The atoll source states of 4U 1608-52

We have studied the atoll source 4U 1608-52 using a large data set obtained with the Rossi X-ray Timing Explorer. We find that the timing properties of 4U 1608-52 are almost exactly identical to those of the atoll sources 4U 0614+09 and 4U 1728-34 despite the fact that contrary to these sources 4U 1608-52 is a transient covering two orders of magnitude in luminosity. The frequencies of the variability components of these three sources follow a universal scheme when plotted versus the frequency of the upper kilohertz QPO, suggesting a very similar accretion flow configuration. If we plot the Z sources on this scheme only the lower kilohertz QPO and HBO follow identical relations. Using the mutual relations between the frequencies of the variability components we tested several models; the transition layer model, the sonic point beat frequency model, and the relativistic precession model. None of these models described the data satisfactory. Recently, it has been suggested that the atoll sources (among them 4U 1608-52) trace out similar three-branch patterns as the Z sources in the color-color diagram. We have studied the relation between the power spectral properties and the position of 4U 1608-52 in the color-color diagram and conclude that the timing behavior is not consistent with the idea that 4U 1608-52 traces out a three-branched Z shape in the color-color diagram along which the timing properties vary gradually, as Z sources do.Comment: 43 pages, 16 figures, ApJ accepte

Study of the Temporal Behavior of 4U 1728-34 as a Function of its Position in the Color-Color Diagram

We study the timing properties of the bursting atoll source 4U 1728-34 as a function of its position in the X-ray color-color diagram. In the island part of the color-color diagram (corresponding to the hardest energy spectra) the power spectrum of 4U 1728-34 shows several features such as a band-limited noise component present up to a few tens of Hz, a low frequency quasi-periodic oscillation (LFQPO) at frequencies between 20 and 40 Hz, a peaked noise component around 100 Hz, and one or two QPOs at kHz frequencies. In addition to these, in the lower banana (corresponding to softer energy spectra) we also find a very low frequency noise (VLFN) component below ~1 Hz. In the upper banana (corresponding to the softest energy spectra) the power spectra are dominated by the VLFN, with a peaked noise component around 20 Hz. We find that the frequencies of the kHz QPOs are well correlated with the position in the X-ray color-color diagram. For the frequency of the LFQPO and the break frequency of the broad-band noise component the relation appears more complex. These frequencies both increase when the frequency of the upper kHz QPO increases from 400 to 900 Hz, but at this frequency a jump in the values of the parameters occurs. We interpret this jump in terms of the gradual appearance of a QPO at the position of the break at high inferred mass accretion rate, while the previous LFQPO disappears. Simultaneously, another kind of noise appears with a break frequency of ~7 Hz, similar to the NBO of Z sources. The 100 Hz peaked noise does not seem to correlate with the position of the source in the color-color diagram, but remains relatively constant in frequency. This component may be similar to several 100 Hz QPOs observed in black hole binaries.Comment: 27 pages, 9 figures, accepted by Ap

Relations Between Timing Features and Colors in the X-Ray Binary 4U 0614+09

We study the correlations between timing and X-ray spectral properties in the low mass X-ray binary 4U 0614+09 using a large (265-ks) data set obtained with the Rossi X-ray Timing Explorer. We find strong quasi-periodic oscillations (QPOs) of the X-ray flux, like the kilohertz QPOs in many other X-ray binaries with accreting neutron stars, with frequencies ranging from 1329 Hz down to 418 Hz and, perhaps, as low as 153 Hz. We report the highest frequency QPO yet from any low mass X-ray binary at 1329+-4 Hz, which has implications for neutron star structure. This QPO has a 3.5-sigma single-trial significance, for an estimated 40 trials the significance is 2.4-sigma. Besides the kilohertz QPOs, the Fourier power spectra show four additional components: high frequency noise (HFN), described by a broken power-law with a break frequency between 0.7 and 45 Hz, very low frequency noise (VLFN), which is fitted as a power-law below 1 Hz, and two broad Lorentzians with centroid frequencies varying from 6 to 38 Hz and 97 to 158 Hz, respectively. We find strong correlations between the frequencies of the kilohertz QPOs, the frequency of the 6 to 38 Hz broad Lorentzian, the break frequency of the HFN, the strength of both the HFN and the VLFN and the position of the source in the hard X-ray color vs. intensity diagram. The frequency of the 97 to 158 Hz Lorentzian does not correlate with these parameters. We also find that the relation between power density and break frequency of the HFN is similar to that established for black hole candidates in the low state. We suggest that the changing mass accretion rate is responsible for the correlated changes in all these parameters.Comment: ApJ, referee

Heteroepitaxial growth of ferromagnetic MnSb(0001) films on Ge/Si(111) virtual substrates

Molecular beam epitaxial growth of ferromagnetic MnSb(0001) has been achieved on high quality, fully relaxed Ge(111)/Si(111) virtual substrates grown by reduced pressure chemical vapor deposition. The epilayers were characterized using reflection high energy electron diffraction, synchrotron hard X-ray diffraction, X-ray photoemission spectroscopy, and magnetometry. The surface reconstructions, magnetic properties, crystalline quality, and strain relaxation behavior of the MnSb films are similar to those of MnSb grown on GaAs(111). In contrast to GaAs substrates, segregation of substrate atoms through the MnSb film does not occur, and alternative polymorphs of MnSb are absent

Direct In Vivo Evidence for Tumor Propagation by Glioblastoma Cancer Stem Cells

High-grade gliomas (World Health Organization grade III anaplastic astrocytoma and grade IV glioblastoma multiforme), the most prevalent primary malignant brain tumors, display a cellular hierarchy with self-renewing, tumorigenic cancer stem cells (CSCs) at the apex. While the CSC hypothesis has been an attractive model to describe many aspects of tumor behavior, it remains controversial due to unresolved issues including the use of ex vivo analyses with differential growth conditions. A CSC population has been confirmed in malignant gliomas by preferential tumor formation from cells directly isolated from patient biopsy specimens. However, direct comparison of multiple tumor cell populations with analysis of the resulting phenotypes of each population within a representative tumor environment has not been clearly described. To directly test the relative tumorigenic potential of CSCs and non-stem tumor cells in the same microenvironment, we interrogated matched tumor populations purified from a primary human tumor transplanted into a xenograft mouse model and monitored competitive in vivo tumor growth studies using serial in vivo intravital microscopy. While CSCs were a small minority of the initial transplanted cancer cell population, the CSCs, not the non-stem tumor cells, drove tumor formation and yielded tumors displaying a cellular hierarchy. In the resulting tumors, a fraction of the initial transplanted CSCs maintained expression of stem cell and proliferation markers, which were significantly higher compared to the non-stem tumor cell population and demonstrated that CSCs generated cellular heterogeneity within the tumor. These head-to-head comparisons between matched CSCs and non-stem tumor cells provide the first functional evidence using live imaging that in the same microenvironment, CSCs more than non-stem tumor cells are responsible for tumor propagation, confirming the functional definition of a CSC

Chronic Myeloid Leukemia Stem Cell Biology

Leukemia progression and relapse is fueled by leukemia stem cells (LSC) that are resistant to current treatments. In the progression of chronic myeloid leukemia (CML), blast crisis progenitors are capable of adopting more primitive but deregulated stem cell features with acquired resistance to targeted therapies. This in turn promotes LSC behavior characterized by aberrant self-renewal, differentiation, and survival capacity. Multiple reports suggest that cell cycle alterations, activation of critical signaling pathways, aberrant microenvironmental cues from the hematopoietic niche, and aberrant epigenetic events and deregulation of RNA processing may facilitate the enhanced survival and malignant transformation of CML progenitors. Here we review the molecular evolution of CML LSC that promotes CML progression and relapse. Recent advances in these areas have identified novel targets that represent important avenues for future therapeutic approaches aimed at selectively eradicating the LSC population while sparing normal hematopoietic progenitors in patients suffering from chronic myeloid malignancies

Stromal Fibroblasts in Digestive Cancer

The normal gastrointestinal stroma consists of extra-cellular matrix and a community of stromal cells including fibroblasts, myofibroblasts, smooth muscle cells, pericytes, endothelium and inflammatory cells. α-smooth muscle actin (α-SMA) positive stromal fibroblasts, often referred to as myofibroblasts or activated fibroblasts, are critical in the development of digestive cancer and help to create an environment that is permissive of tumor growth, angiogenesis and invasion. This review focusses on the contribution of activated fibroblasts in carcinogenesis and where possible directly applies this to, and draws on examples from, gastrointestinal cancer. In particular, the review expands on the definition, types and origins of activated fibroblasts. It examines the molecular biology of stromal fibroblasts and their contribution to the peritumoral microenvironment and concludes by exploring some of the potential clinical applications of this exciting branch of cancer research. Understanding the origin and biology of activated fibroblasts will help in the development of an integrated epithelial-stromal sequence to cancer that will ultimately inform cancer pathogenesis, natural history and future therapeutics

Down syndrome is an oxidative phosphorylation disorder

Down syndrome is the most common genomic disorder of intellectual disability and is caused by trisomy of chromosome 21. Several genes in this chromosome repress mitochondrial biogenesis. The goal of this study was to evaluate whether early overexpression of these genes may cause a prenatal impairment of oxidative phosphorylation negatively affecting neurogenesis. Reduction in the mitochondrial energy production and a lower mitochondrial function have been reported in diverse tissues or cell types, and also at any age, including early fetuses, suggesting that a defect in oxidative phosphorylation is an early and general event in Down syndrome individuals. Moreover, many of the medical conditions associated with Down syndrome are also frequently found in patients with oxidative phosphorylation disease. Several drugs that enhance mitochondrial biogenesis are nowadays available and some of them have been already tested in mouse models of Down syndrome restoring neurogenesis and cognitive defects. Because neurogenesis relies on a correct mitochondrial function and critical periods of brain development occur mainly in the prenatal and early neonatal stages, therapeutic approaches intended to improve oxidative phosphorylation should be provided in these periods.Funding sources: This work was supported by grants from Instituto de Salud Carlos III [FIS-PI17/00021, FIS-PI17/00166]; Fundación Mutua Madrileña [MMA17/01]; Precipita-FECYT crowdfunding program [PR194]; Gobierno de Aragón [LMP135_18, Grupos Consolidados B33_17R] and FEDER 2014–2020 “Construyendo Europa desde Aragón”. CIBERER is an initiative of the ISCIII

Living in a LOFT

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Epitaxial growth of strained Mn5Ge3 nanoislands on Ge(001)

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