Serum antibody opsonic activity against Actinobacillus actinomycetemcomitans in human periodontal diseases

Actinobacillus actinomycetemcomitans is frequently associated with severe periodontitis. Many periodontitis patients have elevated levels of serum IgG antibodies to A. actinomycetemcomitans, but the role of these antibodies is unknown. This study evaluated the functional capacity of anti-A. actinomycetemcomitans IgG antibody to enhance phagocytosis of A. actinomycetemcomitans by polymorphonuclear leukocytes. Chemoluminescence assays were done using sera from 64 subjects, 61 of whom had severe periodontitis; results were compared with the subject's anti-A. actinomycetemcomitans IgG titer and avidity. There was a strong correlation between chemoluminescence and antibody log titer (P < .00001) and a weak correlation between chemoluminescence and antibody avidity (P < .05). The results support the hypothesis that anti-A. actinomycetemcomitans IgG antibodies are important in promoting phagocytosis and killing of A. actinomycetemcomitans. Subjects who develop high levels of highly avid antibodies against A. actinomycetemcomitans may have greater resistance to continued or repeated infection by this pathogen.     

Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical and genetic overlap. In up to 97% of ALS cases and ~50% of FTLD cases, the primary pathological protein observed in affected tissues is TDP-43, which is hyperphosphorylated, ubiquitinated and cleaved. The TDP-43 is observed in aggregates that are abnormally located in the cytoplasm. The pathogenicity of TDP-43 cytoplasmic aggregates may be linked with both a loss of nuclear function and a gain of toxic functions. The cellular processes involved in ALS and FTLD disease pathogenesis include changes to RNA splicing, abnormal stress granules, mitochondrial dysfunction, impairments to axonal transport and autophagy, abnormal neuromuscular junctions, endoplasmic reticulum stress and the subsequent induction of the unfolded protein response. Here, we review and discuss the evidence for alterations to these processes that have been reported in cellular and animal models of TDP-43 proteinopathy.     

Recent Lessons Learned in Structural Fire Engineering for Composite Steel Structures

The knowledge in the field of structural fire engineering has been greatly advanced through assessment of a number of real fires (WTC, Torre Windsor, Broadgate, etc.) and, especially, by the Cardington series of full scale structural fire tests. This knowledge has been used to validate and verify the use of computational finite element models that have expanded the range of structures that can be investigated under severe fire exposure. This paper presents a selection of key lessons learned by the authors through the assessment of structures in fire for real commercial building projects. The key areas of sensitivity that have been encountered are described and a discussion of each point presented. The paper is aimed at describing potential weaknesses that have been observed in the commercial work of the authors, often driven by the requirements for efficient ambient structural design. The paper concludes with some suggested advice for structural engineers aimed at increasing the general robustness of building structures. This is based on designing out as far as possible in the ambient design of a structure the potential weaknesses identified in past project work.     

Problems encountered at work by people with severe acquired hearing loss

A structured questionnaire concerning problems encountered at work was administered to 88 adults of employment age suffering from acquired sensorineural hearing loss (60 dB +). While respondents were not likely to be out of work by virtue of their hearing loss, they found it difficult to cope at work for a variety of reasons. Information from a subsequent open-ended interview threw some light on the validity of the questionnaire and in particular illustrated the need to combine quantitative and qualitative methods of data collection.     

Ionospheric and tropospheric effects on synthetic aperture radar performance†

Synthetic aperture radar (SAR) produces high-resolution images of the Earth's surface (and subsurface, under some conditions) by coherently processing the returns from a pulsed radar. It is an active sensor, hence is not dependent on natural illumination for its operation, and the comparative transparency of the atmosphere at centimetre wavelengths allows penetration of clouds and haze. SAR therefore offers considerable potential as an all-weather, all-time-of-day sensor, as long as propagation effects do not destroy signal coherence. A particularly useful way of viewing SAR performance is in terms of the synthetic antenna gain pattern, and performance measures derived from this pattern (e.g. spatial resolution, sidelobe energy). Perturbations of the phase due to irregularities in the refractive index structure of the ionosphere and troposphere lead to changes in the system performance. We have used a phase screen model to generate phase perturbations of the form expected due to propagation through a disturbed ionosphere. Simulations have been undertaken and used to assess the performance of a variety of SAR systems under particular geophysical conditions. These simulations indicate that at the longer wavelengths (C band and above), severe disturbances may greatly reduce image contrast, to the extent of destroying the image. Geometric distortions will also be introduced.     

The effect of tidal currents on radar backscatter from the sea around Portland Bill

Low grazing angle radar data of the sea surface were collected using three different frequencies (3, 10 and 16?GHz) from a cliff‐top site on the south coast of England. A number of features were observed in the radar imagery that could be related to the tidal current flow around Portland Bill. The strongest, most obvious features occurred near the time of low water, and these features had significantly reduced backscatter levels in horizontal polarization, with reductions up to 20?dB, or more, below the clutter levels around them. In vertical polarization, the reduction in the clutter level was typically somewhat smaller (10?dB or so) than the horizontally polarized backscatter. No convincing explanation of this effect has been found. The strain rate component in the radar line of sight was estimated from measurements of the current component calculated from the radar data. A comparison of range–time intensity images of the radar backscatter and the strain rate showed a number of strongly correlated features that repeated with the semi‐diurnal tidal period. The maximum strain rate was around 0.0005?s^?1, which produced modulations in the radar backscatter of around 2–3?dB. On occasions a number of bright streaks with a separation of around 100?m were also observed, moving away from the radar at a few cm?s^?1. A satellite image from European Remote Sensing Satellite (ERS)‐2 of the Portland area suggests that the slow‐moving streaks may be internal waves generated by tidal flow over raised bathymetry.     

Probabilistic classification of acute myocardial infarction from multiple cardiac markers

Logistic regression and Gaussian mixture model (GMM) classifiers have been trained to estimate the probability of acute myocardial infarction (AMI) in patients based upon the concentrations of a panel of cardiac markers. The panel consists of two new markers, fatty acid binding protein (FABP) and glycogen phosphorylase BB (GPBB), in addition to the traditional cardiac troponin I (cTnI), creatine kinase MB (CKMB) and myoglobin. The effect of using principal component analysis (PCA) and Fisher discriminant analysis (FDA) to preprocess the marker concentrations was also investigated. The need for classifiers to give an accurate estimate of the probability of AMI is argued and three categories of performance measure are described, namely discriminatory ability, sharpness, and reliability. Numerical performance measures for each category are given and applied. The optimum classifier, based solely upon the samples take on admission, was the logistic regression classifier using FDA preprocessing. This gave an accuracy of 0.85 (95% confidence interval: 0.78–0.91) and a normalised Brier score of 0.89. When samples at both admission and a further time, 1–6 h later, were included, the performance increased significantly, showing that logistic regression classifiers can indeed use the information from the five cardiac markers to accurately and reliably estimate the probability AMI.     

Electron tomography of large, multicomponent biological structures

Genome-wide scans for linkage of chromosome regions to type 1 diabetes in affected sib pair families have revealed that the major susceptibility locus resides within the major histocompatibility complex (MHC) on chromosome 6p21 (lambda s = 2.5). It is recognised that the MHC contains multiple susceptibility loci (referred to collectively as IDDM1), including the class II antigen receptor genes, which control the major pathological feature of the disease: T lymphocyte-mediated autoimmune destruction of the insulin-producing pancreatic beta cells. However, the MHC genes, and a second locus, the insulin gene minisatellite on chromosome 11p15 (IDDM2; lambda s = 1.25), cannot account for all of the observed clustering of disease in families (lambda s = 15), and the scans suggested the presence of other susceptibility loci scattered throughout the genome. There are four additional loci for which there is currently sufficient evidence from linkage and association studies to justify fine mapping experiments: IDDM4 (FGF3/11q13), IDDM5 (ESR/6q22), IDDM8 (D6S281/6q27) and IDDM12 (CTLA-4/2q33), IDDM4, 5 and 8 were detected by genome scanning, and IDDM12 by a candidate gene strategy. The results suggest that the clustering of type 1 diabetes in families is due to the sharing of alleles at multiple loci, and that the as yet unidentified environmental factors are not causing clustering, but instead appear to influence the overall penetrance of genetically programmed susceptibility. The data are consistent with a polygenic threshold model for the inheritance of type 1 diabetes.