Application of the fracture mechanics safety analysis to structural steel sections

This contribution presents a fracture mechanics safety analysis with finite element models applied on I-beams with defects in the tension flange. The moment rotation at room temperature was observed in the light of the toughness behaviour in front of initial notches. The results show very early crack initiation due to very large initial defects. The experiments were accompanied by a fracture mechanics safety analysis employing FEM. However, in temperature ranges of buildings plastically designed beams are subjected to sufficient rotation capacity, i.e. rotational ductility could be found.     

Chronic morphine administration increases beta-adrenergic receptor kinase (beta ARK) levels in the rat locus coeruleus

Based on the established role of beta-adrenergic receptor kinase (beta ARK) and beta-arrestin in the desensitization of several G protein-coupled receptors, we investigated the effect of chronic morphine administration on beta ARK and beta-arrestin levels in selected brain areas. Levels of beta ARK were measured by blot immunolabeling analysis using antibodies specific for two known forms of beta ARK, i.e., beta ARK1 and beta ARK2. It was found that chronic morphine treatment produced an approximately 35% increase in levels of beta ARK1 immunoreactivity in the locus coeruleus, but not in several other brain regions studied. In contrast, chronic morphine treatment failed to alter levels of beta ARK2 immunoreactivity in any of the brain regions studied. Levels of beta-arrestin immunoreactivity, measured using an antiserum that recognizes two major forms of this protein in brain, were also found to increase (by approximately 20%) in the locus coeruleus. It is proposed that chronic morphine regulation of beta ARK1 and beta-arrestin levels may contribute to opioid-receptor tolerance that is known to occur in this brain region.     

The calcium channel blocker amlodipine raises serum dehydroepiandrosterone sulfate and androstenedione, but lowers serum cortisol, in insulin-resistant obese and hypertensive men

To determine whether the calcium channel blocker amlodipine improves glucose tolerance and alters serum adrenal androgen and glucocorticoid levels in insulin-resistant men, 24 obese and hypertensive men were enrolled into a single blind, placebo-controlled study. An amlodipine group (n = 12) and a placebo group (n = 12) were studied before and after treatment with either amlodipine (5 mg) or placebo capsule twice daily for 7 days by determining serum insulin, glucose, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and cortisol in the fasting state and during an oral glucose tolerance test. Amlodipine treatment 1) lowered fasting serum insulin (from 273 +/- 19 to 200 +/- 17 pmol/L; P < 0.0005) and glucose (from 5.4 +/- 0.1 to 5.1 +/- 0.1 mmol/L; P < 0.02), 2) reduced the area under the curve for glucose (from 1342 +/- 25 to 1198 +/- 23 mmol/L.min; P = 0.0001) and the area under the curve for insulin (from 155.5 +/- 7.8 to 103.9 +/- 4.3 nmol/L.min; P = 0.0001) during the oral glucose tolerance test, 3) increased fasting serum DHEA-S (from 5.19 +/- 0.37 to 7.95 +/- 0.58 mumol/L; P = 0.0001) and androstenedione (from 5.65 +/- 0.65 to 6.83 +/- 0.53 nmol/L; P < 0.01), and 4) decreased fasting serum cortisol (from 538 +/- 35 to 494 +/- 26 nmol/L; P < 0.05). Fasting serum androstenedione declined slightly in the placebo group (from 5.96 +/- 0.60 to 5.74 +/- 0.57 nmol/L; P < 0.005), but no change occurred in glucose tolerance, fasting serum DHEA-S, or cortisol. We conclude that amlodipine treatment improves glucose tolerance, reduces fasting and glucose-stimulated serum insulin levels, increases serum DHEA-S and androstenedione levels, and decreases circulating cortisol.     

Lewis and Fischer rat strains display differences in biochemical, electrophysiological and behavioral parameters: studies in the nucleus accumbens and locus coeruleus of drug naive and morphine-treated animals

We investigated the effects of the systemic administration of thymosin alpha 1 plus relatively low doses of human recombinant interleukin-2 or very low doses of interferon alpha,beta in untreated and cyclophosphamide (CY)-treated DBA/2 mice challenged either subcutaneously or intravenously (i.v.) with Friend erythroleukemia cells (FLC). Both treatments resulted in the complete regression of subcutaneous tumor and cured a significative percentage of mice. They also increased the survival time of mice i.v. injected with large numbers of FLC. Neither immunotherapy alone nor CY, alone or in combination with single cytokines, produced similar effects. The antitumor action of these combined chemoimmunotherapy protocols seems to involve activation of the immune response since (a) a synergistic increase of the cytotoxicity of spleen cells was demonstrated in treated mice; (b) selective in vivo depletion of asialo-GM1, CD4, or CD8-positive cells abrogated this antitumor activity; and (c) a high lymphoid cell infiltration was found at the tumor site and in the livers of treated mice.     

Chronic morphine induces visible changes in the morphology of mesolimbic dopamine neurons

The mesolimbic dopamine system, which arises in the ventral tegmental area (VTA), is an important neural substrate for opiate reinforcement and addiction. Chronic exposure to opiates is known to produce biochemical adaptations in this brain region. We now show that these adaptations are associated with structural changes in VTA dopamine neurons. Individual VTA neurons in paraformaldehyde-fixed brain sections from control or morphine-treated rats were injected with the fluorescent dye Lucifer yellow. The identity of the injected cells as dopaminergic or nondopaminergic was determined by immunohistochemical labeling of the sections for tyrosine hydroxylase. Chronic morphine treatment resulted in a mean approximately 25% reduction in the area and perimeter of VTA dopamine neurons. This reduction in cell size was prevented by concomitant treatment of rats with naltrexone, an opioid receptor antagonist, as well as by intra-VTA infusion of brain-derived neurotrophic factor. In contrast, chronic morphine treatment did not alter the size of nondopaminergic neurons in the VTA, nor did it affect the total number of dopaminergic neurons in this brain region. The results of these studies provide direct evidence for structural alterations in VTA dopamine neurons as a consequence of chronic opiate exposure, which could contribute to changes in mesolimbic dopamine function associated with addiction.     

Immunological properties of human decidual macrophages--a possible role in intrauterine immunity

Our aim was to investigate the contribution of decidual macrophages, which constitute an important immune component of the decidua in late gestation, to intrauterine defence mechanisms. Using flow cytometry we examined the ability of decidual macrophages, isolated from term decidua, to bind and phagocytose fluorescence-labelled bacterial and yeast bioparticles. We also assessed their ability to generate superoxide radicals and tumour necrosis factor-alpha following lipopolysaccharide challenge. Decidual macrophages bound bacterial and yeast particles in a dose-dependent manner, which subsequently led to phagocytosis. These macrophages also produced superoxide radicals and the pro-inflammatory cytokine TNF-alpha when challenged with bacterial lipopolysaccharides. These results suggest a role for decidual macrophages in pathogen recognition and clearance during pregnancy, and, therefore, they are likely to protect the fetus against intrauterine infections which might otherwise lead to preterm labour.     

Investigation of polymer inserts as prototyping tooling for micro injection moulding

An increasing number of microfluidic applications linked with a strong demand for low-cost solutions has pushed research activities towards the development of polymer-based microfluidic systems. This requires the use of micro injection moulding technology to accurately replicate polymer micro parts; however, the tooling cost associated with this manufacturing route remains relatively high. The purpose of this paper is to investigate the feasibility of utilising polymer inserts for prototype tooling in micro injection moulding that can reduce product development time and cost associated with the design and testing of microfluidic systems prior to mass fabrication.     

Validation of the performance of a GMO multiplex screening assay based on microarray detection

A new screening method for the detection and identification of GMO, based on the use of multiplex PCR followed by microarray, has been developed and is presented. The technology is based on the identification of quite ubiquitous GMO genetic target elements first amplified by PCR, followed by direct hybridisation of the amplicons on a predefined microarray (DualChip^® GMO, Eppendorf, Germany). The validation was performed within the framework of a European project (Co-Extra, contract no 007158) and in collaboration with 12 laboratories specialised in GMO detection. The present study reports the strategy and the results of an ISO complying validation of the method carried out through an inter-laboratory study. Sets of blind samples were provided consisting of DNA reference materials covering all the elements detectable by specific probes present on the array. The GMO concentrations varied from 1% down to 0.045%. In addition, a mixture of two GMO events (0.1% RRS diluted in 100% TOPAS19/2) was incorporated in the study to test the robustness of the assay in extreme conditions. Data were processed according to ISO 5725 standard. The method was evaluated with predefined performance criteria with respect to the EC CRL method acceptance criteria. The overall method performance met the acceptance criteria; in particular, the results showed that the method is suitable for the detection of the different target elements at 0.1% concentration of GMO with a 95% accuracy rate. This collaborative trial showed that the method can be considered as fit for the purpose of screening with respect to its intra- and inter-laboratory accuracy. The results demonstrated the validity of combining multiplex PCR with array detection as provided by the DualChip^® GMO (Eppendorf, Germany) for the screening of GMO. The results showed that the technology is robust, practical and suitable as a screening tool.