Showing papers by "University of Birmingham published in 1995"

A single ataxia telangiectasia gene with a product similar to pi-3 kinase

Abstract: A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer.

The Large Angle Spectroscopic Coronagraph (LASCO)

Abstract: The Large Angle Spectroscopic Coronagraph (LASCO) is a three coronagraph package which has been jointly developed for the Solar and Heliospheric Observatory (SOHO) mission by the Naval Research Laboratory (USA), the Laboratoire d’Astronomie Spatiale (France), the Max-Planck-Institut fur Aeronomie (Germany), and the University of Birmingham (UK) LASCO comprises three coronagraphs, C1, C2, and C3, that together image the solar corona from 11 to 30 R⊙ (C1: 11–3 R⊙, C2: 15–6 R⊙, and C3: 37 – 30 R⊙) The C1 coronagraph is a newly developed mirror version of the classic internally-occulted Lyot coronagraph, while the C2 and C3 coronagraphs are externally occulted instruments High-resolution imaging spectroscopy of the corona from 11 to 3 R⊙ can be performed with the Fabry-Perot interferometer in C1 High-volume memories and a high-speed microprocessor enable extensive on-board image processing Image compression by a factor of about 10 will result in the transmission of 10 full images per hour

Market Orientation and Company Performance: Empirical Evidence From UK Companies

Abstract: SUMMARY There has been little empirical investigation of a relationship between market orientation and performance, which is assumed to exist in the strategic management and marketing literatures. This limited empirical evidence is equivocal, and is dominated by only two US studies. The overall aim of the study reported in this article was to build on this limited empirical evidence about a relationship, by achieving new insights from another national business culture, namely the UK. Unlike the US evidence, the results from this study suggest that the influence of market orientation on performance is moderated by environmental variables. They suggest that market orientation may not be advantageous in highly turbulent markets, and in conditions of low customer power and high technological change.

Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus

Abstract: The IDDM2 locus encoding susceptibility to type 1 diabetes was mapped previously to a 41-kb region spanning the insulin gene and a minisatellite or variable number of tandem repeats (VNTR) locus on human chromosome 11p155 By 'cross-match' haplotype analysis and linkage disequilibrium mapping, we have mapped the mutation IDDM2 to within the VNTR itself Other polymorphisms were systematically excluded as primary disease determinants Transmission of IDDM2 may be influenced by parent-of-origin phenomena Although we show that the insulin gene is expressed biallelically in the adult pancreas, we present preliminary evidence that the level of transcription in vivo is correlated with allelic variation within the VNTR Allelic variation at VNTRs may play an important general role in human disease

Least-squares deconvolution of apparent resistivity pseudosections

Abstract: A fast technique for the inversion of data from resistivity tomography surveys has been developed. This technique is based on the smoothness-constrained, least-squares method, and it produces a 2-D subsurface model that is free of distortions in the apparent resistivity pseudosection caused by the electrode array geometry used. A homogeneous earth model is used as the starting model for which the apparent resistivity partial derivative values can be calculated analytically. Tests with a variety of models and data from field surveys show that this technique is insensitive to random noise, provided a sufficiently large damping factor is used, and that it can resolve structures that cause overlapping anomalies in the pseudosection. On a 33 MHz 80486DX microcomputer, it takes about 5 s to process a single data set.

The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates activation of NF-kappa B and cell surface phenotype via two effector regions in its carboxy-terminal cytoplasmic domain.

Abstract: The Epstein-Barr virus (EBV) encoded latent membrane protein, LMP1, is oncogenic in rodent fibroblasts and is an essential effector protein in EBV-induced growth-transformation of human B lymphocytes. Previous structure-function studies with LMP1 have relied largely on rodent fibroblast transformation as a functional readout, with apparently conflicting results. We have now analysed several LMP1 mutants in various human cell types, including B cells, T cells and epithelial cells, using two independent functional assays; (i) activation of NF-kappa B, and (ii) induction of two cell surface activation markers, CD54 and CD40. The results suggest that the cytosolic N-terminus is not essential for LMP1 function in any cell type studied. The third and fourth transmembrane helices and the intracytosolic loops are dispensable for activation of NF-kappa B, but they do influence the induction of CD54 and CD40. The major effector domain appears to be the cytosolic C-terminus in which were identified two 'C-terminal activating regions', CTAR-1 (residues 194-232) and CTAR-2 (residues 351-386). Whilst the exact results depended upon the host cell line, CTAR-2 was generally more important for activation of NF-kappa B, and both CTAR-1 and CTAR-2 were required for optimal induction of CD54 and CD40. Analysis of NF-kappa B activation by LMP1 in Rat-1 fibroblasts indicated that many mutations that were functional in human cells were poorly tolerated in the rodent cells; a result that is in broad agreement with published Rat-1 transformation data.

A structural model of the dimensions of teacher stress

Abstract: A comprehensive survey of teacher stress, job satisfaction and career commitment among 710 full-time primary school teachers was undertaken by Borg, Riding & Falzon (1991) in the Mediterranean islands of Malta and Gozo. A principal components analysis of a 20-item sources of teacher stress inventory had suggested four distinct dimensions which were labelled: Pupil Misbehaviour, Time/Resource Difficulties, Professional Recognition Needs, and Poor Relationships, respectively. To check on the validity of the Borg et al. factor solution, the group of 710 teachers was randomly split into two separate samples. Exploratory factor analysis was carried out on the data from Sample 1 (N = 335), while Sample 2 (N = 375) provided the cross-validational data for a LISREL confirmatory factor analysis. Results supported the proposed dimensionality of the sources of teacher stress (measurement model), along with evidence of an additional teacher stress factor (Workload). Consequently, structural modelling of the 'causal relationships' between the various latent variables and self-reported stress was undertaken on the combined samples (N = 710). Although both non-recursive and recursive models incorporating Poor Colleague Relations as a mediating variable were tested for their goodness-of-fit, a simple regression model provided the most parsimonious fit to the empirical data, wherein Workload and Student Misbehaviour accounted for most of the variance in predicting teaching stress.

The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Relationship to ethnicity and country of birth.

Abstract: Objective. To establish the point prevalence of systemic lupus erythematosus (SLE) on January 1, 1992, and the incidence of SLE during 1991, in Birmingham, England, a large city with a broad ethnic mix. Methods. Six sources were used to ascertain patients with diagnosed SLE, including notification by attending and primary care physicians, the lupus patient support group, and hospital inpatient and laboratory data. Results. There were 242 SLE patients (227 females, 15 males) identified: prevalence rate 27.7/100,000 (95% confidence interval 24.2–31.2/100,000) in the population and 206.0/100,000 in Afro-Caribbean females. No significant differences in female ethnic prevalence rates by place of birth were observed. Thirty-three patients developed SLE in 1991: incidence rate 3.8/ 100,000/year (95% confidence interval 2.5–5.1/100,000/year). Conclusion. This study illustrates dramatic differences in incidence and prevalence rates in the UK, depending on ethnic group and irrespective of place of birth.

Effect of red wine ingestion on the antioxidant capacity of serum.

Abstract: Aerobic metabolism in biological systems produces reactive oxygen species, and defense against such prooxidants requires antioxidant activity, e.g., predominantly vitamins C and E in serum. Recently, flavonoids (polyphenols occurring widely in plants) have been investigated in vitro for their antioxidant activity; whether they are absorbed after ingestion is not clear. Using a chemiluminescent assay of serum antioxidant capacity (SAOC), we have studied the effects in normal individuals of ingesting red wine, white wine, and high doses of vitamin C. In nine subjects who ingested 300 mL of red wine, the mean SAOC was increased by 18% after 1 h and by 11% at 2 h. The same amount of white wine produced 4% and 7% increases, respectively. The ingestion of 1000 mg (5.7 mmol) of ascorbic acid by four subjects increased their mean SAOC by 22% at 1 h and by 29% at 2 h. An in vitro comparison of red wine, white wine, and various fruit juices showed the high antioxidant capacity of red wine in addition to its ability to increase the antioxidant capacity of serum in vivo. The antioxidant effects of various flavonoids and other polyphenols were also studied.

The control of apoptosis and drug resistance in ovarian cancer: influence of p53 and Bcl-2.

Abstract: Modulation of apoptosis may influence resistance to chemotherapy and therefore affect the outcome of cancer treatment. Ovarian cancer, one of the most fatal malignancies in women, is often associated with drug resistance but the cellular pathways contributing to this effect remain obscure. We have found that Bcl-2 and p53, two proteins implicated in the control of apoptosis, are frequently expressed in fresh biopsies of primary ovarian carcinoma. Examination of Bcl-2 and p53 protein levels in pairs of cis-platin sensitive and resistant ovarian cell lines demonstrated that the resistant variants over-express Bcl-2 and/or p53, apparently due to progressive expansion of Bcl-2 and/or p53 positive subpopulations during the in vitro development of resistance. Exogenous expression of Bcl-2 or a temperature sensitive mutant p53 (ts p53) in the ovarian cell line A2780 resulted in protection from drug-induced apoptosis and a delay in drug-mediated S-phase arrest. Interestingly, p53 accumulation in response to DNA damage induced by different agents was significantly delayed and reduced in the Bcl-2 transfectants compared to the control A2780 line, suggesting that Bcl-2 may act upstream of the p53 pathway. Similarly, the induction of Bax mRNA and protein was also found to be delayed in the presence of Bcl-2. Overall, our data provide further evidence for cross-talk between Bcl-2, p53 and Bax and suggest that these genes are important determinants of drug-induced apoptosis thereby modulating resistance to chemotherapy.

Forms of market orientation in uk companies

Abstract: Despite the importance of market orientation in the marketing and strategic management literature, it has been the subject of few conceptual and empirical studies. Also, the latter have addressed only the degree of market orientation and not its nature or form. the empirical study reported in this article focuses on the form of market orientation. Five different forms of market orientation were identified, along with three factors that discriminate between them. Although there are some performance differences between the forms of market orientation, the market environments that they are associated with are not significantly different. As well as providing additional empirical evidence, the results provide empirical support to, and extensions of, the conceptualization of market orientation given in the literature.

Post-Traumatic Stress Disorder (PTSD) after Childbirth

Abstract: BACKGROUND There has been discussion about the possible occurrence of post-traumatic stress disorder (PTSD) in mothers after difficult childbirth. METHOD Four cases with a symptom profile suggestive of PTSD commencing within 48 hours of childbirth are presented. RESULTS The PTSD was in each case associated with the delivery. In each case, there was an associated depressive illness. All four had persistent disorders, and two had difficulties with mother/infant attachment. CONCLUSION As confirmed by other reports, the prevalence of PTSD associated with childbirth is a matter of concern.

The Darkness of God: Negativity in Christian Mysticism

Abstract: Acknowledgements Introduction Part I. Two Sources and a Synthesis: 1. The allegory and Exodus 2. Cataphatic and the apophatic in Denys the Areopagite 3. The God within: Augustine's Confessions 4. Interiority and ascent: Augustine's De Trinitate 5. Hierarchy interiorised: Bonaventure's Itinerarium Mentis in Deum Part II. Developments: 6. Eckhart: God and the self 7. Eckhart: detachment and the critique of desire 8. The Cloud of Unknowing and the critique of interiority 9. Denys the Carthusian and the problem of experience 10. John of the Cross: the dark nights and depression 11. From mystical theology to mysticism Further reading Index.

Microstrip bandpass filter using degenerate modes of a novel meander loop resonator

Abstract: A novel type of dual-mode microstrip bandpass filter using degenerate modes of a meander loop resonator has been developed for miniaturization of high selectivity narrow-band microwave bandpass filters. A filter of this type having a 2.5% bandwidth at 1.58 GHz was designed and fabricated. The measured filter performance is presented. >

Histone H4 acetylation distinguishes coding regions of the human genome from heterochromatin in a differentiation-dependent but transcription-independent manner.

Abstract: By immunoprecipitation of chromatin fragments from cultured human HL-60 cells with antibodies specific for H4 acetylated at specific lysine residues we have defined the level of H4 acetylation within transcriptionally active and inactive regions of the genome. H4 within or adjacent to coding regions had a similar level of overall acetylation to input (bulk) chromatin and a similar pattern of acetylation of individual lysines (i.e. 16 > 8, 12 > 5). The acetylation of H4 in coding (and adjacent) regions was not correlated with transcriptional activity and did not vary with position along the constitutively active c-myc gene. Turnover of H4 acetates was not selectively increased in transcriptionally active chromatin. H4 associated with centric heterochromatin or with the CCCTAA repeat of telomeric heterochromatin was infrequently acetylated (< 1%) at all lysines. We conclude that nucleosomes containing acetylated H4 are scattered infrequently and possibly randomly through coding and adjacent regions and are essentially absent from heterochromatin. Induction of differentiation of HL-60 cells by exposure to dimethylsulfoxide or 12-o-tetradecanoylphorbol 13-acetate (TPA) did not alter the level of H4 acetylation within either the c-myc or c-fos genes or other coding regions, but did induce a transient increase in H4 acetylation within centric heterochromatin.

Colocalisation of Vascular Endothelial Growth Factor and Its Flt-1 Receptor in Human Placenta

Abstract: Vascular endothelial growth factor (VEGF) is an angiogenic protein which acts on both endothelial and trophoblast cells. In first trimester placenta, VEGF immunoreactive protein was detected in cytotrophoblast shell suggesting a role in the regulation of cytotrophoblast growth and differentiation as they also expressed VEGF receptor (flt-1) protein. VEGF and flt-1 immunoreactive proteins were expressed in Hofbauer cells within the villous mesenchyme, macrophages and in maternal decidual cells while weak VEGF immunoreactive protein was seen in syncytiotrophoblast surrounding the placental villi in first and second trimester placentae. At term, there was relatively weak VEGF and flt-1 immunostaining in the syncytiotrophoblast while intense VEGF immunostaining was seen in the Hofbauer and maternal decidual cells. Extravillous trophoblast showed immunostaining for flt-1 but no staining for VEGF. Both amnion and chorion expressed strong VEGF immunoreactivity throughout gestation. Smooth muscle cells su...

Molecular genetics and transport analysis of the copper-resistance determinant (pco) from Escherichia coli plasmid pRJ1004.

Abstract: The copper-resistance determinant (pco) of Escherichia coli plasmid pRJ1004 was cloned and sequenced. Tn1000 transposon mutagenesis identified four complementation groups, mutations in any of which eliminated copper resistance. DNA sequence analysis showed that the four complementation groups contained six open reading frames, designated pco-ABCDRS. The protein product sequences derived from the nucleotide sequence show close homology between this copper-resistance system and the cop system of a plasmid pPT23D of Pseudomonas syringae pv. tomato. The PcoR and PcoS protein sequences show homology to the family of two-component sensor/responder phosphokinase regulatory systems. A seventh reading frame (pcoE) was identified from DNA sequence data, and lies downstream of a copper-regulated promoter. Transport assays with 64Cu(II) showed that the resistant cells containing the plasmid had reduced copper accumulation during the log phase of growth, while increased accumulation had previously been observed during stationary phase. Chromosomal mutants defective in cellular copper management were obtained and characterized. In two of these mutants pco resistance was rendered totally inactive, whilst in another two mutants pco complemented the defective genes. These data indicate that plasmid-borne copper resistance in E. coli is linked with chromosomal systems for copper management.