Robust, well-characterized methods for purifying small extracellular vesicles (sEV) from blood are needed before their potential as disease biomarkers can be realized. Here, we compared isolation of ...sEV from serum by differential ultracentrifugation (DUC) and by exclusion chromatography using commercially available Exo-spin™ columns. We show that sEV can be purified by both methods but Exo-spin™ columns contain copious additional particles recorded by nanoparticle tracking analysis, invalidating its use for quantifying yields. DUC samples contained higher concentrations of exosome specific proteins CD9, CD63 and CD81 and electron microscopy confirmed that most particles in DUC preparations were sEV, whereas Exo-spin™ samples also contained copious co-purified plasma lipids. MACSPlex bead analysis identified multiple exosome surface proteins, with stronger signals in DUC samples, enabling detection of 21 of 37, compared to only 10 in Exo-spin™ samples. Nevertheless, the pattern of expression was consistent in both preparations, indicating that lipids do not interfere with bead-based technologies. Thus, both DUC and Exo-spin™ can be used to isolate sEV from human serum and what is most appropriate depends on the subsequent use of sEV. In summary, Exo-spin™ enables isolation of sEV from blood with vesicle populations similar to the ones recovered by DUC, but with lower concentrations.
Highlights ► This study shows how to effectively overcome brain computer interface (BCI) inefficiency in patients with neurodegenerative disease. ► Online performance was significantly increased in ...healthy participants ( N = 16) and those with neurodegenerative disease ( N = 9) when using faces as stimulus material in an ERP–BCI paradigm. ► Importantly, two patients who were highly inefficient with the classic BCI paradigm spelled at high accuracy levels with the face flashing paradigm.
Six experiments investigated how the distance between one's initial opinion and advice relates to advice utilization. Going beyond previous research, we relate advice distance to both relative ...adjustments and absolute adjustments towards the advice, and we also investigate a second mode of advice utilization, namely confidence shifts due to social validation. Whereas previous research suggests that advice is weighted less the more it differs from one's initial opinion, we consistently find evidence of a curvilinear pattern. Advice is weighted less when advice distance is low and when it is high. This is in particular because individuals are much more likely to retain their initial opinions in the light of near advice. Also, absolute opinion adjustments towards the advice increases in a monotone fashion as advice distance increases. This finding is in contrast to the predictions of the theoretical framework previous studies on advice distance are based on, social judgment theory. Instead, they data are more in line with a simple stimulus-response model suggesting that absolute adjustments towards the advice increase with advice distance but--potentially--with diminished sensitivity. Finally, our data show that advice can be utilized even when it receives zero weight during belief revision. The closer advice was to the initial opinions, the more it served as a means for social validation, increasing decision-makers' confidence in the accuracy of their final opinions. Thus, our findings suggest that advice utilization is a more complex function of advice distance than previously assumed.
Many plant species are pollinated by butterflies. These insects are primarily attracted by visual flower cues, however, butterflies are also known to respond to flower scents and some ...butterfly-pollinated plants are strongly scented. One of such plants is the butterfly bush,
Buddleja davidii
, which is a magnet for butterflies. It is widespread in its native region in Asia and famous for its success in invasive spreading in regions throughout the world. Due to its attractiveness to butterflies and its beautiful and conspicuous inflorescences, it also is an important ornamental, found in many gardens. Here, we elucidated the signaling between the butterfly bush and one of its abundant visitors, the peacock butterfly (
Aglais io
), using chemical and behavioral approaches. We found that olfactory cues are more attractive than visual cues, and that feeding behavior is only elicited by olfactory cues, most effectively by 4-oxoisophorone and oxoisophorone epoxide. The latter compound was not known to elicit behavioral responses in pollinators before this study. The relative importance of olfactory cues was higher in our study than previously observed in any butterfly pollination system. The identified attractants might contribute to the widespread occurrence of the butterfly bush in its native region in Asia and its success in invasive spreading in regions throughout the world.
We present an atomistic description of the electronic and optical properties of In sub(0.25)Ga sub(0.75)N/GaN quantum wells. Our analysis accounts for fluctuations of well width, local alloy ...composition, strain and built-in field fluctuations as well as Coulomb effects. We find a strong hole and much weaker electron wave function localization in InGaN random alloy quantum wells. The presented calculations show that while the electron states are mainly localized by well-width fluctuations, the holes states are already localized by random alloy fluctuations. These localization effects affect significantly the quantum well optical properties, leading to strong inhomogeneous broadening of the lowest interband transition energy. Our results are compared with experimental literature data.
Opioid-associated overdoses and deaths due to respiratory depression are a major public health problem in the US and other Western countries. In the past decade, much research effort has been ...directed towards the development of G-protein-biased µ-opioid receptor (MOP) agonists as a possible means to circumvent this problem. The bias hypothesis proposes that G-protein signaling mediates analgesia, whereas ß-arrestin signaling mediates respiratory depression. SR-17018 was initially reported as a highly biased µ-opioid with an extremely wide therapeutic window. It was later shown that SR-17018 can also reverse morphine tolerance and prevent withdrawal via a hitherto unknown mechanism of action. Here, we examined the temporal dynamics of SR-17018-induced MOP phosphorylation and dephosphorylation. Exposure of MOP to saturating concentrations of SR-17018 for extended periods of time stimulated a MOP phosphorylation pattern that was indistinguishable from that induced by the full agonist DAMGO. Unlike DAMGO-induced MOP phosphorylation, which is reversible within minutes after agonist washout, SR-17018-induced MOP phosphorylation persisted for hours under otherwise identical conditions. Such delayed MOP dephosphorylation kinetics were also found for the partial agonist buprenorphine. However, buprenorphine, SR-17018-induced MOP phosphorylation was fully reversible when naloxone was included in the washout solution. SR-17018 exhibits a qualitative and temporal MOP phosphorylation profile that is strikingly different from any other known biased, partial, or full MOP agonist. We conclude that detailed analysis of receptor phosphorylation may provide novel insights into previously unappreciated pharmacological properties of newly synthesized MOP ligands.
Effective use of brain–computer interfaces (BCIs) typically requires training. Improved understanding of the neural mechanisms underlying BCI training will facilitate optimisation of BCIs. The ...current study examined the neural mechanisms related to training for electroencephalography (EEG)‐based communication with an auditory event‐related potential (ERP) BCI. Neural mechanisms of training in 10 healthy volunteers were assessed with functional magnetic resonance imaging (fMRI) during an auditory ERP‐based BCI task before (t1) and after (t5) three ERP‐BCI training sessions outside the fMRI scanner (t2, t3, and t4). Attended stimuli were contrasted with ignored stimuli in the first‐level fMRI data analysis (t1 and t5); the training effect was verified using the EEG data (t2‐t4); and brain activation was contrasted before and after training in the second‐level fMRI data analysis (t1 vs. t5). Training increased the communication speed from 2.9 bits/min (t2) to 4 bits/min (t4). Strong activation was found in the putamen, supplementary motor area (SMA), and superior temporal gyrus (STG) associated with attention to the stimuli. Training led to decreased activation in the superior frontal gyrus and stronger haemodynamic rebound in the STG and supramarginal gyrus. The neural mechanisms of ERP‐BCI training indicate improved stimulus perception and reduced mental workload. The ERP task used in the current study showed overlapping activations with a motor imagery based BCI task from a previous study on the neural mechanisms of BCI training in the SMA and putamen. This suggests commonalities between the neural mechanisms of training for both BCI paradigms.
Graphene-based conductors such as films and fibers aim to transfer graphene’s extraordinary properties to the macroscopic scale. They show great potential for large-scale applications, but there is a ...lack of theoretical models to describe their electrical characteristics. We present a network simulation method to model the electrical conductivity of graphene-based conductors. The method considers all of the relevant microscopic parameters such as graphene flake conductivity, interlayer conductivity, packing density, and flake size. To provide a mathematical framework, we derive an analytical expression, which reproduces the essential features of the network model. We also find good agreement with experimental data. Our results offer production guidelines and enable the systematic optimization of high-performance graphene-based conductor materials. A generalization of the model to any conductor based on two-dimensional materials is straightforward.
We present a theory of local electric polarization in crystalline solids and apply it to study the case of wurtzite group-III nitrides. We show that a local value of the electric polarization, ...evaluated at the atomic sites, can be cast in terms of a summation over nearest-neighbor distances and Born effective charges. Finally, we perform tight-binding super-cell calculations to assess the impact of the local polarization potential arising from alloy fluctuations on the electronic properties of InGaN alloys. In particular, we find that the large upward bowing with composition of the InGaN valence-band edge is strongly influenced by local polarization effects. Furthermore, our analysis allows us to extract composition-dependent bowing parameters for the energy gap and valence-and conduction-band edges.
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