New prodrugs derived from 6-aminodopamine and 4-aminophenol as candidates for melanocyte-directed enzyme prodrug therapy (MDEPT)

Two novel tyrosinase mediated drug delivery pathways have been investigated for the selective delivery of cytotoxic units to melanocytes from urea and thiourea prodrugs. The synthesis of these prodrugs is reported, as well as oximetry data that illustrate that the targets are substrates for tyrosinase. The stability of each of the prodrugs in (i) phosphate buffer and (ii) bovine serum is discussed, and the urea prodrugs are identified as lead candidates for further studies. Finally, HPLC studies and preliminary cytotoxicity studies in a melanotic and an amelanotic cell line, that illustrate the feasibility of the approach, are presented.

Organocatalysis with proline derivatives: improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions

Tetrazole and acylsulfonamide organocatalysts derived from proline have been synthesised and applied to the asymmetric Mannich, nitro-Michael and aldol reactions to give results that are superior to the proline-catalysed counterpart.

Recent highlights in modified oligonucleotide chemistry

The synthesis of modified nucleic acids has been the subject of much study ever since the structure of DNA was elucidated by Watson and Crick at Cambridge and Wilkins and Franklin at King's College over half a century ago. This review describes recent developments in the synthesis and application of these artificial nucleic acids, predominantly the phosphoramidites which allow for easy inclusion into oligonucleotides, and is divided into three separate sections. Firstly, modi. cations to the base portion will be discussed followed secondly by modi. cations to the sugar portion. Finally, changes in the type of nucleic acid linker will be discussed in the third section. Peptide Nucleic Acids ( PNAs) are not discussed in this review as they represent a separate and large area of nucleic acid mimics.

What Monte Carlo models can do and cannot do efficiently?

The question "what Monte Carlo models can do and cannot do efficiently" is discussed for some functional spaces that define the regularity of the input data. Data classes important for practical computations are considered: classes of functions with bounded derivatives and Holder type conditions, as well as Korobov-like spaces. Theoretical performance analysis of some algorithms with unimprovable rate of convergence is given. Estimates of computational complexity of two classes of algorithms - deterministic and randomized for both problems - numerical multidimensional integration and calculation of linear functionals of the solution of a class of integral equations are presented. (c) 2007 Elsevier Inc. All rights reserved.

Design and development of a dextrous manipulator

This paper describes a novel method of actuation for robotic hands. The solution employs a Bowden cable routed to each joint. The use of a Bowden cable is shown to be feasible for this purpose, ever, with the changing frictional forces associated with it. This method greatly simplifies the control of the hand by removing the coupling between joints, and provides for direct and accurate translation between the joints and the servo motors driving the cables. The design also allows for two degrees of freedom with the same centre of rotation to be realized in the largest knuckle of each finger; thus biological finger kinematics are more closely emulated.

Control of a compliant two-axis robotic arm

It is common to make the links between actuators and robotic limbs as stiff as possible, in complete contrast to natural systems, where compliance is present. In the past, to create some compliance in a drive, springs have been added to the link between the actuator and load. Many of these springs have been in series with the drive, but recently a more 'biological' approach has been taken where two springs have been used in parallel to counteract each other. This paper describes the application of parallel extension springs in a robot arm in order to give it compliance. Advantages and disadvantages of this application are discussed, along with various control strategies.

Diameter of parallelogramic honeycomb torus

The determination of the diameter of an interconnection network is essential in evaluating the performance of the network. Parallelogramic honeycomb torus is an attractive alternative to classical torus network due to smaller vertex degree, and hence, lower implementation cost. In this paper, we present the expression for the diameter of a parallelogramic, honeycomb torus, which extends a known result about rhombic: honeycomb torus. (c) 2005 Elsevier Ltd. All rights reserved.

Effect of improving representation of horizontal and vertical cloud structure on the Earth's global radiation budget. Part I: review and parametrization

A poor representation of cloud structure in a general circulation model (GCM) is widely recognised as a potential source of error in the radiation budget. Here, we develop a new way of representing both horizontal and vertical cloud structure in a radiation scheme. This combines the ‘Tripleclouds’ parametrization, which introduces inhomogeneity by using two cloudy regions in each layer as opposed to one, each with different water content values, with ‘exponential-random’ overlap, in which clouds in adjacent layers are not overlapped maximally, but according to a vertical decorrelation scale. This paper, Part I of two, aims to parametrize the two effects such that they can be used in a GCM. To achieve this, we first review a number of studies for a globally applicable value of fractional standard deviation of water content for use in Tripleclouds. We obtain a value of 0.75 ± 0.18 from a variety of different types of observations, with no apparent dependence on cloud type or gridbox size. Then, through a second short review, we create a parametrization of decorrelation scale for use in exponential-random overlap, which varies the scale linearly with latitude from 2.9 km at the Equator to 0.4 km at the poles. When applied to radar data, both components are found to have radiative impacts capable of offsetting biases caused by cloud misrepresentation. Part II of this paper implements Tripleclouds and exponential-random overlap into a radiation code and examines both their individual and combined impacts on the global radiation budget using re-analysis data.

Effect of improving representation of horizontal and vertical cloud structure on the Earth's global radiation budget. Part II: The global effects

Reliably representing both horizontal cloud inhomogeneity and vertical cloud overlap is fundamentally important for the radiation budget of a general circulation model. Here, we build on the work of Part One of this two-part paper by applying a pair of parameterisations that account for horizontal inhomogeneity and vertical overlap to global re-analysis data. These are applied both together and separately in an attempt to quantify the effects of poor representation of the two components on radiation budget. Horizontal inhomogeneity is accounted for using the “Tripleclouds” scheme, which uses two regions of cloud in each layer of a gridbox as opposed to one; vertical overlap is accounted for using “exponential-random” overlap, which aligns vertically continuous cloud according to a decorrelation height. These are applied to a sample of scenes from a year of ERA-40 data. The largest radiative effect of horizontal inhomogeneity is found to be in areas of marine stratocumulus; the effect of vertical overlap is found to be fairly uniform, but with larger individual short-wave and long-wave effects in areas of deep, tropical convection. The combined effect of the two parameterisations is found to reduce the magnitude of the net top-of-atmosphere cloud radiative forcing (CRF) by 2.25 W m−2, with shifts of up to 10 W m−2 in areas of marine stratocumulus. The effects of the uncertainty in our parameterisations on radiation budget is also investigated. It is found that the uncertainty in the impact of horizontal inhomogeneity is of order ±60%, while the uncertainty in the impact of vertical overlap is much smaller. This suggests an insensitivity of the radiation budget to the exact nature of the global decorrelation height distribution derived in Part One.

A note on the analysis error associated with 3D-FGAT

The analysis-error variance of a 3D-FGAT assimilation is examined analytically using a simple scalar equation. It is shown that the analysis-error variance may be greater than the error variances of the inputs. The results are illustrated numerically with a scalar example and a shallow-water model.

Vertical velocity variance and skewness in clear and cloud-topped boundary layers as revealed by Doppler lidar

In this paper, observations by a ground-based vertically pointing Doppler lidar and sonic anemometer are used to investigate the diurnal evolution of boundary-layer turbulence in cloudless, cumulus and stratocumulus conditions. When turbulence is driven primarily by surface heating, such as in cloudless and cumulus-topped boundary layers, both the vertical velocity variance and skewness follow similar profiles, on average, to previous observational studies of turbulence in convective conditions, with a peak skewness of around 0.8 in the upper third of the mixed layer. When the turbulence is driven primarily by cloud-top radiative cooling, such as in the presence of nocturnal stratocumulus, it is found that the skewness is inverted in both sign and height: its minimum value of around −0.9 occurs in the lower third of the mixed layer. The profile of variance is consistent with a cloud-top cooling rate of around 30Wm−2. This is also consistent with the evolution of the thermodynamic profile and the rate of growth of the mixed layer into the stable nocturnal boundary layer from above. In conditions where surface heating occurs simultaneously with cloud-top cooling, the skewness is found to be useful for diagnosing the source of the turbulence, suggesting that long-term Doppler lidar observations would be valuable for evaluating boundary-layer parametrization schemes. Copyright c 2009 Royal Meteorological Society