Self-immolative linkers in polymeric delivery systems

There has been significant interest in the methodologies of controlled release for a diverse range of applications spanning drug delivery, biological and chemical sensors, and diagnostics. The advancement in novel substrate-polymer coupling moieties has led to the discovery of self-immolative linkers. This new class of linker has gained popularity in recent years in polymeric release technology as a result of stable bond formation between protecting and leaving groups, which becomes labile upon activation, leading to the rapid disassembly of the parent polymer. This ability has prompted numerous studies into the design and development of self-immolative linkers and the kinetics surrounding their disassembly. This review details the main concepts that underpin self-immolative linker technologies that feature in polymeric or dendritic conjugate systems and outlines the chemistries of amplified self-immolative elimination.

Atmospheric electricity coupling between earthquake regions and the ionosphere

We propose a mechanism to explain suggested links between seismic activity and ionospheric changes detected overhead. Specifically, we explain changes in the natural extremely low-frequency (ELF) radio noise recently observed in the topside ionosphere aboard the DEMETER satellite at night, before major earthquakes. Our mechanism utilises increased electrical conductivity of surface layer air before a major earthquake, which reduces the surface-ionosphere electrical resistance. This increases the vertical fair weather current, and (to maintain continuity of electron flow) lowers the ionosphere. Magnitudes of crucial parameters are estimated and found to be consistent with observations. Natural variability in ionospheric and atmospheric electrical properties is evaluated, and may be overcome using a hybrid detection approach. Suggested experiments to investigate the mechanism involve measuring the cut-off frequency of ELF “tweeks”, the amplitude and phase of very low frequency radio waves in the Earth–ionosphere waveguide, or medium frequency radar, incoherent scatter or rocket studies of the lower ionospheric electron density.

Solar influences on dynamical coupling between the stratosphere and troposphere

We use a simplified atmospheric general circulation model (AGCM) to investigate the response of the lower atmosphere to thermal perturbations in the lower stratosphere. The results show that generic heating of the lower stratosphere tends to weaken the sub-tropical jets and the tropospheric mean meridional circulations. The positions of the jets, and the extent of the Hadley cells, respond to the distribution of the stratospheric heating, with low latitude heating displacing them poleward, and uniform heating displacing them equatorward. The patterns of response to the low latitude heating are similar to those found to be associated with solar variability in previous observational data analysis, and to the effects of varying solar UV radiation in sophisticated AGCMs. In order to investigate the chain of causality involved in converting the stratospheric thermal forcing to a tropospheric climate signal we conduct an experiment which uses an ensemble of model spin-ups to analyse the time development of the response to an applied stratospheric perturbation. We find that the initial effect of the change in static stability at the tropopause is to reduce the eddy momentum flux convergence in this region. This is followed by a vertical transfer of the momentum forcing anomaly by an anomalous mean circulation to the surface, where it is partly balanced by surface stress anomalies. The unbalanced part drives the evolution of the vertically integrated zonal flow. We conclude that solar heating of the stratosphere may produce changes in the circulation of the troposphere even without any direct forcing below the tropopause. We suggest that the impact of the stratospheric changes on wave propagation is key to the mechanisms involved.

The representation of conditional expectations of non-Gaussian noise

For Wiener spaces conditional expectations and $L^{2}$-martingales w.r.t. the natural filtration have a natural representation in terms of chaos expansion. In this note an extension to larger classes of processes is discussed. In particular, it is pointed out that orthogonality of the chaos expansion is not required.

Sudden stratospheric warmings as noise-induced transitions

Sudden stratospheric warmings (SSWs) are usually considered to be initiated by planetary wave activity. Here it is asked whether small-scale variability (e.g., related to gravity waves) can lead to SSWs given a certain amount of planetary wave activity that is by itself not sufficient to cause a SSW. A highly vertically truncated version of the Holton–Mass model of stratospheric wave–mean flow interaction, recently proposed by Ruzmaikin et al., is extended to include stochastic forcing. In the deterministic setting, this low-order model exhibits multiple stable equilibria corresponding to the undisturbed vortex and SSW state, respectively. Momentum forcing due to quasi-random gravity wave activity is introduced as an additive noise term in the zonal momentum equation. Two distinct approaches are pursued to study the stochastic system. First, the system, initialized at the undisturbed state, is numerically integrated many times to derive statistics of first passage times of the system undergoing a transition to the SSW state. Second, the Fokker–Planck equation corresponding to the stochastic system is solved numerically to derive the stationary probability density function of the system. Both approaches show that even small to moderate strengths of the stochastic gravity wave forcing can be sufficient to cause a SSW for cases for which the deterministic system would not have predicted a SSW.

Can the frequency of blocking be described by a red noise process?

The frequency of persistent atmospheric blocking events in the 40-yr ECMWF Re-Analysis (ERA-40) is compared with the blocking frequency produced by a simple first-order Markov model designed to predict the time evolution of a blocking index [defined by the meridional contrast of potential temperature on the 2-PVU surface (1 PVU ≡ 1 × 10−6 K m2 kg−1 s−1)]. With the observed spatial coherence built into the model, it is able to reproduce the main regions of blocking occurrence and the frequencies of sector blocking very well. This underlines the importance of the climatological background flow in determining the locations of high blocking occurrence as being the regions where the mean midlatitude meridional potential vorticity (PV) gradient is weak. However, when only persistent blocking episodes are considered, the model is unable to simulate the observed frequencies. It is proposed that this persistence beyond that given by a red noise model is due to the self-sustaining nature of the blocking phenomenon.

Fine sediment delivery and transfer in lowland catchments: modelling suspended sediment concentrations in response to hydrological forcing

Fine sediment delivery to and storage in stream channel reaches can disrupt aquatic habitats, impact river hydromorphology, and transfer adsorbed nutrients and pollutants from catchment slopes to the fluvial system. This paper presents a modelling toot for simulating the time-dependent response of the fine sediment system in catchments, using an integrated approach that incorporates both land phase and in-stream processes of sediment generation, storage and transfer. The performance of the model is demonstrated by applying it to simulate in-stream suspended sediment concentrations in two lowland catchments in southern England, the Enborne and the Lambourn, which exhibit contrasting hydrological and sediment responses due to differences in substrate permeability. The sediment model performs well in the Enborne catchment, where direct runoff events are frequent and peak suspended sediment concentrations can exceed 600 mg l(-1). The general trends in the in-stream concentrations in the Lambourn catchment are also reproduced by the model, although the observed concentrations are low (rarely exceeding 50 mg l(-1)) and the background variability in the concentrations is not fully characterized by the model. Direct runoff events are rare in this highly permeable catchment, resulting in a weak coupling between the sediment delivery system and the catchment hydrology. The generic performance of the model is also assessed using a generalized sensitivity analysis based on the parameter bounds identified in the catchment applications. Results indicate that the hydrological parameters contributing to the sediment response include those controlling (1) the partitioning of runoff between surface and soil zone flows and (2) the fractional loss of direct runoff volume prior to channel delivery. The principal sediment processes controlling model behaviour in the simulations are the transport capacity of direct runoff and the in-stream generation, storage and release of the fine sediment fraction. The in-stream processes appear to be important in maintaining the suspended sediment concentrations during low flows in the River Enborne and throughout much of the year in the River Lambourn. Copyright (c) 2007 John Wiley & Sons, Ltd.

Habituation and dishabituation to speech and office noise

The authors examined whether background noise can be habituated to in the laboratory by using memory for prose tasks in 3 experiments. Experiment 1 showed that background speech can be habituated to after 20 min exposure and that meaning and repetition had no effect on the degree of habituation seen. Experiment 2 showed that office noise without speech can also be habituated to. Finally, Experiment 3 showed that a 5-min period of quiet, but not a change in voice, was sufficient to partially restore the disruptive effects of the background noise previously habituated to. These results are interpreted in light of current theories regarding the effects of background noise and habituation; practical implications for office planning are discussed.

Theory of enhanced magnetic anisotropy induced by Pt adatoms on two-dimensional Co clusters supported on a Pt(111) substrate

Calculations are reported of the magnetic anisotropy energy of two-dimensional (2D) Co nanostructures on a Pt(111) substrate. The perpendicular magnetic anisotropy (PMA) of the 2D Co clusters strongly depends on their size and shape, and rapidly decreases with increasing cluster size. The PMA calculated is in reasonable agreement with experimental results. The sensitivity of the results to the Co-Pt spacing at the interface is also investigated and, in particular, for a complete Co monolayer we note that the value of the spacing at the interface determines whether PMA or in-plane anisotropy occurs. We find that the PMA can be greatly enhanced by the addition of Pt adatoms to the top surface of the 2D Co clusters. A single Pt atom can induce in excess of 5 meV to the anisotropy energy of a cluster. In the absence of the Pt adatoms the PMA of the Co clusters falls below 1 meV/Co atom for clusters of about 10 atoms whereas, with Pt atoms added to the surface of the clusters, a PMA of 1 meV/Co atom can be maintained for clusters as large as about 40 atoms. The effect of placing Os atoms on the top of the Co clusters is also considered. The addition of 5d atoms and clusters on the top of ferromagnetic nanoparticles may provide an approach to tune the magnetic anisotropy and moment separately.

C-H and C-D interbond coupling in CHDCl2

Laser photoacoustic spectra of vapour phase CHDCl2 reveal the presence of an interaction which has been ascribed to interbond coupling between C-H and C-D local modes. The absolute value of the interbond coupling parameter for the CHD group, determined from a fit of a model local mode hamiltonian to the experimental data, is shown to be given approximately by the geometric mean of the interbond coupling parameters of the CH2 and CD2 groups recently derived from similar studies of CH2Cl2 and CD2Cl2. Such behaviour is understood in terms of a simple analysis in which kinetic coupling effects dominate. It is suggested that C-H stretch/bend Fermi resonance is responsible for some weaker features in the spectra and modelling calculations are described which allow an order of magnitude estimate of the size of the coupling parameter involved.

Effects of solar wind magnetosphere coupling recorded at different geomagnetic latitudes: Separation of directly-driven and storage/release systems

The effect on geomagnetic activity of solar wind speed, compared with that of the strength of the interplanetary magnetic field, differs with geomagnetic latitude. In this study we construct a new index based on monthly standard deviations in the H-component of the geomagnetic field for all geomagnetic latitudes. We demonstrate that for this index the response at auroral regions correlates best with interplanetary coupling functions which include the solar wind speed while mid- and low-latitude regions respond to variations in the interplanetary magnetic field strength. These results are used to isolate the responsible geomagnetic current systems.

Sonogashira coupling on an extended gold surface in vacuo: reaction of phenylacetylene with iodobenzene on Au(111)

Temperature-programmed reaction measurements supported by scanning tunneling microscopy have shown that phenylacetylene and iodobenzene react on smooth Au(111) under vacuum conditions to yield biphenyl and diphenyldiacetylene, the result of homocoupling of the reactant molecules. They also produce diphenylacetylene, the result of Sonogashira cross-coupling, prototypical of a class of reactions that are of paramount importance in synthetic organic chemistry and whose mechanism remains controversial. Roughened Au(111) is completely inert toward all three reactions, indicating that the availability of crystallographically well-defined adsorption sites is crucially important. High-resolution X-ray photoelectron spectroscopy and near-edge X-ray absorption fine structure spectroscopy show that the reactants are initially present as intact, essentially flat-lying molecules and that the temperature threshold for Sonogashira coupling coincides with that for C−I bond scission in the iodobenzene reactant. The fractional-order kinetics and low temperature associated with desorption of the Sonogashira product suggest that the reaction occurs at the boundaries of islands of adsorbed reactants and that its appearance in the gas phase is rate-limited by the surface reaction. These findings demonstrate unambiguously and for the first time that this heterogeneous cross-coupling chemistry is an intrinsic property of extended, metallic pure gold surfaces: no other species, including solvent molecules, basic or charged (ionic) species are necessary to mediate the process.

Rational conversion of substrate and product specificity in a Salvia monoterpene synthase: structural insights into the evolution of terpene synthase function

Terpene synthases are responsible for the biosynthesis of the complex chemical defense arsenal of plants and microorganisms. How do these enzymes, which all appear to share a common terpene synthase fold, specify the many different products made almost entirely from one of only three substrates? Elucidation of the structure of 1,8-cineole synthase from Salvia fruticosa (Sf-CinS1) combined with analysis of functional and phylogenetic relationships of enzymes within Salvia species identified active-site residues responsible for product specificity. Thus, Sf-CinS1 was successfully converted to a sabinene synthase with a minimum number of rationally predicted substitutions, while identification of the Asn side chain essential for water activation introduced 1,8-cineole and alpha-terpineol activity to Salvia pomifera sabinene synthase. A major contribution to product specificity in Sf-CinS1 appears to come from a local deformation within one of the helices forming the active site. This deformation is observed in all other mono- or sesquiterpene structures available, pointing to a conserved mechanism. Moreover, a single amino acid substitution enlarged the active-site cavity enough to accommodate the larger farnesyl pyrophosphate substrate and led to the efficient synthesis of sesquiterpenes, while alternate single substitutions of this critical amino acid yielded five additional terpene synthases.