Multiband optical polarimetry of the BL Lac object PKS 2155--304. Intranight and long term variability

The polarized and total flux of the BL Lac object PKS 2155-304 were monitored intensively and simultaneously in the optical UBVRI bands with the Turin photopolarimeter at the CASLEO 2.15 m telescope during 4 campaigns in June, August, November 1998 and August 1999. The effective observation time amounted to ~47 hours. PKS 2155-304 showed a linear polarization percentage (P) usually ranging between 3% and 7% and a polarization position angle (PA) mainly between 70 and 120 deg. The highest temporal resolution of our observations, 15 minutes, is unprecedented for polarimetric monitoring of this source, and has allowed us to detect amplitude variations of the linear polarization percentage from 6 to 7.5% in time scales of hours. In some nights the polarization percentage seems to increase toward shorter wavelengths, however the polarized spectrum does not vary significantly with time. The most remarkable variability event occurred on 1998 June 18, when the degree of linear polarization decreased by more than a factor 2 in one day in all bands, while the PA rotated by 90 deg. This is consistent with the presence of two emission components, of different polarization degree and position angle. Intranight variability of P and PA can be interpreted with small amplitude physical or geometrical changes within the jet. Measurements of the circular polarization over time intervals of days set upper limits of 0.2%. Simultaneous photometry taken with the Turin Photopolarimeter and with a CCD camera at Cordoba Astronomical Observatory did not show light variations correlated with those of the linearly polarized flux.Comment: 21 pages, 6 eps figures. Accepted for The Astrophysical Journal Supplement Serie

Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas

Loss of the tumor suppressor gene PTEN is implicated in breast cancer progression and resistance to targeted therapies, and is thought to promote tumorigenesis by activating PI3K signaling. In a transgenic model of breast cancer, Pten suppression using a tetracycline-regulatable short hairpin (sh)RNA cooperates with human epidermal growth factor receptor 2 (HER2/neu), leading to aggressive and metastatic disease with elevated signaling through PI3K and, surprisingly, the mitogen-activated protein kinase (MAPK) pathway. Restoring Pten function is sufficient to down-regulate both PI3K and MAPK signaling and triggers dramatic tumor regression. Pharmacologic inhibition of MAPK signaling produces similar effects to Pten restoration, suggesting that the MAPK pathway contributes to the maintenance of advanced breast cancers harboring Pten loss

Sources of Relativistic Jets in the Galaxy

Black holes of stellar mass and neutron stars in binary systems are first detected as hard X-ray sources using high-energy space telescopes. Relativistic jets in some of these compact sources are found by means of multiwavelength observations with ground-based telescopes. The X-ray emission probes the inner accretion disk and immediate surroundings of the compact object, whereas the synchrotron emission from the jets is observed in the radio and infrared bands, and in the future could be detected at even shorter wavelengths. Black-hole X-ray binaries with relativistic jets mimic, on a much smaller scale, many of the phenomena seen in quasars and are thus called microquasars. Because of their proximity, their study opens the way for a better understanding of the relativistic jets seen elsewhere in the Universe. From the observation of two-sided moving jets it is inferred that the ejecta in microquasars move with relativistic speeds similar to those believed to be present in quasars. The simultaneous multiwavelength approach to microquasars reveals in short timescales the close connection between instabilities in the accretion disk seen in the X-rays, and the ejection of relativistic clouds of plasma observed as synchrotron emission at longer wavelengths. Besides contributing to a deeper comprehension of accretion disks and jets, microquasars may serve in the future to determine the distances of jet sources using constraints from special relativity, and the spin of black holes using general relativity.Comment: 39 pages, Tex, 8 figures, to appear in vol. 37 (1999) of Annual Reviews of Astronomy and Astrophysic

Cell-free DNA analysis in healthy individuals by next-generation sequencing: a proof of concept and technical validation study.

Pre-symptomatic screening of genetic alterations might help identify subpopulations of individuals that could enter into early access prevention programs. Since liquid biopsy is minimally invasive it can be used for longitudinal studies in healthy volunteers to monitor events of progression from normal tissue to pre-cancerous and cancerous condition. Yet, cell-free DNA (cfDNA) analysis in healthy individuals comes with substantial challenges such as the lack of large cohort studies addressing the impact of mutations in healthy individuals or the low abundance of cfDNA in plasma. In this study, we aimed to investigate the technical feasibility of cfDNA analysis in a collection of 114 clinically healthy individuals. We first addressed the impact of pre-analytical factors such as cfDNA yield and quality on sequencing performance and compared healthy to cancer donor samples. We then confirmed the validity of our testing strategy by evaluating the mutational status concordance in matched tissue and plasma specimens collected from cancer patients. Finally, we screened our group of healthy donors for genetic alterations, comparing individuals who did not develop any tumor to patients who developed either a benign neoplasm or cancer during 1-10 years of follow-up time. To conclude, we have established a rapid and reliable liquid biopsy workflow that allowed us to study genomic alterations with a limit of detection as low as 0.08% of variant allelic frequency in healthy individuals. We detected pathogenic cancer mutations in four healthy donors that later developed a benign neoplasm or invasive breast cancer up to 10 years after blood collection. Even though larger prospective studies are needed to address the specificity and sensitivity of liquid biopsy as a clinical tool for early cancer detection, systematic screening of healthy individuals will help understanding early events of tumor formation

Time-Resolved Photometry of Kuiper Belt Objects: Rotations, Shapes and Phase Functions

We present a systematic investigation of the rotational lightcurves of trans-Neptunian objects based on extensive optical data from Mauna Kea. Four of 13 objects (corresponding to 31%) in our sample ((33128) 1998 BU48, 2000 GN171, (20000) Varuna and 1999 KR16) were found to exhibit lightcurves with peak-to-peak range > 0.15 magnitude. In a larger sample obtained by combining our data with reliably determined lightcurves from the literature, 7 of 22 objects (32%) display significant (> 0.15 magnitude range) lightcurves. About 23% of the sampled objects have lightcurve ranges > 0.4 magnitudes. Curiously, the objects are very large (> 250 km diameter, assuming an albedo of 0.04) and, in the absence of rotation, should be near spherical due to self compression. We propose that the large amplitude, short period objects are rotationally distorted, low density rubble piles. Statistically, the trans-Neptunian objects are less spherical than their main-belt asteroid counterparts, indicating a higher specific angular momentum perhaps resulting from the formation epoch. In addition to the rotational lightcurves, we measured phase darkening for 7 Kuiper Belt objects in the 0 to 2 degree phase angle range. Unlike Pluto, the measured values show steep slopes and moderate opposition surge indicating backscatter from low albedo porous surface materials.Comment: 22 pages, 33 figures, 12 tables, To appear in AJ sept. 200

Multiband optical polarimetry of BL Lac objects with the Nordic Optical Telescope

Optical polarization of seven selected BL Lac objects in UBVRI bands was studied with the Nordic Optical Telescope from December 10-14, 1999. Two of them, 3C 66A and PKS 0735+178, were monitored for 4 nights for a total integration time of 4.75 and 5.5 hours, respectively. Other objects (1Jy 0138-097, H 0414+009, PKS 0823-223, OJ287 and BL Lac) were observed sparsely during the run. Apart from PKS 0823-223 (more polarized than observed in the past), the sources show levels of flux and polarization consistent with results at previous epochs. 3C 66A and PKS 0735+178 were intensively observed during December 11 and 12 and exhibited variability of polarization, both on internight and intranight time scales. Wavelength dependence of polarization has been investigated, as well as circular polarization. The results are discussed within the standard model for BL Lacs.Comment: 11 pages, 7 figures, accepted to Astronomy & Astrophysic

Taselisib (GDC-0032), a Potent -Sparing Small Molecule Inhibitor of PI3K, Radiosensitizes Head and Neck Squamous Carcinomas Containing Activating PIK3CA Alterations

Activating PIK3CA genomic alterations are frequent in head and neck squamous cell carcinoma (HNSCC), and there is an association between phosphoinositide 3-kinase (PI3K) signaling and radioresistance. Hence, we investigated the therapeutic efficacy of inhibiting PI3K with GDC-0032, a PI3K inhibitor with potent activity against p110α, in combination with radiation in HNSCC

Optical polarization observations of NGC 6231: evidence for a past SN fingerprint

We present the first linear multicolor polarization observations for a sample of 35 stars in the direction of the Galactic cluster NGC 6231. We have found a complex pattern in the angles of the polarimetric vectors. Near the core of this cluster the structure shows a semi-circular pattern that we have interpreted as a re-orientation of the dust particles, showing the morphology of the magnetic field. We propose that a supernova event has occurred some time ago and produced a shock on the local ISM. We discuss in this paper independent confirmations othis event, both from the studies on the diffuse interstellar absorptions Crawford (2001) and the results of the pre-main sequence stars (PMS) given by Sung et al. (1998). We also show that a supernova is supported by the evolutive status of the cluster.Comment: 24 pages, 4 figures, ApJ Accepte