Homochiral oligopeptides by chiral amplification: Interpretation of experimental data with a copolymerization model

We present a differential rate equation model of chiral polymerization based on a simple copolymerization scheme in which the enantiomers are added to, or removed from, the homochiral or heterochiral chains (reversible stepwise isodesmic growth or dissociation). The model is set up for closed systems and takes into account the corresponding thermodynamic constraints implied by the reversible monomer attachments, while obeying a constant mass constraint. In its simplest form, the model depends on a single variable rate constant, the maximum chain length N, and the initial concentrations. We have fit the model to the experimental data from the Rehovot group on lattice-controlled chiral amplification of oligopeptides. We find in all the chemical systems employed except for one, that the model fits the measured relative abundances of the oligopetides with higher degrees of correlation than from a purely random polymerization process.Comment: 18 pages, 12 figures, 9 table

Influence of the moving fluoroscope on gait patterns

<div><p>Video-fluoroscopic analysis can provide important insights for the evaluation of outcome and functionality after total knee arthroplasty, allowing the in vivo assessment of tibiofemoral kinematics without soft tissue artefacts. To enable measurement of the knee throughout activities of daily living such as gait, robotic systems like the moving fluoroscope have been developed that follow the knee movement and maintain the joint in front of the image intensifier. Since it is unclear whether walking while being accompanied by moving fluoroscope affects normal gait, the objective of this study was to investigate its influence on gait characteristics in healthy subjects. In addition, the impact of the motors’ noise was analysed.</p><p>By means of skin markers analysis (VICON MX system, Oxford Metrics Group, UK) and simultaneous measurement of ground reaction forces (Kistler force plates, Kistler, Switzerland), gait characteristics when walking with and without the moving fluoroscope as well as with and without ear protectors in combination with the moving fluoroscope, were obtained in young (n = 10, 24.5y ± 3.0y) and elderly (n = 9, 61.6y ± 5.3y) subjects during level gait and stair descent. Walking with the moving fluoroscope significantly decreased gait velocity in level gait and stair descent over the respective movement without the fluoroscope. Statistical analysis, including gait velocity as a covariate, resulted in no differences on the ground reaction force parameters. However, some kinematic parameters (ankle, knee and hip ranges of motion, minimal knee angle in late stance phase, maximal knee angles in stance and swing phase) seemed to be modified by the presence of the moving fluoroscope, but statistical comparison was limited due to velocity differences between the conditions. Wearing ear protectors to avoid the influence of motor sound during walking with the moving fluoroscope caused no significant difference.</p><p>Walking with the moving fluoroscope has been shown to decrease gait velocity and small alterations in kinematic parameters were observed. Therefore, gait and movement alterations due to the moving fluoroscope cannot completely be excluded. However, based on the absence of differences in ground reaction force parameters (when adjusted for velocity within ANCOVA), as well as based on the comparable shape of the angular curves to the slow control condition, it can be concluded that changes in gait when walking with the moving fluoroscope are small, especially in comparison to natural slow walking. In order to allow assessment of joint replacement with the moving fluoroscope, including an understanding of the effects of joint pain, clinical analyses can only be compared to gait activities showing similarly reduced velocities. Importantly, the reduced gait speeds observed in this study are similar to those observed after total knee arthroplasty, suggesting that analyses in such subjects are appropriate. However, the moving fluoroscope would likely need to be optimized in order to detect natural gait characteristics at the higher gait velocities of healthy young subjects.</p><p>The moving fluoroscope can be applied for comparisons between groups measured with the moving fluoroscope, but care should be taken when comparing data to subjects walking at self-selected speed without the moving fluoroscope.</p></div

Cryogenic requirements for the JT-60SA Tokamak

International audienc

Data acquisition course of action.

Data acquisition course of action.</p

The 3-phosphoinositide-dependent protein kinase 1 is an essential upstream activator of protein kinase A in malaria parasites

AbstractCyclic AMP (cAMP) signalling is crucial for the propagation of asexual malaria blood stage parasites. Recent work on Plasmodium falciparum demonstrated that phosphorylation of the invasion ligand AMA1 by the catalytic subunit of cAMP-dependent protein kinase A (PfPKAc) is an essential step during parasite invasion into red blood cells. However, the exact mechanisms regulating PfPKAc activity are only partially understood and PfPKAc function has not been extensively studied in gametocytes, the sexual blood stage forms that are essential for malaria transmission. By studying a conditional PfPKAc knockdown mutant, we confirm the essential role for PfPKAc in erythrocyte invasion and demonstrate that PfPKAc is involved in regulating gametocyte deformability. Interestingly, we observed that the conditional overexpression of PfPKAc also caused a profound lethal phenotype by preventing intra-erythrocytic parasite multiplication. Whole genome sequencing of parasites selected to tolerate increased PfPKAc expression levels identified missense mutations exclusively in the gene encoding the putative parasite orthologue of 3-phosphoinositide-dependent protein kinase-1 (PfPDK1). Using targeted mutagenesis, we show that PfPDK1 is essential for PfPKAc activation, most likely by phosphorylating T189 in the PfPKAc activation loop. In summary, our results corroborate the importance of tight regulation of PfPKA signalling for parasite survival and identify PfPDK1 as a crucial upstream regulator in this pathway and potential new drug target.</jats:p

A moving fluoroscope to capture tibiofemoral kinematics during complete cycles of free level and downhill walking as well as stair descent

Videofluoroscopy has been shown to provide essential information in the evaluation of the functionality of total knee arthroplasties. However, due to the limitation in the field of view, most systems can only assess knee kinematics during highly restricted movements. To avoid the limitations of a static image intensifier, a moving fluoroscope has been presented as a standalone system that allows tracking of the knee during multiple complete cycles of level- and downhill-walking, as well as stair descent, in combination with the synchronous assessment of ground reaction forces and whole body skin marker measurements. Here, we assess the ability of the system to keep the knee in the field of view of the image intensifier. By measuring ten total knee arthroplasty subjects, we demonstrate that it is possible to maintain the knee to within 1.8 ± 1.4 cm vertically and 4.0 ± 2.6 cm horizontally of the centre of the intensifier throughout full cycles of activities of daily living. Since control of the system is based on real-time feedback of a wire sensor, the system is not dependent on repeatable gait patterns, but is rather able to capture pathological motion patterns with low inter-trial repeatability.ISSN:1932-620

Time distance and kinematic parameters.

<p>Time distance and kinematic parameters.</p

Ground reaction force parameters.

<p>Ground reaction force parameters.</p

Vertical ground reaction forces.

<p>Mean and standard deviation of vertical ground reaction forces (F_z) in level gait for young (A) and elderly (B) subjects as well as in stair descent for young (C) and elderly (D) subjects for the conditions control 1, control 2, FluMo and FluMo intervention.</p

Absolute symmetry indexes (ASI).

<p>Absolute symmetry indexes (ASI).</p