Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights

There is an ongoing debate on the therapeutic potential of vaso-modulatory interventions against glioma invasion. Prominent vasculature-targeting therapies involve functional tumour-associated blood vessel deterioration and normalisation. The former aims at tumour infarction and nutrient deprivation medi- ated by vascular targeting agents that induce occlusion/collapse of tumour blood vessels. In contrast, the therapeutic intention of normalising the abnormal structure and function of tumour vascular net- works, e.g. via alleviating stress-induced vaso-occlusion, is to improve chemo-, immuno- and radiation therapy efficacy. Although both strategies have shown therapeutic potential, it remains unclear why they often fail to control glioma invasion into the surrounding healthy brain tissue. To shed light on this issue, we propose a mathematical model of glioma invasion focusing on the interplay between the mi- gration/proliferation dichotomy (Go-or-Grow) of glioma cells and modulations of the functional tumour vasculature. Vaso-modulatory interventions are modelled by varying the degree of vaso-occlusion. We discovered the existence of a critical cell proliferation/diffusion ratio that separates glioma invasion re- sponses to vaso-modulatory interventions into two distinct regimes. While for tumours, belonging to one regime, vascular modulations reduce the tumour front speed and increase the infiltration width, for those in the other regime the invasion speed increases and infiltration width decreases. We show how these in silico findings can be used to guide individualised approaches of vaso-modulatory treatment strategies and thereby improve success rates

The Excitation of N2_2H+^+ in Interstellar Molecular Clouds. I - Models

We present LVG and non-local radiative transfer calculations involving the rotational and hyperfine structure of the spectrum of N$_2$H$^+$ with collisional rate coefficients recently derived by us. The goal of this study is to check the validity of the assumptions made to treat the hyperfine structure and to study the physical mechanisms leading to the observed hyperfine anomalies. We find that the usual hypothesis of identical excitation temperatures for all hyperfine components of the $J$=1-0 transition is not correct within the range of densities existing in cold dense cores, i.e., a few 10$^4$ \textless n(H$_2$) \textless a few 10$^6$ cm$^{-3}$. This is due to different radiative trapping effects in the hyperfine components. Moreover, within this range of densities and considering the typical abundance of N$_2$H$^+$, the total opacity of rotational lines has to be derived taking into account the hyperfine structure. The error made when only considering the rotational energy structure can be as large as 100%. Using non-local models we find that, due to saturation, hyperfine anomalies appear as soon as the total opacity of the $J$=1-0 transition becomes larger than $\simeq$ 20. Radiative scattering in less dense regions enhance these anomalies, and particularly, induce a differential increase of the excitation temperatures of the hyperfine components. This process is more effective for the transitions with the highest opacities for which emerging intensities are also reduced by self-absorption effects. These effects are not as critical as in HCO$^+$ or HCN, but should be taken into account when interpreting the spatial extent of the N$_2$H$^+$ emission in dark clouds.Comment: 13 pages, 12 figure

Windows through the Dusty Disks Surrounding the Youngest Low Mass Protostellar Objects

The formation and evolution of young low mass stars are characterized by important processes of mass loss and accretion ocurring in the innermost regions of their placentary circumstellar disks. Because of the large obscuration of these disks at optical and infrared wavelengths in the early protostellar stages (Class 0 Sources), they were previously detected only at radio wavelengths using interferometric techniques. We have detected with the Infrared Space Observatory (ISO) the mid-infrared emission associated with the Class 0 protostar VLA1 in the HH1-2 region located in the Orion nebula. The emission arises in the three wavelength windows at 5.3, 6.6 and 7.5 micras where the absorption due to ices and silicates has a local minimum that exposes the central parts of the youngest protostellar systems to mid-infrared investigations. The mid-infrared emission arises from a central source with 4 AU diameter at an averaged temperature of 700 K, deeply embedded in a dense region with a visual extinction of Av=80-100mag.Comment: The article is here and on pres

Yacimientos de estaño del Oeste de España

[Resumen] En este trabajo se realiza una clasificación de los. yacimientos de estaño del oeste español basada, fundamentalmente, en consideraciones económicas. Tras una introducción explicativa de los objetivos y metodología empleados, así como una breve exposición del significado de las explotaciones de estaño españolas en el contexto mundial, se describen y clasifican los indicios y yacimientos más importantes, aportándose además un listado de la bibliografía específica más destacable[Abstract] This work presents a classification of the tin deposits in the westof Spain, based, mainly, on economic reasons. After an explaining introduction of the objetives and the method used, and a short exposition of the importance of spanish tin exploitations in the world context, the most important mines and occurrences are described and classified; in addition a list of the most relevant specific bibliography is given

Contribución al estudio de las mineralizaciones Pb-Zn en el entorno macizo granítico de las Peñas de Haya (Guipúzcoa-Navarra)

Se presenta un primer estudio de las mineralizaciones filonianas PbZn asociadas a pizarras oscuras v granito tardihercínico. Las menas y gangas aparecen fuertemente deformadas y brechificadas y es frecuente la removilización de los sulfuros. En el proceso de formación de estas mineralizaciones se distinguen varias fases: una fase hidrotermal de edad hercínica post-intrusiva y una última fase de removilización. Las paragénesis principales permiten clasificar estos yacimientos como mesotermales. Se discuten los modelos genéticos más probables

Tungsten deposits in the west of Spain

[Resumen] En este trabajo se realiza una clasificación de los yacimientos de volframio del oeste español basada, fundamentalmente, en consideraciones económicas. Tras una introducción en la que se comenta la reciente historia del volframio, así como una breve exposición del significado de las explotaciones de volframioespañolas en el contexto mundial, se describen y clasifican los indicios y yacimientos más importantes, aportándose también un listado de la bibliografía específica más destacable.[Abstract] This work presents a classification of the tungsten deposits en the west of Spain, based, mainly, on economic reasons. Mter an explaining introduction of the recent history of the tungsten, and a short exposition of the importance of spanish exploitations in the world context, the most important mines and occurrences are described and c1assified; in addition a list of the most relevant specific bibliography is given

A Search for H2O in the Strongly Lensed QSO MG 0751+2716 at z=3.2

We present a search for 183 GHz H_2O(3_13-2_20) emission in the infrared-luminous quasar MG 0751+2716 with the NRAO Very Large Array (VLA). At z=3.200+/-0.001, this water emission feature is redshifted to 43.6 GHz. As opposed to the faint rotational transitions of HCN (the standard high-density tracer at high-z), H_2O(3_13-2_20) is observed with high maser amplification factors in Galactic star-forming regions. It therefore holds the potential to trace high-density star-forming regions in the distant universe. If indeed all star-forming regions in massively star-forming galaxies at z>3 have similar physical properties as e.g. the Orion or W49N molecular cloud cores, the flux ratio between the maser-amplified H_2O(3_13-2_20) and the thermally excited CO(1-0) transitions may be as high as factor of 20 (but has to be corrected by their relative filling factor). MG 0751+2716 is a strong CO(4-3) emitter, and therefore one of the most suitable targets to search for H_2O(3_13-2_20) at cosmological redshifts. Our search resulted in an upper limit in line luminosity of L'(H_2O) < 0.6 x 10^9 K km/s pc^2. Assuming a brightness temperature of T_b(H_2O) ~= 500 K for the maser emission and CO properties from the literature, this translates to a H_2O(3_13-2_20)/CO(4-3) area filling factor of less than 1%. However, this limit is not valid if the H_2O(3_13-2_20) maser emission is quenched, i.e. if the line is only thermally excited. We conclude that, if our results were to hold for other high-z sources, H_2O does not appear to be a more luminous alternative to HCN to detect high-density gas in star-forming environments at high redshift.Comment: 6 pages, 1 figure, to appear in ApJ (accepted May 19, 2006

Quasar Feedback in the Ultraluminous Infrared Galaxy F11119+3257: Connecting the Accretion Disk Wind with the Large-Scale Molecular Outflow

In Tombesi et al. (2015), we reported the first direct evidence for a quasar accretion disk wind driving a massive molecular outflow. The target was F11119+3257, an ultraluminous infrared galaxy (ULIRG) with unambiguous type-1 quasar optical broad emission lines. The energetics of the accretion disk wind and molecular outflow were found to be consistent with the predictions of quasar feedback models where the molecular outflow is driven by a hot energy-conserving bubble inflated by the inner quasar accretion disk wind. However, this conclusion was uncertain because the energetics were estimated from the optically thick OH 119 um transition profile observed with Herschel. Here, we independently confirm the presence of the molecular outflow in F11119+3257, based on the detection of broad wings in the CO(1-0) profile derived from ALMA observations. The broad CO(1-0) line emission appears to be spatially extended on a scale of at least ~7 kpc from the center. Mass outflow rate, momentum flux, and mechanical power of (80-200) R_7^{-1} M_sun/yr, (1.5-3.0) R_7^{-1} L_AGN/c, and (0.15-0.40)% R_7^{-1} L_AGN are inferred from these data, assuming a CO-to-H_2 conversion factor appropriate for a ULIRG (R_7 is the radius of the outflow normalized to 7 kpc and L_AGN is the AGN luminosity). These rates are time-averaged over a flow time scale of 7x10^6 yrs. They are similar to the OH-based rates time-averaged over a flow time scale of 4x10^5 yrs, but about a factor 4 smaller than the local ("instantaneous"; <10^5 yrs) OH-based estimates cited in Tombesi et al. The implications of these new results are discussed in the context of time-variable quasar-mode feedback and galaxy evolution. The need for an energy-conserving bubble to explain the molecular outflow is also re-examined.Comment: 15 pages, 6 figures, 4 tables, accepted for publication in Ap