1,453 research outputs found
Changes in the Organization of Excitation-Contraction Coupling Structures in Failing Human Heart
The cardiac myocyte t-tubular system ensures rapid, uniform cell activation and several experimental lines of evidence suggest changes in the t-tubular system and associated excitation-contraction coupling proteins may occur in heart failure
T-tubule disease:Relationship between t-tubule organization and regional contractile performance in human dilated cardiomyopathy
Evidence from animal models suggest that t-tubule changes may play an important role in the contractile deficit associated with heart failure. However samples are usually taken at random with no regard as to regional variability present in failing hearts which leads to uncertainty in the relationship between contractile performance and possible t-tubule derangement. Regional contraction in human hearts was measured by tagged cine MRI and model fitting. At transplant, failing hearts were biopsy sampled in identified regions and immunocytochemistry was used to label t-tubules and sarcomeric z-lines. Computer image analysis was used to assess 5 different unbiased measures of t-tubule structure/organization. In regions of failing hearts that showed good contractile performance, t-tubule organization was similar to that seen in normal hearts, with worsening structure correlating with the loss of regional contractile performance. Statistical analysis showed that t-tubule direction was most highly correlated with local contractile performance, followed by the amplitude of the sarcomeric peak in the Fourier transform of the t-tubule image. Other area based measures were less well correlated. We conclude that regional contractile performance in failing human hearts is strongly correlated with the local t-tubule organization. Cluster tree analysis with a functional definition of failing contraction strength allowed a pathological definition of ‘t-tubule disease’. The regional variability in contractile performance and cellular structure is a confounding issue for analysis of samples taken from failing human hearts, although this may be overcome with regional analysis by using tagged cMRI and biopsy mapping
Identification and characterisation of enteroaggregative Escherichia coli subtypes associated with human disease
Enteroaggregative E. coli (EAEC) are a major cause of diarrhoea worldwide. Due to their heterogeneity and carriage in healthy individuals, identification of diagnostic virulence markers for pathogenic strains has been difficult. In this study, we have determined phenotypic and genotypic differences between EAEC strains of sequence types (STs) epidemiologically associated with asymptomatic carriage (ST31) and diarrhoeal disease (ST40). ST40 strains demonstrated significantly enhanced intestinal adherence, biofilm formation, and pro-inflammatory interleukin-8 secretion compared with ST31 isolates. This was independent of whether strains were derived from diarrhoea patients or healthy controls. Whole genome sequencing revealed differences in putative virulence genes encoding aggregative adherence fimbriae, E. coli common pilus, flagellin and EAEC heat-stable enterotoxin 1. Our results indicate that ST40 strains have a higher intrinsic potential of human pathogenesis due to a specific combination of virulence-related factors which promote host cell colonization and inflammation. These findings may contribute to the development of genotypic and/or phenotypic markers for EAEC strains of high virulence
Charged black holes: Wave equations for gravitational and electromagnetic perturbations
A pair of wave equations for the electromagnetic and gravitational
perturbations of the charged Kerr black hole are derived. The perturbed
Einstein-Maxwell equations in a new gauge are employed in the derivation. The
wave equations refer to the perturbed Maxwell spinor and to the shear
of a principal null direction of the Weyl curvature. The whole
construction rests on the tripod of three distinct derivatives of the first
curvature of a principal null direction.Comment: 12 pages, to appear in Ap.
Demonstration of Universal Parametric Entangling Gates on a Multi-Qubit Lattice
We show that parametric coupling techniques can be used to generate selective
entangling interactions for multi-qubit processors. By inducing coherent
population exchange between adjacent qubits under frequency modulation, we
implement a universal gateset for a linear array of four superconducting
qubits. An average process fidelity of is estimated for
three two-qubit gates via quantum process tomography. We establish the
suitability of these techniques for computation by preparing a four-qubit
maximally entangled state and comparing the estimated state fidelity against
the expected performance of the individual entangling gates. In addition, we
prepare an eight-qubit register in all possible bitstring permutations and
monitor the fidelity of a two-qubit gate across one pair of these qubits.
Across all such permutations, an average fidelity of
is observed. These results thus offer a path to a scalable architecture with
high selectivity and low crosstalk
Ecosystems and People – an inclusive, interdisciplinary journal
Environmental Biolog
Establishing a major cause of discrepancy in the calibration of Affymetrix GeneChips
<p>Abstract</p> <p>Background</p> <p>Affymetrix GeneChips are a popular platform for performing whole-genome experiments on the transcriptome. There are a range of different calibration steps, and users are presented with choices of different background subtractions, normalisations and expression measures. We wished to establish which of the calibration steps resulted in the biggest uncertainty in the sets of genes reported to be differentially expressed.</p> <p>Results</p> <p>Our results indicate that the sets of genes identified as being most significantly differentially expressed, as estimated by the z-score of fold change, is relatively insensitive to the choice of background subtraction and normalisation. However, the contents of the gene list are most sensitive to the choice of expression measure. This is irrespective of whether the experiment uses a rat, mouse or human chip and whether the chip definition is made using probe mappings from Unigene, RefSeq, Entrez Gene or the original Affymetrix definitions. It is also irrespective of whether both Present and Absent, or just Present, Calls from the MAS5 algorithm are used to filter genelists, and this conclusion holds for genes of differing intensities. We also reach the same conclusion after assigning genes to be differentially expressed using t-statistics, although this approach results in a large amount of false positives in the sets of genes identified due to the small numbers of replicates typically used in microarray experiments.</p> <p>Conclusion</p> <p>The major calibration uncertainty that biologists need to consider when analysing Affymetrix data is how their multiple probe values are condensed into one expression measure.</p
Private trade and monopoly structures : the East India Companies and the commodity trade to Europe in the eighteenth century
Our research is about the trade in material goods from Asia to Europe over this period, and its impact on Europe’s consumer and industrial cultures. It entails a comparative study of Europe’s East India Companies and the private trade from Asia over the period. The commodities trade was heavily dependent on private trade. The historiography to date has left a blind spot in this area, concentrating instead on corruption and malfeasance. Taking a global history approach we investigate the trade in specific consumer goods in many qualities and varieties that linked merchant communities and stimulated information flows. We set out how private trade functioned alongside and in connection with the various European East India companies; we investigate how this changed over time, how it drew on the Company infrastructure, and how it took the risks and developed new and niche markets for specific Asian commodities that the Companies could not sustain
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