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Abstract Transport phenomena like diffusion, convection, and drift play key roles in the sciences and engineering disciplines. They belong to the most omnipresent and important phenomena in nature that describe the motion of entities such as mass, charge or heat. Understanding and controlling these transport phenomena is crucial for a host of industrial technologies and applications, from cooling nuclear reactors to nanoscale heat‐management in the semiconductor industry. For decades, macroscopic transport techniques have been used to access important parameters such as charge mobilities or thermal conductivities. While being powerful, they often require physical contacts, which can lead to unwanted effects. Over the past years, an exciting solution has emerged: a technique called spatiotemporal microscopy (SPTM) that accesses crucial transport phenomena in a contactless, all‐optical, fashion. This technique offers powerful advantages in terms of accessible timescales, down to femtoseconds, and length scales, down to nanometres, and, further, selectively observes different species of interest. This tutorial review discusses common experimental configurations of SPTM and explains how they can be implemented by those entering the field. This review highlights the broad applicability of SPTM by presenting several exciting examples of transport phenomena that were unravelled thanks to this technique.

Homomorphic Encryption (HE) allows performing specific algebraic computations on encrypted data without the need for decryption. For this reason, HE is emerging as a strong privacy-preserving solution in cloud computing environments since it allows to keep data secure even in the case the cloud server is not trusted. HE libraries such as Microsoft SEAL have been recently released; however, such libraries are not specifically designed for resource-constrained platforms and they are often expensive in terms of computational resources and memory consumption, which limits their usage in edge devices. This limitation is contained by the SEAL-Embedded library, the first C-based HE library specifically designed for embedded platforms. In this article, we propose a hardware accelerator specifically designed for the SEAL-Embedded library and its implementation of the CKKS scheme: the proposed hardware presents a configurable Number Theoretic Transform (NTT) unit for all the polynomial degrees available on the SEAL-Embedded, a memory architecture able to reduce the I/O latency and a dedicated module for the generation of roots of unity. A complete system that includes a 32-bit RISC-V (RI5CY) processor has been implemented on a Xilinx ZCU106 FPGA board to test the functionality of the hardware accelerator and to measure performance improvements. The results showed a speed-up of around x1000 with the hardware acceleration respect to the pure software implementation of the SEAL-Embedded library for the symmetric encryption function.

ObjectiveMechanisms of neurocognitive injury as post-operative sequelae of coronary artery bypass grafting (CABG) are not understood. The systemic inflammatory response to surgical stress causes skeletal muscle impairment, and this is also worsened by immobility. Since evidence supports a link between muscle vitality and neuroprotection, there is a need to understand the mechanisms by which promotion of muscle activity counteracts the deleterious effects of surgery on long-term cognition.MethodsWe performed a clinical trial to test the hypothesis that adding neuromuscular electrical stimulation (NMES) to standard rehabilitation care in post-CABG patients promotes the maintenance of skeletal muscle strength and the expression of circulating neuroprotective myokines.ResultsWe did not find higher serum levels of neuroprotective myokines, except for interleukin-6, nor better long-term cognitive performance in our intervention group. However, a greater increase in functional connectivity at brain magnetic resonance was seen between seed regions within the default mode, frontoparietal, salience, and sensorimotor networks in the NMES group. Regardless of the treatment protocol, patients with a Klotho increase 3 months after hospital discharge compared to baseline Klotho values showed better scores in delayed memory tests.SignificanceWe confirm the potential neuroprotective effect of Klotho in a clinical setting and for the first time post-CABG.

Multicolor fluorescence imaging is an excellent method for the simultaneous visualization of multiple structures, although it is limited by the available spectral window. More labels can be measured by distinguishing these on properties, such as their fluorescence dynamics, but usually these dynamics must be directly resolvable by the instrument. We propose an approach to distinguish emitters over a much broader range of light-induced dynamics by combining fast modulation of the light source with the detection of the time-integrated fluorescence. We demonstrate our method by distinguishing four spectrally overlapping photochromic fluorophores within Escherichia coli bacteria, showing that we can accurately classify all four probes by acquiring just two to four fluorescence images. Our strategy expands the range of probes and processes that can be used for fluorescence multiplexing.

Neuromuscular diseases (NMDs) are a group of often severely disabling disorders characterized by dysfunction in one of the main constituents of the motor unit, the cardinal anatomic-functional structure behind force and movement production. Irrespective of the different pathogenic mechanisms specifically underlying these disease conditions genetically determined or acquired, and the related molecular pathways involved in doing that, oxidative stress has often been shown to play a relevant role within the chain of events that induce or at least modulate the clinical manifestations of these disorders. Due to such a putative relevance of the imbalance of redox status occurring in contractile machinery and/or its neural drive in NMDs, physical exercise appears as one of the most important conditions able to positively interfere along an ideal axis, going from a deranged metabolic cell homeostasis in motor unit components to the reduced motor performance profile exhibited by the patient in everyday life. If so, it comes out that it would be important to identify a proper training program, suitable for load and type of exercise that is able to improve motor performance in adaptation and response to such a homeostatic imbalance. This review therefore analyzes the role of different exercise trainings on oxidative stress mechanisms, both in healthy and in NMDs, also including preclinical studies, to elucidate at which extent these can be useful to counteract muscle impairment associated to the disease, with the final aim of improving physical functions and quality of life of NMD patients.

Facial mimicry is described by embodied cognition theories as a human mirror system-based neural mechanism underpinning emotion recognition. This could play a critical role in the Self-Mirroring Technique (SMT), a method used in psychotherapy to foster patients’ emotion recognition by showing them a video of their own face recorded during an emotionally salient moment. However, dissociation in facial mimicry during the perception of own and others’ emotions has not been investigated so far. In the present study, we measured electromyographic (EMG) activity from three facial muscles, namely, the zygomaticus major (ZM), the corrugator supercilii (CS), and the levator labii superioris (LLS) while participants were presented with video clips depicting their own face or other unknown faces expressing anger, happiness, sadness, disgust, fear, or a neutral emotion. The results showed that processing self vs. other expressions differently modulated emotion perception at the explicit and implicit muscular levels. Participants were significantly less accurate in recognizing their own vs. others’ neutral expressions and rated fearful, disgusted, and neutral expressions as more arousing in the self condition than in the other condition. Even facial EMG evidenced different activations for self vs. other facial expressions. Increased activation of the ZM muscle was found in the self condition compared to the other condition for anger and disgust. Activation of the CS muscle was lower for self than for others’ expressions during processing a happy, sad, fearful, or neutral emotion. Finally, the LLS muscle showed increased activation in the self condition compared to the other condition for sad and fearful expressions but increased activation in the other condition compared to the self condition for happy and neutral expressions. Taken together, our complex pattern of results suggests a dissociation at both the explicit and implicit levels in emotional processing of self vs. other emotions that, in the light of the Emotion in Context view, suggests that STM effectiveness is primarily due to a contextual–interpretative process that occurs before that facial mimicry takes place.

The role of distinct cortical regions in guiding social orienting needs further investigation. Our aim was to explore the contribution of the frontal eye field (FEF) in early orienting of attention towards stimuli with social value. We used a TMS-EEG approach to investigate event related potentials (ERPs; no-TMS block) and TMS evoked potentials (TEPs; TMS block) during the cueing phase of a modified version of the dot-probe task, comparing competing (face vs. house) and not competing (house vs. house) conditions. Our results revealed an increased amplitude of ERP components in the competing condition, showing greater posterior N170 and fronto-central vertex positive potential (VPP) and an enhanced frontal negative component at 250–270 ms from cue onset. TMS pulses over the FEF induced similar N170 and VPP amplified components. In addition, in the ERPs, a reduced positivity at 400 ms was shown when the face appeared on the left side vs. the right side of space. In contrast, in the TMS blocks, we found lateralized effects on N170 depending on the side of face presentation. The enhanced cortical excitability induced by TMS over the right FEF significantly correlated with the performance on the behavioral task, suggesting a link between the FEF activity during the cueing phase of the dot-probe task and the subsequent behavioral response times to the targets.

Selective visual attention is a primary cognitive function, which allows the selection of the most relevant stimuli in the environment by prioritizing their processing. Several studies showed that this process can be influenced by both social signals, such as gaze direction (i.e., the Gaze Cueing Effect, GCE) and by the motivational valence of gratifying stimuli, such as monetary rewards. The aim of this study was to explore whether GCE could be modulated by a monetary reward. To this end, we created an experiment in which participants performed a gaze cuing task before and after an implicit learning task aiming to induce an association between gaze direction and monetary reward (experimental condition), or after a perceptual task (control condition). Statistical analyses were conducted following both a frequentist and a Bayesian approach. Results supported previous findings showing the presence of the GCE, i.e., faster responses in congruent trials when the target appeared in the gazed-at location. Interestingly, our results did not reveal significant differences among the conditions. Therefore, contrary to what was reported by previous attentional orienting studies with non-social stimuli, monetary reward does not seem to be able to modulate (or interfere with) the orienting of attention mediated by gaze direction as measured by the GCE. Taken together our results suggest that social signals such as gaze direction have a greater impact than monetary reward in orienting selective attention.

It is well established that off-line sentence judgment tasks (oSJTs) typically rely on phonological working memory (WM), beyond specific linguistic processing. Nevertheless, empirical findings suggest that a juvenile level of performance in an oSJT could be associated with the recruitment of age-specific additional supportive neural network in healthy aging. In particular, in one of our previous study, healthy elderlies showed the additional activation of associative visual cortices when compared with young controls. We suggested that age-related hyperactivations, during an auditory sentence judgment task, might represent the neurofunctional correlate of the recruitment of compensatory strategies that are necessary to maintain a juvenile level of performance. To explicitly test this hypothesis we adopted repetitive transcranial magnetic stimulation (rTMS). Twelve healthy elderlies and 12 young participants were engaged in an off-line semantic plausibility judgment task while rTMS was delivered over: (1) the left inferior frontal gyrus (LIFG; i.e., a core region of the WM network); (2) the precuneus; and (3) a Control Site (vertex). Results showed a significant main effect of Stimulation Site and a significant Group-by-Stimulation Site interaction effect. In particular, the rTMS stimulation of the LIFG slowed down reaction times (RTs) both in young and healthy elderly participants, while only healthy elderlies showed an increment of RTs during the stimulation of the precuneus. Taken together our results further support the idea that the maintenance of a juvenile level of performance in graceful aging may be associated with task-specific compensatory processes that would manifest them-selves, from the neurofunctional point of view, by the recruitment of additional neural supportive regions.

When making decisions, people are typically differently sensitive to gains and losses according to the motivational context in which the choice is performed. As hypothesized by Regulatory Focus Theory (RFT), indeed, goals are supposed to change in relation to the set of possible outcomes. In particular, in a promotion context, the goal is achieving the maximal gain, whereas in a prevention context it turns into avoiding the greatest loss. We explored the neurophysiological counterpart of this phenomenon, by applying Transcranial Magnetic Stimulation (TMS) and recording the motor evoked potentials (MEPs) in participants taking part in an economic game, in which they observed actions conveying different goal attainment levels, framed in different motivational contexts. More than the actual value of the economic exchange involved in the game, what affected motor cortex excitability was the goal attainment failure, corresponding to not achieving the maximal payoff in a promotion context and not avoiding the greatest snatch in a prevention context. Therefore, the results provide support for the key predictions of RFT, identifying a neural signature for the goal attainment failure.

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1–42 (Aβ1–42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies. Herein, a small cohort (N = 28) of patients affected by Parkinson’s disease (PD) and age-matched controls were enrolled to detect the content of α-syn (total and oligomeric), Aβ1–42 and tau (total and phosphorylated) in RBCs. Moreover, the presence of α-syn association with tau and Aβ1–42 was explored by co-immunoprecipitation/western blotting in the same cells, and quantitatively confirmed by immunoenzymatic assays. For the first time, PD patients were demonstrated to exhibit α-syn heterocomplexes with Aβ1–42 and tau in peripheral tissues; interestingly, α-syn-Aβ1–42 concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-α-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-α-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-α-syn, phosphorylated-tau and α-syn-Aβ1–42 concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest α-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD.

The loss of protein homeostasis that has been associated with aging leads to altered levels and conformational instability of proteins, which tend to form toxic aggregates. In particular, brain aging presents characteristic patterns of misfolded oligomers, primarily constituted of β-amyloid (Aβ), tau, and α-synuclein (α-syn), which can accumulate in neuronal membranes or extracellular compartments. Such aging-related proteins can also reach peripheral compartments, thus suggesting the possibility to monitor their accumulation in more accessible fluids. In this respect, we have demonstrated that α-syn forms detectable hetero-aggregates with Aβ or tau in red blood cells (RBCs) of healthy subjects. In particular, α-syn levels and its heteromeric interactions are modulated by plasma antioxidant capability (AOC), which increases in turn with physical activity. In order to understand if a specific distribution of misfolded proteins can occur in other blood cells, a cohort of human subjects was enrolled to establish a correlation among AOC, the level of physical exercise and the concentrations of aging-related proteins in platelets. The healthy subjects were divided depending on their level of physical exercise (i.e., athletes and sedentary subjects) and their age (young and older subjects). Herein, aging-related proteins (i.e., α-syn, tau and Aβ) were confirmed to be present in human platelets. Among such proteins, platelet tau concentration was demonstrated to decrease in athletes, while α-syn and Aβ did not correlate with physical exercise. For the first time, α-syn was shown to directly interact with Aβ and tau in platelets, forming detectable hetero-complexes. Interestingly, α-syn interaction with tau was inversely related to plasma AOC and to the level of physical activity. These results suggested that α-syn heterocomplexes, particularly with tau, could represent novel indicators to monitor aging-related proteins in platelets.

The pathophysiological mechanisms of migraine transformation are debated. Modifications of plasma oxidative stress biomarkers have been described in chronic migraine. OnabotulintoxinA (BoNT/A) treatment, approved for chronic migraine prophylaxis, possibly reduces pain neurotransmitters release and oxidative stress products. Aims of our study were to investigate differences in the levels of selected plasmatic oxidative stress biomarkers (Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), Thiolic Groups (SH)) comparing chronic migraineurs (CM) and healthy controls (HC). We also explored possible clinical and biochemical modifications in the CM group after six months of treatment with BoNT/A. At the baseline, we found higher values of AOPP (p < 0.001), and lower values of SH (p < 0.001) and FRAP (p = 0.005) in the CM group. At the six-month follow-up we found a reduction of AOPP (p < 0.001) and an increase of FRAP (p < 0.001) and SH (p = 0.023) within the CM group. BoNT/A treatment improved migraine symptoms in the CM group. We confirmed previous reports of imbalanced antioxidant mechanisms in chronic migraine showing lower antioxidant capacities in patients than controls. BoNT/A improved the levels of plasma oxidative stress biomarkers and confirmed its role as an effective prophylactic treatment for CM. Other studies should investigate the potential antioxidant properties of BoNT/A treatment.