Effects of sub-chronic exposure to naturally occurring N-terminally truncated metabolites of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), GIP(3-42) and GLP-1 (9-36)amide, on insulin secretion and glucose homeostasis in ob/ob mice

Glucose-dependent insulinotrophic polypepticle (GIP) and glucagon-like peptide-1 (GLP-1) are important enteroendocrine hormones that are rapidly degraded by an ubiquitous enzyme dipeptidyl peptidase IV to yield truncated metabolites GIP(3-42) and GLP-1 (9-36)amide. In this study, we investigated the effects of sub-chronic exposure to these major circulating forms of GIP and GLP-1 on blood glucose control and endocrine pancreatic function in obese diabetic (ob/ob) mice. A once daily injection of either peptide for 14 days had no effect on body weight, food intake or pancreatic insulin content or islet morphology. GLP-1(9-36)amide also had no effect on plasma glucose homeostasis or insulin secretion. Mice receiving GIP(3-42) exhibited small but significant improvements in non-fasting plasma glucose, glucose tolerance and glycaemic response to feeding. Accordingly, plasma insulin responses were unchanged suggesting that the observed enhancement of insulin sensitivity was responsible for the improvement in glycaemic control. These data indicate that sub-chronic exposure to GIP and GLP-1 metabolites does not result in physiological impairment of insulin secretion or blood glucose control. GIP(3-42) might exert an overall beneficial effect by improving insulin sensitivity through extrapancreatic action.

La ciudad de Rávena y los paisajes de la abstracción en "Deserto Rosso" de Michelangelo Antonioni

La presente investigación trata de poner énfasis en la importancia del paisaje en Deserto Rosso de Michelangelo Antonioni, erigiéndose este como elemento fundamental de la trama argumental del filme. Partiendo de esta premisa, se analiza el significado de dicho paisaje en el contexto socioartístico de los años 60. La interacción del hombre con su entorno parece ser el punto de partida para una reflexión más profunda sobre el devenir humano. Las nuevas conquistas estéticas alcanzadas y el análisis históricoartístico de los precedentes más inmediatos del filme, sitúan a Deserto Rosso como obra cumbre de la neovanguardia posmoderna europea.

Some thoughts on Juan Antonio Ramírez´s iconologic-paranoid method for the study of Dali´s works

In 1990, Juan Antonio Ramírez made known his iconological paranoiac method to the academic world. It is a system devised to study Dalí´s work, born of happy matrimony between the catalonian artist´s critical paranoiac method and the first iconographic school of Warburg and Panofsky. What, at first sight, seemed to be an extravagant methodology with little academic credibility, turned out to be, by going forward in time, an effective research method when analyzing Dali´s initial works. It is no wonder that, at the beginning of XXI century, this hybridization between Dalí´s and Panofsky’s methods, were regarded as a strange and nonsensical idea. Nevertheless, twenty years after, blatant examples have been noted, which endorse the advantages of this new system for “iconographic” study. As usual, this new contribution by Juan Antonio Ramirez to art history methodology is called upon to have a successful future survival, in forthcoming generations. This article, attempts to analyze this method, inquiring into the validity, effectiveness and practical utility.

Tuberous sclerosis complex: clinical features, diagnosis, and prevalence within Northern Ireland

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 and TSC2 genes on chromosomes 9 and 16 respectively. Diagnosis is based on clinical features but can be difficult as a result of variable phenotypic expression. With the advantage of mutation analysis in making a diagnosis of TSC, and improved identification of the associated clinical features, there have been few new data on its prevalence and on the proportion of cases due to new mutations. We have performed a retrospective epidemiological study on the prevalence of TSC, the clinical features attributed to it, and the availability of mutational analysis. We identified 73 known patients with TSC (5 deceased): 39 were female and 34 male. Ages ranged from 10 months to 69 years, with a mean age of 27 years 11 months (SD 16y 10mo). The point prevalence of TSC in our study was estimated at I out of 24 956 on the prevalence day (30 April 2004). The majority of patients (42.5%) were diagnosed at less than 15 months of age; 25% were not given a diagnosis on first developing symptoms. In all, 93.2% had epilepsy and 71.2% had a learning disability.* A mutation was identified in 95.8% of those tested (26% TSC1 and 74% TSC2). TSC2 mutations were correlated with a more severe phenotype. The new mutation rate was calculated at 64%. We conclude that the prevalence of TSC is higher than previously calculated. We recommend that all children with epilepsy be assessed for features of TSC. Larger studies will be required to assess the prevalence of mutations in each gene, and genotype-phenotype correlation.

Flow-mediated dilatation of the brachial artery is a poorly reproducible indicator of microvascular function in Type I diabetes mellitus

Aim: Two Type I diabetes and control group comparator studies were conducted to assess the reproducibility of FMD and to analyse blood flow data normally discarded during FMD measurement.

Design: The studies were sequential and differed only with regard to operator and ultrasound machine. Seventy-two subjects with diabetes and 71 controls were studied in total.

Methods: Subjects had FMD measured conventionally. Blood velocity waveforms were averaged over 10 pulses post forearm ischaemia and their component frequencies analysed using the wavelet transform, a mathematical tool for waveform analysis. The component frequencies were grouped into 11 bands to facilitate analysis.

Results: Subjects were well-matched between studies. In Study 1, FMD was significantly impaired in subjects with Type I diabetes vs. controls (median 4.35%, interquartile range 3.10-4.80 vs. 6.50, 4.79-9.42, P < 0.001). No differences were detected between groups in Study 2, however. However, analysis of blood velocity waveforms yielded significant differences between groups in two frequency bands in each study.

Conclusions: This report highlights concerns over the reproducibility of FMD measures. Further work is required to fully elucidate the role of analysing velocity waveforms after forearm ischaemia.

Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials

Background: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials. Methods: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast cancer in 46 trials of polychemotherapy versus not (non-taxane-based polychemotherapy, typically about six cycles; trial start dates 1975-96, median 1984) and about 14 000 women with ER-poor breast cancer in 50 trials of tamoxifen versus not (some trials in the presence and some in the absence of polychemotherapy; trial start dates 1972-93, median 1982). Findings: In women with ER-poor breast cancer, polychemotherapy significantly reduced recurrence, breast cancer mortality, and death from any cause, in those younger than 50 years and those aged 50-69 years at entry into trials of polychemotherapy versus not. In those aged younger than 50 years (1907 women, 15% node-positive), the 10-year risks were: recurrence 33% versus 45% (ratio of 10-year risks 0·73, 2p<0·00001), breast cancer mortality 24% versus 32% (ratio 0·73, 2p=0·0002), and death from any cause 25% versus 33% (ratio 0·75, 2p=0·0003). In women aged 50-69 years (3965 women, 58% node-positive), the 10-year risks were: recurrence 42% versus 52% (ratio 0·82, 2p<0·00001), breast cancer mortality 36% versus 42% (ratio 0·86, 2p=0·0004), and death from any cause 39% versus 45% (ratio 0·87, 2p=0·0009). Few were aged 70 years or older. Tamoxifen had little effect on recurrence or death in women who were classified in these trials as having ER-poor disease, and did not significantly modify the effects of polychemotherapy. Interpretation: In women who had ER-poor breast cancer, and were either younger than 50 years or between 50 and 69 years, these older adjuvant polychemotherapy regimens were safe (ie, had little effect on mortality from causes other than breast cancer) and produced substantial and definite reductions in the 10-year risks of recurrence and death. Current and future chemotherapy regimens could well yield larger proportional reductions in breast cancer mortality.

Novel anti-inflammatory compound SEN1176 alleviates behavioural deficits induced following bilateral intrahippocampal injection of aggregated amyloid-beta(1-42).

Behavioral effects of a novel anti-inflammatory SEN1176 were investigated. This pyrrolo[3,2-e][1,2,4]triazolo[1,5-a]pyrimidine suppresses amyloid-ß (Aß)1-42-induced macrophage production of nitric oxide, TNF-a, IL-1ß, and IL-6 in a dose-dependent fashion, an activity profile consistent with SEN1176 being a neuroinflammation inhibitor. Using male Sprague-Dawley rats, SEN1176 was examined relative to detrimental behavioral effects induced following bilateral intrahippocampal (IH) injections of aggregated Aß1-42. The rats were trained to respond under an alternating-lever cyclic-ratio (ALCR) schedule of food reinforcement, enabling measurement of parameters of operant performance that reflect aspects of learning and memory. Under the ALCR schedule, orally administered SEN1176 at 5, 20, or 30 mg/kg was effective in reducing the behavioral deficit caused by bilateral IH aggregated Aß1-42 injections in a dose-related manner over a 90-day treatment period. SEN1176 at 20 and 30 mg/kg significantly reduced lever switching errors and, at doses of 5, 10, and 30 mg/kg, significantly reduced incorrect lever perseverations, indicating a reduction of the behavioral deficit induced as a result of inflammation following IH Aß1-42 injections. When treatment with SEN1176 was instigated 30 days after IH Aß1-42 injections, it resulted in progressive protection, and withdrawal of SEN1176 treatment 60 days after IH Aß1-42 injections revealed partial retention of the protective effect. SEN1176 also significantly reduced numbers of activated astrocytes adjacent to the aggregated Aß1-42 injection sites. These results indicate the potential of SEN1176 for alleviating chronic neuroinflammatory processes related to brain Aß deposition that affect learning and memory in Alzheimer's disease.

A three-position spectral line survey of Sagittarius B2 between 218 and 263 GHz. I. The observational data

We have surveyed the frequency band 218.30-263.55 GHz toward the core positions N and M and the quiescent cloud position NW in the Sgr B2 molecular cloud using the Swedish-ESO Submillimetre Telescope. In total 1730, 660, and 110 lines were detected in N, M, and NW, respectively, and 42 different molecular species were identified. The number of unidentified lines are 337, 51, and eight. Toward the N source, spectral line emission constitutes 22% of the total detected flux in the observed band, and complex organic molecules are the main contributors. Toward M, 14% of the broadband flux is caused by lines, and SO2 is here the dominant source of emission. NW is relatively poor in spectral lines and continuum. In this paper we present the spectra together with tables of suggested line identifications.

Evolution of Organisational Structure and Capabilities in Internationalising Banks: The CEE Operations of UniCredit's Vienna Office

Cross-border integration is the central management issue for banks that expand internationally, and this is especially true in Central and Eastern Europe, where the pace of internationalisation through mergers and acquisitions has been rapid. A critical challenge in cross-border integration is aligning a multinational company's formal organizational structure with the distribution of capabilities across its subsidiary units, and this issue is explored by tracking the co-evolution of organizational structure and capabilities during the internationalisation of a large banking network into this region. Our focus is the Vienna head office of Bank Austria Creditanstalt, which was acquired first by HypoVereinsbank (Germany) and then UniCredit (Italy). Despite its formal role being downgraded during these changes, the unit continued to develop its distinctive capabilities. The key insight our article offers is that managing cross-border integration is not simply about recognizing the value of the distinctive capabilities of individual units and designing formal structures that successfully align with them. It is also about understanding the need for dynamic interaction between formal corporate structure and individual units' desires to retain power and influence, which have significant implications for the development of their organizational capabilities.

Numerical analysis of intralaminar failure mechanisms in composite structures, Part I: FE implementation

This paper presents a three-dimensional continuum damage mechanics-based material model which was implemented in an implicit finite element code to simulate the progressive intralaminar degradation of fibre reinforced laminates. The damage model is based on ply failure mechanisms and uses seven damage variables assigned to tensile, compressive and shear damage at a ply level. Non-linear behaviour and irreversibility were taken into account and modelled. Some issues on the numerical implementation of the damage model are discussed and solutions proposed. Applications of the methodology are presented in Part II

Klebsiella pneumoniae outer membrane protein A is required to prevent the activation of airway epithelial cells

Outer membrane protein A (OmpA) is a class of proteins highly conserved among the Enterobacteriaceae family and throughout evolution. Klebsiella pneumoniae is a capsulated Gram-negative pathogen. It is an important cause of community-acquired and nosocomial pneumonia. Evidence indicates that K. pneumoniae infections are characterized by a lack of an early inflammatory response. Data from our laboratory indicate that K. pneumoniae CPS helps to suppress the host inflammatory response. However, it is unknown whether K. pneumoniae employs additional factors to modulate host inflammatory responses. Here, we report that K. pneumoniae OmpA is important for immune evasion in vitro and in vivo. Infection of A549 and normal human bronchial cells with 52OmpA2, an ompA mutant, increased the levels of IL-8. 52145-?wca ompA, which does not express CPS and ompA, induced the highest levels of IL-8. Both mutants could be complemented. In vivo, 52OmpA2 induced higher levels of tnfa, kc, and il6 than the wild type. ompA mutants activated NF-?B, and the phosphorylation of p38, p44/42, and JNK MAPKs and IL-8 induction was via NF-?B-dependent and p38- and p44/42-dependent pathways. 52OmpA2 engaged TLR2 and -4 to activate NF-?B, whereas 52145-?wca ompA activated not only TLR2 and TLR4 but also NOD1. Finally, we demonstrate that the ompA mutant is attenuated in the pneumonia mouse model. The results of this study indicate that K. pneumoniae OmpA contributes to attenuate airway cell responses. This may facilitate pathogen survival in the hostile environment of the lung. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Dissection of Host Cell Signal Transduction during Acinetobacter baumannii – Triggered Inflammatory Response

Infected airway epithelial cells up-regulate the expression of chemokines, chiefly IL-8, and antimicrobial molecules including ß-defensins (BD). Acinetobacter baumannii is a cause of hospital-acquired pneumonia. We examined whether A. baumannii induced the expressions of IL-8 and BD2 by airway epithelial cells and the receptors implicated in bacterial detection. A549 and human primary airway cells released IL-8 upon infection. A. baumannii-infected cells also increased the expression of BD2 which killed A. baummannii strains. IL-8 induction was via NF-B and mitogen-activated kinases p38 and p44/42-dependent pathways. A. baumannii engaged Toll-like receptor (TLR) 2 and TLR4 pathways and A549 cells could use soluble CD14 as TLRs co-receptor. A. baumannii lipopolysaccharide stimulated IL-8 release by A549 cells and sCD14 facilitated the recognition of the lipopolysaccharide. Mass spectrometry analysis revealed that A. baumannii lipid A structure matches those with endotoxic potential. These results demonstrate that airway epithelial cells produce mediators important for A. baumannii clearance. © 2010 March et al.

Comparison between laser scanning tomography and computerised image analysis of the optic disc

Aims - To study the interchangeability of the measurements of the optic disc topography obtained by one computerised image analyser and one confocal laser tomographic scanner. Methods - One eye of 28 patients with glaucoma or glaucoma suspects was studied. All cases had simultaneous stereoscopic disc photographs taken with the fundus camera Topcon TRC-SS and optic disc examination with the Heidelberg retina tomograph (HRT) during the same visit. The optic disc photographs were digitised and analysed with the Topcon ImageNet (TI) system. Three variables of the optic disc topography provided by the TI and the HRT were compared - cup volume (CV), rim area (RA), and cup area to disc area ratio (CA/DA). Results - The mean values of CV and RA provided by the TI (0.52 (SD 0.32) mm and 1.58 (0.39) mm , respectively) were greater (p <0.01) than the mean values of CV and RA determined by the HRT (0.32 (0.25) mm , and 1.33 (0.47) mm , respectively). The mean value of CA/DA provided by the TI (0.42 (0.14)) and the HRT (0.42 (0.18)) was similar (p = 0.93). Correlation coefficients between measurements obtained by the two methods ranged from 0.53 to 0.73. Conclusion - There was a significant discrepancy in the measurements of rim area and cup volume of the optic disc obtained by a computerised image analyser and a laser scanning tomograph.