Gaucher disease: expression and characterization of mild and severe acid beta-glucosidase mutations in Portuguese type 1 patients

Type 1 Gaucher disease (GD), the most prevalent lysosomal storage disease, results from the deficient activity of acid alpha-glucosidase. Molecular analysis of 12 unrelated Portuguese patients with type 1 GD identified three novel acid â-glucosidase mutations (F109V, W184R and R395P), as well as three previously reported, but uncharacterized, lesions (R359Q, G377S and N396T). The type 1 probands were either heteroallelic for the well-characterized common lesion, N370S, and the F109V, W184R, R359Q or N396T lesions or homoallelic for the G377S or N396T mutations. Expression of the W184R, R359Q, and R395P mutations revealed very low specific activities based on cross-reacting immunologic material (CRIM SAs of 0.0004, 0.016 and 0.045, respectively), consistent with their being found only in type 1 patients who had a neuroprotective N370S allele. In contrast, the F109V, G377S and N396T alleles had significant acid â-glucosidase activity (CRIM specific activities of 0.15, 0.17, 0.14, respectively), in agreement with their being mild type 1 alleles. Thus, these studies identified additional acid â-glucosidase mutations in the Portuguese population and demonstrated that the G377S and N396T mutations were neuroprotective, consistent with the mild clinical phenotypes of the type 1 patients who were homoallelic for the G377S and N396T lesions

Cross-over behaviour in a communication network

We address the problem of message transfer in a communication network. The network consists of nodes and links, with the nodes lying on a two dimensional lattice. Each node has connections with its nearest neighbours, whereas some special nodes, which are designated as hubs, have connections to all the sites within a certain area of influence. The degree distribution for this network is bimodal in nature and has finite variance. The distribution of travel times between two sites situated at a fixed distance on this lattice shows fat fractal behaviour as a function of hub-density. If extra assortative connections are now introduced between the hubs so that each hub is connected to two or three other hubs, the distribution crosses over to power-law behaviour. Cross-over behaviour is also seen if end-to-end short cuts are introduced between hubs whose areas of influence overlap, but this is much milder in nature. In yet another information transmission process, namely, the spread of infection on the network with assortative connections, we again observed cross-over behaviour of another type, viz. from one power-law to another for the threshold values of disease transmission probability. Our results are relevant for the understanding of the role of network topology in information spread processes.Comment: 12 figure

Cosmology of the Lifshitz universe

We study the ultraviolet complete non-relativistic theory recently proposed by Horava. After introducing a Lifshitz scalar for a general background, we analyze the cosmology of the model in Lorentzian and Euclidean signature. Vacuum solutions are found and it is argued the existence of non-singular bouncing profiles. We find a general qualitative agreement with both the picture of Causal Dynamical Triangulations and Quantum Einstein Gravity. However, inflation driven by a Lifshitz scalar field on a classical background might not produce a scale-invariant spectrum when the principle of detailed balance is assumed.Comment: 23 pages. v2: one reference and one equation added, main conclusions unchanged; v3: matches published version, discussion improved, typos correcte

Dynamics with Infinitely Many Derivatives: The Initial Value Problem

Differential equations of infinite order are an increasingly important class of equations in theoretical physics. Such equations are ubiquitous in string field theory and have recently attracted considerable interest also from cosmologists. Though these equations have been studied in the classical mathematical literature, it appears that the physics community is largely unaware of the relevant formalism. Of particular importance is the fate of the initial value problem. Under what circumstances do infinite order differential equations possess a well-defined initial value problem and how many initial data are required? In this paper we study the initial value problem for infinite order differential equations in the mathematical framework of the formal operator calculus, with analytic initial data. This formalism allows us to handle simultaneously a wide array of different nonlocal equations within a single framework and also admits a transparent physical interpretation. We show that differential equations of infinite order do not generically admit infinitely many initial data. Rather, each pole of the propagator contributes two initial data to the final solution. Though it is possible to find differential equations of infinite order which admit well-defined initial value problem with only two initial data, neither the dynamical equations of p-adic string theory nor string field theory seem to belong to this class. However, both theories can be rendered ghost-free by suitable definition of the action of the formal pseudo-differential operator. This prescription restricts the theory to frequencies within some contour in the complex plane and hence may be thought of as a sort of ultra-violet cut-off.Comment: 40 pages, no figures. Added comments concerning fractional operators and the implications of restricting the contour of integration. Typos correcte

α-intercalated cells defend the urinary system from bacterial infection

{alpha}–Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC–dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2. The presence of LCN2 in urine was both necessary and sufficient to control the urinary tract infection through iron sequestration, even in the harsh condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and urinary acidification were reduced, and consequently bacterial clearance was limited. Together these results indicate that A-ICs, which are known to regulate acid-base metabolism, are also critical for urinary defense against pathogenic bacteria. They respond to both cystitis and pyelonephritis by delivering bacteriostatic chemical agents to the lower urinary system

Anisotropy studies around the galactic centre at EeV energies with the Auger Observatory

Data from the Pierre Auger Observatory are analyzed to search for anisotropies near the direction of the Galactic Centre at EeV energies. The exposure of the surface array in this part of the sky is already significantly larger than that of the fore-runner experiments. Our results do not support previous findings of localized excesses in the AGASA and SUGAR data. We set an upper bound on a point-like flux of cosmic rays arriving from the Galactic Centre which excludes several scenarios predicting sources of EeV neutrons from Sagittarius $A$. Also the events detected simultaneously by the surface and fluorescence detectors (the `hybrid' data set), which have better pointing accuracy but are less numerous than those of the surface array alone, do not show any significant localized excess from this direction.Comment: Matches published versio

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters