683 research outputs found

    Preliminary experimental results for a cryogenic brush seal configuration

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    Preliminary fluid nitrogen flow data are reported for a five-brush, ceramic-coated-rub-runner brush seal system, where the brushes and the rub runner were placed at each end of a centrally pressurized multifunction tester ('back-to-back' set of brushes) and tested at rotor speeds of 0, 10, 18, and 22.5 krpm. After testing, both the brushes and the ceramic-coated rub runner appeared pristine. The coating withstood both the thermomechanical and dynamic loadings with minor wear track scarring. The bristle tips showed some indication of material shearing (smearing) wear. The Ergun porous flow equation was applied to the brush seal data. The Ergun relation, which required heuristic information to characterize the coefficients, fit the gaseous data but was in poor agreement with the fluid results. The brush seal exit conditions were two phase. Two-phase, choked-flow design charts were applied but required one data point at each rotor speed to define the (C(sub f)A x Constant) flow and area coefficients. Reasonable agreement between prediction and data was found, as expected, but such methods are not to be construed as two-phase-flow brush seal analyses

    Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

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    Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers

    The mimetic politics of lone-wolf terrorism

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    Written at a time of crisis in the project of social and political modernity, Fyodor Dostoevsky’s 1864 novel Notes from Underground offers an intriguing parallel for the twenty-first century lone-wolf; it portrays an abject, outcast, spiteful unnamed anti-hero boiling with rage, bitter with resentment and on the verge of radicalisation. A Girardian reading of the poetic truths contained in Dostoevsky’s work is able to provide important keys to explain the contemporary transformation from ‘fourth-wave’ religious terrorism to ‘fifth-wave’ lone-wolf terrorism. Such a reading argues that it is mimetic rivalry – rather than much-trumpeted forms of religious violence or cultural differences – that fuels the triangular relation between governments, terrorists and civilian victims at heart of terrorist acts. This approach is further able to blend social inquiry with an account of the individual, in fact anthropological, conditions of lone-wolf terrorism by tracing the globalisation of resentment and the individualisation of violence to the hyper-mimeticism characterising the globalisation of late modernity. Finally, a mimetic reading of ‘fifth-wave’ terrorism accounts for the turbulence of a global politics in which victimhood and scapegoating no longer have the ability to stabilise social order and warns against a future where violence proliferates and escalates unchecked

    Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis

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    Computational approaches have promised to organize collections of functional genomics data into testable predictions of gene and protein involvement in biological processes and pathways. However, few such predictions have been experimentally validated on a large scale, leaving many bioinformatic methods unproven and underutilized in the biology community. Further, it remains unclear what biological concerns should be taken into account when using computational methods to drive real-world experimental efforts. To investigate these concerns and to establish the utility of computational predictions of gene function, we experimentally tested hundreds of predictions generated from an ensemble of three complementary methods for the process of mitochondrial organization and biogenesis in Saccharomyces cerevisiae. The biological data with respect to the mitochondria are presented in a companion manuscript published in PLoS Genetics (doi:10.1371/journal.pgen.1000407). Here we analyze and explore the results of this study that are broadly applicable for computationalists applying gene function prediction techniques, including a new experimental comparison with 48 genes representing the genomic background. Our study leads to several conclusions that are important to consider when driving laboratory investigations using computational prediction approaches. While most genes in yeast are already known to participate in at least one biological process, we confirm that genes with known functions can still be strong candidates for annotation of additional gene functions. We find that different analysis techniques and different underlying data can both greatly affect the types of functional predictions produced by computational methods. This diversity allows an ensemble of techniques to substantially broaden the biological scope and breadth of predictions. We also find that performing prediction and validation steps iteratively allows us to more completely characterize a biological area of interest. While this study focused on a specific functional area in yeast, many of these observations may be useful in the contexts of other processes and organisms

    Political opportunity structures, democracy, and civil war

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    Theories of mobilization suggest that groups are more likely to resort to violence in the presence of political opportunity structures that afford greater prospects for extracting concessions from the government or better opportunities to topple ruling governments. However, existing efforts to consider the possible influences of political opportunity structures on incentives for violence and civil war empirically have almost invariably relied upon measures of democracy to proxy for the hypothesized mechanisms, most notably the argument that the opposing effects of political accommodation and repression will give rise to an inverted U-shaped relationship between democracy and the risk of civil war. The authors detail a number of problems with measures of democracy as proxies for political opportunity structures and develop alternative measures based on the likely risks that political leaders will lose power in irregular challenges and their implications for the incentives for resort to violence. The authors evaluate empirically how the security with which leaders hold office influences the prospects of violent civil conflict. The findings indicate that recent irregular leader entry and transitions indeed increase the risk of conflict onset, while democratic institutions are found to decrease the risk of civil war, after controlling for the new measures of state weakness. </jats:p

    The relative orientation of the TM3 and TM4 domains varies between α1 and α3 glycine receptors

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    Glycine receptors (GlyRs) are anion-conducting members of the pentameric ligand-gated ion channel family. We previously showed that the dramatic difference in glycine efficacies of α1 and α3 GlyRs is largely attributable to their nonconserved TM4 domains. Because mutation of individual nonconserved TM4 residues had little effect, we concluded that the efficacy difference was a distributed effect of all nonconserved TM4 residues. We therefore hypothesized that the TM4 domains of α1 and α3 GlyRs differ in structure, membrane orientation, and/or molecular dynamic properties. Here we employed voltage-clamp fluorometry to test whether their TM4 domains interact differently with their respective TM3 domains. We found a rhodamine fluorophore covalently attached to a homologous TM4 residue in each receptor interacts differentially with a conserved TM3 residue. We conclude that the α1 and α3 GlyR TM4 domains are orientated differently relative to their TM3 domains. This may underlie their differential ability to influence glycine efficacy

    NeatMap - non-clustering heat map alternatives in R

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    <p>Abstract</p> <p>Background</p> <p>The clustered heat map is the most popular means of visualizing genomic data. It compactly displays a large amount of data in an intuitive format that facilitates the detection of hidden structures and relations in the data. However, it is hampered by its use of cluster analysis which does not always respect the intrinsic relations in the data, often requiring non-standardized reordering of rows/columns to be performed post-clustering. This sometimes leads to uninformative and/or misleading conclusions. Often it is more informative to use dimension-reduction algorithms (such as Principal Component Analysis and Multi-Dimensional Scaling) which respect the topology inherent in the data. Yet, despite their proven utility in the analysis of biological data, they are not as widely used. This is at least partially due to the lack of user-friendly visualization methods with the visceral impact of the heat map.</p> <p>Results</p> <p>NeatMap is an R package designed to meet this need. NeatMap offers a variety of novel plots (in 2 and 3 dimensions) to be used in conjunction with these dimension-reduction techniques. Like the heat map, but unlike traditional displays of such results, it allows the entire dataset to be displayed while visualizing relations between elements. It also allows superimposition of cluster analysis results for mutual validation. NeatMap is shown to be more informative than the traditional heat map with the help of two well-known microarray datasets.</p> <p>Conclusions</p> <p>NeatMap thus preserves many of the strengths of the clustered heat map while addressing some of its deficiencies. It is hoped that NeatMap will spur the adoption of non-clustering dimension-reduction algorithms.</p

    In situ proliferation and differentiation of macrophages in dental pulp

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    The presence of macrophages in dental pulp is well known. However, whether these macrophages proliferate and differentiate in the dental pulp in situ, or whether they constantly migrate from the blood stream into the dental pulp remains unknown. We have examined and compared the development of dental pulp macrophages in an organ culture system with in vivo tooth organs to clarify the developmental mechanism of these macrophages. The first mandibular molar tooth organs from ICR mice aged between 16 days of gestation (E16) to 5 days postnatally were used for in vivo experiments. Those from E16 were cultured for up to 14 days with or without 10% fetal bovine serum. Dental pulp tissues were analyzed with immunohistochemistry to detect the macrophages and with reverse transcription and the polymerase chain reaction (RT-PCR) for the detection of factors related to macrophage development. The growth curves for the in vivo and in vitro cultured cells revealed similar numbers of F4/80-positive macrophages in the dental pulp. RT-PCR analysis indicated the constant expression of myeloid colony-stimulating factor (M-CSF) in both in-vivo- and in-vitro-cultured dental pulp tissues. Anti-M-CSF antibodies significantly inhibited the increase in the number of macrophages in the dental pulp. These results suggest that (1) most of the dental pulp macrophages proliferate and differentiate in the dental pulp without a supply of precursor cells from the blood stream, (2) M-CSF might be a candidate molecule for dental pulp macrophage development, and (3) serum factors might not directly affect the development of macrophages
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