Alterations in source-sink patterns by modifications of source strength

Bean plants, trimmed to a simplified “double source, double sink” translocation system (the paired primary leaves serving as the double source and the paired lateral leaflets of the immature first trifoliate leaf as the double sink) were used to study the magnitude and short-term time course of change in the allocation ratio (partition ratio) of assimilates translocated from the labeled primary leaf to its respective “near” and “far leaflet” sinks in response to an increase or decrease in the source strength of the opposite primary leaf (the “control” leaf). If the rates of net photosynthesis in the two primary leaves were similar, assimilates from the labeled source leaf partitioned to the leaflet sinks in the ratio of 5:1 or higher, the dominant sink being the leaflet “nearer” to the labeled source leaf. If the rate of net photosynthesis in the control leaf was increased substantially above that of the labeled source leaf, the rate of translocation from the labeled source to either the near leaflet sink or far leaflet sink remained unaffected, despite, presumably, a higher translocation rate from the control leaf, and hence a higher phloem pressure gradient (or increased cross-sectional area) in the transport pathway from the control leaf to the leaflet sinks. If the control leaf was excised, thus reducing the source leaf area by about a half, the translocation rate from the remaining source leaf rapidly doubled, the partition ratio becoming equal to unity. If the control leaf was darkened, the partition ratio adjusted to an intermediate value. Although export rates from the labeled source leaf were increased either by excising or darkening the control leaf, the rate of net photosynthesis in the labeled leaf remained constant.     

Ovary-autonomous maternal inheritance at a developmental locus in Drosophila

The sex-linked temperature-sensitive mutation shibire^ts of Drosophila melanogaster shows a maternal effect causing embryonic lethality at 29°C. The maternal influence is due to gene action autonomous to the ovary. Embryos carrying the paternally derived wild-type gene can survive at 29°C but only if heat pulses are begun at least 9 hr after oviposition. The paternal rescue is presumably due to zygotic gene action at this locus beginning part way through embryogenesis. A maternal wild-type genome, however, can produce shi embryos that have sufficient shi⁺ product to support embryogenesis up to the hatching stage even at 29°C.     

Microdetermination of caffeine in blood by gas chromatography—mass spectrometry

A micromethod for the quantitative analysis of caffeine present in small quantities (100 μl) of whole blood is described. It is based on the gas chromatographic—mass spectrometric analysis of chloroform extracts of biological samples. The method is relatively simple, rapid, specific and sensitive, as little as 20 ng of caffeine can be measured.     

Hexazonium pararosaniline as a fixative for animal tissues

Hexazonium pararosaniline is a valuable reagent that has been used in enzyme activity histochemistry for 50 years. It is an aqueous solution containing the tris-diazonium ion derived from pararosaniline, an aminotriarylmethane dye, and it contains an excess of nitrous acid that was not consumed in the diazotization reaction. Other investigators have found that immersion for 2 min in an acidic (pH 3.5) 0.0015 M hexazonium pararosaniline solution can protect cryostat sections of unfixed animal tissues from the deleterious effects of aqueous reagents such as buffered solutions used in immunohistochemistry, while preserving specific affinities for antibodies. In the present investigation hexazonium pararosaniline protected lymphoid tissue and striated muscle against the damaging effects of water or saline. The same protection was conferred on unfixed sections treated with dilute nitrous or hydrochloric acid in concentrations similar to those in hexazonium pararosaniline solutions. Model tissues (solutions, gels or films containing gelatin and/or bovine albumin) responded predictably to well known cross-linking (formaldehyde) or coagulant (mercuric chloride) fixatives. Hexazonium pararosaniline solutions prevented the dissolution of protein gels in water only after 9 or more days of contact, during which time considerable swelling occurred. It is concluded that there is no evidence for a “fixative” action of hexazonium pararosaniline. The protective effect on frozen sections of unfixed tissue is attributable probably to the low pH of the solution.     

Toward Patient-Specific,Biologically Optimized Radiation Therapy Plans for the Treatment of Glioblastoma

Purpose

To demonstrate a method of generating patient-specific, biologically-guided radiotherapy dose plans and compare them to the standard-of-care protocol.

Methods and Materials

We integrated a patient-specific biomathematical model of glioma proliferation, invasion and radiotherapy with a multiobjective evolutionary algorithm for intensity-modulated radiation therapy optimization to construct individualized, biologically-guided plans for 11 glioblastoma patients. Patient-individualized, spherically-symmetric simulations of the standard-of-care and optimized plans were compared in terms of several biological metrics.

Results

The integrated model generated spatially non-uniform doses that, when compared to the standard-of-care protocol, resulted in a 67% to 93% decrease in equivalent uniform dose to normal tissue, while the therapeutic ratio, the ratio of tumor equivalent uniform dose to that of normal tissue, increased between 50% to 265%. Applying a novel metric of treatment response (Days Gained) to the patient-individualized simulation results predicted that the optimized plans would have a significant impact on delaying tumor progression, with increases from 21% to 105% for 9 of 11 patients.

Conclusions

Patient-individualized simulations using the combination of a biomathematical model with an optimization algorithm for radiation therapy generated biologically-guided doses that decreased normal tissue EUD and increased therapeutic ratio with the potential to improve survival outcomes for treatment of glioblastoma.