Lise Christensen

Bio: Lise Christensen is an academic researcher from University of Copenhagen. The author has contributed to research in topics: Galaxy & Redshift. The author has an hindex of 59, co-authored 305 publications receiving 14249 citations. Previous affiliations of Lise Christensen include Max Planck Society & Niels Bohr Institute.

The urokinase-type plasminogen activator system in cancer metastasis: a review

Abstract: The urokinase-type plasminogen activator (u-PA) system consists of the serine proteinases plasmin and u-PA; the serpin inhibitors alpha2-anti-plasmin, PAI-1 and PAI-2; and the u-PA receptor (u-PAR). Two lines of evidence have strongly suggested an important and apparently causal role for the u-PA system in cancer metastasis: results from experimental model systems with animal tumor metastasis and the finding that high levels of u-PA, PAI-1 and u-PAR in many tumor types predict poor patient prognosis. We discuss here recent observations related to the molecular and cellular mechanisms underlying this role of the u-PA system. Many findings suggest that the system does not support tumor metastasis by the unrestricted enzyme activity of u-PA and plasmin. Rather, pericellular molecular and functional interactions between u-PA, u-PAR, PAI-1, extracellular matrix proteins, integrins, endocytosis receptors and growth factors appear to allow temporal and spatial re-organizations of the system during cell migration and a selective degradation of extracellular matrix proteins during invasion. Differential expression of components of the system by cancer and non-cancer cells, regulated by paracrine mechanisms, appear to determine the involvement of the system in cancer cell-directed tissue remodeling. A detailed knowledge of these processes is necessary for utilization of the therapeutic potential of interfering with the action of the system in cancers.

X-shooter, the new wide band intermediate resolution spectrograph at the ESO Very Large Telescope

Abstract: X-shooter is the first 2nd generation instrument of the ESO Very Large Telescope(VLT). It is a very efficient, single-target, intermediate-resolution spectrograph that was installed at the Cassegrain focus of UT2 in 2009. The instrument covers, in a single exposure, the spectral range from 300 to 2500 nm. It is designed to maximize the sensitivity in this spectral range through dichroic splitting in three arms with optimized optics, coatings, dispersive elements and detectors. It operates at intermediate spectral resolution (R~4,000 - 17,000, depending on wavelength and slit width) with fixed echelle spectral format (prism cross-dispersers) in the three arms. It includes a 1.8"x4" Integral Field Unit as an alternative to the 11" long slits. A dedicated data reduction package delivers fully calibrated two-dimensional and extracted spectra over the full wavelength range. We describe the main characteristics of the instrument and present its performance as measured during commissioning, science verification and the first months of science operations.

New constraints on the free-streaming of warm dark matter from intermediate and small scale Lyman-α forest data

Abstract: We present new measurements of the free-streaming of warm dark matter (WDM) from Lyman-α flux-power spectra. We use data from the medium resolution, intermediate redshift XQ-100 sample observed with the X-shooter spectrograph (z = 3 – 4.2) and the high-resolution, high-redshift sample used in Viel et al. (2013) obtained with the HIRES/MIKE spectrographs (z = 4.2 - 5.4). Based on further improved modelling of the dependence of the Lyman-α flux-power spectrum on the free-streaming of dark matter, cosmological parameters, as well as the thermal history of the intergalactic medium (IGM) with hydrodynamical simulations, we obtain the following limits, expressed as the equivalent mass of thermal relic WDM particles. The XQ-100 flux power spectrum alone gives a lower limit of 1.4 keV, the re-analysis of the HIRES/MIKE sample gives 4.1 keV while the combined analysis gives our best and significantly strengthened lower limit of 5.3 keV (all 2σ C.L.). The further improvement in the joint analysis is partly due to the fact that the two data sets have different degeneracies between astrophysical and cosmological parameters that are broken when the data sets are combined, and more importantly on chosen priors on the thermal evolution. These results all assume that the temperature evolution of the IGM can be modelled as a power law in redshift. Allowing for a non-smooth evolution of the temperature of the IGM with sudden temperature changes of up to 5000K reduces the lower limit for the combined analysis to 3.5 keV. A WDM with smaller thermal relic masses would require, however, a sudden temperature jump of 5000K or more in the narrow redshift interval z = 4.6 - 4.8, in disagreement with observations of the thermal history based on high-resolution resolution Lyman-α forest data and expectations for photo-heating and cooling in the low density IGM at these redshifts.

Low-resolution Spectroscopy of Gamma-ray Burst Optical Afterglows: Biases in the Swift Sample and Characterization of the Absorbers

Abstract: We present a sample of 77 optical afterglows (OAs) of Swift detected gamma-ray bursts (GRBs) for which spectroscopic follow-up observations have been secured. Our first objective is to measure the redshifts of the bursts. For the majority (90%) of the afterglows, the redshifts have been determined from the spectra. We provide line lists and equivalent widths (EWs) for all detected lines redward of Lyα covered by the spectra. In addition to the GRB absorption systems, these lists include line strengths for a total of 33 intervening absorption systems. We discuss to what extent the current sample of Swift bursts with OA spectroscopy is a biased subsample of all Swift detected GRBs. For that purpose we define an X-ray-selected statistical sample of Swift bursts with optimal conditions for ground-based follow-up from the period 2005 March to 2008 September; 146 bursts fulfill our sample criteria. We derive the redshift distribution for the statistical (X-ray selected) sample and conclude that less than 18% of Swift bursts can be at z > 7. We compare the high-energy properties (e.g., γ-ray (15-350 keV) fluence and duration, X-ray flux, and excess absorption) for three subsamples of bursts in the statistical sample: (1) bursts with redshifts measured from OA spectroscopy; (2) bursts with detected optical and/or near-IR afterglow, but no afterglow-based redshift; and (3) bursts with no detection of the OA. The bursts in group (1) have slightly higher γ-ray fluences and higher X-ray fluxes and significantly less excess X-ray absorption than bursts in the other two groups. In addition, the fractions of dark bursts, defined as bursts with an optical to X-ray slope βOX 39% in group (3). For the full sample, the dark burst fraction is constrained to be in the range 25%-42%. From this we conclude that the sample of GRBs with OA spectroscopy is not representative for all Swift bursts, most likely due to a bias against the most dusty sight lines. This should be taken into account when determining, e.g., the redshift or metallicity distribution of GRBs and when using GRBs as a probe of star formation. Finally, we characterize GRB absorption systems as a class and compare them to QSO absorption systems, in particular the damped Lyα absorbers (DLAs). On average GRB absorbers are characterized by significantly stronger EWs for H I as well as for both low and high ionization metal lines than what is seen in intervening QSO absorbers. However, the distribution of line strengths is very broad and several GRB absorbers have lines with EWs well within the range spanned by QSO-DLAs. Based on the 33 z > 2 bursts in the sample, we place a 95% confidence upper limit of 7.5% on the mean escape fraction of ionizing photons from star-forming galaxies. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile, under programs 275.D-5022 (PI: Chincarini), 075.D-0270 (PI: Fynbo), 077.D-0661 (PI: Vreeswijk), 077.D-0805 (PI: Tagliaferri), 177.A-0591 (PI: Hjorth), 078.D-0416 (PI: Vreeswijk), 079.D-0429 (PI: Vreeswijk), 080.D-0526 (PI: Vreeswijk), 081.A-0135 (PI: Greiner), 281.D-5002 (PI: Della Valle), and 081.A-0856 (PI: Vreeswijk). Also based on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias. Some of the data obtained herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck foundation.

Low-Resolution Spectroscopy of Gamma-ray Burst Optical Afterglows: Biases in the Swift Sample and Characterization of the Absorbers

Abstract: (Abridged). We present a sample of 77 optical afterglows (OAs) of Swift detected GRBs for which spectroscopic follow-up observations have been secured. We provide linelists and equivalent widths for all detected lines redward of Ly-alpha. We discuss to what extent the current sample of Swift bursts with OA spectroscopy is a biased subsample of all Swift detected GRBs. For that purpose we define an X-ray selected sample of Swift bursts with optimal conditions for ground-based follow up from the period March 2005 to September 2008; 146 bursts fulfill our sample criteria. We derive the redshift distribution for this sample and conclude that less than 19% of Swift bursts are at z>7. We compare the high energy properties for three sub-samples of bursts in the sample: i) bursts with redshifts measured from OA spectroscopy, ii) bursts with detected OA, but no OA-based redshift, and iii) bursts with no detection of the OA. The bursts in group i) have significantly less excess X-ray absorption than bursts in the other two groups. In addition, the fraction of dark bursts is 14% in group i), 38% in group ii) and > 39% in group iii). From this we conclude that the sample of GRBs with OA spectroscopy is not representative for all Swift bursts, most likely due to a bias against the most dusty sight-lines. Finally, we characterize GRB absorption systems as a class and compare them to QSO absorption systems, in particular DLAs. On average GRB absorbers are characterized by significantly stronger EWs for HI as well as for both low and high ionization metal lines than what is seen in intervening QSO absorbers. Based on the z>2 bursts in the sample we place a 95% confidence upper limit of 7.5% on the mean escape fraction of ionizing photons from star-forming galaxies.

The microenvironment of the tumour-host interface

Abstract: Throughout the entire process of cancer aetiology, progression and metastasis, the microenvironment of the local host tissue can be an active participant. Invasion occurs within a tumour-host microecology, where stroma and tumour cells exchange enzymes and cytokines that modify the local extracellular matrix, stimulate migration, and promote proliferation and survival. A new class of cancer therapies that targets this pathological communication interface between tumour cells and host cells is currently under development.

TGF-beta signaling in tumor suppression and cancer progression.

Abstract: Epithelial and hematopoietic cells have a high turnover and their progenitor cells divide continuously, making them prime targets for genetic and epigenetic changes that lead to cell transformation and tumorigenesis. The consequent changes in cell behavior and responsiveness result not only from genetic alterations such as activation of oncogenes or inactivation of tumor suppressor genes, but also from altered production of, or responsiveness to, stimulatory or inhibitory growth and differentiation factors. Among these, transforming growth factor β (TGF-β) and its signaling effectors act as key determinants of carcinoma cell behavior. The autocrine and paracrine effects of TGF-β on tumor cells and the tumor micro-environment exert both positive and negative influences on cancer development. Accordingly, the TGF-β signaling pathway has been considered as both a tumor suppressor pathway and a promoter of tumor progression and invasion. Here we evaluate the role of TGF-β in tumor development and attempt to reconcile the positive and negative effects of TGF-β in carcinogenesis.

Breast cancer metastasis: markers and models

Abstract: Breast cancer starts as a local disease, but it can metastasize to the lymph nodes and distant organs. At primary diagnosis, prognostic markers are used to assess whether the transition to systemic disease is likely to have occurred. The prevailing model of metastasis reflects this view--it suggests that metastatic capacity is a late, acquired event in tumorigenesis. Others have proposed the idea that breast cancer is intrinsically a systemic disease. New molecular technologies, such as DNA microarrays, support the idea that metastatic capacity might be an inherent feature of breast tumours. These data have important implications for prognosis prediction and our understanding of metastasis.

Gravitational Waves and Gamma-rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

Abstract: On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anticoincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is $5.0\times 10^{-8}$. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short gamma-ray bursts. We use the observed time delay of $(+1.74 \pm 0.05)\,$s between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between $-3\times 10^{-15}$ and $+7\times 10^{-16}$ times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1--1.4 per year during the 2018-2019 observing run and 0.3--1.7 per year at design sensitivity.