Model studies of fluctuations in the background for jets in heavy ion collisions

Jets produced in high energy heavy ion collisions are quenched by the production of the quark gluon plasma. Measurements of these jets are influenced by the methods used to suppress and subtract the large, fluctuating background and the assumptions inherent in these methods. We compare the measurements of the background in Pb+Pb collisions at $\sqrt{s_{NN}}$ = 2.76 TeV by the ALICE collaboration to calculations in TennGen (a data-driven random background generator) and PYTHIA Angantyr. The standard deviation of the energy in random cones in TennGen is approximately in agreement with the form predicted in the ALICE paper, with deviations of 1-6 $\%$. The standard deviation of energy in random cones in Angantyr exceeds the same predictions by approximately 40 $\%$. Deviations in both models can be explained by the assumption that the single particle $d^2N/dydp_T$ is a Gamma distribution in the derivation of the prediction. This indicates that model comparisons are potentially sensitive to the treatment of the background

Fabry disease: will markers of early disease enable early treatment and better outcomes?

PURPOSE OF REVIEW: This review explores the clinical and pathological features of Fabry disease. New modalities of imaging, biomarkers and long-term treatment effects are discussed. RECENT FINDINGS: Fabry disease is clinically heterogeneous, and in women the clinical severity has recently been linked to skewing of X-inactivation. Two phenotypes have been described, one with early onset manifestation including pain and one with later onset single organ manifestations; however, the cardiac outcomes in these two groups appear similar. Fibrosis is found in renal and cardiac tissues on biopsy and appears to be a critical point in the pathology of Fabry disease after which response to enzyme replacement therapy is more limited. In-vitro studies have suggested that lyso-globotriaosylceramide may have an important role in the generation of fibrosis. Imaging, including cardiac magnetic resonance imaging, may have a role in detection of early stages of the disease. Long-term outcomes for patients treated with enzyme replacement therapy are now being described with some suggestion that patients treated at earlier points in the disease course may have better outcomes. SUMMARY: Recent advances in understanding pathology, disease processes and treatment effects may enable future rational targeting of treatment with improved outcomes

Application of satellite-derived rainfall estimates to extend water resource simulation modelling in South Africa

Spatially interpolated rainfall estimates from rain-gauges are widely used as input to hydrological models, but deriving accurate estimates at appropriate space and time scales remain a major problem. In South Africa there has been a gradual decrease in the number of active rain-gauges over time. Satellite-based estimates of spatial rainfall are becoming more readily available and offer a viable substitute. The paper presents the potential of using Climate Prediction Center African daily precipitation climatology (CPCAPC) satellite-based datasets (2001-2006) to drive a Pitman hydrological model which has been calibrated using gauge-based rainfall data (1920-1990). However, if two sources of rainfall data are to be used together, it is necessary to ensure that they are compatible in terms of their statistical properties. A non-linear frequency of exceedance transformation technique was used to correct the satellite data to be more consistent with historical spatial rainfall estimates. The technique generated simulation results for the 2001 to 2006 period that were greatly improved compared to the direct use of the untransformed satellite data. While there remain some further questions about the use of satellite-derived rainfall data in different parts of the country, they do seem to have the potential to contribute to extending water resource modelling into the future.Keywords: satellite-based rainfall, hydrological model, water resources, South Afric

Lysosomal Acid Lipase Deficiency: Therapeutic Options

Lysosomal acid lipase (LAL) deficiency is a metabolic (storage) disorder, encompassing a severe (Wolman disease) and attenuated (Cholesterol ester storage disease) subtype; both inherited as autosomal recessive traits. Cardinal clinical features include the combination of hepatic dysfunction and dyslipidemia, as a consequence of cholesteryl esters and triglyceride accumulation, predominately in the liver and vascular and reticuloendothelial system. Significant morbidity can arise, due to liver failure and/or atherosclerosis; in part related to the severity of the underlying gene defect and corresponding enzyme deficiency. Diagnosis is based on demonstration of decreased LAL enzyme activity, complemented by analysis of the cognate gene defects. Therapeutic options include dietary manipulation and the use of lipid-lowering drugs. Sebelipase alfa, a recombinant enzyme replacement therapy, has garnered regulatory approval, following demonstration of improvements in disease-relevant markers and clinical benefit in clinical trials, which included increased survival in the most severe cases

Relationship between membrane phosphatidylinositol-4,5-bisphosphate and receptor-mediated inhibition of native neuronal M channels

The relationship between receptor-induced membrane phosphatidylinositol-4'5'-bisphosphate (PIP2) hydrolysis and M-current inhibition was assessed in single-dissociated rat sympathetic neurons by simultaneous or parallel recording of membrane current and membrane-to-cytosol translocation of the fluorescent PIP2/inositol 1,4,5-trisphosphate (IP3)-binding peptide green fluorescent protein-tagged pleckstrin homology domain of phospholipase C (GFP-PLC delta-PH). The muscarinic receptor agonist oxotremorine-M produced parallel time- and concentration-dependent M-current inhibition and GFP-PLC delta-PH translocation; bradykinin also produced parallel time- dependent inhibition and translocation. Phosphatidylinositol-4-phosphate-5-kinase (PI5-K) overexpression reduced both M-current inhibition and GFP-PLC delta-PH translocation by both oxotremorine-M and bradykinin. These effects were partly reversed by wortmannin, which inhibits phosphatidylinositol-4-kinase (PI4-K). PI5-K overexpression also reduced the inhibitory action of oxotremorine-M on PIP2-gated G-protein-gated inward rectifier (Kir3.1/3.2) channels; bradykinin did not inhibit these channels. Overexpression of neuronal calcium sensor-1 protein (NCS-1), which increases PI4-K activity, did not affect responses to oxotremorine-M but reduced both fluorescence translocation and M-current inhibition by bradykinin. Using an intracellular IP3 membrane fluorescence-displacement assay, initial mean concentrations of membrane [PIP2] were estimated at 261 mu M (95% confidence limit; 192-381 mu M), rising to 693 mu M (417-1153 mu M) in neurons overexpressing PI5-K. Changes in membrane [PIP2] during application of oxotremorine-M were calculated from fluorescence data. The results, taken in conjunction with previous data for KCNQ2/3 (Kv7.2/Kv7.3) channel gating by PIP2 (Zhang et al., 2003), accorded with the hypothesis that the inhibitory action of oxotremorine-M on M current resulted from depletion of PIP2. The effects of bradykinin require additional components of action, which might involve IP3-induced Ca2+ release and consequent M-channel inhibition (as proposed previously) and stimulation of PIP2 synthesis by Ca2+-dependent activation of NCS-1

Monte Carlo simulation of HIV-1 evolution in response to selection by antibodies

Held in conjunction with the 16th International Parallel and Distributed Processing Symposium Copyright © 2002 IEEE – All Rights ReservedThe persistence of human immunodeficiency virus type 1 (HIV-1) infection may be in part attributed to its ability to evolve to evade neutralizing antibody (NAb) surveillance. We have tested the prediction that positive selection of V3 is positively correlated with the strength of a patient’s NAb response by analyzing a data set containing both sequences from the principal neutralizing domain of HIV-1 (V3) and measures of the strength of the NAb responses of several patients. Only viral sequences from the patient with the strongest NAb response exhibited evidence of significant positive selection. To investigate the nature of selection by NAbs, we simulated the evolution of V3 at the nucleotide level. Two forms of plausible NAb selection were used: negative frequency-dependent selection and negative viral-age-dependent selection. Assuming negative age-dependent selection rather than negative frequency-dependent selection better simulated the temporal pattern of V3 variation from the patient with the strongest NAb response.Jack da Silva; Austin Hughe

A parallel multigrid solver for multi-patch Isogeometric Analysis

Isogeometric Analysis (IgA) is a framework for setting up spline-based discretizations of partial differential equations, which has been introduced around a decade ago and has gained much attention since then. If large spline degrees are considered, one obtains the approximation power of a high-order method, but the number of degrees of freedom behaves like for a low-order method. One important ingredient to use a discretization with large spline degree, is a robust and preferably parallelizable solver. While numerical evidence shows that multigrid solvers with standard smoothers (like Gauss Seidel) does not perform well if the spline degree is increased, the multigrid solvers proposed by the authors and their co-workers proved to behave optimal both in the grid size and the spline degree. In the present paper, the authors want to show that those solvers are parallelizable and that they scale well in a parallel environment.Comment: The first author would like to thank the Austrian Science Fund (FWF) for the financial support through the DK W1214-04, while the second author was supported by the FWF grant NFN S117-0

Pregnancies and associated events in women receiving Enzyme Replacement Therapy for late onset Glycogen Storage Disease Type II (Pompe disease)

AIM: Glycogen storage disease type II (GSD II or Pompe disease; OMIM; 232 300) is a rare autosomal recessive lysosomal storage disorder resulting from deficiency of α-glucosidase and accumulation of glycogen in muscle. Clinical symptoms include weakness of skeletal and respiratory muscles and, in infants, cardiomyopathy. Patients with GSD II receive infusions of recombinant α-glucosidase (enzyme replacement therapy; ERT), which slow the progression of the disease. ERT is given to male and female patients of all ages but as yet little is documented on the effects of continuing ERT during pregnancy. The aim of this case series was therefore to ascertain the pregnancy outcomes of women with GSD II on ERT and to describe adverse events associated with pregnancy, delivery and therapy. METHODS: The medical records of eight women attending the Royal Free Hospital Lysosomal Storage Disorders Unit were reviewed. Four of the eight women had seven pregnancies over a period of 8 years. RESULTS: In this series GSD II was associated with interventional deliveries but normal neonates. Cessation of ERT in early pregnancy resulted in deterioration of maternal symptoms and emergence of allergic reactions on restarting ERT. CONCLUSION: Individualized care plans are required to ensure the best neonatal and maternal outcomes. Consideration should be given to the potential benefits to mother and fetus of continuing ERT during pregnancy

Cu-Ni-PGE mineralisation at the Aurora Project and potential for a new PGE province in the Northern Bushveld Main Zone

This is the final version of the article. Available from Elsevier via the DOI in this record.he Aurora Project is a Cu-Ni-PGE magmatic sulphide deposit in the northern limb of the Bushveld Complex of South Africa. Since 1992 mining in the northern limb has focussed on the Platreef deposit, located along the margin of the complex. Aurora has previously been suggested to represent a far-northern facies of the Platreef located along the basal margin of the complex and this study provides new data with which to test this assertion. In contrast to the Platreef, the base metal sulphide mineralisation at Aurora is both Cu-rich (Ni/Cu 50,000) reflecting the preferential removal of Pd over Cu in the sulphides below. Similarly high Cu/Pd ratios characterise the Upper Main Zone in the northern limb above the pigeonite + orthopyroxene interval and suggest that Aurora-style sulphide mineralisation may be developed here as well. The same mineralogy and geochemical features also appear to be present in the T Zone of the Waterberg PGE deposit, located under younger cover rocks to the north of Aurora. If these links are proved they indicate the potential for a previously unsuspected zone of Cu-Ni-PGE mineralisation extending for over 40 km along strike through the Upper Main Zone of the northern Bushveld.Sulphur isotope analyses were carried out by Alison MacDonald at the Scottish Universities Environmental Research Centre as part of NERC Isotope Geoscience Facilities Committee award IP/909/0506. HSRH is sponsored by the Claude Leon Foundation

Sulphide sinking in magma conduits: Evidence from mafic–ultramafic plugs on Rum and the wider North Atlantic Igneous Province

This is the final version of the article. Available from the publisher via the DOI in this record.Ni–Cu–PGE (platinum group element) sulphide mineralization is commonly found in magmatic conduit systems. In many cases the trigger for formation of an immiscible sulphide liquid involves assimilation of S-bearing crustal rocks. Conceptually, the fluid dynamics of sulphide liquid droplets within such conduits is essentially a balance between gravitational sinking and upwards entrainment. Thus, crustal contamination signatures may be present in sulphides preserved both up- and down-flow from the point of interaction with the contaminant. We examine a suite of ultramafic volcanic plugs on the Isle of Rum, Scotland, to decipher controls on sulphide accumulation in near-surface magma conduits intruded into a variable sedimentary stratigraphy. The whole-rock compositions of the plugs broadly overlap with the compositions of ultramafic units within the Rum Layered Complex, although subtle differences between each plug highlight their individuality. Interstitial base metal sulphide minerals occur in all ultramafic plugs on Rum. Sulphide minerals have magmatic δ34S (ranging from –1·3 to +2·1‰) and S/Se ratios (mean = 2299), and demonstrate that the conduit magmas were already S-saturated. However, two plugs in NW Rum contain substantially coarser (sometimes net-textured) sulphides with unusually light δ34S (–14·7 to +0·3‰) and elevated S/Se ratios (mean = 4457), not represented by the immediate host-rocks. Based on the Hebrides Basin sedimentary stratigraphy, it is likely that the volcanic con duits would have intruded through a package of Jurassic mudrocks with characteristically light δ34S (–33·8 to –14·7‰). We propose that a secondary crustal S contamination event took place at a level above that currently exposed, and that these sulphides sank back to their present position. Modelling suggests that upon the cessation of active magma transport, sulphide liquids could have sunk back through the conduit over a distance of several hundreds of metres, over a period of a few days. This sulphide ‘withdrawal’ process may be observed in other vertical or steeply inclined magma conduits globally; for example, in the macrodykes of East Greenland. Sulphide liquid sinking within a non-active conduit or during magma ‘suck-back’ may help to explain crustal S-isotopic compositions in magma conduits that appear to lack appropriate lithologies to support this contamination, either locally or deeper in the system.Sulphur isotope analyses were funded by NERC Isotope Geosciences Facilities grant, IP-1356-1112. H.S.R.H. acknowledges the financial support of the Natural Environment Research Council (NERC) for her PhD studentship (NE/J50029X) and funding of open access publication. This is a contribution to the TeaSe (Te and Se Cycling and Supply) research consortium supported by NERC award NE/M011615/1 to Cardiff University and the University of Leicester