Transcriptomic and ChIP-sequence interrogation of EGFR signaling in HER2+ breast cancer cells reveals a dynamic chromatin landscape and S100 genes as targets.

BACKGROUND:The Human Epidermal Growth Factor Receptor (EGFR/HER1) can be activated by several ligands including Transforming Growth Factor alpha (TGF-α) and Epidermal Growth Factor (EGF). Following ligand binding, EGFR heterodimerizes with other HER family members, such as HER2 (human epidermal growth factor receptor-2). Previously, we showed that the EGFR is upregulated in trastuzumab resistant HER2 positive (HER2+) breast cancer cells. This study is aimed to determine the downstream effects on transcription following EGFR upregulation in HER2+ breast cancer cells. METHODS:RNA-sequence and ChIP-sequence for H3K18ac and H3K27ac (Histone H3 lysine K18 and K27 acetylation) were conducted following an Epidermal Growth Factor (EGF) treatment time course in HER2+ breast cancer cells, SKBR3. The levels of several proteins of interest were confirmed by western blot analysis. The cellular localization of proteins of interest was examined using biochemically fractionated lysates followed by western blot analysis. RESULTS:Over the course of 24 h, EGFR stimulation resulted in the modulation of over 4000 transcripts. Moreover, our data demonstrates that EGFR/HER2 signaling regulates the epigenome, with global H3K18ac and H3K27ac oscillating as a function of time following EGF treatment. RNA-sequence data demonstrates the activation of immediate early genes (IEGs) and delayed early genes (DEGs) within 1 h of EGF treatment. More importantly, we have identified members of the S100 (S100 Calcium Binding Protein) gene family as likely direct targets of EGFR signaling as H3K18ac, H3K27ac and pol2 (RNA polymerase II) increase near the transcription start sites of some of these genes. CONCLUSIONS:Our data suggests that S100 proteins, which act as Ca2+ sensors, could play a role in EGF induced tumor cell growth and metastasis, contribute to trastuzumab resistance and cell migration and that they are likely drug targets in HER2+ breast cancer

Improving Airline Bankruptcy Prediction

The airline industry plays an important role in the global economy but faces financial challenges. Numerous firms have filed for bankruptcy protection or have liquidated completely, each instance having a devastating effect on the company’s stakeholders. The objective of this study is to compare a traditional bankruptcy prediction model with a proposed alternative model, with the goal of identifying a means of predicting the combinations of characteristics that are present when an airline is likely to fail. The alternate model proved to be more accurate than the traditional model in predicting bankruptcy, providing improved forecasting up to four years prior to the bankruptcy filing date. Airlines can use this model to deploy corrective measures to alter the firm’s underlying problems, redefine strategies, and avoid bankruptcy, while investors can use this model to avoid or reduce investments in questionable firms that cannot be salvaged

Influence of nearly resonant light on the scattering length in low-temperature atomic gases

We develop the idea of manipulating the scattering length $a$ in low-temperature atomic gases by using nearly resonant light. As found, if the incident light is close to resonance with one of the bound $p$ levels of electronically excited molecule, then virtual radiative transitions of a pair of interacting atoms to this level can significantly change the value and even reverse the sign of $a$. The decay of the gas due to photon recoil, resulting from the scattering of light by single atoms, and due to photoassociation can be minimized by selecting the frequency detuning and the Rabi frequency. Our calculations show the feasibility of optical manipulations of trapped Bose condensates through a light-induced change in the mean field interaction between atoms, which is illustrated for $^7$Li.Comment: 12 pages, 1 Postscript figur

Luttinger model approach to interacting one-dimensional fermions in a harmonic trap

A model of interacting one--dimensional fermions confined to a harmonic trap is proposed. The model is treated analytically to all orders of the coupling constant by a method analogous to that used for the Luttinger model. As a first application, the particle density is evaluated and the behavior of Friedel oscillations under the influence of interactions is studied. It is found that attractive interactions tend to suppress the Friedel oscillations while strong repulsive interactions enhance the Friedel oscillations significantly. The momentum distribution function and the relation of the model interaction to realistic pair interactions are also discussed.Comment: 12 pages latex, 1 eps-figure in 1 tar file, extended Appendix, added and corrected references, new eq. (53), corrected typos, accepted for PR

Calculation of the interspecies s-wave scattering length in an ultracold Na-Rb vapor

We report the calculation of the interspecies scattering length for the sodium-rubidium (Na-Rb) system. We present improved hybrid potentials for the singlet $X^1\Sigma^+$ and triplet $a^3\Sigma^+$ ground states of the NaRb molecule, and calculate the singlet and triplet scattering lengths $a_{s}$ and $a_{t}$ for the isotopomers $^{23}$Na$^{87}$Rb and $^{23}$Na$^{85}$Rb. Using these values, we assess the prospects for producing a stable two-species Bose-Einstein condensate in the Na-Rb system.Comment: v2: report correct units in Table captions, fix error in conclusions for $^{23}$Na$^{85}$Rb TBEC. Otherwise, more concise presentation, typos fixed. 6 pages, 1 figur

Useful immunohistochemical indicators in canine mast cell tumours

Morphological and immunohistochemical analysis of 45 canine mast cell tumours was performed to determine whether the proteins examined are useful for a more precise description of tumour morphology and a more reliable determination of the prognosis in patients. Tissue sections were stained according to the standard haematoxylin and eosin (HE) technique and with toluidine blue to demonstrate cytoplasmic granules. Immunohistochemical studies were performed, using the cell markers CD117 (c-kit), p16 and von Willebrand factor (FVIII). In CD117 three different staining patterns were observed: (1) membranous reaction, (2) intense staining of cytoplasm, and (3) a diffuse, delicate cytoplasmic reaction. Von Willebrand antibody was evaluated on the basis of the number of blood vessels stained. p16 expression was evaluated by scoring positive nuclear reaction. Positive expression was demonstrated for all examined antigens, but their level of expression differed depending on the grades of tumour malignancy. Statistical analysis of the results documented a pronounced positive correlation between the markers studied and the grade of tumour malignancy (P < 0.001). It was shown that each of the cell markers examined represents a useful prognostic indicator for patients with mast cell tumours. The calculated correlation coefficients demonstrate a strong association between the expressions of CD117, FVIII and p16, and the histological malignancy of a tumour

Limit on suppression of ionization in metastable neon traps due to long-range anisotropy

This paper investigates the possibility of suppressing the ionization rate in a magnetostatic trap of metastable neon atoms by spin-polarizing the atoms. Suppression of the ionization is critical for the possibility of reaching Bose-Einstein condensation with such atoms. We estimate the relevant long-range interactions for the system, consisting of electric quadrupole-quadrupole and dipole-induced dipole terms, and develop short-range potentials based on the Na_2 singlet and triplet potentials. The auto-ionization widths of the system are also calculated. With these ingredients we calculate the ionization rate for spin-polarized and for spin-isotropic samples, caused by anisotropy of the long-range interactions. We find that spin-polarization may allow for four orders of magnitude suppression of the ionization rate for Ne. The results depend sensitively on a precise knowledge of the interaction potentials, however, pointing out the need for experimental input. The same model gives a suppression ratio close to unity for metastable xenon in accordance with experimental results, due to a much increased anisotropy in this case.Comment: 15 pages including figures, LaTex/RevTex, uses epsfig.st

Quo vadis, cold molecules? - Editorial review

We give a snapshot of the rapidly developing field of ultracold polar molecules abd walk the reader through the papers appearing in this topical issue