3,621 research outputs found
Factorization scheme and scale dependence in diffractive dijet production at low Q^2
We calculate diffractive dijet production in deep-inelastic scattering at
next-to-leading order of perturbative QCD, including contributions from direct
and resolved photons, and compare our predictions to preliminary data from the
H1 collaboration at HERA. We study how the cross section depends on the
factorization scheme and scale M_\gamma at the virtual photon vertex for the
occurrence of factorization breaking. The strong M_\gamma-dependence, which is
present when only the resolved cross section is suppressed, is tamed by
introducing the suppression also into the initial-state NLO correction of the
direct part.Comment: 14 pages, 6 figure
Miroslav Frýdek a kolektiv: Právní, náboženské a politické aspekty starověké římské rodiny
Recenze publikace - Miroslav Frýdek a kolektiv: Právní, náboženské a politické aspekty starověké římské rodiny1. vyd. Ostrava: KEY Publishing s.r.o., 2012, 122 s. ISBN 978-80-7418-157-
Identification of small-molecule inhibitors of the antiapoptotic protein myeloid cell leukaemia-1 (Mcl-1)
Protein–protein interactions (PPIs) control many cellular processes in cancer and tumour growth. Of significant interest is the role PPIs play in regulating apoptosis. The overexpression of the antiapoptosis regulating Bcl-2 family of proteins is commonly observed in several cancers, leading to resistance towards both radiation and chemotherapies. From this family, myeloid cell leukemia-1 (Mcl-1) has proven the most difficult to target, and one of the leading causes of treatment resistance. Exploiting the selective PPI between the apoptosis-regulating protein Noxa and Mcl-1, utilising a fluorescence polarization assay, we have identified four small molecules with the ability to modulate Mcl-1. The identified compounds were computationally modelled and docked against the Mcl-1 binding interface to obtain structural information about their binding sites allowing for future analogue design. When examined for their activity towards pancreatic cell lines that overexpress Mcl-1 (MiaPaCa-2 and BxPC-3), the identified compounds demonstrated growth inhibition, suggesting effective Mcl-1 modulation
Comparison of niti orthodontic archwires and a determination of the characteristic properties
The aim of this paper was to analyse the characteristic properties of six different, commercially available nickel-titanium orthodontic wires with a diameter of 0.305 mm (0.014"). The characteristic properties were determined by using semi-quantitative EDX analyses, DSC analyses for a determination of the phase temperatures, and a tensile test to obtain the mechanical properties of the wires. The investigation of the chemical composition showed an equiatomic NiTi alloy. Analyses of phase temperatures showed that the nickel-titanium orthodontic wires were, in an austenitic microstructure, exhibiting a superelastic effect in the oral environment. The uniaxial tensile stress strain curves showed different values for the beginning and the end of the transformation range during the loading
Selective and potent proteomimetic inhibitors of intracellular protein–protein interactions
Inhibition of protein–protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed “proteomimetics”, which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified
Relative luminosity measurement of the LHC with the ATLAS forward calorimeter
In this paper it is shown that a measurement of the relative luminosity
changes at the LHC may be obtained by analysing the currents drawn from the
high voltage power supplies of the electromagnetic section of the forward
calorimeter of the ATLAS detector. The method was verified with a reproduction
of a small section of the ATLAS forward calorimeter using proton beams of known
beam energies and variable intensities at the U-70 accelerator at IHEP in
Protvino, Russia. The experimental setup and the data taking during a test beam
run in April 2008 are described in detail. A comparison of the measured high
voltage currents with reference measurements from beam intensity monitors shows
a linear dependence on the beam intensity. The non-linearities are measured to
be less than 0.5 % combining statistical and systematic uncertainties.Comment: 16 page
Measurement of the Spin-Dependence of the pbar-p Interaction at the AD-Ring
We propose to use an internal polarized hydrogen storage cell gas target in
the AD ring to determine for the first time the two total spin-dependent pbar-p
cross sections sigma_1 and sigma_2 at antiproton beam energies in the range
from 50 to 450 MeV. The data obtained are of interest by themselves for the
general theory of pbar-p interactions since they will provide a first
experimental constraint of the spin-spin dependence of the nucleon-antinucleon
potential in the energy range of interest. In addition, measurements of the
polarization buildup of stored antiprotons are required to define the optimum
parameters of a future, dedicated Antiproton Polarizer Ring (APR), intended to
feed a double-polarized asymmetric pbar-p collider with polarized antiprotons.
Such a machine has recently been proposed by the PAX collaboration for the new
Facility for Antiproton and Ion Research (FAIR) at GSI in Darmstadt, Germany.
The availability of an intense stored beam of polarized antiprotons will
provide access to a wealth of single- and double-spin observables, thereby
opening a new window on QCD spin physics.Comment: 51 pages, 23 figures, proposal submitted to the SPS committee of CER
Unveiling the "Three Finger Pharmacophore" required for p53-MDM2 Inhibition by Saturation Transfer Difference NMR Initial Growth Rates Approach
Inhibitors of the p53-MDM2 protein-protein interaction are emerging as a novel and validated approach to treating cancer. In this work we describe the synthesis and inhibitory evaluation of a series of isoquinolin-1-one analogues, and highlight the utility of an initial growth rates STD NMR approach supported by protein-ligand docking to investigate p53-MDM2 inhibition. The approach is illustrated by the study of compound 1, providing key insights into the binding mode of this kind of MDM2 ligands and, more importantly, readily unveiling the previously proposed three finger pharmacophore requirement for p53-MDM2 inhibition
S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth
Escape from apoptosis is one of the major hallmarks of cancer cells. The B-cell Lymphoma 2 (BCL-2) gene family encodes pro-apoptotic and anti-apoptotic proteins that are key regulators of the apoptotic process. Overexpression of the pro-survival member BCL-2 is a well-established mechanism contributing to oncogenesis and chemoresistance in several cancers, including lymphoma and leukemia. Thus, BCL-2 has become an attractive target for therapeutic strategy in cancer, as demonstrated by the recent approval of ABT-199 (Venclexta™) in relapsed or refractory Chronic Lymphocytic Leukemia with 17p deletion. Here, we describe a novel orally bioavailable BCL-2 selective and potent inhibitor called S55746 (also known as BCL201). S55746 occupies the hydrophobic groove of BCL-2. Its selectivity profile demonstrates no significant binding to MCL-1, BFL-1 (BCL2A1/A1) and poor affinity for BCL-XL. Accordingly, S55746 has no cytotoxic activity on BCL-XL-dependent cells, such as platelets. In a panel of hematological cell lines, S55746 induces hallmarks of apoptosis including externalization of phosphatidylserine, caspase-3 activation and PARP cleavage. Ex vivo, S55746 induces apoptosis in the low nanomolar range in primary Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma patient samples. Finally, S55746 administered by oral route daily in mice demonstrated robust anti-tumor efficacy in two hematological xenograft models with no weight lost and no change in behavior. Taken together, these data demonstrate that S55746 is a novel, well-tolerated BH3-mimetic targeting selectively and potently the BCL-2 protein
Forward pi^0 Production and Associated Transverse Energy Flow in Deep-Inelastic Scattering at HERA
Deep-inelastic positron-proton interactions at low values of Bjorken-x down
to x \approx 4.10^-5 which give rise to high transverse momentum pi^0 mesons
are studied with the H1 experiment at HERA. The inclusive cross section for
pi^0 mesons produced at small angles with respect to the proton remnant (the
forward region) is presented as a function of the transverse momentum and
energy of the pi^0 and of the four-momentum transfer Q^2 and Bjorken-x.
Measurements are also presented of the transverse energy flow in events
containing a forward pi^0 meson. Hadronic final state calculations based on QCD
models implementing different parton evolution schemes are confronted with the
data.Comment: 27 pages, 8 figures and 3 table
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