542 research outputs found
Intramolecular Acylal Cyclisation (IAC) as an Efficient Synthetic Strategy towards the Total Synthesis of Erythrina Alkaloid Derivatives
Compounds that comprise the erythrina alkaloid class of natural products are based on a tetracyclic spiroamine framework and exhibit a range of biological activities on the central nervous system. Herein, we report a new and efficient total synthesis of this multiple-ring system based on an intramolecular acylal cyclisation (IAC) approach. Using this methodology, the tetracyclic core was rapidly assembled over a two-step domino process catalysed by a Lewis acid. The effect of heteroatoms, substituents and ring size on the IAC has also been investigated, and the broad application of this procedure is demonstrated by the synthesis of a library of derivatives in good yields with excellent regioselectivity
The Evolution of X-ray Clusters of Galaxies
Considerable progress has been made over the last decade in the study of the
evolutionary trends of the population of galaxy clusters in the Universe. In
this review we focus on observations in the X-ray band. X-ray surveys with the
ROSAT satellite, supplemented by follow-up studies with ASCA and Beppo-SAX,
have allowed an assessment of the evolution of the space density of clusters
out to z~1, and the evolution of the physical properties of the intra-cluster
medium out to z~0.5. With the advent of Chandra and Newton-XMM, and their
unprecedented sensitivity and angular resolution, these studies have been
extended beyond redshift unity and have revealed the complexity of the
thermodynamical structure of clusters. The properties of the intra-cluster gas
are significantly affected by non-gravitational processes including star
formation and Active Galactic Nucleus (AGN) activity. Convincing evidence has
emerged for modest evolution of both the bulk of the X-ray cluster population
and their thermodynamical properties since redshift unity. Such an
observational scenario is consistent with hierarchical models of structure
formation in a flat low density universe with Omega_m=0.3 and sigma_8=0.7-0.8
for the normalization of the power spectrum. Basic methodologies for
construction of X-ray-selected cluster samples are reviewed and implications of
cluster evolution for cosmological models are discussed.Comment: 40 pages, 15 figures. Full resolution figures can be downloaded from
http://www.eso.org/~prosati/ARAA
Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy
<p>Abstract</p> <p>Background</p> <p>Antisense-mediated exon skipping is currently one of the most promising therapeutic approaches for Duchenne muscular dystrophy (DMD). Using antisense oligonucleotides (AONs) targeting specific exons the DMD reading frame is restored and partially functional dystrophins are produced. Following proof of concept in cultured muscle cells from patients with various deletions and point mutations, we now focus on single and multiple exon duplications. These mutations are in principle ideal targets for this approach since the specific skipping of duplicated exons would generate original, full-length transcripts.</p> <p>Methods</p> <p>Cultured muscle cells from DMD patients carrying duplications were transfected with AONs targeting the duplicated exons, and the dystrophin RNA and protein were analyzed.</p> <p>Results</p> <p>For two brothers with an exon 44 duplication, skipping was, even at suboptimal transfection conditions, so efficient that both exons 44 were skipped, thus generating, once more, an out-of-frame transcript. In such cases, one may resort to multi-exon skipping to restore the reading frame, as is shown here by inducing skipping of exon 43 and both exons 44. By contrast, in cells from a patient with an exon 45 duplication we were able to induce single exon 45 skipping, which allowed restoration of wild type dystrophin. The correction of a larger duplication (involving exons 52 to 62), by combinations of AONs targeting the outer exons, appeared problematic due to inefficient skipping and mistargeting of original instead of duplicated exons.</p> <p>Conclusion</p> <p>The correction of DMD duplications by exon skipping depends on the specific exons targeted. Its options vary from the ideal one, restoring for the first time the true, wild type dystrophin, to requiring more 'classical' skipping strategies, while the correction of multi-exon deletions may need the design of tailored approaches.</p
The dependence of dijet production on photon virtuality in ep collisions at HERA
The dependence of dijet production on the virtuality of the exchanged photon,
Q^2, has been studied by measuring dijet cross sections in the range 0 < Q^2 <
2000 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of
38.6 pb^-1.
Dijet cross sections were measured for jets with transverse energy E_T^jet >
7.5 and 6.5 GeV and pseudorapidities in the photon-proton centre-of-mass frame
in the range -3 < eta^jet <0. The variable xg^obs, a measure of the photon
momentum entering the hard process, was used to enhance the sensitivity of the
measurement to the photon structure. The Q^2 dependence of the ratio of low- to
high-xg^obs events was measured.
Next-to-leading-order QCD predictions were found to generally underestimate
the low-xg^obs contribution relative to that at high xg^obs. Monte Carlo models
based on leading-logarithmic parton-showers, using a partonic structure for the
photon which falls smoothly with increasing Q^2, provide a qualitative
description of the data.Comment: 35 pages, 6 eps figures, submitted to Eur.Phys.J.
Beauty photoproduction measured using decays into muons in dijet events in ep collisions at =318 GeV
The photoproduction of beauty quarks in events with two jets and a muon has
been measured with the ZEUS detector at HERA using an integrated luminosity of
110 pb. The fraction of jets containing b quarks was extracted from the
transverse momentum distribution of the muon relative to the closest jet.
Differential cross sections for beauty production as a function of the
transverse momentum and pseudorapidity of the muon, of the associated jet and
of , the fraction of the photon's momentum participating in
the hard process, are compared with MC models and QCD predictions made at
next-to-leading order. The latter give a good description of the data.Comment: 32 pages, 6 tables, 7 figures Table 6 and Figure 7 revised September
200
Search for a narrow charmed baryonic state decaying to D^*+/- p^-/+ in ep collisions at HERA
A resonance search has been made in the D^*+/- p^-/+ invariant-mass spectrum
with the ZEUS detector at HERA using an integrated luminosity of 126 pb^-1. The
decay channels D^*+ -> D^0 pi^+_s -> (K^- pi^+) pi^+_s and D^*+ -> D^0 pi^+_s
-> (K^- pi^+ pi^+ pi^-) pi^+_s (and the corresponding antiparticle decays) were
used to identify D^*+/- mesons. No resonance structure was observed in the
D^*+/- p^-/+ mass spectrum from more than 60000 reconstructed D^*+/- mesons.
The results are not compatible with a report of the H1 Collaboration of a
charmed pentaquark, Theta^0_c.Comment: 22 pages, 7 figures, 1 table; minor text revisions; 2 references
adde
Toll-Like Receptor 2 Induced Angiogenesis and Invasion Is Mediated through the Tie2 Signalling Pathway in Rheumatoid Arthritis
BACKGROUND: Angiogenesis is a critical early event in inflammatory arthritis, facilitating leukocyte migration into the synovium resulting in invasion and destruction of articular cartilage and bone. This study investigates the effect of TLR2 on angiogenesis, EC adhesion and invasion using microvascular endothelial cells and RA whole tissue synovial explants ex-vivo. METHODS: Microvascular endothelial cells (HMVEC) and RA synovial explants ex vivo were cultured with the TLR2 ligand, Pam3CSK4 (1 Âľg/ml). Angiopoietin 2 (Ang2), Tie2 and TLR2 expression in RA synovial tissue was assessed by immunohistology. HMVEC tube formation was assessed using Matrigel matrix assays. Ang2 was measured by ELISA. ICAM-1 cell surface expression was assessed by flow cytometry. Cell migration was assessed by wound repair scratch assays. ECM invasion, MMP-2 and -9 expression were assessed using transwell invasion chambers and zymography. To examine if the angiopoietin/Tie2 signalling pathway mediates TLR2 induced EC tube formation, invasion and migration assays were performed in the presence of a specific neutralising anti-Tie2mAb (10 ug/ml) and matched IgG isotype control Ab (10 ug/ml). RESULTS: Ang2 and Tie2 were localised to RA synovial blood vessels, and TLR2 was localised to RA synovial blood vessels, sub-lining infiltrates and the lining layer. Pam3CSK4 significantly increased angiogenic tube formation (p<0.05), and upregulated Ang2 production in HMVEC (p<0.05) and RA synovial explants (p<0.05). Pam3CSK4 induced cell surface expression of ICAM-1, from basal level of 149Âą54 (MFI) to 617Âą103 (p<0.01). TLR-2 activation induced an 8.8Âą2.8 fold increase in cell invasion compared to control (p<0.05). Pam3CSK4 also induced HMVEC cell migration and induced MMP-2 and -9 from RA synovial explants. Neutralisation of the Ang2 receptor, Tie2 significantly inhibited Pam3CSK4-induced EC tube formation and invasion (p<0.05). CONCLUSION: TLR2 activation promotes angiogenesis, cell adhesion and invasion, effects that are in part mediated through the Tie2 signalling pathway, key mechanisms involved in the pathogenesis of RA
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV
The azimuthal anisotropy of charged particles in PbPb collisions at
nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS
detector at the LHC over an extended transverse momentum (pt) range up to
approximately 60 GeV. The data cover both the low-pt region associated with
hydrodynamic flow phenomena and the high-pt region where the anisotropies may
reflect the path-length dependence of parton energy loss in the created medium.
The anisotropy parameter (v2) of the particles is extracted by correlating
charged tracks with respect to the event-plane reconstructed by using the
energy deposited in forward-angle calorimeters. For the six bins of collision
centrality studied, spanning the range of 0-60% most-central events, the
observed v2 values are found to first increase with pt, reaching a maximum
around pt = 3 GeV, and then to gradually decrease to almost zero, with the
decline persisting up to at least pt = 40 GeV over the full centrality range
measured.Comment: Replaced with published version. Added journal reference and DO
- âŚ