Staggered Fermion Actions with Improved Rotational Invariance

We introduce a class of improved actions for staggered fermions which to O(p^4) and O(p^6), respectively, lead to rotationally invariant propagators. We discuss the resulting reduction of flavour symmetry breaking in the meson spectrum and comment on the improvement in the calculation of thermodynamic observables.Comment: 3 pages and 4 figures, Contribution to Lattice 97 (Poster Session), late

Extensive transcriptional complexity during hypoxia-regulated expression of the myoglobin gene in cancer

Recently, the ectopic expression of myoglobin (MB) was reported in human epithelial cancer cell lines and breast tumor tissues, where MB expression increased with hypoxia. The better prognosis of MB-positive breast cancer patients suggested that the globin exerts a tumor-suppressive role, possibly by impairing mitochondrial activity in hypoxic breast carcinoma cells. To better understand MB gene regulation in cancer, we systematically investigated the architecture of the human MB gene, its transcripts and promoters. In silico analysis of transcriptome data from normal human tissues and cancer cell lines, followed by RACE-PCR verification, revealed seven novel exons in the MB gene region, most of which are untranslated exons located 5′-upstream of the coding DNA sequence (CDS). Sixteen novel alternatively spliced MB transcripts were detected, most of which predominantly occur in tumor tissue or cell lines. Quantitative RT-PCR analyses of MB expression in surgical breast cancer specimen confirmed the preferential usage of a hitherto unknown, tumor-associated MB promoter, which was functionally validated by luciferase reporter gene assays. In line with clinical observations of MB up-regulation in avascular breast tumors, the novel cancer-associated MB splice variants exhibited increased expression in tumor cells subjected to experimental hypoxia. The novel gene regulatory mechanisms unveiled in this study support the idea of a non-canonical role of MB during carcinogenesi

The role of E+A and post-starburst galaxies – II. Spectral energy distributions and comparison with observations

‘The definitive version is available at www3.interscience.wiley.com '. Copyright Royal Astronomical Society. DOI: 10.1111/j.1365-2966.2009.15036.xIn a previous paper, we have shown that the classical definition of E+A galaxies excludes a significant number of post-starburst galaxies. We suggested that analysing broad-band spectral energy distributions (SEDs) is a more comprehensive method to select and distinguish post-starburst galaxies than the classical definition of measuring equivalent widths of (Hδ) and [O ii] lines. In this paper, we will carefully investigate this new method and evaluate it by comparing our model grid of post-starburst galaxies to observed E+A galaxies from the MORPHS catalogue. In the first part, we investigate the UV-optical-NIR (near-infrared) SEDs of a large variety in terms of progenitor galaxies, burst strengths and time-scales of post-starburst models and compare them to undisturbed spiral, S0 and E galaxies as well as to galaxies in their starburst phase. In the second part, we compare our post-starburst models with the observed E+A galaxies in terms of Lick indices, luminosities and colours. We then use the new method of comparing the model SEDs with SEDs of the observed E+A galaxies. We find that the post-starburst models can be distinguished from undisturbed spiral, S0 and E galaxies and galaxies in their starburst phase on the basis of their SEDs. It is even possible to distinguish most of the different post-starbursts by their SEDs. From the comparison with observations, we find that all observed E+A galaxies from the MORPHS catalogue can be matched by our models. However, only models with short decline time-scales for the star formation rate are possible scenarios for the observed E+A galaxies in agreement with our results from the first paper.Peer reviewe

Pro-Apoptotic and Anti-Invasive Properties Underscore the Tumor-Suppressing Impact of Myoglobin on a Subset of Human Breast Cancer Cells

The expression of myoglobin (MB), well known as the oxygen storage and transport protein of myocytes, is a novel hallmark of the luminal subtype in breast cancer patients and correlates with better prognosis. The mechanisms by which MB impacts mammary tumorigenesis are hitherto unclear. We aimed to unravel this role by using CRISPR/Cas9 technology to generate MB-deficient clones of MCF7 and SKBR3 breast cancer cell lines and subsequently characterize them by transcriptomics plus molecular and functional analyses. As main findings, loss of MB at normoxia upregulated the expression of cell cyclins and increased cell survival, while it prevented apoptosis in MCF7 cells. Additionally, MB-deficient cells were less sensitive to doxorubicin but not ionizing radiation. Under hypoxia, the loss of MB enhanced the partial epithelial to mesenchymal transition, thus, augmenting the migratory and invasive behavior of cells. Notably, in human invasive mammary ductal carcinoma tissues, MB and apoptotic marker levels were positively correlated. In addition, MB protein expression in invasive ductal carcinomas was associated with a positive prognostic value, independent of the known tumor suppressor p53. In conclusion, we provide multiple lines of evidence that endogenous MB in cancer cells by itself exerts novel tumor-suppressive roles through which it can reduce cancer malignancy

Endogenous myoglobin expression in mouse models of mammary carcinoma reduces hypoxia and metastasis in PyMT mice

Myoglobin (MB) is expressed in different cancer types and may act as a tumor suppressor in breast cancer. The mechanisms by which basal MB expression level impacts murine mammary tumorigenesis are unclear. We investigated how MB expression in breast cancer influences proliferation, metastasis, tumor hypoxia, and chemotherapy treatment in vivo. We crossed PyMT and WapCreTrp53$^{flox}$ mammary cancer mouse models that differed in tumor grade/type and onset of mammary carcinoma with MB knockout mice. The loss of MB in WapCre;Trp53$^{flox}$ mice did not affect tumor development and progression. On the other hand, loss of MB decreased tumor growth and increased tissue hypoxia as well as the number of lung metastases in PyMT mice. Furthermore, Doxorubicin therapy prevented the stronger metastatic propensity of MB-deficient tumors in PyMT mice. This suggests that, although MB expression predicts improved prognosis in breast cancer patients, MB-deficient tumors may still respond well to first-line therapies. We propose that determining the expression level of MB in malignant breast cancer biopsies will improve tumor stratification, outcome prediction, and personalized therapy in cancer patients

Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells

Myoglobin (MB) is known to bind and deliver oxygen in striated muscles at high expression levels. MB is also expressed at much reduced levels in mammary epithelial cells, where the protein´s function is unclear. In this study, we aim to determine whether MB impacts fatty acid trafficking and facilitates aerobic fatty acid ß-oxidation in mammary epithelial cells. We utilized MB-wildtype versus MB-knockout mice and human breast cancer cells to examine the impact of MB and its oxygenation status on fatty acid metabolism in mouse milk and mammary epithelia. MB deficient cells were generated through CRISPR/Cas9 and TALEN approaches and exposed to various oxygen tensions. Fatty acid profiling of milk and cell extracts were performed along with cell labelling and immunocytochemistry. Our findings show that MB expression in mammary epithelial cells promoted fatty acid oxidation while reducing stearyl-CoA desaturase activity for lipogenesis. In cells and milk product, presence of oxygenated MB significantly elevated indices of limited fatty acid ß-oxidation, i.e., the organelle-bound removal of a C2 moiety from long-chain saturated or monounsaturated fatty acids, thus shifting the composition toward more saturated and shorter fatty acid species. Presence of the globin also increased cytoplasmic fatty acid solubility under normoxia and fatty acid deposition to lipid droplets under severe hypoxia. We conclude that MB can function in mammary epithelia as intracellular O$_{2}$-dependent shuttle of oxidizable fatty acid substrates. MB’s impact on limited oxidation of fatty acids could generate inflammatory mediator lipokines, such as 7-hexadecenoate. Thus, the novel functions of MB in breast epithelia described herein range from controlling fatty acid turnover and homeostasis to influencing inflammatory signalling cascade. Future work is needed to analyse to what extent these novel roles of MB also apply to myocytic cell physiology and malignant cell behaviour, respectively

RC J0311+0507: A Candidate for Superpowerful Radio Galaxies in the Early Universe at Redshift z=4.514

A strong emission line at 6703A has been detected in the optical spectrum for the host galaxy (R=23.1) of the radio source RC J0311+0507 (4C+04.11). This radio galaxy, with a spectral index of 1.31 in the frequency range 365-4850 MHz, is one of the ultrasteep spectrum objects from the deep survey of a sky strip conducted with RATAN-600 in 1980-1981. We present arguments in favor of the identification of this line with Ly\alpha at redshift z=4.514. In this case, the object belongs to the group of extremely distant radio galaxies of ultrahigh radio luminosity (P_{1400}=1.3 x 10^{29}W Hz^{-1}). Such power can be provided only by a fairly massive black hole (~10^9M_\sun}) that formed in a time less than the age of the Universe at the observed z(1.3 Gyr) or had a primordial origin.Comment: 8 pages, 3 figure

First Measurement of Chiral Dynamics in \pi^- \gamma -> \pi^- \pi^- \pi^+

The COMPASS collaboration at CERN has investigated the \pi^- \gamma -> \pi^- \pi^- \pi^+ reaction at center-of-momentum energy below five pion masses, sqrt(s) < 5 m(\pi), embedded in the Primakoff reaction of 190 GeV pions impinging on a lead target. Exchange of quasi-real photons is selected by isolating the sharp Coulomb peak observed at smallest momentum transfers, t' < 0.001 (GeV/c)^2. Using partial-wave analysis techniques, the scattering intensity of Coulomb production described in terms of chiral dynamics and its dependence on the 3\pi-invariant mass m(3\pi) = sqrt(s) were extracted. The absolute cross section was determined in seven bins of $\sqrt{s}$ with an overall precision of 20%. At leading order, the result is found to be in good agreement with the prediction of chiral perturbation theory over the whole energy range investigated.Comment: 10 pages, 5 figure

Transverse-momentum-dependent Multiplicities of Charged Hadrons in Muon-Deuteron Deep Inelastic Scattering

A semi-inclusive measurement of charged hadron multiplicities in deep inelastic muon scattering off an isoscalar target was performed using data collected by the COMPASS Collaboration at CERN. The following kinematic domain is covered by the data: photon virtuality $Q^{2}>1$ (GeV/$c$)$^2$, invariant mass of the hadronic system $W > 5$ GeV/$c^2$, Bjorken scaling variable in the range $0.003 < x < 0.4$, fraction of the virtual photon energy carried by the hadron in the range $0.2 < z < 0.8$, square of the hadron transverse momentum with respect to the virtual photon direction in the range 0.02 (GeV/$c)^2 < P_{\rm{hT}}^{2} < 3$ (GeV/$c$)$^2$. The multiplicities are presented as a function of $P_{\rm{hT}}^{2}$ in three-dimensional bins of $x$, $Q^2$, $z$ and compared to previous semi-inclusive measurements. We explore the small-$P_{\rm{hT}}^{2}$ region, i.e. $P_{\rm{hT}}^{2} < 1$ (GeV/$c$)$^2$, where hadron transverse momenta are expected to arise from non-perturbative effects, and also the domain of larger $P_{\rm{hT}}^{2}$, where contributions from higher-order perturbative QCD are expected to dominate. The multiplicities are fitted using a single-exponential function at small $P_{\rm{hT}}^{2}$ to study the dependence of the average transverse momentum $\langle P_{\rm{hT}}^{2}\rangle$ on $x$, $Q^2$ and $z$. The power-law behaviour of the multiplicities at large $P_{\rm{hT}}^{2}$ is investigated using various functional forms. The fits describe the data reasonably well over the full measured range.Comment: 28 pages, 20 figure