Semi-synthetic qualestatins: Squalene synthase inhibition and antifungal activity. The SAR of C6 and C7 modifications

We describe herein a protection/deprotection strategy that enables efficient transformation of natural Squalestatin S1 into C6 and C7 acyl analogues. We present the mammalian and fungal SQS enzyme activity and whole cell antifungal activity of the semi-synthetic Squalestatins.     

Application of an independent dose calculation software for estimating the impact of inter-fractional setup shifts in Helical Tomotherapy treatments

The purpose of this study is to validate the capability of in-house independent point dose calculation software to be used as a second check for Helical Tomotherapy treatment plans. The software performed its calculations in homogenous conditions (using the Cheese phantom, which is a cylindrical phantom with radius 15 cm and length 18 cm) using a factor-based algorithm. Fifty patients, who were treated for pelvic (10), prostate (14), lung (10), head & neck (12) and brain (4) cancers, were used. Based on the individual patient kVCT images and the pretreatment MVCT images for each treatment fraction, the corresponding daily patient setup shifts in the IEC-X, IEC-Y, and IEC-Z directions were registered. For each patient, the registered fractional setup shifts were grouped into systematic and random shifts. The average systematic dosimetric variations showed small dose deviation for the different cancer types (1.0%–3.0%) compared to the planned dose. Of the fifty patients, only three had percent differences larger than 5%. The average random dosimetric variations showed relatively small dose deviations (0.2%–1.1%) compared to the planned dose. None of the patients had percent differences larger than 5%. By examining the individual fractions of each patient, it is observed that only in 31 out of 1358 fractions the percent differences exceeded the border of 5%. These results indicate that the overall dosimetric impact from systematic and random variations is small and that the software is a capable platform for independent point dose validation for the Helical Tomotherapy modality.     

TAIL SHEDDING IN ISLAND LIZARDS [LACERTIDAE, REPTILIA]: DECLINE OF ANTIPREDATOR DEFENSES IN RELAXED PREDATION ENVIRONMENTS

The ability of an animal to shed its tail is a widespread antipredator strategy among lizards. The degree of expression of this defense is expected to be shaped by prevailing environmental conditions including local predation pressure. We test these hypotheses by comparing several aspects of caudal autotomy in 15 Mediterranean lizard taxa existing across a swath of mainland and island localities that differ in the number and identity of predator species present. Autotomic ease varied substantially among the study populations, in a pattern that is best explained by the presence of vipers. Neither insularity nor the presence of other types of predators explain the observed autotomy rates. Final concentration of accumulated tail muscle lactate and duration of movement of a shed tail, two traits that were previously thought to relate to predation pressure, are in general not shaped by either predator diversity or insularity. Under conditions of relaxed predation selection, an uncoupling of different aspects of caudal autotomy exists, with some elements (ease of autotomy) declining faster than others (duration of movement, lactate concentration). We compared rates of shed tails in the field against rates of laboratory autotomies conducted under standardized conditions and found very high correlation values ( r > 0.96). This suggests that field autotomy rates, rather than being a metric of predatory attacks, merely reflect the innate predisposition of a taxon to shed its tail.