Tumor angiogenesis and anti-angiogenic therapy in malignant gliomas revisited

The cellular and molecular mechanisms of tumor angiogenesis and its prospects for anti-angiogenic cancer therapy are major issues in almost all current concepts of both cancer biology and targeted cancer therapy. Currently, (1) sprouting angiogenesis, (2) vascular co-option, (3) vascular intussusception, (4) vasculogenic mimicry, (5) bone marrow-derived vasculogenesis, (6) cancer stem-like cell-derived vasculogenesis and (7) myeloid cell-driven angiogenesis are all considered to contribute to tumor angiogenesis. Many of these processes have been described in developmental angiogenesis; however, the relative contribution and relevance of these in human brain cancer remain unclear. Preclinical tumor models support a role for sprouting angiogenesis, vascular co-option and myeloid cell-derived angiogenesis in glioma vascularization, whereas a role for the other four mechanisms remains controversial and rather enigmatic. The anti-angiogenesis drug Avastin (Bevacizumab), which targets VEGF, has become one of the most popular cancer drugs in the world. Anti-angiogenic therapy may lead to vascular normalization and as such facilitate conventional cytotoxic chemotherapy. However, preclinical and clinical studies suggest that anti-VEGF therapy using bevacizumab may also lead to a pro-migratory phenotype in therapy resistant glioblastomas and thus actively promote tumor invasion and recurrent tumor growth. This review focusses on (1) mechanisms of tumor angiogenesis in human malignant glioma that are of particular relevance for targeted therapy and (2) controversial issues in tumor angiogenesis such as cancer stem-like cell-derived vasculogenesis and bone-marrow-derived vasculogenesis

Systematic Errors in the Estimation of Black Hole Masses by Reverberation Mapping

The mass of the central black hole in many active galactic nuclei has been estimated on the basis of the assumption that the dynamics of the broad emission line gas are dominated by the gravity of the black hole. The most commonly-employed method is to estimate a characteristic size-scale $r_*$ from reverberation mapping experiments and combine it with a characteristic velocity $v_*$ taken from the line profiles; the inferred mass is then estimated by $r_* v_*^2/G$. We critically discuss the evidence supporting the assumption of gravitational dynamics and find that the arguments are still inconclusive. We then explore the range of possible systematic error if the assumption of gravitational dynamics is granted. Inclination relative to a flattened system may cause a systematic underestimate of the central mass by a factor $\sim (h/r)^2$, where $h/r$ is the aspect ratio of the flattening. The coupled effects of a broad radial emissivity distribution, an unknown angular radiation pattern of line emission, and sub-optimal sampling in the reverberation experiment can cause additional systematic errors as large as a factor of 3 or more in either direction.Comment: 19 pages, 4 figures, AASLaTeX, accepted by Ap

Double-Peaked Broad Emission Lines in NGC 4450 and Other LINERs

Spectra taken with HST reveal that NGC 4450 emits Balmer emission lines with displaced double peaks and extremely high-velocity wings. This characteristic line profile, previously seen in a few nearby LINERs and in a small fraction of broad-line radio galaxies, can be interpreted as a kinematic signature of a relativistic accretion disk. We can reproduce the observed profile with a model for a disk with a radial range of 1000-2000 gravitational radii and inclined by 27 degrees along the line of sight. The small-aperture HST data also allow us to detect, for the first time, the featureless continuum at optical wavelengths in NGC 4450; the nonstellar nucleus is intrinsically very faint, with M_B = -11.2 mag for D = 16.8 Mpc. We have examined the multiwavelength properties of NGC 4450 collectively with those of other low-luminosity active nuclei which possess double-peaked broad lines and find a number of common features. These objects are all classified spectroscopically as "type 1" LINERs or closely related objects. The nuclear luminosities are low, both in absolute terms and relative to the Eddington rates. All of them have compact radio cores, whose strength relative to the optical nuclear emission places them in the league of radio-loud active nuclei. The broad-band spectral energy distributions of these sources are most notable for their deficit of ultraviolet emission compared to those observed in luminous Seyfert 1 nuclei and quasars. The double-peaked broad-line radio galaxies Arp 102B and Pictor A have very similar attributes. We discuss how these characteristics can be understood in the context of advection-dominated accretion onto massive black holes.Comment: To appear in The Astrophysical Journal. Latex, 15 pages, embedded figures and tabl

The End of the Lines for OX 169: No Binary Broad-Line Region

We show that unusual Balmer emission line profiles of the quasar OX 169, frequently described as either self-absorbed or double peaked, are actually neither. The effect is an illusion resulting from two coincidences. First, the forbidden lines are quite strong and broad. Consequently, the [N II]6583 line and the associated narrow-line component of H-alpha present the appearance of twin H-alpha peaks. Second, the redshift of 0.2110 brings H-beta into coincidence with Na I D at zero redshift, and ISM absorption in Na I D divides the H-beta emission line. In spectra obtained over the past decade, we see no substantial change in the character of the line profiles, and no indication of intrinsic double-peaked structure. The H-gamma, Mg II, and Ly-alpha emission lines are single peaked, and all of the emission-line redshifts are consistent once they are correctly attributed to their permitted and forbidden-line identifications. A systematic shift of up to 700 km/s between broad and narrow lines is seen, but such differences are common, and could be due to gravitational and transverse redshift in a low-inclination disk. Stockton & Farnham (1991) had called attention to an apparent tidal tail in the host galaxy of OX 169, and speculated that a recent merger had supplied the nucleus with a coalescing pair of black holes which was now revealing its existence in the form of two physically distinct broad-line regions. Although there is no longer any evidence for two broad emission-line regions in OX 169, binary black holes should form frequently in galaxy mergers, and it is still worthwhile to monitor the radial velocities of emission lines which could supply evidence of their existence in certain objects.Comment: 19 pages, 5 figures, accepted for publication in Ap.

La solitude chez les jeunes : recension des écrits

Contrairement à la croyance populaire qui veut que la solitude soit avant tout un problème vécu par les adultes, notamment par les personnes âgées, ce sentiment peut se manifester tôt dans la vie. Un nombre croissant d'études révèlent qu'un pourcentage important d'adolescents vivent un épisode intense de solitude. Cette recension des écrits trace un portrait de l'expérience de la solitude chez les jeunes. Il sera question de l'importance du problème, de la description du phénomène, des sentiments reliés à cette expérience, des facteurs qui prédisposent les jeunes à une telle expérience, des facteurs susceptibles de déclencher le phénomène et des stratégies d'ajustement déployées pour faire face à une situation d'isolement.Contrary to the popular belief that loneliness is typically associated with adults, and especially with older persons, this state can occur early in life. In fact, an increasing number of studies indicate that an important proportion of adolescents experience an intense episode of loneliness. This literature review describes loneliness among younger persons. We discuss the ampleness of the problem, the definition of the phenomenon, the feeling associated with loneliness, precipitating and predisposating factors and, finally, coping strategies to deal with this experience

The Lateral Instability of Deep Rectangular Beams

Experimental and analytical studies were made of solid and hollow deep rectangular beams to study their lateral instability under various conditions of loading and restraint. The tests were made on bars and tubes of 17ST aluminum alloy. Failure by lateral buckling occurred only in tests on the solid beams. It was found that, within the elastic range, the test results were in agreement with the classical theory for the lateral buckling of deep beams as given by Prandtl, Mitchell, and Timoshenko. The tests were extended to the inelastic range, where it was found that the substitution for Young's modulus of an average modulus of elasticity derived from the stress-strain curve made it possible to predict instability at high stresses

Morphological and mathematical analysis of asymmetrical fluvial pattern : a study case from the Ucayali river (Peru)

Nous avons étudié la disposition asymétrique du cours inférieur de l'Ucayali. Ces morphologies asymétriques sont observables à différentes échelles : bande enveloppe des méandres, forme du chenal, et taux de migration des méandres. Les relations qui existent entre l'orientation de la rivière, la direction du bord de la plaine alluviale et les failles néotectoniques suggèrent que la disposition de la rivière est contrôlée par des déformations actives. L'analyse mathématique des images permet une étude plus détaillée de la migration des méandres. Des portions des scènes SPOT XS initiales comprenant des morphologies fluviales élémentaires ont été délimitées. L'image a été traitée par des méthodes non linéaires, ouverture morphologique et reconstruction géodésique. Ensuite nous avons utilisé le traitement Adonis pour analyser les courbes restantes, qui correspondent aux éléments les plus importants des rides alluviales. Les traces de l'évolution des méandres sont ainsi obtenues, plus précisément et plus rapidement que par une observation visuelle. Les méandres situés du côté de l'escarpement bordant la plaine sont contrôlés par l'orientation de cet escarpement. Ce résultat est cohérent avec d'autres données néotectoniques, et suggère que la rivière est affectée par des déformations actives localisées le long de la marge de la plaine alluviale, au pied de l'escarpement qui la borde. (Résumé d'auteur