Localization of tyrosine kinase-coding region in v-abl oncogene by the expression of v-abl-encoded proteins in bacteria

A series of plasmids containing different segments of the v-abl oncogene have been constructed to express different portions of the v- abl protein in bacteria. The tyrosine kinase activity of these proteins was determined by an in vitro assay employing histones or angiotensin II as substrates for the v-abl-encoded tyrosine kinase. These experiments show that the 5'-1.2 kilobases of v-abl is necessary and sufficient to produce an active tyrosine kinase which is functional as a monomeric soluble protein. The kinase-coding region corresponds to the minimal region of v-abl required for the transformation of fibroblasts. The kinase-coding region also coincides with the conserved protein sequences which are found in other tyrosine kinases. A compact domain of the v-abl protein including this kinase-coding region can accumulate to high levels in bacteria. The C-terminal region of the v- abl protein is not needed for the kinase activity and is rapidly degraded in bacteria

Black Hole and Neutron Star Transients in Quiescence

We consider the X-ray luminosity difference between neutron star and black hole soft X-ray transients (NS and BH SXTs) in quiescence. The current observational data suggest that BH SXTs are significantly fainter than NS SXTs. The luminosities of quiescent BH SXTs are consistent with the predictions of binary evolution models for the mass transfer rate if (1) accretion occurs via an ADAF in these systems and (2) the accreting compact objects have event horizons. The luminosities of quiescent NS SXTs are not consistent with the predictions of ADAF models when combined with binary evolution models, unless most of the mass accreted in the ADAF is prevented from reaching the neutron star surface. We consider the possibility that mass accretion is reduced in quiescent NS SXTs because of an efficient propeller and develop a model of the propeller effect that accounts for the observed luminosities. We argue that modest winds from ADAFs are consistent with the observations while strong winds are probably not.Comment: LateX, 37 pages, 7 figures; Accepted for publication in The Astrophysical Journa

Investigating electron interacting dark matter

Some extensions of the Standard Model provide Dark Matter candidate particles which can have a dominant coupling with the lepton sector of the ordinary matter. Thus, such Dark Matter candidate particles ($\chi^{0}$) can be directly detected only through their interaction with electrons in the detectors of a suitable experiment, while they are lost by experiments based on the rejection of the electromagnetic component of the experimental counting rate. These candidates can also offer a possible source of the 511 keV photons observed from the galactic bulge. In this paper this scenario is investigated. Some theoretical arguments are developed and related phenomenological aspects are discussed. Allowed intervals and regions for the characteristic phenomenological parameters of the considered model and of the possible mediator of the interaction are also derived considering the DAMA/NaI data.Comment: 16 pages, 6 figures. Accepted for publication in PRD. One typo correcte

The influence of feature selection methods on accuracy, stability and interpretability of molecular signatures

Motivation: Biomarker discovery from high-dimensional data is a crucial problem with enormous applications in biology and medicine. It is also extremely challenging from a statistical viewpoint, but surprisingly few studies have investigated the relative strengths and weaknesses of the plethora of existing feature selection methods. Methods: We compare 32 feature selection methods on 4 public gene expression datasets for breast cancer prognosis, in terms of predictive performance, stability and functional interpretability of the signatures they produce. Results: We observe that the feature selection method has a significant influence on the accuracy, stability and interpretability of signatures. Simple filter methods generally outperform more complex embedded or wrapper methods, and ensemble feature selection has generally no positive effect. Overall a simple Student's t-test seems to provide the best results. Availability: Code and data are publicly available at http://cbio.ensmp.fr/~ahaury/

The multiple solutions of self-consistency condition in Walecka model and the validity of the Brown-Rho scaling law

We investigate the self-consistency condition (SCC) of mean-field theory in Walecka model and find that the solutions of the SCC are multiple at high temperature and chemical potential. Using the effective Lagrangian approach, we study medium effects on the $\omega$ meson mass by taking into account of vacuum effects. We show that the $\omega$ meson mass decreases with both temperature and chemical potential with a general tendency, while near the critical point several $\omega$ meson masses become degenerate due to the multiple solutions of the SCC. We check the validity of Brown-Rho scaling law in this case. Finally, we calculate the thermodynamic potential and prove that the multiple solutions of the SCC result from a first-order phase transition of nuclear matter in the Walecka model at high temperature and chemical potential.Comment: 10 pages in Revtex with 9 figure

Exclusion of c-Abl from the nucleus restrains the p73 tumor suppression function

The p73alpha protein is a functional homolog of the p53 tumor suppressor. Although the TP53 gene is frequently mutated in human cancers, the TP73 gene is rarely inactivated. We have found that p73alpha is highly expressed in a significant fraction of anaplastic thyroid cancer, whereas it is not detectable in normal thyroid epithelial cells or in papillary and follicular thyroid cancer cells. Interestingly, the tumor suppression function of p73alpha is actively restrained in anaplastic thyroid cancer cells. We have also found that c-Abl tyrosine kinase, an activator of p73, is excluded from the nucleus of p73alpha-positive thyroid cancer cells; whereas c-Abl undergoes nuclear-cytoplasmic shuttling in normal thyroid and p73-negative thyroid cancer cells. We constructed an AblNuk-FK506-binding protein (FKBP) fusion protein to enforce the nuclear accumulation of an inducible Abl kinase. Activation of this nuclear AblNuk-FKBP by dimerization with AP20187 in anaplastic thyroid cancer cells increased the levels of p73alpha and p21Cip1 and caused p73-dependent apoptosis. These results suggest subcellular segregation of c-Abl from p73 to be a strategy for disrupting the tumor suppression function of p73alpha

Fundamental constants and tests of general relativity - Theoretical and cosmological considerations

The tests of the constancy of the fundamental constants are tests of the local position invariance and thus of the equivalence principle. We summarize the various constraints that have been obtained and then describe the connection between varying constants and extensions of general relativity. To finish, we discuss the link with cosmology, and more particularly with the acceleration of the Universe. We take the opportunity to summarize various possibilities to test general relativity (but also the Copernican principle) on cosmological scales.Comment: Proceedings of the workshop ``The nature of gravity, confronting theory and experiment in space'', ISSI, Bern, october 200

Microbiome profiling by Illumina sequencing of combinatorial sequence-tagged PCR products

We developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequence tags attached to PCR primers that amplify the rRNA V6 region. Amplified PCR products are sequenced using an Illumina paired-end protocol to generate millions of overlapping reads. Combinatorial sequence tagging can be used to examine hundreds of samples with far fewer primers than is required when sequence tags are incorporated at only a single end. The number of reads generated permitted saturating or near-saturating analysis of samples of the vaginal microbiome. The large number of reads al- lowed an in-depth analysis of errors, and we found that PCR-induced errors composed the vast majority of non-organism derived species variants, an ob- servation that has significant implications for sequence clustering of similar high-throughput data. We show that the short reads are sufficient to assign organisms to the genus or species level in most cases. We suggest that this method will be useful for the deep sequencing of any short nucleotide region that is taxonomically informative; these include the V3, V5 regions of the bac- terial 16S rRNA genes and the eukaryotic V9 region that is gaining popularity for sampling protist diversity.Comment: 28 pages, 13 figure