems that reflect the main features of current conceptual models and empirical data, especially positive feedbacks and linear interactions among plants, AMF and the component of soil structure dependent on aggregates. We found that systems become increasingly unstable the more positive effects with Type I functional response (i.e., the growth rate of a mutualist is modified by the density of its partner through linear proportionality) are added to the model, to the point that increasing the realism of models by adding linear effects produces the most unstable systems. The present theoretical analysis thus offers a framework for modelling and suggests new directions for experimental studies on the interrelationship between soil structure, plants and AMF. Non-linearity in functional responses, spatial and temporal heterogeneity, and indirect effects can be invoked on a theoretical basis and experimentally tested in laboratory and field experiments in order to account for and buffer the local instability of the simplest of current scenarios. This first model presented here may generate interest in more explicitly representing the role of biota in soil physical structure, a phenomenon that is typically viewed in a more process- and management-focused context. (C) 2011 Elsevier Ltd. All rights reserved.

Shifting Ground:Beyond National Architecture

The Irish Pavilion at the Venice Architecture Biennale 2012 charts a position for Irish architecture in a global culture where the modes of production of architecture are radically altered. Ireland is one of the most globalised countries in the world, yet it has developed a national culture of architecture derived from local place as a material construct. We now have to evolve our understanding in the light of the globalised nature of economic processes and architectural production which is largely dependent on internationally networked flows of products, data, and knowledge. We have just begun to represent this situation to ourselves and others. How should a global architecture be grounded culturally and philosophically? How does it position itself outside of shared national reference points?
heneghan peng architects were selected as participants because they are working across three continents on a range of competition-winning projects. Several of these are in sensitive and/or symbolic sites that include three UNESCO World Heritage sites, including the Grand Egyptian Museum in Cairo, the Giants Causeway Visitor Centre in Northern Ireland, and the new Rhine Bridge near Lorelei.
Our dialogue led us to discussing the universal languages of projective geometry and number are been shared by architects and related professionals. In the work of heneghan peng, the specific embodiment of these geometries is carefully calibrated by the choice of materials and the detailed design of their physical performance on site. The stone facade of the Giant’s Causeway Visitor Centre takes precise measure of the properties of the volcanic basalt seams from which it is hewn. The extraction of the stone is the subject of the pavilion wall drawings which record the cutting of stones to create the façade of the causeway centre.
We also identified water as an element which is shared across the different sites. Venice is a perfect place to take measure of this element which suggests links to another site – the Nile Valley which was enriched by the annual flooding of the River Nile. An ancient Egyptian rod for measuring the water level of the Nile inspired the design of the Nilometre - a responsive oscillating bench that invites visitors to balance their respective weights. This action embodies the ways of thinking that are evolving to operate in the globalised world, where the autonomous architectural object is dissolving into an expanded field of conceptual rules and systems. The bench constitutes a shifting ground located in the unstable field of Venice. It is about measurement and calibration of the weight of the body in relation to other bodies; in relation to the site of the installation; and in relation to water. The exhibit is located in the Artiglierie section of the Arsenale. Its level is calibrated against the mark of the acqua alta in the adjacent brickwork of the building which embodies a liminal moment in the fluctuating level of the lagoon.
The weights of bodies, the level of water, changes over time, are constant aspects of design across cultures and collectively they constitute a common ground for architecture - a ground shared with other design professionals. The movement of the bench required complex engineering design and active collaboration between the architects, engineers and fabricators. It is a kind of prototype – a physical object produced from digital data that explores the mathematics at play – the see-saw motion invites the observer to become a participant, to give it a test drive. It shows how a simple principle can generate complex effects that are difficult to predict and invites visitors to experiment and play with them.

Gold-based optical biosensor for single-mismatched DNA detection using salt-induced hybridization

In this study, a gold nanoparticle (Au-NP)-based detection method for sensitive and specific DNA-based diagnostic applications is described. A sandwich format consisting of Au-NPs/DNA/PMP (Streptavidin-coated MagnetSphere Para-Magnetic Particles) was fabricated. PMPs captured and separated target DNA while Au-NPs modified with oligonucleotide detection sequences played a role in recognition and signal production. Due to the much lower stability of mismatched DNA strands caused by unstable duplex structures in solutions of relatively low salt concentration, hybridization efficiency in the presence of different buffers was well investigated, and thus, the optimized salt concentration allowed for discrimination of single-mismatched DNA (MMT) from perfectly matched DNA (PMT). Therefore, quantitative information concerning the target analyte was translated into a colorimetric signal, which could easily and quantitatively measured by low-cost UV–vis spectrophotometric analysis. The results indicated this to be a very simple and economic strategy for detection of single-mismatched DNA strands.

Patriotism or Integrity?:Constitutional Community in Divided Societies

Some commentators worry that a plurinational constitutional order can only ever be an inherently unstable modus vivendi. They fear that the accommodation of sub-state nationalism will tend to undermine the viability of constitutional democracies. This article enlists Ronald Dworkin’s theory of ‘law as integrity’ to show how these concerns might be assuaged. My central claim is that the expressive value of integrity can drive a divided society in the direction of an eventual community of principle, even in the absence of a common political identity. I argue that this model of political community is a more plausible prescription for divided societies than the theory that competing nationalisms might be superseded by constitutional patriotism. I go on to explain, however, that integrity has a better chance of realizing this potential if the generally judge-centric focus of Dworkin’s theory is expanded to make greater room for non-judicial interpretative responsibility. Occasional references are made to the example of Northern Ireland to illustrate my points.

The transport of cosmic rays in self-excited magnetic turbulence

The process of diffusive shock acceleration relies on the efficacy with which hydromagnetic waves can scatter charged particles in the precursor of a shock. The growth of self-generated waves is driven by both resonant and non-resonant processes. We perform high-resolution magnetohydrodynamic simulations of the non-resonant cosmic ray driven instability, in which the unstable waves are excited beyond the linear regime. In a snapshot of the resultant field, particle transport simulations are carried out. The use of a static snapshot of the field is reasonable given that the Larmor period for particles is typically very short relative to the instability growth time. The diffusion rate is found to be close to, or below, the Bohm limit for a range of energies. This provides the first explicit demonstration that self-excited turbulence reduces the diffusion coefficient and has important implications for cosmic-ray transport and acceleration in supernova remnants.

A cosmic ray current-driven instability in partially ionised media

Context. We investigate the growth of hydromagnetic waves driven by streaming cosmic rays in the precursor environment of a supernova remnant shock.

Aims. It is known that transverse waves propagating parallel to the mean magnetic field are unstable to anisotropies in the cosmic ray distribution, and may provide a mechanism to substantially amplify the ambient magnetic field. We quantify the extent to which temperature and ionisation fractions modify this picture.

Methods. Using a kinetic description of the plasma we derive the dispersion relation for a collisionless thermal plasma with a streaming cosmic ray current. Fluid equations are then used to discuss the effects of neutral-ion collisions.

Results. We calculate the extent to which the environment into which the cosmic rays propagate influences the growth of the magnetic field, and determines the range of possible growth rates.

Conclusions. If the cosmic ray acceleration is efficient, we find that very large neutral fractions are required to stabilise the growth of the non-resonant mode. For typical supernova parameters in our Galaxy, thermal effects do not significantly alter the growth rates. For weakly driven modes, ion-neutral damping can dominate over the instability at more modest ionisation fractions. In the case of a supernova shock interacting with a molecular clouds, such as in RX J1713.7-3946, with high density and low ionisation, the modes can be rapidly damped.

Preparation of Highly Stable OEG derivatives-functionalized AuNPs and Its Application in LSPR-based Detection of PSA/ACT Complex

The zero-length crosslinker EDC has been widely used to make amide bonds between carboxylic acid and amine groups for bioconjugation because no residues remain in the crosslinked protein. During the conjugation process, EDC activates the carboxyl groups (negatively charged) and forms an unstable amine-reactive intermediate (positively charged). However, the process turns to be a problematic issue if it is applied to modify carboxyl-functionalized and –stabilized Au nanoparticles (AuNPs) due to the fact that the negatively repulsive forces which help to stabilize the AuNPs were disrupted leading to the colloid aggregation. Therefore, to modify the negatively carboxyl-terminated AuNPs while their stability can be maintained yet, we assume that functionalization of the AuNPs using 02 kinds of negatively charged groups which one serves as a linking agent, and the other one plays a role of negative charge maintainer could overcome the impediment.

In this study, the colloidal gold nanoparticles were synthesized by Turkevitch’s method, and then their surface was rationally functionalized with different molar ratios of HS(CH2)11(OCH2CH2)6OCH2COOH and HS(CH2)11(OCH2CH2)3OH (OEG6-COOH/OEG3-OH) by self assembling technique. As a result, the most appropriate molar ratio was found to be 1:10, and the AuNP aggregation was prevented not only in the activation process by EDC but also in the present of high concentration of NaCl as well as over in a wide pH range. This is the first time that extremely stable OEG derivatives-functionalized Au nanoparticles for protein bioconjugation using EDC chemistry is reported, and the results open the door for covalent bioconjugation of AuNPs in biological applications.

Alkylated organic cages: from porous crystals to neat liquids

Rigid organic iminospherand cages are rendered meltable by multiple alkylation; below their melting points they can take the form of permanently porous crystals, crystals unstable to desolvation or nonporous glassy solids depending on chain length and branching; melting points as low as 50 degrees C are observed and a fully Newtonian liquid phase is obtained above 80 degrees C. Thin glassy fibres can be drawn out from a molten phase.

A comparison of Diamond Forrester and coronary calcium scores as gatekeepers for investigations of stable chest pain

To determine if calcium scores (CS) could act as a more effective gatekeeper than Diamond Forrester (DF) in the assessment of patients with suspected coronary artery disease (CAD). A sub-study of the Cardiac CT for the Assessment of Chest Pain and Plaque (CAPP) study, a randomised control trial evaluating the cost-effectiveness of cardiac CT in symptomatic patients with stable chest pain. Stable pain was defined as troponin negative pain without symptoms of unstable angina. 250 patients undergoing cardiac CT had both DF scores and CS calculated, with the accuracy of both evaluated against CT coronary angiogram. Criteria given in UK national guidelines were compared. Of the 250 patients, 4 withdrew. 140 (57 %) patients were male. The mean DF was 47.8 and mean CS 172.5. Of the 144 patients with non-anginal pain 19.4 % had significant disease (>50 % stenosis). In general the DF over estimated the presence of CAD whereas the CS reclassified patients to lower risk groups, with 91 in the high risk DF category compared to 26 in the CS. Both receiver operating curve and McNemar Bowker test analysis suggested the DF was less accurate in the prediction of CAD compared to CS [Formula: see text] Projected downstream investigations were also calculated, with the cost per number of significant stenoses identified cheaper with the CS criteria. Patients with suspected stable CAD are more accurately risk stratified by CS compared to the traditional DF. CS was more successful in the prediction of significant stenosis and appears to be more effective at targeting clinical resources to those patients that are in need of them.

Nicotinamide Benzimidazolide Dinucleotides, Non-Cyclisable Analogues of NAD+

Benzimidazole-based nucleotides and dinucleotides have been synthesised to increase the range of chemical tools available to probe the NAD+ biology space. They were examined for their reactivity in alkylation-type reactions, where they yielded unstable alkylated heteoaromatic adducts, both chemically and enzymatically. While unsuited for NAD+ cyclases, these NAD+ analogues could be viable substrates for non-adenine modifying NAD+-dependent enzyme classes.