PREDIVAC: CD4+T-cell epitope prediction for vaccine design that covers 95% of HLA class II DR protein diversity

Background: CD4+ T-cell epitopes play a crucial role in eliciting vigorous protective immune responses during peptide (epitope)-based vaccination. The prediction of these epitopes focuses on the peptide binding process by MHC class II proteins. The ability to account for MHC class II polymorphism is critical for epitope-based vaccine design tools, as different allelic variants can have different peptide repertoires. In addition, the specificity of CD4+ T-cells is often directed to a very limited set of immunodominant peptides in pathogen proteins. The ability to predict what epitopes are most likely to dominate an immune response remains a challenge

Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals

Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals

The comparison of macroseismic intensity scales

The number of different macroseismic scales that have been used to express earthquake shaking in the course of the last 200 years is not known; it may reach three figures. The number of important scales that have been widely adopted is much smaller, perhaps about eight, not counting minor variants. Where data sets exist that are expressed in different scales, it is often necessary to establish some sort of equivalence between them, although best practice would be to reassign intensity values rather than convert them. This is particularly true because difference between workers in assigning intensity is often greater than differences between the scales themselves, particularly in cases where one scale may not be very well defined. The extent to which a scale guides the user to arrive at a correct assessment of the intensity is a measure of the quality of the scale. There are a number of reasons why one should prefer one scale to another for routine use, and some of these tend in different directions. If a scale has many tests (diagnostics) for each degree, it is more likely that the scale can be applied in any case that comes to hand, but if the diagnostics are so numerous that they include ones that do not accurately indicate any one intensity level, then the use of the scale will tend to produce false values. The purpose of this paper is chiefly to discuss in a general way the principles involved in the analysis of intensity scales. Conversions from different scales to the European Macroseismic Scale are discussed

A history of British seismology

The work of John Milne, the centenary of whose death is marked in 2013, has had a large impact in the development in global seismology. On his return from Japan to England in 1895, he established for the first time a global earthquake recording network, centred on his observatory at Shide, Isle of Wight. His composite bulletins, the “Shide Circulars” developed, in the twentieth century, into the world earthquake bulletins of the International Seismological Summary and eventually the International Seismological Centre, which continues to publish the definitive earthquake parameters of world earthquakes on a monthly basis. In fact, seismology has a long tradition in Britain, stretching back to early investigations by members of the Royal Society after 1660. Investigations in Scotland in the early 1840s led to a number of firsts, including the first network of instruments, the first seismic bulletin, and indeed, the first use of the word “seismometer”, from which words like “seismology” are a back-formation. This paper will present a chronological survey of the development of seismology in the British Isles, from the first written observations of local earthquakes in the seventh century, and the first theoretical writing on earthquakes in the twelfth century, up to the monitoring of earthquakes in Britain in the present day

Intensity Scale ESI 2007 for Assessing Earthquake Intensities

Earthquake intensity scales were introduced at the end of the nineteenth century (e.g., Rossi-Forel, Cancani, Mercalli) in order to characterize source parameters, damage distribution, and environmental impact of relevant seismic events. These intensity scales were based on a classification of earthquake effects on humans, on buildings, and on the natural environment. Intensity provides a measure of earthquake-induced damage both at a site (local intensity) and at the epicenter (epicentral intensity). It is important to note that intensity evaluations consider the coseismic effects in the whole range of frequencies of vibratory ground motion, together with those resulting from static, finite deformations (fault ground ruptures)