Visual and proprioceptive contributions to postural control of upright stance in unilateral vestibulopathy

Preserving upright stance requires central integration of the sensory systems and appropriate motor output from the neuromuscular system to keep the centre of pressure (COP) within the base of support. Unilateral peripheral vestibular disorder (UPVD) causes diminished stance stability. The aim of this study was to determine the limits of stability and to examine the contribution of multiple sensory systems to upright standing in UPVD patients and healthy subjects. We hypothesized that closure of the eyes and Achilles tendon vibration during upright stance will augment the postural sway in UPVD patients more than in healthy subjects. Seventeen UPVD patients and 17 healthy subjects performed six tasks on a force plate: forwards and backwards leaning, to determine limits of stability, and upright standing with and without Achilles tendon vibration, each with eyes open and closed (with blackout glasses). The COP displacement of the patients was significantly greater in the vibration tasks than the controls and came closer to the posterior base of support boundary than the controls in all tasks. Achilles tendon vibration led to a distinctly more backward sway in both subject groups. Five of the patients could not complete the eyes closed with vibration task. Due to the greater reduction in stance stability when the proprioceptive, compared with the visual, sensory system was disturbed, we suggest that proprioception may be more important for maintaining upright stance than vision. UPVD patients, in particular, showed more difficulty in controlling postural stability in the posterior direction with visual and proprioceptive sensory disturbance.     

Structure based de novo design of novel glycogen synthase kinase 3 inhibitors

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase that has captured great attention in drug discovery projects. Structure based design has been successfully carried out to find a novel class of GSK-3 inhibitors using the Ludi de novo ligand design program. A total of 15 potential leads are suggested from the study. The structures have been validated through detailed analysis of the Ludi score values and by molecular docking experiment using FlexX. The hits have been further verified through: (1) visual examination of how well the hits dock into the GSK-3beta binding site; (2) comparative analysis of their FlexX, G_Score, PMF_Score, ChemScore, and D_scores values; (3) a comparative investigation of the docking scores of the hits with those of the reported inhibitors after calibration of the docking procedure with 17 previously reported inhibitors; (4) determination of the binding mode of the hits and comparison with that of the so far known inhibitors. Hits retaining interactions with the common amino acids of GSK-3beta binding site were taken to represent potential leads. Structurally the hits designed are mainly flat nitrogen heterocycles. These hits are expected to be important additions to the search of GSK-3 inhibitors and may provide invaluable insights to further understand the structural basis of catalysis and inhibition of this kinase.     

Sorption of phenol from synthetic aqueous solution by activated saw dust: Optimizing parameters with response surface methodology

Organic pollutants have an adverse effect on the neighboring environment. Industrial activates are the major sources of different organic pollutants. These primary pollutants react with surrounding and forms secondary pollutant, which persists for a long time. The present investigation has been carried out on the surface of activated sawdust for phenol eliminations. The process parameters initial concentration, contact time, adsorbent dose and pH were optimized by the response surface methodology (RSM). The numerical optimization of sawdust (SD), initial concentration 10 mg/l, contact time 1.5 h, adsorbent dose 4 g and pH 2, the optimum response result was 78.3% adsorption. Analysis of variance (ANOVA) was used to judge the adequacy of the central composite design and quadratic model found to be suitable. The coefficient of determination values was found to be maximum Adj R² 0.7223, and Pre R² 0.5739 and significant regression at 95% confidence level values.     

Insufficient Evidence of <Emphasis Type="Italic">Jatropha curcas</Emphasis> L. Invasiveness: Experimental Observations in Burkina Faso,West Africa

Biofuel plants such as Jatropha curcas L. have potential to support the livelihoods of rural communities and contribute to sustainable rural development in Africa, if risks and uncertainties are minimized. Yet, recent papers have warned of the risk of biological invasions in such tropical regions as a consequence of the introduction of exotic biofuel crops. We investigated the seed dispersal risk and invasiveness potential of both J. curcas monoculture plantations and live fences into adjacent cultivated and uncultivated land use systems in Sissili province, Burkina Faso. Invasiveness potential was assessed through (i) detecting evidence of natural regeneration in perimeters around J. curcas plantations and live fences, (ii) assessing seed dispersal mechanisms, and (iii) assessing seedling establishment potential through in situ direct seed sowing. Spontaneous regeneration around the plantation perimeters of the three sites was very low. Individual seedling density around J. curcas live fences was less than 0.01 m^?2 in all sites. Seventy percent of the seedlings were found close to the live fence and most of them derived from the same year (96 %), which indicates low seed-bank longevity and seedling survival. J. curcas can be dispersed by small mammals and arthropods, particularly rodents and ants. In some sites, such as in Onliassan, high secondary seed dispersal by animals (up to 98 %) was recorded. There were highly significant differences in germination rates between seeds at the soil surface (11 %) and those buried artificially at 1–2-cm depth (64 %). In conclusion, we failed to find convincing evidence of the spreading of J. curcas or any significant impact on the surrounding environment.     

Adaptational responses in dynamic stability during disturbed walking in the elderly

The purpose of this study was to examine the age-related predictive and feedback adaptive locomotor improvements in the components of dynamic stability control during disturbed walking. Thirteen old (62–74 yrs) and ten young (23–30 yrs) male subjects performed a gait protocol on a gangway, which included one covered element. By exchanging this element, the subjects walked either solely over hard surface or experienced a perturbation of the gait on the soft surface element. The gait protocol consisted of a baseline on hard surface and an adaptation phase with 19 trials on soft or hard (2nd, 8th and 19th) surface. The investigation of dynamic stability was made by using the margin of stability (MS), which was calculated as the difference between the base of support and the extrapolated center of mass (CM). Horizontal velocity of CM and its vertical projection in anterior–posterior direction as well as the eigenfrequency of an inverted pendulum generate the extrapolated CM. As a result of the first unexpected disturbance, MS was decreased in the step following the perturbation compared to baselines in both age-groups. This decrease was higher for the old participants compared to the young ones, indicating a more unstable position in the step after the perturbation for the elderly. In the following adaptation phase, MS returned to baseline values in both age-groups. In the hard trial after the first unexpected perturbation, both age-groups increased MS at touchdown of the disturbed leg compared to baseline, reflecting fast predictive adjustments. Our findings show that the well-known age-related biological impairments did not inhibit the adaptive improvements in the components of dynamic stability in the elderly. However, the feedback corrections after the first unexpected perturbation were less effective for the elderly. This may increase the risk of falling.     

QSAR study on dual SET and NET reuptake inhibitors: an insight into the structural requirement for antidepressant activity

Monoamine transporters have emerged as important drug targets with a multitude of therapeutic potentials for their inhibitors. With the purpose of designing new chemical entities with enhanced inhibitory potencies against norepinephrine and serotonin transporters, the QSAR study carried out on N-arylmethylpiperidinamine derivatives as known inhibitors of these transporters is presented. The developed model was validated by standard QSAR parameters and through a detailed structural analysis on how it reproduces and explains the differences in the experimentally known activity data. The model showed a good correlative and predictive ability having a squared cross validated correlation co-efficient of 0.716 and 0.700 respectively for SET and NET inhibition. The squared conventional correlation coefficient was found to be 0.731 for SET antagonism and 0.777 for norepinephrine reuptake inhibition. The study confirmed that the serotonin reuptake inhibitory activity exhibited by the series is largely explained by steric factors of substituents emphasizing the role of size and shape of the inhibitors in making effective inhibitor-SET binding interactions whereas substituent lipophilicity was found to govern inhibitor-NET interaction chemistry. A detailed comparative investigation was made between the two models and the insights gleaned from the study could be usefully employed to design inhibitors with a much more enhanced potency and selectivity.     

A Bayesian approach to functional-based multilevel modeling of longitudinal data: applications to environmental epidemiology

Flexible multilevel models are proposed to allow for cluster-specific smooth estimation of growth curves in a mixed-effects modeling format that includes subject-specific random effects on the growth parameters. Attention is then focused on models that examine between-cluster comparisons of the effects of an ecologic covariate of interest (e.g. air pollution) on nonlinear functionals of growth curves (e.g. maximum rate of growth). A Gibbs sampling approach is used to get posterior mean estimates of nonlinear functionals along with their uncertainty estimates. A second-stage ecologic random-effects model is used to examine the association between a covariate of interest (e.g. air pollution) and the nonlinear functionals. A unified estimation procedure is presented along with its computational and theoretical details. The models are motivated by, and illustrated with, lung function and air pollution data from the Southern California Children's Health Study.     

Ethnic Pluralism as an Organizing Principle of the Ethiopian Federation

In 1991 the Ethiopian government employed ethnic pluralism as an organizing principle, creating multiple ethnic-based territorial units with a right of secession provision. Ethiopians are watching this experiment with considerable apprehension. This paper: (1) provides a concise historical background of ethnic relations in Ethiopia, (2) examines the type of ethnic federal state established in Ethiopia, and (3) points out some problems encountered with ethnicity as an organizing principle and attempts a preliminary assessment of the ethnic-based federal experiment. The sources of data for this paper include public documents, fieldwork, and interviews with 30 knowledgeable Ethiopians in Addis Ababa. I spent several months during 2000–2002 observing political developments in the country as they pertain to ethnic federalism. Within Africa, a nation-state fully acknowledging and based on ethnic pluralism is unique. Thus far, the Ethiopian federation appears to have undercut the drive for secession by largely removing its rallying cause, manifest ethnic oppression. Nonetheless, the fact that the ruling group comes predominantly from a small ethnic group has raised serious protest from other ethnic groups, larger and smaller. Its use of democratic centralism has also undermined effective decentralization and democratization. Ethnic pluralism as an organizing principle underpinning the federal government in Ethiopia is a fragile and perilous experiment.     

QSAR study on dual SET and NET reuptake inhibitors: An insight into the structural requirement for antidepressant activity

Monoamine transporters have emerged as important drug targets with a multitude of therapeutic potentials for their inhibitors. With the purpose of designing new chemical entities with enhanced inhibitory potencies against norepinephrine and serotonin transporters, the QSAR study carried out on N-arylmethylpiperidinamine derivatives as known inhibitors of these transporters is presented. The developed model was validated by standard QSAR parameters and through a detailed structural analysis on how it reproduces and explains the differences in the experimentally known activity data. The model showed a good correlative and predictive ability having a squared cross validated correlation co-efficient of 0.716 and 0.700 respectively for SET and NET inhibition. The squared conventional correlation coefficient was found to be 0.731 for SET antagonism and 0.777 for norepinephrine reuptake inhibition. The study confirmed that the serotonin reuptake inhibitory activity exhibited by the series is largely explained by steric factors of substituents emphasizing the role of size and shape of the inhibitors in making effective inhibitor-SET binding interactions whereas substituent lipophiliCIT000y was found to govern inhibitor-NET interaction chemistry. A detailed comparative investigation was made between the two models and the insights gleaned from the study could be usefully employed to design inhibitors with a much more enhanced potency and selectivity.