Outcomes of Spatially Fractionated Radiotherapy (GRID) for Bulky Soft Tissue Sarcomas in a Large Animal Model

GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later. Acute Radiation Therapy Oncology Group grade I skin toxicity was observed in 3 of the 6 dogs; none experienced a measurable response, per Response Evaluation Criteria in Solid Tumors. Serum vascular endothelial growth factor, tumor necrosis factor α, and secretory sphingomyelinase were assayed at baseline, 1, 4, 24, and 48 hours after treatment. There was a trend toward platelet-corrected serum vascular endothelial growth factor concentration being lower 1 and 48 hours after GRID than at baseline. There was a significant decrease in secretory sphingomyelinase activity 48 hours after 25 Gy GRID (P = .03). Serum tumor necrosis factor α was quantified measurable at baseline in 4 of the 6 dogs and decreased in each of those subjects at all post-GRID time points. The new information generated by this study includes the observation that high-dose, single fraction application of GRID does not induce measurable reduction in volume of canine soft tissue sarcomas. In contrast to previously published data, these data suggest that GRID may be associated with at least short-term reduction in serum concentration of vascular endothelial growth factor and serum activity of secretory sphingomyelinase. Because GRID can be applied safely, and these tumors can be subsequently surgically resected as part of routine veterinary care, pet dogs with sarcomas are an appealing model for studying the radiobiologic responses to spatially fractionated radiotherapy

Outcomes of Spatially Fractionated Radiotherapy (GRID) for Bulky Soft Tissue Sarcomas in a Large Animal Model

GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later. Acute Radiation Therapy Oncology Group grade I skin toxicity was observed in 3 of the 6 dogs; none experienced a measurable response, per Response Evaluation Criteria in Solid Tumors. Serum vascular endothelial growth factor, tumor necrosis factor α, and secretory sphingomyelinase were assayed at baseline, 1, 4, 24, and 48 hours after treatment. There was a trend toward platelet-corrected serum vascular endothelial growth factor concentration being lower 1 and 48 hours after GRID than at baseline. There was a significant decrease in secretory sphingomyelinase activity 48 hours after 25 Gy GRID (P = .03). Serum tumor necrosis factor α was quantified measurable at baseline in 4 of the 6 dogs and decreased in each of those subjects at all post-GRID time points. The new information generated by this study includes the observation that high-dose, single fraction application of GRID does not induce measurable reduction in volume of canine soft tissue sarcomas. In contrast to previously published data, these data suggest that GRID may be associated with at least short-term reduction in serum concentration of vascular endothelial growth factor and serum activity of secretory sphingomyelinase. Because GRID can be applied safely, and these tumors can be subsequently surgically resected as part of routine veterinary care, pet dogs with sarcomas are an appealing model for studying the radiobiologic responses to spatially fractionated radiotherapy

The Einstein Observatory catalog of IPC x ray sources. Volume 1E: Documentation

The Einstein Observatory (HEAO-2, launched November 13, 1978) achieved radically improved sensitivity over previous x-ray missions through the use of focusing optics, which simultaneously afforded greatly reduced background and produced true images. During its 2.5-yr mission, the Einstein X-Ray Telescope was pointed toward some 5,000 celestial targets, most of which were detected, and discovered several thousand additional 'serendipitous' sources in the observed fields. This catalog contains contour diagrams and source data, obtained with the imaging proportional counter in the 0.16 to 3.5 keV energy band, and describes methods for recovering upper limits for any sky position within the observed images. The main catalog consists of six volumes (numbered 2 through 7) of right ascension ordered pages, each containing data for one observation. Along with the primary documentation describing how the catalog was constructed, volume 1 contains a complete source list, results for merged fields, a reference system to published papers, and data useful for calculating upper limits and fluxes

Aldehydes phase shift the Gonyaulax clock

Aliphatic aldehydes ranging in chain length from one to four carbon atoms have a significant phase shifting effect upon the circadian rhythm of bioluminescence (glow) in the dinoflagellate ( Gonyaulax polyedra . Cells exposed for two hours to 18 mM acetaldehyde starting at about circadian time 12 experience a permanent phase delay of up to about 12 h. The phase response curve relationship with acetaldehyde is presented, as well as the relationship between concentration and phase delay for the four aldehydes studied. Reactions of aldehydes which may be implicated are discussed. The possibility that sulfhydryl reagents generally may perturb circadian systems is suggested.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47121/1/360_2004_Article_BF00689855.pd

The Einstein Observatory catalog of IPC x ray sources. Volume 4E: Right ascension range 08h 00m to 11h 59m

The Einstein Observatory (HEAO-2, launched November 13, 1978) achieved radically improved sensitivity over previous x-ray missions through the use of focusing optics which simultaneously afforded greatly reduced background and produced true images. During its 2.5-yr mission, the Einstein X-Ray Telescope was pointed toward some 5,000 celestial targets, most of which were detected, and discovered several thousand additional 'serendipitous' sources in the observed fields. This catalog contains contour diagrams and source data, obtained with the imaging proportional counter in the 0.16 to 3.5 keV energy band, and describes methods for recovering upper limits for any sky position within the observed images, The main catalog consists of six volumes (numbered 2 through 7) of right ascension ordered pages, each containing data for one observation. Along with the primary documentaion describing how the catalog was constructed, volume 1 contains a complete source list, results for merged fields, a reference system to published papers, and data useful for calculating upper limits and fluxes

The Einstein Observatory catalog of IPC x ray sources. Volume 7E: Right ascension range 20h 00m to 23h 59m

The Einstein Observatory (HEAO-2, launched November 13, 1978) achieved radically improved sensitivity over previous x-ray missions through the use of focusing optics which simultaneously afforded greatly reduced background and produced true images. During its 2.5-yr mission, the Einstein X-Ray Telescope was pointed toward some 5,000 celestial targets, most of which were detected, and discovered several thousand additional 'serendipitous' sources in the observed fields. This catalog contains contour diagrams and source data, obtained with the imaging proportional counter in the 0.16 to 3.5 keV energy band, and describes methods for recovering upper limits for any sky position within the observed images. The main catalog consists of six volumes (numbered 2 through 7) of right ascension ordered pages, each containing data for one observation. Along with the primary documentation describing how the catalog was constructed, volume 1 contains a complete source list, results for merged fields, a reference system to published papers, and data useful for calculating upper limits and fluxes

Developmentally Regulated Sphingolipid Degradation in Leishmania major

Leishmania parasites alternate between extracellular promastigotes in sandflies and intracellular amastigotes in mammals. These protozoans acquire sphingolipids (SLs) through de novo synthesis (to produce inositol phosphorylceramide) and salvage (to obtain sphingomyelin from the host). A single ISCL (Inositol phosphoSphingolipid phospholipase C-Like) enzyme is responsible for the degradation of both inositol phosphorylceramide (the IPC hydrolase or IPCase activity) and sphingomyelin (the SMase activity). Recent studies of a L. major ISCL-null mutant (iscl−) indicate that SL degradation is required for promastigote survival in stationary phase, especially under acidic pH. ISCL is also essential for L. major proliferation in mammals. To further understand the role of ISCL in Leishmania growth and virulence, we introduced a sole IPCase or a sole SMase into the iscl− mutant. Results showed that restoration of IPCase only complemented the acid resistance defect in iscl− promastigotes and improved their survival in macrophages, but failed to recover virulence in mice. In contrast, a sole SMase fully restored parasite infectivity in mice but was unable to reverse the promastigote defects in iscl−. These findings suggest that SL degradation in Leishmania possesses separate roles in different stages: while the IPCase activity is important for promastigote survival and acid tolerance, the SMase activity is required for amastigote proliferation in mammals. Consistent with these findings, ISCL was preferentially expressed in stationary phase promastigotes and amastigotes. Together, our results indicate that SL degradation by Leishmania is critical for parasites to establish and sustain infection in the mammalian host

The evolution of language: a comparative review

For many years the evolution of language has been seen as a disreputable topic, mired in fanciful "just so stories" about language origins. However, in the last decade a new synthesis of modern linguistics, cognitive neuroscience and neo-Darwinian evolutionary theory has begun to make important contributions to our understanding of the biology and evolution of language. I review some of this recent progress, focusing on the value of the comparative method, which uses data from animal species to draw inferences about language evolution. Discussing speech first, I show how data concerning a wide variety of species, from monkeys to birds, can increase our understanding of the anatomical and neural mechanisms underlying human spoken language, and how bird and whale song provide insights into the ultimate evolutionary function of language. I discuss the ‘‘descended larynx’ ’ of humans, a peculiar adaptation for speech that has received much attention in the past, which despite earlier claims is not uniquely human. Then I will turn to the neural mechanisms underlying spoken language, pointing out the difficulties animals apparently experience in perceiving hierarchical structure in sounds, and stressing the importance of vocal imitation in the evolution of a spoken language. Turning to ultimate function, I suggest that communication among kin (especially between parents and offspring) played a crucial but neglected role in driving language evolution. Finally, I briefly discuss phylogeny, discussing hypotheses that offer plausible routes to human language from a non-linguistic chimp-like ancestor. I conclude that comparative data from living animals will be key to developing a richer, more interdisciplinary understanding of our most distinctively human trait: language