Estimation of distal arm joint angles from EMG and shoulder orientation for transhumeral prostheses

In this paper, we quantify the extent to which shoulder orientation, upper-arm electromyography (EMG), and forearm EMG are predictors of distal arm joint angles during reaching in eight subjects without disability as well as three subjects with a unilateral transhumeral amputation and targeted reinnervation. Prior studies have shown that shoulder orientation and upper-arm EMG, taken separately, are predictors of both elbow flexion/extension and forearm pronation/supination. We show that, for eight subjects without disability, shoulder orientation and upper-arm EMG together are a significantly better predictor of both elbow flexion/extension during unilateral ($R^2=0.72$) and mirrored bilateral ($R^2=0.72$) reaches and of forearm pronation/supination during unilateral ($R^2=0.77$) and mirrored bilateral ($R^2=0.70$) reaches. We also show that adding forearm EMG further improves the prediction of forearm pronation/supination during unilateral ($R^2=0.82$) and mirrored bilateral ($R^2=0.75$) reaches. In principle, these results provide the basis for choosing inputs for control of transhumeral prostheses, both by subjects with targeted motor reinnervation (when forearm EMG is available) and by subjects without target motor reinnervation (when forearm EMG is not available). In particular, we confirm that shoulder orientation and upper-arm EMG together best predict elbow flexion/extension ($R^2=0.72$) for three subjects with unilateral transhumeral amputations and targeted motor reinnervation. However, shoulder orientation alone best predicts forearm pronation/supination ($R^2=0.88$) for these subjects, a contradictory result that merits further study.     

Protein crystal’s shape and polymorphism prediction within the limits resulting from the exploration of the Miyazawa–Jernigan matrix

A computer study of the prediction of the protein crystal’s shape and polymorphism of crystal’s structures within the limits resulting from the exploration of the Miyazawa–Jernigan matrix is presented. In this study, a coarse-graining procedure was applied to prepare a two-dimensional growth unit, where instead of full atom representation of the protein a two-type (hydrophobic–hydrophilic, HP) aminoacidal representation was used. The interaction energies between hydrophobic ($E_{\text{HH}}$) aminoacids were chosen from the well-known HP-type models ($E_{\text{HH}}\in [-4\text{,}-3\text{,}-2.3\text{,}-1]$), whereas interaction energies between hydrophobic and hydrophilic aminoacids ($E_{\text{HP}}$) as well as interaction energies between hydrophilic aminoacids ($E_{\text{PP}}$) were chosen from the range: $<-1\text{,}1>$, but not all values from this range fulfiled limitations resulting from the exploration of the Miyazawa–Jernigan matrix. Exploring every positively vetted combinations of energy interactions a polymorphism of the unit cell was observed what led to the fact that different final crystal’s shapes were obtained.     

The consequences of dominance and gene flow for local adaptation and differentiation at two linked loci

For a subdivided population the consequences of dominance and gene flow for the maintenance of multilocus polymorphism, local adaptation, and differentiation are investigated. The dispersing population inhabits two demes in which selection acts in opposite direction. Fitness is determined additively by two linked diallelic loci with arbitrary intermediate dominance (no over- or underdominance). For weak as well as strong migration, the equilibrium structure is derived. As a special case, a continuous-time continent–island model (CI model) is analyzed, with one-way migration from the continent to the island. For this CI model, the equilibrium and stability configuration is obtained explicitly for weak migration, for strong migration, for independent loci, and for complete linkage. For independent loci, the possible bifurcation patterns are derived as functions of the migration rate. These patterns depend strongly on the degree of dominance. The effects of dominance, linkage, and migration on the amount of linkage disequilibrium (LD) and the degree of local adaptation are explored. Explicit formulas are obtained for $D$   $(=x_1{x}_4-x_2{x}_3)$ and $r^2$ (the squared correlation in allelic state). They demonstrate that dominant island alleles increase $D$ and decrease $r^2$. Local adaptation is elevated by dominance of the locally adaptive alleles. The effective migration rate at a linked neutral locus is calculated. If advantageous alleles are dominant, it is decreased only slightly below the actual migration rate. For a quantitative trait that is determined by two additive loci, the influence of dominance on measures of differentiation is studied. Explicit expressions for $Q_{ST}$ and two types of $F_{ST}$ at equilibrium are deduced and their relation is discussed.     

Structural Analysis of a Trimer of β2-Microgloblin Fragment by Molecular Dynamics Simulations

A peptide ${\beta }_2$-${\text{m}}_{21?31}$, which is a fragment from residue 21 to residue 31 of ${\beta }_2$-microgloblin, is experimentally known to self-assemble and form amyloid fibrils. In order to understand the mechanism of amyloid fibril formations, we applied the replica-exchange molecular dynamics method to the system consisting of three fragments of ${\beta }_2$-${\text{m}}_{21?31}$. From the analyses on the temperature dependence, we found that there is a clear phase transition temperature in which the peptides aggregate with each other. Moreover, we found by the free energy analyses that there are two major stable states: One of them is like amyloid fibrils and the other is amorphous aggregates.     

Synthesis and optimization of novel (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as orally active renin inhibitors

We report synthesis and optimization of a series of (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as renin inhibitors. Chemical modification of ${{\text{P}}_1}^{\prime }$, ${{\text{P}}_2}^{\prime }$ and P₃ portions led to a promising 3,5-disubstituted piperidine 32o showing high renin inhibitory activity and favorable oral exposure in both rats and cynomolgus monkeys with acceptable CYP and hERG current inhibition. Compound 32o exhibited a significant blood pressure lowering effect by oral administration in two hypertensive animal models, double transgenic rats and furosemide pretreated cynomolgus monkeys.