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Abstract Optical microscopy techniques are a popular choice for visualizing micro-agents. They generate images with relatively high spatiotemporal resolution but do not reveal encoded information for distinguishing micro-agents and surroundings. This study presents multicolor fluorescence microscopy for rendering color-coded identification of mobile micro-agents and dynamic surroundings by spectral unmixing. We report multicolor microscopy performance by visualizing the attachment of single and cluster micro-agents to cancer spheroids formed with HeLa cells as a proof-of-concept for targeted drug delivery demonstration. A microfluidic chip is developed to immobilize a single spheroid for the attachment, provide a stable environment for multicolor microscopy, and create a 3D tumor model. In order to confirm that multicolor microscopy is able to visualize micro-agents in vascularized environments, in vitro vasculature network formed with endothelial cells and ex ovo chicken chorioallantoic membrane are employed as experimental models. Full visualization of our models is achieved by sequential excitation of the fluorophores in a round-robin manner and synchronous individual image acquisition from three-different spectrum bands. We experimentally demonstrate that multicolor microscopy spectrally decomposes micro-agents, organic bodies (cancer spheroids and vasculatures), and surrounding media utilizing fluorophores with well-separated spectrum characteristics and allows image acquisition with 1280 $$\times$$ × 1024 pixels up to 15 frames per second. Our results display that real-time multicolor microscopy provides increased understanding by color-coded visualization regarding the tracking of micro-agents, morphology of organic bodies, and clear distinction of surrounding media.

Given the dynamic nature of engineered vascular networks within biofabricated tissue analogues, it is instrumental to have control over the constantly evolving biochemical cues within synthetic matrices throughout tissue remodeling. Incorporation of pro-angiogenic vascular endothelial growth factor (VEGF165) specific aptamers into cell-instructive polymer networks is shown to be pivotal for spatiotemporally controlling the local bioactivity of VEGF that selectively elicit specific cell responses. To harness this effect and quantitatively unravel its spatial resolution, herein, bicomponent micropatterns consisting of VEGF165 specific aptamer-functionalized gelatin methacryloyl (GelMA) (aptamer regions) overlaid with pristine GelMA regions using visible-light photoinitiators (Ru/SPS) were fabricated via two-step photopatterning approach. For the 3D co-culture study, human umbilical vein-derived endothelial cells and mesenchymal stromal cells were used as model cell types. Bicomponent micropatterns with spatially defined spacings (300/500/800 ​μm) displayed high aptamer retention, aptamer-fluorescent complementary sequence (CSF) molecular recognition and VEGF sequestration localized within patterned aptamer regions. Stiffness gradient at the interface of aptamer and GelMA regions was observed with high modulus in aptamer region followed by low stiffness GelMA regions. Leveraging aptamer-tethered VEGF's dynamic affinity interactions with CS that upon hybridization facilitates triggered VEGF release, co-culture studies revealed unique characteristics of aptamer-tethered VEGF to form spatially defined luminal vascular networks covered with filopodia-like structures in vitro (spatial control) and highlights their ability to control network properties including orientation over time using CS as an external trigger (temporal control). Moreover, the comparison of single and double exposed regions within micropatterns revealed differences in cell behavior among both regions. Specifically, the localized aptamer-tethered VEGF within single exposed aptamer regions exhibited higher cellular alignment within the micropatterns till d5 of culture. Taken together, this study highlights the potential of photopatterned aptamer-tethered VEGF to spatiotemporally regulate vascular morphogenesis as a tool for controlling vascular remodeling in situ.

Multicolor fluorescence microscopy is a powerful technique to fully visualize many biological phenomena by acquiring images from different spectrum channels. This study expands the scope of multicolor fluorescence microscopy by serial imaging of polystyrene micro-beads as surrogates for drug carriers, cancer spheroids formed using HeLa cells, and microfluidic channels. Three fluorophores with different spectral characteristics are utilized to perform multicolor microscopy. According to the spectrum analysis of the fluorophores, a multicolor widefield fluorescence microscope is developed. Spectral crosstalk is corrected by exciting the fluorophores in a round-robin manner and synchronous emitted light collection. To report the performance of the multicolor microscopy, a simplified 3D tumor model is created by placing beads and spheroids inside a channel filled with the cell culture medium is imaged at varying exposure times. As a representative case and a method for bio-hybrid drug carrier fabrication, a spheroid surface is coated with beads in a channel utilizing electrostatic forces under the guidance of multicolor microscopy. Our experiments show that multicolor fluorescence microscopy enables crosstalk-free and spectrally-different individual image acquisition of beads, spheroids, and channels with the minimum exposure time of 5.5 ms. The imaging technique has the potential to monitor drug carrier transportation to cancer cells in real-time.

Abstract The high-cost pressure caused by the level of competition poses major challenges for breweries. While microbreweries can develop local strengths and brewery groups develop synergies, this does not represent a decisive improvement. The application of machine learning, on the other hand, could give breweries a significant advantage in their brewing process. Several approaches to the application of machine learning in the brewing process have already been proposed in the literature. To guide possible areas of applications and the respective available solution approaches to improve the brewing process based on machine learning, a systematic review of the application of machine learning in the brewing process is presented in this paper. In this systematic review, all potentially relevant publications were included at first. Subsequently, irrelative publications were filtered out by using a clustering approach. Afterward, the remaining 21 publications were analyzed and synthesized. Based on a developed framework considering the brewing process steps, areas of improvement, machine learning tasks, and machine learning algorithms, these publications were classified. Upon the classification, a descriptive analysis was performed to identify common approaches in the existing literature. One result was that research on artificial intelligence in brewing lags significantly behind the general trend of artificial intelligence research. Additionally, there is very limited research into the association between the recipe and the desired chemical properties of the beer. Furthermore, it was noticeable that machine learning tasks utilizing artificial neural networks or support vector machines were preferred over others.

By applying machine learning algorithms, predictive business process monitoring (PBPM) techniques provide an opportunity to counteract undesired outcomes of processes. An especially complex variation of business processes is the engineering change (EC) process. Here, failing to adhere to planned implementation dates can have severe impacts on assembly lines, and it is paramount that potential negative cases are identified as early as possible. Current PBPM research, however, has seldomly investigated the predictive performance of machine learning approaches and their applicability at early process steps, let alone for the EC process. In our research, we show that given adequate feature encoding, shallow learners can accurately predict schedule adherence after process initialisation. Based on EC data from an automotive manufacturer, we provide a case sensitive performance overview on algorithm-encoding combinations. For that, three algorithms (XGBoost, Random Forest, LSTM) were combined with four encoding techniques. The encoding techniques used were the two common aggregation-based and index-based last state encoding, and two new combinations of these, which we term advanced aggregation-based and complex aggregation-based encoding. The study indicates that XGBoost-index-encoded approaches outclass regarding average predictive performance, whereas Random-Forest-aggregation-encoded approaches perform better regarding temporal stability due to reduced influence by dynamic features. Our research provides a case-based reasoning approach for deciding on which algorithm-encoding combination and evaluation metrics to apply. In doing so, we provide a blueprint for an early warning and monitoring method within the EC process and other similarly complex processes.

Background: Supply chain optimisation is critical for companies in today’s globalised world. Efficient supply chains ensure product quality and freshness in the food industry. For products like beer, efficiency extends beyond transportation and includes the management of logistics containers such as returnable kegs. Objectives: This study investigated the impact of tracking logistics data on the efficiency of container logistics in a small regional brewery. The focus was reducing fleet size, processing times and pick-up distances. Method: A simulation of a small brewery was used to analyse the impact of tracking logistics data. The study examined how kegs equipped with real-time tracking technology could improve logistics operations. Results: The simulation showed that tracking logistics data significantly improved logistics processes. It led to a reduction in the fleet size, turnaround times and pick-up distances for empty kegs. These improvements were attributed to better resource allocation and more efficient management of reusable containers. Conclusion: The study showed that smart kegs could reduce logistical inefficiencies in the brewing industry. The use of smart technologies in container logistics improves operational efficiency and sustainability. Contribution: This research provides insights into how smart technologies can transform traditional logistics models. The results suggest that smart containers can revolutionise supply chains with efficient resource allocation, real-time tracking and automation. This shift towards smart logistics aligns with the broader adoption of the Industrial Internet of Things, offering a blueprint for future innovations in supply chain management. The implications extend beyond brewing, highlighting the potential for greater sustainability and a positive reduction in environmental impact in global supply chains.

For a wide range of applications, a fast, non-destructive, remote, and sensitive identification of samples with predefined characteristics is preferred instead of their full characterization. In this work, we report on the experimental implementation of a nonlocal quantum measurement scheme, which allows for differentiation among samples out of a predefined set of transparent and birefringent objects in a distant optical channel. The measurement is enabled by application of polarization-entangled photon pairs and is based on remote state preparation. On an example set of more than 80 objects characterized by different Mueller matrices, we show that only two coincidence measurements are already sufficient for successful discrimination. The number of measurements needed for sample differentiation is significantly decreased compared to a comprehensive polarimetric analysis. Our results demonstrate the potential of this polarization detection method for polarimetric applications in biomedical diagnostics, remote sensing, and other classification/detection tasks.

Abstract Information exchange between two distant parties, where information is shared without physically transporting it, is a crucial resource in future quantum networks. Doing so with high-dimensional states offers the promise of higher information capacity and improved resilience to noise, but progress to date has been limited. Here we demonstrate how a nonlinear parametric process allows for arbitrary high-dimensional state projections in the spatial degree of freedom, where a strong coherent field enhances the probability of the process. This allows us to experimentally realise quantum transport of high-dimensional spatial information facilitated by a quantum channel with a single entangled pair and a nonlinear spatial mode detector. Using sum frequency generation we upconvert one of the photons from an entangled pair resulting in high-dimensional spatial information transported to the other. We realise a d = 15 quantum channel for arbitrary photonic spatial modes which we demonstrate by faithfully transferring information encoded into orbital angular momentum, Hermite-Gaussian and arbitrary spatial mode superpositions, without requiring knowledge of the state to be sent. Our demonstration merges the nascent fields of nonlinear control of structured light with quantum processes, offering a new approach to harnessing high-dimensional quantum states, and may be extended to other degrees of freedom too.

Abstract Quantum communication has seen rapid progress towards practical large-scale networks, with quantum key distribution (QKD) spearheading this development. While fibre-based systems have been shown to be well suited for metropolitan scales, suitable fibre infrastructure may not always be in place. Here, we make the case for an entanglement-based free-space quantum network as a practical and efficient alternative for metropolitan applications. We developed a deployable free-space QKD system and demonstrated its use in realistic scenarios. For a representative 1.7-km free-space link, we showcase its ad hoc deployability and achieve secure key rates of up to 5.7 kbps, with 2.5 kbps in direct noon sunlight. By extrapolating experimental data, we show that kbps key rates are achievable even for 10-km distances and multi-user scenarios. We anticipate that our work will establish free-space networks as a viable solution for metropolitan applications and an indispensable complementary building block in the future global quantum internet.

In the era of (re)legalisation of medicinal and recreational cannabis, accidental and intentional exposure to edibles, cannabis-infused food products, has increased substantially. However, there is particular concern regarding younger age groups. Most concerning is the increase in hospitalisations. According to a study by Myran et al. (1), provinces in Canada, where the sale of edibles is permitted, saw an increase in paediatric poisonings due to unintentional consumption of edibles. Similar trends have been observed in “legalised states” in the US, such as Colorado (2). The impact of using cannabis at an early age, but particularly the impact of accidental exposure to high THC quantities, may have negative mental or physical health outcomes. Whilst regulatory restrictions vary significantly from one legalised region to another, it is difficult to identify a best practice. The aim of this study is to identify and discuss new and existing risk mitigation strategies to give guidance to policymakers. Furthermore, practical aspects, such as compliance (e.g. audits by authorities), are discussed. It is noted that edibles have been around much longer than recent political attempts to regulate them.

Frequency shift chirp modulation (FSCM) is the modulation technique utilized by the LoRa physical layer, a widely used and relatively new communication technique for radio low-power wide area networks (LPWANs). In this paper, we adapt and implement FSCM for low-power acoustic underwater communication. Opposed to over-water communication based on the electromagnetic wave, the acoustic wave in water travels much slower. Consequently, acoustic underwater communication is more sensitive to motion-based Doppler shifts. For resilient acoustic underwater communication, Doppler tracking and removal is mandatory. In this paper, we mathematically derive the effect of Doppler shifts to FSCM symbols. Afterwards, we describe a novel algorithm for a low-power receiver to track Doppler shifts without modification of the transmitted packet. Finally, we evaluate and compare our algorithm to another Doppler estimation algorithm from literature and study the effect on the bit error rate (BER). We show, that our algorithm can improve with little additional computational overhead the BER by a factor of more than 104 in some cases.

Although Machine Learning (ML) in supply chain management (SCM) has become a popular topic, predictive uses of ML in SCM remain an understudied area. A specific area that needs further attention is the prediction of late deliveries by suppliers. Recent approaches showed promising results but remained limited in their use of classification algorithms and struggled with the curse of dimensionality, making them less applicable to low-volume-high-variety production settings. In this paper, we show that a prediction model using a regression algorithm is capable to predict the severity of late deliveries of suppliers in a representative case study of a low-volume-high-variety machinery manufacturer. Here, a detailed understanding of the manufacturer’s procurement process is built, relevant features are identified, and different ML algorithms are compared. In detail, our approach provides three key contributions: First, we develop an ML-based regression model predicting the severity of late deliveries by suppliers. Second, we demonstrate that prediction within the earlier phases of the purchasing process is possible. Third, we show that there is no need to reduce the dimensionality of high-dimensional input features. Nevertheless, our approach has scope for improvement. The inclusion of information such as component identifiers may improve the prediction quality.

Abstract High-dimensional quantum entanglement is currently one of the most prolific fields in quantum information processing due to its high information capacity and error resilience. A versatile method for harnessing high-dimensional entanglement has long been hailed as an absolute necessity in the exploration of quantum science and technologies. Here we exploit Hong-Ou-Mandel interference to manipulate discrete frequency entanglement in arbitrary-dimensional Hilbert space. The generation and characterization of two-, four- and six-dimensional frequency entangled qudits are theoretically and experimentally investigated, allowing for the estimation of entanglement dimensionality in the whole state space. Additionally, our strategy can be generalized to engineer higher-dimensional entanglement in other photonic degrees of freedom. Our results may provide a more comprehensive understanding of frequency shaping and interference phenomena, and pave the way to more complex high-dimensional quantum information processing protocols.

Navigation in ever-changing environments requires effective motor behaviors. Many insects have developed adaptive movement patterns which increase their success in achieving navigational goals. A conserved brain area in the insect brain, the Lateral Accessory Lobe, is involved in generating small scale search movements which increase the efficacy of sensory sampling. When the reliability of an essential navigational stimulus is low, searching movements are initiated whereas if the stimulus reliability is high, a targeted steering response is elicited. Thus, the network mediates an adaptive switching between motor patterns. We developed Spiking Neural Network models to explore how an insect inspired architecture could generate adaptive movements in relation to changing sensory inputs. The models are able to generate a variety of adaptive movement patterns, the majority of which are of the zig-zagging kind, as seen in a variety of insects. Furthermore, these networks are robust to noise. Because a large spread of network parameters lead to the correct movement dynamics, we conclude that the investigated network architecture is inherently well-suited to generating adaptive movement patterns.

Abstract Transcranial direct current stimulation (tDCS) is a promising tool to enhance cognitive performance. However, its effectiveness has not yet been unequivocally shown. Thus, here we tested whether coupling tDCS with a bout of aerobic exercise (AE) is more effective in modulating cognitive functions than tDCS or AE alone. One hundred twenty-two healthy participants were assigned to five randomized controlled crossover experiments. Two multimodal target experiments (EXP-4: anodal vs. sham tDCS during AE; EXP-5: cathodal vs. sham tDCS during AE) investigated whether anodal (a-tDCS) or cathodal tDCS (c-tDCS) applied during AE over the left dorsolateral prefrontal cortex (left DLPFC) affects executive functioning (inhibition ability). In three unimodal control experiments, the participants were either stimulated (EXP-1: anodal vs. sham tDCS, EXP-2: cathodal vs. sham tDCS) or did AE (EXP-3: AE vs. active control). Participants performed an Eriksen flanker task during ergometer cycling at moderate intensity (in EXP. 3-5). Only c-tDCS during AE had a significant adverse effect on the inhibition task, with decreased accuracy. This outcome provides preliminary evidence that c-tDCS during AE over the left DLPFC might effectively modulate inhibition performance compared to c-tDCS alone. However, more systematic research is needed in the future.

For manufacturing companies, especially for machine and plant manufacturers, the assembly of products in time has an essential impact on meeting delivery dates. Often missing individual components lead to a delayed assembly start, hereinafter referred to as assembly start delayers. Identifying the assembly start delayers early in the production process can help to set countermeasures to meet the required delivery dates. In order to achieve this, we set up 24 prediction models on four different levels of detail utilizing different machine learning-algorithms – six prediction models on every level of detail – and applying a case-based research approach in order to identify the model with the highest model quality. The modeling approach on the four levels of detail is different. The models on the coarsest level of detail predict assembly start delayers utilizing a classification approach. The models on the three finer levels of detail predict assembly start delayers via a regression of different lead times and subsequent postprocessing operations to identify the assembly start delayers. After training of the 24 prediction models based on a real data set of a machine and plant manufacturer and evaluating their model quality, the classification model utilizing a Gradient Boosting classifier showed best results. Thus, performing a binary classification to identify assembly start delayers was the best modelling approach. With the achieved results, our study is a first approach to predict assembly start delayers and gives insights in the performance of different modeling approaches in the area of a production planning and control.

Abstract Quantum key distribution (QKD) is a pioneering quantum technology on the brink of widespread deployment. Nevertheless, the distribution of secret keys beyond a few 100 km at practical rates remains a major challenge. One approach to circumvent lossy terrestrial transmission of entangled photon pairs is the deployment of optical satellite links. Optimizing these non-static quantum links to yield the highest possible key rate is essential for their successful operation. We therefore developed a high-brightness polarization-entangled photon pair source and a receiver module with a fast steering mirror capable of satellite tracking. We employed this state-of-the-art hardware to distribute photons over a terrestrial free-space link with a distance of 143 km, and extracted secure key rates up to 300 bits per second. Contrary to fiber-based links, the channel loss in satellite downlinks is time-varying and the link time is limited to a few minutes. We therefore propose a model-based optimization of link parameters based on current channel and receiver conditions. This model and our field test will prove helpful in the design and operation of future satellite missions and advance the distribution of secret keys at high rates on a global scale.

The interest of manufacturing companies in a sufficient prediction of lead times is continuously increasing - especially in engineer to order environments with typically a large number of individual parts and complex production processes. A multitude of approaches have been proposed in the literature for predicting lead times considering different data and methods or algorithms from operations research (OR) and machine learning (ML). In order to provide guidance at setting up prediction models and developing new approaches, a systematic review of the available approaches for predicting lead times is presented in this paper. Forty-two publications were analyzed and synthetized: Based on a developed framework considering the used data class (e.g. product data or system status), the data origin (master data or real data) and the used method and algorithm from OR and ML, the publications are classified. Based on the classification, a descriptive analysis is performed to identify common approaches in the existing literature as well as implications for further research. One result is, that mostly order data and the status of the production system are used for predicting lead times whereas material data are used seldom. Additionally, ML approaches primarily use artificial neural networks and regression models for predicting lead times, while OR approaches use mainly combinatorial optimization or heuristics. Furthermore, with increasing model complexity the use of real data decreased. Thus, we identified as an implication for further research to set up a complex data model considering material data, which uses real data as data origin.

In the original publication [...]

Traditionally, underwater acoustic modems and positioning systems were developed for military and Oil & Gas industries, that require deep water deployments and extremely reliable systems, focusing on high power expensive systems and leaving the use of low-cost devices only attractive for academic studies. Conversely, recent developments of low-cost unmanned vehicles, such as remotely operated vehicles (ROVs) and autonomous underwater vehicles (AUVs), suitable for shallow water coastal missions, and the need of sensors network deployments for measuring water quality and studying the effect of climate change in coastal areas, called to the need of low-cost and low-power acoustic modems and positioning systems that are gaining more and more momentum to date. The use of these devices can enable a wide set of applications, often based on low-cost AUV swarm formations, where an acoustic link between the vehicles is required to coordinate the mission, perform the maneuvers, and maintain the formation along the time. Moreover, they can make environmental wireless sensor deployment cost effective by substituting wired systems. Underwater positioning systems, usually used in large-scale operations, can be finally applied to small-scale application thanks to the reduction in costs, at the price of a lower transmission and positioning range and precision. While in open-sea application this performance reduction is a huge limitation, in river, lagoon, port and lake deployments this is not an issue, given that the extremely shallow water and the presence of many obstacles would deteriorate the acoustic signal anyway, not allowing long range transmissions even with expensive and sophisticated acoustic devices. In this paper, we review the recent developments of low-cost and low-power acoustic communication and positioning systems, both analyzing University prototypes and new commercial devices available in the market, identifying advantages and limitations of these devices, and we describe potential new applications that can be enabled by these systems.

Abstract Background Gait disorders are major symptoms of neurological diseases affecting the quality of life. Interventions that restore walking and allow patients to maintain safe and independent mobility are essential. Robot-assisted gait training (RAGT) proved to be a promising treatment for restoring and improving the ability to walk. Due to heterogenuous study designs and fragmentary knowlegde about the neural correlates associated with RAGT and the relation to motor recovery, guidelines for an individually optimized therapy can hardly be derived. To optimize robotic rehabilitation, it is crucial to understand how robotic assistance affect locomotor control and its underlying brain activity. Thus, this study aimed to investigate the effects of robotic assistance (RA) during treadmill walking (TW) on cortical activity and the relationship between RA-related changes of cortical activity and biomechanical gait characteristics. Methods Twelve healthy, right-handed volunteers (9 females; M = 25 ± 4 years) performed unassisted walking (UAW) and robot-assisted walking (RAW) trials on a treadmill, at 2.8 km/h, in a randomized, within-subject design. Ground reaction forces (GRFs) provided information regarding the individual gait patterns, while brain activity was examined by measuring cerebral hemodynamic changes in brain regions associated with the cortical locomotor network, including the sensorimotor cortex (SMC), premotor cortex (PMC) and supplementary motor area (SMA), using functional near-infrared spectroscopy (fNIRS). Results A statistically significant increase in brain activity was observed in the SMC compared with the PMC and SMA (p

Abstract Backround Several studies have demonstrated a direct correlation between lymph node yield and survival after colectomy for cancer. Complete mesocolic excision (CME) in right colectomy (RC) reduces local recurrence but is technically demanding. Here we report our early single center experience with robotic right colectomy comparing our standardized bottom-to-up (BTU) approach of robotic RC with CME and central vessel ligation (CVL) facilitated by a suprapubic access with the “classical” medial-to-lateral (MTL) strategy. Methods A 4-step BTU approach of robotic RC guided by embryonal planes in the process of retrocolic mobilization with suprapubic port placement was performed in the BTU-group (n = 24; all with intention to treat cancer). In step 1 CME was initiated with caudolateral mobilization of the right colon guided by the fascia of Toldt across the duodenum and up to the Trunk of Henle. Subsequently, dissection was performed BTU right of the middle supramesenteric vessels with central ileocolic vessel ligation in step 2. Subsequent to separation of the transverse retromesenteric space and completion of mobilization the hepatic flexure in step 3, the transverse mesocolon was then transected right of the middle colic vessels in step 4. An extracorporeal side to side anastomosis was performed. We compared the outcome of the BTU-group with a MTL-group (n = 7). Results Patient characteristics like age, gender, BMI, comorbidity (ASA) and M-status were comparable among groups. There was no conversion. Overall complication rate was 35.5%. We experienced no anastomoses insufficiency, grade Dindo/Clavien III/IV complication or mortality in this study. Type I and II complications and surgical characteristics incl. OR-time, ICU- and hospital-stay were comparable between the two groups. However, the lymph node yield was superior in the BTU-group (mean 40.2 ± 17.1) when compared with the MTL-group (16,3 nodes ±8.5; p

Downlink precoding is considered for multi-path multi-input single-output channels where the base station uses orthogonal frequency-division multiplexing and low-resolution signaling. A quantized coordinate minimization (QCM) algorithm is proposed and its performance is compared to other precoding algorithms including squared infinity-norm relaxation (SQUID), multi-antenna greedy iterative quantization (MAGIQ), and maximum safety margin precoding. MAGIQ and QCM achieve the highest information rates and QCM has the lowest complexity measured in the number of multiplications. The information rates are computed for pilot-aided channel estimation and data-aided channel estimation. Bit error rates for a 5G low-density parity-check code confirm the information-theoretic calculations. Simulations with imperfect channel knowledge at the transmitter show that the performance of QCM and SQUID degrades in a similar fashion as zero-forcing precoding with high resolution quantizers.

Motor control is associated with suppression of oscillatory activity in alpha (8–12 Hz) and beta (12–30 Hz) ranges and elevation of oxygenated hemoglobin levels in motor-cortical areas. Aging leads to changes in oscillatory and hemodynamic brain activity and impairments in motor control. However, the relationship between age-related changes in motor control and brain activity is not yet fully understood. Therefore, this study aimed to investigate age-related and task-complexity-related changes in grip force control and the underlying oscillatory and hemodynamic activity. Sixteen younger [age (mean ± SD) = 25.4 ± 1.9, 20–30 years] and 16 older (age = 56.7 ± 4.7, 50–70 years) healthy men were asked to use a power grip to perform six trials each of easy and complex force tracking tasks (FTTs) with their right dominant hand in a randomized within-subject design. Grip force control was assessed using a sensor-based device. Brain activity in premotor and primary motor areas of both hemispheres was assessed by electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Older adults showed significantly higher inaccuracies and higher hemodynamic activity in both FTTs than did young adults. Correlations between grip force control owing to task complexity and beta activity were different in the contralateral premotor cortex (PMC) between younger and older adults. Collectively, these findings suggest that aging leads to impairment of grip force control and an increase in hemodynamic activity independent of task complexity. EEG beta oscillations may represent a task-specific neurophysiological marker for age-related decline in complex grip force control and its underlying compensation strategies. Further EEG-fNIRS studies are necessary to determine neurophysiological markers of dysfunctions underlying age-related motor disabilities for the improvement of individual diagnosis and therapeutic approaches.

The quantum phase noise in a pulsed semiconductor laser is studied thoroughly in the context of its utilization as a quantum entropy source in a quantum random number generator (QRNG) device. We performed a numerical analysis of the phase diffusion process for a semiconductor laser in the continuous-wave operation mode and gain-switched (GS) mode. The result demonstrates the amplification of randomness in the GS mode, which is gauged physically by the variance VarΔϕ. The variance value, which is mathematically related to the temporal distance between the laser pulses used in the experimental setup, also determines the stability of the setup. Furthermore, we show how the QRNG probability distribution is influenced by several experimental factors such as the quality of the interference process and the noise in the detection system.

Abstract Background Adenomatoid tumor is one of the most common histological subtypes of paratesticular cancer arising from the epididymis. In very rare cases, these tumors appear as intratesticular lesions originating in the tunica albuginea, representing a diagnostic challenge. Case presentation We present a case of a 51-year-old man with a small (0.9 cm) hyperechoic lesion of the left testicle mimicking testicular cancer on multiparametric ultrasound. The lesion was localized in the peripheral zone, confirming vascularization and increased stiffness on contrast-enhanced ultrasound and real-time elastography. Preoperative tumor markers and hormone levels were within normal ranges. Staging computed tomography was negative. Organ-sparing surgery with tumor enucleation and frozen section analysis was performed, confirming testicular adenomatoid tumor. Conclusion Currently, no typical ultrasound features can definitively distinguish intratesticular adenomatoid tumors from malignant testicular masses. Thus, a surgical approach is almost always considered in such a case for both diagnostic and therapeutic purposes.

Increasing the dimensionality of entangled states improves robustness and capacity of secure quantum communications, but it requires suitably modified setups. Here the authors report the distribution of high-dimensional polarization and energy-time entangled photons via a 1.2 km-long free-space link.

The unification of the theory of relativity and quantum mechanics is a long-standing challenge in physics. Here the authors investigate the effects of a wide range of accelerations on an entangled photon pair, providing an upper bound for the effects of non-inertial frames on quantum systems.

Polymeric nanoparticles (NPs) are increasingly used as therapeutics, diagnostics, and building blocks in (bio)materials science. Current barriers to translation are limited control over NP physicochemical properties and robust scale-up of their production. Flow-based devices have emerged for controlled production of polymeric NPs, both for rapid formulation screening (~μg min−1) and on-scale production (~mg min−1). While flow-based devices have improved NP production compared to traditional batch processes, automated processes are desired for robust NP production at scale. Therefore, we engineered an automated coaxial jet mixer (CJM), which controlled the mixing of an organic stream containing block copolymer and an aqueous stream, for the continuous nanoprecipitation of polymeric NPs. The CJM was operated stably under computer control for up to 24 h and automated control over the flow conditions tuned poly(ethylene glycol)-block-polylactide (PEG5K-b-PLA20K) NP size between ≈56 nm and ≈79 nm. In addition, the automated CJM enabled production of NPs of similar size (Dh ≈ 50 nm) from chemically diverse block copolymers, PEG5K-b-PLA20K, PEG-block-poly(lactide-co-glycolide) (PEG5K-b-PLGA20K), and PEG-block-polycaprolactone (PEG5K-b-PCL20K), by tuning the flow conditions for each block copolymer. Further, the automated CJM was used to produce model nanotherapeutics in a reproducible manner without user intervention. Finally, NPs produced with the automated CJM were used to scale the formation of injectable polymer–nanoparticle (PNP) hydrogels, without modifying the mechanical properties of the PNP gel. In conclusion, the automated CJM enabled stable, tunable, and continuous production of polymeric NPs, which are needed for the scale-up and translation of this important class of biomaterials.

Gait and balance impairments are frequently considered as the most significant concerns among individuals suffering from neurological diseases. Robot-assisted gait training (RAGT) has shown to be a promising neurorehabilitation intervention to improve gait recovery in patients following stroke or brain injury by potentially initiating neuroplastic changes. However, the neurophysiological processes underlying gait recovery through RAGT remain poorly understood. As non-invasive, portable neuroimaging techniques, electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) provide new insights regarding the neurophysiological processes occurring during RAGT by measuring different perspectives of brain activity. Due to spatial information about changes in cortical activation patterns and the rapid temporal resolution of bioelectrical changes, more features correlated with brain activation and connectivity can be identified when using fused EEG-fNIRS, thus leading to a detailed understanding of neurophysiological mechanisms underlying motor behavior and impairments due to neurological diseases. Therefore, multi-modal integrations of EEG-fNIRS appear promising for the characterization of neurovascular coupling in brain network dynamics induced by RAGT. In this brief review, we surveyed neuroimaging studies focusing specifically on robotic gait rehabilitation. While previous studies have examined either EEG or fNIRS with respect to RAGT, a multi-modal integration of both approaches is lacking. Based on comparable studies using fused EEG-fNIRS integrations either for guiding non-invasive brain stimulation or as part of brain-machine interface paradigms, the potential of this methodologically combined approach in RAGT is discussed. Future research directions and perspectives for targeted, individualized gait recovery that optimize the outcome and efficiency of RAGT in neurorehabilitation were further derived.

Since little is known concerning the psychological, cognitive, and neurophysiological factors that are involved in and important for phases of prolonged breath-holding (pBH) in freedivers, the present study uses electroencephalography (EEG) to investigate event-related neurocognitive markers during pBH of experienced freedivers that regularly train pBH. The purpose was to determine whether the well-known neurophysiological modulations elicited by hypoxic and hypercapnic conditions can also be detected during pBH induced hypoxic hypercapnia. Ten experienced free-divers (all male, aged 35.10 ± 7.89 years) were asked to hold their breath twice for 4 min per instance. During the first pBH, a checker board reversal task was presented and in the second four-min pBH phase a classical visual oddball paradigm was performed. A visual evoked potential (VEP) as an index of early visual processing (i.e., latencies and amplitudes of N75, P100, and N145) and the latency and amplitude of a P300 component (visual oddball paradigm) as an index of cognitive processing were investigated. In a counter-balanced cross-over design, all tasks were once performed during normal breathing (B), and once during pBH. All components were then compared between an early pBH (0–2 min) and a later pBH stage (2–4 min) and with the same time phases without pBH (i.e., during normal breathing). Statistical analyses using analyses of variance (ANOVA) revealed that comparisons between B and pBH yielded no significant changes either in the amplitude and latency of the VEP or in the P300. This indicates that neurocognitive markers, whether in an early visual processing stream or at a later cognitive processing stage, were not affected by pBH in experienced free-divers.

Today, several pharmaceutic and non-pharmaceutic approaches exist to treat psychiatric and neurological diseases. Because of the lack of treatment procedures that are medication free and without severe side effects, transcranial direct current stimulation (tDCS) and aerobic exercise (AE) have been tested to explore the potential for initiating and modulating neuroplasticity in the human brain. Both tDCS and AE could support cognition and behavior in the clinical and non-clinical context to improve the recovery process within neurological or psychiatric conditions or to increase performance. As these techniques still lack meaningful effects, although they provide multiple beneficial opportunities within disease and health applications, there is emerging interest to find improved tDCS and AE protocols. Since multimodal approaches could provoke synergetic effects, a few recent studies have begun to combine tDCS and AE within different settings such as in cognitive training in health or for treatment purposes within clinical settings, all of which show superior effects compared to single technique applications. The beneficial outcomes of both techniques depend on several parameters and the understanding of neural mechanisms that are not yet fully understood. Recent studies have begun to directly combine tDCS and AE within one session, although their interactions on the behavioral, neurophysiological and neurochemical levels are entirely unclear. Therefore, this review: (a) provides an overview of acute behavioral, neurophysiological, and neurochemical effects that both techniques provoke within only one single application in isolation; (b) gives an overview regarding the mechanistic pathways; and (c) discusses potential interactions and synergies between tDCS and AE that might be provoked when directly combining both techniques. From this literature review focusing primarily on the cognitive domain in term of specific executive functions (EFs; inhibition, updating, and switching), it is concluded that a direct combination of tDCS and AE provides multiple beneficial opportunities for synergistic effects. A combination could be useful within non-clinical settings in health and for treating several psychiatric and neurologic conditions. However, there is a lack of research and there are several possibly interacting moderating parameters that must be considered and more importantly must be systematically investigated in the future.

Motor control is associated with synchronized oscillatory activity at alpha (8–12 Hz) and beta (12–30 Hz) frequencies in a cerebello-thalamo-cortical network. Previous studies demonstrated that transcranial alternating current stimulation (tACS) is capable of entraining ongoing oscillatory activity while also modulating motor control. However, the modulatory effects of tACS on both motor control and its underlying electro- and neurophysiological mechanisms remain ambiguous. Thus, the purpose of this study was to contribute to gathering neurophysiological knowledge regarding tACS effects by investigating the after-effects of 10 Hz tACS and 20 Hz tACS at parietal brain areas on bimanual coordination and its concurrent oscillatory and hemodynamic activity. Twenty-four right-handed healthy volunteers (12 females) aged between 18 and 30 (M = 22.35 ± 3.62) participated in the study and performed a coordination task requiring bimanual movements. Concurrent to bimanual motor training, participants received either 10 Hz tACS, 20 Hz tACS or a sham stimulation over the parietal cortex (at P3/P4 electrode positions) for 20 min via small gel electrodes (3,14 cm2 Ag/AgCl, amperage = 1 mA). Before and three time-points after tACS (immediately, 30 min and 1 day), bimanual coordination performance was assessed. Oscillatory activities were measured by electroencephalography (EEG) and hemodynamic changes were examined using functional near-infrared spectroscopy (fNIRS). Improvements of bimanual coordination performance were not differently between groups, thus, no tACS-specific effect on bimanual coordination performance emerged. However, physiological measures during the task revealed significant increases in parietal alpha activity immediately following 10 Hz tACS and 20 Hz tACS which were accompanied by significant decreases of Hboxy concentration in the right hemispheric motor cortex compared to the sham group. Based on the physiological responses, we conclude that tACS applied at parietal brain areas provoked electrophysiological and hemodynamic changes at brain regions of the motor network which are relevant for bimanual motor behavior. The existence of neurophysiological alterations immediately following tACS, especially in the absence of behavioral effects, are elementary for a profound understanding of the mechanisms underlying tACS. The lack of behavioral modifications strengthens the need for further research on tACS effects on neurophysiology and behavior using combined electrophysiological and neuroimaging methods.

Nivolumab belongs to the standard treatment options in metastatic renal cell carcinoma. Despite promising responses, a new spectrum of “immune-related” adverse effects has to be managed in daily clinical practice. A 74-year-old patient was treated with nivolumab in fourth-line. After 18 cycles, treatment was stopped due to severe adverse mucocutaneous reactions confirming a lichen ruber pemphigoides. CT scans during treatment discontinuation show stable disease since more than 14 months. Immunotherapy can cause mucocutaneous immune-mediated adverse reactions. The time of onset to cutaneous adverse effects is variable. Early recognition and treatment are essential in mitigating the severity of those adverse events. Keywords: Renal cell cancer, Nivolumab, Lichen ruber, Side effects, Cutaneous adverse event

Was soll man vom Recht halten? Ob das Recht überhaupt haltbar ist, das steht in Frage. Ich beschäftige mich mit der Frage nach seiner Haltbarkeit, indem ich mich mit dem Scheiden beschäftige. Dem liegt keine allgemeine These zugrunde, aber eine besondere. Sie lautet, dass das Recht auch aufgrund von Techniken halten kann, und dazu gehören (ausgerechnet, aber auch traditionell schon reflektiert) Scheidetechniken. Scheiden ist in diesem Sinne eine juristische Kulturtechnik. Ich möchte die Frage nach der Haltbarkeit des Rechts nicht auf Substanzen und Prädikate zurückführen, sondern auf technische Vorgänge. Regarding the law, should we hold on? Whether it is actually possible to think about the law as being in any way tenable is open to question. I concern myself with the question of the tenability of the law in con‐sidering techniques of ‘parting‘, separating, deciding and distinguishing. Parting, in this sense, is a juristic cultural technique. I would like to base the question of the tena‐bility of the law not on substances and predicates, but on technical processes.

Many daily activities, such as tying one’s shoe laces, opening a jar of jam or performing a free throw in basketball, require the skillful coordinated use of both hands. Even though the non-invasive method of transcranial direct current stimulation (tDCS) has been repeatedly shown to improve unimanual motor performance, little is known about its effects on bimanual motor performance. More knowledge about how tDCS may improve bimanual behavior would be relevant to motor recovery, e.g., in persons with bilateral impairment of hand function. We therefore examined the impact of high-definition anodal tDCS (HD-atDCS) on the performance of a bimanual sequential sensorimotor task. Thirty-two volunteers (age M = 24.25; SD = 2.75; 14 females) participated in this double-blind study and performed sport stacking in six experimental sessions. In sport stacking, 12 specially designed cups must be stacked (stacked up) and dismantled (stacked down) in predefined patterns as fast as possible. During a pretest, posttest and follow-up test, two sport stacking formations (3-6-3 stack and 1-10-1 stack) were performed. Between the pretest and posttest, all participants were trained in sport stacking with concurrent brain stimulation for three consecutive days. The experimental group (STIM-M1) received HD-atDCS over both primary motor cortices (M1), while the control group received a sham stimulation (SHAM). Three-way analysis of variance (ANOVA) revealed a significant main effect of TIME and a significant interaction of TIME × GROUP. No significant effects were found for GROUP, nor for the three-way interaction of TIME × GROUP × FORMATION. Further two-way ANOVAs showed a significant main effect of TIME and a non-significant main effect for GROUP in both sport stacking formations. A significant interaction between TIME × GROUP was found only for the 3-6-3 formation, indicating superior performance gains for the experimental group (STIM-M1). To account and control for baseline influences on the outcome measurements, ANCOVAs treating pretest scores as covariates revealed a significant effect of the stimulation. From this, we conclude that bilateral HD-atDCS over both M1 improves motor performance in a bimanual sequential sensorimotor task. These results may indicate a beneficial use of tDCS for learning and recovery of bimanual motor skills.