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Cloud base height (CBH) is an important parameter for many applications such as aviation, climatology or solar irradiance nowcasting (forecasting for the next seconds to hours ahead). The latter application is of increasing importance for the operation of distribution grids and photovoltaic power plants, energy storage systems and flexible consumers. To nowcast solar irradiance, systems based on all-sky imagers (ASIs), cameras monitoring the entire sky dome above their point of installation, have been demonstrated. Accurate knowledge of the CBH is required to nowcast the spatial distribution of solar irradiance around the ASI's location at a resolution down to 5 m. To measure the CBH, two ASIs located at a distance of usually less than 6 km can be combined into an ASI pair. However, the accuracy of such systems is limited. We present and validate a method to measure the CBH using a network of ASIs to enhance accuracy. To the best of our knowledge, this is the first method to measure the CBH with a network of ASIs which is demonstrated experimentally. In this study, the deviations of 42 ASI pairs are studied in comparison to a ceilometer and are characterized by camera distance. The ASI pairs are formed from seven ASIs and feature camera distances of 0.8…5.7 km. Each of the 21 tuples of two ASIs formed from seven ASIs yields two independent ASI pairs as the ASI used as the main and auxiliary camera, respectively, is swapped. Deviations found are compiled into conditional probabilities that tell how probable it is to receive a certain reading of the CBH from an ASI pair given that the true CBH takes on some specific value. Based on such statistical knowledge, in the inference, the likeliest actual CBH is estimated from the readings of all 42 ASI pairs. Based on the validation results, ASI pairs with a small camera distance (especially if km) are accurate for low clouds (CBH km). In contrast, ASI pairs with a camera distance of more than 3 km provide smaller deviations for greater CBH. No ASI pair provides the most accurate measurements under all conditions. The presented network of ASIs at different distances proves that, under all cloud conditions, the measurements of the CBH are more accurate than using a single ASI pair.

Europe is facing the challenge of increasing shares of energy from variable renewable sources. Furthermore, it is heading towards a fully integrated electricity market, i.e. a Europe-wide electricity system. The stable operation of this large-scale renewable power system requires detailed information on the amount of electricity being transmitted now and in the future. To estimate the actual amount of electricity, upscaling algorithms are applied. Those algorithms – until now – however, only exist for smaller regions (e.g. transmission zones and single wind farms). The aim of this study is to introduce a new approach to estimate Europe-wide wind power generation based on spatio-temporal clustering. We furthermore show that training the upscaling model for different prevailing weather situations allows to further reduce the number of reference sites without losing accuracy.

An intentional yaw misalignment of wind turbines is currently discussed as one possibility to increase the overall energy yield of wind farms. The idea behind this control is to decrease wake losses of downstream turbines by altering the wake trajectory of the controlled upwind turbines. For an application of such an operational control, precise knowledge about the inflow wind conditions, the magnitude of wake deflection by a yawed turbine and the propagation of the wake is crucial. The dependency of the wake deflection on the ambient wind conditions as well as the uncertainty of its trajectory are not sufficiently covered in current wind farm control models. In this study we analyze multiple sources that contribute to the uncertainty of the estimation of the wake deflection downstream of yawed wind turbines in different ambient wind conditions. We find that the wake shapes and the magnitude of deflection differ in the three evaluated atmospheric boundary layers of neutral, stable and unstable thermal stability. Uncertainty in the wake deflection estimation increases for smaller temporal averaging intervals. We also consider the choice of the method to define the wake center as a source of uncertainty as it modifies the result. The variance of the wake deflection estimation increases with decreasing atmospheric stability. Control of the wake position in a highly convective environment is therefore not recommended.

Printed Circuit Boards (PCB) play an important role in the manufacturing of electronic devices. To ensure a correct function of the PCBs a certain amount of solder paste is needed during the placement of components. The aim of the current research is to develop an real-time, closed-loop solution for the analysis of the printing process where solder is printed onto PCBs. Close range photogrammetry allows for determination of the solder volume and a subsequent correction if necessary. Photogrammetry is an image based method for three dimensional reconstruction from two dimensional image data of an object. A precise camera calibration is indispensable for an accurate reconstruction. In our certain application it is not possible to use calibration methods with two dimensional calibration targets. Therefore a special calibration target was developed and manufactured, which allows for single image camera calibration.

Characterizing spatiotemporal irradiance variability is important for the successful grid integration of increasing numbers of photovoltaic (PV) power systems. Using 1 Hz data recorded by as many as 99 pyranometers during the HD(CP)2 Observational Prototype Experiment (HOPE), we analyze field variability of clear-sky index k* (i.e., irradiance normalized to clear-sky conditions) and sub-minute k* increments (i.e., changes over specified intervals of time) for distances between tens of meters and about 10 km. By means of a simple classification scheme based on k* statistics, we identify overcast, clear, and mixed sky conditions, and demonstrate that the last of these is the most potentially problematic in terms of short-term PV power fluctuations. Under mixed conditions, the probability of relatively strong k* increments of ±0.5 is approximately twice as high compared to increment statistics computed without conditioning by sky type. Additionally, spatial autocorrelation structures of k* increment fields differ considerably between sky types. While the profiles for overcast and clear skies mostly resemble the predictions of a simple model published by Hoff and Perez (2012), this is not the case for mixed conditions. As a proxy for the smoothing effects of distributed PV, we finally show that spatial averaging mitigates variability in k* less effectively than variability in k* increments, for a spatial sensor density of 2 km−2.

Clouds are the dominant source of small-scale variability in surface solar radiation and uncertainty in its prediction. However, the increasing share of solar energy in the worldwide electric power supply increases the need for accurate solar radiation forecasts. In this work, we present results of a very short term global horizontal irradiance (GHI) forecast experiment based on hemispheric sky images. A 2-month data set with images from one sky imager and high-resolution GHI measurements from 99 pyranometers distributed over 10 km by 12 km is used for validation. We developed a multi-step model and processed GHI forecasts up to 25 min with an update interval of 15 s. A cloud type classification is used to separate the time series into different cloud scenarios. Overall, the sky-imager-based forecasts do not outperform the reference persistence forecasts. Nevertheless, we find that analysis and forecast performance depends strongly on the predominant cloud conditions. Especially convective type clouds lead to high temporal and spatial GHI variability. For cumulus cloud conditions, the analysis error is found to be lower than that introduced by a single pyranometer if it is used representatively for the whole area in distances from the camera larger than 1–2 km. Moreover, forecast skill is much higher for these conditions compared to overcast or clear sky situations causing low GHI variability, which is easier to predict by persistence. In order to generalize the cloud-induced forecast error, we identify a variability threshold indicating conditions with positive forecast skill.

A European power system mainly based on renewable sources will have dominant contributions from wind and solar power. However, wind and solar generation facilities have, due to the weather dependent nature of their resources, highly fluctuating feed-in profiles. To overcome the mismatch between power consumption and generation it is important to study and understand the generation patterns and balancing potentials. High temporally and spatially resolved long term weather data was used to simulate the feed-in from wind and photovoltaics for European countries for the years 2003 to 2012. We investigate storage energy and capacity needs in Europe in dependency of the generation mix from wind onshore, wind offshore and photovoltaics and the share of renewables. Furthermore we compute the storage energy and capacity needs for different transmission scenarios. We show that for unlimited transmission storage needs are reduced mostly by high wind offshore shares. We also show that higher shares above 100% of renewables can decrease the required storage capacity to a higher extent than the required storage energy.

Wind and solar power are known to be highly influenced by weather events and may ramp up or down abruptly. Such events in the power production influence not only the availability of energy, but also the stability of the entire power grid. By analysing significant amounts of data from several regions around the world with resolutions of seconds to minutes, we provide strong evidence that renewable wind and solar sources exhibit multiple types of variability and nonlinearity in the time scale of seconds and characterise their stochastic properties. In contrast to previous findings, we show that only the jumpy characteristic of renewable sources decreases when increasing the spatial size over which the renewable energies are harvested. Otherwise, the strong non-Gaussian, intermittent behaviour in the cumulative power of the total field survives even for a country-wide distribution of the systems. The strong fluctuating behaviour of renewable wind and solar sources can be well characterised by Kolmogorov-like power spectra and q -exponential probability density functions. Using the estimated potential shape of power time series, we quantify the jumpy or diffusive dynamic of the power. Finally we propose a time delayed feedback technique as a control algorithm to suppress the observed short term non-Gaussian statistics in spatially strong correlated and intermittent renewable sources.

Brillouin Light Scattering (BLS) spectroscopy is a non-invasive, non-contact, label-free optical technique that can provide information on the mechanical properties of a material on the sub-micron scale. Over the last decade it has seen increased applications in the life sciences, driven by the observed significance of mechanical properties in biological processes, the realization of more sensitive BLS spectrometers and its extension to an imaging modality. As with other spectroscopic techniques, BLS measurements not only detect signals characteristic of the investigated sample, but also of the experimental apparatus, and can be significantly affected by measurement conditions. The aim of this consensus statement is to improve the comparability of BLS studies by providing reporting recommendations for the measured parameters and detailing common artifacts. Given that most BLS studies of biological matter are still at proof-of-concept stages and use different--often self-built--spectrometers, a consensus statement is particularly timely to assure unified advancement.

Background: The early and specific detection of abiotic and biotic stresses, particularly their combinations, is a major challenge for maintaining and increasing plant productivity in sustainable agriculture under changing environmental conditions. Optical imaging techniques enable cost-efficient and non-destructive quantification of plant stress states. Monomodal detection of certain stressors is usually based on non-specific/indirect features and therefore is commonly limited in their cross-specificity to other stressors. The fusion of multi-domain sensor systems can provide more potentially discriminative features for machine learning models and potentially provide synergistic information to increase cross-specificity in plant disease detection when image data are fused at the pixel level., Results: In this study, we demonstrate successful multi-modal image registration of RGB, hyperspectral (HSI) and chlorophyll fluorescence (ChlF) kinetics data at the pixel level for high-throughput phenotyping of A. thaliana grown in Multi-well plates and an assay with detached leaf discs of Rosa × hybrida inoculated with the black spot disease-inducing fungus Diplocarpon rosae. Here, we showcase the effects of (i) selection of reference image selection, (ii) different registrations methods and (iii) frame selection on the performance of image registration via affine transform. In addition, we developed a combined approach for registration methods through NCC-based selection for each file, resulting in a robust and accurate approach that sacrifices computational time. Since image data encompass multiple objects, the initial coarse image registration using a global transformation matrix exhibited heterogeneity across different image regions. By employing an additional fine registration on the object-separated image data, we achieved a high overlap ratio. Specifically, for the A. thaliana test set, the overlap ratios (OR Convex ) were 98.0 ± 2.3% for RGB-to-ChlF and 96.6 ± 4.2% for HSI-to-ChlF. For the Rosa × hybrida test set, the values were 98.9 ± 0.5% for RGB-to-ChlF and 98.3 ± 1.3% for HSI-to-ChlF., Conclusion: The presented multi-modal imaging pipeline enables high-throughput, high-dimensional phenotyping of different plant species with respect to various biotic or abiotic stressors. This paves the way for in-depth studies investigating the correlative relationships of the multi-domain data or the performance enhancement of machine learning models via multi modal image fusion., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Decellularized extracellular matrix (dECM) is an excellent natural source for 3D bioprinting materials due to its inherent cell compatibility. In vat photopolymerization, the use of dECM-based bioresins is just emerging, and extensive research is needed to fully exploit their potential. In this study, two distinct methacryloyl-functionalized, photocrosslinkable dECM-based bioresins were prepared from digested porcine liver dECM through functionalization with glycidyl methacrylate (GMA) or conventional methacrylic anhydride (MA) under mild conditions for systematic comparison. Although the chemical modifications did not significantly affect the structural integrity of the dECM proteins, mammalian cells encapsulated in the respective hydrogels performed differently in long-term culture. In either case, photocrosslinking during 3D (bio)printing resulted in transparent, highly swollen, and soft hydrogels with good shape fidelity, excellent biomimetic properties and tunable mechanical properties (~ 0.2-2.5 kPa). Interestingly, at a similar degree of functionalization (DOF ~ 81.5-83.5 %), the dECM-GMA resin showed faster photocrosslinking kinetics in photorheology resulting in lower final stiffness and faster enzymatic biodegradation compared to the dECM-MA gels, yet comparable network homogeneity as assessed via Brillouin imaging. While human hepatic HepaRG cells exhibited comparable cell viability directly after 3D bioprinting within both materials, cell proliferation and spreading were clearly enhanced in the softer dECM-GMA hydrogels at a comparable degree of crosslinking. These differences were attributed to the additional hydrophilicity introduced to dECM via methacryloylation through GMA compared to MA. Due to its excellent printability and cytocompatibility, the functional porcine liver dECM-GMA biomaterial enables the advanced biofabrication of soft 3D tissue analogs using vat photopolymerization-based bioprinting., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marie Weinhart reports financial support was provided by German Research Foundation. Sebastian Seiffert reports financial support was provided by German Research Foundation. Beate Koksch reports financial support was provided by German Research Foundation. Igor Maximilian Sauer reports financial support was provided by German Research Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Recent research suggests that patients with neurological disorders without overt seizures may also experience accelerated long-term forgetting (ALF). This term describes unimpaired learning and memory performance after standard retention intervals, but an excessive rate of forgetting over delays of days or weeks. The objective of this retrospective study was to investigate ALF in patients with an acquired brain injury (ABI) and to associate memory performance with executive functions., Methods: Verbal memory performance (short-term recall, 30-min recall, 1-week recall) was assessed in 34 adult patients with ABI and compared to a healthy control group ( n  = 54) using an auditory word learning and memory test., Results: Repeated measure analysis showed significant effects of time and group as well as interaction effects between time and group regarding recall and recognition performance. Patients with ABI had a significantly impaired 1-week recall and recognition performance compared to the healthy control group. Correlations between recall performance and executive functions were nonsignificant., Discussion: Our results demonstrate that non-epileptic patients with ABI, especially patients with frontal and fronto-temporal lesions, are prone to ALF. Additionally, our data support the assumption that ALF results from a consolidation impairment since verbal recall and recognition were impaired in patients with ABI.

Processive enzymes like polymerases or ribosomes are often studied in bulk experiments by monitoring time-dependent signals, such as fluorescence time traces. However, due to biomolecular process stochasticity, ensemble signals may lack the distinct features of single-molecule signals. Here, we demonstrate that, under certain conditions, bulk signals from processive reactions can be decomposed to unveil hidden information about individual reaction steps. Using mRNA translation as a case study, we show that decomposing a noisy ensemble signal generated by the translation of mRNAs with more than a few codons is an ill-posed problem, addressable through Tikhonov regularization. We apply our method to the fluorescence signatures of in-vitro translated LepB mRNA and determine codon-position dependent translation rates and corresponding state-specific fluorescence intensities. We find a significant change in fluorescence intensity after the fourth and the fifth peptide bond formation, and show that both codon position and encoded amino acid have an effect on the elongation rate. This demonstrates that our approach enhances the information content extracted from bulk experiments, thereby expanding the range of these time- and cost-efficient methods., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Haase et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Triple-negative breast cancer is an aggressive subtype of breast cancer that has a poor five-year survival rate. The tumor's extracellular matrix is a major compartment of its microenvironment and influences the proliferation, migration and the formation of metastases. The study of such dependencies requires methods to analyze the tumor matrix in its native form. In this work, the limits of SHG-microscopy, namely limited penetration depth, sample size and specificity, are addressed by correlative three-dimensional imaging. We present the combination of scanning laser optical tomography (SLOT) and multiphoton microscopy, to depict the matrix collagen on different scales. Both methods can be used complementarily to generate full-volume views and allow for in-depth analysis. Additionally, we explore the use of SHG as a contrast mechanism for complex samples in SLOT. It was possible to depict the overall collagen structure and specific fibers using marker free imaging on different scales. An appropriate sample preparation enables the fixation of the structures while simultaneously conserving the fluorescence of antibody staining. We find that SHG is a suitable contrast mechanism to depict matrix collagen even in complex samples and using SLOT. The insights presented here shall further facilitate the study of the tumor extracellular matrix by correlative 3d imaging., Competing Interests: The authors declare no conflicts of interest., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Interest has grown in less invasive surgical treatment and early use of oral antibiotics in the treatment of Cutibacterium acnes prosthetic joint infection. We report a series of patients who were successfully treated with single-stage exchange and an all-oral course of rifampin and linezolid., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Oxidative stress is a cause for numerous diseases and aging processes. Thus, researchers are keen to tune the level of intracellular stress and to learn from that. An unusual approach is presented here. The methodology involves multifunctional surfactants. Although their molecular design is nonbiological-a fullerenol head group attached covalently to pi-conjugated dyes-the surfactants possess superior biocompatibility. Using an intrinsic fluorescence signal as a probe, it is shown that the amphiphiles become incorporated into the Caco-2 cells. There, they are able to exhibit additional functions. The compound reduces cellular stress in dark reaction pathways. The antagonistic property is activated under irradiation, the photocatalytic production of reactive oxygen species (ROS), resulting in cell damage. The feature is activated even by near-infrared light (NIR-light) via a two-photon process. The properties as molecular semiconductors lead to a trojan horse situation and allows the programming of the spatial distribution of cytotoxicity., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Lasers enable modification of living and non-living matter with submicron precision in a contact-free manner which has raised the interest of researchers for decades. Accordingly, laser technologies have drawn interest across disciplines. They have been established as a valuable tool to permeabilize cellular membranes for molecular delivery in a process termed photoinjection. Laser-based molecular delivery was first reported in 1984, when normal kidney cells were successfully transfected with a frequency-multiplied Nd:YAG laser. Due to the rapid development of optical technologies, far more sophisticated laser platforms have become available. In particular, near infrared femtosecond (NIR fs) laser sources enable an increasing progress of laser-based molecular delivery procedures and opened up multiple variations and applications of this technique.This review is intended to provide a plant science audience with the physical principles as well as the application potentials of laser-based molecular delivery. The historical origins and technical development of laser-based molecular delivery are summarized and the principle physical processes involved in these approaches and their implications for practical use are introduced. Successful cases of laser-based molecular delivery in plant science will be reviewed in detail, and the specific hurdles that plant materials pose will be discussed. Finally, we will give an outlook on current limitations and possible future applications of laser-based molecular delivery in the field of plant science., (© 2022. The Author(s).)

Background: In this study, the tear resistance of porcine lens capsules after continuous curvilinear capsulorhexis (CCC) and femtosecond (fs)-laser-assisted capsulotomy for cataract surgery (FLC) with different laser parameters is measured with a custom-made testing setup., Methods: Forty-five fresh porcine lenses were randomly chosen for CCC (n = 15) or FLC 1 (n = 15) and FLC 2 (n = 15). The FLC 1-group was treated with smaller spot distances than the FLC 2-group. The force necessary to break the opening of the anterior capsule and the maximum displacement were measured., Results: The mean tear resistance of the CCC-group (150 ± 70 mN) was higher than that of the FLC 1-group (60 ± 20 mN) and the FLC 2-group (30 ± 20 mN)., Conclusion: It could be shown that CCC leads to a significantly higher tear resistance of the opening than FLC in porcine lenses. The femtosecond laser group demonstrated that smaller spot distances lead to a higher tear resistance., (© 2021. The Author(s).)

Avoiding damage of the endothelial cells, especially in thin corneas, remains a challenge in corneal collagen crosslinking (CXL). Knowledge of the riboflavin gradients and the UV absorption characteristics after topical application of riboflavin in concentrations ranging from 0.1% to 0.5% could optimize the treatment. In this study, we present a model to calculate the UV-intensity depending on the corneal thickness. Ten groups of de-epithelialized porcine corneas were divided into 2 subgroups. Five groups received an imbibition of 10 min and the other five groups for 30 min. The applied riboflavin concentrations were 0.1%, 0.2%, 0.3%, 0.4% and 0.5% diluted in a 15% dextran solution for each subgroup. After the imbibition process, two-photon fluorescence microscopy was used to determine fluorescence intensity, which was compared to samples after saturation, yielding the absolute riboflavin concentration gradient of the cornea. The extinction coefficient of riboflavin solutions was measured using a spectrophotometer. Combining the obtained riboflavin concentrations and the extinction coefficients, a depth-dependent UV-intensity profile was calculated for each group. With increasing corneal depth, the riboflavin concentration decreased for all imbibition solutions and application times. The diffusion coefficients of 10 min imbibition time were higher than for 30 min. A higher RF concentration and a longer imbibition time resulted in higher UV-absorption and a lower UV-intensity in the depth of the cornea. Calculated UV-transmission was 6 percentage points lower compared to the measured transmission. By increasing the riboflavin concentration of the imbibition solution, a substantially higher UV-absorption inside the cornea is achieved. This offers a simple treatment option to control the depth of crosslinking e.g. in thin corneas, resulting in a lower risk of endothelial damage., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Light as a tool in medical therapy and biological research has been studied extensively and its application is subject to continuous improvement. However, safe and efficient application of light-based methods in photomedicine or optogenetics requires knowledge about the optical properties of the target tissue as well as the response characteristics of the stimulated cells. Here, we used tissue phantoms and a heart-like light-sensitive cell line to investigate optogenetic stimulation through tissue layers. The input power necessary for successful stimulation could be described as a function of phantom thickness. A model of light transmission through the tissue phantoms gives insights into the expected stimulation efficiency. Cell-type specific effects are identified that result in deviations of the stimulation threshold from the modelled predictions. This study provides insights into the complex interplay between light, tissue and cells during deep-tissue optogenetics. It can serve as an orientation for safe implementation of light-based methods in vivo ., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Hydrogels are favored materials in tissue engineering as they can be used to imitate tissues, provide scaffolds, and guide cell behavior. Recent advances in the field of optogenetics have created a need for biocompatible optical waveguides, and hydrogels have been investigated to meet these requirements. However, combining favorable waveguiding characteristics, high biocompatibility, and controllable bioactivity in a single device remains challenging. Here, we investigate the use of poly(ethylene glycol) hydrogels as carriers and illumination systems for in vitro cell culture. We present a comprehensive and reproducible protocol for selective bioactivation of the hydrogels, achieving high proliferation rates and strong cell adhesion on the treated surface. A cell model expressing the photoconvertible fluorescent protein Dendra2 confirmed that light-cell interactions occur at the hydrogel surface. Monte Carlo simulations were performed as a tool to predict the extent of these interactions. This study demonstrates a hydrogel-based waveguiding system for targeted cell stimulation in vitro and potentially in vivo environments.

Hydrogel waveguides have found increased use for variety of applications where biocompatibility and flexibility are important. In this work, we demonstrate the use of polyethylene glycol diacrylate (PEGDA) waveguides to realize a monolithic lab-on-a-chip device. We performed a comprehensive study on the swelling and optical properties for different chain lengths and concentrations in order to realize an integrated biocompatible waveguide in a microfluidic device for chemical sensing. Waveguiding properties of PEGDA hydrogel were used to guide excitation light into a microfluidic channel to measure the fluorescence emission profile of rhodamine 6G as well as collect the fluorescence signal from the same device. Overall, this work shows the potential of hydrogel waveguides to facilitate delivery and collection of optical signals for potential use in wearable and implantable lab-on-a-chip devices.

Background: In the field of hearing research a variety of imaging techniques are available to study molecular and cellular structures of the cochlea. Most of them are based on decalcifying, embedding, and cutting of the cochlea. By means of scanning laser optical tomography (SLOT), the complete cochlea can be visualized without cutting. The Ca v 1.3 -/- mice have already been extensively characterized and show structural changes in the inner ear. Therefore, they were used in this study as a model to investigate whether SLOT can detect structural differences in the murine cochlea., Materials and Methods: Whole undissected cochleae from Ca v 1.3 -/- and wildtype mice of various postnatal stages were immunostained and analyzed by SLOT. The results were compared to cochlea preparations that were immunostained and analyzed by fluorescence microscopy. In addition, cochlea preparations were stained with osmium tetraoxide., Results: Visualization by SLOT showed that the staining of nerve fibers at P27 in Ca v 1.3 -/- mice was almost absent compared to wildtype mice and earlier timepoints (P9). The analysis of cochlea preparations confirmed a reduction of the radial nerve fibers. In addition, a significantly reduced number of ribbon synapses per inner hair cell (IHC) at P20 and P27 in the apical part of the cochlea of Ca v 1.3 -/- mice was detected., Conclusion: The visualization of whole non-dissected cochleae by SLOT is a suitable tool for the analysis of gross phenotypic changes, as demonstrated by means of the Ca v 1.3 -/- mouse model. For the analysis of finer structures of the cochlea, however, further methods must be used.

Background: Postural tachycardia syndrome (POTS) is a form of autonomic dysregulation and is characterized by an excessive heart rate (HR) increment upon the upright body position while blood pressure is maintained. Patients experience typical symptoms of orthostatic intolerance such as dizziness, nausea and cognitive impairments. The present study assessed position-dependent attentional and cognitive functioning in POTS patients compared to healthy subjects and tested the response of cognitive performance to acute water intake. Methods: Data was obtained from eight patients with neuropathic POTS and eight healthy subjects of similar age and gender. All participants completed questionnaires that assessed health-related quality of life and depression and underwent four rounds of neuropsychological testing overall, each before and after the intake of 500 ml still mineral water and both in the supine and in the upright posture. Results: Postural tachycardia syndrome patients showed deficits in working memory (WM) exclusively in the upright position compared to healthy subjects, but no position-dependent impairments in alertness or divided attention. Rapid water ingestion had a beneficial effect on WM in the upright posture, lead to a decrease in HR increment and to an improvement of subjective symptom experience. Conclusion: The results provide support for the occurrence of purely orthostatic cognitive deficits in POTS, especially when increased executive control and cognitive resources are required and document a favorable effect of water intake on cognitive performance. These findings have important implications for the management of cognitive symptoms in POTS as high water intake is an easy and accessible strategy.

Stimulation of neuronal cells generally resorts to electric signals. Recent advances in laser-based stimulation methods could present an alternative with superior spatiotemporal resolution. The avoidance of electronic crosstalk makes these methods attractive for in vivo therapeutic application. In particular, nano-mediators, such as gold nanoparticles, can be used to transfer the energy from a laser pulse to the cell membrane and subsequently activate excitable cells. Although the underlying mechanisms of neuronal activation have been widely unraveled, the overall effect on the targeted cell is not understood. Little is known about the physiological and pathophysiological impact of a laser pulse targeted onto nanoabsorbers on the cell membrane. Here, we analyzed the reaction of the neuronal murine cell line Neuro-2A and murine primary cortical neurons to gold nanoparticle mediated laser stimulation. Our study reveals a severe, complex and cell-type independent stress response after laser irradiation, emphasizing the need for a thorough assessment of this approach's efficacy and safety.

The integration of metal microstructures and soft materials is promising for the realization of novel optical and biomedical devices owing to the flexibility and biocompatibility of the latter. Nevertheless, the fabrication of three-dimensional metal structures within a soft material is still challenging. In this study, we demonstrate the fabrication of a silver diffraction grating inside a biocompatible poly(ethylene glycol) diacrylate (PEGDA) hydrogel by using a 522-nm femtosecond laser via multi-photon photoreduction of silver ions. The optical diffraction pattern obtained with the grating showed equally spaced diffraction spots, which indicated that a regular, periodic silver grating was formed. Notably, the distance between the diffraction spots changed when the water content in the hydrogel was reduced. The grating period decreased when the hydrogel shrank owing to the loss of water, but the straight shapes of the line structures were preserved, which demonstrated the optical tunability of the fabricated structure. Our results demonstrate the potential of the femtosecond laser-based photoreduction technique for the fabrication of novel tunable optical devices as well as highly precise structures.

Micro-/nanosphere-mediated femtosecond laser cell perforation is one of the high throughput technologies used for macro-molecule-delivery into multiple cells. We have demonstrated the delivery of plasmid-DNA/liposome complexes into cells using biodegradable polymer microspheres and a femtosecond laser and investigated the intracellular localization of the complexes by delivering fluorescence-labeled plasmid-DNA/liposome complexes into cells. The utilization of liposomes increases the number of complexes delivered into the cytoplasm by laser illumination, which contributed to the increased transfection rate. In the experiment involving polystyrene (PS) microspheres of different diameters, the fluorescence of the complexes was detected in the nucleus as well as cytoplasm after laser illumination for PS microspheres of 3.0 μm diameter. The direct delivery of complexes into the nucleus is probably attributed to the enhancement of the nuclear membrane permeability by the enhanced optical field obtained close to the nucleus. These revelations on the intracellular localization of foreign DNA would provide effective laser-based transfection. Picture: Intranuclear delivery of plasmid-DNA/liposome complexes by utilizing dielectric microspheres and a femtosecond laser., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Laser-exposed plasmonic substrates permeabilize the plasma membrane of cells when in close contact to deliver cell-impermeable cargo. While studies have determined the cargo delivery efficiency and viability of laser-exposed plasmonic substrates, morphological changes in a cell have not been quantified. We porated myoblast C2C12 cells on a plasmonic pyramid array using a 532-nm laser with 850-ps pulse length and time-lapse fluorescence imaging to quantify cellular changes. We obtain a poration efficiency of 80%, viability of 90%, and a pore radius of 20 nm. We quantified area changes in the plasma membrane attached to the substrate (10% decrease), nucleus (5 - 10% decrease), and cytoplasm (5 - 10% decrease) over 1 h after laser treatment. Cytoskeleton fibers show a change of 50% in the alignment, or coherency, of fibers, which stabilizes after 10 mins. We investigate structural and morphological changes due to the poration process to enable the safe development of this technique for therapeutic applications.

Background: Haematuria is a common finding in the population and the diagnostic workflow of this symptom represents a large proportion of "work-load" in the urological outpatient clinic., Aims: The intention of this study was to verify if the intensive diagnostic procedures of haematuria patients is justified by detection of a significant proportion of genito-urinary tract cancers., Materials and Methods: In a retrospective design 1049 consecutive patients, who presented themselves with macro- or microhaematuria in the outpatient clinic PURR in the time from 2011 to 2012, were included in the study and the diagnostic procedures including ultrasound, intravenous urography, computed tomography of the abdomen and urethrocystoscopy as well as therapeutic consequences with its results were analysed., Results: The study group comprised 570 women (54.3%) and 479 men (45.7%) with a median age of 58 years and macrohaematuria occurred in 89 patients. Diagnostics revealed seven patients with renal cell cancer, six patients with urothelial cell cancer of the renal pelvis, four patients with urothelial cell cancer of the ureter, 65 patients with urothelial cell cancer of the lower urinary tract and 17 patients with prostate cancer. Age, male gender and macrohaematuria were associated with a higher risk of cancer., Conclusions: The high incidence of urinary tract cancer in the data presented here support the rationale for diagnostic work-up of patients with micro- or macrohaematuria. Prospective randomised trials are necessary to identify index patients for second work-up after a primarily negative investigation as well as the role of molecular markers, which possibly enable to omit invasive work-up., (© 2017 John Wiley & Sons Ltd.)

The mammalian cochlea is a complex macroscopic structure due to its helical shape and the microscopic arrangements of the individual layers of cells. To improve the outcomes of hearing restoration in deaf patients, it is important to understand the anatomic structure and composition of the cochlea ex vivo. Hitherto, only one histological technique based on confocal laser scanning microscopy and optical clearing has been developed for in toto optical imaging of the murine cochlea. However, with a growing size of the specimen, e.g., human cochlea, this technique reaches its limitations. Here, we demonstrate scanning laser optical tomography (SLOT) as a valuable imaging technique to visualize the murine cochlea in toto without any physical slicing. This technique can also be applied in larger specimens up to cm3 such as the human cochlea. Furthermore, immunolabeling allows visualization of inner hair cells (otoferlin) or spiral ganglion cells (neurofilament) within the whole cochlea. After image reconstruction, the 3D dataset was used for digital segmentation of the labeled region. As a result, quantitative analysis of position, length and curvature of the labeled region was possible. This is of high interest in order to understand the interaction of cochlear implants (CI) and cells in more detail.

Can photothermal gold nanoparticle mediated laser manipulation be applied to induce cardiac contraction? Based on our previous work, we present a novel concept of cell stimulation. A 532 nm picosecond laser was employed to heat gold nanoparticles on cardiomyocytes. This leads to calcium oscillations in the HL-1 cardiomyocyte cell line. As calcium is connected to the contractility, we aimed to alter the contraction rate of native and stem cell derived cardiomyocytes. A contraction rate increase was particularly observed in calcium containing buffer with neonatal rat cardiomyocytes. Consequently, the study provides conceptual ideas for a light based, nanoparticle mediated stimulation system.

Introduction: Despite the ongoing debate on the role of renal sympathetic denervation (RSD) in the management of therapy-resistant hypertension, little is known about its possible effects on exercise blood pressure (BP), a known predictor for future cardiovascular events. We sought to evaluate the effect of RSD on exercise BP in a randomized, sham-controlled trial in patients with mild hypertension., Methods and Results: Patients with therapy-resistant mild hypertension (defined by mean daytime systolic BP between 135 and 149 mmHg or mean daytime diastolic BP between 90 and 94 mmHg on 24-h ambulatory BP measurement) were randomized to either radiofrequency-based RSD or a sham procedure. Patients underwent cardiopulmonary exercise testing at baseline and after 6 months. Of the 71 patients randomized, data from cardiopulmonary exercise testing were available for 48 patients (22 in the RSD group, 26 in the sham group). After 6 months, patients undergoing RSD had a significantly lower systolic BP at maximum exercise workload compared to baseline (-14.2 ± 26.1 mmHg, p = 0.009). In contrast, no change was observed in the sham group (0.6 ± 22.9 mmHg, p = 0.45, p = 0.04 for between-group comparison). When analyzing patients with exaggerated baseline exercise BP only, the effect was even more pronounced (RSD vs. sham -29.5 ± 23.4 vs. 0.1 ± 25.3 mmHg, p = 0.008)., Conclusion: Exercise systolic BP values in patients with mild therapy-resistant hypertension are reduced after RSD as compared to a sham-procedure.

The use of small particles has expanded the capability of ultrashort pulsed laser optoinjection technology toward simultaneous treatment of multiple cells. The microfluidic platform is one of the attractive systems that has obtained synergy with laser-based technology for cell manipulation, including optoinjection. We have demonstrated the delivery of molecules into suspended-flowing cells in a microfluidic channel by using biodegradable polymer microspheres and a near-infrared femtosecond laser pulse. The use of polylactic-co-glycolic acid microspheres realized not only a higher optoinjection ratio compared to that with polylactic acid microspheres but also avoids optical damage to the microfluidic chip, which is attributable to its higher optical intensity enhancement at the localized spot under a microsphere. Interestingly, optoinjection ratios to nucleus showed a difference for adhered cells and suspended cells. The use of biodegradable polymer microspheres provides high throughput optoinjection; i.e., multiple cells can be treated in a short time, which is promising for various applications in cell analysis, drug delivery, and ex vivo gene transfection to bone marrow cells and stem cells without concerns about residual microspheres.

The fabrication of three-dimensional (3D) metal microstructures in a synthetic polymer-based hydrogel is demonstrated by femtosecond laser-induced photoreduction. The linear-shaped silver structure of approximately 2 micrometers in diameter is fabricated inside a biocompatible poly(ethylene glycol) diacrylate (PEGDA) hydrogel. The silver structure is observed and confirmed by scanning electron microscopy (SEM) and elemental analysis using energy-dispersive X-ray spectroscopy (EDX). Shrinking and swelling of the fabricated structure is also demonstrated experimentally, which shows the potential of the present method for realizing 3D flexible electronic and optical devices, as well as for fabricating highly integrated devices at submicron scales.

Introduction: Over the past decade, the use of opioid analgesics has risen dramatically both in the U.S. and South Dakota. Opioids have been increasingly used to treat chronic non-cancer pain; however, the utilization of opioids for this role has limited and questionable utility. The U.S. has also seen a rise of opioid abuse, addiction, misuse, and overdose. The various pharmacological and non-pharmacological strategies to help physicians manage chronic non-cancer pain and a guideline on appropriate opioid prescribing are presented., Discussion: Before the decision is made to begin opioid therapy for chronic non-cancer pain, other pharmacological and non-pharmacological therapeutic strategies should be explored. The schema for responsible opioid prescribing can be dived into the following: the initial assessment, initiating opioid therapy, maintenance therapy, and the discontinuation of opioid treatment. These categories are explored, and a general approach to prescribing opioids for chronic non-cancer pain is presented., Conclusion: The Centers for Disease Control and Prevention (CDC) has declared opioid prescription abuse an "epidemic." There are a variety of methods clinicians can utilize to relieve chronic non-cancer pain. If opioid therapy is sought, clinicians should be mindful of the current state of opioid abuse and misuse. This guideline may aid clinicians in appropriate opioid prescribing.

Laser-based transfection techniques have proven high applicability in several cell biologic applications. The delivery of different molecules using these techniques has been extensively investigated. In particular, new high-throughput approaches such as gold nanoparticle–mediated laser transfection allow efficient delivery of antisense molecules or proteins into cells preserving high cell viabilities. However, the cellular response to the perforation procedure is not well understood. We herein analyzed the perforation kinetics of single cells during resonant gold nanoparticle–mediated laser manipulation with an 850-ps laser system at a wavelength of 532 nm. Inflow velocity of propidium iodide into manipulated cells reached a maximum within a few seconds. Experiments based on the inflow of FM4-64 indicated that the membrane remains permeable for a few minutes for small molecules. To further characterize the cellular response postmanipulation, we analyzed levels of oxidative heat or general stress. Although we observed an increased formation of reactive oxygen species by an increase of dichlorofluorescein fluorescence, heat shock protein 70 was not upregulated in laser-treated cells. Additionally, no evidence of stress granule formation was visible by immunofluorescence staining. The data provided in this study help to identify the cellular reactions to gold nanoparticle–mediated laser manipulation.

Purpose: A case is presented and a systematic review of the literature is provided to update our current knowledge of induction of fear by cortical stimulation., Methods: We present a case of refractory epilepsy associated with a lesion where fear could be induced by intraoperative electrical stimulation of the posterior inner part of the superior temporal gyrus. We performed a systematic review of the literature using PubMed with the key words "epilepsy AND emotion", "cortical stimulation AND emotion," and "human brain stimulation AND behavior"., Results: Intraoperative cortical stimulation of the inner part of the posterior superior temporal gyrus reliably induced fear and progressive screaming behavior. Stimulation through subdural grid electrodes did not induce this phenomenon. A systematic review of the literature identified fear induction by stimulation of different widespread cortical areas including the temporal pole, the insula, and the anterior cingulate cortex. The posterior part of the superior temporal gyrus has so far not been associated with fear induction after electrical stimulation., Conclusion: Although our observation suggests that this area of the brain could be part of a network involved in the elicitation of fear, dysfunction of this network induced by epilepsy could also explain the observed phenomenon. Electrophysiologic and imaging studies must be conducted to improve our understanding of the cortical networks forming the neuroanatomical substrate of higher brain functions and experiences such as fear., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Gold nanoparticle mediated (GNOME) laser transfection is a powerful technique to deliver small biologically relevant molecules into cells. However, the transfection of larger and especially negatively charged DNA remains challenging. The efficiency for pDNA was 0.57% using parameter that does not influence the endo- and exogenous DNA. In order to gain a deeper understanding of the actual molecule uptake process, the uptake efficiency was determined using molecules of different sizes. It was evaluated that uncharged dextran molecules (2000 kDa) were delivered with an efficiency of 68%. The intracellular distribution of injected molecules was visualized and larger molecules were primary found in the cytoplasm. Patch clamp measurements suggested a permeabilization time up to 15 minutes. The uptake efficiency depended on the size and charge of the molecule to deliver as well as the cell size. A minor role for transfection plays the cell type since primary stem cells were successfully transfected. The perforation efficiency of semi-adherent and suspension cells is influenced by the cell and molecule size., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Unlabelled: Few data are available with regard to the effectiveness of renal sympathetic denervation in patients with resistant hypertension yet only mildly elevated blood pressure (BP). Patients with resistant hypertension and slightly elevated BP (day-time systolic pressure, 135-149 and diastolic pressure, 90-94 mm Hg on 24-hour ambulatory measurement) were randomized in a 1:1 ratio to renal sympathetic denervation with the Symplicity Flex Catheter (Medtronic) or an invasive sham procedure. The primary efficacy end point was the change in 24-hour systolic BP at 6 months between groups in the intention to treat population. A total of 71 patients underwent randomization. Baseline day-time systolic BP was 144.4±4.8 mm Hg in patients assigned to denervation and 143.0±4.7 mm Hg in patients randomized to the sham procedure. The mean change in 24-hour systolic BP in the intention to treat cohort at 6 months was -7.0 mm Hg (95% confidence interval, -10.8 to -3.2) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.7 to -0.2) in the sham group (P=0.15). In the per protocol population, the change in 24-hour systolic BP at 6 months was -8.3 mm Hg (95% confidence interval, -11.7 to -5.0) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.8 to -0.2) in the sham group (P=0.042). In patients with mild resistant hypertension, renal sympathetic denervation failed to show a significant reduction in the primary end point of 24-hour systolic BP at 6 months between groups in the intention to treat analysis., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01656096., (© 2015 American Heart Association, Inc.)

Laser based cell manipulation has proven to be a versatile tool in biomedical applications. In this context, combining weakly focused laser pulses and nanostructures, e.g. gold nanoparticles, promises to be useful for high throughput cell manipulation, such as transfection and photothermal therapy. Interactions between laser pulses and gold nanoparticles are well understood. However, it is still necessary to study cell behavior in gold nanoparticle mediated laser manipulation. While parameters like cell viability or perforation efficiency are commonly addressed, the influence of the manipulation process on other essential cell parameters is not sufficiently investigated yet. Thus, we set out to study four relevant cell properties: cell volume and area, ion exchange and cytoskeleton structure after gold nanoparticle based laser manipulation. For this, we designed a multimodal imaging and manipulation setup. 200 nm gold nanoparticles were attached unspecifically to canine cells and irradiated by weakly focused 850 ps laser pulses. Volume and area change in the first minute post laser manipulation was monitored using digital holography. Calcium imaging and cells expressing a marker for filamentous actin (F-actin) served to analyze the ion exchange and the cytoskeleton, respectively. High radiant exposures led to cells exhibiting a tendency to shrink in volume and area, possibly due to outflow of cytoplasm. An intracellular raise in calcium was observed and accompanied by an intercellular calcium wave. This multimodal approach enabled for the first time a comprehensive analysis of the cell behavior in gold nanoparticle mediated cell manipulation. Additionally, this work can pave the way for a better understanding and the evaluation of new applications in the context of cell transfection or photothermal therapy.

Background: In molecular medicine, the manipulation of cells is prerequisite to evaluate genes as therapeutic targets or to transfect cells to develop cell therapeutic strategies. To achieve these purposes it is essential that given transfection techniques are capable of handling high cell numbers in reasonable time spans. To fulfill this demand, an alternative nanoparticle mediated laser transfection method is presented herein. The fs-laser excitation of cell-adhered gold nanoparticles evokes localized membrane permeabilization and enables an inflow of extracellular molecules into cells., Results: The parameters for an efficient and gentle cell manipulation are evaluated in detail. Efficiencies of 90% with a cell viability of 93% were achieved for siRNA transfection. The proof for a molecular medical approach is demonstrated by highly efficient knock down of the oncogene HMGA2 in a rapidly proliferating prostate carcinoma in vitro model using siRNA. Additionally, investigations concerning the initial perforation mechanism are conducted. Next to theoretical simulations, the laser induced effects are experimentally investigated by spectrometric and microscopic analysis. The results indicate that near field effects are the initial mechanism of membrane permeabilization., Conclusion: This methodical approach combined with an automated setup, allows a high throughput targeting of several 100,000 cells within seconds, providing an excellent tool for in vitro applications in molecular medicine. NIR fs lasers are characterized by specific advantages when compared to lasers employing longer (ps/ns) pulses in the visible regime. The NIR fs pulses generate low thermal impact while allowing high penetration depths into tissue. Therefore fs lasers could be used for prospective in vivo applications.

Several cell transfection techniques have been developed in the last decades for specific applications and for various types of molecules. In this context, laser based approaches are of great interest due to their minimal invasiveness and spatial selectivity. In particular, laser induced plasmon based delivery of exogenous molecules into cells can have great impact on future applications. This approach allows high-throughput laser transfection by excitation of plasmon resonances at gold nanoparticles non-specifically attached to the cell membrane. In this study, we demonstrate specific gene-knockdown by transfection of Morpholino oligos using this technique with optimized particle size. Furthermore, we evaluated the cytotoxicity of plasmonic laser treatment by various assays, including LDH activity and ROS formation. In summary, this study gives important insights into this new approach and clearly demonstrates its relevance for possible biological applications., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gold nanoparticle mediated (GNOME) laser transfection/perforation fulfills the demands of a reliable transfection technique. It provides efficient delivery and has a negligible impact on cell viability. Furthermore, it reaches high-throughput applicability. However, currently only large gold particles (> 80 nm) allow successful GNOME laser perforation, probably due to insufficient sedimentation of smaller gold nanoparticles. The objective of this study is to determine whether this aspect can be addressed by a modification of silica particles with gold nanoparticles. Throughout the analysis, we show that after the attachment of gold nanoparticles to silica particles, comparable or better efficiencies to GNOME laser perforation are reached. In combination with 1 µm silica particles, we report laser perforation with gold nanoparticles with sizes down to 4 nm. Therefore, our investigations have great importance for the future research in and the fields of laser transfection combined with plasmonics.

The use of laser induced surface plasmons on metal nanoparticles has proven to be an excellent tool for the delivery of molecules like siRNA and DNA into cells. However, a detailed understanding of the basic mechanisms of molecular uptake and the influence of parameters like biological environment is missing. In this study we analyzed the uptake of fluorescent dextrans with sizes from 10 to 2000 kDa, which resembles a wide range of biologically relevant molecules in size using a 532 nm picosecond laser system and 200 nm gold nanoparticles. Our results show a strong uptake-dependence on cell medium or buffer, but no dominant dependence on osmotic conditions. The relation between pulse energy and number of pulses for a given perforation efficiency revealed that multiphoton ionization of water might contribute to perforation. Moreover, a seven-fold uptake-enhancement could be reached with optimized parameters, providing a very promising basis for further studies and applications., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nanoparticle laser interactions are in widespread use in cell manipulation. In particular, molecular medicine needs techniques for the directed delivery of molecules into mammalian cells. Proteins are the final mediator of most cellular cascades. However, despite several methodical approaches, the efficient delivery of proteins to cells remains challenging. This paper presents a new protein transfection technique via laser scanning of cells previously incubated with gold nanoparticles. The laser-induced plasmonic effects on the gold nanoparticles cause a transient permeabilization of the cellular membrane, allowing proteins to enter the cell. Applying this technique, it was possible to deliver green fluorescent protein into mammalian cells with an efficiency of 43%, maintaining a high level of cell viability. Furthermore, a functional delivery of Caspase 3, an apoptosis mediating protein, was demonstrated and evaluated in several cellular assays. Compared to conventional protein transfection techniques such as microinjection, the methodical approach presented here enables high-throughput transfection of about 10 000 cells per second. Moreover, a well-defined point in time of delivery is guaranteed by gold nanoparticle mediated laser transfection, allowing the detailed temporal analysis of cellular pathways and protein trafficking.

The deterioration of performance over time is characteristic for sustained attention tasks. This so-called "performance decrement" is measured by the increase of reaction time (RT) over time. Some behavioural and neurobiological mechanisms of this phenomenon are not yet fully understood. Behaviourally, we examined the increase of RT over time and the inter-individual differences of this performance decrement. On the neurophysiological level, we investigated the task-relevant brain areas where neural activity was modulated by RT and searched for brain areas involved in good performance (i.e. participants with no or moderate performance decrement) as compared to poor performance (i.e. participants with a steep performance decrement). For this purpose, 20 healthy, young subjects performed a carefully designed task for simple sustained attention, namely a low-demanding version of the Rapid Visual Information Processing task. We employed a rapid event-related functional magnetic resonance imaging (fMRI) design. The behavioural results showed a significant increase of RT over time in the whole group, and also revealed that some participants were not as prone to the performance decrement as others. The latter was statistically significant comparing good versus poor performers. Moreover, high BOLD-responses were linked to longer RTs in a task-relevant bilateral fronto-cingulate-insular-parietal network. Among these regions, good performance was associated with significantly higher RT-BOLD correlations in the pre-supplementary motor area (pre-SMA). We concluded that the task-relevant bilateral fronto-cingulate-insular-parietal network was a cognitive control network responsible for goal-directed attention. The pre-SMA in particular might be associated with the performance decrement insofar that good performers could sustain activity in this brain region in order to monitor performance declines and adjust behavioural output., (Copyright © 2012 Elsevier Inc. All rights reserved.)