98 research outputs found

    Fly ash-derived MCM-41 as a low-cost silica support for polyethyleneimine in post-combustion CO2 capture

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    The mesoporous silicate molecular sieve, MCM-41, has been synthesized from pulverized coal fly ash (PFA), where the silicate filtrate used is a by-product from hydrothermal zeolite production. Rice husk ash was also used for comparison but fusion with sodium hydroxide was used to prepare the silicate filtrate, along similar lines to earlier reports of using PFA as a precursor for MCM-41 synthesis. The MCM-41 samples are chemically and mineralogically similar to a commercially available sample, but with higher pore volumes dominated by mesopores (0.92–1.13 cf. 0.88 cm3 g−1). After polyethyleneimine (PEI) impregnation for CO2 capture, the ash derived MCM-41 samples displayed higher uptakes than the commercial sample with the maximum achievable PEI loading of 60 Wt.% PEI (dry basis) before particle agglomeration occurs, approximately 13 compared to 11 Wt.%, respectively, the latter being comparable to earlier reports in the literature. The PFA sample that displays the fastest kinetics to achieve 90% of the equilibrium uptake had the largest mesopore volume of 1.13 cm3 g−1. Given the PFA-derived MCM-41 uses a waste silicate solution for hydrothermal preparation and no prior preparation is needed, production costs are estimated to be considerable lower where silicate solutions need to be prepared by base treatment, even if ash is used, as for the RHA derived MCM-41 used here

    Enabling large-scale design, synthesis and validation of small molecule protein-protein antagonists

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    Although there is no shortage of potential drug targets, there are only a handful known low-molecular-weight inhibitors of protein-protein interactions (PPIs). One problem is that current efforts are dominated by low-yield high-throughput screening, whose rigid framework is not suitable for the diverse chemotypes present in PPIs. Here, we developed a novel pharmacophore-based interactive screening technology that builds on the role anchor residues, or deeply buried hot spots, have in PPIs, and redesigns these entry points with anchor-biased virtual multicomponent reactions, delivering tens of millions of readily synthesizable novel compounds. Application of this approach to the MDM2/p53 cancer target led to high hit rates, resulting in a large and diverse set of confirmed inhibitors, and co-crystal structures validate the designed compounds. Our unique open-access technology promises to expand chemical space and the exploration of the human interactome by leveraging in-house small-scale assays and user-friendly chemistry to rationally design ligands for PPIs with known structure. © 2012 Koes et al

    An observational study on the expression levels of MDM2 and MDMX proteins, and associated effects on P53 in a series of human liposarcomas

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    Background: Inactivation of wild type P53 by its main cellular inhibitors (MDM2 and MDMX) is a well recognised feature of tumour formation in liposarcomas. MDM2 over-expression has been detected in approximately 80% of liposarcomas but only limited information is available about MDMX over-expression. To date, we are not aware of any study that has described the patterns of MDM2 and MDMX co-expression in liposarcomas. Such information has become more pertinent as various novel MDM2 and/or MDMX single and dual affinity antagonist compounds are emerging as an alternative approach for potential targeted therapeutic strategies. Methods. We analysed a case series of 61 fully characterized liposarcomas of various sub-types by immunohistochemistry, to assess the expression levels of P53, MDM2 and MDMX, simultaneously. P53 sequencing was performed in all cases that expressed P53 protein in 10% or more of cells to rule out mutation-related over-expression. Results: 50 cases over-expressed MDM2 and 42 of these co-expressed MDMX at varying relative levels. The relative expression levels of the two proteins with respect to each other were subtype-dependent. This apparently affected the detected levels of P53 directly in two distinct patterns. Diminished levels of P53 were observed when MDM2 was significantly higher in relation to MDMX, suggesting a dominant role for MDM2 in the degradation of P53. Higher levels of P53 were noted with increasing MDMX levels suggesting an interaction between MDM2 and MDMX that resulted in a reduced efficiency of MDM2 in degrading P53. Of the 26 cases of liposarcoma with elevated P53 expression, 5 were found to have a somatic mutation in the P53 gene. Conclusions: The results suggest that complex dynamic interactions between MDM2 and MDMX proteins may directly affect the cellular levels of P53. This therefore suggests that careful characterization of both these markers will be necessary in tumours when considering in vivo evaluation of novel blocker compounds for MDM proteins, as a therapeutic strategy to restore wild type P53 function

    A Qualitative Exploration of Factors Affecting Group Cohesion and Team Play in Multiplayer Online Battle Arenas (MOBAs)

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    Previous research examining the social psychology of video-gaming has tended to focus on Massively Multiplayer Online Role Playing Game (MMORPG) environments, such as World of Warcraft. Although many online group processes have been examined using this game, this genre does not enforce cooperative play and studies tend to be based on very large groups. Newer genres are being developed and played which have so far not been studied. The genre known as Multiplayer Online Battle Arenas (MOBAs) are attracting large numbers of players and success depends on effective team playing within smaller groups. The study reported here explores team play within MOBAs. Due to the lack of literature examining this genre, Corbin and Strauss’ (2008) Grounded Theory was used to analyse participants’ subjective experiences of playing MOBAs to create a conceptual model. A focus group pilot study informed the development of questions and then semi-structured interviews took place with twelve participants; 1 female and 11 male students aged between 18-21 years. Participants were required to have recent and frequent MOBA exposure, but with different preferences regarding roles and experience. Data was analysed using open, axial and selective coding and the resulting model depicts a scale, as optimal team performance was linked to a balance between factors. The core category “Communication” was heavily influenced by the relationship between teammates (friends or strangers). The balance of “Communication” affected the balance of the final three categories: “Team Composition”, “Psychological State” and “Level of Play”. The conceptual model is critically linked with traditional group processes, such as Belbin’s (1993) team roles, Tuckman’s (1965) model of group development and the perceptions and behaviour during the state of deindividuation (Taylor & MacDonald, 2002). The model has real-world application in both social and professional virtual environments, whilst contributing more broadly to research in Cyberpsychology and Social Psychology. Further research is suggested which will test predictions based on a predictive model

    Roadside verges and cemeteries: Comparative analysis of anthropogenic orchid habitats in the Eastern Mediterranean

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    Several important habitats have become threatened in the last few centuries in the Mediterranean Basin due to major changes adopted in land-use practices. The consequent loss of natural and seminatural orchid habitats leads to the appreciation of small anthropogenic habitats, such as cemeteries and roadside verges. Colonization of cemeteries and roadside verges by orchids has long been known, but no study to date compared the suitability of these two anthropogenic habitats for orchids. Therefore, in this paper our aim was to survey cemeteries and roadside verges and to compare these two habitats regarding their role in conserving Mediterranean terrestrial orchids. We conducted field surveys in three Mediterranean islands, Cyprus, Crete, and Lesbos, where both cemeteries and roadside verges were sampled on a geographically representative scale. We found a total of almost 7,000 orchid individuals, belonging to 77 species in the two anthropogenic habitat types. Roadside verges hosted significantly more individuals than cemeteries in Crete and Lesbos, and significantly more species across all three islands. Our results suggest that although cemeteries have a great potential conservation value in other parts of the world, intensive maintenance practices that characterized cemeteries in these three islands renders them unable to sustain valuable plant communities. On the other hand, roadside verges play a prominent role in the conservation of Mediterranean orchids in Cyprus and Greece. The pioneer status of roadside verges facilitates their fast colonization, while roads serve as ecological corridors in fragmented landscapes

    Energization-dependent endogenous activation of proton conductance in skeletal muscle mitochondria

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    Leak of protons into the mitochondrial matrix during substrate oxidation partially uncouples electron transport from phosphorylation of ADP, but the functions and source of basal and inducible proton leak in vivo remain controversial. In the present study we describe an endogenous activation of proton conductance in mitochondria isolated from rat and mouse skeletal muscle following addition of respiratory substrate. This endogenous activation increased with time, required a high membrane potential and was diminished by high concentrations of serum albumin. Inhibition of this endogenous activation by GDP [classically considered specific for UCPs (uncoupling proteins)], carboxyatractylate and bongkrekate (considered specific for the adenine nucleotide translocase) was examined in skeletal muscle mitochondria from wild-type and Ucp3-knockout mice. Proton conductance through endogenously activated UCP3 was calculated as the difference in leak between mitochondria from wild-type and Ucp3-knockout mice, and was found to be inhibited by carboxyatractylate and bongkrekate, but not GDP. Proton conductance in mitochondria from Ucp3-knockout mice was strongly inhibited by carboxyatractylate, bongkrekate and partially by GDP. We conclude the following: (i) at high protonmotive force, an endogenously generated activator stimulates proton conductance catalysed partly by UCP3 and partly by the adenine nucleotide translocase; (ii) GDP is not a specific inhibitor of UCP3, but also inhibits proton translocation by the adenine nucleotide translocase; and (iii) the inhibition of UCP3 by carboxyatractylate and bongkrekate is likely to be indirect, acting through the adenine nucleotide translocase

    The mental health continuum-short form: the structure and application for cross-cultural studies-A 38 nation study

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    Objective: The Mental Health Continuum-Short Form (MHC-SF) is a brief scale measuring positive human functioning. The study aimed to examine the factor structure and to explore the cross-cultural utility of the MHC-SF using bifactor models and exploratory structural equation modelling. Method: Using multigroup confirmatory analysis (MGCFA) we examined the measurement invariance of the MHC-SF in 38 countries (university students, N = 8,066; 61.73% women, mean age 21.55 years). Results: MGCFA supported the cross-cultural replicability of a bifactor structure and a metric level of invariance between student samples. The average proportion of variance explained by the general factor was high (ECV =.66), suggesting that the three aspects of mental health (emotional, social, and psychological well-being) can be treated as a single dimension of well-being. Conclusion: The metric level of invariance offers the possibility of comparing correlates and predictors of positive mental functioning across countries; however, the comparison of the levels of mental health across countries is not possible due to lack of scalar invariance. Our study has preliminary character and could serve as an initial assessment of the structure of the MHC-SF across different cultural settings. Further studies on general populations are required for extending our findings.info:eu-repo/semantics/acceptedVersio

    As cold as a fish? Relationships between the Dark Triad personality traits and affective experience during the day: A day reconstruction study

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    The Dark Triad of personality is a cluster of three socially aversive personality traits: Machiavellianism, narcissism and psychopathy. These traits are associated with a selfish, aggressive and exploitative interpersonal strategy. The objective of the current study was to establish relationships between the Dark Triad traits (and their dimensions) and momentary affect. Machiavellianism, grandiose narcissism, vulnerable narcissism and the dimensions of the Triarchic model of psychopathy (namely, boldness, meanness and disinhibition) were examined. We used the Day Reconstruction Method, which is based on reconstructing affective states experienced during the previous day. The final sample consisted of 270 university students providing affective ratings of 3047 diary episodes. Analyses using multilevel modelling showed that only boldness had a positive association with positive affective states and affect balance, and a negative association with negative affective states. Grandiose narcissism and its sub-dimensions had no relationship with momentary affect. The other dark traits were related to negative momentary affect and/or inversely related to positive momentary affect and affect balance. As a whole, our results empirically demonstrated distinctiveness of the Dark Triad traits in their relationship to everyday affective states. These findings are not congruent with the notion that people with the Dark Triad traits, who have a dispositional tendency to manipulate and exploit others, are generally cold and invulnerable to negative feelings. The associations between the Dark Triad and momentary affect were discussed in the contexts of evolutionary and positive psychology, in relation to the role and adaptive value of positive and negative emotions experienced by individuals higher in Machiavellianism, narcissism and psychopathy

    Circadian oscillator proteins across the kingdoms of life : Structural aspects 06 Biological Sciences 0601 Biochemistry and Cell Biology

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    Circadian oscillators are networks of biochemical feedback loops that generate 24-hour rhythms and control numerous biological processes in a range of organisms. These periodic rhythms are the result of a complex interplay of interactions among clock components. These components are specific to the organism but share molecular mechanisms that are similar across kingdoms. The elucidation of clock mechanisms in different kingdoms has recently started to attain the level of structural interpretation. A full understanding of these molecular processes requires detailed knowledge, not only of the biochemical and biophysical properties of clock proteins and their interactions, but also the three-dimensional structure of clockwork components. Posttranslational modifications (such as phosphorylation) and protein-protein interactions, have become a central focus of recent research, in particular the complex interactions mediated by the phosphorylation of clock proteins and the formation of multimeric protein complexes that regulate clock genes at transcriptional and translational levels. The three-dimensional structures for the cyanobacterial clock components are well understood, and progress is underway to comprehend the mechanistic details. However, structural recognition of the eukaryotic clock has just begun. This review serves as a primer as the clock communities move towards the exciting realm of structural biology
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