The bridge towards a more stable and active side-on-peroxido (Cu2II(µ-η2:η2-O2)) complex as a tyrosinase model system.

A novel dinucleating bis(pyrazolyl)methane ligand was developed for tyrosinase model systems. After ligand synthesis, the corresponding Cu(I) complex was synthesized and upon oxygenation, formation of a µ-η2:η2 peroxido complex could be observed and monitored using UV/Vis-spectroscopy. Due to the high stability of this species even at room temperature, a molecular structure of the complex could be characterized via single-crystal XRD. Additional to its promising stability, the peroxido complex showed catalytic tyrosinase activity which was investigated via UV/Vis-spectroscopy. Products of the catalytic conversion could be isolated and characterized and the ligand could be successfully recycled after catalysis experiments. Furthermore, the peroxido complex was reduced by reductants with different reduction potentials. The characteristics of the electron transfer reactions were investigated with the help of the Marcus relation. The combination of the high stability and catalytic activity of the peroxido complex with the new dinucleating ligand, enables the shift of oxygenation reactions for selected substrates towards green chemistry, which is furthered by the efficient ligand recycling capability.

Placebo hampers ability to self-regulate brain activity: A double-blind sham-controlled neurofeedback study.

It is still poorly understood how unspecific effects peripheral to the supposed action mechanism of neurofeedback (NF) influence the ability to self-regulate one's own brain signals. Recently, skeptical researchers have even attributed the lion's part of therapeutic outcomes of NF to placebo and other psychosocial factors. Here, we investigated whether and by which mechanisms unspecific factors influence neural self-regulation during NF. To manipulate the impact of unspecific influences on NF performance, we used a sham transcranial direct current stimulation (tDCS) as active placebo intervention suggesting positive effects on NF performance. Our results show that the expectation of receiving brain stimulation, which should boost neural self-regulation, interferes with the ability to self-regulate the sensorimotor rhythm in the EEG. Hence, these results provide evidence that placebo reduces NF performance, and thereby challenge current theories on unspecific effects related to NF.

[Cu6 (NGuaS)6 ]2+ and its oxidized and reduced derivatives: Confining electrons on a torus.

The hexanuclear thioguanidine mixed-valent copper complex cation [Cu6 (NGuaS)6 ]+2 (NGuaS = o-SC6 H4 NC(NMe2 )2 ) and its oxidized/reduced states are theoretically analyzed by means of density functional theory (DFT) (TPSSh + D3BJ/def2-TZV (p)). A detailed bonding analysis using overlap populations is performed. We find that a delocalized Cu-based ring orbital serves as an acceptor for donated S p electrons. The formed fully delocalized orbitals give rise to a confined electron cloud within the Cu6 S6 cage which becomes larger on reduction. The resulting strong electrostatic repulsion might prevent the fully reduced state. Experimental UV/Vis spectra are explained using time-dependent density functional theory (TD-DFT) and analyzed with a natural transition orbital analysis. The spectra are dominated by MLCTs within the Cu6 S6 core over a wide range but LMCTs are also found. The experimental redshift of the reduced low energy absorption band can be explained by the clustering of the frontier orbitals. © 2017 Wiley Periodicals, Inc.

Relativistic effects at the Cu2O2 core - a density functional theory study.

This work presents for the first time the impact of relativistic effects on the Cu2O2 peroxide dicopper(ii)-bis(µ-oxo) dicopper (iii) equilibrium bonding motif in existing tyrosinase model complexes [Cu2(btmgp)2(µ-O)2]2+ and [Cu2{HC(tBuPz)2Py}2(O2)]2+ [S. Herres et al., Inorg. Chim. Acta, 2005, 358, 1089; S. Herres-Pawlis et al., Eur. J. Inorg. Chem., 2005, 3815; A. Hoffmann et al., Angew. Chem., Int. Ed., 2013, 52, 5398]. We use density functional theory (TPSSh/cc-pVTZ+D3BJ) with various relativistic approaches (ECPs, DKH, ZORA) to tackle the question of impact and find, as already known for small model complexes in the literature, that the O core is more stabilized with respect to the P core by the relativistic influence [D. G. Liakos and F. Neese, J. Chem. Theory Comput., 2011, 7, 1511]. Whereas DKH and ZORA yield similar results, ECPs underestimate the predicted effect. By calculating the functional of the relativistic overlap change, we can exactly identify the relativistic changes at the molecular orbital level and narrow down the affected MOs. Thus, by performing a detailed bond analysis utilizing the overlap population, we are able to rationalize the effects at the chemical level by finding relativistic bond stabilization in both isomers, which is more dominating in the O core. In conclusion, relativistic effects already play an important role in dicopper cores and should be considered.

Neural Entrainment in Drum Rhythms with Silent Breaks: Evidence from Steady-state Evoked and Event-related Potentials.

The fusion of rhythm, beat perception, and movement is often summarized under the term "entrainment" and becomes obvious when we effortlessly tap our feet or snap our fingers to the pulse of music. Entrainment to music involves a large network of brain structures, and neural oscillations at beat-related frequencies can help elucidate how this network is connected. Here, we used EEG to investigate steady-state evoked potentials (SSEPs) and event-related potentials (ERPs) during listening and tapping to drum clips with different rhythmic structures that were interrupted by silent breaks of 2-6 sec. This design allowed us to address the question of whether neural entrainment processes persist after the physical presence of musical rhythms and to link neural oscillations and event-related neural responses. During stimulus presentation, SSEPs were elicited in both tasks (listening and tapping). During silent breaks, SSEPs were only present in the tapping task. Notably, the amplitude of the N1 ERP component was more negative after longer silent breaks, and both N1 and SSEP results indicate that neural entrainment was increased when listening to drum rhythms compared with an isochronous metronome. Taken together, this suggests that neural entrainment to music is not solely driven by the physical input but involves endogenous timing processes. Our findings break ground for a tighter linkage between steady-state and transient evoked neural responses in rhythm processing. Beyond music perception, they further support the crucial role of entrained oscillatory activity in shaping sensory, motor, and cognitive processes in general.

Optical response of the Cu2 S2 diamond core in Cu2II(NGuaS)2 Cl2.

Density functional theory (DFT) and time-dependent DFT calculations are presented for the dicopper thiolate complex Cu2 (NGuaS)2 Cl2 [NGuaS=2-(1,1,3,3-tetramethylguanidino) benzenethiolate] with a special focus on the bonding mechanism of the Cu2 S2 Cl2 core and the spectroscopic response. This complex is relevant for the understanding of dicopper redox centers, for example, the CuA center. Its UV/Vis absorption is theoretically studied and found to be similar to other structural CuA models. The spectrum can be roughly divided in the known regions of metal d-d absorptions and metal to ligand charge transfer regions. Nevertheless the chloride ions play an important role as electron donors, with the thiolate groups as electron acceptors. The bonding mechanism is dissected by means of charge decomposition analysis which reveals the large covalency of the Cu2 S2 diamond core mediated between Cu dz2 and S-S π and π* orbitals forming Cu-S σ bonds. Measured resonant Raman spectra are shown for 360- and 720-nm excitation wavelength and interpreted using the calculated vibrational eigenmodes and frequencies. The calculations help to rationalize the varying resonant behavior at different optical excitations. Especially the phenylene rings are only resonant for 720 nm. © 2016 Wiley Periodicals, Inc.

Specific effects of EEG based neurofeedback training on memory functions in post-stroke victims.

BACKGROUND: Using EEG based neurofeedback (NF), the activity of the brain is modulated directly and, therefore, the cortical substrates of cognitive functions themselves. In the present study, we investigated the ability of stroke patients to control their own brain activity via NF and evaluated specific effects of different NF protocols on cognition, in particular recovery of memory. METHODS: N = 17 stroke patients received up to ten sessions of either SMR (N = 11, 12-15 Hz) or Upper Alpha (N = 6, e.g. 10-12 Hz) NF training. N = 7 stroke patients received treatment as usual as control condition. Furthermore, N = 40 healthy controls performed NF training as well. To evaluate the NF training outcome, a test battery assessing different cognitive functions was performed before and after NF training. RESULTS: About 70 % of both patients and controls achieved distinct gains in NF performance leading to improvements in verbal short- and long-term memory, independent of the used NF protocol. The SMR patient group showed specific improvements in visuo-spatial short-term memory performance, whereas the Upper Alpha patient group specifically improved their working memory performance. NF training effects were even stronger than effects of traditional cognitive training methods in stroke patients. NF training showed no effects on other cognitive functions than memory. CONCLUSIONS: Post-stroke victims with memory deficits could benefit from NF training as much as healthy controls. The used NF training protocols (SMR, Upper Alpha) had specific as well as unspecific effects on memory. Hence, NF might offer an effective cognitive rehabilitation tool improving memory deficits of stroke survivors.

Concurrent stable and unstable cortical correlates of human wrist movements.

Cortical activity has been shown to correlate with different parameters of movement. However, the dynamic properties of cortico-motor mappings still remain unexplored in humans. Here, we show that during the repetition of simple stereotyped wrist movements both stable and unstable correlates simultaneously emerge in human sensorimotor cortex. Using visual feedback of wrist movement target inferred online from MEG, we assessed the dynamics of the tuning properties of two neuronal signals: the MEG signal below 1.6 Hz and within the 4 to 6 Hz range. We found that both components are modulated by wrist movement allowing for closed-loop inference of movement targets. Interestingly, while tuning of 4 to 6 Hz signals remained stable over time leading to stable inference of movement target using a static classifier, the tuning of cortical signals below 1.6 Hz significantly changed resulting in steadily decreasing inference accuracy. Our findings demonstrate that non-invasive neuronal population signals in human sensorimotor cortex can reflect a stable correlate of voluntary movements. Hence, we provide first evidence for a stable control signal in non-invasive human brain-machine interface research. However, as not all neuronal signals initially tuned to movement were stable across days, a careful selection of features for real-life applications seems to be mandatory.

Triathletes are experts in self-regulating physical activity - But what about self-regulating neural activity?

Regular exercise improves cognitive control abilities and successful self-regulation of physical activity. However, it is not clear whether exercising also improves the ability to self-regulate one's own brain activity. We investigated this in 26 triathletes and 25 control participants who did not exercise regularly. Within each group half of the participants performed one session of sensorimotor rhythm (SMR, 12-15 Hz) upregulation neurofeedback training, the other half received a sham neurofeedback training. The neurofeedback training session took about 45 min. In a separate session, participants underwent structural magnetic resonance imaging (MRI) to investigate possible differences in brain structure between triathletes and controls. Triathletes and controls were able to voluntarily upregulate their SMR activity during neurofeedback when receiving real feedback. Triathletes showed a stronger increase in SMR activity in the second half of the training compared to controls, suggesting that triathletes are able to self-regulate their own brain activity over a longer period of time. Further, triathletes and controls showed differences in brain structure as reflected by larger gray and white matter volumes in the inferior frontal gyrus and insula compared to controls. These brain areas are generally involved in cognitive control mechanisms. Our results provide new evidence regarding self-regulation abilities of people who exercise regularly and might impact the practical application of neurofeedback.

Role of local field potentials in encoding hand movement kinematics.

How the brain orchestrates the musculoskeletal system to produce complex three-dimensional movements is still poorly understood. Despite first promising results in brain-machine interfaces that translate cortical activity to control output, there is an ongoing debate about which brain signals provide richest information related to movement planning and execution. Novel results by Bansal and colleagues (2011) now suggest that neuronal spiking and local field potentials jointly encode kinematics during skilled reach and grasp movements.

Molecular RNA Correlates of the SOFA Score in Patients with Sepsis.

The most common scoring system for critically ill patients is the Sequential Organ Failure Assessment (SOFA) score. Little is known about specific molecular signaling networks underlying the SOFA criteria. We characterized these networks and identified specific key regulatory molecules. We prospectively studied seven patients with sepsis and six controls with high-throughput RNA sequencing (RNAseq). Quantitative reverse transcription PCR (RT-qPCR) confirmation was performed in a second independent cohort. Differentially and significantly expressed miRNAs and their target mRNA transcripts were filtered for admission SOFA criteria and marker RNAs for the respective criteria identified. We bioinformatically constructed molecular signaling networks specifically reflecting these criteria followed by RT-qPCR confirmation of RNAs with important regulatory functions in the networks in the second cohort. RNAseq identified 82 miRNAs (45% upregulated) and 3254 mRNAs (50% upregulated) differentially expressed between sepsis patients and controls. Bioinformatic analysis characterized 6 miRNAs and 76 mRNA target transcripts specific for the SOFA criteria. RT-qPCR validated miRNA and mRNAs included IGFBP2 (respiratory system); MMP9 and PDE4B (nervous system); PPARG (cardiovascular system); AKR1B1, ANXA1, and LNC2/NGAL (acute kidney injury); GFER/ALR (liver); and miR-30c-3p (coagulopathy). There are specific canonical networks underlying the SOFA score. Key regulatory miRNA and mRNA transcripts support its biologic validity.

Harbor seal vibrissa morphology suppresses vortex-induced vibrations.

Harbor seals (Phoca vitulina) often live in dark and turbid waters, where their mystacial vibrissae, or whiskers, play an important role in orientation. Besides detecting and discriminating objects by direct touch, harbor seals use their whiskers to analyze water movements, for example those generated by prey fish or by conspecifics. Even the weak water movements left behind by objects that have passed by earlier can be sensed and followed accurately (hydrodynamic trail following). While scanning the water for these hydrodynamic signals at a swimming speed in the order of meters per second, the seal keeps its long and flexible whiskers in an abducted position, largely perpendicular to the swimming direction. Remarkably, the whiskers of harbor seals possess a specialized undulated surface structure, the function of which was, up to now, unknown. Here, we show that this structure effectively changes the vortex street behind the whiskers and reduces the vibrations that would otherwise be induced by the shedding of vortices from the whiskers (vortex-induced vibrations). Using force measurements, flow measurements and numerical simulations, we find that the dynamic forces on harbor seal whiskers are, by at least an order of magnitude, lower than those on sea lion (Zalophus californianus) whiskers, which do not share the undulated structure. The results are discussed in the light of pinniped sensory biology and potential biomimetic applications.

Siloxane in baking moulds, emission to indoor air and migration to food during baking with an electric oven.

Linear and cyclic volatile methylsiloxanes (l-VMS and c-VMS) are man-made chemicals with no natural source. They have been widely used in cosmetics, personal care products, coatings and many other products. As a consequence of their wide use, VMS can be found in different environmental media, as well as in humans. We bought 14 new silicone baking moulds and 3 metallic moulds from the market and used them in different baking experiments. Four of the silicone baking moulds were produced in Germany, two in Italy, four in China, and for the other moulds were no information available. The metal forms were all produced in Germany. VMS were measured in the indoor air throughout the baking process and at the edge and in the center of the finished cakes using a GC/MS system. Additionally, the particle number concentration (PNC) and particle size distribution were measured in the indoor air. The highest median concentrations of VMS were observed immediately following baking: 301 µg/m3 of D7, 212 µg/m3 of D6, and 130 µg/m3 of D8. The silicone moulds containing the highest concentrations of c-VMS corresponded with distinctly higher concentrations of the compounds in indoor air. Using a mould for more than one baking cycle reduced the indoor air concentrations substantially. Samples collected from the edge of the cake had higher concentrations relative to samples from the center, with a mean initial concentration of 6.6 mg/kg of D15, 3.9 mg/kg of D9, 3.7 mg/kg of D12, and 4.8 mg/kg of D18. D3 to D5 were measured only at very low concentrations. Before starting the experiment, an average PNC of 7300 particles/cm3 was observed in the room's air, while a PNC of 140,000 particles/cm3 was observed around the electric stove while it was baking, but this PNC slowly decreased after the oven was switched off. Baking with 4 of the moulds exceeded the German indoor precaution guide value for c-VMS, but the health hazard guide value was not reached during every experiment. Compared to other exposure routes, c-VMS contamination of cake from silicone moulds seems to be low, as demonstrated by the low concentrations of D4 and D6 measured. For less volatile c-VMS > D6 the results of the study indicate that food might play a more important role for daily intake. As a general rule, silicone moulds should be used only after precleaning and while strictly following the temperature suggestions of the producers.

Large eddy simulation in a rotary blood pump: Viscous shear stress computation and comparison with unsteady Reynolds-averaged Navier-Stokes simulation.

PURPOSE:: Numerical flow analysis (computational fluid dynamics) in combination with the prediction of blood damage is an important procedure to investigate the hemocompatibility of a blood pump, since blood trauma due to shear stresses remains a problem in these devices. Today, the numerical damage prediction is conducted using unsteady Reynolds-averaged Navier-Stokes simulations. Investigations with large eddy simulations are rarely being performed for blood pumps. Hence, the aim of the study is to examine the viscous shear stresses of a large eddy simulation in a blood pump and compare the results with an unsteady Reynolds-averaged Navier-Stokes simulation. METHODS:: The simulations were carried out at two operation points of a blood pump. The flow was simulated on a 100M element mesh for the large eddy simulation and a 20M element mesh for the unsteady Reynolds-averaged Navier-Stokes simulation. As a first step, the large eddy simulation was verified by analyzing internal dissipative losses within the pump. Then, the pump characteristics and mean and turbulent viscous shear stresses were compared between the two simulation methods. RESULTS:: The verification showed that the large eddy simulation is able to reproduce the significant portion of dissipative losses, which is a global indication that the equivalent viscous shear stresses are adequately resolved. The comparison with the unsteady Reynolds-averaged Navier-Stokes simulation revealed that the hydraulic parameters were in agreement, but differences for the shear stresses were found. CONCLUSION:: The results show the potential of the large eddy simulation as a high-quality comparative case to check the suitability of a chosen Reynolds-averaged Navier-Stokes setup and turbulence model. Furthermore, the results lead to suggest that large eddy simulations are superior to unsteady Reynolds-averaged Navier-Stokes simulations when instantaneous stresses are applied for the blood damage prediction.

Modulation of human corticomuscular beta-range coherence with low-level static forces.

Although corticomuscular synchronization in the beta range (15-30 Hz) was shown to occur during weak steady-state contractions, an examination of low-level forces around 10% of the maximum voluntary contraction (MVC) is still missing. We addressed this question by investigating coherence between electroencephalogram (EEG) and electromyogram (EMG) as well as cortical spectral power during a visuomotor task. Eight healthy right-handed subjects compensated isometrically static forces at a level of 4% and 16% of MVC with their right index finger. While 4% MVC was accompanied by low coherence values in the middle to high beta frequency range (25-30 Hz), a significant increase of coherence mainly confined to low beta frequencies (19-20 Hz) was observed with force of 16% MVC. Furthermore, this increase was associated with better performance, as reflected in decreased relative error in force during 16% MVC. We additionally show that periods of good motor performance within each condition were associated with higher values of EEG-EMG coherence and spectral power. In conclusion, our results suggest a role for beta-range corticomuscular coherence in effective sensorimotor integration, thus stabilizing corticospinal communication.

Corticomuscular synchronization with small and large dynamic force output.

BACKGROUND: Over the last few years much research has been devoted to investigating the synchronization between cortical motor and muscular activity as measured by EEG/MEG-EMG coherence. The main focus so far has been on corticomuscular coherence (CMC) during static force condition, for which coherence in beta-range has been described. In contrast, we showed in a recent study 1 that dynamic force condition is accompanied by gamma-range CMC. The modulation of the CMC by various dynamic force amplitudes, however, remained uninvestigated. The present study addresses this question. We examined eight healthy human subjects. EEG and surface EMG were recorded simultaneously. The visuomotor task consisted in isometric compensation for 3 forces (static, small and large dynamic) generated by a manipulandum. The CMC, the cortical EEG spectral power (SP), the EMG SP and the errors in motor performance (as the difference between target and exerted force) were analyzed. RESULTS: For the static force condition we found the well-documented, significant beta-range CMC (15-30 Hz) over the contralateral sensorimotor cortex. Gamma-band CMC (30-45 Hz) occurred in both small and large dynamic force conditions without any significant difference between both conditions. Although in some subjects beta-range CMC was observed during both dynamic force conditions no significant difference between conditions could be detected. With respect to the motor performance, the lowest errors were obtained in the static force condition and the highest ones in the dynamic condition with large amplitude. However, when we normalized the magnitude of the errors to the amplitude of the applied force (relative errors) no significant difference between both dynamic conditions was observed. CONCLUSION: These findings confirm that during dynamic force output the corticomuscular network oscillates at gamma frequencies. Moreover, we show that amplitude modulation of dynamic force has no effect on the gamma CMC in the low force range investigated. We suggest that gamma CMC is rather associated with the internal state of the sensorimotor system as supported by the unchanged relative error between both dynamic conditions.

Neural Entrainment to Polyrhythms: A Comparison of Musicians and Non-musicians.

Music can be thought of as a dynamic path over time. In most cases, the rhythmic structure of this path, such as specific sequences of strong and weak beats or recurring patterns, allows us to predict what and particularly when sounds are going to happen. Without this ability we would not be able to entrain body movements to music, like we do when we dance. By combining EEG and behavioral measures, the current study provides evidence illustrating the importance of ongoing neural oscillations at beat-related frequencies-i.e., neural entrainment-for tracking and predicting musical rhythms. Participants (13 musicians and 13 non-musicians) listened to drum rhythms that switched from a quadruple rhythm to a 3-over-4 polyrhythm. After a silent period of ~2-3 s, participants had to decide whether a target stimulus was presented on time with the triple beat of the polyrhythm, too early, or too late. Results showed that neural oscillations reflected the rhythmic structure of both the simple quadruple rhythm and the more complex polyrhythm with no differences between musicians and non-musicians. During silent periods, the observation of time-frequency plots and more commonly used frequency spectra analyses suggest that beat-related neural oscillations were more pronounced in musicians compared to non-musicians. Neural oscillations during silent periods are not driven by an external input and therefore are thought to reflect top-down controlled endogenous neural entrainment. The functional relevance of endogenous neural entrainment was demonstrated by a positive correlation between the amplitude of task-relevant neural oscillations during silent periods and the number of correctly identified target stimuli. In sum, our findings add to the evidence supporting the neural resonance theory of pulse and meter. Furthermore, they indicate that beat-related top-down controlled neural oscillations can exist without external stimulation and suggest that those endogenous oscillations are strengthened by musical expertise. Finally, this study shows that the analysis of neural oscillations can be a useful tool to assess how we perceive and process complex auditory stimuli such as polyrhythms.

Specific or nonspecific? Evaluation of band, baseline, and cognitive specificity of sensorimotor rhythm- and gamma-based neurofeedback.

Neurofeedback (NF) is often criticized because of the lack of empirical evidence of its specificity. Our present study thus focused on the specificity of NF on three levels: band specificity, cognitive specificity, and baseline specificity. Ten healthy middle-aged individuals performed ten sessions of SMR (sensorimotor rhythm, 12-15Hz) NF training. A second group (N=10) received feedback of a narrow gamma band (40-43Hz). Effects of NF on EEG resting measurements (tonic EEG) and cognitive functions (memory, intelligence) were evaluated using a pre-post design. Both training groups were able to linearly increase the target training frequencies (either SMR or gamma), indicating the trainability of these EEG frequencies. Both NF training protocols led to nonspecific changes in other frequency bands during NF training. While SMR NF only led to concomitant changes in slower frequencies, gamma training affected nearly the whole power spectrum. SMR NF specifically improved memory functions. Gamma training showed only marginal effects on cognitive functions. SMR power assessed during resting measurements significantly increased after SMR NF training compared to a pre-assessment, indicating specific effects of SMR NF on baseline/tonic EEG. The gamma group did not show any pre-post changes in their EEG resting activity. In conclusion, SMR NF specifically affects cognitive functions (cognitive specificity) and tonic EEG (baseline specificity), while increasing SMR during NF training nonspecifically affects slower EEG frequencies as well (band non-specificity). Gamma NF was associated with nonspecific effects on the EEG power spectrum during training, which did not lead to considerable changes in cognitive functions or baseline EEG activity.