Comparison of three formal methods used to estimate the functional axis of rotation: an extensive in-vivo analysis performed on the knee joint

Estimating the main axis of rotation (AoR) of a human joint represents an important issue in biomechanics. This study compared three formal methods used to estimate functional AoR, namely a cylindrical fitting method, a mean helical axis transformation, and a symmetrical axis approach. These methods were tested on 106 subjects undergoing navigated total knee arthroplasty. AoR orientation in 3D and in the frontal and coronal planes provided by each method was compared to the transepicondylar axis direction. Although all the methods resulted effective, significant differences were identified among them, relatively to the orientation in 3D and in the frontal plane projection. This was probably due to the presence of secondary rotations during the first degrees of knee flexion.     

A molecular overview of the primary dystroglycanopathies

Dystroglycan is a major non‐integrin adhesion complex that connects the cytoskeleton to the surrounding basement membranes, thus providing stability to skeletal muscle. In Vertebrates, hypoglycosylation of α‐dystroglycan has been strongly linked to muscular dystrophy phenotypes, some of which also show variable degrees of cognitive impairments, collectively termed dystroglycanopathies. Only a small number of mutations in the dystroglycan gene, leading to the so called primary dystroglycanopathies, has been described so far, as opposed to the ever‐growing number of identified secondary or tertiary dystroglycanopathies (caused by genetic abnormalities in glycosyltransferases or in enzymes involved in the synthesis of the carbohydrate building blocks). The few mutations found within the autonomous N‐terminal domain of α‐dystroglycan seem to destabilise it to different degrees, without influencing the overall folding and targeting of the dystroglycan complex. On the contrary other mutations, some located at the α/β interface of the dystroglycan complex, seem to be able to interfere with its maturation, thus compromising its stability and eventually leading to the intracellular engulfment and/or partial or even total degradation of the dystroglycan uncleaved precursor.     

Community assembly processes along a sub-Mediterranean elevation gradient: analyzing the interdependence of trait community weighted mean and functional diversity

Plant Ecology - Community-weighted mean (CWM) and functional diversity (FD) describe the two aspects of plant communities’ functional structure. While they have been often used separately to...     

Gene-based sequence diversity analysis of field pea (Pisum)

Sequence diversity of 39 dispersed gene loci was analyzed in 48 diverse individuals representative of the genus Pisum. The different genes show large variation in diversity parameters, suggesting widely differing levels of selection and a high overall diversity level for the species. The data set yields a genetic diversity tree whose deep branches, involving wild samples, are preserved in a tree derived from a polymorphic retrotransposon insertions in an identical sample set. Thus, gene regions and intergenic "junk DNA" share a consistent picture for the genomic diversity of Pisum, despite low linkage disequilibrium in wild and landrace germplasm, which might be expected to allow independent evolution of these very different DNA classes. Additional lines of evidence indicate that recombination has shuffled gene haplotypes efficiently within Pisum, despite its high level of inbreeding and widespread geographic distribution. Trees derived from individual gene loci show marked differences from each other, and genetic distance values between sample pairs show high standard deviations. Sequence mosaic analysis of aligned sequences identifies nine loci showing evidence for intragenic recombination. Lastly, phylogenetic network analysis confirms the non-treelike structure of Pisum diversity and indicates the major germplasm classes involved. Overall, these data emphasize the artificiality of simple tree structures for representing genomic sequence variation within Pisum and emphasize the need for fine structure haplotype analysis to accurately define the genetic structure of the species.     

Slow conformational dynamics of the guanine nucleotide-binding protein Ras complexed with the GTP analogue GTPgammaS

The guanine nucleotide-binding protein Ras occurs in solution in two different conformational states, state 1 and state 2 with an equilibrium constant K(12) of 2.0, when the GTP analogue guanosine-5'-(beta,gamma-imido)triphosphate or guanosine-5'-(beta,gamma-methyleno)triphosphate is bound to the active centre. State 2 is assumed to represent a strong binding state for effectors with a conformation similar to that found for Ras complexed to effectors. In the other state (state 1), the switch regions of Ras are most probably dynamically disordered. Ras variants that exist predominantly in state 1 show a drastically reduced affinity to effectors. In contrast, Ras(wt) bound to the GTP analogue guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS) leads to (31)P NMR spectra that indicate the prevalence of only one conformational state with K(12) > 10. Titration with the Ras-binding domain of Raf-kinase (Raf-RBD) shows that this state corresponds to effector binding state 2. In the GTPgammaS complex of the effector loop mutants Ras(T35S) and Ras(T35A) two conformational states different to state 2 are detected, which interconvert over a millisecond time scale. Binding studies with Raf-RBD suggest that both mutants exist mainly in low-affinity states 1a and 1b. From line-shape analysis of the spectra measured at various temperatures an activation energy DeltaH(|) (1a1b) of 61 kJ.mol(-1) and an activation entropy DeltaS(|) (1a1b) of 65 J.K(-1).mol(-1) are derived. Isothermal titration calorimetry on Ras bound to the different GTP-analogues shows that the effective affinity K(A) for the Raf-RBD to Ras(T35S) is reduced by a factor of about 20 compared to the wild-type with the strongest reduction observed for the GTPgammaS complex.     

Impact of ramp-up on the optimal capacity-related reconfiguration policy

This paper presents an optimal solution, based on Markov decision theory, for the problem of optimal capacity-related reconfiguration of manufacturing systems, under stochastic market demand. Both capacity expansion and reduction are considered. The solution quantitatively takes into account the effect of the ramp-up phenomenon, following each reconfiguration, on the optimal policy. A closed-form solution is presented for when product demand is independently and generally distributed over time. A real case concerning a flexible manufacturing line in the automotive sector is shown, to prove that ignoring the ramp-up effect in the decision process can lead to significant increases in overall costs.