164 research outputs found

    The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

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    This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intentionβ€”thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world

    Alpha-2-Macroglobulin Is Acutely Sensitive to Freezing and Lyophilization: Implications for Structural and Functional Studies.

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    Alpha-2-macroglobulin is an abundant secreted protein that is of particular interest because of its diverse ligand binding profile and multifunctional nature, which includes roles as a protease inhibitor and as a molecular chaperone. The activities of alpha-2-macroglobulin are typically dependent on whether its conformation is native or transformed (i.e. adopts a more compact conformation after interactions with proteases or small nucleophiles), and are also influenced by dissociation of the native alpha-2-macroglobulin tetramer into stable dimers. Alpha-2-macroglobulin is predominately present as the native tetramer in vivo; once purified from human blood plasma, however, alpha-2-macroglobulin can undergo a number of conformational changes during storage, including transformation, aggregation or dissociation. We demonstrate that, particularly in the presence of sodium chloride or amine containing compounds, freezing and/or lyophilization of alpha-2-macroglobulin induces conformational changes with functional consequences. These conformational changes in alpha-2-macroglobulin are not always detected by standard native polyacrylamide gel electrophoresis, but can be measured using bisANS fluorescence assays. Increased surface hydrophobicity of alpha-2-macroglobulin, as assessed by bisANS fluorescence measurements, is accompanied by (i) reduced trypsin binding activity, (ii) increased chaperone activity, and (iii) increased binding to the surfaces of SH-SY5Y neurons, in part, via lipoprotein receptors. We show that sucrose (but not glycine) effectively protects native alpha-2-macroglobulin from denaturation during freezing and/or lyophilization, thereby providing a reproducible method for the handling and long-term storage of this protein.Early Career Fellowship from the National Health and Medical Research Council GNT1012521(A.R.W.); Wellcome Trust Programme Grant (J.R.K., C.M.D.) 094425/Z/10/Z; Samsung GRO Grant (M.R.W.)This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013003

    How do we know that research ethics committees are really working? The neglected role of outcomes assessment in research ethics review

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    <p>Abstract</p> <p>Background</p> <p>Countries are increasingly devoting significant resources to creating or strengthening research ethics committees, but there has been insufficient attention to assessing whether these committees are actually improving the protection of human research participants.</p> <p>Discussion</p> <p>Research ethics committees face numerous obstacles to achieving their goal of improving research participant protection. These include the inherently amorphous nature of ethics review, the tendency of regulatory systems to encourage a focus on form over substance, financial and resource constraints, and conflicts of interest. Auditing and accreditation programs can improve the quality of ethics review by encouraging the development of standardized policies and procedures, promoting a common base of knowledge, and enhancing the status of research ethics committees within their own institutions. However, these mechanisms focus largely on questions of structure and process and are therefore incapable of answering many critical questions about ethics committees' actual impact on research practices.</p> <p>The first step in determining whether research ethics committees are achieving their intended function is to identify what prospective research participants and their communities hope to get out of the ethics review process. Answers to this question can help guide the development of effective outcomes assessment measures. It is also important to determine whether research ethics committees' guidance to investigators is actually being followed. Finally, the information developed through outcomes assessment must be disseminated to key decision-makers and incorporated into practice. This article offers concrete suggestions for achieving these goals.</p> <p>Conclusion</p> <p>Outcomes assessment of research ethics committees should address the following questions: First, does research ethics committee review improve participants' understanding of the risks and potential benefits of studies? Second, does the process affect prospective participants' decisions about whether to participate in research? Third, does it change participants' subjective experiences in studies or their attitudes about research? Fourth, does it reduce the riskiness of research? Fifth, does it result in more research responsive to the local community's self-identified needs? Sixth, is research ethics committees' guidance to researchers actually being followed?</p

    Functional clustering of yeast proteins from the protein-protein interaction network

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    BACKGROUND: The abundant data available for protein interaction networks have not yet been fully understood. New types of analyses are needed to reveal organizational principles of these networks to investigate the details of functional and regulatory clusters of proteins. RESULTS: In the present work, individual clusters identified by an eigenmode analysis of the connectivity matrix of the protein-protein interaction network in yeast are investigated for possible functional relationships among the members of the cluster. With our functional clustering we have successfully predicted several new protein-protein interactions that indeed have been reported recently. CONCLUSION: Eigenmode analysis of the entire connectivity matrix yields both a global and a detailed view of the network. We have shown that the eigenmode clustering not only is guided by the number of proteins with which each protein interacts, but also leads to functional clustering that can be applied to predict new protein interactions

    Abnormal Intracellular Accumulation and Extracellular AΞ² Deposition in Idiopathic and Dup15q11.2-q13 Autism Spectrum Disorders

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    <div><h3>Background</h3><p>It has been shown that amyloid ß (AΞ²), a product of proteolytic cleavage of the amyloid Ξ² precursor protein (APP), accumulates in neuronal cytoplasm in non-affected individuals in a cell type–specific amount.</p> <h3>Methodology/Principal Findings</h3><p>In the present study, we found that the percentage of amyloid-positive neurons increases in subjects diagnosed with idiopathic autism and subjects diagnosed with duplication 15q11.2-q13 (dup15) and autism spectrum disorder (ASD). In spite of interindividual differences within each examined group, levels of intraneuronal AΞ² load were significantly greater in the dup(15) autism group than in either the control or the idiopathic autism group in 11 of 12 examined regions (p<0.0001 for all comparisons; Kruskall-Wallis test). In eight regions, intraneuronal AΞ² load differed significantly between idiopathic autism and control groups (p<0.0001). The intraneuronal AΞ² was mainly N-terminally truncated. Increased intraneuronal accumulation of AΞ²<sub>17–40/42</sub> in children and adults suggests a life-long enhancement of APP processing with Ξ±-secretase in autistic subjects. AΞ² accumulation in neuronal endosomes, autophagic vacuoles, Lamp1-positive lysosomes and lipofuscin, as revealed by confocal microscopy, indicates that products of enhanced Ξ±-secretase processing accumulate in organelles involved in proteolysis and storage of metabolic remnants. Diffuse plaques containing AΞ²<sub>1–40/42</sub> detected in three subjects with ASD, 39 to 52 years of age, suggest that there is an age-associated risk of alterations of APP processing with an intraneuronal accumulation of a short form of AΞ² and an extracellular deposition of full-length AΞ² in nonfibrillar plaques.</p> <h3>Conclusions/Significance</h3><p>The higher prevalence of excessive AΞ² accumulation in neurons in individuals with early onset of intractable seizures, and with a high risk of sudden unexpected death in epilepsy in autistic subjects with dup(15) compared to subjects with idiopathic ASD, supports the concept of mechanistic and functional links between autism, epilepsy and alterations of APP processing leading to neuronal and astrocytic AΞ² accumulation and diffuse plaque formation.</p> </div

    The mammalian centrosome and its functional significance

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    Primarily known for its role as major microtubule organizing center, the centrosome is increasingly being recognized for its functional significance in key cell cycle regulating events. We are now at the beginning of understanding the centrosome’s functional complexities and its major impact on directing complex interactions and signal transduction cascades important for cell cycle regulation. The centrosome orchestrates entry into mitosis, anaphase onset, cytokinesis, G1/S transition, and monitors DNA damage. Recently, the centrosome has also been recognized as major docking station where regulatory complexes accumulate including kinases and phosphatases as well as numerous other cell cycle regulators that utilize the centrosome as platform to coordinate multiple cell cycle-specific functions. Vesicles that are translocated along microtubules to and away from centrosomes may also carry enzymes or substrates that use centrosomes as main docking station. The centrosome’s role in various diseases has been recognized and a wealth of data has been accumulated linking dysfunctional centrosomes to cancer, Alstrom syndrome, various neurological disorders, and others. Centrosome abnormalities and dysfunctions have been associated with several types of infertility. The present review highlights the centrosome’s significant roles in cell cycle events in somatic and reproductive cells and discusses centrosome abnormalities and implications in disease

    Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma

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    Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (pβ€Š=β€Š0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research

    Rational design of polymer-based absorbents: application to the fermentation inhibitor furfural

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    BACKGROUND: Reducing the amount of water-soluble fermentation inhibitors like furfural is critical for downstream bio-processing steps to biofuels. A theoretical approach for tailoring absorption polymers to reduce these pretreatment contaminants would be useful for optimal bioprocess design. RESULTS: Experiments were performed to measure aqueous furfural partitioning into polymer resins of 5 bisphenol A diglycidyl ether (epoxy) and polydimethylsiloxane (PDMS). Experimentally measured partitioning of furfural between water and PDMS, the more hydrophobic polymer, showed poor performance, with the logarithm of PDMS-to-water partition coefficient falling between βˆ’0.62 and βˆ’0.24 (95% confidence). In contrast, the fast setting epoxy was found to effectively partition furfural with the logarithm of the epoxy-to-water partition coefficient falling between 0.41 and 0.81 (95% confidence). Flory-Huggins theory is used to predict the partitioning of furfural into diverse polymer absorbents and is useful for predicting these results. CONCLUSION: We show that Flory-Huggins theory can be adapted to guide the selection of polymer adsorbents for the separation of low molecular weight organic species from aqueous solutions. This work lays the groundwork for the general design of polymers for the separation of a wide range of inhibitory compounds in biomass pretreatment streams
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