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With the globally increasing awareness regarding the interconnectivity between freshwater ecosystems, projects for re-establishing connectivity with fishways as well as stock management are increasing. To ensure the quality and impact of such projects and for extending the scientific state of knowledge on this topic, a detailed monitoring of these measures is mandatory. Automatic, passive, and contactless counting devices can play a major role in these long-term monitoring projects, both for animal protection (non-invasive methods) and technical issues (comparatively low-cost systems in terms of time). Infrared fish counters can be used in a variety of fisheries applications and have proven particularly valuable in situations when long-term or continuous monitoring in lotic systems is required. Herein, we describe the function and technical capabilities of the VAKI Riverwatcher fish counter, provide information regarding its installation, and highlight some specific, practical applications of this technology. We discuss how the Riverwatcher can be used to validate the functionality of fish passage structures and to provide abundance estimates of migratory fish populations. Finally, we call attention to the challenges associated with operating monitoring equipment in variable river systems and briefly discuss potential sources of error that can influence the monitoring results and approaches to minimize or alleviate these errors. [ABSTRACT FROM AUTHOR]

The control of molecular motions is a central topic of molecular machine research. Molecular brakes are fundamental building blocks towards such goal as they allow deliberately decelerating specific motions after an outside stimulus is applied. Here we present azotriptycenes as structural framework for light‐controlled molecular brakes. The intrinsic kinetics and their changes upon azotriptycene isomerization are scrutinized comprehensively by a mixed theoretical and variable temperature NMR approach. With azotriptycenes C−N bond rotation rates can be decelerated or accelerated reversibly by up to five orders of magnitude. Rate change effects are highly localized and are strongest for the C−N bond connecting a triptycene rotor fragment to the central diazo group. The detailed mechanistic insights provide a solid basis for further conscious design and applications in the future. [ABSTRACT FROM AUTHOR]

In the case of a fire event, structural components are exposed to a thermal load. To determine the fire resistivity of building components standardized fire resistance tests (FRTs) have to be carried out. Besides the heating and the deformation of building components during the FRT, also the fire response of the adjacent wall construction is important. In the past, the fire response (deformation) of masonry brick and stud walls was examined without building components placed in the wall. However, the thermal expansion of doors and other components is causing a mechanical load on the wall, which is affecting its deformation. Thus, in the present study the deformation of masonry brick walls and gypsum‐sheathed stud walls with fire safety steel doors placed in the walls were determined during FRTs. Furthermore, the effect of the different door types, door size and wall thickness on the wall deformation was evaluated. Single leaf doors were approx. 1.3 m × 2.5 m, while double leaf doors were twice the size. The maximum deformation of the masonry brick walls was between 20 and 40 mm, and was hardly affected by the door type and size. However, larger doors with a higher temperature and thermal expansion showed a slightly increasing deformation. In contrast, stud walls were significantly affected by the door, especially when small doors were used. The wall was deformed up to approx. 100 mm for small doors. Using large doors in the stud wall, the wall deformation was limited to 20 mm. [ABSTRACT FROM AUTHOR]

In complete digital ring avulsions, amputation is usually carried out when replantation of the avulsed tissue is not an option or has failed. The purpose of this study was to report our experience in treating Urbaniak Class III degloved fingers using an ultra-thinned pedicled groin flap. Sixteen patients from ages 11 to 26 years were included. In all cases, the flexor digitorum superficialis tendon, extensor apparatus and proximal interphalangeal joint were intact. Rehabilitation included immediate active mobilization, with flap division at day 21. At a mean follow-up of 15 months, all patients but one were satisfied with the appearance. Two had mild subjective cold intolerance. No flap failure was recorded. The mean total active motion was 183° and the mean QuickDASH score was 8.8/100. Patients recovered S1 sensibility according to the Mackinnon and Dellon classification. The ultra-thinned groin flap has proved to be a reliable technique for non-replantable ring avulsions. Level of evidence: IV [ABSTRACT FROM AUTHOR]

The article focuses on expediency of such investigations lies not least in the fact that digital games have a significant influence, especially among young people on the development of historical image. It mentions digital game are popular historical images penned by game writers and via the code blocks of programmers in virtual form come to life. It also mentions various techniques of constructing historical authenticity and thus the illusion of a time machine that is more historical accuracy.

An interview with German author Robert Jütte is presented. Topics discussed include research landscape on the senses in the 1990s and 1990s circulating in the Middle Ages; changing the need for security and calls as well the methodological difficulties that historians face who choose such a diffuse object are usually asked and cultural philosophy, social theory and social psychology.

An introduction is presented in which editor discusses various articles within the issue on topics including limits of the narrow urban space the changes in location; concept of third space and space production and sensory experiences and spatial practices in the insane asylum in Hall.

Bionic prostheses have restorative potential. However, the complex interplay between intuitive motor control, proprioception, and touch that represents the hallmark of human upper limb function has not been revealed. Here, we show that the neurorobotic fusion of touch, grip kinesthesia, and intuitive motor control promotes levels of behavioral performance that are stratified toward able-bodied function and away from standard-of-care prosthetic users. This was achieved through targeted motor and sensory reinnervation, a closed-loop neural-machine interface, coupled to a noninvasive robotic architecture. Adding touch to motor control improves the ability to reach intended target grasp forces, find target durometers among distractors, and promote prosthetic ownership. Touch, kinesthesia, and motor control restore balanced decision strategies when identifying target durometers and intrinsic visuomotor behaviors that reduce the need to watch the prosthetic hand during object interactions, which frees the eyes to look ahead to the next planned action. The combination of these three modalities also enhances error correction performance. We applied our unified theoretical, functional, and clinical analyses, enabling us to define the relative contributions of the sensory and motor modalities operating simultaneously in this neural-machine interface. This multiperspective framework provides the necessary evidence to show that bionic prostheses attain more human-like function with effective sensory-motor restoration. [ABSTRACT FROM AUTHOR]

Tuning the thermal behavior of light driven molecular motors is fundamentally important for their future rational design. In many molecular motors thermal ratcheting steps are comprised of helicity inversions, energetically stabilizing the initial photoproducts. In this work we investigated a series of five hemithioindigo (HTI) based molecular motors to reveal the influence of steric hindrance in close proximity to the rotation axle on this process. Applying a high yielding synthetic procedure, we synthesized constitutional isomeric derivatives to distinguish between substitution effects at the aromatic and aliphatic position on the rotor fragment. The kinetics of thermal helix inversions were elucidated using low temperature 1H NMR spectroscopy and an in situ irradiation technique. In combination with a detailed theoretical description, a comparative analysis of substituent effects on the thermal helix inversions of the rotation cycle is now possible. Such deeper understanding of the rotational cycle of HTI molecular motors is essential for speed regulation and future applications of visible light triggered nanomachines. [ABSTRACT FROM AUTHOR]

Stroke patients often have difficulty completing motor tasks even after substantive rehabilitation. Poor recovery of motor function can often be linked to stroke-induced damage to motor pathways. However, stroke damage in pathways that impact effective integration of sensory feedback with motor control may represent an unappreciated obstacle to smooth motor coordination. In this study we investigated the effects of augmenting movement proprioception during a reaching task in six stroke patients as a proof of concept. We used a wearable neurorobotic proprioceptive feedback system to induce illusory kinaesthetic sensation by vibrating participants' upper arm muscles over active limb movements. Participants were instructed to extend their elbow to reach-and-point to targets of differing sizes at various distances, while illusion-inducing vibration (90 Hz), sham vibration (25 Hz), or no vibration was applied to the distal tendons of either their biceps brachii or their triceps brachii. To assess the impact of augmented kinaesthetic feedback on motor function we compared the results of vibrating the biceps or triceps during arm extension in the affected arm of stroke patients and able-bodied participants. We quantified performance across conditions and participants by tracking limb/hand kinematics with motion capture, and through Fitts' law analysis of reaching target acquisition. Kinematic analyses revealed that injecting 90 Hz illusory kinaesthetic sensation into the actively contracting (agonist) triceps muscle during reaching increased movement smoothness, movement directness, and elbow extension. Conversely, injecting 90 Hz illusory kinaesthetic sensation into the antagonistic biceps during reaching negatively impacted those same parameters. The Fitts' law analyses reflected similar effects with a trend toward increased throughput with triceps vibration during reaching. Across all analyses, able-bodied participants were largely unresponsive to illusory vibrational augmentation. These findings provide evidence that vibration-induced movement illusions delivered to the primary agonist muscle involved in active movement may be integrated into rehabilitative approaches to help promote functional motor recovery in stroke patients. [ABSTRACT FROM AUTHOR]

Efficiency and performance of light triggered molecular motors are crucial features that need to be mechanistically understood to improve the performance and enable conscious property tailoring for specific applications. In this work, three different hemithioindigo‐based molecular motors are investigated and all four steps in their complete unidirectional rotation are unraveled fully quantitatively. Transient absorption spectroscopy across twelve orders of magnitude in time is used to probe the fs nuclear motions up to the ms thermal kinetics, covering the timeframe of the whole motor rotation. The newly known full mechanisms allow simulation of the motor systems to scrutinize their performance at realistic illumination conditions. This highlights the importance of photoisomerization quantum yields for the rotation speed. The substitution pattern in close proximity to the rotation axle influences the excited and ground state properties. Reduction of electron donation and concomitant increase of steric hindrance leads to faster photoisomerization reactions with quasi‐ballistic behavior, but also to a slight decrease in the quantum efficiency. The expected decelerating effects of increased sterics are primarily manifested in the ground state. A promising approach for next‐generation hemithioindigo motors is to elevate electron donation at the rotor fragment followed by an increase of steric hindrance. [ABSTRACT FROM AUTHOR]

The article explores how the perspective of medicine has increasingly shifted from the macroscopic view to the molecular depth. It mentions that the development of medicine accompanied by an increased fragmentation of humans into their body parts, cells, DNA sequences and other building blocks. It discusses the nature for medical decision-making processes during the Covid-19 pandemic and explores ethical aspects of the medicine. It also mentions the increasing use of computer programs to enhance the drug development.

When developing meaningful curricula, institutions must engage with the desired disciplinary attributes of their graduates. Successfully employed in several areas, including psychology and chemistry, disciplinary literacies provide structure for the development of core competencies‐pursuing progressive education. To this end, we have sought to develop a comprehensive blueprint of a graduate biochemist, providing detailed insight into the development of skills in the context of disciplinary knowledge. The Biochemical Literacy Framework (BCLF) aspires to encourage innovative course design in both the biochemical field and beyond through stimulating discussion among individuals developing undergraduate biochemistry degree courses based on pedagogical best practice. Here, we examine the concept of biochemical literacy aiming to start answering the question: What must individuals do and know to approach and transform ideas in the context of the biochemical sciences? The BCLF began with the guidance published by relevant learned societies – including the Royal Society of Biology, the Biochemical Society, the American Society for Biochemistry and Molecular Biology and the Quality Assurance Agency, before considering relevant pedagogical literature. We propose that biochemical literacy is comprised of seven key skills: critical thinking, self‐management, communication, information literacy, visual literacy, practical skills and content knowledge. Together, these form a dynamic, highly interconnected and interrelated meta‐literacy supporting the use of evidence‐based, robust learning techniques. The BCLF is intended to form the foundation for discussion between colleagues, in addition to forming the groundwork for both pragmatic and exploratory future studies into facilitating and further defining biochemical literacy. [ABSTRACT FROM AUTHOR]

Opioid receptor activation was shown to enhance the efficacy of anti‐neoplastic drugs in several human cancer cell lines. In these cell lines, doxorubicin increased the number of opioid receptors and methadone concurrently enhanced cellular doxorubicin uptake. Triggered through lay press and media, animal owners started to challenge veterinary oncologists with questions about methadone use in anti‐cancer therapy. Especially in veterinary medicine, where side effects of chemotherapy are tolerated to a lesser extent and hence smaller doses are given, agents potentiating chemotherapeutic agents would be an optimal approach to treatment. Canine transitional cell carcinoma cells (TCC, K9TCC), canine osteosarcoma cells (OSA, Abrams) and canine hemangiosarcoma cells (HSA, DAL‐4) were incubated with different combinations of methadone, buprenorphine and doxorubicin, in order to test inhibition of cell proliferation. Opioid receptor density was assessed with fluorescence‐activated cell sorting in drug native and doxorubicin pretreated cells. In TCC and OSA cell lines opioid receptor density increased after doxorubicin pretreatment. In combination treatment, however, we did not find significant potentiation of doxorubicin's inhibitory effect on proliferation in these cell lines. Neither was there a significant increase of the effect of doxorubicin when the opioids were added 24 hr before doxorubicin. Hence, we could not confirm the hypothesis that opioids increase the anti‐proliferative effect of the anti‐neoplastic drug doxorubicin in any of these canine tumour cell lines. The lack of effect on a cellular level does not warrant a clinical approach to use opioids together with doxorubicin in dogs with cancer. [ABSTRACT FROM AUTHOR]

Pre-treatment of tumors with hyperthermia is often used to increase the efficacy of radiotherapy. One of the main proteins induced in response to hyperthermia is heat shock protein 70 (HSP70). The aim of our study was to investigate up- and down-regulated genes in response to (thermo)radiotherapy in HSP70 proficient and deficient canine osteosarcoma cell line (Abrams), and functional role of HSP70 in the mechanism of thermoradiosensitization. Cells were transfected with negative control siRNA or siRNA targeting HSP70 and treated with hyperthermia (HT), radiotherapy (RT), and thermoradiotherapy (HTRT). RNA sequencing was used to analyze gene expression. Hyperthermia and thermoradiotherapy, but not radiotherapy alone, induced differential gene expression. We identified genes differentially expressed only in HSP70 knockdown (thus HSP70-dependent) cells in response to hyperthermia and thermoradiotherapy. Interestingly, cell proliferation but not clonogenicity and apoptosis/necrosis was affected by the HSP70 knockdown in response to thermoradiotherapy. The results suggest that HSP70 regulates expression of specific genes in response to hyperthermia and thermoradiotherapy. Further investigations into the role of specific genes regulated in a HSP70-dependent manner in response to thermoradiotherapy could pave a way into new, combinatorial treatment options for (canine) osteosarcoma and other cancer types. [ABSTRACT FROM AUTHOR]

Cutaneous sensation is vital to controlling our hands and upper limbs. It helps close the motor control loop by informing adjustments of grasping forces during object manipulations and provides much of the information the brain requires to perceive our limbs as a part of our bodies. This sensory information is absent to upper-limb prosthesis users. Although robotic prostheses are becoming increasingly sophisticated, the absence of feedback imposes a reliance on open-loop control and limits the functional potential as an integrated part of the body. Experimental systems to restore physiologically relevant sensory information to prosthesis users are beginning to emerge. However, the impact of their long-term use on functional abilities, body image, and neural adaptation processes remains unclear. Understanding these effects is essential to transition sensate prostheses from sophisticated assistive tools to integrated replacement limbs. We recruited three participants with high-level upper-limb amputation who previously received targeted reinnervation surgery. Each participant was fit with a neural-machine-interface prosthesis that allowed participants to operate their device by thinking about moving their missing limb. Additionally, we fit a sensory feedback system that allowed participants to experience touch to the prosthesis as touch on their missing limb. All three participants performed a long-term take-home trial. Two participants used their neural-machine-interface systems with touch feedback and one control participant used his prescribed, insensate prosthesis. A series of functional outcome metrics and psychophysical evaluations were performed using sensate neural-machine-interface prostheses before and after the take-home period to capture changes in functional abilities, limb embodiment, and neural adaptation. Our results demonstrated that the relationship between users and sensate neural-machine-interface prostheses is dynamic and changes with long-term use. The presence of touch sensation had a near-immediate impact on how the users operated their prostheses. In the multiple independent measures of users' functional abilities employed, we observed a spectrum of performance changes following long-term use. Furthermore, after the take-home period, participants more appropriately integrated their prostheses into their body images and psychophysical tests provided strong evidence that neural and cortical adaptation occurred. [ABSTRACT FROM AUTHOR]

Dogs develop cancer spontaneously with age, with breed-specific risk underlying differences in genetics. Mammary tumors are reported as the most frequent neoplasia in intact female dogs. Their high prevalence in certain breeds suggests a genetic component, as it is the case in human familial breast cancer, distinctly in BRCA2-associated cancers. However, the molecular genetics of BRCA2 in the pathogenesis of canine cancer are still under investigation. Genetic variations of canine BRCA2 comprised single nucleotide polymorphisms, insertions and deletions. The BRCA2 level has been shown to be reduced in tumor gland samples, suggesting that low expression of BRCA2 is contributing to mammary tumor development in dogs. Additionally, specific variations of the BRCA2 gene affect RAD51 binding strength, critically damage the BRCA2-RAD51 binding and further provoke a defective repair. In humans, preclinical and clinical data revealed a synthetic lethality interaction between BRCA2 mutations and PARP inhibition. PARP inhibitors are successfully used to increase chemo- and radiotherapy sensitivity, although they are also associated with numerous side effects and acquired resistance. Cancer treatment of canine patients could benefit from increased chemo- and radiosensitivity, as their cancer therapy protocols usually include only low doses of drugs or radiation. Early investigations show tolerability of iniparib in dogs. PARP inhibitors also imply higher therapy costs and consequently are less likely to be accepted by pet owners. We summarized the current evidence of canine BRCA2 gene alterations and their association with mammary tumors. Mutations in the canine BRCA2 gene have the potential to be exploited in clinical therapy through the usage of PARP inhibitors. However, further investigations are needed before introducing PARP inhibitors in veterinary clinical practice. [ABSTRACT FROM AUTHOR]

We describe use of a bidirectional neuromyoelectric prosthetic hand that conveys biomimetic sensory feedback. Electromyographic recordings from residual arm muscles were decoded to provide independent and proportional control of a six-DOF prosthetic hand and wrist—the DEKA LUKE arm. Activation of contact sensors on the prosthesis resulted in intraneural microstimulation of residual sensory nerve fibers through chronically implanted Utah Slanted Electrode Arrays, thereby evoking tactile percepts on the phantom hand. With sensory feedback enabled, the participant exhibited greater precision in grip force and was better able to handle fragile objects. With active exploration, the participant was also able to distinguish between small and large objects and between soft and hard ones. When the sensory feedback was biomimetic—designed to mimic natural sensory signals—the participant was able to identify the objects significantly faster than with the use of traditional encoding algorithms that depended on only the present stimulus intensity. Thus, artificial touch can be sculpted by patterning the sensory feedback, and biologically inspired patterns elicit more interpretable and useful percepts. [ABSTRACT FROM AUTHOR]

The maximum speed of light‐driven molecular motors is an important key‐property governing not only their overall performances but also many advanced functions. Currently, special emphasis lies on increasing the rate of unidirectional rotations to surpass natural systems and harness the full potential of artificial motors. Herein, we report a new molecular setup for a prospective light‐powered three‐step motor based on the hemithioindigo chromophore. Comprehensive quantum chemical treatment predicts a very low energy barrier for the only thermal ratcheting step in the unidirectional 360° rotation. Thus an ultrafast motion in the THz range could be possible with this motor at high light intensities and consequently a precise control of rotation speeds solely by light intensity variations could potentially be achieved. Experimental analyses using X‐ray crystallography and solution spectroscopy deliver first insights into the working mechanism and show that visible‐light photoswitching is feasible in both stable switching states. Additionally, significant alterations of the ground‐state energies can be induced by pH changes without hampering photoswitching capabilities. [ABSTRACT FROM AUTHOR]

Objective: Aims were to investigate sensitivity of various human and canine cancer cell lines to hyperthermia and the influence of particular treatment conditions, and to analyze the DNA-damage response and mode of cell death in cell line radiosensitized by hyperthermia. Additionally, we were interested in the involvement of HSP70 in radiosensitization. Methods: Radiosensitization by hyperthermia was determined in a panel of human and canine cancer cell lines using clonogenic cell survival assay, as well as levels of heat shock proteins (HSPs) using immunoblotting. The influence of the hyperthermia-radiotherapy time gap, different temperatures and the order of treatments on clonogenicity of hyperthermia-sensitive A549 cells was investigated. Additionally, DNA damage and cell death were assessed by Comet assay and an apoptosis/necrosis assay. Further we induced transient knockdown in A549 cells to test HSP70’s involvement in radiosensitization. Results: Out of eight cell lines tested, only two (A549 and Abrams) showed significant decrease in clonogenic cell survival when pre-treated with hyperthermia at 42°C. Strong induction of HSP70 upon thermoradiotherapy (HT-RT) treatment was found in all cell lines. Transient knockdown of HSP70 in A549 cells did not result in decrease of clonogenic cell survival in response to HT-RT. Conclusion: Tumor cell-type, temperature and order of treatment play an important role in radiosensitization by hyperthermia. However, hyperthermia has limited potency to radiosensitize canine cancer cells grown in a 2D cell culture setting presented here. DNA damage and apoptosis/necrosis did not increase upon combined treatment and cytosolic levels of HSP70 appear not to play critical role in the radiosensitization of A549 cells. [ABSTRACT FROM AUTHOR]

Copyright of Reti Medievali is the property of Firenze University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The purpose of the article is to show how the questions of anomality and animality belong together in phenomenology. The figure of the human animal serves as the guideline of the study, namely the figure of a person who is not considered as similar to myself in the frame of a Husserlian characterization of normality. Husserl's thinking is analyzed with respect to the problem of an intersubjective co-constitution of a common world. It is shown that Husserl only accepts animality and anomality within the restrictive perspective of a so-called normal humanity, that of the adult man, healthy, reasonable and European. However, he constantly strives to include the anomality and animality into humanity as well, an intention that distinguishes him from Heidegger. Heidegger radicalized the question with respect to race, which serves him as a guideline for thinking the very own of the human being. Defending a thinking of exclusion, Heidegger refuses to animals as well as to anomals all right of citizenship in the community of human beings. The article ends by proposing to overcome this duality between an inclusive thinking and an exclusive thinking. [ABSTRACT FROM AUTHOR]

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Molecular motors undergo repetitive directional motions upon external energy input. A profound challenge is the defined transfer of directional motor motions to remote entities at the molecular scale. Herein, we present a molecular setup that allows for the transfer of the directional rotation of a light‐powered motor unit onto a remote biaryl axis via an ethylene glycol chain link. Based on a combination of X‐ray crystallographic analysis, ECD, and NMR experiments as well as a comprehensive theoretical assessment, we provide evidence for the coupled stepwise directional motions of both molecular units. With the presented setup, facile integration of molecular motor units into larger functional frameworks and complex molecular machines can be explored consciously in the future. [ABSTRACT FROM AUTHOR]

Photoisomerization reactions are quintessential processes driving molecular machines and motors, govern smart materials, catalytic processes, and photopharmacology, and lie at the heart of vision, phototaxis, or vitamin production. Despite this plethora of applications fundamental photoisomerization mechanisms are not well understood at present. The famous hula-twist motion—a coupled single and double-bond rotation—was proposed to explain proficient photoswitching in restricted environments but fast thermal follow-up reactions hamper identification of primary photo products. Herein we describe an asymmetric chromophore possessing four geometrically distinct diastereomeric states that do not interconvert thermally and can be crystallized separately. Employing this molecular setup direct and unequivocal evidence for the hula-twist photoreaction and for photoinduced single-bond rotation is obtained. The influences of the surrounding medium and temperature are quantified and used to favor unusual photoreactions. Based on our findings molecular engineers will be able to implement photo control of complex molecular motions more consciously. [ABSTRACT FROM AUTHOR]

Fitts' law models the relationship between amplitude, precision, and speed of rapid movements. It is widely used to quantify performance in pointing tasks, study human-computer interaction, and generally to understand perceptual-motor information processes, including research to model performance in isometric force production tasks. Applying Fitts' law to an isometric grip force task would allow for quantifying grasp performance in rehabilitative medicine and may aid research on prosthetic control and design. We examined whether Fitts' law would hold when participants attempted to accurately produce their intended force output while grasping a manipulandum when presented with images of various everyday objects (we termed this the implicit task). Although our main interest was the implicit task, to benchmark it and establish validity, we examined performance against a more standard visual feedback condition via a digital force-feedback meter on a video monitor (explicit task). Next, we progressed from visual force feedback with force meter targets to the same targets without visual force feedback (operating largely on feedforward control with tactile feedback). This provided an opportunity to see if Fitts' law would hold without vision, and allowed us to progress toward the more naturalistic implicit task (which does not include visual feedback). Finally, we changed the nature of the targets from requiring explicit force values presented as arrows on a force-feedback meter (explicit targets) to the more naturalistic and intuitive target forces implied by images of objects (implicit targets). With visual force feedback the relation between task difficulty and the time to produce the target grip force was predicted by Fitts' law (average r 2 = 0.82). Without vision, average grip force scaled accurately although force variability was insensitive to the target presented. In contrast, images of everyday objects generated more reliable grip forces without the visualized force meter. In sum, population means were well-described by Fitts' law for explicit targets with vision (r 2 = 0.96) and implicit targets (r 2 = 0.89), but not as well-described for explicit targets without vision (r 2 = 0.54). Implicit targets should provide a realistic see-object-squeeze-object test using Fitts' law to quantify the relative speed-accuracy relationship of any given grasper. [ABSTRACT FROM AUTHOR]

Remote control of complex molecular behavior and function is one key problem in modern chemistry. Using light signaling for this purpose has many advantages, however the integration of different photo processes into a wholesome yet complex system is highly challenging. Here we report an alternative approach to increase complexity of light control-simultaneous complementary photoswitching-in which spectral overlap is used as an advantage to drastically reduce the signaling needed for controlling multipart supramolecular assemblies. Two photoswitchable molecular tweezers respond to the same light signals with opposite changes in their binding affinities. In this way the configuration of two host tweezers and ultimately the dynamic relocation of a guest molecule can be trigged by only one signal reversibly in the same solution. This approach should provide a powerful tool for the construction of sophisticated, integrated, and multi-responsive smart molecular systems in any application driven field of chemistry. [ABSTRACT FROM AUTHOR]

A perceptual illusion provides the sensation of complex bionic hand movements to human amputees, allowing real-time movement control without the necessity of vision. Good vibrations for movement perception: The ability to sense the spatial position and movements of one's own body (kinesthetic sense) is critical for limb use. Because prostheses do not provide physical feedback during movement, amputees may not feel that they are in control of their bodily movements (sense of agency) when manipulating a prosthesis. Marasco et al. developed an automated neural-machine interface that vibrates the muscles used for control of prosthetic hands. This system instilled kinesthetic sense in amputees, allowing them to control prosthetic hand movements in the absence of visual feedback and increasing their sense of agency. This approach might be an effective strategy for improving motor performance and quality of life in amputees. To effortlessly complete an intentional movement, the brain needs feedback from the body regarding the movement's progress. This largely nonconscious kinesthetic sense helps the brain to learn relationships between motor commands and outcomes to correct movement errors. Prosthetic systems for restoring function have predominantly focused on controlling motorized joint movement. Without the kinesthetic sense, however, these devices do not become intuitively controllable. We report a method for endowing human amputees with a kinesthetic perception of dexterous robotic hands. Vibrating the muscles used for prosthetic control via a neural-machine interface produced the illusory perception of complex grip movements. Within minutes, three amputees integrated this kinesthetic feedback and improved movement control. Combining intent, kinesthesia, and vision instilled participants with a sense of agency over the robotic movements. This feedback approach for closed-loop control opens a pathway to seamless integration of minds and machines. [ABSTRACT FROM AUTHOR]

Background: Estrogen is a vital hormone that regulates many biological functions within the body. These include roles in the development of the secondary sexual organs in both sexes, plus uterine angiogenesis and proliferation during the menstrual cycle and pregnancy in women. The varied biological roles of estrogens in human health also make them a therapeutic target for contraception, mitigation of the adverse effects of the menopause, and treatment of estrogen-responsive tumours. In addition, endogenous (e.g. genetic variation) and external (e.g. exposure to estrogen-like chemicals) factors are known to impact estrogen biology. To understand how these multiple factors interact to determine an individual's response to therapy is complex, and may be best approached through a systems approach. Methods: We present a physiologically-based pharmacokinetic model (PBPK) of estradiol, and validate it against plasma kinetics in humans following intravenous and oral exposure. We extend this model by replacing the intrinsic clearance term with: a detailed kinetic model of estrogen metabolism in the liver; or, a genome-scale model of liver metabolism. Both models were validated by their ability to reproduce clinical data on estradiol exposure. We hypothesise that the enhanced mechanistic information contained within these models will lead to more robust predictions of the biological phenotype that emerges from the complex interactions between estrogens and the body. Results: To demonstrate the utility of these models we examine the known drug-drug interactions between phenytoin and oral estradiol. We are able to reproduce the approximate 50% reduction in area under the concentration-time curve for estradiol associated with this interaction. Importantly, the inclusion of a genome-scale metabolic model allows the prediction of this interaction without directly specifying it within the model. In addition, we predict that PXR activation by drugs results in an enhanced ability of the liver to excrete glucose. This has important implications for the relationship between drug treatment and metabolic syndrome. Conclusions: We demonstrate how the novel coupling of PBPK models with genome-scale metabolic networks has the potential to aid prediction of drug action, including both drug-drug interactions and changes to the metabolic landscape that may predispose an individual to disease development. [ABSTRACT FROM AUTHOR]

River system measurement and mapping using UAVs is both lean and agile, with the added advantage of increased safety for the surveying crew. A common parameter of fluvial geomorphological studies is the flow velocity, which is a major driver of sediment behavior. Advances in fluid mechanics now include metrics describing the presence and interaction of coherent structures within a flow field and along its boundaries. These metrics have proven to be useful in studying the complex turbulent flows but require time-resolved flow field data, which is normally unavailable in geomorphological studies. Contactless UAV-based velocity measurement provides a new source of velocity field data for measurements of extreme hydrological events at a safe distance, and could allow for measurements of inaccessible areas. Recent works have successfully applied large-scale particle image velocimetry (LSPIV) using UAVs in rivers, focusing predominantly on surficial flow estimation by tracking intensity differences between georeferenced images. The objective of this work is to introduce a methodology for UAV based real-time particle tracking in rivers (RAPTOR) in a case study along a short test reach of the Brigach River in the German Black Forest. This methodology allows for large-scale particle tracking velocimetry (LSPTV) using a combination of floating, infrared light-emitting particles and a programmable embedded color vision sensor in order to simultaneously detect and track the positions of objects. The main advantage of this approach is its ability to rapidly collect and process the position data, which can be done in real time. The disadvantages are that the method requires the use of specialized light-emitting particles, which in some cases cannot be retrieved from the investigation area, and that the method returns velocity data in unscaled units of px/s. This work introduces the RAPTOR system with its hardware, data processing workflow, and provides an example of unscaled velocity field estimation using the proposed method. First experiences with the method show that the tracking rate of 50 Hz allows for position estimation with sub-pixel accuracy, even considering UAV self-motion. A comparison of the unscaled tracks after Savitzky-Golay filtering shows that although the time-averaged velocities remain virtually the same, the filter reduces the standard deviation by more than 40% and the maxima by 20%. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Hemithioindigo molecular motors undergo very fast unidirectional rotation upon irradiation with visible light, which has prevented a complete analysis of their working mechanism. In this work, we have considerably slowed down their motion by using a new synthesis for sterically hindered motor derivatives. This method allowed the first observation of all four intermediate states populated during rotation. The exact order in which each isomeric state is formed under irradiation conditions was elucidated using low temperature 1H NMR spectroscopy in conjunction with other analytical methods. At the same time, complete unidirectionality could also be directly shown. Access to slowly rotating hemithioindigo motors opens up a plethora of new applications for visible-light-induced unidirectional motions, especially in areas such as catalysis, smart materials, and supramolecular chemistry. [ABSTRACT FROM AUTHOR]

Hemithioindigo molecular motors undergo very fast unidirectional rotation upon irradiation with visible light, which has prevented a complete analysis of their working mechanism. In this work, we have considerably slowed down their motion by using a new synthesis for sterically hindered motor derivatives. This method allowed the first observation of all four intermediate states populated during rotation. The exact order in which each isomeric state is formed under irradiation conditions was elucidated using low temperature 1H NMR spectroscopy in conjunction with other analytical methods. At the same time, complete unidirectionality could also be directly shown. Access to slowly rotating hemithioindigo motors opens up a plethora of new applications for visible-light-induced unidirectional motions, especially in areas such as catalysis, smart materials, and supramolecular chemistry. [ABSTRACT FROM AUTHOR]

Imagery collected with an unmanned aerial vehicle (UAV) in conjunction with image processing provides new sources of environmental intelligence data and can be implemented in river habitat studies. High-resolution RGB orthomosaic images with 1 cm/px resolution are generated from RGB images acquired with a UAV. Ground truth mapping of the dominant substrate of the river bottom is then used to classify each spatial region. Several texture parameters are examined using image processing techniques to determine the presence and extent of each of the dominant grain classes, providing a method to classify and map the river bed. The method differentiates between submerged, dry exposed, and vegetated regions. The image cover was classified via application and examination of a variety of pixel-based image classification methods. The highest classification accuracy for pixel based analysis was achieved using the thresholding and masking algorithm which achieved an overall 97% correct classification. In addition, object-based image classification was applied using different grey-level co-occurrence matrices (GLCM) in all directions. The classification accuracy for segmentation based classification was found to be lower, at 61%. [ABSTRACT FROM PUBLISHER]

Die sogenannte Forschungsdokumentation stellt für die fachwissenschaftliche Forschung über die Hand- und Druckschriftenbestände der Bayerischen Staatsbibliothek (BSB) ein unverzichtbares und somit stark nachgefragtes Hilfsmittel dar, das seit nunmehr sechseinhalb Jahrzehnten unterhalten und kontinuierlich ausgebaut wird. Die seit 2004 verfügbare Datenbank ist Anfang 2015 in einer neuen, technisch deutlich verbesserten Version unter der Adresse https://hsslit.bsb-muenchen.de zugänglich gemacht worden. Dabei galt es, sowohl auf die enorm gestiegenen Nutzererwartungen der Fachcommunity zu reagieren, als auch auf die vorhandenen personellen Ressourcen im Bibliotheksbereich eine Antwort zu finden und somit auch die Mitarbeiterperspektive entsprechend zu berücksichtigen. Trotz aller Anpassungen an die spezifischen Bedürfnisse der Bibliothek hat diese technische Lösung einen gewissen Modellcharakter. The Research Documentation Interface is an important and indispensable tool for international scholarship on the manuscripts and early printed books of the Bavarian State Library (Bayerische Staatsbibliothek, BSB). It has been maintained and continuously expanded for more than six decades. After being transformed into an online database in 2004, it was relaunched in form of a redesigned and technically much improved version early in 2015. It can be consulted, in both German and English, via https://hsslit.bsb-muenchen.de. The two main objectives for creating the new interface have been to adapt to user expectations and at the same time to consider the needs of library staff. Despite all adjustments to suit the specific requirements of the BSB this technical infrastructure may well serve as a model. [ABSTRACT FROM AUTHOR]

Rigorous descriptions of ocular motor mechanics are often needed for models of ocular motor circuits. The mouse has become an important tool for ocular motor studies, yet most mechanical data come from larger species. Recordings of mouse abducens neurons indicate the mouse mechanics share basic viscoelastic properties with larger species but have considerably longer time constants. Time constants can also be extracted from the rate at which the eye re-centers when released from an eccentric position. The displacement can be accomplished by electrically stimulating ocular motor nuclei, but electrical stimulation may also activate nearby ocular motor circuitry. We achieved specific activation of abducens motoneurons through photostimulation in transgenic mice expressing channelrhodopsin in cholinergic neurons. Histology confirmed strong channelrhodopsin expression in the abducens nucleus with relatively little expression in nearby ocular motor structures. Stimulation was delivered as 20- to 1,000-ms pulses and 40-Hz trains. Relaxations were modeled best by a two-element viscoelastic system. Time constants were sensitive to stimulus duration. Analysis of isometric relaxation of isolated mouse extraocular muscles suggest the dependence is attributable to noninstantaneous decay of active forces in non-twitch fibers following stimulus offset. Time constants were several times longer than those obtained in primates, confirming that the mouse ocular motor mechanics are relatively sluggish. Finally, we explored the effects of 0.1- to 20-Hz sinusoidal photostimuli and demonstrated their potential usefulness in characterizing ocular motor mechanics, although this application will require further data on the temporal relationship between photostimulation and neuronal firing in extraocular motoneurons. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including political involvement of women in Switzerland, transformation in political power of women and gender discrimination seen in political participation.

This contribution challenges the prevalent opinion in research that the letter collection of Petrus de Vinea was compiled around 1270 at the papal Curia. Analysing the short five-part redaction, it determines that this represents the earliest transmitted compilation, which is entirely focussed on Emperor Frederick II and the Staufen Kingdom of Sicily, probably took its origin at the royal court there and was most likely strongly determined by the participation of the notary Nicolaus de Rocca. It pays homage to the important author (dictator) of the preceding years, Petrus de Vinea, and recalls a golden period under the governance of an exemplary ruler. Between the summer of 1264 and early 1266, it was reworked to the long five-part and this then to the short six-part redactions, both including additional letters. They may have been composed at the studium of Naples where such an Ars dictaminis with a focus on politics and administration was needed. [ABSTRACT FROM AUTHOR]

Mutation of the Cacna1a gene for the P/Q (CaV2.1) calcium channel invariably leads to cerebellar dysfunction. The dysfunction has been attributed to disrupted rhythmicity of cerebellar Purkinje cells, but the hypothesis remains unproven. If irregular firing rates cause cerebellar dysfunction, then the irregularity and behavioral deficits should covary in a series of mutant strains of escalating severity. We compared firing irregularity in floccular and anterior vermis Purkinje cells in the mildly affected rocker and moderately affected tottering Cacna1a mutants and normal C57BL/6 mice. We also measured the amplitude and timing of modulations of floccular Purkinje cell firing rate during the horizontal vestibuloocular reflex (VOR, 0.25-1 Hz) and the horizontal and vertical optokinetic reflex (OKR, 0.125-1 Hz). We recorded Purkinje cells selective for rotational stimulation about the vertical axis (VAPCs) and a horizontal axis (HAPCs). Irregularity scaled with behavioral deficit severity in the flocculus but failed to do so in the vermis, challenging the irregularity hypothesis. Mutant VAPCs exhibited unusually strong modulation during VOR and OKR, the response augmentation scaling with phenotypic severity. HAPCs exhibited increased OKR modulation but in tottering only. The data contradict prior claims that modulation amplitude is unaffected in tottering but support the idea that attenuated compensatory eye movements in Cacna1a mutants arise from defective transfer of Purkinje cell signals to downstream circuitry, rather than attenuated synaptic transmission within the cerebellar cortex. Shifts in the relative sizes of the VAPC and HAPC populations raise the possibility that Cacna1a mutations influence the development of floccular zone architecture. [ABSTRACT FROM AUTHOR]

Sleep restriction and circadian clock disruption are associated with metabolic disorders such as obesity, insulin resistance, and diabetes. The metabolic pathways involved in human sleep, however, have yet to be investigated with the use of a metabolomics approach. Here we have used untargeted and targeted liquid chromatography (LC)/MS metabolomics to examine the effect of acute sleep deprivation on plasma metabolite rhythms. Twelve healthy young male subjects remained in controlled laboratory conditions with respect to environmental light, sleep, meals, and posture during a 24-h wake/ sleep cycle, followed by 24 h of wakefulness. Two-hourly plasma samples collected over the 48 h period were analyzed by LC/MS. Principal component analysis revealed a clear time of day variation with a significant cosine fit during the wake/sleep cycle and during 24 h of wakefulness in untargeted and targeted analysis. Of 171 metabolites quantified, daily rhythms were observed in the majority (n = 109), with 78 of these maintaining their rhythmicity during 24 h of wakefulness, most with reduced amplitude (n = 66). During sleep deprivation, 27 metabolites (tryptophan, serotonin, taurine, 8 acylcar-nitines, 13 glycerophospholipids, and 3 sphingolipids) exhibited significantly increased levels compared with during sleep. The increased levels of serotonin, tryptophan, and taurine may explain the antidepressive effect of acute sleep deprivation and deserve further study. This report, to our knowledge the first of metabolic profiling during sleep and sleep deprivation and characterization of 24 h rhythms under these conditions, offers a novel view of human sleep/wake regulation. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide production by glucose oxidase (GOx) and its negative effect on laccase performance have been studied. Simultaneously, FAD-dependent glucose dehydrogenase (FAD-GDH), an O2-insensitive enzyme, has been evaluated as a substitute. Experiments focused on determining the effect of the side reaction of GOx between its natural electron acceptor O2 (consumed) and hydrogen peroxide (produced) in the electrolyte. Firstly, oxygen consumption was investigated by both GOx and FAD-GDH in the presence of substrate. Relatively high electrocatalytic currents were obtained with both enzymes. O2 consumption was observed with immobilized GOx only, whilst O2 concentration remained stable for the FAD-GDH. Dissolved oxygen depletion effects on laccase electrode performances were investigated with both an oxidizing and a reducing electrode immersed in a single compartment. In the presence of glucose, dramatic decreases in cathodic currents were recorded when laccase electrodes were combined with a GOx-based electrode only. Furthermore, it appeared that the major loss of performance of the cathode was due to the increase of H2O2 concentration in the bulk solution induced laccase inhibition. 24 h stability experiments suggest that the use of O2-insensitive FAD-GDH as to obviate in situ peroxide production by GOx is effective. Open-circuit potentials of 0.66 ± 0.03 V and power densities of 122.2 ± 5.8 μW cm−2 were observed for FAD-GDH/laccase biofuel cells. [ABSTRACT FROM AUTHOR]

The potassium channel antagonist 4-aminopyridine (4-AP) improves a variety of motor abnormalities associated with disorders of the cerebellum. The most rigorous quantitative data relate to 4-AP's ability to improve eye movement deficits in humans referable to dysfunction of the cerebellar flocculus. Largely based on work in the ataxic mouse mutant tottering (which carries a mutation of the Cacna1a gene of the P/Q voltage-activated calcium channel), 4-AP is hypothesized to function by enhancing excitability or rhythmicity of floccular Purkinje cells. We tested this hypothesis by determining whether systemic or intrafloccular administration of 4-AP would ameliorate the eye movement deficits in tottering that are attributable to flocculus dysfunction, including the reductions in amplitude of the yaw-axis vestibulo-ocular reflex (VOR) and vision-enhanced vestibulo-ocular reflex (VVOR), and the optokinetic reflex (OKR) about yaw and roll axes. Because tottering's deficits increase with age, both young and elderly mutants were tested to detect any age-dependent 4-AP effects. 4-AP failed to improve VOR, VVOR, and OKR gains during sinusoidal stimuli, although it may have reduced the tendency of the mutants' responses to VOR and VVOR to decline over the course of a one-hour recording session. For constant-velocity optokinetic stimuli, 4-AP generated some enhancement of yaw OKR and upward-directed roll OKR, but the effects were also seen in normal C57BL/6 controls, and thus do not represent a specific reversal of the electrophysiological consequences of the tottering mutation. Data support a possible extra-floccular locus for the effects of 4-AP on habituation and roll OKR. Unilateral intrafloccular 4-AP injections did not affect ocular motility, except to generate mild eye elevations, consistent with reduced floccular output. Because 4-AP did not produce the effects expected if it normalized outputs of floccular Purkinje cells, there is a need for further studies to elucidate the drug's mechanism of action on cerebellar motor dysfunction. [ABSTRACT FROM AUTHOR]

The mechanics of the eyeball and orbital tissues (the "ocular motor plant") are a fundamental determinant of ocular motor signal processing. The mouse is used increasingly in ocular motor physiology, but little is known about its plant mechanics. One way to characterize the mechanics is to determine relationships between extraocular motoneuron firing and eye movement. We recorded abducens nucleus neurons in mice executing compensatory eye movements during 0.1- to 1.6-Hz oscillation in the light. We analyzed firing rates to extract eye position and eye velocity sensitivities, from which we determined time constants of a viscoelastic model of the plant. The majority of abducens neurons were already active with the eye in its central rest position, with only 6% recruited at more abducted positions. Firing rates exhibited largely linear relationships to eye movement, although there was a nonlinearity consisting of increasing modulation in proportion to eye movement as eye amplitudes became small (due to reduced stimulus amplitude or reduced alertness). Eye position and velocity sensitivities changed with stimulus frequency as expected for an ocular motor plant dominated by cascaded viscoelasticities. Transfer function poles lay at approximately 0.1 and 0.9 s. Compared with previously studied animal species, the mouse plant is stiffer than the rabbit but laxer than cat and rhesus. Differences between mouse and rabbit can be explained by scaling for eye size (allometry). Differences between the mouse and cat or rhesus can be explained by differing ocular motor repertoires of animals with and without a fovea or area centralis. [ABSTRACT FROM AUTHOR]

Downbeat nystagmus (DBN) is a common eye movement complication of cerebellar disease. Use of mice to study pathophysiology of vestibulocerebellar disease is increasing, but it is unclear if mice can be used to study DBN; it has not been reported in this species. We determined whether DBN occurs in the ataxic mutant tottering, which carries a mutation in the Cacna1a gene for P/Q calcium channels. Spontaneous DBN occurred only rarely, and its magnitude did not exhibit the relationship to head tilt seen in human patients. DBN during yaw rotation was more common and shares some properties with the tilt-independent, gaze-independent component of human DBN, but differs in its dependence on vision. Hyperactivity of otolith circuits responding to pitch tilts is hypothesized to contribute to the gaze-independent component of human DBN. Mutants exhibited hyperactivity of the tilt maculo-ocular reflex (tiltMOR) in pitch. The hyperactivity may serve as a surrogate for DBN in mouse studies. TiltMOR hyperactivity correlates with hyperdeviation of the eyes and upward deviation of the head during ambulation; these may be alternative surrogates. Muscimol inactivation of the cerebellar flocculus suggests a floccular role in the tiltMOR hyperactivity and provides insight into the rarity of frank DBN in ataxic mice. [ABSTRACT FROM AUTHOR]

Although daily rhythms regulate multiple aspects of human physiology, rhythmic control of the metabolome remains poorly understood. The primary objective of this proof-of-concept study was identification of metabolites in human plasma that exhibit significant 24-h variation. This was assessed via an untargeted metabolomic approach using liquid chromatography-mass spectrometry (LC-MS). Eight lean, healthy, and unmedicated men, mean age 53.6 (SD ± 6.0) yrs, maintained a fixed sleep/wake schedule and dietary regime for 1 wk at home prior to an adaptation night and followed by a 25-h experimental session in the laboratory where the light/dark cycle, sleep/wake, posture, and calorific intake were strictly controlled. Plasma samples from each individual at selected time points were prepared using liquid-phase extraction followed by reverse-phase LC coupled to quadrupole time-of-flight MS analysis in positive ionization mode. Time-of-day variation in the metabolites was screened for using orthogonal partial least square discrimination between selected time points of 10:00 vs. 22:00 h, 16:00 vs. 04:00 h, and 07:00 (d 1) vs. 16:00 h, as well as repeated-measures analysis of variance with time as an independent variable. Subsequently, cosinor analysis was performed on all the sampled time points across the 24-h day to assess for significant daily variation. In this study, analytical variability, assessed using known internal standards, was low with coefficients of variation <10%. A total of 1069 metabolite features were detected and 203 (19%) showed significant time-of-day variation. Of these, 34 metabolites were identified using a combination of accurate mass, tandem MS, and online database searches. These metabolites include corticosteroids, bilirubin, amino acids, acylcarnitines, and phospholipids; of note, the magnitude of the 24-h variation of these identified metabolites was large, with the mean ratio of oscillation range over MESOR (24-h time series mean) of 65% (95% confidence interval [CI]: 49-81%). Importantly, several of these human plasma metabolites, including specific acylcarnitines and phospholipids, were hitherto not known to be 24-h variant. These findings represent an important baseline and will be useful in guiding the design and interpretation of future metabolite-based studies. (Author correspondence: or ) [ABSTRACT FROM AUTHOR]