330 research outputs found
Modelling ponatinib resistance in tyrosine kinase inhibitor-naive and dasatinib resistant BCR-ABL1+ cell lines
TKI resistance remains a major impediment to successful treatment of CML. In this study, we investigated the emerging modes of ponatinib resistance in TKI-naĂŻve and dasatinib resistant BCR-ABL1+ cell lines. To investigate potential resistance mechanisms, ponatinib resistance was generated in BCR-ABL1+ cell-lines by long-term exposure to increasing concentrations of ponatinib. Two cell lines with prior dasatinib resistance demonstrated BCR-ABL1 kinase domain (KD) mutation(s) upon exposure to ponatinib. In one of these cell lines the T315I mutation had emerged during dasatinib exposure. When further cultured with ponatinib, the T315I mutation level and BCR-ABL1 mRNA expression level were increased. In the other cell line, compound mutations G250E/E255K developed with ponatinib exposure. In contrast, the ponatinib resistant cell lines that had no prior exposure to other TKIs (TKI-naĂŻve) did not develop BCR-ABL1 KD mutations. Rather, both of these cell lines demonstrated Bcr-Abl-independent resistance via Axl overexpression. Axl, a receptor tyrosine kinase, has previously been associated with imatinib and nilotinib resistance. Ponatinib sensitivity was restored following Axl inhibition or shRNA-mediated-knockdown of Axl, suggesting that Axl was the primary driver of resistance and a potential target for therapy in this setting.Liu Lu, Chung Hoow Kok, Verity Ann Saunders, Jueqiong Wang, Jennifer Anne McLean, Timothy Peter Hughes, and Deborah Lee Whit
Correlation effects in ionic crystals: I. The cohesive energy of MgO
High-level quantum-chemical calculations, using the coupled-cluster approach
and extended one-particle basis sets, have been performed for (Mg2+)n (O2-)m
clusters embedded in a Madelung potential. The results of these calculations
are used for setting up an incremental expansion for the correlation energy of
bulk MgO. This way, 96% of the experimental cohesive energy of the MgO crystal
is recovered. It is shown that only 60% of the correlation contribution to the
cohesive energy is of intra-ionic origin, the remaining part being caused by
van der Waals-like inter-ionic excitations.Comment: LaTeX, 20 pages, no figure
Wavenumber-explicit continuity and coercivity estimates in acoustic scattering by planar screens
We study the classical first-kind boundary integral equation reformulations
of time-harmonic acoustic scattering by planar sound-soft (Dirichlet) and
sound-hard (Neumann) screens. We prove continuity and coercivity of the
relevant boundary integral operators (the acoustic single-layer and
hypersingular operators respectively) in appropriate fractional Sobolev spaces,
with wavenumber-explicit bounds on the continuity and coercivity constants. Our
analysis is based on spectral representations for the boundary integral
operators, and builds on results of Ha-Duong (Jpn J Ind Appl Math 7:489--513
(1990) and Integr Equat Oper Th 15:427--453 (1992)).Comment: v2 has minor corrections compared to v1. arXiv admin note:
substantial text overlap with arXiv:1401.280
Study of the B^0 Semileptonic Decay Spectrum at the Upsilon(4S) Resonance
We have made a first measurement of the lepton momentum spectrum in a sample
of events enriched in neutral B's through a partial reconstruction of B0 -->
D*- l+ nu. This spectrum, measured with 2.38 fb**-1 of data collected at the
Upsilon(4S) resonance by the CLEO II detector, is compared directly to the
inclusive lepton spectrum from all Upsilon(4S) events in the same data set.
These two spectra are consistent with having the same shape above 1.5 GeV/c.
From the two spectra and two other CLEO measurements, we obtain the B0 and B+
semileptonic branching fractions, b0 and b+, their ratio, and the production
ratio f+-/f00 of B+ and B0 pairs at the Upsilon(4S). We report b+/b0=0.950
(+0.117-0.080) +- 0.091, b0 = (10.78 +- 0.60 +- 0.69)%, and b+ = (10.25 +- 0.57
+- 0.65)%. b+/b0 is equivalent to the ratio of charged to neutral B lifetimes,
tau+/tau0.Comment: 14 page, postscript file also available at
http://w4.lns.cornell.edu/public/CLN
Observation of the Charmed Baryon Decays to , , and
We have observed two new decay modes of the charmed baryon into
and using data collected with the
CLEO II detector. We also present the first measurement of the branching
fraction for the previously observed decay mode . The branching fractions for these three modes relative to
are measured to be , , and , respectively.Comment: 12 page uuencoded postscript file, postscript file also available
through http://w4.lns.cornell.edu/public/CLN
Measurement of the Mass Splittings between the States
We present new measurements of photon energies and branching fractions for
the radiative transitions: Upsilon(2S)->gamma+chi_b(J=0,1,2). The masses of the
chi_b states are determined from the measured radiative photon energies. The
ratio of mass splittings between the chi_b substates,
r==(M[J=2]-M[J=1])/(M[J=1]-M[J=0]) with M the chi_b mass, provides information
on the nature of the bbbar confining potential. We find
r(1P)=0.54+/-0.02+/-0.02. This value is in conflict with the previous world
average, but more consistent with the theoretical expectation that r(1P)<r(2P);
i.e., that this mass splittings ratio is smaller for the chi_b(1P) triplet than
for the chi_b(2P) triplet.Comment: 11 page postscript file, postscript file also available through
http://w4.lns.cornell.edu/public/CLN
Radiative Decay Modes of the Meson
Using data recorded by the CLEO-II detector at CESR we have searched for four
radiative decay modes of the meson: ,
, , and . We
obtain 90% CL upper limits on the branching ratios of these modes of , , and
respectively.Comment: 15 page postscript file, postscript file also available through
http://w4.lns.cornell.edu/public/CLN
First observation of the decay and a measurement of the ratio of branching fractions
The first observation of the decay using
data collected by the LHCb detector at a centre-of-mass energy of 7 TeV,
corresponding to an integrated luminosity of 36 pb, is reported. A
signal of events is obtained and the absence of signal is
rejected with a statistical significance of more than nine standard deviations.
The branching fraction is measured relative to
that of : , where the first uncertainty is statistical, the second systematic and
the third is due to the uncertainty on the ratio of the and
hadronisation fractions.Comment: 10 pages, 3 figures, submitted to Phys. Lett. B; ISSN 0370-269
The roles of the formal and informal sectors in the provision of effective science education
For many years, formal school science education has been criticised by students, teachers, parents and employers throughout the world. This article presents an argument that a greater collaboration between the formal and the informal sector could address some of these criticisms. The causes for concern about formal science education are summarised and the major approaches being taken to address them are outlined. The contributions that the informal sector currently makes to science education are identified. It is suggested that the provision of an effective science education entails an enhanced complementarity between the two sectors. Finally, there is a brief discussion of the collaboration and communication still needed if this is to be effective
Disentangling the response of fishes to recreational fishing over 30âŻyears within a fringing coral reef reserve network
Few studies assess the effects of recreational fishing in isolation from commercial fishing. We used meta-analysis to synthesise 4444 samples from 30âŻyears (1987â2017) of fish surveys inside and outside a large network of highly protected reserves in the Ningaloo Marine Park, Western Australia, where the major fishing activity is recreational. Data were collected by different agencies, using varied survey designs and sampling methods. We contrasted the relative abundance and biomass of target and non-target fish groups between fished and reserve locations. We considered the influence of, and possible interactions between, seven additional variables: age and size of reserve, one of two reserve network configurations, reef habitat type, recreational fishing activity, shore-based fishing regulations and survey method. Taxa responded differently: the abundance and biomass inside reserves relative to outside was higher for targeted lethrinids, while other targeted (and non-targeted) fish groups were indistinguishable. Reef habitat was important for explaining lethrinid response to protection, and this factor interacted with reserve size, such that larger reserves were demonstrably more effective in the back reef and lagoon habitats. There was little evidence of changes in relative abundance and biomass of fishes with reserve age, or after rezoning and expansion of the reserve network. Our study demonstrates the complexities in quantifying fishing effects, highlighting some of the key factors and interactions that likely underlie the varied results in reserve assessments that should be considered in future reserve design and assessment
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