VMC++ versus BEAMnrc: a comparison of simulated linear accelerator heads for photon beams

BEAMnrc, a code for simulating medical linear accelerators based on EGSnrc, has been bench-marked and used extensively in the scientific literature and is therefore often considered to be the gold standard for Monte Carlo simulations for radiotherapy applications. However, its long computation times make it too slow for the clinical routine and often even for research purposes without a large investment in computing resources. VMC++ is a much faster code thanks to the intensive use of variance reduction techniques and a much faster implementation of the condensed history technique for charged particle transport. A research version of this code is also capable of simulating the full head of linear accelerators operated in photon mode (excluding multileaf collimators, hard and dynamic wedges). In this work, a validation of the full head simulation at 6 and 18 MV is performed, simulating with VMC++ and BEAMnrc the addition of one head component at a time and comparing the resulting phase space files. For the comparison, photon and electron fluence, photon energy fluence, mean energy, and photon spectra are considered. The largest absolute differences are found in the energy fluences. For all the simulations of the different head components, a very good agreement (differences in energy fluences between VMC++ and BEAMnrc <1%) is obtained. Only a particular case at 6 MV shows a somewhat larger energy fluence difference of 1.4%. Dosimetrically, these phase space differences imply an agreement between both codes at the <1% level, making VMC++ head module suitable for full head simulations with considerable gain in efficiency and without loss of accuracy.

Focal adhesion kinase is a load-dependent governor of the slow contractile and oxidative muscle phenotype

Striated muscle exhibits a pronounced structural-functional plasticity in response to chronic alterations in loading. We assessed the implication of focal adhesion kinase (FAK) signalling in mechano-regulated differentiation of slow-oxidative muscle. Load-dependent consequences of FAK signal modulation were identified using a multi-level approach after electrotransfer of rat soleus muscle with FAK-expression plasmid vs. empty plasmid-transfected contralateral controls. Muscle fibre-targeted over-expression of FAK in anti-gravitational muscle for 9 days up-regulated transcript levels of gene ontologies underpinning mitochondrial metabolism and contraction in the transfected belly portion. Concomitantly, mRNA expression of the major fast-type myosin heavy chain (MHC) isoform, MHC2A, was reduced. The promotion of the slow-oxidative expression programme by FAK was abolished after co-expression of the FAK inhibitor FAK-related non-kinase (FRNK). Elevated protein content of MHC1 (+9%) and proteins of mitochondrial respiration (+165-610%) with FAK overexpression demonstrated the translation of transcript differentiation in targeted muscle fibres towards a slow-oxidative muscle phenotype. Coincidentally MHC2A protein was reduced by 50% due to protection of muscle from de-differentiation with electrotransfer. Fibre cross section in FAK-transfected muscle was elevated by 6%. The FAK-modulated muscle transcriptome was load-dependent and regulated in correspondence to tyrosine 397 phosphorylation of FAK. In the context of overload, the FAK-induced gene expression became manifest at the level of contraction by a slow transformation and the re-establishment of normal muscle force from the lowered levels with transfection. These results highlight the analytic power of a systematic somatic transgene approach by mapping a role of FAK in the dominant mechano-regulation of muscular motor performance via control of gene expression.

Male reproductive pattern in a polygynous ungulate with a slow life-history: the role of age, social status and alternative mating tactics

According to life-history theory age-dependent investments into reproduction are thought to co-vary with survival and growth of animals. In polygynous species, in which size is an important determinant of reproductive success, male reproduction via alternative mating tactics at young age are consequently expected to be the less frequent in species with higher survival. We tested this hypothesis in male Alpine ibex (Capra ibex), a highly sexually dimorphic mountain ungulate whose males have been reported to exhibit extremely high adult survival rates. Using data from two offspring cohorts in a population in the Swiss Alps, the effects of age, dominance and mating tactic on the likelihood of paternity were inferred within a Bayesian framework. In accordance with our hypothesis, reproductive success in male Alpine ibex was heavily biased towards older, dominant males that monopolized access to receptive females by adopting the 'tending' tactic, while success among young, subordinate males via the sneaking tactic 'coursing' was in general low and rare. In addition, we detected a high reproductive skew in male Alpine ibex, suggesting a large opportunity for selection. Compared with other ungulates with higher mortality rates, reproduction among young male Alpine ibex was much lower and more sporadic. Consistent with that, further examinations on the species level indicated that in polygynous ungulates the significance of early reproduction appears to decrease with increasing survival. Overall, this study supports the theory that survival prospects of males modulate the investments into reproduction via alternative mating tactics early in life. In the case of male Alpine ibex, the results indicate that their life-history strategy targets for long life, slow and prolonged growth and late reproduction.

Hemozoin formation in malaria: a two-step process involving histidine-rich proteins and lipids

Major blood stage antimalarial drugs like chloroquine and artemisinin target the heme detoxification process of the malaria parasite. Hemozoin formation reactions in vitro using the Plasmodium falciparum histidine-rich protein-2 (Pfhrp-2), lipids, and auto-catalysis are slow and could not explain the speed of detoxification needed for parasite survival. Here, we show that malarial hemozoin formation is a coordinated two component process involving both lipids and histidine-rich proteins. Hemozoin formation efficiency in vitro is 1-2% with Pfhrp-2 and 0.25-0.5% with lipids. We added lipids after 9h in a 12h Pfhrp-2 mediated reaction that resulted in sixfold increase in hemozoin formation. However, a lipid mediated reaction in which Pfhrp-2 was added after 9h produced only twofold increase in hemozoin production compared to the reaction with Pfhrp-2 alone. Synthetic peptides corresponding to the Pfhrp-2 heme binding sequences, based on repeats of AHHAAD, neither alone nor in combination with lipids were able to generate hemozoin in vitro. These results indicate that hemozoin formation in malaria parasite involves both the lipids and the scaffolding proteins. Histidine-rich proteins might facilitate hemozoin formation by binding with a large number of heme molecules, and facilitating the dimer formation involving iron-carboxylate bond between two heme molecules, and lipids may then subsequently assist the mechanism of long chain formation, held together by hydrogen bonds or through extensive networking of hydrogen bonds.

Planet formation models: the interplay with the planetesimal disc

Context. According to the sequential accretion model (or core-nucleated accretion model), giant planet formation is based first on the formation of a solid core which, when massive enough, can gravitationally bind gas from the nebula to form the envelope. The most critical part of the model is the formation time of the core: to trigger the accretion of gas, the core has to grow up to several Earth masses before the gas component of the protoplanetary disc dissipates. Aims: We calculate planetary formation models including a detailed description of the dynamics of the planetesimal disc, taking into account both gas drag and excitation of forming planets. Methods: We computed the formation of planets, considering the oligarchic regime for the growth of the solid core. Embryos growing in the disc stir their neighbour planetesimals, exciting their relative velocities, which makes accretion more difficult. Here we introduce a more realistic treatment for the evolution of planetesimals' relative velocities, which directly impact on the formation timescale. For this, we computed the excitation state of planetesimals, as a result of stirring by forming planets, and gas-solid interactions. Results: We find that the formation of giant planets is favoured by the accretion of small planetesimals, as their random velocities are more easily damped by the gas drag of the nebula. Moreover, the capture radius of a protoplanet with a (tiny) envelope is also larger for small planetesimals. However, planets migrate as a result of disc-planet angular momentum exchange, with important consequences for their survival: due to the slow growth of a protoplanet in the oligarchic regime, rapid inward type I migration has important implications on intermediate-mass planets that have not yet started their runaway accretion phase of gas. Most of these planets are lost in the central star. Surviving planets have masses either below 10 M⊕ or above several Jupiter masses. Conclusions: To form giant planets before the dissipation of the disc, small planetesimals (~0.1 km) have to be the major contributors of the solid accretion process. However, the combination of oligarchic growth and fast inward migration leads to the absence of intermediate-mass planets. Other processes must therefore be at work to explain the population of extrasolar planets that are presently known.

Comparison of partial least squares regression and principal component regression for pelvic shape prediction.

This paper studied two different regression techniques for pelvic shape prediction, i.e., the partial least square regression (PLSR) and the principal component regression (PCR). Three different predictors such as surface landmarks, morphological parameters, or surface models of neighboring structures were used in a cross-validation study to predict the pelvic shape. Results obtained from applying these two different regression techniques were compared to the population mean model. In almost all the prediction experiments, both regression techniques unanimously generated better results than the population mean model, while the difference on prediction accuracy between these two regression methods is not statistically significant (α=0.01).

On the evolution of the oceanic component of the IPSL climate models from CMIP3 to CMIP5: A mean state comparison

This study analyses the impact on the oceanic mean state of the evolution of the oceanic component (NEMO) of the climate model developed at Institut Pierre Simon Laplace (IPSL-CM), from the version IPSL-CM4, used for third phase of the Coupled Model Intercomparison Project (CMIP3), to IPSL-CM5A, used for CMIP5. Several modifications have been implemented between these two versions, in particular an interactive coupling with a biogeochemical module, a 3-band model for the penetration of the solar radiation, partial steps at the bottom of the ocean and a set of physical parameterisations to improve the representation of the impact of turbulent and tidal mixing. A set of forced and coupled experiments is used to single out the effect of each of these modifications and more generally the evolution of the oceanic component on the IPSL coupled models family. Major improvements are located in the Southern Ocean, where physical parameterisations such as partial steps and tidal mixing reinforce the barotropic transport of water mass, in particular in the Antarctic Circumpolar Current) and ensure a better representation of Antarctic bottom water masses. However, our analysis highlights that modifications, which substantially improve ocean dynamics in forced configuration, can yield or amplify biases in coupled configuration. In particular, the activation of radiative biophysical coupling between biogeochemical cycle and ocean dynamics results in a cooling of the ocean mean state. This illustrates the difficulty to improve and tune coupled climate models, given the large number of degrees of freedom and the potential compensating effects masking some biases.

Evidence for mental ability related individual differences in the attentional blink obtained by an analysis of the P300 component

Attentional blink (AB) refers to impaired identification of a target (T2) when this target follows a preceding target (T1) after about 150-450 ms within a stream of rapidly presented stimuli. Previous research on a possible relation between AB and mental ability (MA) turned out to be highly ambiguous. The present study investigated MA-related individual differences in consolidation of T2 in working memory during the AB as indicated by the P300 component of the event-related potential. Thirty high (HA) and 30 low MA (LA) female participants performed an AB task while their brain activity was recorded. The AB did not differ between the two groups. HA individuals exhibited a larger P300 amplitude and longer P300 latencies during the AB suggesting higher mental effort. This higher mental effort, however, did not result in better performance presumably because of more competition between target and distractor stimuli in HA than LA individuals.