Measurement of tissue optical properties and modeling of optimal light delivery for tumor treatment

Oblique-incidence reflectometry was used to measure the optical properties of rat tumors with injected absorption- enhancement dye. The measured optical properties were used to model light delivery into the tissues for optimal therapeutic effects. The goal was to efficiently deliver the maximum amount of optical power into buried tumors being treated while avoiding potential damage to normal tissue caused by strong optical power deposition underneath the tissue surface illuminated by the laser beam. The distribution of power deposition was simulated for single beam delivery and multiple beam delivery as well. The simulated results showed that with an appropriate dye enhancement and an optimal laser delivery configuration, a high selectivity for laser treatment of tumors could be achieved

Local and Large scale Environment of Seyfert Galaxies

We present a three-dimensional study of the local (<100 h^-1} kpc) and the large scale (<1 h^{-1} Mpc) environment of the two main types of Seyfert AGN galaxies. For this purpose we use 48 Sy1 galaxies (with redshifts in the range 0.007<z<0.036) and 56 Sy2 galaxies (with 0.004<z<0.020), located at high galactic latitudes, as well as two control samples of non-active galaxies having the same morphological, redshift, and diameter size distributions as the corresponding Seyfert samples. Using the Center for Astrophysics (CfA2) and Southern Sky Redshift Survey (SSRS) galaxy catalogues (m_B~15.5) and our own spectroscopic observations (m_B~18.5), we find that within a projected distance of 100 h^-1 kpc and a radial velocity separation of dv<600 km/sec around each of our AGNs, the fraction of Seyfert 2 galaxies with a close neighbor is significantly higher than that of their control (especially within 75 h^{-1} kpc) and Seyfert 1 galaxy samples, confirming a previous two-dimensional analysis of Dultzin-Hacyan et al. We also find that the large-scale environment around the two types of Seyfert galaxies does not vary with respect to their control sample galaxies. However, in the Seyfert 2 and control galaxy samples do differ significantly when compared to the corresponding Seyfert 1 samples. Since the main difference between these samples is their morphological type distribution, we argue that the large-scale environmental difference cannot be attributed to differences in nuclear activity but rather to their different type of host galaxies.Comment: accepted for publication in ApJ, Abstract size reduced (according to new rules) and corrected reference

Cyclotron production of high–specific activity 55Co and in vivo evaluation of the stability of 55Co metal-chelate-peptide complexes

This work describes the production of high–specific activity 55 Co and the evaluation of the stability of 55 Co-metal-chelate-peptide complexes in vivo. 55 Co was produced via the 58 Ni(p,α) 55 Co reaction and purified using anion exchange chromatography with an average recovery of 92% and an average specific activity of 1.96 GBq/μmol. 55 Co-DO3A and 55 Co-NO2A peptide complexes were radiolabeled at 3.7 MBq/μg and injected into HCT-116 tumor xenografted mice. Positron emission tomography (PET) and biodistribution studies were performed at 24 and 48 hours postinjection and compared to those of 55 CoCl 2 . Both 55 Co-metal-chelate complexes demonstrated good in vivo stability by reducing the radiotracers’ uptake in the liver by sixfold at 24 hours with ˜ 1% ID/g and at 48 hours with ˜ 0.5% ID/g and reducing uptake in the heart by fourfold at 24 hours with ˜ 0.7% ID/g and sevenfold at 48 hours with ˜ 0.35% ID/g. These results support the use of 55 Co as a promising new radiotracer for PET imaging of cancer and other diseases

ALMA reveals the feeding of the Seyfert 1 nucleus in NGC 1566

We report ALMA observations of CO(3-2) emission in the Seyfert 1 galaxy NGC 1566, at a spatial resolution of 25 pc. Our aim is to investigate the morphology and dynamics of the gas inside the central kpc, and to probe nuclear fueling and feedback phenomena. NGC 1566 has a nuclear bar of 1.7 kpc radius and a conspicuous grand design spiral starting from this radius. The ALMA field of view, of diameter 0.9 kpc, lies well inside the nuclear bar and reveals a molecular trailing spiral structure from 50 to 300~pc in size, which is contributing to fuel the nucleus, according to its negative gravity torques. The spiral starts with a large pitch angle from the center and then winds up in a pseudo-ring at the inner Lindblad resonance (ILR) of the nuclear bar. This is the first time that a trailing spiral structure is clearly seen driving the gas inwards inside the ILR ring of the nuclear bar. This phenomenon shows that the massive central black hole has a significant dynamical influence on the gas, triggering its fueling. The gaseous spiral is well correlated with the dusty spiral seen through extinction in HST images, and also with a spiral feature emitting 0.87mm continuum. This continuum emission must come essentially from cold dust heated by the interstellar radiation field. The HCN(4-3) and HCO+(4-3) lines were simultaneously mapped and detected in the nuclear spiral. The HCO+(4-3) line is 3 times stronger than the HCN(4-3), as expected when star formation excitation dominates over active galactic nucleus (AGN) heating. The CO(3-2)/HCO+(4-3) integrated intensity ratio is \sim 100. The molecular gas is in remarkably regular rotation, with only slight non-circular motions at the periphery of the nuclear spiral arms. These perturbations are quite small, and no outflow nor AGN feedback is detected.Comment: 11 pages, 16 figures, accepted in Astronomy and Astrophysic

ALMA observations of feeding and feedback in nearby Seyfert galaxies: an AGN-driven outflow in NGC 1433

We report ALMA observations of CO(3-2) emission in the Seyfert 2 double-barred galaxy NGC1433, at the unprecedented spatial resolution of 0.5"=24 pc. Our aim is to probe AGN feeding and feedback phenomena through the morphology and dynamics of the gas inside the central kpc. The CO map, which covers the whole nuclear region (nuclear bar and ring), reveals a nuclear gaseous spiral structure, inside the nuclear ring encircling the nuclear stellar bar. This gaseous spiral is well correlated with the dusty spiral seen in Hubble Space Telescope images. The nuclear spiral winds up in a pseudo-ring at 200 pc radius, which might correspond to the inner ILR. Continuum emission is detected at 0.87 mm only at the very centre, and its origin is more likely thermal dust emission than non-thermal emission from the AGN. It might correspond to the molecular torus expected to exist in this Seyfert 2 galaxy. The HCN(4-3) and HCO+(4-3) lines were observed simultaneously, but only upper limits are derived, with a ratio to the CO(3-2) line lower than 1/60 at 3sigma, indicating a relatively low abundance of very dense gas. The kinematics of the gas over the nuclear disk reveal rather regular rotation only slightly perturbed by streaming motions due to the spiral; the primary and secondary bars are too closely aligned with the galaxy major or minor axis to leave a signature in the projected velocities. Near the nucleus, there is an intense high-velocity CO emission feature redshifted to 200 km/s (if located in the plane), with a blue-shifted counterpart, at 2" (100 pc) from the centre. While the CO spectra are quite narrow in the centre, this wide component is interpreted as an outflow involving a molecular mass of 3.6 10^6 Mo and a flow rate 7 Mo/yr. The flow could be in part driven by the central star formation, but is mainly boosted by the AGN through its wind or radio jets.Comment: 11 pages, 9 figures, Accepted in Astronomy and Astrophysic

Gravitational stability and dynamical overheating of stellar disks of galaxies

We use the marginal stability condition for galactic disks and the stellar velocity dispersion data published by different authors to place upper limits on the disk local surface density at two radial scalelengths $R=2h$. Extrapolating these estimates, we constrain the total mass of the disks and compare these estimates to those based on the photometry and color of stellar populations. The comparison reveals that the stellar disks of most of spiral galaxies in our sample cannot be substantially overheated and are therefore unlikely to have experienced a significant merging event in their history. The same conclusion applies to some, but not all of the S0 galaxies we consider. However, a substantial part of the early type galaxies do show the stellar velocity dispersion well in excess of the gravitational stability threshold suggesting a major merger event in the past. We find dynamically overheated disks among both seemingly isolated galaxies and those forming pairs. The ratio of the marginal stability disk mass estimate to the total galaxy mass within four radial scalelengths remains within a range of 0.4---0.8. We see no evidence for a noticeable running of this ratio with either the morphological type or color index.Comment: 25 pages, 5 figures, accepted to Astronomy Letter

HST FOC spectroscopy of the NLR of NGC 4151. I. Gas kinematics

We present the results from a detailed kinematic analysis of both ground-based, and Hubble Space Telescope/Faint Object Camera long-slit spectroscopy at sub-arcsec spatial resolution, of the narrow-line region of NGC 4151. In agreement with previous work, the extended emission gas (R > 4") is found to be in normal rotation in the galactic plane, a behaviour that we were able to trace even across the nuclear region, where the gas is strongly disturbed by the interaction with the radio jet, and connects smoothly with the large scale rotation defined by the neutral gas emission. The HST data, at 0.029" spatial resolution, allow us for the first time to truly isolate the kinematic behaviour of the individual clouds in the inner narrow-line region. We find that, underlying the perturbations introduced by the radio ejecta, the general velocity field can still be well represented by planar rotation down to a radius of ~ 0.5" (30 pc), distance at which the rotation curve has its turnover. The most striking result that emerges from our analysis is that the galaxy potential derived fitting the rotation curve changes from a "dark halo" at the ENLR distances to dominated by the central mass concentration in the NLR, with an almost Keplerian fall-off in the 1"< R < 4" interval. The observed velocity of the gas at 0.5" implies a mass of M ~ 10E9 M(sol) within the inner 60 pc. The presence of a turnover in the rotation curve indicates that this central mass concentration is extended. The first measured velocity point (outside the region saturated by the nucleus) would imply an enclosed mass of ~ 5E7 M(sol) within R ~ 0.15" (10 pc) which represents an upper limit to any nuclear point mass.Comment: 30 pages (aaspp4.sty), 14 figures. Fig. 1, 2 and 4 available by anonymous FTP at 143.54.2.51 (cd /pub/winge) as GIF files; or upon request to [email protected]. Accepted for publication in the Astrophysical Journal (part 1

Mendelian randomization with fine-mapped genetic data: choosing from large numbers of correlated instrumental variables

Mendelian randomization uses genetic variants to make causal inferences about the effect of a risk factor on an outcome. With fine-mapped genetic data, there may be hundreds of genetic variants in a single gene region any of which could be used to assess this causal relationship. However, using too many genetic variants in the analysis can lead to spurious estimates and inflated Type 1 error rates. But if only a few genetic variants are used, then the majority of the data is ignored and estimates are highly sensitive to the particular choice of variants. We propose an approach based on summarized data only (genetic association and correlation estimates) that uses principal components analysis to form instruments. This approach has desirable theoretical properties: it takes the totality of data into account and does not suffer from numerical instabilities. It also has good properties in simulation studies: it is not particularly sensitive to varying the genetic variants included in the analysis or the genetic correlation matrix, and it does not have greatly inflated Type 1 error rates. Overall, the method gives estimates that are not so precise as those from variable selection approaches (such as using a conditional analysis or pruning approach to select variants), but are more robust to seemingly arbitrary choices in the variable selection step. Methods are illustrated by an example using genetic associations with testosterone for 320 genetic variants to assess the effect of sex hormone-related pathways on coronary artery disease risk, in which variable selection approaches give inconsistent inferences.Stephen Burgess and Verena Zuber are supported by Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 204623/Z/16/Z). Jemma C Hopewell is supported by a British Heart Foundation Basic Science Research Fellowship (grant number FS/14/55/30806)

The protein tyrosine phosphatase receptor type R gene is an early and frequent target of silencing in human colorectal tumorigenesis

BACKGROUND: Tumor development in the human colon is commonly accompanied by epigenetic changes, such as DNA methylation and chromatin modifications. These alterations result in significant, inheritable changes in gene expression that contribute to the selection of tumor cells with enhanced survival potential. RESULTS: A recent high-throughput gene expression analysis conducted by our group identified numerous genes whose transcription was markedly diminished in colorectal tumors. One of these, the protein-tyrosine phosphatase receptor type R (PTPRR) gene, was dramatically downregulated from the earliest stages of cellular transformation. Here, we show that levels of both major PTPRR transcript variants are markedly decreased (compared with normal mucosal levels) in precancerous and cancerous colorectal tumors, as well in colorectal cancer cell lines. The expression of the PTPRR-1 isoform was inactivated in colorectal cancer cells as a result of de novo CpG island methylation and enrichment of transcription-repressive histone-tail marks, mainly H3K27me3. De novo methylation of the PTPRR-1 transcription start site was demonstrated in 29/36 (80%) colorectal adenomas, 42/44 (95%) colorectal adenocarcinomas, and 8/8 (100%) liver metastases associated with the latter tumors. CONCLUSIONS: Epigenetic downregulation of PTPRR seems to be an early alteration in colorectal cell transformation, which is maintained during the clonal selection associated with tumor progression. It may represent a preliminary step in the constitutive activation of the RAS/RAF/MAPK/ERK signalling, an effect that will later be consolidated by mutations in genes encoding key components of this pathway