159 research outputs found
When signalling goes wrong:pathogenic variants in structural and signalling proteins causing cardiomyopathies
Cardiomyopathies are a diverse group of cardiac disorders with distinct phenotypes, depending on the proteins and pathways affected. A substantial proportion of cardiomyopathies are inherited and those will be the focus of this review article. With the wide application of high-throughput sequencing in the practice of clinical genetics, the roles of novel genes in cardiomyopathies are recognised. Here, we focus on a subgroup of cardiomyopathy genes [TTN, FHL1, CSRP3, FLNC and PLN, coding for Titin, Four and a Half LIM domain 1, Muscle LIM Protein, Filamin C and Phospholamban, respectively], which, despite their diverse biological functions, all have important signalling functions in the heart, suggesting that disturbances in signalling networks can contribute to cardiomyopathies
Software compensation in particle flow reconstruction.
The particle flow approach to calorimetry benefits from highly granular calorimeters and sophisticated software algorithms in order to reconstruct and identify individual particles in complex event topologies. The high spatial granularity, together with analogue energy information, can be further exploited in software compensation. In this approach, the local energy density is used to discriminate electromagnetic and purely hadronic sub-showers within hadron showers in the detector to improve the energy resolution for single particles by correcting for the intrinsic non-compensation of the calorimeter system. This improvement in the single particle energy resolution also results in a better overall jet energy resolution by improving the energy measurement of identified neutral hadrons and improvements in the pattern recognition stage by a more accurate matching of calorimeter energies to tracker measurements. This paper describes the software compensation technique and its implementation in particle flow reconstruction with the Pandora Particle Flow Algorithm (PandoraPFA). The impact of software compensation on the choice of optimal transverse granularity for the analogue hadronic calorimeter option of the International Large Detector (ILD) concept is also discussed
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Analysis of three epoetin alpha products by LC and LC-MS indicates differences in glycosylation critical quality attributes, including sialic acid content
Erythropoietin (EPO) is one of the main therapeutics used to treat anaemic patients, greatly improving their quality of life. In this study, biosimilars Binocrit and a development product, called here CIGB-EPO, were compared to the originator product, Eprex. All three are epoetin alpha products, reputed to have similar glycosylation profiles. The quality, safety and efficacy of this biotherapeutic depend on the following glycosylation critical quality attributes (GCQAs): sialylation, N-glycolyl-neuraminic acid (Neu5Gc) content, branching, N-acetyl-lactosamine (LacNAc) extensions and O-acetylation pattern. Reverse-phase ultra high pressure liquid chromatography (RP-UHPLC) analysis of acid-released, 1,2-diamino-4,5-methylenedioxybenzene (DMB) labelled sialic acid derivatives and hydrophilic interaction liquid chromatography (HILIC) in combination with mass spectrometry (HILIC-UHPLC-MS) of procainamide (PROC) labelled N-glycans were the analytical tools used. An automated method for enzymatic release and PROC labelling was applied for the first time to the erythropoiesis stimulating agent (ESA) products, which facilitated novel, in-depth characterisation, and allowed identification of precise structural features including the location of O-acetyl groups on sialic acid (SA) moie-ties. Samples were digested by a sialate-O-acetylesterase (NanS) to confirm the presence of O-acetyl groups. It was found that Eprex contained the greatest relative abundance of O-acetylated derivatives, Binocrit expressed the least Neu5Gc, and CIGB-EPO showed the greatest variety of high-mannose-phosphate structures. The sialylation and LacNAc extension patterns of the three ESAs were similar, with a maximum of four N-acetyl-neuraminic acid (Neu5Ac) moieties detected per glycan. Such differences in SA derivatisation, particularly O-acetylation, could have consequences for the quality and safety of a biotherapeutic, as well as its efficacy
Tests of model of color reconnection and a search for glueballs using gluon jets with a rapidity gap
Gluon jets with a mean energy of 22 GeV and purity of 95% are selected from
hadronic Z0 decay events produced in e+e- annihilations. A subsample of these
jets is identified which exhibits a large gap in the rapidity distribution of
particles within the jet. After imposing the requirement of a rapidity gap, the
gluon jet purity is 86%. These jets are observed to demonstrate a high degree
of sensitivity to the presence of color reconnection, i.e. higher order QCD
processes affecting the underlying color structure. We use our data to test
three QCD models which include a simulation of color reconnection: one in the
Ariadne Monte Carlo, one in the Herwig Monte Carlo, and the other by Rathsman
in the Pythia Monte Carlo. We find the Rathsman and Ariadne color reconnection
models can describe our gluon jet measurements only if very large values are
used for the cutoff parameters which serve to terminate the parton showers, and
that the description of inclusive Z0 data is significantly degraded in this
case. We conclude that color reconnection as implemented by these two models is
disfavored. The signal from the Herwig color reconnection model is less clear
and we do not obtain a definite conclusion concerning this model. In a separate
study, we follow recent theoretical suggestions and search for glueball-like
objects in the leading part of the gluon jets. No clear evidence is observed
for these objects.Comment: 42 pages, 18 figure
W Boson Polarisation at LEP2
Elements of the spin density matrix for W bosons in e+e- -> W+W- -> qqln
events are measured from data recorded by the OPAL detector at LEP. This
information is used calculate polarised differential cross-sections and to
search for CP-violating effects. Results are presented for W bosons produced in
e+e- collisions with centre-of-mass energies between 183 GeV and 209 GeV. The
average fraction of W bosons that are longitudinally polarised is found to be
(23.9 +- 2.1 +- 1.1)% compared to a Standard Model prediction of (23.9 +-
0.1)%. All results are consistent with CP conservation.Comment: 20 pages, 3 figures, Submitted to Phys. Letts.
Search for Yukawa Production of a Light Neutral Higgs Boson at LEP
Within a Two-Higgs-Doublet Model (2HDM) a search for a light Higgs boson in
the mass range of 4-12 GeV has been performed in the Yukawa process e+e- -> b
bbar A/h -> b bbar tau+tau-, using the data collected by the OPAL detector at
LEP between 1992 and 1995 in e+e- collisions at about 91 GeV centre-of-mass
energy. A likelihood selection is applied to separate background and signal.
The number of observed events is in good agreement with the expected
background. Within a CP-conserving 2HDM type II model the cross-section for
Yukawa production depends on xiAd = |tan beta| and xihd = |sin alpha/cos beta|
for the production of the CP-odd A and the CP-even h, respectively, where tan
beta is the ratio of the vacuum expectation values of the Higgs doublets and
alpha is the mixing angle between the neutral CP-even Higgs bosons. From our
data 95% C.L. upper limits are derived for xiAd within the range of 8.5 to 13.6
and for xihd between 8.2 to 13.7, depending on the mass of the Higgs boson,
assuming a branching fraction into tau+tau- of 100%. An interpretation of the
limits within a 2HDM type II model with Standard Model particle content is
given. These results impose constraints on several models that have been
proposed to explain the recent BNL measurement of the muon anomalous magnetic
moment.Comment: 24 pages, 9 figures, Submitted to Euro. Phys. J.
A study of charm production in beauty decays with the OPAL detector at LEP
Using an inclusive method, BR(b -> D\bar{D}X) has been measured in hadronic
Z^0 decays with the OPAL detector at LEP. The impact parameter significance of
tracks opposite tagged b-jets is used to differentiate b -> D\bar{D}X decays
from other decays. Using this result, the average number of charm and
anti-charm quarks produced per beauty quark decay, n_c, is determined.Comment: 20 pages, 4 figure
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