The growth of paracoccus halodenitrificans in a defined medium

A synthetic medium, consisting of inorganic salts and any of a number of carbon sources, supported the aerobic growth of Paracoccus halodenitrificans when supplemented with thiamine. The same medium plus a nitrogenous oxide supported anaerobic growth when additionally supplemented with methionine. The observation that vitamin B12 or betaine replaced methionine suggested that P. halodenitrificans had a defect in the cobalamin dependent pathway for methionine biosynthesis, as well as the inability to synthesize betaine when growing anaerobically

Rethinking the Process of Operational Research & Systems Analysis

Both practitioners and teachers of OR and Applied Systems Analysis have suffered from the fact that, until the present, the subject has lacked a firm methodological base. A simple explanation for this is that the subject has its formal origins in traditional laboratory science, but that its practice lies firmly in the realm of applied social science. Both supporters and opponents of the subject, have, therefore tended to define it to suit their own purposes, and practitioners have, by and large, explained themselves in terms of "this is what I do". There has been increasing dissatisfaction with this state of affairs and in recent years a number of researchers and practitioners in different countries have set out to provide a more rigorous framework for understanding what the subject is really about; based on successful experience, rather than on hypothetical ideas as to what the subject should be. This book is the consequence of a meeting between a distinguished group of such practitioners and methodologists at a seminar at the International Institute for Applied Systems Analysis in August 1980. They found that there was a substantial agreement as to how the subject should be described and went away to write their own personal commentary on this common overview. The papers are diverse in style and intention -- some are intensely practical, others are deeply philosophical. Together they provide, perhaps for the first time a coherent, interlocking, set of ideas which can be considered as the foundations on which we may describe the subject as a science in its own right. Practitioners and teachers of OR and Systems Analysis will find the book directly useful as well as intellectualy stimulating, and philosophers of science will find much in it that is relevant to their thinking

Electrochemical characterisation of single crystal boron doped diamond

Interest and employment of boron doped diamond (BDD) as an electrode material has grown rapidly over the last decade, due to its unique advantageous properties over traditional electrode materials. BDD has minimal background currents and can offer an increased potential range allowing for the detection of an increased range of analytes. Furthermore BDD stability in harsh conditions, elevated temperatures and pressures offers a wealth of applications. Polycrystalline BDD (pBDD) is commercially available in large wafers for industrial applications. This material is comparatively easy to grow when compared to single crystal BDD (scBDD) which requires careful homoepitaxial growth. This thesis aims to characterise scBDD grown with differing boron dopant densities, crystal orientation and growth procedures; with a view to determining the most suitable scBDD material for employment in electroanalytical applications. Characterisation is performed using high resolution microscopic and spectroscopic techniques which show sample variations relating to growth parameters. No non-diamond like carbon is detected and boron concentrations are all ~1020 cm-3 or greater. Electrochemical characterisation is performed using the scBDD in disc electrode format, where wide potential windows, minimal background currents and close to reversible behaviour is observed for outer sphere mediators FcTMA+/2+, IrCl6 2-/3- and Ru(NH3)6 3+/2+. Electrode pre-treatments demonstrate the importance of surface termination supporting faster or slower electron transfer kinetics of selected inner sphere mediators. scBDD was functionalised with gold nanoparticles to aid in sample homogeneity determination, highlighted some heterogeneities as a direct result of a failed growth process. This was performed at both macro and micro scales, giving rise to differing nucleation theories. Finally electrochemical imaging using scanning electrochemical microscopy is reported, enabling the determination of FcTMA+/2+ and Ru(NH3)6 3+/2+ kinetic electron transfer rates at well-defined tip-substrate distances

Superlubricity - a new perspective on an established paradigm

Superlubricity is a frictionless tribological state sometimes occurring in nanoscale material junctions. It is often associated with incommensurate surface lattice structures appearing at the interface. Here, by using the recently introduced registry index concept which quantifies the registry mismatch in layered materials, we prove the existence of a direct relation between interlayer commensurability and wearless friction in layered materials. We show that our simple and intuitive model is able to capture, down to fine details, the experimentally measured frictional behavior of a hexagonal graphene flake sliding on-top of the surface of graphite. We further predict that superlubricity is expected to occur in hexagonal boron nitride as well with tribological characteristics very similar to those observed for the graphitic system. The success of our method in predicting experimental results along with its exceptional computational efficiency opens the way for modeling large-scale material interfaces way beyond the reach of standard simulation techniques.Comment: 18 pages, 7 figure

Modelling the consequences of interactions between tumour cells.

Classical models of tumorigenesis assume that the mutations which cause tumours to grow act in a cell-autonomous fashion. This is not necessarily true. Sometimes tumour cells may adopt genetic strategies that boost their own replication and which also influence other cells in the tumour, whether directly or as a side-effect. Tumour growth as a whole might be enhanced or retarded. We have used mathematical models to study two non-autonomous strategies that tumour cells may use. First, we have considered the production by tumour cells of an angiogenesis growth factor that benefits both the cell from which it originates and neighbouring cells. Second, we have analysed a situation in which tumour cells produce autocrine-only or paracrine-only growth factors to prevent programmed cell death. In the angiogenesis model, stable genetic polymorphisms are likely to occur between cells producing and not producing the growth factor. In the programmed cell death model, cells with autocrine growth factor production can spread throughout the tumour. Production of paracrine-only growth factor is never selected because it is 'altruistic' (that is of no benefit to the cell that makes the growth factor), despite being potentially beneficial to tumour growth as a whole. No polymorphisms can occur in the programmed cell death model. Production of angiogenesis and other growth factors in tumours may be under stable genetic, rather than epigenetic, control, with implications for therapies aimed at such targets. Many of the mutations observed in tumours may have non-autonomous effects

Discrete solitons and nonlinear surface modes in semi-infinite waveguide arrays

We discuss the formation of self-trapped localized states near the edge of a semi-infinite array of nonlinear waveguides. We study a crossover from nonlinear surface states to discrete solitons by analyzing the families of odd and even modes centered at different distances from the surface, and reveal the physical mechanism of the nonlinearity-induced stabilization of surface modes.Comment: 4 double-column pages, 5 figures, submitted to Optics Letter

Allele loss occurs frequently at hMLH1, but rarely at hMSH2, in sporadic colorectal cancers with microsatellite instability.

Mutations at the hMSH2 and hMLH1 mismatch repair loci have been implicated in the pathogenesis of colorectal cancer. Tumours with two allelic mutations at a mismatch repair locus develop replication errors (RERs). In the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, one mutation is inherited and the other acquired somatically: in RER+ sporadic colorectal cancers, both mutations are somatic. RER+ tumours tend to have a low frequency of allele loss, presumably because they acquire most mutations through RERs. However, before a second mismatch repair mutation has occurred somatically, there is no reason to suppose that allele loss occurs less frequently in tumours that are to become RER+. Indeed, this second mutation might itself occur by allele loss. We have searched for allele loss at the hMSH2 and hMLH1 loci in RER+ and RER- sporadic colorectal cancers. Loss occurred at the hMLH1 locus in 7/17 (41%) RER+ tumours, compared with 6/40 (15%) RER- cancers (chi2=3.82, P approximately 0.05). At hMSH2, 2/22 RER+ sporadic cancers (9%) had lost an allele, compared with 2/40 (5%) RER- cancers (chi2=0.03, P>0.5). Taken together with previous studies which focused on colorectal cancers from HNPCC families, the data suggest that allele loss at hMLH1, but not at hMSH2, contributes to defective mismatch repair in inherited and sporadic colorectal cancer

Microsatellite-stable diploid carcinoma: a biologically distinct and aggressive subset of sporadic colorectal cancer

Chromosomal instability and microsatellite instability represent the major pathways for colorectal cancer (CRC) progression. However, a significant percentage of CRC shows neither pattern of instability, and thus represents a potentially distinctive form of the disease. Flow cytometry was used to determine the degree of DNA aneuploidy in 46 consecutive sporadic colorectal cancers. Microsatellite status was determined by PCR amplification using standard markers, while immunostaining was used to examine the expression of p53. K- ras status was determined by restriction-mediated PCR assay. Twenty-five (54%) tumours were aneuploid, 14 (30%) were diploid and microsatellite-stable and seven (15%) were diploid and microsatellite-unstable. Tumours with microsatellite instability were more likely to be right sided, to occur in women and to be associated with an improved survival. Aneuploid tumours were significantly more common in men and were likely to be left sided. The diploid microsatellite-stable (MSS) tumours did not show a sex or site predilection, but were strongly associated with the presence of metastatic disease at the time of diagnosis. Our data suggests that diploid, MSS tumours represent a biologically and phenotypically distinct subset of colorectal carcinoma, and one that is associated with the early development of metastases. We suggest that the genetic stability that characterizes these tumours may favour the maintenance of an invasive phenotype, and thus facilitate disease progression. These findings may have important implications for treatment options in this disease subset. © 2001 Cancer Research Campaign http://www.bjcancer.co

Risk factors for developing acute kidney injury in older people with diabetes and community-acquired pneumonia: a population-based UK cohort study.

BACKGROUND: Acute kidney injury (AKI) is being increasingly recognised in ageing populations. There are a paucity of data about AKI risk factors among older individuals with diabetes and infections, who are at particularly high risk of AKI. The objective of this study was to evaluate the risk factors for developing acute kidney injury (AKI) amongst older patients with diabetes and community-acquired pneumonia (CAP) in England, and whether the impact of underlying kidney function varied with age. METHODS: This was a population-based retrospective cohort study over 7 years (01/04/2004-31/3/2011) using electronic health records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics. The study population comprised individuals with diabetes aged ≥65 years with CAP. Associations between demographic, lifestyle factors, co-morbidities and medications and development of AKI within 28 days of CAP were explored in a logistic regression model. RESULTS: Among 3471 patients with CAP and complete covariate data, 298 patients developed subsequent AKI. In multivariable analyses, factors found to be independently associated with AKI included: male sex (adjusted odds ratio, aOR: 1.56 95% confidence interval (CI): 1.20-2.04), hypertension (aOR1.36 95% CI 1.01-1.85), being prescribed either angiotensin-converting-enzyme inhibitors or angiotensin-II-receptor-blockers (aOR: 1.59 95% CI: 1.19-2.13), or insulin (aOR: 2.27 95% CI: 1.27-4.05), presence of proteinuria (aOR 1.27 95% CI 0.98-1.63), and low estimated glomerular filtration rate (eGFR). The odds of AKI were more graded amongst older participants aged ≥80 years compared to those of younger age: for eGFR of ≤29 mL/min/1.73m2 (vs 60 ml/min/1.73m2) aOR: 5.51 95% CI 3.28-9.27 and for eGFR 30-59 mL/min/1.73m2 1.96 95% CI 1.30-2.96, whilst any eGFR < 60 ml/min/1.73m2 was associated with approximately 3-fold increase in the odds of AKI amongst younger individuals (p-value for interaction = 0.007). CONCLUSIONS: The identified risk factors should help primary care and hospital providers identify high risk patients in need of urgent management including more intensive monitoring, and prevention of AKI following pneumonia