To investigate the global changes accompanying human dilated cardiomyopathy (DCM) we performed a large-scale expression screen using myocardial biopsies from a group of DCM patients with moderate ...heart failure. By hierarchical clustering and functional annotation of the deregulated genes we examined extensive changes in the cellular and molecular processes associated to DCM.
The expression profiles were obtained using a whole genome covering library (UniGene RZPD1) comprising 30336 cDNA clones and amplified RNA from myocardiac biopsies from 10 DCM patients in comparison to tissue samples from four non-failing, healthy donors.
By setting stringent selection criteria 364 differentially expressed, sequence-verified non-redundant transcripts were identified with a false discovery rate of <0.001. Numerous genes and ESTs were identified representing previously recognised, as well as novel DCM-associated transcripts. Many of them were found to be upregulated and involved in cardiomyocyte energetics, muscle contraction or signalling. Two hundred and twenty-two deregulated transcripts were functionally annotated and hierarchically clustered providing an insight into the pathophysiology of DCM. Data was validated using the MLP-deficient mouse, in which several differentially expressed transcripts identified in the human DCM biopsies could be confirmed.
We report the first genome-wide expression profile analysis using cardiac biopsies from DCM patients at various stages of the disease. Although there is a diversity of links between the cytoskeleton and the initiation of DCM, we speculate that genes implicated in intracellular signalling and in muscle contraction are associated with early stages of the disease. Altogether this study represents the most comprehensive and inclusive molecular portrait of human cardiomyopathy to date.
: The use of DNA microarray technology in biomedical research has dramatically increased during the past years. In the present report, we provide an overview on the basic DNA microarray technology ...and biostatistical methods for gene expression analysis. A focus is then put on its applications in dermatological research. In recent years, a series of gene expression studies have been performed for various dermatological diseases, such as malignant melanoma, psoriasis and lupus erythematosus. These analyses have identified interesting target genes as well as putative disease susceptibility loci. However, further functional studies will be needed for a more complete understanding of the pathogenesis of these diseases. This may be performed by means of the recently developed RNA interference technology. Besides its role in large‐scale gene expression studies, DNA microarray technology has proved to be a valuable tool for genomic screens of genetic alterations, e.g. single nucleotide polymorphisms. These play a role in tumour development and progression, and also function as genetic markers for disease susceptibility. Taken together, DNA microarray technology opens enormous perspectives for dermatologists. It may help us understand the complex pathogenesis of a wide variety of dermatologic diseases and identify their genetic background.
We investigated the incorporation of Se into the proteins of liver and muscle, the two main Se pools, during replenishment of Se-deficient rats with normal or large doses of 75Se-labeled selenite and ...selenomethionine, doses equivalent to the amounts ingested from a diet with 0.2 or 2 mg Se/kg. With the higher intake, Se levels were elevated. More Se was retained from selenomethionine than from selenite. After separation of the labeled proteins, it was apparent that the higher tissue Se contents were mainly due to nonspecific incorporation into a large number of proteins. We observed no differences between the two chemical forms with regard to the formation of the specific selenoproteins. The 10-fold increase in the Se supply led to a relatively small rise in the levels of these compounds. The results indicate that after ingestion of normal amounts of selenite nearly all of the element is present in the specific selenoproteins. With increasing doses a part is also incorporated nonspecifically into numerous other proteins. In the case of selenomethionine, a part of the element follows the same metabolic pathways, but a percentage is also deposited directly and nonspecifically into proteins in place of methionine
The interaction of
K
-
with protons is characterised by the presence of several coupled channels, systems like
K
¯
0
n and
π
Σ
with a similar mass and the same quantum numbers as the
K
-
p state. The ...strengths of these couplings to the
K
-
p system are of crucial importance for the understanding of the nature of the
Λ
(
1405
)
resonance and of the attractive
K
-
p strong interaction. In this article, we present measurements of the
K
-
p correlation functions in relative momentum space obtained in pp collisions at
s
=
13
Te, in p–Pb collisions at
s
NN
=
5.02
Te, and (semi)peripheral Pb–Pb collisions at
s
NN
=
5.02
Te. The emitting source size, composed of a core radius anchored to the
K
+
p correlation and of a resonance halo specific to each particle pair, varies between 1 and 2 fm in these collision systems. The strength and the effects of the
K
¯
0
n and
π
Σ
inelastic channels on the measured
K
-
p correlation function are investigated in the different colliding systems by comparing the data with state-of-the-art models of chiral potentials. A novel approach to determine the conversion weights
ω
, necessary to quantify the amount of produced inelastic channels in the correlation function, is presented. In this method, particle yields are estimated from thermal model predictions, and their kinematic distribution from blast-wave fits to measured data. The comparison of chiral potentials to the measured
K
-
p interaction indicates that, while the
π
Σ
–
K
-
p dynamics is well reproduced by the model, the coupling to the
K
¯
0
n channel in the model is currently underestimated.
A
bstract
The jet angularities are a class of jet substructure observables which characterize the angular and momentum distribution of particles within jets. These observables are sensitive to ...momentum scales ranging from perturbative hard scatterings to nonperturbative fragmentation into final-state hadrons. We report measurements of several groomed and ungroomed jet angularities in pp collisions at
s
= 5
.
02 TeV with the ALICE detector. Jets are reconstructed using charged particle tracks at midrapidity (
|η| <
0
.
9). The anti-
k
T
algorithm is used with jet resolution parameters
R
= 0
.
2 and
R
= 0
.
4 for several transverse momentum
p
T
ch
jet
intervals in the 20–100 GeV/
c
range. Using the jet grooming algorithm Soft Drop, the sensitivity to softer, wide-angle processes, as well as the underlying event, can be reduced in a way which is well-controlled in theoretical calculations. We report the ungroomed jet angularities,
λ
α
, and groomed jet angularities,
λ
α
,g
, to investigate the interplay between perturbative and nonperturbative effects at low jet momenta. Various angular exponent parameters
α
= 1, 1.5, 2, and 3 are used to systematically vary the sensitivity of the observable to collinear and soft radiation. Results are compared to analytical predictions at next-to-leading-logarithmic accuracy, which provide a generally good description of the data in the perturbative regime but exhibit discrepancies in the nonperturbative regime. Moreover, these measurements serve as a baseline for future ones in heavy-ion collisions by providing new insight into the interplay between perturbative and nonperturbative effects in the angular and momentum substructure of jets. They supply crucial guidance on the selection of jet resolution parameter, jet transverse momentum, and angular scaling variable for jet quenching studies.
A
bstract
The cross section for coherent photonuclear production of J/
ψ
is presented as a function of the electromagnetic dissociation (EMD) of Pb. The measurement is performed with the ALICE ...detector in ultra-peripheral Pb-Pb collisions at a centre-of-mass energy per nucleon pair of
s
NN
= 5.02 TeV. Cross sections are presented in five different J/
ψ
rapidity ranges within |
y
| < 4, with the J/
ψ
reconstructed via its dilepton decay channels. In some events the J/
ψ
is not accompanied by EMD, while other events do produce neutrons from EMD at beam rapidities either in one or the other beam direction, or in both. The cross sections in a given rapidity range and for different configurations of neutrons from EMD allow for the extraction of the energy dependence of this process in the range 17 <
W
γ
Pb
,
n
< 920 GeV, where
W
γ
Pb
,
n
is the centre-of-mass energy per nucleon of the
γ
Pb system. This range corresponds to a Bjorken-
x
interval spanning about three orders of magnitude: 1.1 × 10
−
5
<
x
< 3.3 × 10
−
2
. In addition to the ultra-peripheral and photonuclear cross sections, the nuclear suppression factor is obtained. These measurements point to a strong depletion of the gluon distribution in Pb nuclei over a broad, previously unexplored, energy range. These results, together with previous ALICE measurements, provide unprecedented information to probe quantum chromodynamics at high energies.
This report summarizes the work of the EMMI Rapid Reaction Task Force on "Real and Virtual Photon Production at Ultra-Low Transverse Momentum and Low Mass at the LHC". We provide an overview of the ...soft-photon puzzle, i.e., of the long-standing discrepancy between experimental data and predictions based on Low's soft-photon theorem, also referred to as "anomalous" soft photon production, and we review the current theoretical understanding of soft radiation and soft theorems. We also focus on low-mass dileptons as a tool for determining the electrical conductivity of the medium produced in high-energy nucleus-nucleus collisions. We discuss how both topics can be addressed with the planned ALICE 3 detector at the LHC.
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