The preparation of a new "safety catch" ester linker for solid-phase synthesis

A new "safety catch" linker for esters has been synthesized on polystyrene resin. This 2-tert-butoxyphenol resin 10 may be acylated to give a relatively stable ester that will allow nucleophilic chemistry without reaction at the linking ester group. Removal of the tert-butyl group with acid unmasks a highly reactive 2-hydroxyphenyl ester that reacts readily with nucleophiles to cause release of the product from the resin. This sequence has been exemplified by acylating the resin with various bromo acids, carrying out nucleophilic displacements with thiols, phenols, or amines, activating the ester with trifluoroacetic acid and cleaving from the resin with amines to give the (nucleophile) substituted carboxamides in high yield and purity. Kinetic studies with a model ester revealed half-lives for reaction with morpholine of 119 h for the tert-butoxyphenyl ester and 1 min for the corresponding phenol.     

Crystallization of poly(ethylene oxide) fractions: Crystallization isotherms

The crystallization kinetics of a range of fractions of poly(ethylene oxide) are presented and analyzed. It is concluded that deviations from the Avrami equation with exponent of 3 are mainly due to rejection of low molecular weight molecules for the low molecular weight fractions (M?_n < 6,000) and to a process of crystal perfecting for the high molecular weight fractions (M?_n > 6,000).     

(−)‐Englerin A is a Potent and Selective Activator of TRPC4 and TRPC5 Calcium Channels

Current therapies for common types of cancer such as renal cell cancer are often ineffective and unspecific, and novel pharmacological targets and approaches are in high demand. Here we show the unexpected possibility for the rapid and selective killing of renal cancer cells through activation of calcium‐permeable nonselective transient receptor potential canonical (TRPC) calcium channels by the sesquiterpene (?)‐englerin A. This compound was found to be a highly efficient, fast‐acting, potent, selective, and direct stimulator of TRPC4 and TRPC5 channels. TRPC4/5 activation through a high‐affinity extracellular (?)‐englerin A binding site may open up novel opportunities for drug discovery aimed at renal cancer.     

Separation of parasites from human blood using deterministic lateral displacement

We present the use of a simple microfluidic technique to separate living parasites from human blood. Parasitic trypanosomatids cause a range of human and animal diseases. African trypanosomes, responsible for human African trypanosomiasis (sleeping sickness), live free in the blood and other tissue fluids. Diagnosis relies on detection and due to their often low numbers against an overwhelming background of predominantly red blood cells it is crucial to separate the parasites from the blood. By modifying the method of deterministic lateral displacement, confining parasites and red blood cells in channels of optimized depth which accentuates morphological differences, we were able to achieve separation thus offering a potential route to diagnostics.     

Planning midwifery services to deliver continuity of care

This paper describes a simulation model of maternity services which was developed to support the planning of midwifery services to meet demands for continuity of care. A Government report of maternity services in 1992 emphasised the need to replace the fragmented care offered to pregnant women by a more personalised type of approach. One way of doing this is by the implementation of team midwifery in which care is provided, antenatally, during labour, and then postnatally by either the same midwife or, more usually a small team of midwives.The model described in this paper attempts to assess the effects of team size upon the continuity of care provided to pregnant women under different implementations. Continuity is measured in terms of the percentage of occasions a team midwife will be available to meet the health care demands of pregnant women. The model may be used not only for the evaluation of services already in use, but also for the planning of alternative and better services.     

Modification of surface properties of a poly(dimethylsiloxane)-based elastomer, RTV11, upon exposure to seawater

Atomic force microscopy (AFM) was combined with surface analytical techniques to investigate the rarely addressed issue of the effect of seawater on the surface properties of a selected fouling-release coating, silicon elastomer RTV11 (trademark of General Electric). The exposure of the RTV11 surface to seawater resulted in a modification of its morphology and mechanical properties, as confirmed by AFM and scanning electron microscopy (SEM). Surface modification was dependent on sample preparation and curing process, namely, curing agent concentration and relative humidity during curing. The RTV11 surface remained largely unaltered for samples cured under 100% relative humidity. SEM and X-ray photoelectron spectroscopy studies confirmed that the modified surface of RTV11 had the same elemental composition as the unexposed surface of the elastomer and showed excess Ca. However, the modified surface deformed plastically under load and was stiffer than the original surface. No major change was found on surfaces exposed to nanopure water during similar times of exposure as in seawater, regardless of curing conditions. The rate of increase in the aggregate formation in seawater can be described by an exponential function, with a decay constant of approximately 4.99 x 10(-)(3) min(-)(1) and a pre-exponential factor of approximately 1.77 x 10(-)(2) microm/min.     

Thermal and electron paramagnetic resonance studies on pyridine perchromate

A number of physical techniques including scanning calorimetry and electron paramagnetic resonance have been used in an attempt to elucidate the course of the decomposition reaction of pyridine perchromate.     

Tuneable separation in elastomeric microfluidics devices

We describe how the elastomeric properties of PDMS (polydimethylsiloxane) can be utilised to achieve tuneable particle separation in Deterministic Lateral Displacement devices via strain controlled alteration of inter-obstacle distances, a development that opens up new avenues toward more effective separation of particles in microfluidics devices.     

Nanoconfinement-enhanced conformational response of single DNA molecules to changes in ionic environment

We show that the ionic environment plays a critical role in determining the configurational properties of DNA confined in silica nanochannels. The extension of DNA in the nanochannels increases as the ionic strength is reduced, almost tripling over two decades in ionic strength for channels around 100 x 100 nm in dimension. Surprisingly, we find that the variation of the persistence length alone with ionic strength is not enough to explain our results. The effect is due mainly to increasing self-avoidance created by the reduced screening of electrostatic interactions at low ionic strength. To quantify the increase in self-avoidance, we introduce a new parameter into the de Gennes theory: an effective DNA width that gives the increase in the excluded volume due to electrostatic repulsion.     

The Development of a Decision-support System for Planning Services within Hospitals

The planning of services within district health authorities is a complex task, but the process of planning is often crude: few options for addressing issues are considered, and these are inadequately assessed. These deficiencies led to research of which the aim was to identify the types of information and systems needed for improved planning. This paper describes the product of that research, the Hospital Planning Model. It is a decision-support system which gives planners fast access to relevant information for planning hospital services. This allows them to consider quickly a range of options for addressing a particular planning issue, and to test how sensitive the implications of proposals are to differing planning assumptions. The system has been shown to be generalizable, and is currently used in 28 health districts and other health organizations throughout the United Kingdom. The proposed reforms of the NHS are likely to increase the relevance of the system: the purchaser/provider market will result in a greater awareness by hospitals of the importance of identifying measures to improve the cost-effectiveness of care. Purchasers too may want to scrutinize hospitals in terms of their efficiency.