A role for the thiol-dependent reductase ERp57 in the assembly of MHC class I molecules

AbstractAn important mammalian defence strategy against intracellular pathogens is the presentation of cytoplasmically derived short peptides by major histocompatibility complex (MHC) class I molecules to cytotoxic T lymphocytes. MHC class I molecules assemble in the endoplasmic reticulum (ER) with chaperones, including calnexin and calreticulin, before binding to the transporter associated with antigen processing (TAP). We show here that the thiol-dependent reductase ERp57 (also known as ER60 protease) is involved in MHC class I assembly. ERp57 co-purified with the rat TAP complex (comprising TAP1 and TAP2), and associated with MHC class I molecules at an early stage in their biosynthesis. This association was sensitive to castanospermine, which inhibits the processing of glycoproteins. Human MHC class I molecules were also found to associate with ERp57. We conclude that ERp57 is a newly identified component of the MHC class I pathway, and that it appears to interact with MHC class I molecules before they associate with TAP

A method for ensemble expansion and improved definition of forecast distributions from climate simulations

Because of the inherently chaotic nature of the atmosphere, ensemble simulations are required to characterize a model’s response to the prescribed boundary forcing in probabilistic terms, particularly if the focus is on the probabilities of extreme events. At the same time, substantial computer resources are needed to produce routinely ensemble seasonal climate forecasts of sufficient size to make suitably reproducible estimates of such probabilities. We describe a method for artificially expanding the effective number of members in ensemble climate simulations on a seasonal basis, thereby reducing uncertainty in estimated probability distributions. As described here, the method involves calculating seasonal statistics using monthly values from all possible combinations of ensemble members. Under certain assumptions, this method is able to increase the effective ensemble size of an N-member M-month seasonal forecast by a factor of (asymptotically) M. One key assumption in this regard is that, aside from the effects of prescribed boundary conditions, the month-to-month values from a particular ensemble member are linear independent. This paper describes the behaviour of the ensemble expansion technique using both idealized and actual ensemble forecast data under a variety of conditions, drawing comparisons with an alternative parametric approach for ensemble expansion. A method for testing the assumption of linear independence in model simulations is also presented

Conditional probabilities, relative operating characteristics, and relative operating levels

The relative operating characteristic (ROC) curve is a highly flexible method for representing the quality of dichotomous, categorical, continuous, and probabilistic forecasts. The method is based on ratios that measure the proportions of events and nonevents for which warnings were provided. These ratios provide estimates of the probabilities that an event will be forewarned and that an incorrect warning will be provided for a nonevent. Some guidelines for interpreting the ROC curve are provided. While the ROC curve is of direct interest to the user, the warning is provided in advance of the outcome and so there is additional value in knowing the probability of an event occurring contingent upon a warning being provided or not provided. An alternative method to the ROC curve is proposed that represents forecast quality when expressed in terms of probabilities of events occurring contingent upon the warnings provided. The ratios used provide estimates of the probability of an event occurring given the forecast that is issued. Some problems in constructing the curve in a manner that is directly analogous to that for the ROC curve are highlighted, and so an alternative approach is proposed. In the context of probabilistic forecasts, the ROC curve provides a means of identifying the forecast probability at which forecast value is optimized. In the context of continuous variables, the proposed relative operating levels curve indicates the exceedence threshold for defining an event at which forecast skill is optimized, and can enable the forecast user to estimate the probabilities of events other than that defined by the forecaster

Origin and significance of 'dispersed facies' basal ice: Svínafellsjökull, Iceland

Dispersed facies basal ice - massive (i.e. structureless) ice with dispersed debris aggregates - is present at the margins of many glaciers and, as a product of internal glacial processes, has the potential to provide important information about the mechanisms of glacier flow and the nature of the subglacial environment. The origin of dispersed facies is poorly understood, with several hypotheses having been advanced for its formation, and there is disagreement as to whether it is largely a sedimentary or a tectonic feature. We test these established hypotheses at the temperate glacier Svfnafellsjokull, Iceland, and find that none fully account for dispersed facies characteristics at this location. Instead, dispersed facies physical, sedimentological and stable-isotope (5180, 8D) characteristics favour a predominantly tectonic origin that we suggest comprises the regelation and straininduced metamorphism of debris-rich basal ice that has been entrained into an englacial position by tectonic processes operating at the base of an icefall. Further thickening of the resultant dispersed facies may also occur tectonically as a result of ice flow against the reverse bed slope of a terminal overdeepening. Lack of efficient subglacial drainage in the region of the overdeepening may limit basal melting and thus favour basal ice preservation, including the preservation of dispersed facies. Despite the relatively low sediment content of dispersed facies (~1.6% by volume), its thickness (up to 25 m) and ubiquity at Svfnafellsjokull results in a significant contribution to annual sediment discharge (1635-3270 m3 a"1) that is ~6.5 times that contributed by debris-rich stratified facies basal ice

The Millennium Galaxy Catalogue: morphological classification and bimodality in the colour-concentration plane

Using 10 095 galaxies (B < 20 mag) from the Millennium Galaxy Catalogue, we derive B-band luminosity distributions and selected bivariate brightness distributions for the galaxy population. All subdivisions extract highly correlated sub-sets of the galaxy population which consistently point towards two overlapping distributions. A clear bimodality in the observed distribution is seen in both the rest-(u-r) colour and log(n) distributions. The rest-(u-r) colour bimodality becomes more pronounced when using the core colour as opposed to global colour. The two populations are extremely well separated in the colour-log(n) plane. Using our sample of 3 314 (B < 19 mag) eyeball classified galaxies, we show that the bulge-dominated, early-type galaxies populate one peak and the bulge-less, late-type galaxies occupy the second. The early- and mid-type spirals sprawl across and between the peaks. This constitutes extremely strong evidence that the fundamental way to divide the luminous galaxy population is into bulges and discs and that the galaxy bimodality reflects the two component nature of galaxies and not two distinct galaxy classes. We argue that these two-components require two independent formation mechanisms/processes and advocate early bulge formation through initial collapse and ongoing disc formation through splashback, infall and merging/accretion. We calculate the B-band luminosity-densities and stellar-mass densities within each subdivision and estimate that the z ~ 0 stellar mass content in spheroids, bulges and discs is 35 +/- 2 per cent, 18 +/- 7 and 47 +/- 7 per cent respectively. [Abridged]Comment: Accepted for publication in MNRAS, 23 pages, 17 figures. Comments welcome. MGC website is at: http://www.eso.org/~jliske/mgc

Solution phase, solid state, and theoretical investigations on the MacMillan imidazolidinone

A combination of soln. phase NMR, X-ray crystallog. studies, and DFT calcns. provide a consistent structural conformation for iminium ions derived from the MacMillan imidazolidinone