Dosimetric impact of statistical uncertainty on Monte Carlo dose calculation algorithm in volumetric modulated arc therapy using Monaco TPS for three different clinical cases

AimTo study the dosimetric impact of statistical uncertainty (SU) per plan on Monte Carlo (MC) calculation in Monaco? treatment planning system (TPS) during volumetric modulated arc therapy (VMAT) for three different clinical cases.BackgroundDuring MC calculation SU is an important factor to decide dose calculation accuracy and calculation time. It is necessary to evaluate optimal acceptance of SU for quality plan with reduced calculation time.Materials and methodsThree different clinical cases as the lung, larynx, and prostate treated using VMAT technique were chosen. Plans were generated with Monaco? V5.11 TPS with 2% statistical uncertainty. By keeping all other parameters constant, plans were recalculated by varying SU, 0.5%, 1%, 2%, 3%, 4%, and 5%. For plan evaluation, conformity index (CI), homogeneity index (HI), dose coverage to PTV, organ at risk (OAR) dose, normal tissue receiving dose ≥5 Gy and ≥10 Gy, integral dose (NTID), calculation time, gamma pass rate, calculation reproducibility and energy dependency were analyzed.ResultsCI and HI improve as SU increases from 0.5% to 5%. No significant dose difference was observed in dose coverage to PTV, OAR doses, normal tissue receiving dose ≥5 Gy and ≥10 Gy and NTID. Increase of SU showed decrease in calculation time, gamma pass rate and increase in PTV max dose. No dose difference was seen in calculation reproducibility and dependent on energy.ConclusionFor VMAT plans, SU can be accepted from 1% to 3% per plan with reduced calculation time without compromising plan quality and deliverability by accepting variations in point dose within the target.     

Developmental changes in intestinal brush border enzymes of rats prenatally exposed to ethanol

The activities of lactase, sucrase, alkaline phosphatase (AP) and y-glutamyl transpeptidase (gamma-GTP) were studied in the intestinal brush border membranes of pups born to rat mothers exposed to ethanol (1 ml of 30% ethanol daily during gestation) at different days of postnatal development. The activities of lactase (at day 4-20) and sucrase (at day 20-30) were considerably reduced in response to prenatal exposure to ethanol, while AP (at day 4-30) and gamma-GTP activities were significantly enhanced (p < 0.05) at day 4, 8, 14 and 20, but there was no significant difference by day 30 of postnatal development. The observed changes in enzyme activities were corroborated by Western blot analysis of lactase, sucrase and AP. Kinetic studies revealed a change in Vmax without affecting apparent Km of enzymes under these conditions. The present findings suggest that in utero ethanol exposure to rats is embryotoxic and affects the postnatal development of various brush border enzymes, which persist long after the ethanol was withdrawn prior to birth.     

Biochemical signaling networks decode temporal patterns of synaptic input

Synapses exhibit a wide repertoire of responses to different temporal patterns of synaptic input. Many of these responses are expressed as short and long-term changes in synaptic strength. Electrical properties of channels and calcium buildup can account for rapid aspects of pattern decoding, but it is not clear how more complex input patterns, especially those lasting over many minutes, could be discriminated. This paper shows that a network of signaling pathways can discriminate between complex input patterns lasting tens of minutes, and can give rise to distinct combinatorial patterns of biochemical signaling activity in pathways involved in synaptic change. Regulatory signaling input can alter and even reverse the strengths of responses to input patterns. Thus the synaptic signaling network may function as a temporal decoder that transforms patterns from the time domain into the domain of chemical signaling. This may underlie different synaptic responses to different stimulus patterns.Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1023/A:1019644427655     

Hypoallergenic derivatives of major grass pollen allergens for allergy vaccination

Grass pollen-induced hay-fever and allergic asthma represent a major health problem in industrialized countries. Whereas the symptoms of these allergic conditions can be controlled by pharmacotherapy, specific immunotherapy vaccination is the only causative approach towards the treatment of these type 1 allergies. Specific immunotherapy is based on administration of increasing amounts of the disease-causing allergens in the form of allergen-containing extracts. However, the extracts used for immunotherapy consist of allergenic and non-allergenic components and may induce severe anaphylactic side-effects upon therapeutic administration. With recent developments in molecular biology of pollen allergens it has become feasible to produce modified hypoallergenic derivatives of recombinant allergens with abrogated or greatly reduced likelihood of anaphylactic side-effects as compared to extract-based treatments. We have demonstrated this concept through reducing the anaphylactic potential of major rye grass pollen allergens by introducing a few point mutations which leave the overall structural fold of the molecule unaltered. These modified forms are expected to make allergen-specific immunotherapy more widely used in the future.     

Plant homologue of human excision repair gene ERCC1 points to conservation of DNA repair mechanisms

Nucleotide excision repair (NER), a highly versatile DNA repair mechanism, is capable of removing various types of DNA damage including those induced by UV radiation and chemical mutagens. NER has been well characterized in yeast and mammalian systems but its presence in plants has not been reported. Here it is reported that a plant gene isolated from male germline cells of lily (Lilium longiflorum) shows a striking amino acid sequence similarity to the DNA excision repair proteins human ERCC1 and yeast RAD10. Homologous genes are also shown to be present in a number of taxonomically diverse plant genera tested, suggesting that this gene may have a conserved function in plants. The protein encoded by this gene is able to correct significantly the sensitivity to the cross-linking agent mitomycin C in ERCC1-deficient Chinese hamster ovary (CHO) cells. These findings suggest that the NER mechanism is conserved in yeast, animals and higher plants.     

Differential Regulation of Germline Apoptosis in Response to Meiotic Checkpoint Activation

In Caenorhabditis elegans, germline apoptosis is promoted by egl-1 and ced-13 in response to meiotic checkpoint activation. We report that the requirement for these two factors depends on which checkpoints are active. We also identify a regulatory region of egl-1 required to inhibit germline apoptosis in response to DNA damage incurred during meiotic recombination.