M-theory on `toric' G_2 cones and its type II reduction

We analyze a class of conical G_2 metrics admitting two commuting isometries, together with a certain one-parameter family of G_2 deformations which preserves these symmetries. Upon using recent results of Calderbank and Pedersen, we write down the explicit G_2 metric for the most general member of this family and extract the IIA reduction of M-theory on such backgrounds, as well as its type IIB dual. By studying the asymptotics of type II fields around the relevant loci, we confirm the interpretation of such backgrounds in terms of localized IIA 6-branes and delocalized IIB 5-branes. In particular, we find explicit, general expressions for the string coupling and R-R/NS-NS forms in the vicinity of these objects. Our solutions contain and generalize the field configurations relevant for certain models considered in recent work of Acharya and Witten.Comment: 45 pages, references adde

Domain walls of N=2 supergravity in five dimensions from hypermultiplet moduli spaces

We study domain wall solutions in d=5, N=2 supergravity coupled to a single hypermultiplet whose moduli space is described by certain inhomogeneous, toric ESD manifolds constructed recently by Calderbank and Singer. Upon gauging a generic U(1) isometry of these spaces, we obtain an infinite family of models whose "superpotential" admits an arbitrary number of isolated critical points. By investigating the associated supersymmetric flows, we prove the existence of domain walls of Randall-Sundrum type for each member of our family, and find chains of domain walls interpolating between various AdS_5 backgrounds. Our models are described by a discrete infinity of smooth and complete one-hypermultiplet moduli spaces, which live on an open subset of the minimal resolution of certain cyclic quotient singularities. These spaces generalize the Pedersen metrics considered recently by Behrndt and Dall' Agata.Comment: 39 pages, numerous figures; v4: two references adde

External beam radiation "salvage" therapy in transgenic murine retinoblastoma

To determine the efficacy of low-dose "salvage" external beam radiation therapy (EBRT) following failed subconjunctival carboplatin chemotherapy in a murine model of heritable retinoblastoma. Eighty-four eyes from 8-week-old, simian virus 40, T-antigen-positive mice were treated with 6 serial subconjunctival carboplatin injections (100 microg/25 microL). At 12 weeks of age, 64 eyes received EBRT for a total dose of 480 (4.8 Gy), 1200 (12.0 Gy), 1560 (15.6 Gy), or 3000 (30.0 Gy) rad. Twenty eyes received no additional therapy following subconjunctival carboplatin injections. Ten eyes received a total dose EBRT of only 3000 rad. Eight eyes received subconjuctival injections of only an isotonic sodium chloride solution. Ten eyes served as untreated controls. Eyes were enucleated at 20 weeks to assess the presence of tumor on histopathological examination. Salvage therapy using low-dose EBRT was able to reestablish tumor control in a dose-dependent manner. Increasing the EBRT dose to 3000 rad resulted in 100% tumor control. The dose-dependent curves were significantly different between the treatment groups-EBRT alone vs salvage EBRT after receiving subconjunctival carboplatin injections (P<.001). Low-dose hyperfractionated salvage EBRT following failed primary subconjunctival carboplatin chemotherapy is efficacious in the treatment of retinoblastoma in this animal model. Clinical Relevance Salvage EBRT using a reduced total radiation dose could be associated with a radiation-related treatment enhancement in pediatric retinoblastoma

Hyperfractionated external beam radiation therapy in the treatment of murine transgenic retinoblastoma

To determine the in vivo efficacy of hyperfractionated external beam radiation therapy (EBRT) in comparison with standard daily EBRT in a murine model of heritable retinoblastoma. Two hundred twenty eyes from 6-week-old simian virus-40 large T-antigen--positive mice were treated with a total dose of EBRT ranging from 10-76 Gy (1000 to 7600 rad). One hundred ten eyes underwent EBRT administered in 2.0-Gy (200-rad) fractions once per day. Forty-two eyes received hyperfractionated EBRT administered in 1.2-Gy (120-rad) fractions twice per day, while 48 eyes received EBRT twice daily in fractions of 5.0 Gy (500 rad). Twenty eyes served as untreated controls. All eyes were obtained for histopathologic examination and graded positive if any tumor was present. A dose-dependent inhibition of ocular tumor was observed for EBRT in these transgenic retinoblastoma mice. The tumor control dose for 50% of eyes (TCD(50)) treated with 2.0 Gy fractions of EBRT was 45 Gy (4500 rad) when treatments were administered once daily. A significant increase in tumor control was observed when treatments were administered twice per day at fractions of 1.2 Gy, resulting in a TCD(50) of 33 Gy (3300 rad) (P =.003). A further increase in tumor control was observed when twice-daily EBRT was administered in 5.0 Gy fractions resulting in a TCD(50) of 28 Gy (2800 rad). Hyperfractionated EBRT safely and effectively controls intraocular retinoblastoma in this transgenic animal model. Use of hyperfractionation allows for a reduction in total radiation delivered dose, while shortening the total treatment time. This treatment approach may be applicable in the management of pediatric retinoblastoma by maintaining excellent tumor control, while reducing treatment-associated complications