Showing papers by "University of Cambridge published in 1990"

A logic of authentication

Abstract: Authentication protocols are the basis of security in many distributed systems, and it is therefore essential to ensure that these protocols function correctly. Unfortunately, their design has been extremely error prone. Most of the protocols found in the literature contain redundancies or security flaws. A simple logic has allowed us to describe the beliefs of trustworthy parties involved in authentication protocols and the evolution of these beliefs as a consequence of communication. We have been able to explain a variety of authentication protocols formally, to discover subtleties and errors in them, and to suggest improvements. In this paper we present the logic and then give the results of our analysis of four published protocols, chosen either because of their practical importance or because they serve to illustrate our method.

Phonological Skills And Learning To Read

Abstract: Phonological Awareness and Reading. How Children Read Words. Spelling and Phonological Awareness. How Children Read and Write New Words. Comparisons with Backward Readers and Spellers. Correlations and Longitudinal Predictions. Teaching Children About Sound. Do Children Read and Fail to Learn to Read in Different Ways from Each Other. Theories About Learning to Read.

Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: An index of cell proliferation with evidence of deregulated expression in some, neoplasms

Abstract: Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression

Statics and dynamics of worm-like surfactant micelles

Abstract: In certain surfactant solutions, such as aqueous cetyltrimethylammonium bromide (CTAB) in 0.1 M KBr, the amphiphiles are found to assemble reversibly into long, flexible worm-like micelles. Above a few per cent surfactant, these form an entangled viscoelastic fluid, reminiscent of a polymer solution. The authors review some recent experimental and theoretical progress concerning the equilibrium statistics and dynamics of these systems, which differ from normal polymer solutions in that the chains can break and reform reversibly.

Three-Dimensional Elastic Bodies in Rolling Contact

Abstract: 1 The Rolling Contact Problem.- 2 Review.- 3 The Simplified Theory of Contact.- 4 Variational and Numerical Theory of Contact.- 5 Results.- 6 Conclusion.- Appendix A The basic equations of the linear theory of elasticity.- Appendix B Some notions of mathematical programming.- Appendix C Numerical calculation of the elastic field in a half-space.- Appendix D Three-dimensional viscoelastic bodies in steady state frictional rolling contact with generalisation to contact perturbations.- Appendix E Tables.

An enlarged and updated internally consistent thermodynamic dataset with uncertainties and correlations: the system K2O–Na2O–CaO–MgO–MnO–FeO–Fe2O3–Al2O3–TiO2–SiO2–C–H2–O2

Abstract: We present, as a progress report, a revised and much enlarged version of the thermodynamic dataset given earlier (Holland & Powell, 1985). This new set includes data for 123 mineral and fluid end-members made consistent with over 200 P–T–XCO2–fO2 phase equilibrium experiments. Several improvements and advances have been made, in addition to the increased coverage of mineral phases: the data are now presented in three groups ranked according to reliability; a large number of iron-bearing phases has been included through experimental and, in some cases, natural Fe:Mg partitioning data; H2O and CO2 contents of cordierites are accounted for with the solution model of Kurepin (1985); simple Landau theory is used to model lambda anomalies in heat capacity and the Al/Si order–disorder behaviour in some silicates, and Tschermak-substituted end-members have been derived for iron and magnesium end-members of chlorite, talc, muscovite, biotite, pyroxene and amphibole. For the subset of data which overlap those of Berman (1988), it is encouraging to find both (1) very substantial agreement between the two sets of thermodynamic data and (2) that the two sets reproduce the phase equilibrium experimental brackets to a very similar degree of accuracy. The main differences in the two datasets involve size (123 as compared to 67 end-members), the methods used in data reduction (least squares as compared to linear programming), and the provision for estimation of uncertainties with this dataset. For calculations on mineral assemblages in rocks, we aim to maximize the information available from the dataset, by combining the equilibria from all the reactions which can be written between the end-members in the minerals. For phase diagram calculations, we calculate the compositions of complex solid solutions (together with P and T) involved in invariant, univariant and divariant assemblages. Moreover we strongly believe in attempting to assess the probable uncertainties in calculated equilibria and hence provide a framework for performing simple error propagation in all calculations in thermocalc, the computer program we offer for an effective use of the dataset and the calculation methods we advocate.

Diatoms and pH Reconstruction

Abstract: Palaeolimnological diatom data comprise counts of many species expressed as percentages for each sample. Reconstruction of past lake-water pH from such data involves two steps; (i) regression, where responses of modern diatom abundances to pH are modelled and (ii) calibration where the modelled responses are used to infer pH from diatom assemblages preserved in lake sediments. In view of the highly multivariate nature of diatom data, the strongly nonlinear response of diatoms to pH, and the abundance of zero values in the data, a compromise between ecological realism and computational feasability is essential. The two numerical approaches used are (i) the computationally demanding but formal statistical approach of maximum likelihood (ML) Gaussian logit regression and calibration and (ii) the computationally straightforward but heuristic approach of weighted averaging (WA) regression and calibration. When the Surface Water Acidification Project (SWAP) modern training set of 178 lakes is reduced by data-screening to 167 lakes, WA gives superior results in terms of lowest root mean squared errors of prediction in cross-validation. Bootstrapping is also used to derive prediction errors, not only for the training set as a whole but also for individual pH reconstructions by WA for stratigraphic samples from Round Loch of Glenhead, southwest Scotland covering the last 10 000 years. These reconstructions are evaluated in terms of lack-of-fit to pH and analogue measures and are interpreted in terms of rate of change by using bootstrapping of the reconstructed pH time-series.

The Validation of the Edinburgh Post-natal Depression Scale on a Community Sample

Abstract: The Edinburgh Post-natal Depression Scale (EPDS) was validated on a community sample of 702 women at six weeks post-partum using Research Diagnostic Criteria for depression. The estimates of sensitivity, specificity and positive predictive value, being based on a large random sample, offer improved guidelines for the use of the EPDS by the primary care team.

Calcic amphibole equilibria and a new amphibole-plagioclase geothermometer

Abstract: There is currently a dearth of reliable thermobarometers for many hornblende and plagioclase-bearing rocks such as granitoids and amphibolites. A semi-empirical thermodynamic evaluation of the available experimental data on amphibole+plagioclase assemblages leads to a new thermometer based on the Aliv content of amphibole coexisting with plagioclase in silica saturated rocks. The principal exchange vector in amphiboles as a function of temperature in both the natural and experimental studies is $$\left( {Na\square _{ - 1} } \right)^A \left( {AlSi_{ - 1} } \right)^{T1}$$ . We have analysed the data using 3 different amphibole activity models to calibrate the thermometer reactions 1. $$1. Edenite + 4 Quartz = Tremolite + Albite$$ 2. $$2. Pargasite + 4 Quartz = Hornblende + Albite.$$ The equilibrium relation for both (1) and (2) leads to the proposed new thermometer $$T = \frac{{0.677P - 48.98 + Y}}{{ - 0.0429 - 0.008314 ln K}} and K = \left( {\frac{{Si - 4}}{{8 - Si}}} \right)X_{Ab}^{Plag} ,$$ where Si is the number of atoms per formula unit in amphiboles, with P in kbar and T in K; the term Y represents plagioclase non-ideality, RTlnγab, from Darken's Quadratic formalism (DQF) with Y=0 for X ab>0.5 and Y=-8.06+25.5(1-X ab)2 for X ab<0.5. The best fits to the data were obtained by assuming complete coupling between Al on the T1 site and Na in the A site of amphibole, and the standard deviation of residuals in the fit is ±38°C. The thermometer is robust to ferric iron recalculation procedures from electron probe data and should yield temperatures of equilibration for hornblende-plagioclase assemblages with uncertainties of around ±75° C for rocks equilibrated at temperatures in the range 500°–1100° C. The thermometer should only be used in this temperature range and for assemblages with plagioclase less calcic than An92 and with amphiboles containing less than 7.8 Si atoms pfu. Good results have been attained on natural examples from greenschist to granulite facies metamorphic rocks as well as from a variety of mafic to acid intrusive and extrusive igneous rocks. Our analysis shows that the pressure dependence is poorly constrained and the equilibria are not suitable for barometry.

Clinical Features and Natural History of von Hippel-Lindau Disease

Abstract: The clinical features, age at onset and survival of 152 patients with von Hippel-Lindau disease were studied. Mean age at onset was 26.3 years and 97 per cent of patients had presented by aged 60 years. Retinal angioma was the first manifestation in 65 patients (43 per cent), followed by cerebellar haemangioblastoma (n = 60, 39 per cent) and renal cell carcinoma (n = 15, 10 per cent). Overall, 89 patients (59 per cent) developed a cerebellar haemangioblastoma, 89 (59 per cent) a retinal angioma, 43 (28 per cent) renal cell carcinoma, 20 (13 per cent) spinal haemangioblastoma and 11 (7 per cent) a phaeochromocytoma. Renal, pancreatic and epididymal cysts were frequent findings but their exact incidence was not accurately assessed. Mean age at diagnosis of renal cell carcinoma (44.0 +/- 10.9 years) was significantly older than that for cerebellar haemangioblastoma (29.0 +/- 10.0 years) and retinal angioma (25.4 +/- 12.7 years). The probability of a patient with von Hippel-Lindan disease developing a cerebellar haemangioblastoma, retinal angioma or renal cell carcinoma by age 60 years was 0.84, 0.7 and 0.69, respectively. A comprehensive screening protocol for affected patients and at-risk relatives is presented, based on detailed analysis of age at onset data for each of the major complications. Median actuarial survival was 49 years, with renal cell carcinoma the leading cause of death.

Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nucleolar form.

Abstract: The proliferating cell nuclear antigen, PCNA, has recently been identified as the polymerase delta accessory protein. PCNA is essential for cellular DNA synthesis and is also required for the in vitro replication of simian virus 40 (SV40) DNA where it acts to coordinate leading and lagging strand synthesis at the replication fork. The cDNA for rat PCNA was cloned into a series of bacterial expression vectors and the resulting protein used to immunize mice. Eleven new monoclonal antibodies to PCNA have been isolated and characterized. Some of the antibodies recognize epitopes conserved from man to fission yeast. Immunocytochemical analysis of primate epithelial cell lines showed that the antibodies recognized antigenically distinct forms of PCNA and that these forms were localized to different compartments of the nucleus. One antibody reacted exclusively with PCNA in the nucleolus. These results suggest that the PCNA protein may fulfil several separate roles in the cell nucleus associated with changes in its antigenic structure.

Redesign of the coenzyme specificity of a dehydrogenase by protein engineering

Abstract: Directed mutagenesis and molecular modelling have been used to identify a set of amino-acid side chains in glutathione reductase that confer specificity for the coenzyme NADP+. Systematic replacement of these amino acids, all of which occur in a 'fingerprint' structural motif in the NADP+-binding domain, leaves the substrate specificity unchanged but converts the enzyme into one displaying a marked preference for the coenzyme NAD+.

Anatomic and Disease Specificity of NADH CoQ1 Reductase (Complex I) Deficiency in Parkinson's Disease

Abstract: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is thought to produce parkinsonism in humans and other primates through its inhibition of complex I The recent discovery of mitochondrial complex I deficiency in the substantia nigra of patients with Parkinson's disease has provided a remarkable link between the idiopathic disease and the action of the neurotoxin MPTP This article shows that complex I deficiency in Parkinson's disease is anatomically specific for the substantia nigra, and is not present in another neurodegenerative disorder involving the substantia nigra Evidence is also provided to show that there is no correlation between L-3,4-dihydroxyphenylalanine therapy and complex I deficiency These results suggest that complex I deficiency may be the underlying cause of dopaminergic cell death in Parkinson's disease

Partly pedogenic origin of magnetic variations in Chinese loess

Abstract: QUATERNARY sequences of interbedded aeolian silts (loess) and buried soils (palaeosols) potentially provide one of the best terrestrial records of past climates1–5. Magnetic susceptibility variations in loess and palaeosol sequences from China are strongly correlated with climate-induced fluctuations of oxygen isotope ratios in deep-sea sediments2–4,6–8. As an explanation of this correlation, it has been suggested that the recorded variations in magnetic susceptibility depend primarily on the degree of dilution by non-magnetic bulk loess constituents of a uniform magnetic assemblage derived from remote but unknown sources6–8. It has also been suggested that such a model, involving changes in the accumulation rate of loess superimposed on a constant flux of magnetic particles, provides a relative geological timescale through the control of loess deposition by astronomically modulated climate fluctuations7. Here we report a preliminary test of this model using rock magnetic properties especially sensitive to variations in magnetic grain size. Our results show that palaeosols are characterized by much finer magnetic grain size assemblages than are the intervening loess units. This suggests that a simple model based on constant magnetic influx and dilution by variable amounts of non-magnetic loess is inadequate. Our magnetic measurements establish the close comparability of the fine grained magnetic minerals in the palaeosol samples to those in contemporary soils and thus point to a partially pedogenic origin for the magnetic mineral assemblages in the palaeosols.

Reasoning about belief in cryptographic protocols

Abstract: A mechanism is presented for reasoning about belief as a systematic way to understand the working of cryptographic protocols. The mechanism captures more features of such protocols than that given by M. Burrows et al. (1989) to which the proposals are a substantial extension. The notion of possession incorporated in the approach assumes that principles can include in messages data they do not believe in, but merely possess. This also enables conclusions such as 'Q possesses the shared key', as in an example to be derived. The approach places a strong emphasis on the separation between the content and the meaning of messages. This can increase consistency in the analysis and, more importantly, introduce the ability to reason at more than one level. The final position in a given run will depend on the level of mutual trust of the specified principles participating in that run. >

Geometry of quantum evolution

Abstract: For an arbitrary quantum evolution, it is shown that the integral of the uncertainty of energy with respect to time is independent of the particular Hamiltonian used to transport the quantum system along a given curve in the projective Hilbert space. It is the distance along this curve measured by the Fubini-Study metric. This gives a new time-energy uncertainty principle. New geometric meanings to time as measured by a clock and the transition probability during a quantum measurement are also obtained.

Segmentation in the chick embryo hindbrain is defined by cell lineage restrictions

Abstract: In the chick embryo hindbrain, morphological segmentation into rhombomeres is matched by metameric patterns of early neuronal differentiation and axonogenesis. Boundaries between rhombomeres coincide with boundaries of expression of murine regulatory genes. By clonal analysis using intracellular marking, we show here that the rhombomere boundaries are partitions across which cells do not move. When a parent cell is marked before the appearance of rhombomere boundaries, the resulting clone is able to spread into the neighbouring rhombomere. When marked after boundary appearance, the clone still expands freely within the rhombomere of origin, but it is now restricted at the boundaries. Rhombomeres in the chick embryo thus behave like polyclonal units, raising the possibility that they are analogous to the compartments of insects.

Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines.

Abstract: The expression of the tumour suppressor gene p53 was analysed in 11 human breast cancer cell lines by immunohistochemistry, immunoprecipitation and cDNA sequencing. We used a panel of anti-p53 monoclonal antibodies for cell staining and found abnormalities in every case. Eight of the cell lines produce a form of p53 which can be immunoprecipitated by the monoclonal antibody PAb240 but not by PAb1620. In the murine system PAb240 only immunoprecipitates mutant p53. We sequenced p53 cDNA directly from four of the PAb240 positive cell lines using asymmetric PCR templates. All four contained missense mutations in p53 RNA, with no detectable expression of the wild type sequence. Different residues were affected in each cell line, but all the mutations changed amino acids conserved from man to Xenopus. These results imply that as in the murine system, the PAb240 antibody reliably detects a wide variety of p53 mutations and that these mutations have a common effect on the structure of p53. Immunohistochemical data suggest that p53 mutation is the commonest genetic alteration so far detected in primary breast cancer.

The damage mechanics of brittle solids in compression

Abstract: The development of microcrack damage in brittle solids in compression is analyzed, using a simple model. The model is developed from recent detailed analysis of the initiation, propagation and linkage of microfractures from pre-existing cracks, voids, or other inhomogeneities. It describes the evolution of damage with strain and from it a criteria for failure can be established. The results are used to construct failure surfaces in stress space which combine information about brittle failure with data describing the onset of plastic yielding. Such failure surfaces are constructed for a number of rocks and are compared with previously published experimental data.

An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea.

Abstract: ERYTHROMYCIN A, a clinically important polyketide antibiotic, is produced by the Gram-positive bacterium Saccharopolyspora erythraea In an arrangement that seems to be generally true of antibiotic biosynthetic genes in Streptomyces and related bacteria like S erythraea1, the ery genes encoding the biosynthetic pathway to erythromvein are clustered around the gene (ermE) that confers self-resistance on S erythraea2–6 The aglycone core of erythro-mycin A is derived from one propionyl-CoA and six methylmalonyl-CoA units, which are incorporated head-to-tail7–10 into the growing polyketide chain, in a process similar to that of fatty-acid biosynthesis1, to generate a macrolide intermediate, 6-deoxyeryth-ronolide B10 6-Deoxyerythronolide B is converted into erythro-mycin A through the action2–5,10 of specific hydroxylases, glycosyItransferases and a methyltransferase We report here the analysis of about 10 kilobases of DNA from S erythraea, cloned by chromosome 'walking' outwards from the erythromycin-resistance determinant ermE, and previously shown to be essential for erythromycin biosynthesis5,11 Partial sequencing of this region12 indicates that it encodes the synthase Our results confirm this, and reveal a novel organization of the erythromycin-producing polyketide synthase, which provides further insight into the mechanism of chain assembly