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Over the last 20 years, there have been significant changes in UK surgical training. Civilian surgical training may no longer prepare military surgeons for the range of skills they require on operations. One method to address gaps in knowledge or experience is to use telemedicine to facilitate specialist consultations from UK-based specialists to deployed medical teams. In the UK Defence Medical Services (DMS), this capability is called real-time clinical support (RTCS). RTCS provides a direct audio-visual link from a deployed location anywhere in the world to a supporting medical specialist in the UK. RTCS is currently delivered via a combination of off-the-shelf hardware and commercially available software. This article will outline the current use of RTCS, with emphasis on deployed surgical teams in austere environments, and discuss the advantages and limitations of this capability. However, it must be emphasised that no technology can be a substitute for clinical training and experience. Although several limitations remain, the authors believe that RTCS offers potential benefits for the DMS and could be an important tool aiding deployed clinicians. It can also be argued that by engaging with the concept now, the DMS can shape future developments in this sphere.

Water and carbon are transferred from the ocean to the mantle in a process that alters mantle peridotite to create serpentinite and supports diverse ecosystems. Serpentinized mantle rocks are found beneath the sea floor at slow- to ultraslow-spreading mid-ocean ridges and are thought to be present at about half the world’s rifted margins. Serpentinite is also inferred to exist in the downgoing plate at subduction zones, where it may trigger arc magmatism or hydrate the deep Earth. Water is thought to reach the mantle via active faults. Here we show that serpentinization at the rifted continental margin offshore from western Spain was probably initiated when the whole crust cooled to become brittle and deformation was focused along large normal faults. We use seismic tomography to image the three-dimensional distribution of serpentinization in the mantle and find that the local volume of serpentinite beneath thinned, brittle crust is related to the amount of displacement along each fault. This implies that sea water reaches the mantle only when the faults are active. We estimate the fluid flux along the faults and find it is comparable to that inferred for mid-ocean ridge hydrothermal systems. We conclude that brittle processes in the crust may ultimately control the global flux of sea water into the Earth.

The underlying stochastic nature of the requirements for the Solvency II regulations has introduced significant challenges if the required calculations are to be performed correctly, without resorting to excessive approximations, within practical timescales. It is generally acknowledged by practising actuaries within UK life offices that it is currently impossible to correctly fulfil the requirements imposed by Solvency II using existing computational techniques based on commercially available valuation packages. Our work has already shown that it is possible to perform profitability calculations at a far higher rate than is achievable using commercial packages. One of the key factors in achieving these gains is to calculate reserves using recurrence relations that scale linearly with the number of time steps. Here, we present a general vector recurrence relation which can be used for a wide range of non-unit linked policies that are covered by Solvency II; such contracts include annuities, term assurances, and endowments. Our results suggest that by using an optimised parallel implementation of this algorithm, on an affordable hardware platform, it is possible to perform the ‘brute force’ approach to demonstrating solvency in a realistic timescale (of the order of a few hours).

The Afanasy Nikitin seamount (ANS) is a major structural feature (400 km-long and 150 km-wide) in the Central Indian Basin, situated at the southern end of the so-called 85°E Ridge. Combined analyses of new multibeam bathymetric, seismic reflection and geochronological data together with previously described magnetic data provide new insights into the growth of the ANS through time, and its relationship with the 85°E Ridge. The ANS comprises a main plateau, rising 1200 m above the surrounding ocean floor (4800 m), and secondary elevated seamount highs, two of which (lie at 1600 and 2050 m water depths) have the morphology of a guyot, suggesting that they were formed above or close to sea-level. An unbroken sequence of spreading anomalies 34 through 32n.1 identified over the ANS reveal that the main plateau of the ANS was formed at 80–73 Ma, at around the same time as that of the underlying oceanic crust. The 40Ar/39Ar dates for two basalt samples dredged from the seamount highs are consistent, within error, at 67 Ma. These results, together with published results of late Cretaceous to early Cenozoic Indian Ocean plate reconstructions, indicate that the Conrad Rise hotspot emplaced both the main plateau of the ANS and Conrad Rise (including the Marion Dufresne, Ob and Lena seamounts) at 80–73 Ma, close to the India–Antarctica Ridge system. Subsequently, the seamount highs were formed by late-stage volcanism c. 6–13 Myr after the main constructional phase of the seamount plateau. Flexural analysis indicates that the main plateau and seamount highs of the ANS are consistent with Airy-type isostatic compensation, which suggest emplacement of the entire seamount in a near spreading-center setting. This is contrary to the flexural compensation of the 85°E Ridge further north, which is interpreted as being emplaced in an intraplate setting, i.e., 25–35 Myr later than the underlying oceanic crust. Therefore, we suggest that the ANS and the 85°E Ridge appear to be unrelated as they were formed by different mantle sources, and that the proximity of the southern end of the 85°E Ridge to the ANS is coincidental.

MCNP6 is simply and accurately described as the merger of MCNP5 and MCNPX capabilities, but it is much more than the sum of those two computer codes. MCNP6 is the result of five years of effort by the MCNP5 and MCNPX code development teams. These groups of people, residing in Los Alamos National Laboratory’s (LANL) X Computational Physics Division, Monte Carlo Codes Group (XCP-3), and Decision Applications Division, Radiation Transport and Applications Team (D-5), respectively, have combined their code development efforts to produce the next evolution of MCNP. While maintenance and bug fixes will continue for MCNP5 1.60 and MCNPX 2.7.0 for upcoming years, new code development capabilities only will be developed and released in MCNP6. In fact, the initial release of MCNP6 contains 16 new features not previously found in either code. These new features include the abilities to import unstructured mesh geometries from the finite element code Abaqus, to transport photons down to 1.0 eV, to transport electrons down to 10.0 eV, to model complete atomic relaxation emissions, and to generate or read mesh geometries for use with the LANL discrete ordinates code Partisn. The first release of MCNP6, MCNP6 Beta 2, is now available through the Radiation Safety Information Computational Center, and the first production release is expected in calendar year 2012. High confidence in the MCNP6 code is based on its performance with the verification and validation test suites, comparisons to its predecessor codes, the regression test suite, its code development process, and the underlying high-quality nuclear and atomic databases.

Two classes of phages yield profoundly different levels of recovery in mice experimentally infected with an Escherichia coli O18:K1:H7 strain. Phages requiring the K1 capsule for infection (K1-dep) rescue virtually all infected mice, whereas phages not requiring the capsule (K1-ind) rescue modest numbers (∼30%). To rescue infected mice, K1-ind phages require at least a 106-fold-higher inoculum than K1-dep phages. Yet their in vivo growth dynamics are only modestly inferior to those of K1-dep phages, and competition between the two phage types in the same mouse reveals only a slight growth advantage for the K1-dep phage. The in vivo growth rate seems unlikely to be the primary determinant of phage therapy success. An alternative explanation is that the success of K1-dep phages is due substantially to their proteomic composition. They encode an enzyme that degrades the K1 capsule, which has been shown in other work to be sufficient to cure infection in the complete absence of phages.

ABSTRACTTwo classes of phages yield profoundly different levels of recovery in mice experimentally infected with an Escherichia coliO18:K1:H7 strain. Phages requiring the K1 capsule for infection (K1-dep) rescue virtually all infected mice, whereas phages not requiring the capsule (K1-ind) rescue modest numbers (∼30%). To rescue infected mice, K1-ind phages require at least a 106-fold-higher inoculum than K1-dep phages. Yet their in vivogrowth dynamics are only modestly inferior to those of K1-dep phages, and competition between the two phage types in the same mouse reveals only a slight growth advantage for the K1-dep phage. The in vivogrowth rate seems unlikely to be the primary determinant of phage therapy success. An alternative explanation is that the success of K1-dep phages is due substantially to their proteomic composition. They encode an enzyme that degrades the K1 capsule, which has been shown in other work to be sufficient to cure infection in the complete absence of phages.

The article presents a study that examined the role of the drive towards greater use of animal-based measures for welfare assessment in raising important issues for how farm visits by welfare assessors are performed. To offer a new approach to examining the practice and performance of farm animal assessment, the authors relied on a number of contemporary social science ideas. They called for a greater awareness of how sets of knowledge are made and become an integral component of the procedures and discourses around farm animal welfare assessment.

Post-mortem examinations of harbour porpoises, Phocoena phocoena, regularly reveal heavy parasitic worm burdens. These same post-mortem records show varying levels of polychlorinated biphenyls (PCBs) accumulating in the blubber of porpoises. Although a number of papers have documented geospatial and temporal changes of PCBs and their detrimental effects on marine mammal health, as yet none have examined their role in determining nematode burdens in wild marine mammal populations. Using a data set consisting of harbour porpoises stranded in the UK between 1989 and 2002, we found a significant, positive association between PCB levels and nematode burdens, although the nature of the relationship was confounded with porpoise sex, age and cause of death. It was also apparent that individuals with the heaviest infestations of nematodes did not have the highest PCB level: while PCBs are important, they are clearly not the sole determinants of nematode burdens in wild populations of the harbour porpoise around the UK.

Plant breeders in the Australian sugar industry conduct yield assessment trials each year to assess the yielding ability of clones in the sugarcane breeding programme. Several endemic diseases impinge on the yield of these clones and the tested clones vary greatly in disease susceptibility. In this study, resistance to the diseases orange rust and yellow spot was assessed in final stage trials in the Northern Queensland programme. Clonal yielding ability was related to disease resistance. The results indicate that both diseases, but particularly yellow spot, influenced the yield (tonnes cane/ha and tonnes sugar/ha) of clones in northern breeding trials in 2000. Yield loss estimates were calculated, as well as the relationship between resistance and yield. There was a high level of resistance to orange rust in clones in these trials but much less resistance to yellow spot; the resistance index or orange rust was 2.2 while for yellow spot it was 5.5. Yield loss resistance index values of 5.0 and above for orange rust suggest there is adequate resistance in clones to minimise losses from this disease. In contrast, the yield loss resistance index for yellow spot (tonnes cane/ha) was below 5.0, therefore, it is concluded that during the 2000 harvest season, there was inadequate resistance to minimise losses. The information gathered from this research will be used to determine the level of leaf disease resistance needed in commercial cultivars to optimise yielding ability. Such decisions should improve the efficiency of selection and the performance of commercial cultivars in the Australian sugar industry.

Increasing interest is being shown in the use of Java for scientific applications. The Java Grande benchmark suite was designed with such applications primarily in mind. The perceived lack of performance of Java still deters many potential users, despite recent advances in just-in-time and adaptive compilers. There are, however, few benchmark results available comparing Java to more traditional languages such as C and Fortran. To address this issue, a subset of the Java Grande benchmarks has been re-written in C and Fortran allowing direct performance comparisons between the three languages. The performance of a range of Java execution environments, C and Fortran compilers have been tested across a number of platforms using the suite. These demonstrate that on some platforms (notable Intel Pentium) the performance gap is now quite small. Copyright © 2003 John Wiley & Sons, Ltd.

Abstract. Surfactant spreading on thin viscous films is of interest in the context of surfactant and liquid transport in the lungs, for both normal lung function and treatment of disease, as well as for many industrial processes. This paper presents experimental techniques for the measurement of film deformations due to spreading surfactant and for the investigation of the effects of periodic stretching of the wall supporting the thin film to mimic airway wall motion in the lung due to breathing. Additionally, we present results from both types of experiments, which agree favorably with our theoretical work.

High-resolution seismic and ground-penetrating-radar (GPR) data have been acquired over Lake Nikolay in the western Lena Delta in order to study the uppermost basin fill and the bordering frozen margins. GPR (100 MHz antenna pair) measurements were completed on the frozen lake and its permafrost margins, while high-resolution seismic data were acquired from the lake during open-water conditions in summer using a 1.5–11.5 kHz Chirp profiler. The combined use of the two profiling systems allows stratigraphic profiling in both frozen and unfrozen parts of the lake. Shallow seismic reflection images of the uppermost 4 to 5 m of sediments are compared to GPR sections, which have approximately the same horizontal and vertical resolution. Short sediment cores aid calibrate the geophysical data. Copyright © 2002 John Wiley & Sons, Ltd.

High‐resolution seismic and ground‐penetrating‐radar (GPR) data have been acquired over Lake Nikolay in the western Lena Delta in order to study the uppermost basin fill and the bordering frozen margins. GPR (100 MHz antenna pair) measurements were completed on the frozen lake and its permafrost margins, while high‐resolution seismic data were acquired from the lake during open‐water conditions in summer using a 1.5–11.5 kHz Chirp profiler. The combined use of the two profiling systems allows stratigraphic profiling in both frozen and unfrozen parts of the lake. Shallow seismic reflection images of the uppermost 4 to 5 m of sediments are compared to GPR sections, which have approximately the same horizontal and vertical resolution. Short sediment cores aid calibrate the geophysical data. Copyright © 2002 John Wiley & Sons, Ltd.

Abstract Evolutionary biology is widely perceived as a discipline with relevance that lies purely in academia. Until recently, that perception was largely true, except for the often neglected role of evolutionary biology in the improvement of agricultural crops and animals. In the past two decades, however, evolutionary biology has assumed a broad relevance extending far outside its original bounds. Phylogenetics, the study of Darwin's theory of "descent with modification," is now the foundation of disease tracking and of the identification of species in medical, pharmacological, or conservation settings. It further underlies bioinformatics approaches to the analysis of genomes. Darwin's "evolution by natural selection" is being used in many contexts, from the design of biotechnology protocols to create new drugs and industrial enzymes, to the avoidance of resistant pests and microbes, to the development of new computer technologies. These examples present opportunities for education of the public and for nontraditional career paths in evolutionary biology. They also provide new research material for people trained in classical approaches.

This paper describes the definition and implementation of an OpenMP-like set of directives and library routines for shared memory parallel programming in Java. A specification of the directives and routines is proposed and discussed. A prototype implementation, consisting of a compiler and a runtime library, both written entirely in Java, is presented, which implements most of the proposed specification. Some preliminary performance results are reported. Copyright © 2001 John Wiley & Sons, Ltd.

When a liquid is instilled in the pulmonary airways during medical therapy, the method of instillation affects the liquid distribution throughout the lung. To investigate the fluid transport dynamics, exogenous surfactant (Survanta) mixed with a radiopaque tracer is instilled into tracheae of vertical, excised rat lungs (ventilation 40 breaths/min, 4 ml tidal volume). Two methods are compared: For case A, the liquid drains by gravity into the upper airways followed by inspiration; for case B, the liquid initially forms a plug in the trachea, followed by inspiration. Experiments are continuously recorded using a microfocal X-ray source and an image-intensifier, charge-coupled device image train. Video images recorded at 30 images/s are digitized and analyzed. Transport dynamics during the first few breaths are quantified statistically and follow trends for liquid plug propagation theory. A plug of liquid driven by forced air can reach alveolar regions within the first few breaths. Homogeneity of distribution measured at end inspiration for several breaths demonstrates that case Bis twice as homogeneous as case A. The formation of a liquid plug in the trachea, before inspiration, is important in creating a more uniform liquid distribution throughout the lungs.

EMERGE is a fully automatic and highly flexible program for producing low-weight, low-stress structures, developed by the self-designing structures project at Newcastle and Durham Universities. A brief review of the development and features of existing evolutionary methods is first given before going on to discuss evolutionary material translation (EMT)—the core algorithm embedded within EMERGE—and its relative advantages. Most of the existing work done on automatic evolutionary methods has concentrated upon material removal only, the main drawback of this approach being its inability to find improved structural forms outside a predetermined domain. Three notional problems and one industrial problem are presented. These problems demonstrate the flexibility of EMT to design outside or within the preconceptions of the engineer, to produce improved structures with superior boundaries, and to do so with modelling and computational efficiency. Copyright © 2001 John Wiley & Sons, Ltd.

Genomes of the closely related bacteriophages φX174 and S13 are 5386 bases long and differ at 114 nucleotides, affecting 28 amino acids. Both parental phages were adapted to laboratory culture conditions in replicate lineages and analysed for nucleotide changes that accumulated experimentally. Of the 126 experimental substitutions, 90 encoded amino–acid changes, and 62 of the substitutions occurred in parallel in more than one experimental line. Furthermore, missense changes at 12 of the experimental sites were at residues differing between the parental phages; in ten cases the φX174 experimental lineages were convergent with the S13 parent, or vice versa, at both the nucleotide and amino–acid levels. Convergence at a site was even obtained in both directions in three cases. These results point to a limited number of pathways taken during evolution in these viruses, and also raise the possibility that much of the amino–acid variation in the natural evolution of these viruses has been selected.

Abstract:  Ethanol fixation combined with microwave pretreatment allows rapid and simple detection of signals produced by cycling primed in situ (PRINS) amplification, which uses a single primer, and in situ polymerase chain reaction (ISPCR) in intact cells. After thermal cycling, signals remain as discrete subnuclear spots in the region of amplification and are clearly distinguishable from non-specific background labelling. These methods are applicable to routine blood smears, even after Giemsa staining or immunocytochemistry, and cellular morphology is retained. Chromosome enumeration by cycling PRINS is demonstrated using primers for repeat DNA sequences, whilst single copy sequence detection is demonstrated using bcl-2, CFTR and chromosome 21 specific primer pairs in ISPCR. We show that ethanol fixation supports efficient extension of cycling PRINS products to approximately 550 bp using up to 70 rounds of thermal cycling.

This paper presents a new method, Reverse Adaptivity, for automatically generating solutions to initial design and redesign problems. The method is based on a combination of existing adaptive finite element methods and evolutionary structural optimization methods. The usual difficulties inherent in structural optimization problems, and the shortcomings of the evolutionary methods in tackling these difficulties, are reviewed as a prelude to discussing Reverse Adaptivity. Once the initial finite element problem is defined, the method proceeds with reverse adaptive analysis, which refines low stress regions of the finite element mesh by element subdivision. Following this, any low stress subdivided elements are removed and the process is repeated. With successive decrements of adapted element size, the process satisfies many of the shortcomings of existing evolutionary optimization methods, yet is simple to understand and can be readily implemented. The results produced by the method are superior to those produced by existing methods, yet can be obtained with highly practicable computational resources. As a demonstration, solutions to a number of well- known classical problems are presented, and highlight the method's ability to distinguish new classes of solutions for some problems. Full implementation and parameter details are also presented. Copyright © 1999 John Wiley & Sons, Ltd.

The evolution of virulence was studied in a virus subjected to alternating episodes of vertical and horizontal transmission. Bacteriophage f1 was used as the parasite because it establishes a debilitating but non–fatal infection that can be transmitted vertically (from a host to its progeny) as well as horizontally (infection of new hosts). Horizontal transmission was required of all phage at specific intervals, but was prevented otherwise. Each episode of horizontal transmission was followed by an interval of obligate vertical transmission, followed by an interval of obligate horizontal transmission etc. The duration of vertical transmission was eight times longer per episode in one treatment than in the other, thus varying the relative intensity of selection against virulence while maintaining selection for some level of virus production. Viral lines with the higher enforced rate of infectious transmission evolved higher virulence and higher rates of virus production. These results support the trade–off model for the evolution of virulence.

High power combined NBI + ICRF heating experiments have been carried out in the JET Mark IIa divertor configuration in the hot ion ELM-free H mode regime, both in deuterium (DD) and in deuterium-tritium (DT) plasmas. Results are presented from a wide range of additional heating power levels, ICRF up to 9.5 MW tuned to the fundamental hydrogen minority, NBI up to 22 MW, and for plasma currents up to 4.2 MA and toroidal fields up to 3.6 T. Discharges with combined NBI + ICRF heating show a clear improvement in electron temperature, DD neutron yield and stored energy with respect to NBI only discharges. High energy neutral particle analyser data show that acceleration of the NBI deuterons takes place due to absorption of ICRF power at the second harmonic deuterium resonance. This is confirmed by numerical simulations with the PION code, indicating that up to 40% of the ICRF power is absorbed by bulk and NBI ions. ICRF heating has been an essential ingredient in the DT experiments in the ELM-free hot ion regime, contributing to the achievement of a record fusion power of 16.1 MW and a record stored energy of 17 MJ.

This article critically examines current parallel programming practice and optimizing compiler development. The general strategies employed by compiler and programmer to optimize a Fortran program are described, and then illustrated for a specific case by applying them to a well-known scientific program, TRED2, using the KSR-1 as the target architecture. Extensive measurement is applied to the resulting versions of the program, which are compared with a version produced by a commercial optimizing compiler, KAP. The compiler strategy significantly outperforms KAP and does not fall far short of the performance achieved by the programmer. Following the experimental section each approach is critiqued by the other. Perceived flaws, advantages, and common ground are outlined, with an eye to improving both schemes.

Flows in estuarial and coastal regions may be described by the shallow-water equations. The processes of pollution transport, sediment transport, and plume dispersion are driven by the underlying hydrodynamics. Accurate resolution of these processes requires a three-dimensional formulation with turbulence modeling, which is very demanding computationally. A numerical scheme has been developed which is both stable and accurate – we show that this scheme is also well suited to parallel processing, making the solution of massive complex problems a practical computing possibility. We describe the implementation of the numerical scheme on a Kendall Square Research KSR-1 multiprocessor, and present experimental results which demonstrate that a problem requiring 600,000 mesh points and 6,000 time steps can be solved in under 8 hours using 32 processors.

A cornerstone of evolutionary theory is that the phenotypic variance of a population may be partitioned into genetic and environmental (nonheritable) components. The traditional motivation for this distinction is that the rate of evolution under natural selection depends on the (relative) magnitudes of certain genetic components of variance. The components of variation are also interesting from another perspective, as illustrated here. Phenotypic variation may be selectively maintained in a population according to its components: selection may favor the maintenance of only the environmental components, only the genetic components, or be indifferent to the composition of the variance. Even when selection is shown to favor phenotypic variation regardless of its components, the possibility exists that environmental variance will evolve to displace the genetic components or vice versa. Environmental and genetic factors may thus compete to produce a given selected level of phenotypic variance. A test of some of these models is provided from the example of seed dormancy: the prediction that variation in seed germination time should be purely environmental is supported by the demonstration of low heritability of germination time in the two available studies.

1. The jejunal motor response to gastric distension has been quantified in the conscious dog and compared with that of feeding in order to determine the role of the physical bulk of a meal in the conversion from fasted to fed motor activity. 2. In six dogs gastric distension abolished the cyclical migrating motor complex (m.m.c.) and evoked a pattern of continuous irregular jejunal motility similar to that seen postprandially, but only after a latency of 21.5 +/‐ 2.7 min compared to that of 7.1 +/‐ 1.2 min for the response to feeding. Computer analysis of distension and fed jejunal motility revealed similar distributions of intervals between contractions and contraction amplitudes with comparable mean values for both. 3. In two dogs with antrum and corpus surgically divided distension of the corpus had a similar effect on jejunal motility although the latency to both distension and feeding were considerably less. 4. By varying the period of distension it has been possible to control accurately the duration of the jejunal motor response and so assess its effectiveness in disrupting the timing of the m.m.c. The return to m.m.c. cycling following deflation was independent of preceding complexes. The occurrence of the post‐distension activity front was closely related to the act of deflation itself (R = 0.94) following a latency of 26.2 +/‐ 2.1 min (n = 39). 5. It is concluded that the bulk of a meal contributes significantly to the early part of postprandial motility and is capable of disrupting the timing of subsequent migrating motor complexes.

The effect of D‐ and L‐isomers of tryptophan and phenylalanine on fasting motor activity of canine jejunum were investigated. Only L‐tryptophan had any effect on jejunal motility. The concentration of L‐tryptophan required to elicit a motor effect in 50% of animals was estimated at 28 mM. 50 mM‐L‐tryptophan stimulated jejunal motility after a latency of 4.5 +/‐ 0.7 min. The pattern of motility was similar to that evoked by feeding but continued for only 41 +/‐ 5 min and failed to disrupt the normal timing of the interdigestive migrating motor complex (m.m.c.). The duration of the subsequent phase II of the complex was, however, significantly reduced. Multiple infusion of L‐tryptophan also failed to disrupt the timing of the m.m.c. These data are consistent with the hypothesis that specific breakdown components of protein digestion are implicated in the stimulation of postprandial motor activity. The mechanisms involved in the motor response to L‐tryptophan are discussed.

The enzyme ACC oxidase catalyses the last step of ethylene biosynthesis in plants, converting 1-aminocyclopropane-1-carboxylic acid (ACC) to ethylene. We have previously described the isolation and characterization of a cDNA clone (pMEL1) encoding an ACC oxidase homolog from melon (Cucumis melo L.). Here we report the isolation and characterization of three genomic clones, corresponding to three putative members of the ACC oxidase gene family in melon. All are transcriptionally active. The sequences of these genes have been determined. One genomic clone (CM-ACO1), corresponding to the cDNA previously isolated, presents a coding region interrupted by three introns. Its transcription initiation site has been defined with RNA from ripe fruit and ethylene-treated leaves. The other two genes (CM-ACO2, CM-ACO3) have only two introns, at positions identical to their counterparts inCM-ACO1. The degree of DNA homology in the coding regions ofCM-ACO2 andCM-ACO3 relative toCM-ACO1 is 59% and 75%, respectively.CM-ACO2 andCM-ACO3 are 59% homologous in their coding regions. These three genes have close homology toPH-ACO3, a member of the ACC oxidase multigene family of petunia. The predicted amino acid sequences of CM-ACO1 and CM-ACO3 are 77% to 81% identical to those encoded by the tomato and petunia genes, while the deduced amino acid sequence ofCM-ACO2 shows only 42% to 45% homology. RT-PCR analysis using gene-specific primers shows that the three genes are differentially expressed during development, ethylene treatment and wounding.CM-ACO1 is induced in ripe fruit and in response to wounding and to ethylene treatment in leaves.CM-ACO2 is detectable at low level in etiolated hypocotyls.CM-ACO3 is expressed in flowers and is not induced by any of the stimuli tested.

The effect of whole-body hyperthermia (41.5°c, 2 h) on doxorubicin (DOX) tissue distribution and plasma pharmacokinetics was examined in rats bearing a subcutaneous fibrosarcoma. Tumour response to the hyperthermia regimen alone was minimal, but the combination of heat with DOX (5.0 mg/kg, i.v.) enhanced tumour growth delay. The combined therapy, however, showed increased toxicity to normal tissue (especially renal and cardiac). Although DOX levels in spleen tissue were higher in rats exposed to hyperthermia than in control normothermic rats, both groups had comparable levels of drug in tumour, heart, kidney, and small intestine tissue at all time-points examined. Compared with normothermic animals, hyperthermia-treated rats showed decreased DOX in the mean area under the concentration-time curve (AUC) and decreased plasma DOX t1/2 but increased plasma drug clearance. These heat-mediated alterations in DOX pharmacokinetic parameters, however, do not account for the significant increases in thermochemotherapy-mediated cytotoxicities observed in tumour, and in normal renal and cardiac tissues.

1. 65Zn was injected intravenously during transjugular liver biopsy and, from simultaneous hepatic and peripheral venous blood samples, hepatointestinal 65Zn extraction was calculated. Hepatic zinc content was measured in biopsy specimens. 2. On the same occasion samples of liver tissue were taken and their zinc content was measured by atomic absorption spectrophotometry. 3. Seven patients with cirrhosis had significantly lower hepatic zinc content and hepatointestinal zinc extraction than six control patients with mild liver disease. Six patients with chronic hepatitis had a mean hepatointestinal zinc extraction higher than control patients, whereas their mean hepatic zinc content was lower, although the former difference did not achieve statistical significance. 4. These results demonstrate that hepatointestinal extraction of zinc is impaired in cirrhosis, but not in chronic hepatitis.

A variety of methods have been developed to amplify DNA and RNA. These methods vary in their susceptibility to evolve new molecular species differing from the starting template. PCR is exceptionally resistant to in vitro evolution, whereas methods such as Qß replicase and 3SR are much less robust. This paper develops some simple mathematical models which suggest that PCR is resistant to in vitro evolution because the reaction controls replication in discrete cycles: fast replication is of little advantage during PCR because the reaction limits fast replicators as well as slow ones to a single copy per cycle. In contrast, continuous (isothermal) reactions, as in the Qß replicase reaction, favor fast replicators. The advantage of fast replication is compounded in continuous reactions, because a fast replicator can complete many generations of replication during the time it takes a slow replicator to complete one generation. These models suggest that continuous amplication protocols will never achieve the robustness against in vitro evolution observed with PCR.

Whole-body hyperthermia (WBH) is a well-described investigational adjunct to systemic chemotherapy for the treatment of advanced malignancies. The hemodynamic consequences of this physiologic state may include tachycardia, which can produce acute myocardial ischemia in patients with coronary artery disease. Ischemic heart disease is currently considered a contraindication to WBH. We chose to investigate the consequences of using a new β1-adrenergic antagonist, esmolol, to attempt to control the tachycardia associated with WBH. After institutional approval and patient consent, nine consecutive patients with normal cardiac function presenting for WBH with carboplatin infusion were studied. Along with standard monitors, radial arterial and oximetric thermodilution pulmonary artery catheters were placed. Patients were sedated and heated in a radiant warmer (Enthermics). Spontaneous ventilation was maintained and hemodynamic data were gathered at 37°C, and at 41.8°C (before, during and after esmolol infusion). Heart rate and cardiac output increased (by 46% (p = 0.001) and 35% (p=0.04) respectively) while mean arterial pressure and systemic vascular resistance fell (by 18% (p = 0.02) and 44% (p = 0.006) respectively) during hyperthermia. Heart rate was significantly reduced during esmolol administration (mean dose 180 μg/kg/min) in the absence of changes in cardiac index and calculated oxygen delivery. Ventricular filling pressures and stroke work were unchanged. No heart failure, pulmonary edema, or other adverse event was observed. Hemodynamic changes seen during esmolol administration were completely reversed 15 min after the infusion was stopped. We conclude that the administration of moderate doses of esmolol is safe for this population of patients undergoing WBH, and that this technique raises the question of whether patients with ischemic heart disease could safely undergo WBH.

This study examines antitumour effect and induction of apoptosis and necrosis after treatment with long-duration, mild whole body hyperthermia (LL-WBH, 40-0°C, for 6 h) in simultaneous combination with cisplatin (CDDP) on primary and metastatic tumour growth in a rat mammary adenocarcinoma. A significantly greater delay in primary mammary tumour growth was observed after treatment with LL-WBH + CDDP, compared to either modality alone (p < 0.05). LL-WBH alone caused a significant delay in spontaneous metastasis to the axillary lymph node (ALN) and LL-WBH + CDDP tended to further increase the delay in ALN metastasis. Survival was longest in rats receiving LL-WBH + CDDP, compared to other groups (p < 0.05). CDDP induced a peak of tumour apoptosis at 24 h after treatment beginning that was significantly greater than LL-WBH alone (p < 0.05). The peak of tumour apoptosis induced by LL-WBH + CDDP from 12 to 24 h was significantly greater than any other group (p < 0.01). These results suggest that the extent of treatment-induced apoptosis seems to correlate positively with antitumour response and the combination of LL-WBH with CDDP may lead to a promising adjuvant therapy for breast cancer.