Aryl Hydrocarbon Receptor Ligands Inhibit IGF-II and Adipokine Stimulated Breast Cancer Cell Proliferation

Obesity increases human cancer risk and the risk for cancer recurrence. Adipocytes secrete paracrine factors termed adipokines that stimulate signaling in cancer cells that induce proliferation. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays roles in tumorigenesis, is regulated by exogenous lipophilic chemicals, and has been explored as a therapeutic target for cancer therapy. Whether exogenous AHR ligands modulate adipokine stimulated breast cancer cell proliferation has not been investigated. We provide evidence that adipocytes secrete insulin-like growth factor 2 (IGF-2) at levels that stimulate the proliferation of human estrogen receptor (ER) positive breast cancer cells. Using highly specific AHR ligands and AHR short interfering RNA (AHR-siRNA), we show that specific ligand-activated AHR inhibits adipocyte secretome and IGF-2-stimulated breast cancer cell proliferation. We also report that a highly specific AHR agonist significantly ( \u3c 0.05) inhibits the expression of E2F1, CCND1 (known as Cyclin D1), MYB, SRC, JAK2, and JUND in breast cancer cells. Collectively, these data suggest that drugs that target the AHR may be useful for treating cancer in human obesity

An analysis of photoemission and inverse photoemission spectra of Si(111) and sulphur-passivated InP(001) surfaces

Photoemission (PES) and inverse-photoemission spectra (IPES) for the sulphur-passivated InP(001) surface are compared with theoretical predictions based on density-functional calculations. As a test case for our methods, we also present a corresponding study of the better known Si(111) surface. The reported spectra for InP(001)-S agree well with the calculated ones if the surface is assumed to consist of a mixture of two phases, namely, the fully S-covered $(2\times2)$-reconstructed structure, which contains four S atoms in the surface unit-cell, and a $(2\times2)$ structure containing two S and two P atoms per unit cell. The latter has recently been identified in total-energy calculations as well as in core-level spectra of S-passivated Si(111)-$(2\times1)$ is in excellent agreement with the calculations. The comparison of the experimental-PES with our calculations provides additional considerations regarding the nature of the sample surface. It is also found that the commonly-used density-of-states approximation to the photo- and inverse- photoemission spectra is not valid for these systems.Comment: Submitted to Phys. Rev. B; 6 postscript formatted pages; 7 figures in gif format; postscript figures available upon reques

The Radio Structure of High-Energy Peaked BL Lacertae Objects

We present VLA and first-epoch VLBA observations that are part of a program to study the parsec-scale radio structure of a sample of fifteen high-energy-peaked BL Lacs (HBLs). The sample was chosen to span the range of logarithmic X-ray to radio flux ratios observed in HBLs. As this is only the first epoch of observations, proper motions of jet components are not yet available; thus we consider only the structure and alignment of the parsec- and kiloparsec-scale jets. Like most low-energy-peaked BL Lacs (LBLs), our HBL sample shows parsec-scale, core-jet morphologies and compact, complex kiloparsec-scale morphologies. Some objects also show evidence for bending of the jet 10-20pc from the core, suggesting interaction of the jet with the surrounding medium. Whereas LBLs show a wide distribution of parsec- to kpc-scale jet misalignment angles, there is weak evidence that the jets in HBLs are more well-aligned, suggesting that HBL jets are either intrinsically straighter or are seen further off-axis than LBL jets.Comment: Accepted, A

Aryl Hydrocarbon Receptor Ligands Inhibit IGF-II and Adipokine Stimulated Breast Cancer Cell Proliferation

Obesity increases human cancer risk and the risk for cancer recurrence. Adipocytes secrete paracrine factors termed adipokines that stimulate signaling in cancer cells that induce proliferation. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays roles in tumorigenesis, is regulated by exogenous lipophilic chemicals, and has been explored as a therapeutic target for cancer therapy. Whether exogenous AHR ligands modulate adipokine stimulated breast cancer cell proliferation has not been investigated. We provide evidence that adipocytes secrete insulin-like growth factor 2 (IGF-2) at levels that stimulate the proliferation of human estrogen receptor (ER) positive breast cancer cells. Using highly specific AHR ligands and AHR short interfering RNA (AHR-siRNA), we show that specific ligand-activated AHR inhibits adipocyte secretome and IGF-2-stimulated breast cancer cell proliferation. We also report that a highly specific AHR agonist significantly (P < 0.05) inhibits the expression of E2F1, CCND1 (known as Cyclin D1), MYB, SRC, JAK2, and JUND in breast cancer cells. Collectively, these data suggest that drugs that target the AHR may be useful for treating cancer in human obesity

Detecting Exoplanets Closer to Stars with Moderate Spectral Resolution Integral-Field Spectroscopy

While radial velocity surveys have demonstrated that the population of gas giants peaks around $3~\text{au}$, the most recent high-contrast imaging surveys have only been sensitive to planets beyond $\sim~10~\text{au}$. Sensitivity at small angular separations from stars is currently limited by the variability of the point spread function. We demonstrate how moderate-resolution integral field spectrographs can detect planets at smaller separations ($\lesssim~0.3$ arcseconds) by detecting the distinct spectral signature of planets compared to the host star. Using OSIRIS ($R$ $\approx$ 4000) at the W. M. Keck Observatory, we present the results of a planet search via this methodology around 20 young targets in the Ophiuchus and Taurus star-forming regions. We show that OSIRIS can outperform high-contrast coronagraphic instruments equipped with extreme adaptive optics and non-redundant masking in the $0.05-0.3$ arcsecond regime. As a proof of concept, we present the $34\sigma$ detection of a high-contrast M dwarf companion at $\approx0.1$" with a flux ratio of $\approx0.92\%$ around the field F2 star HD 148352. We developed an open-source Python package, breads, for the analysis of moderate-resolution integral field spectroscopy data in which the planet and the host star signal are jointly modeled. The diffracted starlight continuum is forward-modeled using a spline model, which removes the need for prior high-pass filtering or continuum normalization. The code allows for analytic marginalization of linear hyperparameters, simplifying posterior sampling of other parameters (e.g., radial velocity, effective temperature). This technique could prove very powerful when applied to integral field spectrographs like NIRSpec on the JWST and other upcoming first-light instruments on the future Extremely Large Telescopes.Comment: Accepted for publication in the Astronomical Journal on May 12, 202

Dynamical Mass Measurement of the Young Spectroscopic Binary V343 Normae AaAb Resolved With the Gemini Planet Imager

We present new spatially resolved astrometry and photometry from the Gemini Planet Imager of the inner binary of the young multiple star system V343 Normae, which is a member of the beta Pictoris moving group. V343 Normae comprises a K0 and mid-M star in a ~4.5 year orbit (AaAb) and a wide 10" M5 companion (B). By combining these data with archival astrometry and radial velocities we fit the orbit and measure individual masses for both components of M_Aa = 1.10 +/- 0.10 M_sun and M_Ab = 0.290 +/- 0.018 M_sun. Comparing to theoretical isochrones, we find good agreement for the measured masses and JHK band magnitudes of the two components consistent with the age of the beta Pic moving group. We derive a model-dependent age for the beta Pic moving group of 26 +/- 3 Myr by combining our results for V343 Normae with literature measurements for GJ 3305, which is another group member with resolved binary components and dynamical masses.Comment: 12 pages, 7 figures. Accepted to A

Metabolic Signatures of Lung Cancer in Biofluids: NMR-Based Metabonomics of Blood Plasma

In this work, the variations in the metabolic profile of blood plasma from lung cancer patients and healthy controls were investigated through NMR-based metabonomics, to assess the potential of this approach for lung cancer screening and diagnosis. PLS-DA modeling of CPMG spectra from plasma, subjected to Monte Carlo Cross Validation, allowed cancer patients to be discriminated from controls with sensitivity and specificity levels of about 90%. Relatively lower HDL and higher VLDL + LDL in the patients' plasma, together with increased lactate and pyruvate and decreased levels of glucose, citrate, formate, acetate, several amino acids (alanine, glutamine, histidine, tyrosine, valine), and methanol, could be detected. These changes were found to be present at initial disease stages and could be related to known cancer biochemical hallmarks, such as enhanced glycolysis, glutaminolysis, and gluconeogenesis, together with suppressed Krebs cycle and reduced lipid catabolism, thus supporting the hypothesis of a systemic metabolic signature for lung cancer. Despite the possible confounding influence of age, smoking habits, and other uncontrolled factors, these results indicate that NMR-based metabonomics of blood plasma can be useful as a screening tool to identify suspicious cases for subsequent, more specific radiological tests, thus contributing to improved disease management.ERDF - Competitive Factors Thematic Operational ProgrammeFCT/PTDC/ QUI/68017/2006FCOMP-01-0124-FEDER-007439SFRH/BD/ 63430/2009National UNESCO Committee - L'Oréal Medals of Honor for Women in Science 200Portuguese National NMR Network - RNRM

Evidence Use and the Institutions of the State: The Role of Parliament and the Judiciary

This chapter explores the role of parliaments and the judiciary in shaping evidence use in health policy making. Most analyses of the role of scientific evidence focus on the executive, i.e. national governments and ministries of health, as the key state actors in health policy and health system governance. This chapter shifts attention to the other two powers within the state, the legislative and the judiciary. Using the examples analysed in this book the chapter examines how parliaments can use evidence to inform legislative processes and to hold governments to account, although there are substantial differences between countries and political systems. However, there was little suggestion that such approaches were undertaken systematically. In cases in which policies are brought to court, judges may have to deal with scientific evidence within a country’s legal and constitutional framework, again with significant differences between national legal practices

Early glandular neoplasia of the lung

Although bronchogenic carcinomas progress through a very well defined sequence of metaplasia, dysplasia and carcinoma in situ, very little is known about the early progression of glandular neoplasms of the lung. In particular, the early precursor lesion from which fully malignant adenocarcinomas arise has effectively eluded recognition, at least until recently. Several lines of evidence now implicate atypical adenomatous hyperplasia (AAH) as an initial morphologic stage in multistep lung tumorigenesis. Despite its small size, AAH can be appreciated at the light microscopic level and characterized at the molecular genetic level. Indeed, the genetic characterization of AAH promises to further our understanding of lung cancer development and might facilitate the design of novel strategies for early detection of lung cancer