462 research outputs found
Delta isobar masses, large N_c relations, and the quark model
Motivated by recent remarks on the Delta+ mass and comparisons between the
quark model and relations based on large-N_c with perturbative flavor breaking,
two sets of Delta masses consistent with these constraints are constructed.
These two sets, based either on an experimentally determined mass splitting or
a quark model of isospin symmetry breaking, are shown to be inconsistent. The
model dependence of this inconsistency is examined, and suggestions for
improved experiments are made. An explicit quark model calculation and mass
relations based on the large-N_c limit with perturbative flavor breaking are
compared. The expected level of accuracy of such relations is realized in the
quark model, except for mass relations spanning more than one SU(6)
representation. It is shown that the Delta0 and Delta++ pole masses and Delta0
- Delta+ = (Delta- - Delta++)/3 about 1.5 MeV are more consistent with model
expectations than the analogous Breit-Wigner masses and their splittings.Comment: 10 pages, including 1 eps figure, revte
On the pion-nucleon coupling constant
In view of persisting misunderstanding about the determination of the
pion-nucleon coupling constants in the Nijmegen multienergy partial-wave
analyses of pp, np, and pbar-p scattering data, we present additional
information which may clarify several points of discussion. We comment on
several recent papers addressing the issue of the pion-nucleon coupling
constant and criticizing the Nijmegen analyses.Comment: 19 pages, Nijmegen preprint THEF-NYM-92-0
Virtual-pion and two-photon production in pp scattering
Two-photon production in pp scattering is proposed as a means of studying
virtual-pion emission. Such a process is complementary to real-pion emission in
pp scattering. The virtual-pion signal is embedded in a background of
double-photon bremsstrahlung. We have developed a model to describe this
background process and show that in certain parts of phase space the
virtual-pion signal gives significant contribution. In addition, through
interference with the two-photon bremsstrahlung background, one can determine
the relative phase of the virtual-pion process
Correlation between nucleotide composition and folding energy of coding sequences with special attention to wobble bases
Background: The secondary structure and complexity of mRNA influences its
accessibility to regulatory molecules (proteins, micro-RNAs), its stability and
its level of expression. The mobile elements of the RNA sequence, the wobble
bases, are expected to regulate the formation of structures encompassing coding
sequences.
Results: The sequence/folding energy (FE) relationship was studied by
statistical, bioinformatic methods in 90 CDS containing 26,370 codons. I found
that the FE (dG) associated with coding sequences is significant and negative
(407 kcal/1000 bases, mean +/- S.E.M.) indicating that these sequences are able
to form structures. However, the FE has only a small free component, less than
10% of the total. The contribution of the 1st and 3rd codon bases to the FE is
larger than the contribution of the 2nd (central) bases. It is possible to
achieve a ~ 4-fold change in FE by altering the wobble bases in synonymous
codons. The sequence/FE relationship can be described with a simple algorithm,
and the total FE can be predicted solely from the sequence composition of the
nucleic acid. The contributions of different synonymous codons to the FE are
additive and one codon cannot replace another. The accumulated contributions of
synonymous codons of an amino acid to the total folding energy of an mRNA is
strongly correlated to the relative amount of that amino acid in the translated
protein.
Conclusion: Synonymous codons are not interchangable with regard to their
role in determining the mRNA FE and the relative amounts of amino acids in the
translated protein, even if they are indistinguishable in respect of amino acid
coding.Comment: 14 pages including 6 figures and 1 tabl
The HSP90 Inhibitor NVP-AUY922 Radiosensitizes by Abrogation of Homologous Recombination Resulting in Mitotic Entry with Unresolved DNA Damage
Heat shock protein 90 (HSP90) is a molecular chaperone responsible for the conformational maintenance of a number of client proteins that play key roles in cell cycle arrest, DNA damage repair and apoptosis following radiation. HSP90 inhibitors exhibit antitumor activity by modulating the stabilisation and activation of HSP90 client proteins. We sought to evaluate NVP-AUY922, the most potent HSP90 inhibitor yet reported, in preclinical radiosensitization studies.NVP-AUY922 potently radiosensitized cells in vitro at low nanomolar concentrations with a concurrent depletion of radioresistance-linked client proteins. Radiosensitization by NVP-AUY922 was verified for the first time in vivo in a human head and neck squamous cell carcinoma xenograft model in athymic mice, as measured by delayed tumor growth and increased surrogate end-point survival (p = <0.0001). NVP-AUY922 was shown to ubiquitously inhibit resolution of dsDNA damage repair correlating to delayed Rad51 foci formation in all cell lines tested. Additionally, NVP-AUY922 induced a stalled mitotic phenotype, in a cell line-dependent manner, in HeLa and HN5 cell lines irrespective of radiation exposure. Cell cycle analysis indicated that NVP-AUY922 induced aberrant mitotic entry in all cell lines tested in the presence of radiation-induced DNA damage due to ubiquitous CHK1 depletion, but resultant downstream cell cycle effects were cell line dependent.These results identify NVP-AUY922 as the most potent HSP90-mediated radiosensitizer yet reported in vitro, and for the first time validate it in a clinically relevant in vivo model. Mechanistic analysis at clinically achievable concentrations demonstrated that radiosensitization is mediated by the combinatorial inhibition of cell growth and survival pathways, ubiquitous delay in Rad51-mediated homologous recombination and CHK1-mediated G(2)/M arrest, but that the contribution of cell cycle perturbation to radiosensitization may be cell line specific
Micro-spectroscopic investigation of selenium-bearing minerals from the Western US Phosphate Resource Area
Mining activities in the US Western Phosphate Resource Area (WPRA) have released Se into the environment. Selenium has several different oxidation states and species, each having varying degrees of solubility, reactivity, and bioavailability. In this study we are investigating the speciation of Se in mine-waste rocks. Selenium speciation was determined using bulk and micro-x-ray absorption spectroscopy (XAS), as well as micro-x-ray fluorescence mapping. Rocks used for bulk-XAS were ground into fine powders. Shale used for micro-XAS was broken along depositional planes to expose unweathered surfaces. The near edge region of the XAS spectra (XANES) for the bulk rock samples revealed multiple oxidation states, with peaks indicative of Se(-II), Se(IV), and Se(+VI) species. Micro-XANES analysis of the shale indicated that three unique Se-bearing species were present. Using the XANES data together with ab initio fitting of the extended x-ray absorption fine structure region of the micro-XAS data (micro-EXAFS) the three Se-bearing species were identified as dzharkenite, a di-selenide carbon compound, and Se-substituted pyrite. Results from this research will allow for a better understanding of the biogeochemical cycling of Se in the WPRA
On the Manifestation for Longitudinally Polarized
The contribution of the structure function to polarized deep inelastic
scattering is slightly redefined in order to avoid kinematical zeros. Its
strong -dependence implied by the Burkhardt-Cottingham (BC) sum rule
naturally explains the sign change of the generalized Gerasimov-Drell-Hearn
(GDH) sum rule. The status of the BC sum rule and implications for other spin
processes are discussed.Comment: 16 pages,CPT-94/P.3014,late
Resistance to HSP90 inhibition involving loss of MCL1 addiction
YesInhibition of the chaperone heat-shock protein 90 (HSP90) induces apoptosis, and it is a promising anti-cancer strategy. The mechanisms underpinning apoptosis activation following HSP90 inhibition and how they are modified during acquired drug resistance are unknown. We show for the first time that, to induce apoptosis, HSP90 inhibition requires the cooperation of multi BH3-only proteins (BID, BIK, PUMA) and the reciprocal suppression of the pro-survival BCL-2 family member MCL1, which occurs via inhibition of STAT5A. A subset of tumour cell lines exhibit dependence on MCL1 expression for survival and this dependence is also associated with tumour response to HSP90 inhibition. In the acquired resistance setting, MCL1 suppression in response to HSP90 inhibitors is maintained; however, a switch in MCL1 dependence occurs. This can be exploited by the BH3 peptidomimetic ABT737, through non-BCL-2-dependent synthetic lethality
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