Enantiopure water-soluble [Fe4L6] cages: host-guest chemistry and catalytic activity.

This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/anie.20130213

Modulation of locomotor activity in complete spinal cord injury

The aim of this study was to evaluate the modulation of muscle activity during locomotor-like movements by different walking speeds in subjects with a motor complete spinal cord injury (SCI) compared to actively- and passively-walking control subjects without neurological deficit. Stepping movements on a treadmill were induced and assisted by a driven gait orthosis. Electromyographic (EMG) muscle activity of one leg (rectus and biceps femoris, tibialis anterior and gastrocnemius) was recorded and analyzed at three stepping velocities with similar body weight support in both subject groups. In SCI subjects, the EMG amplitude of biceps femoris, tibialis anterior and gastrocnemius was in general similar or weaker than in passively- and actively-stepping control subjects, but that of rectus femoris was larger. The degree of co-activation between tibialis anterior and gastrocnemius was higher in SCI than in control subjects. A significant velocity-dependent EMG modulation was present in all four-leg muscles in both subject groups. In SCI subjects, this EMG modulation was similar to that in actively stepping control subjects. It is concluded that in complete spastic SCI subjects, spinal neuronal circuits underlying locomotion can to a large extent adequately respond to a change in external drive to adapt the neuronal pattern to a new locomotion speed. The application of various speeds might enhance the effect of locomotor training in incomplete SCI subject

Computerized visual feedback: an adjunct to robotic-assisted gait training

BACKGROUND AND PURPOSE: Robotic devices for walking rehabilitation allow new possibilities for providing performance-related information to patients during gait training. Based on motor learning principles, augmented feedback during robotic-assisted gait training might improve the rehabilitation process used to regain walking function. This report presents a method to provide visual feedback implemented in a driven gait orthosis (DGO). The purpose of the study was to compare the immediate effect on motor output in subjects during robotic-assisted gait training when they used computerized visual feedback and when they followed verbal instructions of a physical therapist. SUBJECTS: Twelve people with neurological gait disorders due to incomplete spinal cord injury participated. METHODS: Subjects were instructed to walk within the DGO in 2 different conditions. They were asked to increase their motor output by following the instructions of a therapist and by observing visual feedback. In addition, the subjects' opinions about using visual feedback were investigated by a questionnaire. RESULTS: Computerized visual feedback and verbal instructions by the therapist were observed to result in a similar change in motor output in subjects when walking within the DGO. Subjects reported that they were more motivated and concentrated on their movements when using computerized visual feedback compared with when no form of feedback was provided. DISCUSSION AND CONCLUSION: Computerized visual feedback is a valuable adjunct to robotic-assisted gait training. It represents a relevant tool to increase patients' motor output, involvement, and motivation during gait training, similar to verbal instructions by a therapist

T Cell Receptor (TCR) Antagonism without a Negative Signal: Evidence from T Cell Hybridomas Expressing Two Independent TCRs

Antagonist peptides inhibit T cell responses by an unknown mechanism. By coexpressing two independent T cell receptors (TCRs) on a single T cell hybridoma, we addressed the question of whether antagonist ligands induce a dominant-negative signal that inhibits the function of a second, independent TCR. The two receptors, Vα2Vβ5 and Vα2Vβ10, restricted by H-2Kb and specific for the octameric peptides SIINFEKL and SSIEFARL, respectively, were coexpressed on the same cell. Agonist stimulation demonstrated that the two receptors behaved independently with regard to antigen-induced TCR downregulation and intracellular biochemical signaling. The exposure of one TCR (Vα2Vβ5) to antagonist peptides could not inhibit a second independent TCR (Vα2Vβ10) from responding to its antigen. Thus, our data clearly demonstrate that these antagonist ligands do not generate a dominant-negative signal which affects the responsiveness of the entire cell. In addition, a kinetic analysis showed that even 12 h after engagement with their cognate antigen and 10 h after reaching a steady-state of TCR internalization, T cells were fully inhibited by the addition of antagonist peptides. The window of susceptibility to antagonist ligands correlated exactly with the time required for the responding T cells to commit to interleukin 2 production. The data support a model where antagonist ligands can competitively inhibit antigenic peptides from productively engaging the TCR. This competitive inhibition is effective during the entire commitment period, where sustained TCR engagement is essential for full T cell activation

A Triphasic Sorting System: Coordination Cages in Ionic Liquids.

Host-guest chemistry is usually carried out in either water or organic solvents. To investigate the utility of alternative solvents, three different coordination cages were dissolved in neat ionic liquids. By using (19) F NMR spectroscopy to monitor the presence of free and bound guest molecules, all three cages were demonstrated to be stable and capable of encapsulating guests in ionic solution. Different cages were found to preferentially dissolve in different phases, allowing for the design of a triphasic sorting system. Within this system, three coordination cages, namely Fe4 L6 2, Fe8 L12 3, and Fe4 L4 4, each segregated into a distinct layer. Upon the addition of a mixture of three different guests, each cage (in each separate layer) selectively bound its preferred guest.This work was supported by the European Research Council (259352). We also thank the Cambridge Chemistry NMR service for experimental assistance.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/anie.20150577

Haemodilution-induced profibrinolytic state is mitigated by fresh-frozen plasma: implications for early haemostatic intervention in massive haemorrhage

Background Fibrinolysis contributes to coagulopathy after major trauma and surgery. We hypothesized that progressive haemodilution is responsible, at least in part, for increased fibrinolytic tendency of blood clot. Methods The study was performed in two parts. First, whole blood (WB) samples collected from six healthy, consented volunteers were diluted in vitro with either saline or fresh-frozen plasma (FFP) to 40% and 15% of baseline. We quantified factor levels related to coagulation and fibrinolysis, and measured endogenous thrombin generation in undiluted control plasma samples and in samples diluted with saline or FFP. Additionally, thromboelastometry was used to assess susceptibility to fibrinolysis after adding tissue plasminogen activator in undiluted WB samples and in samples diluted with saline before and after substitution of fibrinogen or FFP. Secondly, as a model of in vivo haemodilution, we evaluated the same parameters before and after operation in nine consented patients undergoing off-pump coronary artery bypass surgery. Results The dilution with saline caused dose-dependent decreases in plasma levels of coagulation and antifibrinolytic factors, and in thrombin generation. In FFP-supplemented samples, factor levels and thrombin generation were maintained within normal ranges. Fibrinolytic tendency was significantly higher after haemodilution with saline independent of fibrinogen substitution compared with FFP. Similarly, increased tendency for fibrinolysis was also observed in the in vivo haemodilution. Conclusions We demonstrated in vitro and in vivo that progressive haemodilution decreases endogenous antifibrinolytic proteins including α2-antiplasmin and thrombin-activatable fibrinolysis inhibitor, resulting in increased fibrinolytic tendency. Therefore, early fluid replacement therapy with FFP might be advantageous after massive haemorrhag

Volatile anaesthetics and positive pressure ventilation reduce left atrial performance: a transthoracic echocardiographic study in young healthy adults

Background Animal and in vitro studies suggest that volatile anaesthetics affect left atrial (LA) performance. We hypothesized that human LA pump function and dimensions are altered by volatile anaesthetics in vivo. Methods We performed transthoracic echocardiographic (TTE) measurements in 59 healthy subjects (aged 18-48 yr) undergoing minor surgery under general anaesthesia. The unpremedicated patients were randomly assigned to anaesthesia with sevoflurane, desflurane, or isoflurane. TTE examinations were performed at baseline and after induction of anaesthesia and upon placement of a laryngeal mask during spontaneous breathing. After changing to intermittent positive pressure ventilation (IPPV), an additional TTE was performed. The study focused on the velocity-time integral of late peak transmitral inflow velocity (AVTI) and maximum LA volume. Results We found no evidence for relevant differences in the effects of the three volatile anaesthetics. AVTI decreased significantly from 4.1 (1.2) cm at baseline to 3.2 (1.1) cm during spontaneous breathing of 1 minimum alveolar concentration of volatile anaesthetics. AVTI decreased further to 2.8 (1.0) cm after changing to IPPV. The maximum LA volume was 45.4 (18.6) cm3 at baseline and remained unchanged during spontaneous breathing but decreased to 34.5 (16.7) cm3 during IPPV. Other parameters of LA pump function and dimensions decreased similarly. Conclusions Volatile anaesthetics reduced active LA pump function in humans in vivo. Addition of IPPV decreased LA dimensions and further reduced LA pump function. Effects in vivo were less pronounced than previously found in in vitro and animal studies. Further studies are warranted to evaluate the clinical implications of these findings. Clinical trial registration NCT002445

Can we have it all? The role of grassland conservation in supporting forage production and plant diversity

Context A key global challenge is to meet both the growing demand for food and feed while maintaining biodiversity’s supporting functions. Protected grasslands, such as Natura 2000 sites in Europe, may play an important role in harmonising productivity and biodiversity goals. This work contributes to an understanding of the relationship between forage production and plant diversity in protected and non-protected grasslands. Objectives We aimed to identify differences in plant diversity and forage production between protected and non-protected grasslands by assessing the effects of land-use intensity (i.e. mowing, grazing, fertilising) on these variables. Methods Data were available for 95 managed grassland plots (50 × 50 m) in real-managed landscapes. After controlling for site conditions in the analysis, we tested for significant differences between protected and non-protected grasslands and used a multi-group structural equation modelling (SEM) framework to investigate the linkages between land-use intensity, biomass and plant diversity. Results In protected grasslands, plant diversity was significantly higher while forage production was significantly lower. In non-protected grasslands we found significantly higher land-use intensity, particularly in relation to mowing and fertilisation. Grazing intensity did not significantly differ between protected and non-protected grasslands. In non-protected grasslands we found a significant negative association between forage production and plant diversity. However, this effect was not significant in protected grasslands. We also found a negative association between land-use and plant diversity in both grassland types that was related to mowing and fertilising intensity. These two management aspects also influenced the positive association between land-use intensity and forage production. Furthermore, environmental conditions had a positive effect on forage production and a negative effect on plant diversity in protected grasslands. Conclusions Our results confirm that the protection of grassland sites is successful in achieving higher plant diversity compared to non-protected grasslands and that protected grasslands do not necessarily trade-off with forage production. This is possible under moderate grazing intensities as higher land-use intensity has a negative effect on plant diversity, particularly on rare species. However, forage production is lower in protected sites as it is driven by mowing and fertilisation intensity. Future research needs to further investigate if the nature of these relationships depends on the livestock type or other management practices

Effect of environmental assessment on primary energy of modular prefabricated panel for building renovation in Portugal

While facing increasingly strict regulations regarding energy efficiency, the construction sector should also adopt sustainable solutions in terms of new constructions and renovations of buildings. In particular, energy renovation of existing buildings has specific technical and economic constraints that are generally addressed through implementation of new materials and building integrated systems, whose environmental impact should be considered when assessing the most adequate solution. Within the context of the More-Connect Project, which aims to develop modular prefabricated solutions for energy renovation of buildings, several renovation scenarios for a pilot building in Portugal were assessed using a methodology to compare the cost-effectiveness of renovation measures. The article explores the use of lifecycle assessment to analyse the effect of considering embodied primary energy in cost-effectiveness calculations.The MORE-CONNECT project is funded by the European Commission within the framework of the Horizon 2020 program

ScanDL: A Diffusion Model for Generating Synthetic Scanpaths on Texts

Eye movements in reading play a crucial role in psycholinguistic research studying the cognitive mechanisms underlying human language processing. More recently, the tight coupling between eye movements and cognition has also been leveraged for language-related machine learning tasks such as the interpretability, enhancement, and pre-training of language models, as well as the inference of reader- and text-specific properties. However, scarcity of eye movement data and its unavailability at application time poses a major challenge for this line of research. Initially, this problem was tackled by resorting to cognitive models for synthesizing eye movement data. However, for the sole purpose of generating human-like scanpaths, purely data-driven machine-learning-based methods have proven to be more suitable. Following recent advances in adapting diffusion processes to discrete data, we propose ScanDL, a novel discrete sequence-to-sequence diffusion model that generates synthetic scanpaths on texts. By leveraging pre-trained word representations and jointly embedding both the stimulus text and the fixation sequence, our model captures multi-modal interactions between the two inputs. We evaluate ScanDL within- and across-dataset and demonstrate that it significantly outperforms state-of-the-art scanpath generation methods. Finally, we provide an extensive psycholinguistic analysis that underlines the model's ability to exhibit human-like reading behavior. Our implementation is made available at https://github.com/DiLi-Lab/ScanDL.Comment: EMNLP 202