Direct Band Gap Semiconductors with Two- and Three-Dimensional Triel-Phosphide Frameworks (Triel=Al, Ga, In).

Recently, several ternary phosphidotrielates and -tetrelates have been investigated with respect to their very good ionic conductivity, while less focus was pointed towards their electronic structures. Here, we report on a novel series of compounds, in which several members possess direct band gaps. We investigated the known compounds Li3AlP2, Li3GaP2, Li3InP2, and Na3InP2 and describe the synthesis and the crystal structure of novel Na3In2P3. For all mentioned phosphidotrielates reflectance UV-Vis measurements reveal direct band gaps in the visible light region with decreasing band gaps in the series: Li3AlP2 (2.45 eV), Li3GaP2 (2.18 eV), Li3InP2 (1.99 eV), Na3InP2 (1.37 eV), and Na3In2P3 (1.27 eV). All direct band gaps are confirmed by quantum chemical calculations. The unexpected property occurs despite different structure types. As a common feature all compounds contain EP4 tetrahedra, which share exclusively vertices for E=In and vertices as well as edges for E=Al and Ga. The structure of the novel Na3In2P3 is built up by a polyanionic framework of six-membered rings of corner-sharing InP4 tetrahedra. As a result, the newly designed semiconductors with direct band gaps are suitable for optoelectronic applications, and they can provide significant guidance for the design of new functional semiconductors.

Towards a validated glossary of usability attributes for the evaluation of wearable robotic devices.

BACKGROUND: Despite technical advances in the field of wearable robotic devices (WRD), there is still limited user acceptance of these technologies. While usability often comes as a key factor influencing acceptance, there is a scattered landscape of definitions and scopes for the term. To advance usability evaluation, and to integrate usability features as design requirements during technology development, there is a need for benchmarks and shared terminology. These should be easily accessible and implementable by developers. METHODS: An initial set of usability attributes (UA) was extracted from a literature survey on usability evaluation in WRD. The initial set of attributes was enriched and locally validated with seven developers of WRD through an online survey and a focus group. The locally validated glossary was then externally validated through a globally distributed online survey. RESULTS: The result is the Robotics Usability Glossary (RUG), a comprehensive glossary of 41 UA validated by 70 WRD developers from 17 countries, ensuring its generalizability. 31 of the UA had high agreement scores among respondents and 27 were considered highly relevant in the field, but only 11 of them had been included as design criteria by the respondents. CONCLUSIONS: Multiple UA ought to be considered for a comprehensive usability assessment. Usability remains inadequately incorporated into device development, indicating a need for increased awareness and end-user perspective. The RUG can be readily accessed through an online platform, the Interactive Usability Toolbox (IUT), developed to provide context-specific outcome measures and usability evaluation methods. Overall, this effort is an important step towards improving and promoting usability evaluation practices within WRD. It has the potential to pave the way for establishing usability evaluation benchmarks that further endorse the acceptance of WRD.

Rapid Fluorescence Lifetime Imaging Reveals That TRPV4 Channels Promote Dysregulation of Neuronal Na+ in Ischemia.

Fluorescence imaging is an indispensable method for analysis of diverse cellular and molecular processes, enabling, for example, detection of ions, second messengers, or metabolites. Intensity-based approaches, however, are prone to artifacts introduced by changes in fluorophore concentrations. This drawback can be overcome by fluorescence lifetime imaging (FLIM) based on time-correlated single-photon counting. FLIM often necessitates long photon collection times, resulting in strong temporal binning of dynamic processes. Recently, rapidFLIM was introduced, exploiting ultra-low dead-time photodetectors together with rapid electronics. Here, we demonstrate the applicability of rapidFLIM, combined with new and improved correction schemes, for spatiotemporal fluorescence lifetime imaging of low-emission fluorophores in a biological system. Using tissue slices of hippocampi of mice of either sex, loaded with the Na+ indicator ING2, we show that improved rapidFLIM enables quantitative, dynamic imaging of neuronal Na+ signals at a full-frame temporal resolution of 0.5 Hz. Induction of transient chemical ischemia resulted in unexpectedly large Na+ influx, accompanied by considerable cell swelling. Both Na+ loading and cell swelling were dampened on inhibition of TRPV4 channels. Together, rapidFLIM enabled the spatiotemporal visualization and quantification of neuronal Na+ transients at unprecedented speed and independent from changes in cell volume. Moreover, our experiments identified TRPV4 channels as hitherto unappreciated contributors to neuronal Na+ loading on metabolic failure, suggesting this pathway as a possible target to ameliorate excitotoxic damage. Finally, rapidFLIM will allow faster and more sensitive detection of a wide range of dynamic signals with other FLIM probes, most notably those with intrinsic low-photon emission.SIGNIFICANCE STATEMENT FLIM is an indispensable method for analysis of cellular processes. FLIM often necessitates long photon collection periods, requiring the sacrifice of temporal resolution at the expense of spatial information. Here, we demonstrate the applicability of the recently introduced rapidFLIM for quantitative, dynamic imaging with low-emission fluorophores in brain slices. RapidFLIM, combined with improved correction schemes, enabled intensity-independent recording of neuronal Na+ transients at unprecedented full-frame rates of 0.5 Hz. It also allowed quantitative imaging independent from changes in cell volume, revealing a surprisingly strong and hitherto uncovered contribution of TRPV4 channels to Na+ loading on energy failure. Collectively, our study thus provides a novel, unexpected insight into the mechanisms that are responsible for Na+ changes on energy depletion.

Unraveling Sodium-Ion Dynamics in Honeycomb-Layered Na2MgxZn2-xTeO6 Solid Electrolytes with Solid-State NMR.

All-solid-state sodium-ion batteries (SIBs) have the potential to offer large-scale, safe, cost-effective, and sustainable energy storage solutions by supplementing the industry-leading lithium-ion batteries. However, for the enhanced bulk properties of SIB components (e.g., solid electrolytes), a comprehensive understanding of their atomic-scale structure and the dynamic behavior of sodium (Na) ions is essential. Here, we utilize a robust multinuclear (23Na, 125Te, 25Mg, and 67Zn) magnetic resonance approach to explore a novel Mg/Zn homogeneously mixed-cation honeycomb-layered oxide Na2MgxZn2-xTeO6 solid solution series. These new intermediate compounds exhibit tailorable bulk Na-ion conductivity (σ) with the highest σ = 0.14 × 10-4 S cm-1 for Na2MgZnTeO6 at room temperature suitable for SIB solid electrolyte applications as observed by powder electrochemical impedance spectroscopy (EIS). A combination of powder X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, and field emission scanning electron microscopy (FESEM) reveals highly crystalline phase-pure compounds in the P6322 space group. We show that the Mg/Zn disorder is random within the honeycomb layers using 125Te nuclear magnetic resonance (NMR) and resolve multiple Na sites using two-dimensional (triple-quantum magic-angle spinning (3QMAS)) 23Na NMR. The medium-range disorder in the honeycomb layer is revealed through the combination of 25Mg and 67Zn NMR, complemented by electronic structure calculations using density functional theory (DFT). Furthermore, we expose very fast local Na-ion hopping processes (hopping rate, 1/τNMR = 0.83 × 109 Hz) by using a laser to achieve variable high-temperature (∼860 K) 23Na NMR, which are sensitive to different Mg/Zn ratios. The Na2MgZnTeO6 with maximum Mg/Zn disorder displays the highest short-range Na-ion dynamics among all of the solid solution members.

Mixed methods usability evaluation of an assistive wearable robotic hand orthosis for people with spinal cord injury.

BACKGROUND: Robotic hand orthoses (RHO) aim to provide grasp assistance for people with sensorimotor hand impairment during daily tasks. Many of such devices have been shown to bring a functional benefit to the user. However, assessing functional benefit is not sufficient to evaluate the usability of such technologies for daily life application. A comprehensive and structured evaluation of device usability not only focusing on effectiveness but also efficiency and satisfaction is required, yet often falls short in existing literature. Mixed methods evaluations, i.e., assessing a combination of quantitative and qualitative measures, allow to obtain a more holistic picture of all relevant aspects of device usability. Considering these aspects already in early development stages allows to identify design issues and generate generalizable benchmarks for future developments. METHODS: We evaluated the short-term usability of the RELab tenoexo, a RHO for hand function assistance, in 15 users with tetraplegia after a spinal cord injury through a comprehensive mixed methods approach. We collected quantitative data using the Action Research Arm Test (ARAT), the System Usability Scale (SUS), and timed tasks such as the donning process. In addition, qualitative data were collected through semi-structured interviews and user observations, and analyzed with a thematic analysis to enhance the usability evaluation. All insights were attributed and discussed in relation to specifically defined usability attributes such as comfort, ease of use, functional benefit, and safety. RESULTS: The RELab tenoexo provided an immediate functional benefit to the users, resulting in a mean improvement of the ARAT score by 5.8 points and peaking at 15 points improvement for one user (clinically important difference: 5.7 points). The mean SUS rating of 60.6 represents an adequate usability, however, indicating that especially the RHO donning (average task time = 295 s) was perceived as too long and cumbersome. The participants were generally very satisfied with the ergonomics (size, dimensions, fit) of the RHO. Enhancing the ease of use, specifically in donning, increasing the provided grasping force, as well as the availability of tailoring options and customization were identified as main improvement areas to promote RHO usability. CONCLUSION: The short-term usability of the RELab tenoexo was thoroughly evaluated with a mixed methods approach, which generated valuable data to improve the RHO in future iterations. In addition, learnings that might be transferable to the evaluation and design of other RHO were generated, which have the potential to increase the daily life applicability and acceptance of similar technologies.

Exacerbation of Epilepsy by Astrocyte Alkalization and Gap Junction Uncoupling.

Seizures invite seizures. At the initial stage of epilepsy, seizures intensify with each episode; however, the mechanisms underlying this exacerbation remain to be solved. Astrocytes have a strong control over neuronal excitability and the mode of information processing. This control is accomplished by adjusting the levels of various ions in the extracellular space. The network of astrocytes connected via gap junctions allows a wider or more confined distribution of these ions depending on the open probability of the gap junctions. K+ clearance relies on the K+ uptake by astrocytes and the subsequent diffusion of K+ through the astrocyte network. When astrocytes become uncoupled, K+ clearance becomes hindered. Accumulation of extracellular K+ leads to hyperexcitability of neurons. Here, using acute hippocampal slices from mice, we uncovered that brief periods of epileptiform activity result in gap junction uncoupling. In slices that experienced short-term epileptiform activity, extracellular K+ transients in response to glutamate became prolonged. Na+ imaging with a fluorescent indicator indicated that intercellular diffusion of small cations in the astrocytic syncytium via gap junctions became rapidly restricted after epileptiform activity. Using a transgenic mouse with astrocyte-specific expression of a pH sensor (Lck-E2GFP), we confirmed that astrocytes react to epileptiform activity with intracellular alkalization. Application of Na+/HCO3- cotransporter blocker led to the suppression of intracellular alkalization of astrocytes and to the prevention of astrocyte uncoupling and hyperactivity intensification both in vitro and in vivo Therefore, the inhibition of astrocyte alkalization could become a promising therapeutic strategy for countering epilepsy development.SIGNIFICANCE STATEMENT We aimed to understand the mechanisms underlying the plastic change of forebrain circuits associated with the intensification of epilepsy. Here, we demonstrate that first-time exposure to only brief periods of epileptiform activity results in acute disturbance of the intercellular astrocyte network formed by gap junctions in hippocampal tissue slices from mice. Moreover, rapid clearance of K+ from the extracellular space was impaired. Epileptiform activity activated inward Na+/HCO3- cotransport in astrocytes by cell depolarization, resulting in their alkalization. Our data suggest that alkaline pH shifts in astrocytes lead to gap junction uncoupling, hampering K+ clearance, and thereby to exacerbation of epilepsy. Pharmacological intervention could become a promising new strategy to dampen neuronal hyperexcitability and epileptogenesis.

A survey on the influence of CYBATHLON on the development and acceptance of advanced assistive technologies.

BACKGROUND: Advanced assistive technologies (AAT) aim to exploit the vast potential of technological developments made in the past decades to improve the quality of life of people with disabilities. Combining complex robotic technologies with the unique needs of people with disabilities requires a strong focus on user-centered design to ensure that the AAT appropriately addresses the daily life struggles of target users. The CYBATHLON aims to promote this mindset by empowering the AAT target users ("pilots") to compete on race tracks that represent approximations of daily life obstacles. The objective of this work was to investigate the AAT technology development, usability, and user involvement (i.e., application of user-centered design) in the context of the CYBATHLON. METHODS: With an online survey targeting the pilots and technical leads of teams preparing for the CYBATHLON 2020 Global Edition, we investigated to what extent the pilots were involved in device development and how this influences the perceived usability of the showcased AAT. Furthermore, the effects of user-centered design variables on the individual race performances were analyzed. RESULTS: A total of 81 responses from 35 pilots and 46 technical leads were collected in the two weeks prior to the event. Of all teams partaking in the included disciplines of the CYBATHLON 2020 Global Edition, 81.8% (36 of 44) were included in the study. User-centered design appeared to be a prevalent practice among the teams, as 85.7% of all pilots reported a certain level of involvement. However, only 25.5% of the pilots reported daily life usage, despite QUEST usability scores of both respondent groups showing moderate to high satisfaction with the respected AAT across all investigated disciplines. An explorative linear mixed model indicated that daily life usage (p < 0.05) and prolonged user involvement (e.g., more than 2 years, p < 0.001) have a significant positive effect on the race performance at the competition. CONCLUSIONS: We conclude that the CYBATHLON positively fulfills its conceptual goals of promoting active participation and inclusion of people with disabilities in the design and evaluation of AAT, thereby stimulating the development of promising novel technological solutions. Also, our data could underline the value of the competition as a benchmark, highlighting remaining usability limitations or technology adoption hurdles.

Usability of an exosuit in domestic and community environments.

BACKGROUND: Exosuits have been shown to reduce metabolic cost of walking and to increase gait performance when used in clinical environment. Currently, these devices are transitioning to private use to facilitate independent training at home and in the community. However, their acceptance in unsupervised settings remains unclear. Therefore, the aim of this study was to investigate end-user perspectives and the adoption of an exosuit in domestic and community settings. METHODS: We conducted a mixed-method study to investigate the usability and user experience of an exosuit, the Myosuit. We leveraged on a cohort of seven expert users, who had the device available at home for at least 28 days. Each participant completed two standardized questionnaires (SUS and QUEST) and one personalized, custom questionnaire. Furthermore, a semi-structured interview with each participant was recorded, verbatim transcribed and analyzed using descriptive thematic analysis. Data collected from device sensors quantified the frequency of use. RESULTS: A mean SUS score of 75.4 out of 100 was reported. Five participants scored above the threshold for above-average usability. Participants also expressed high satisfaction with most of the technical features in the QUEST with an average score of 4.1 (3.86-4.71) out of 5. Participants used the Myosuit mainly for walking outside and exercising at home. However, the frequency of use did not meet the recommendations for physical activity established by the World Health Organization. Five participants used the Myosuit approximately once per week. The two other participants integrated the device in their daily life and used the Myosuit to a greater extent (approx. five times per week). Major factors that prevented an extensive use of the technology were: (i) difficulties in donning that led to (ii) lack of independence and (iii) lack of motivation in exercising. CONCLUSIONS: Although usable for various activities and well perceived, the adoption of the exosuit in domestic and community settings is yet limited. Use outside the clinic poses further challenges that should be considered when developing new wearable robots. Primarily, design should meet the users' claim for independence and increased adjustability of the device.

An analysis of usability evaluation practices and contexts of use in wearable robotics.

BACKGROUND: User-centered design approaches have gained attention over the past decade, aiming to tackle the technology acceptance issues of wearable robotic devices to assist, support or augment human capabilities. While there is a consensus that usability is key to user-centered design, dedicated usability evaluation studies are scarce and clear evaluation guidelines are missing. However, the careful consideration and integration of user needs appears to be essential to successfully develop an effective, efficient, and satisfactory human-robot interaction. It is primarily the responsibility of the developer, to ensure that this users involvement takes place throughout the design process. METHODS: Through an online survey for developers of wearable robotics, we wanted to understand how the design and evaluation in actual daily practice compares to what is reported in literature. With a total of 31 questions, we analyzed the most common wearable robotic device applications and their technology maturity, and how these influence usability evaluation practices. RESULTS: A total of 158 responses from a heterogeneous population were collected and analyzed. The dataset representing contexts of use for augmentation (16.5%), assistance (38.0%), therapy (39.8%), as well as few other specific applications (5.7%), allowed for an insightful analysis of the influence of technology maturity on user involvement and usability evaluation. We identified functionality, ease of use, and performance as the most evaluated usability attributes and could specify which measures are used to assess them. Also, we could underline the frequent use of qualitative measures alongside the expected high prevalence of performance-metrics. In conclusion of the analysis, we derived evaluation recommendations to foster user-centered design and usability evaluation. CONCLUSION: This analysis might serve as state-of-the-art comparison and recommendation for usability studies in wearable robotics. We believe that by motivating for more balanced, comparable and user-oriented evaluation practices, we may support the wearable robotics field in tackling the technology acceptance limitations.

High-speed fixed-target serial virus crystallography.

We report a method for serial X-ray crystallography at X-ray free-electron lasers (XFELs), which allows for full use of the current 120-Hz repetition rate of the Linear Coherent Light Source (LCLS). Using a micropatterned silicon chip in combination with the high-speed Roadrunner goniometer for sample delivery, we were able to determine the crystal structures of the picornavirus bovine enterovirus 2 (BEV2) and the cytoplasmic polyhedrosis virus type 18 polyhedrin, with total data collection times of less than 14 and 10 min, respectively. Our method requires only micrograms of sample and should therefore broaden the applicability of serial femtosecond crystallography to challenging projects for which only limited sample amounts are available. By synchronizing the sample exchange to the XFEL repetition rate, our method allows for most efficient use of the limited beam time available at XFELs and should enable a substantial increase in sample throughput at these facilities.

Quasi-bound states in the continuum for deep subwavelength structural information retrieval for DUV nano-optical polarizers.

We demonstrate the retrieval of deep subwavelength structural information in nano-optical polarizers by scatterometry of quasi-bound states in the continuum (quasi-BICs). To this end, we investigate titanium dioxide wire grid polarizers for application wavelengths in the deep ultraviolet (DUV) spectral range fabricated with a self-aligned double-patterning process. In contrast to the time-consuming and elaborate measurement techniques like scanning electron microscopy, asymmetry induced quasi-BICs occurring in the near ultraviolet and visible spectral range provide an easily accessible and efficient probe mechanism. Thereby, dimensional parameters are retrieved with uncertainties in the sub-nanometer range. Our results show that BICs are a promising tool for process control in optics and semiconductor technology.

Manufacturing and Characterization of Femtosecond Laser-Inscribed Bragg Grating in Polymer Waveguide Operation in an IR-A Wavelength Range.

Optical sensors, such as fiber Bragg gratings, offer advantages compared to other sensors in many technological fields due to their outstanding characteristics. This sensor technology is currently transferred to polymer waveguides that provide the potential for cost-effective, easy, and flexible manufacturing of planar structures. While sensor production itself, in the majority of cases, is performed by means of phase mask technique, which is limited in terms of its degrees of freedom, other inscription techniques enable the manufacture of more adaptable sensor elements for a wider range of applications. In this article, we demonstrate the point-by-point femtosecond laser direct inscription method for the processing of polymer Bragg gratings into waveguides of the epoxy-based negative photoresist material EpoCore for a wavelength range around 850 nm. By characterizing the obtained grating back-reflection of the produced sensing element, we determined the sensitivity for the state variables temperature, humidity, and strain to be 45 pm/K, 19 pm/%, and 0.26 pm/µÎµ, respectively. Individual and more complex grating structures can be developed from this information, thus opening new fields of utilization.

The Energy Challenge in Historical Perspective.

This essay highlights the great potential that historical research offers for discussing energy-related issues more reflexively in current debates on the "great global challenges." Tracing the historical roots of present-day energy regimes not only reveals societies' long and contentious relationship with-and dependence on-energy sources of various kinds but also challenges essentialist, linear, and at times utopian notions of "energy transitions" in public and political debates. We argue that historical research is particularly able to reveal how energy transitions have been and continue to be embedded within larger societal transitions and are subject to asymmetrical power relations as well as to circumstance, contingencies, and unanticipated effects and consequences. In order to disentangle the complex relations of society and energy, we propose focusing on three topics in particular: (1) renewable energies and environmental issues; (2) actors, networks and institutions in incumbent systems; and (3) discourses and perceptions as agents of change.

Relation between activity-induced intracellular sodium transients and ATP dynamics in mouse hippocampal neurons.

KEY POINTS: Employing quantitative Na+ -imaging and Förster resonance energy transfer-based imaging with ATeam1.03YEMK (ATeam), we studied the relation between activity-induced Na+ influx and intracellular ATP in CA1 pyramidal neurons of the mouse hippocampus. Calibration of ATeam in situ enabled a quantitative estimate of changes in intracellular ATP concentrations. Different paradigms of stimulation that induced global Na+ influx into the entire neuron resulted in decreases in [ATP] in the range of 0.1-0.6 mm in somata and dendrites, while Na+ influx that was locally restricted to parts of dendrites did not evoke a detectable change in dendritic [ATP]. Our data suggest that global Na+ transients require global cellular activation of the Na+ /K+ -ATPase resulting in a consumption of ATP that transiently overrides its production. For recovery from locally restricted Na+ influx, ATP production as well as fast intracellular diffusion of ATP and Na+ might prevent a local drop in [ATP]. ABSTRACT: Excitatory neuronal activity results in the influx of Na+ through voltage- and ligand-gated channels. Recovery from accompanying increases in intracellular Na+ concentrations ([Na+ ]i ) is mainly mediated by the Na+ /K+ -ATPase (NKA) and is one of the major energy-consuming processes in the brain. Here, we analysed the relation between different patterns of activity-induced [Na+ ]i signalling and ATP in mouse hippocampal CA1 pyramidal neurons by Na+ imaging with sodium-binding benzofurane isophthalate (SBFI) and employing the genetically encoded nanosensor ATeam1.03YEMK (ATeam). In situ calibrations demonstrated a sigmoidal dependence of the ATeam Förster resonance energy transfer ratio on the intracellular ATP concentration ([ATP]i ) with an apparent KD of 2.6 mm, indicating its suitability for [ATP]i measurement. Induction of recurrent network activity resulted in global [Na+ ]i oscillations with amplitudes of ∼10 mm, encompassing somata and dendrites. These were accompanied by a steady decline in [ATP]i by 0.3-0.4 mm in both compartments. Global [Na+ ]i transients, induced by afferent fibre stimulation or bath application of glutamate, caused delayed, transient decreases in [ATP]i as well. Brief focal glutamate application that evoked transient local Na+ influx into a dendrite, however, did not result in a measurable reduction in [ATP]i . Our results suggest that ATP consumption by the NKA following global [Na+ ]i transients temporarily overrides its availability, causing a decrease in [ATP]i . Locally restricted Na+ transients, however, do not result in detectable changes in local [ATP]i , suggesting that ATP production, together with rapid intracellular diffusion of both ATP and Na+ from and to unstimulated neighbouring regions, counteracts a local energy shortage under these conditions.

SOLO-based task to improve self-evaluation and capacity to integrate concepts in first-year physiology students.

An accurate self-assessment of student work can enhance student learning and subsequently improve academic performance. Instructors can facilitate this process by providing "standards" that students can utilize as feedback when self-evaluating their understanding. Traditional forms of feedback, such as marked assessment tasks, are limited in their ability to serve as standards, as they do not adequately capture variations corresponding to different levels of understanding. To develop a complex understanding in physiology, students have to integrate concepts pertaining to different subcomponents of body systems. The present study attempted to ascertain if exposing students to variations in complexity would refine their ability to self-evaluate their understanding and capacity to integrate concepts. Students were tasked to answer an essay-length, open-ended physiology question to expose their current understanding of the topic. The change in students' self-marking of their answer before and after being exposed to the variations in conceptual understanding of the topic were used to determine whether improvements in self-evaluation accuracy occurred. These variations were presented as instructor-generated answers to the open-ended question, framed using the structure of the observed learning outcome (SOLO) taxonomy. Student scores in the integrative questions of the end-of-semester exam were used as a measure of student ability to integrate concepts. Findings indicated that this intervention led to improvements in student self-evaluation and exam performance, and the positive outcomes were replicated across multiple iterations of the activity.

Bioorthogonal Masking of Circulating Antibody-TCO Groups Using Tetrazine-Functionalized Dextran Polymers.

Pretargeting strategies have gained popularity for the in vivo imaging and therapy of cancer by combining antibodies with small molecule radioligands. In vivo recombination of both moieties can be achieved using the bioorthogonal inverse electron demand Diels-Alder (IEDDA) chemistry between tetrazine (Tz) and trans-cyclooctene (TCO). An issue that arises with pretargeting strategies is that while part of the antibody dose accumulates at antigen-expressing tumor tissue, there is a significant portion of the injected antibody that remains in circulation, causing a reduction in target-to-background ratios. Herein, we report the development of a novel TCO scavenger, the masking agent DP-Tz. DP-Tz is based on Tz-modified dextran polymers (DP, MW = 0.5-2 MDa). Large dextran polymers were reported to exhibit low penetration of tumor vasculature and appeared nontoxic, nonimmunogenic, and easily modifiable. Our newly developed masking agent deactivates the remaining TCO-moieties on the circulating mAbs yet does not impact the tumor uptake of the Tz-radioligand. In pretargeting studies utilizing a 68Ga-labeled tetrazine radioligand ([68Ga]Ga-NOTA-PEG11-tetrazine), DP-Tz constructs (Tz/DP ratios of 62-254) significantly increased TTB ratios from 0.8 ± 0.3 (control cohorts) to up to 5.8 ± 2.3 at 2 h postinjection. Tumor tissue delineation in PET imaging experiments employing DP-Tz is significantly increased compared to control. Uptake values of other significant organs, such as heart, lungs, pancreas, and stomach, were decreased on average by 2-fold when using DP-Tz. Overall, pretargeting experiments utilizing DP-Tz showed significantly improved tumor delineation, enhanced PET image quality, and reduced uptake in vital organs. We believe that this new masking agent is a powerful new addition to the IEDDA-based pretargeting tool box and, due to its properties, an excellent candidate for clinical translation.

Direct inscription and evaluation of fiber Bragg gratings in carbon-coated optical sensor glass fibers for harsh environment oil and gas applications.

In this research work, we show the successful inscription of fiber Bragg gratings into carbon-coated pure silica as well as germanium-doped glass fibers by applying the pulsed laser point-by-point manufacturing technique. First, the parameters used for the Ti:sapphire femtosecond laser process are demonstrated. Without removing the polymeric carbon coating, destruction-free formation of highly reflective Bragg gratings is performed with selected types of hermetically enclosed fibers. We demonstrate the advantage of the carbon coating by long-term exposure to a pure hydrogen atmosphere at an elevated temperature. Such harsh conditions exist in the oil and gas industry, which means there is high application potential for technologically advanced optical sensors. Compared to the also examined standard glass fibers with a distinct signal attenuation, carbon-coated fibers show no significant degradation. Finally, we analyze the mechanical stability of the processed fibers via standardized tensile tests. No substantial decrease in strength occurs among the sensor-integrated samples.

Assisting hand function after spinal cord injury with a fabric-based soft robotic glove.

BACKGROUND: Spinal cord injury is a devastating condition that can dramatically impact hand motor function. Passive and active assistive devices are becoming more commonly used to enhance lost hand strength and dexterity. Soft robotics is an emerging discipline that combines the classical principles of robotics with soft materials and could provide a new class of active assistive devices. Soft robotic assistive devices enable a human-robot interaction facilitated by compliant and light-weight structures. The scope of this work was to demonstrate that a fabric-based soft robotic glove can effectively assist participants affected by spinal cord injury in manipulating objects encountered in daily living. METHODS: The Toronto Rehabilitation Institute Hand Function Test was administered to 9 participants with C4-C7 spinal cord injuries to assess the functionality of the soft robotic glove. The test included object manipulation tasks commonly encountered during activities of daily living (ADL) and lift force measurements. The test was administered to each participant twice; once without the assistive glove to provide baseline data and once while wearing the assistive glove. The object manipulation subtests were evaluated using a linear mixed model, including interaction effects of variables such as time since injury. The lift force measures were separately evaluated using the Wilcoxon signed-rank test. RESULTS: The soft robotic glove improved object manipulation in ADL tasks. The difference in mean scores between baseline and assisted conditions was significant across all participants and for all manipulated objects. An improvement of 33.42 ± 15.43% relative to the maximal test score indicates that the glove sufficiently enhances hand function during ADL tasks. Moreover, lift force also increased when using the assistive soft robotic glove, further demonstrating the effectiveness of the device in assisting hand function. CONCLUSIONS: The results gathered in this study validate our fabric-based soft robotic glove as an effective device to assist hand function in individuals who have suffered upper limb paralysis following a spinal cord injury.

Genomic Profiles of Diversification and Genotype-Phenotype Association in Island Nematode Lineages.

Understanding how new species form requires investigation of evolutionary forces that cause phenotypic and genotypic changes among populations. However, the mechanisms underlying speciation vary and little is known about whether genomes diversify in the same ways in parallel at the incipient scale. We address this using the nematode, Pristionchus pacificus, which resides at an interesting point on the speciation continuum (distinct evolutionary lineages without reproductive isolation), and inhabits heterogeneous environments subject to divergent environmental pressures. Using whole genome re-sequencing of 264 strains, we estimate FST to identify outlier regions of extraordinary differentiation (∼1.725 Mb of the 172.5 Mb genome). We find evidence for shared divergent genomic regions occurring at a higher frequency than expected by chance among populations of the same evolutionary lineage. We use allele frequency spectra to find that, among lineages, 53% of divergent regions are consistent with adaptive selection, whereas 24% and 23% of such regions suggest background selection and restricted gene flow, respectively. In contrast, among populations from the same lineage, similar proportions (34-48%) of divergent regions correspond to adaptive selection and restricted gene flow, whereas 13-22% suggest background selection. Because speciation often involves phenotypic and genomic divergence, we also evaluate phenotypic variation, focusing on pH tolerance, which we find is diverging in a manner corresponding to environmental differences among populations. Taking a genome-wide association approach, we functionally validate a significant genotype-phenotype association for this trait. Our results are consistent with P. pacificus undergoing heterogeneous genotypic and phenotypic diversification related to both evolutionary and environmental processes.

Functional Conservation and Divergence of daf-22 Paralogs in Pristionchus pacificus Dauer Development.

Small-molecule signaling in nematode dauer formation has emerged as a major model to study chemical communication in development and evolution. Developmental arrest as nonfeeding and stress-resistant dauer larvae represents the major survival and dispersal strategy. Detailed studies in Caenorhabditis elegans and Pristionchus pacificus revealed that small-molecule communication changes rapidly in evolution resulting in extreme structural diversity of small-molecule compounds. In C. elegans, a blend of ascarosides constitutes the dauer pheromone, whereas the P. pacificus dauer pheromone includes additional paratosides and integrates building blocks from diverse primary metabolic pathways. Despite this complexity of small-molecule structures and functions, little is known about the biosynthesis of small molecules in nematodes outside C. elegans Here, we show that the genes encoding enzymes of the peroxisomal ß-oxidation pathway involved in small-molecule biosynthesis evolve rapidly, including gene duplications and domain switching. The thiolase daf-22, the most downstream factor in C. elegans peroxisomal ß-oxidation, has duplicated in P. pacificus, resulting in Ppa-daf-22.1, which still contains the sterol-carrier-protein (SCP) domain that was lost in C. elegans daf-22, and Ppa-daf-22.2. Using the CRISPR/Cas9 system, we induced mutations in both P. pacificus daf-22 genes and identified an unexpected complexity of functional conservation and divergence. Under well-fed conditions, ascaroside biosynthesis proceeds exclusively via Ppa-daf-22.1 In contrast, starvation conditions induce Ppa-daf-22.2 activity, resulting in the production of a specific subset of ascarosides. Gene expression studies indicate a reciprocal up-regulation of both Ppa-daf-22 genes, which is, however, independent of starvation. Thus, our study reveals an unexpected functional complexity of dauer development and evolution.