632 research outputs found

    Managing risks within international hotel construction projects

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    The study highlights risk identification, mitigation, management and evaluation in relation to hotel construction, more specifically to the hotels built and owned by the 'Hotel Investments Company Limited', who construct and operate four and five star hotels globally. The Company constructed a hotel in Tripoli, Libya and was bound by certain economical and/or political constraints. The study outlines the benefits achieved in building the hotel and establishes the reason why the company chose to do so. Firstly it outlines, information regarding the Company, to better understand how the company functions and how management deals with situations they maybe faced with in relation to international hotel development. Secondly, an analysis on the hotel project in Tripoli, how the concept evolved, its viability, what risk procedures were adopted initially, what risks were identified during the process, reactions to such risks and the measures adopted to control them and how they saw the project through to its completion. During the course of this research it will be demonstrated that having prior knowledge in anticipating situations will be beneficial to making informed decisions and to a certain degree will prevent setbacks from occurring. All names and sources of information pertaining to this case study have been substituted

    The effect of turmeric (Curcumin) supplementation on cytokine and inflammatory marker responses following 2 hours of endurance cycling

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    Background: Endurance exercise induces IL-6 production from myocytes that is thought to impair intracellular defence mechanisms. Curcumin inhibits NF-κB and activator protein 1, responsible for cytokine transcription, in cell lines. The aim of this study was to investigate the effect of curcumin supplementation on the cytokine and stress responses following 2 h of cycling. Methods: Eleven male recreational athletes (35.5 ± 5.7 years; Wmax275 ± 6 W; 87.2 ± 10.3 kg) consuming a low carbohydrate diet of 2.3 ± 0.2 g/kg/day underwent three double blind trials with curcumin supplementation, placebo supplementation, and no supplementation (control) to observe the response of serum interleukins (IL-6, IL1-RA, IL-10), cortisol, c-reactive protein (CRP), and subjective assessment of training stress. Exercise was set at 95% lactate threshold (54 ± 7% Wmax) to ensure that all athletes completed the trial protocol. Results: The trial protocol elicted a rise in IL-6 and IL1-RA, but not IL-10. The supplementation regimen failed to produce statistically significant results when compared to placebo and control. IL-6 serum concentrations one hour following exercise were (Median (IQR): 2.0 (1.8-3.6) Curcumin; 4.8 (2.1-7.3) Placebo; 3.5 (1.9-7.7) Control). Differences between supplementation and placebo failed to reach statistical significance (p = 0.18) with the median test. Repeated measures ANOVA time-trial interaction was at p = 0.06 between curcumin supplementation and placebo. A positive correlation (p = 0.02) between absolute exercise intensity and 1 h post-exercise for IL-6 concentration was observed. Participants reported “better than usual” scores in the subjective assessment of psychological stress when supplementing with curcumin, indicating that they felt less stressed during training days (p = 0.04) compared to placebo even though there was no difference in RPE during any of the training days or trials. Conclusion: The limitations of the current regimen and trial involved a number of factors including sample size, mode of exercise, intensity of exercise, and dose of curcumin. Nevertheless these results provide insight for future studies with larger samples, and multiple curcumin dosages to investigate if different curcumin regimens can lead to statistically different interleukin levels when compared to a control and placebo

    Effects of Benzopyrene-7,8-Diol-9,10-Epoxide (BPDE) In Vitro and of Maternal Smoking In Vivo on Micronuclei Frequencies in Fetal Cord Blood

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    Up to 20% of pregnant women smoke and there is indirect evidence that certain tobacco-specific metabolites can cross the placental barrier and are genotoxic to the fetus. The presence of micronuclei results from chromosome damage and reflects the degree of underlying genetic instability. Fetal blood was obtained from the cord blood of 143 newborns (102 from nonsmoking mothers and 41 from mothers smoking >10 cigarettes/d during pregnancy). The micronucleus assay was performed following the guidelines established by the Human MicroNucleus project with modifications. To test the micronucleus assay, we evaluated the effect of a range of benzopyrene-7,8-diol-9,10-epoxide concentrations (from 3.125 nM to 4 microM) on cord blood from nonsmoking mothers. This validation showed that the number of micronuclei and apoptotic cells increased with benzopyrene-7,8-diol-9,10-epoxide dose (p < 0.0001 and p = 0.001, respectively); the minimal detectable effect was induced by 12.5 nM benzopyrene-7,8-diol-9,10-epoxide. In our sample, the number of MN was significantly higher in the 41 cord blood samples from mothers who smoked during pregnancy [smokers: 4 (1; 10.5); nonsmokers: 3 (0; 8); p = 0.016]. Therefore, the data reported herein support the hypothesis that tobacco compounds are able to induce chromosomal losses and breaks that are detectable as an increased number of micronuclei

    Black Stork Down: Military Discourses in Bird Conservation in Malta

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    Tensions between Maltese hunters and bird conservation NGOs have intensified over the past decade. Conservation NGOs have become frustrated with the Maltese State for conceding to the hunter lobby and negotiating derogations from the European Union’s Bird Directive. Some NGOs have recently started to organize complex field-operations where volunteers are trained to patrol the landscape, operate drones and other surveillance technologies, detect illegalities, and lead police teams to arrest poachers. We describe the sophisticated military metaphors which conservation NGOs have developed to describe, guide and legitimize their efforts to the Maltese public and their fee-paying members. We also discuss why such groups might be inclined to adopt these metaphors. Finally, we suggest that anthropological studies of discourse could help understand delicate contexts such as this where conservation NGOs, hunting associations and the State have ended in political deadlock

    Non-viral gene therapy that targets motor neurons in vivo

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    A major challenge in neurological gene therapy is safe delivery of transgenes to sufficient cell numbers from the circulation or periphery. This is particularly difficult for diseases involving spinal cord motor neurons such as amyotrophic lateral sclerosis (ALS). We have examined the feasibility of non-viral gene delivery to spinal motor neurons from intraperitoneal injections of plasmids carried by "immunogene" nanoparticles targeted for axonal retrograde transport using antibodies. PEGylated polyethylenimine (PEI-PEG12) as DNA carrier was conjugated to an antibody (MLR2) to the neurotrophin receptor p75 (p75NTR). We used a plasmid (pVIVO2) designed for in vivo gene delivery that produces minimal immune responses, has improved nuclear entry into post mitotic cells and also expresses green fluorescent protein (GFP). MLR2-PEI-PEG12 carried pVIVO2 and was specific for mouse motor neurons in mixed cultures containing astrocytes. While only 8% of motor neurons expressed GFP 72 h post transfection in vitro, when the immunogene was given intraperitonealy to neonatal C57BL/6J mice, GFP specific motor neuron expression was observed in 25.4% of lumbar, 18.3% of thoracic and 17.0% of cervical motor neurons, 72 h post transfection. PEI-PEG12 carrying pVIVO2 by itself did not transfect motor neurons in vivo, demonstrating the need for specificity via the p75NTR antibody MLR2. This is the first time that specific transfection of spinal motor neurons has been achieved from peripheral delivery of plasmid DNA as part of a non-viral gene delivery agent. These results stress the specificity and feasibility of immunogene delivery targeted for p75NTR expressing motor neurons, but suggests that further improvements are required to increase the transfection efficiency of motor neurons in vivo.Mary-Louise Rogers, Kevin S. Smith, Dusan Matusica, Matthew Fenech, Lee Hoffman, Robert A. Rush and Nicolas H. Voelcke

    Diffuse X-Ray Emission in the Cygnus OB2 Association

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    © 2023, The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/We present a large-scale study of diffuse X-ray emission in the nearby massive stellar association Cygnus OB2 as part of the Chandra Cygnus OB2 Legacy Program. We used 40 Chandra X-ray ACIS-I observations covering ∼1.0 deg2. After removing 7924 point sources detected in our survey and applying adaptive smoothing to the background-corrected X-ray emission, the adaptive smoothing reveals large-scale diffuse X-ray emission. Diffuse emission was detected in the subbands soft (0.5−1.2 keV) and medium (1.2−2.5 keV) and marginally in the hard (2.5−7.0 keV) band. From X-ray spectral analysis of stacked spectra we compute a total (0.5–7.0 keV) diffuse X-ray luminosity of LXdiff≈ 4.2 × 1034 erg s−1, characterized by plasma temperature components at kT ≈ 0.11, 0.40, and 1.18 keV, respectively. The H i absorption column density corresponding to these temperatures has a distribution consistent with N H = (0.43, 0.80, 1.39) × 1022 cm−2. The extended medium-band energy emission likely arises from O-type stellar winds thermalized by wind−wind collisions in the most populated regions of the association, while the soft-band emission probably arises from less energetic termination shocks against the surrounding interstellar medium. Supersoft and soft diffuse emission appears more widely dispersed and intense than the medium-band emission. The diffuse X-ray emission is generally spatially coincident with low-extinction regions that we attribute to the ubiquitous influence of powerful stellar winds from massive stars and their interaction with the local interstellar medium. Diffuse X-ray emission is volume filling, rather than edge brightened, oppositely to other star-forming regions. We reveal the first observational evidence of X-ray halos around some evolved massive stars.Peer reviewe

    Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

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    Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

    The role of GDP-L-galactose phosphorylase in the control of ascorbate biosynthesis

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    This is the final version. Available from American Society of Plant Biologists via the DOI in this record. Sequence data were sourced from The Arabidopsis Information Resource (https://www.arabidopsis.org/) under the following accession numbers: AT2G39770 for GMP, AT5G28840 for GME, AT4G26850 for GGP, AT3G02870 for GPP, AT4G33670 for L-GalDH, and AT3G47930 for L-GalLDH.The enzymes involved in L-ascorbate biosynthesis in photosynthetic organisms (the Smirnoff-Wheeler [SW] pathway) are well established. Here, we analyzed their subcellular localizations and potential physical interactions and assessed their role in the control of ascorbate synthesis. Transient expression of C terminal-tagged fusions of SW genes in Nicotiana benthamiana and Arabidopsis thaliana mutants complemented with genomic constructs showed that while GDP-D-mannose epimerase is cytosolic, all the enzymes from GDP-D-mannose pyrophosphorylase (GMP) to L-galactose dehydrogenase (L-GalDH) show a dual cytosolic/nuclear localization. All transgenic lines expressing functional SW protein green fluorescent protein fusions driven by their endogenous promoters showed a high accumulation of the fusion proteins, with the exception of those lines expressing GDP-L-galactose phosphorylase (GGP) protein, which had very low abundance. Transient expression of individual or combinations of SW pathway enzymes in N. benthamiana only increased ascorbate concentration if GGP was included. Although we did not detect direct interaction between the different enzymes of the pathway using yeast-two hybrid analysis, consecutive SW enzymes, as well as the first and last enzymes (GMP and L-GalDH) associated in coimmunoprecipitation studies. This association was supported by gel filtration chromatography, showing the presence of SW proteins in highmolecular weight fractions. Finally, metabolic control analysis incorporating known kinetic characteristics showed that previously reported feedback repression at the GGP step, combined with its relatively low abundance, confers a high-flux control coefficient and rationalizes why manipulation of other enzymes has little effect on ascorbate concentration.Biotechnology and Biological Sciences Research Council (BBSRC)Biotechnology and Biological Sciences Research Council (BBSRC)panish Ministerio de Educación, Cultura y Deporte para la formación del Profesorado UniversitarioI Plan Propio de Investigación, Transferencia y Divulgación Científica de la Universidad de Málaga, The Ministerio de Economía, Industria y CompetitividadEuropean Regional Development Fund (ERDF)panish “Ministerio de Economía, Industria y Competitividad/FEDER”Spanish Ministerio de Ciencia, Innovación y Universidade
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