The role of user preference in the customized control of robotic exoskeletons.

User preference is a promising objective for the control of robotic exoskeletons because it may capture the multifactorial nature of exoskeleton use. However, to use it, we must first understand its characteristics in the context of exoskeleton control. Here, we systematically measured the control preferences of individuals wearing bilateral ankle exoskeletons during walking. We investigated users' repeatability identifying their preferences and how preference changes with walking speed, device exposure, and between individuals with different technical backgrounds. Twelve naive and 12 knowledgeable nondisabled participants identified their preferred assistance in repeated trials by simultaneously self-tuning the magnitude and timing of peak torque. They were blinded to the control parameters and relied solely on their perception of the assistance to guide their tuning. We found that participants' preferences ranged from 7.9 to 19.4 newton-meters and 54.1 to 59.2 percent of the gait cycle. Across trials, participants repeatably identified their preferences with a mean standard deviation of 1.7 newton-meters and 1.5 percent of the gait cycle. Within a trial, participants converged on their preference in 105 seconds. As the experiment progressed, naive users preferred higher torque magnitude. At faster walking speeds, these individuals were more precise at identifying the magnitude of their preferred assistance. Knowledgeable users preferred higher torque than naive users. These results highlight that although preference is a dynamic quantity, individuals can reliably identify their preferences. This work motivates strategies for the control of lower limb exoskeletons in which individuals customize assistance according to their unique preferences and provides meaningful insight into how users interact with exoskeletons.

AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice.

Brain inflammation is a double-edged sword. It is required for brain repair in acute damage, whereas chronic inflammation and autoimmune disorders are neuropathogenic. Certain proinflammatory cytokines and chemokines are closely related to cognitive dysfunction and neurodegeneration. Representative anti-inflammatory cytokines, such as interleukin (IL)-10, can suppress neuroinflammation and have significant therapeutic potentials in ameliorating neurodegenerative disorders such as Alzheimer's disease (AD). Here, we show that adeno-associated virus (AAV) serotype 2/1 hybrid-mediated neuronal expression of the mouse IL-10 gene ameliorates cognitive dysfunction in amyloid precursor protein+ presenilin-1 bigenic mice. AAV2/1 infection of hippocampal neurons resulted in sustained expression of IL-10 without its leakage into the blood, reduced astro/microgliosis, enhanced plasma amyloid-ß peptide (Aß) levels and enhanced neurogenesis. Moreover, increased levels of IL-10 improved spatial learning, as determined by the radial arm water maze. Finally, IL-10-stimulated microglia enhanced proliferation but not differentiation of primary neural stem cells in the co-culture system, whereas IL-10 itself had no effect. Our data suggest that IL-10 gene delivery has a therapeutic potential for a non-Aß-targeted treatment of AD.

Lipid modification of prelipoproteins is dispensable for growth in vitro but essential for virulence in Streptococcus pneumoniae.

A Deltalgt (Lgt, lipoprotein diacylglyceryl transferase) isogenic mutant was obtained which indicates that lgt is not essential for cell growth in vitro, like in the Gram-positive bacterium Bacillus subtilis, but unlike in the proteobacteria Escherichia coli and Salmonella typhimurium. The mutation was transduced to a virulent strain. A 5 log attenuation was observed in a respiratory tract model of infection. Metabolic labeling by [U-14C]palmitate revealed the presence of eight to ten lipoproteins in the wild-type strain only, with molecular masses between 15 and 80 kDa. Our findings suggest a major difference in the role of lipoproteins in Gram-positive bacteria versus the proteobacteria.

Genetic characterization of gram-positive homologs of the XerCD site-specific recombinases.

Homologs of the XerCD enzymes, which in Escherichia coli have been shown to be responsible for resolving chromosomal multimers prior to chromosome segregation, were identified in the genomes of Staphylococcus aureus and Streptococcus pneumoniae. Phylogenetic and conservation pattern analysis suggests that the S. aureus gene products are orthologs of XerC and D. A S. aureus xerC null mutant displayed in vitro characteristics consistent with the segregation defect reported for E. coli xer mutants, and was found to be attenuated in a murine infection model. Strikingly, the S. aureus xerD gene appears to be absolutely required for viability, and may therefore be the first example of an essential gene of the lambda integrase family. In contrast, phylogenetic and conservation pattern analysis show that the S. pneumoniae gene products are more closely related to phage integrases than to XerCD. S. pneumoniae xer1, 2 and 3 null mutants were each found to be attenuated in a murine infection model, suggesting that they may control processes which affect virulence.

Identification, evolution, and essentiality of the mevalonate pathway for isopentenyl diphosphate biosynthesis in gram-positive cocci.

The mevalonate pathway and the glyceraldehyde 3-phosphate (GAP)-pyruvate pathway are alternative routes for the biosynthesis of the central isoprenoid precursor, isopentenyl diphosphate. Genomic analysis revealed that the staphylococci, streptococci, and enterococci possess genes predicted to encode all of the enzymes of the mevalonate pathway and not the GAP-pyruvate pathway, unlike Bacillus subtilis and most gram-negative bacteria studied, which possess only components of the latter pathway. Phylogenetic and comparative genome analyses suggest that the genes for mevalonate biosynthesis in gram-positive cocci, which are highly divergent from those of mammals, were horizontally transferred from a primitive eukaryotic cell. Enterococci uniquely encode a bifunctional protein predicted to possess both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and acetyl-CoA acetyltransferase activities. Genetic disruption experiments have shown that five genes encoding proteins involved in this pathway (HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, and mevalonate diphosphate decarboxylase) are essential for the in vitro growth of Streptococcus pneumoniae under standard conditions. Allelic replacement of the HMG-CoA synthase gene rendered the organism auxotrophic for mevalonate and severely attenuated in a murine respiratory tract infection model. The mevalonate pathway thus represents a potential antibacterial target in the low-G+C gram-positive cocci.

A genomic analysis of two-component signal transduction in Streptococcus pneumoniae.

A genomics-based approach was used to identify the entire gene complement of putative two-component signal transduction systems (TCSTSs) in Streptococcus pneumoniae. A total of 14 open reading frames (ORFs) were identified as putative response regulators, 13 of which were adjacent to genes encoding probable histidine kinases. Both the histidine kinase and response regulator proteins were categorized into subfamilies on the basis of phylogeny. Through a systematic programme of mutagenesis, the importance of each novel TCSTS was determined with respect to viability and pathogenicity. One TCSTS was identified that was essential for the growth of S. pneumoniaeThis locus was highly homologous to the yycFG gene pair encoding the essential response regulator/histidine kinase proteins identified in Bacillus subtilis and Staphylococcus aureus. Separate deletions of eight other loci led in each case to a dramatic attenuation of growth in a mouse respiratory tract infection model, suggesting that these signal transduction systems are important for the in vivo adaptation and pathogenesis of S. pneumoniae. The identification of conserved TCSTSs important for both pathogenicity and viability in a Gram-positive pathogen highlights the potential of two-component signal transduction as a multicomponent target for antibacterial drug discovery.

Growth and development of heather voles.

Data on growth and development are presented for eight litters of captive-born Phenacomys intermedius. Neonates from litters of four averaged 2.26 g at birth, significantly heavier than neonates from litters of five (1.96 g). Weights on day one showed a statistically significant decrease of 0.20 g per increase in litter size of one neonate. In general, large litters had lower growth rates. Growth of Phenacomys intermedius can be described by the equation Y = 1.17 + 0.62 X and the geometric growth constant is K = 0.079. Pinnae unfolded at 3.7 days, lower incisors erupted at 7.0 days, and eyes opened at 14.6 days. Data on growth and development are compared to other species of Phenacomys and to other microtines.