Comfort of two shoulder actuation mechanisms for arm therapy exoskeletons: a comparative study in healthy subjects

Robotic exoskeletons can be used to study and treat patients with neurological impairments. They can guide and support the human limb over a large range of motion, which requires that the movement trajectory of the exoskeleton coincide with the one of the human arm. This is straightforward to achieve for rather simple joints like the elbow, but very challenging for complex joints like the human shoulder, which is comprised by several bones and can exhibit a movement with multiple rotational and translational degrees of freedom. Thus, several research groups have developed different shoulder actuation mechanism. However, there are no experimental studies that directly compare the comfort of two different shoulder actuation mechanisms. In this study, the comfort and the naturalness of the new shoulder actuation mechanism of the ARMin III exoskeleton are compared to a ball-and-socket-type shoulder actuation. The study was conducted in 20 healthy subjects using questionnaires and 3D-motion records to assess comfort and naturalness. The results indicate that the new shoulder actuation is slightly better than a ball-and-socket-type actuation. However, the differences are small, and under the tested conditions, the comfort and the naturalness of the two tested shoulder actuations do not differ a lot.

The Incidence of AIDS-Defining Illnesses at a Current CD4 Count >=200 Cells/ L in the Post-Combination Antiretroviral Therapy Era

Background. Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. Methods. Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. Results. A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0–21.1 per 1000 PYFU) with current CD4 200–349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6–4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500–749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10–1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79–1.07), compared to a current CD4 of 750–999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25–1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01–1.25), comparing persons with a current CD4 of 500–749 cells/µL to 750–999 cells/µL. Discussion. The incidence of ADIs was higher in individuals with a current CD4 count of 500–749 cells/µL compared to those with a CD4 count of 750–999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.

Antagonizing Nogo-receptor 1 promotes the number of cultured dopaminergic neurons and elongates their neurites

The myelin-associated protein Nogo-A and its receptor Nogo-receptor 1 (NgR1) are known as potent growth inhibitors of the adult central nervous system (CNS). Nogo-A is mostly expressed on the surface of oligodendrocytes, but is also found in neurons of the adult and developing CNS. This observation suggests that Nogo-A serves additional functions in the brain. Hence, in the present study, we investigated the effects of antagonizing NgR1 on cultured organotypic and dissociated dopaminergic neurons. For that purpose ventral mesencephalic cultures from E14 rat embryos were grown in absence or presence of the NgR1 antagonist NEP1-40 for 1 week. Treatment with NEP1-40 significantly increased cell densities of tyrosine hydroxylase-immunoreactive neurons. Moreover, organotypic ventral mesencephalic cultures displayed a significantly bigger volume after NEP1-40 treatment. Morphological analysis of tyrosine hydroxylase-positive neurons disclosed longer neurites and higher numbers of primary neurites in dissociated cultures incubated with NEP1-40, whereas soma size was not changed. In conclusion, our findings demonstrate that interfering with Nogo-A signaling by antagonizing NgR1 modulates dopaminergic neuron properties during development. These observations highlight novel aspects of the role of Nogo-A in the CNS and might have an impact in the context of Parkinson's disease.

Geocenter coordinates estimated from GNSS data as viewed by perturbation theory

Time series of geocenter coordinates were determined with data of two global navigation satellite systems (GNSSs), namely the U.S. GPS (Global Positioning System) and the Russian GLONASS (Global’naya Nawigatsionnaya Sputnikowaya Sistema). The data was recorded in the years 2008–2011 by a global network of 92 permanently observing GPS/GLONASS receivers. Two types of daily solutions were generated independently for each GNSS, one including the estimation of geocenter coordinates and one without these parameters. A fair agreement for GPS and GLONASS was found in the geocenter x- and y-coordinate series. Our tests, however, clearly reveal artifacts in the z-component determined with the GLONASS data. Large periodic excursions in the GLONASS geocenter z-coordinates of about 40 cm peak-to-peak are related to the maximum elevation angles of the Sun above/below the orbital planes of the satellite system and thus have a period of about 4 months (third of a year). A detailed analysis revealed that the artifacts are almost uniquely governed by the differences of the estimates of direct solar radiation pressure (SRP) in the two solution series (with and without geocenter estimation). A simple formula is derived, describing the relation between the geocenter z-coordinate and the corresponding parameter of the SRP. The effect can be explained by first-order perturbation theory of celestial mechanics. The theory also predicts a heavy impact on the GNSS-derived geocenter if once-per-revolution SRP parameters are estimated in the direction of the satellite’s solar panel axis. Specific experiments using GPS observations revealed that this is indeed the case. Although the main focus of this article is on GNSS, the theory developed is applicable to all satellite observing techniques. We applied the theory to satellite laser ranging (SLR) solutions using LAGEOS. It turns out that the correlation between geocenter and SRP parameters is not a critical issue for the SLR solutions. The reasons are threefold: The direct SRP is about a factor of 30–40 smaller for typical geodetic SLR satellites than for GNSS satellites, allowing it in most cases to not solve for SRP parameters (ruling out the correlation between these parameters and the geocenter coordinates); the orbital arc length of 7 days (which is typically used in SLR analysis) contains more than 50 revolutions of the LAGEOS satellites as compared to about two revolutions of GNSS satellites for the daily arcs used in GNSS analysis; the orbit geometry is not as critical for LAGEOS as for GNSS satellites, because the elevation angle of the Sun w.r.t. the orbital plane is usually significantly changing over 7 days.

A new tool based on two micromanipulators facilitates the handling of ultrathin cryosection ribbons

A close to native structure of bulk biological specimens can be imaged by cryo-electron microscopy of vitreous sections (CEMOVIS). In some cases structural information can be combined with X-ray data leading to atomic resolution in situ. However, CEMOVIS is not routinely used. The two critical steps consist of producing a frozen section ribbon of a few millimeters in length and transferring the ribbon onto an electron microscopy grid. During these steps, the first sections of the ribbon are wrapped around an eyelash (unwrapping is frequent). When a ribbon is sufficiently attached to the eyelash, the operator must guide the nascent ribbon. Steady hands are required. Shaking or overstretching may break the ribbon. In turn, the ribbon immediately wraps around itself or flies away and thereby becomes unusable. Micromanipulators for eyelashes and grids as well as ionizers to attach section ribbons to grids were proposed. The rate of successful ribbon collection, however, remained low for most operators. Here we present a setup composed of two micromanipulators. One of the micromanipulators guides an electrically conductive fiber to which the ribbon sticks with unprecedented efficiency in comparison to a not conductive eyelash. The second micromanipulator positions the grid beneath the newly formed section ribbon and with the help of an ionizer the ribbon is attached to the grid. Although manipulations are greatly facilitated, sectioning artifacts remain but the likelihood to investigate high quality sections is significantly increased due to the large number of sections that can be produced with the reported tool.

Jazz drummers recruit language-specific areas for the processing of rhythmic structure

Rhythm is a central characteristic of music and speech, the most important domains of human communication using acoustic signals. Here, we investigated how rhythmical patterns in music are processed in the human brain, and, in addition, evaluated the impact of musical training on rhythm processing. Using fMRI, we found that deviations from a rule-based regular rhythmic structure activated the left planum temporale together with Broca's area and its right-hemispheric homolog across subjects, that is, a network also crucially involved in the processing of harmonic structure in music and the syntactic analysis of language. Comparing the BOLD responses to rhythmic variations between professional jazz drummers and musical laypersons, we found that only highly trained rhythmic experts show additional activity in left-hemispheric supramarginal gyrus, a higher-order region involved in processing of linguistic syntax. This suggests an additional functional recruitment of brain areas usually dedicated to complex linguistic syntax processing for the analysis of rhythmical patterns only in professional jazz drummers, who are especially trained to use rhythmical cues for communication.

Coloured Letters and Numbers (CLaN): A reliable factor-analysis based synaesthesia questionnaire

Synaesthesia is a heterogeneous phenomenon, even when considering one particular sub-type. The purpose of this study was to design a reliable and valid questionnaire for grapheme-colour synaesthesia that captures this heterogeneity. By the means of a large sample of 628 synaesthetes and a factor analysis, we created the Coloured Letters and Numbers (CLaN) questionnaire with 16 items loading on 4 different factors (i.e., localisation, automaticity/attention, deliberate use, and longitudinal changes). These factors were externally validated with tests which are widely used in the field of synaesthesia research. The questionnaire showed good test–retest reliability and construct validity (i.e., internally and externally). Our findings are discussed in the light of current theories and new ideas in synaesthesia research. More generally, the questionnaire is a useful tool which can be widely used in synaesthesia research to reveal the influence of individual differences on various performance measures and will be useful in generating new hypotheses.

Individual differences in inhibitory control - relationship between baseline activation in lateral PFC and an electrophysiological index of response inhibition

The capacity to inhibit inappropriate responses is crucial for goal-directed behavior. Inhibiting such responses seems to come more easily to some of us than others, however. From where do these individual differences originate? Here, we measured 263 participants' neural baseline activation using resting electroencephalogram. Then, we used this stable neural marker to predict a reliable electrophysiological index of response inhibition capacity in the cued Continuous Performance Test, the NoGo-Anteriorization (NGA). Using a source-localization technique, we found that resting delta, theta, and alpha1 activity in the left middle frontal gyrus and resting alpha1 activity in the right inferior frontal gyrus were negatively correlated with the NGA. As a larger NGA is thought to represent better response inhibition capacity, our findings demonstrate that lower levels of resting slow-wave oscillations in the lateral prefrontal cortex, bilaterally, are associated with a better response inhibition capacity.

Studying the neurobiology of social interaction with transcranial direct current stimulation--the example of punishing unfairness.

Studying social behavior often requires the simultaneous interaction of many subjects. As yet, however, no painless, noninvasive brain stimulation tool existed that allowed the simultaneous affection of brain processes in many interacting subjects. Here we show that transcranial direct current stimulation (tDCS) can overcome these limits. We apply right prefrontal cathodal tDCS and show that subjects' propensity to punish unfair behavior is reduced significantly.

Suppressing versus releasing a habit: frequency-dependent effects of prefrontal transcranial magnetic stimulation.

When subjects are required to generate a random sequence of numbers they typically produce too many forward and backward 'counts' (e.g. 5-6, 4-3). This counting bias is interpreted as the consequence of an interference by overlearned tendencies to arrange numbers according to their natural order. Inhibition of such well-learned routines is known to rely on frontal lobe functioning. We examined differential effects of slow (1 Hz) and fast (10 Hz) repetitive transcranial magnetic stimulation (rTMS) over the left or right dorsolateral prefrontal cortex (DLPFC) on random number generation (RNG) performance. Eighteen healthy men performed an RNG task. Those subjects stimulated over the left DLPFC showed a frequency-dependent rTMS effect: counting bias was significantly reduced after the 1 Hz stimulation compared with baseline, but significantly exaggerated after the 10 Hz stimulation compared with 1 Hz stimulation. In contrast, the sequences of the subjects stimulated over the right DLPFC showed the well-known excess of counting in all conditions (i.e. baseline, 1 Hz and 10 Hz). These findings confirm the functional importance of specifically the left DLPFC in sequential response production and show, for the first time, that rTMS affects cognitive processing in a frequency-dependent manner.

Induction of the autophagy-associated gene MAP1S via PU.1 supports APL differentiation

The PU.1 transcription factor is essential for myeloid development. We investigated if the microtubule-associated protein 1S (MAP1S) is a novel PU.1 target with a link to autophagy, a cellular recycling pathway. Comparable to PU.1, MAP1S expression was significantly repressed in primary AML blasts as compared to mature neutrophils. Accordingly, MAP1S expression was induced during neutrophil differentiation of CD34(+) progenitor and APL cells. Moreover, PU.1 bound to the MAP1S promoter and induced MAP1S expression during APL differentiation. Inhibiting MAP1S resulted in aberrant neutrophil differentiation and autophagy. Taken together, our findings implicate the PU.1-regulated MAP1S gene in neutrophil differentiation and autophagy control.

2D and 3D crystallization of a bacterial homologue of human vitamin C membrane transport proteins

Most organisms are able to synthesize vitamin C whereas humans are not. In order to contribute to the elucidation of the molecular working mechanism of vitamin C transport through biological membranes, we cloned, overexpressed, purified, functionally characterized, and 2D- and 3D-crystallized a bacterial protein (UraDp) with 29% of amino acid sequence identity to the human sodium-dependent vitamin C transporter 1 (SVCT1). Ligand-binding experiments by scintillation proximity assay revealed that uracil is a substrate preferably bound to UraDp. For structural analysis, we report on the production of tubular 2D crystals and present a first projection structure of UraDp from negatively stained tubes. On the other hand the successful growth of UraDp 3D crystals and their crystallographic analysis is described. These 3D crystals, which diffract X-rays to 4.2Å resolution, pave the way towards the high-resolution crystal structure of a bacterial homologue with high amino acid sequence identity to human SVCT1.

GOCE: precise orbit determination for the entire mission

The Gravity field and steady-state Ocean Circulation Explorer (GOCE) was the first Earth explorer core mission of the European Space Agency. It was launched on March 17, 2009 into a Sun-synchronous dusk-dawn orbit and re-entered into the Earth’s atmosphere on November 11, 2013. The satellite altitude was between 255 and 225 km for the measurement phases. The European GOCE Gravity consortium is responsible for the Level 1b to Level 2 data processing in the frame of the GOCE High-level processing facility (HPF). The Precise Science Orbit (PSO) is one Level 2 product, which was produced under the responsibility of the Astronomical Institute of the University of Bern within the HPF. This PSO product has been continuously delivered during the entire mission. Regular checks guaranteed a high consistency and quality of the orbits. A correlation between solar activity, GPS data availability and quality of the orbits was found. The accuracy of the kinematic orbit primarily suffers from this. Improvements in modeling the range corrections at the retro-reflector array for the SLR measurements were made and implemented in the independent SLR validation for the GOCE PSO products. The satellite laser ranging (SLR) validation finally states an orbit accuracy of 2.42 cm for the kinematic and 1.84 cm for the reduced-dynamic orbits over the entire mission. The common-mode accelerations from the GOCE gradiometer were not used for the official PSO product, but in addition to the operational HPF work a study was performed to investigate to which extent common-mode accelerations improve the reduced-dynamic orbit determination results. The accelerometer data may be used to derive realistic constraints for the empirical accelerations estimated for the reduced-dynamic orbit determination, which already improves the orbit quality. On top of that the accelerometer data may further improve the orbit quality if realistic constraints and state-of-the-art background models such as gravity field and ocean tide models are used for the reduced-dynamic orbit determination.

Dendritic spine morphology determines membrane-associated protein exchange between dendritic shafts and spine heads.

The purpose of this study was to examine whether variability in the shape of dendritic spines affects protein movement within the plasma membrane. Using a combination of confocal microscopy and the fluorescence loss in photobleaching technique in living hippocampal CA1 pyramidal neurons expressing membrane-linked GFP, we observed a clear correlation between spine shape parameters and the diffusion and compartmentalization of membrane-associated proteins. The kinetics of membrane-linked GFP exchange between the dendritic shaft and the spine head compartment were slower in dendritic spines with long necks and/or large heads than in those with short necks and/or small heads. Furthermore, when the spine area was reduced by eliciting epileptiform activity, the kinetics of protein exchange between the spine compartments exhibited a concomitant decrease. As synaptic plasticity is considered to involve the dynamic flux by lateral diffusion of membrane-bound proteins into and out of the synapse, our data suggest that spine shape represents an important parameter in the susceptibility of synapses to undergo plastic change.