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Magnetic Resonance Imaging (MRI) offers strong soft tissue contrast but suffers from long acquisition times and requires tedious annotation from radiologists. Traditionally, these challenges have been addressed separately with reconstruction and image analysis algorithms. To see if performance could be improved by treating both as end-to-end, we hosted the K2S challenge, in which challenge participants segmented knee bones and cartilage from 8× undersampled k-space. We curated the 300-patient K2S dataset of multicoil raw k-space and radiologist quality-checked segmentations. 87 teams registered for the challenge and there were 12 submissions, varying in methodologies from serial reconstruction and segmentation to end-to-end networks to another that eschewed a reconstruction algorithm altogether. Four teams produced strong submissions, with the winner having a weighted Dice Similarity Coefficient of 0.910 ± 0.021 across knee bones and cartilage. Interestingly, there was no correlation between reconstruction and segmentation metrics. Further analysis showed the top four submissions were suitable for downstream biomarker analysis, largely preserving cartilage thicknesses and key bone shape features with respect to ground truth. K2S thus showed the value in considering reconstruction and image analysis as end-to-end tasks, as this leaves room for optimization while more realistically reflecting the long-term use case of tools being developed by the MR community.

Background: Gadolinium (Gd)-enhanced Magnetic Resonance Imaging (MRI) is crucial in several applications, including oncology, cardiac imaging, and musculoskeletal inflammatory imaging. One use case is rheumatoid arthritis (RA), a widespread autoimmune condition for which Gd MRI is crucial in imaging synovial joint inflammation, but Gd administration has well-documented safety concerns. As such, algorithms that could synthetically generate post-contrast peripheral joint MR images from non-contrast MR sequences would have immense clinical utility. Moreover, while such algorithms have been investigated for other anatomies, they are largely unexplored for musculoskeletal applications such as RA, and efforts to understand trained models and improve trust in their predictions have been limited in medical imaging. Methods: A dataset of 27 RA patients was used to train algorithms that synthetically generated post-Gd IDEAL wrist coronal T1-weighted scans from pre-contrast scans. UNets and PatchGANs were trained, leveraging an anomaly-weighted L1 loss and global generative adversarial network (GAN) loss for the PatchGAN. Occlusion and uncertainty maps were also generated to understand model performance. Results: UNet synthetic post-contrast images exhibited stronger normalized root mean square error (nRMSE) than PatchGAN in full volumes and the wrist, but PatchGAN outperformed UNet in synovial joints (UNet nRMSEs: volume = 6.29 ± 0.88, wrist = 4.36 ± 0.60, synovial = 26.18 ± 7.45; PatchGAN nRMSEs: volume = 6.72 ± 0.81, wrist = 6.07 ± 1.22, synovial = 23.14 ± 7.37; n = 7). Occlusion maps showed that synovial joints made substantial contributions to PatchGAN and UNet predictions, while uncertainty maps showed that PatchGAN predictions were more confident within those joints. Conclusions: Both pipelines showed promising performance in synthesizing post-contrast images, but PatchGAN performance was stronger and more confident within synovial joints, where an algorithm like this w

PbTe crystals have a soft transverse optical phonon mode in the terahertz frequency range, which is known to efficiently decay into heat-carrying acoustic phonons, resulting in anomalously low thermal conductivity. Here, we studied this phonon via polarization-dependent terahertz spectroscopy. We observed softening of this mode with decreasing temperature, indicative of incipient ferroelectricity, which we explain through a model including strong anharmonicity with a quartic displacement term. In magnetic fields up to 25 T, the phonon mode splits into two modes with opposite handedness, exhibiting circular dichroism. Their frequencies display Zeeman splitting together with an overall diamagnetic shift with increasing magnetic field. Using a group-theoretical approach, we demonstrate that these observations are the result of magnetic field-induced morphic changes in the crystal symmetries through the Lorentz force exerted on the lattice ions. Thus, our Letter reveals a novel process of controlling phonon properties in a soft ionic lattice by a strong magnetic field.

PbTe crystals have a soft transverse optical phonon mode in the terahertz frequency range, which is known to efficiently decay into heat-carrying acoustic phonons, resulting in anomalously low thermal conductivity. Here, we studied this phonon via polarization-dependent terahertz spectroscopy. We observed softening of this mode with decreasing temperature, indicative of incipient ferroelectricity, which we explain through a model including strong anharmonicity with a quartic displacement term. In magnetic fields up to 25 T, the phonon mode splits into two modes with opposite handedness, exhibiting circular dichroism. Their frequencies display Zeeman splitting together with an overall diamagnetic shift with increasing magnetic field. Using a group-theoretical approach, we demonstrate that these observations are the result of magnetic field-induced morphic changes in the crystal symmetries through the Lorentz force exerted on the lattice ions. Thus, our Letter reveals a novel process of controlling phonon properties in a soft ionic lattice by a strong magnetic field.

Peptides play important roles in regulating biological processes and form the basis of a multiplicity of therapeutic drugs. To date, only about 300 peptides in human have confirmed bioactivity, although tens of thousands have been reported in the literature. The majority of these are inactive degradation products of endogenous proteins and peptides, presenting a needle-in-a-haystack problem of identifying the most promising candidate peptides from large-scale peptidomics experiments to test for bioactivity. To address this challenge, we conducted a comprehensive analysis of the mammalian peptidome across seven tissues in four different mouse strains and used the data to train a machine learning model that predicts hundreds of peptide candidates based on patterns in the mass spectrometry data. We provide in silico validation examples and experimental confirmation of bioactivity for two peptides, demonstrating the utility of this resource for discovering lead peptides for further characterization and therapeutic development.

Peptides play important roles in regulating biological processes and form the basis of a multiplicity of therapeutic drugs. To date, only about 300 peptides in human have confirmed bioactivity, although tens of thousands have been reported in the literature. The majority of these are inactive degradation products of endogenous proteins and peptides, presenting a needle-in-a-haystack problem of identifying the most promising candidate peptides from large-scale peptidomics experiments to test for bioactivity. To address this challenge, we conducted a comprehensive analysis of the mammalian peptidome across seven tissues in four different mouse strains and used the data to train a machine learning model that predicts hundreds of peptide candidates based on patterns in the mass spectrometry data. We provide in silico validation examples and experimental confirmation of bioactivity for two peptides, demonstrating the utility of this resource for discovering lead peptides for further characterization and therapeutic development.

Spin-Crossover nanomaterials have been actively studied in the past decade for their potential technological applications in sensing, actuating, and information processing devices. Unfortunately, an increasing number of the metallic centers become inactive at reduced sizes, presumably due to surface effects, limiting their switching ability and thus the scope of applications. Here we report on the investigation of "frozen" metallic centers in nanoparticles (2-80 nm size) of the spin-crossover compound Fe(pyrazine)[Ni(CN) 4 ]. Magnetic measurements reveal both high-spin and low-spin residual fractions at atmospheric pressure. A pressure-induced transition of the high-spin residue is observed at around 1.5 GPa by synchrotron Mössbauer spectroscopy. We show that it is equivalent to a downshift of the transition temperature by ca. 400 K due to the size reduction. Unexpectedly, small-angle neutron scattering experiments demonstrate that these high-spin residual centers are not confined to the surface, which contradicts general theoretical considerations.

The northward-flowing Humboldt Current hosts perpetually high levels of productivity along the western coast of South America. Here, we aim to elucidate the deep-time history of this globally important ecosystem based on a detailed palaeoecological analysis of the exceptionally preserved middle–upper Miocene vertebrate assemblages of the Pisco Formation of the East Pisco Basin, southern Peru. We summarise observations on hundreds of fossil whales, dolphins, seals, seabirds, turtles, crocodiles, sharks, rays, and bony fishes to reconstruct ecological relationships in the wake of the Middle Miocene Climatic Optimum, and the marked cooling that followed it. The lowermost, middle Miocene Pisco sequence (P0) and its vertebrate assemblage testify to a warm, semi-enclosed, near-shore palaeoenvironment. During the first part of the Tortonian (P1), high productivity within a prominent upwelling system supported a diverse assemblage of mesopredators, at least some of which permanently resided in the Pisco embayment and used it as a nursery or breeding/calving area. Younger portions of the Pisco Formation (P2) reveal a more open setting, with wide-ranging species like rorquals increasingly dominating the vertebrate assemblage, but also local differences reflecting distance from the coast. Like today, these ancient precursors of the modern Humboldt Current Ecosystem were based on sardines, but notably differed from their present-day equivalent in being dominated by extremely large-bodied apex predators like Livyatan melvillei and Carcharocles megalodon.

The Miocene Pisco Formation, broadly exposed in the Ica Desert of southern Peru, is among the most outstanding Cenozoic marine Fossil-Lagerstätten worldwide. It is renowned for its exceptional preservation and abundance of vertebrate fossils, including a rich assemblage of whales and dolphins (Cetacea). Here, we integrate taphonomic data on 890 marine vertebrate fossils, gathered through 16 different localities. Our observations range from the taxonomic distribution, articulation, completeness, disposition and orientation of skeletons, to the presence of bite marks, associations with shark teeth and macro-invertebrates, bone and soft tissue preservation, and the formation of attendant carbonate concretions and sedimentary structures. We propose that the exceptional preservation characterising many Pisco vertebrates, as well as their exceptionally high abundance, cannot be ascribed to a single cause like high sedimentation rates (as proposed in the past), but rather to the interplay of several favourable factors including: (i) low levels of dissolved oxygen at the seafloor (with the intervention of seasonal anoxic events); (ii) the early onset of mineralisation processes like apatite dissolution/recrystallisation and carbonate mineral precipitation; (iii) rapid burial of carcasses in a soupy substrate and/or a novel mechanism involving scour-induced self-burial; and (iv) original biological richness. Collectively, our observations provide a comprehensive overview of the taphonomic processes that shaped one of South America’s most important fossil deposits, and suggest a model for the formation of other marine vertebrate Fossil-Lagerstätten.

It has been proposed that classical filtering methods, like the Kalman filter and 3DVAR, can be used to solve linear statistical inverse problems. In the work of Iglesias, Lin, Lu, & Stuart (2017), error estimates were obtained for this approach. By optimally tuning a regularization parameter in the filters, the authors were able to show that the mean squared error could be systematically reduced. Building on the aforementioned work of Iglesias, Lin, Lu, & Stuart, we prove that by (i) considering the problem in a weaker norm and (ii) applying simple iterate averaging of the filter output, 3DVAR will converge in mean square, unconditionally on the choice of parameter. Without iterate averaging, 3DVAR cannot converge by running additional iterations with a fixed choice of parameter. We also establish that the Kalman filter's performance in this setting cannot be improved through iterate averaging. We illustrate our results with numerical experiments that suggest our convergence rates are sharp., Comment: revision 1, 20 pages, 3 figures

The Miocene Pisco Formation, broadly exposed in the Ica Desert of southern Peru, is among the most outstanding Cenozoic marine Fossil-Lagerstätten worldwide. It is renowned for its exceptional preservation and abundance of vertebrate fossils, including a rich assemblage of whales and dolphins (Cetacea). Here, we integrate taphonomic data on 890 marine vertebrate fossils, gathered through 16 different localities. Our observations range from the taxonomic distribution, articulation, completeness, disposition and orientation of skeletons, to the presence of bite marks, associations with shark teeth and macro-invertebrates, bone and soft tissue preservation, and the formation of attendant carbonate concretions and sedimentary structures. We propose that the exceptional preservation characterising many Pisco vertebrates, as well as their exceptionally high abundance, cannot be ascribed to a single cause like high sedimentation rates (as proposed in the past), but rather to the interplay of several favourable factors including: (i) low levels of dissolved oxygen at the seafloor (with the intervention of seasonal anoxic events); (ii) the early onset of mineralisation processes like apatite dissolution/recrystallisation and carbonate mineral precipitation; (iii) rapid burial of carcasses in a soupy substrate and/or a novel mechanism involving scour-induced self-burial; and (iv) original biological richness. Collectively, our observations provide a comprehensive overview of the taphonomic processes that shaped one of South America’s most important fossil deposits, and suggest a model for the formation of other marine vertebrate Fossil-Lagerstätten.

The northward-flowing Humboldt Current hosts perpetually high levels of productivity along the western coast of South America. Here, we aim to elucidate the deep-time history of this globally important ecosystem based on a detailed palaeoecological analysis of the exceptionally preserved middle–upper Miocene vertebrate assemblages of the Pisco Formation of the East Pisco Basin, southern Peru. We summarise observations on hundreds of fossil whales, dolphins, seals, seabirds, turtles, crocodiles, sharks, rays, and bony fishes to reconstruct ecological relationships in the wake of the Middle Miocene Climatic Optimum, and the marked cooling that followed it. The lowermost, middle Miocene Pisco sequence (P0) and its vertebrate assemblage testify to a warm, semi-enclosed, near-shore palaeoenvironment. During the first part of the Tortonian (P1), high productivity within a prominent upwelling system supported a diverse assemblage of mesopredators, at least some of which permanently resided in the Pisco embayment and used it as a nursery or breeding/calving area. Younger portions of the Pisco Formation (P2) reveal a more open setting, with wide-ranging species like rorquals increasingly dominating the vertebrate assemblage, but also local differences reflecting distance from the coast. Like today, these ancient precursors of the modern Humboldt Current Ecosystem were based on sardines, but notably differed from their present-day equivalent in being dominated by extremely large-bodied apex predators like Livyatan melvillei and Carcharocles megalodon.

Speciation is thought to be predominantly driven by the geographical separation of populations of the ancestral species. Yet, in the marine realm, there is substantial biological diversity despite a lack of pronounced geographical barriers. Here, we investigate this paradox by considering the biogeography of marine mammals: cetaceans (whales and dolphins) and pinnipeds (seals and sea lions). We test for associations between past evolutionary diversification and current geographical distributions, after accounting for the potential effects of current environmental conditions. In general, cetacean lineages are widely dispersed and show few signs of geographically driven speciation, albeit with some notable exceptions. Pinnipeds, by contrast, show a more mixed pattern, with true seals (phocids) tending to be dispersed, whereas eared seals (otariids) are more geographically clustered. Both cetaceans and pinnipeds show strong evidence for environmental clustering of their phylogenetic lineages in relation to factors such as sea temperature, the extent of sea ice, and nitrate concentrations. Overall, current marine mammal biogeography is not indicative of geographical speciation mechanisms, with environmental factors being more important determinants of current species distributions. However, geographical isolation appears to have played a role in some important taxa, with evidence from the fossil record showing good support for these cases.

Chimeric antigen receptor (CAR) redirected T cells are efficacious in the treatment of leukemia/lymphoma, however, showed less capacities in eliminating solid tumors which is thought to be partly due to the lack of cytokine support in the tumor lesion. In order to deliver supportive cytokines, we took advantage of the inherent ability of mesenchymal stem cells (MSCs) to actively migrate to tumor sites and engineered MSCs to release both IL7 and IL12 to promote homeostatic expansion and Th1 polarization. There is a mutual interaction between engineered MSCs and CAR T cells; in presence of CAR T cell released IFN-gamma and TNF-alpha, chronic inflammatory Th2 MSCs shifted towards a Th17/Th1 pattern with IL2 and IL15 release that mutually activated CAR T cells with extended persistence, amplification, killing and protection from activation induced cell death. MSCs releasing IL7 and IL12 were superior over non-modified MSCs in supporting the CAR T cell response and improved the anti-tumor attack in a transplant tumor model. Data demonstrate the first use of genetically modified MSCs as vehicles to deliver immuno-modulatory proteins to the tumor tissue in order to improve the efficacy of CAR T cells in the treatment of solid malignancies.

Speciation is thought to be predominantly driven by the geographical separation of populations of the ancestral species. Yet, in the marine realm, there is substantial biological diversity despite a lack of pronounced geographical barriers. Here, we investigate this paradox by considering the biogeography of marine mammals: cetaceans (whales and dolphins) and pinnipeds (seals and sea lions). We test for associations between past evolutionary diversification and current geographical distributions, after accounting for the potential effects of current environmental conditions. In general, cetacean lineages are widely dispersed and show few signs of geographically driven speciation, albeit with some notable exceptions. Pinnipeds, by contrast, show a more mixed pattern, with true seals (phocids) tending to be dispersed, whereas eared seals (otariids) are more geographically clustered. Both cetaceans and pinnipeds show strong evidence for environmental clustering of their phylogenetic lineages in relation to factors such as sea temperature, the extent of sea ice, and nitrate concentrations. Overall, current marine mammal biogeography is not indicative of geographical speciation mechanisms, with environmental factors being more important determinants of current species distributions. However, geographical isolation appears to have played a role in some important taxa, with evidence from the fossil record showing good support for these cases.

Chimeric antigen receptor (CAR) redirected T cells are efficacious in the treatment of leukemia/lymphoma, however, showed less capacities in eliminating solid tumors which is thought to be partly due to the lack of cytokine support in the tumor lesion. In order to deliver supportive cytokines, we took advantage of the inherent ability of mesenchymal stem cells (MSCs) to actively migrate to tumor sites and engineered MSCs to release both IL7 and IL12 to promote homeostatic expansion and Th1 polarization. There is a mutual interaction between engineered MSCs and CAR T cells; in presence of CAR T cell released IFN-gamma and TNF-alpha, chronic inflammatory Th2 MSCs shifted towards a Th17/Th1 pattern with IL2 and IL15 release that mutually activated CAR T cells with extended persistence, amplification, killing and protection from activation induced cell death. MSCs releasing IL7 and IL12 were superior over non-modified MSCs in supporting the CAR T cell response and improved the anti-tumor attack in a transplant tumor model. Data demonstrate the first use of genetically modified MSCs as vehicles to deliver immuno-modulatory proteins to the tumor tissue in order to improve the efficacy of CAR T cells in the treatment of solid malignancies.

The human brain provides a range of functions such as expressing emotions, controlling the rate of breathing, etc., and its study has attracted the interest of scientists for many years. As machine learning models become more sophisticated, and bio-metric data becomes more readily available through new non-invasive technologies, it becomes increasingly possible to gain access to interesting biometric data that could revolutionize Human-Computer Interaction. In this research, we propose a method to assess and quantify human attention levels and their effects on learning. In our study, we employ a brain computer interface (BCI) capable of detecting brain wave activity and displaying the corresponding electroencephalograms (EEG). We train recurrent neural networks (RNNS) to identify the type of activity an individual is performing.

As generation Z's big data is flooding the Internet through social nets, neural network based data processing is turning an important cornerstone, showing significant potential for fast extraction of data patterns. Online course delivery and associated tutoring are transforming into customizable, on-demand services driven by the learner. Besides automated grading, strong potential exists for the development and deployment of next generation intelligent tutoring software agents. Self-adaptive, online tutoring agents exhibiting "intelligent-like" behavior, being capable "to learn" from the learner, will become the next educational superstars. Over the past decade, computer-based tutoring agents were deployed in a variety of extended reality environments, from patient rehabilitation to psychological trauma healing. Most of these agents are driven by a set of conditional control statements and a large answers/questions pairs dataset. This article provides a brief introduction on Generation Z's addiction to digital information, highlights important efforts for the development of intelligent dialogue systems, and explains the main components and important design decisions for Intelligent Tutoring System., Comment: 4 pages

Speciation is thought to be predominantly driven by the geographical separation of populations of the ancestral species. Yet, in the marine realm, there is substantial biological diversity despite a lack of pronounced geographical barriers. Here, we investigate this paradox by considering the biogeography of marine mammals: cetaceans (whales and dolphins) and pinnipeds (seals and sea lions). We test for associations between past evolutionary diversification and current geographical distributions, after accounting for the potential effects of current environmental conditions. In general, cetacean lineages are widely dispersed and show few signs of geographically driven speciation, albeit with some notable exceptions. Pinnipeds, by contrast, show a more mixed pattern, with true seals (phocids) tending to be dispersed, whereas eared seals (otariids) are more geographically clustered. Both cetaceans and pinnipeds show strong evidence for environmental clustering of their phylogenetic lineages in relation to factors such as sea temperature, the extent of sea ice, and nitrate concentrations. Overall, current marine mammal biogeography is not indicative of geographical speciation mechanisms, with environmental factors being more important determinants of current taxonomic distributions. However, geographical isolation appears to have played a role in some important taxa, with evidence from the fossil record showing good support for these cases.

Speciation is thought to be predominantly driven by the geographical separation of populations of the ancestral species. Yet, in the marine realm, there is substantial biological diversity despite a lack of pronounced geographical barriers. Here, we investigate this paradox by considering the biogeography of marine mammals: cetaceans (whales and dolphins) and pinnipeds (seals and sea lions). We test for associations between past evolutionary diversification and current geographical distributions, after accounting for the potential effects of current environmental conditions. In general, cetacean lineages are widely dispersed and show few signs of geographically driven speciation, albeit with some notable exceptions. Pinnipeds, by contrast, show a more mixed pattern, with true seals (phocids) tending to be dispersed, whereas eared seals (otariids) are more geographically clustered. Both cetaceans and pinnipeds show strong evidence for environmental clustering of their phylogenetic lineages in relation to factors such as sea temperature, the extent of sea ice, and nitrate concentrations. Overall, current marine mammal biogeography is not indicative of geographical speciation mechanisms, with environmental factors being more important determinants of current taxonomic distributions. However, geographical isolation appears to have played a role in some important taxa, with evidence from the fossil record showing good support for these cases.

Data organized into hierarchical structures (e.g., phylogenies or cell types) arises in several biological fields. It is therefore of interest to have data containers that store the hierarchical structure together with the biological profile data, and provide functions to easily access or manipulate data at different resolutions. Here, we present TreeSummarizedExperiment, a R/S4 class that extends the commonly used SingleCellExperiment class by incorporating tree representations of rows and/or columns (represented by objects of the phylo class). It follows the convention of the SummarizedExperiment class, while providing links between the assays and the nodes of a tree to allow data manipulation at arbitrary levels of the tree. The package is designed to be extensible, allowing new functions on the tree (phylo) to be contributed. As the work is based on the SingleCellExperiment class and the phylo class, both of which are popular classes used in many R packages, it is expected to be able to interact seamlessly with many other tools.

PURPOSE: Glenoid retroversion is a known independent risk factor for recurrent posterior instability. The purpose was to investigate progressive angles of glenoid retroversion and their influence on humeral head centration and posterior translation with intact, detached, and repaired posterior labrum in a cadaveric human shoulder model. METHODS: A total of 10 fresh-frozen human cadaveric shoulders were investigated for this study. After CT- canning, the glenoids were aligned parallel to the floor, with the capsule intact, and the humerus was fixed in 60° of abduction and neutral rotation. Version of the glenoid was created after wedge resection from posterior and fixed with an external fixator throughout the testing. Specimens underwent three conditions: intact, detached, and repaired posterior labrum, while version of the glenoid was set from + 5° anteversion to - 25° retroversion by 5° increments. Within the biomechanical setup, the glenohumeral joint was axially loaded (22 N) to center the joint. At 0° of glenoid version and intact labrum, the initial position was used as baseline and served as point zero of centerization. After cyclic preloading, posterior translation force (20 N) was then applied by a material testing machine, while start and endpoints of the scapula placed on an X-Y table were measured. RESULTS: The decentralization of the humeral head at glenoid version angles of 5°, 10°, 15°, and 20° of retroversion and 5° of anteversion was significantly different (P < 0.001). Every increment of 5° of retroversion led to an additional decentralization of the humeral head overall by (average ± SD) 2.0 mm ± 0.3 in the intact and 2.0 mm ± 0.7 in the detached labrum condition. The repaired showed significantly lower posterior translation compared to the intact condition at 10° (P = 0.012) and 15° (P < 0.01) of retroversion. In addition, CT measured parameters (depth, diameter, and native version) of the glenoid showed no correlation with angle of dislocation of

Tyramine, formed by the decarboxylation of tyrosine, is a natural constituent of numerous food products. As an indirect sympathomimetic, it can have potentially dangerous hypertensive effects. In vitro data indicated that the pharmacokinetics of tyramine possibly depend on the organic cation transporter OCT1 genotype and on the CYP2D6 genotype. Since tyramine is a prototypic substrate of monoamine oxidase A (MAO-A), genetic polymorphisms in MAO-A may also be relevant. The aims of this study were to identify to what extent the interindividual variation in pharmacokinetics and pharmacodynamics of tyramine is determined by genetic polymorphisms in OCT1, CYP2D6, and MAO-A. Beyond that, we wanted to evaluate tyramine as probe drug for the in vivo activity of MAO-A and OCT1. Therefore, the pharmacokinetics, pharmacodynamics, and pharmacogenetics of tyramine were studied in 88 healthy volunteers after oral administration of a 400 mg dose. We observed a strong interindividual variation in systemic tyramine exposure, with a mean AUC of 3.74 min*µg/ml and a high mean CL/F ratio of 107 l/min. On average, as much as 76.8% of the dose was recovered in urine in form of the MAO-catalysed metabolite 4-hydroxyphenylacetic acid (4-HPAA), confirming that oxidative deamination by MAO-A is the quantitatively most relevant metabolic pathway. Systemic exposure of 4-HPAA varied only up to 3-fold, indicating no strong heritable variation in peripheral MAO-A activity. Systolic blood pressure increased by more than 10 mmHg in 71% of the volunteers and correlated strongly with systemic tyramine concentration. In less than 10% of participants, individually variable blood pressure peaks by >40 mmHg above baseline were observed at tyramine concentrations of >60 µg/l. Unexpectedly, the functionally relevant polymorphisms in OCT1 and CYP2D6, including the CYP2D6 poor and ultra-rapid metaboliser genotypes, did not significantly affect tyramine pharmacokinetics or pharmacodynamics. Also, the MOA-A ge

BackgroundCurrent studies in cardiothoracic clinical research frequently fail to use end points that are most meaningful to patients, including measures associated with quality of life. Patient-reported outcomes (PROs) represent an underused but important component of high-quality patient-centered care. Our objective was to highlight important principles of PRO measurement, describe current use in cardiothoracic operations, and discuss the potential for and challenges associated with integration of PROs into large clinical databases.MethodsWe performed a literature review by using the PubMed/EMBASE databases. Clinical articles that focused on the use of PROs in cardiothoracic surgical outcomes measurement or clinical research were included in this review.ResultsPROs measure the outcomes that matter most to patients and facilitate the delivery of patient-centered care. When effectively used, PRO measures have provided detailed and nuanced quality-of-life data for comparative effectiveness research. However, further steps are needed to better integrate PROs into routine clinical care.ConclusionsIncorporation of PROs into routine clinical practice is essential for delivering high-quality patient-centered care. Future integration of PROs into prospectively collected registries and databases, including that The Society of Thoracic Surgeons National Database, has the potential to enrich comparative effectiveness research in cardiothoracic surgery.

Autonomous Wireless Sensors (AWSs) are at the core of every Wireless Sensor Network (WSN). Current AWS technology allows the development of many IoT-based applications, ranging from military to bioengineering and from industry to education. The energy optimization of AWSs depends mainly on: Structural, functional, and application specifications. The holistic design methodology addresses all the factors mentioned above. In this sense, we propose an original solution based on a novel architecture that duplicates the transceivers and also the power source using a hybrid storage system. By identifying the consumption needs of the transceivers, an appropriate methodology for sizing and controlling the power flow for the power source is proposed. The paper emphasizes the fusion between information, communication, and energy consumption of the AWS in terms of spectrum information through a set of transceiver testing scenarios, identifying the main factors that influence the sensor node design and their inter-dependencies. Optimization of the system considers all these factors obtaining an energy efficient AWS, paving the way towards autonomous sensors by adding an energy harvesting element to them.

Vehicular Ad Hoc Networks (VANETs) are a particular subclass of mobile ad hoc networks that raise a number of security challenges, notably from the way users authenticate the network. Authentication technologies based on existing security policies and access control rules in such networks assume full trust on Roadside Unit (RSU) and authentication servers. The disclosure of authentication parameters enables user's trace-ability over the network. VANETs' trusted entities (e.g. RSU) can utilize such information to track a user traveling behavior, violating user privacy and anonymity. In this paper, we proposed a novel, light-weight, Adaptive Group-based Zero Knowledge Proof-Authentication Protocol (AGZKP-AP) for VANETs. The proposed authentication protocol is capable of offering various levels of users' privacy settings based on the type of services available on such networks. Our scheme is based on the Zero-Knowledge-Proof (ZKP) crypto approach with the support of trade-off options. Users have the option to make critical decisions on the level of privacy and the amount of resources usage they prefer such as short system response time versus the number of private information disclosures. Furthermore, AGZKP-AP is incorporated with a distributed privilege control and revoking mechanism that render user's private information to law enforcement in case of a traffic violation.

A large number of sensors deployed in recent years in various setups and their data is readily available in dedicated databases or in the cloud. Of particular interest is real-time data processing and 3D visualization in web-based user interfaces that facilitate spatial information understanding and sharing, hence helping the decision making process for all the parties involved. In this research, we provide a prototype system for near real-time, continuous X3D-based visualization of processed sensor data for two significant applications: thermal monitoring for residential/commercial buildings and nitrogen cycle monitoring in water beds for aquaponics systems. As sensors are sparsely placed, in each application, where they collect data for large periods (of up to one year), we employ a Finite Differences Method and a Neural Networks model to approximate data distribution in the entire volume.

Haptic sensory feedback has been shown to complement the visual and auditory senses, improve user performance and provide a greater sense of togetherness in collaborative and interactive virtual environments. However, we are faced with numerous challenges when deploying these systems over the present day Internet. The most significant of these challenges are the network performance limitations of the Wide Area Networks. In this paper, we offer a structured examination of the current challenges in the deployment of haptic-based distributed systems by analyzing the recent advances in the understanding of these challenges and the progress that has been made to overcome them.

The teaching of abstract physics concepts can be enhanced by incorporating visual and haptic sensory modalities in the classroom, using the correct perspectives. We have developed virtual reality simulations to assist students in learning the Coriolis effect, an apparent deflection on an object in motion when observed from within a rotating frame of reference. Twenty four undergraduate physics students participated in this study. Students were able to feel the forces through feedback on a Novint Falcon device. The assessment results show an improvement in the learning experience and better content retention as compared with traditional instruction methods. We prove that large scale deployment of visuo-haptic reconfigurable applications is now possible and feasible in a science laboratory setup., Comment: ISSN: 1844-8933

Extensible 3D (X3D) modeling language is one of the leading Web3D technologies. Despite the rich functionality, the language does not currently provide tools for rapid development of conventional graphical user interfaces (GUIs). Every X3D author is responsible for building from primitives a purpose specific set of required interface components, often for a single use. We address the challenge of creating consistent, efficient, interactive, and visually appealing GUIs by proposing the X3D User Interface (X3DUI) library. This library includes a wide range of cross-compatible X3D widgets, equipped with configurable appearance and behavior. With this library, we attempt to standardize the GUI construction across various X3D-driven projects, and improve the usability, compatibility, adaptability, readability, and flexibility of many existing applications.

Recent advances in haptic hardware and software technology have generated interest in novel, multimodal interfaces based on the sense of touch. Such interfaces have the potential to revolutionize the way we think about human computer interaction and open new possibilities for simulation and training in a variety of fields. In this paper we review several frameworks, APIs and toolkits for haptic user interface development. We explore these software components focusing on minimally invasive surgical simulation systems. In the area of medical diagnosis, there is a strong need to determine mechanical properties of biological tissue for both histological and pathological considerations. Therefore we focus on the development of affordable visuo-haptic simulators to improve practice-based education in this area. We envision such systems, designed for the next generations of learners that enhance their knowledge in connection with real-life situations while they train in mandatory safety conditions., Comment: ISSN: 1844-8933

The simulation of tactile sensation using haptic devices is increasingly investigated in conjunction with simulation and training. In this paper we explore the most popular haptic frameworks and APIs. We provide a comprehensive review and comparison of their features and capabilities, from the perspective of the need to develop a haptic simulator for medical training purposes. In order to compare the studied frameworks and APIs, we identified and applied a set of 11 criteria and we obtained a classification of platforms, from the perspective of our project. According to this classification, we used the best platform to develop a visual-haptic prototype for liver diagnostics.

Mechanical properties of biological tissue for both histological and pathological considerations are often required in disease diagnostics. Such properties can be simulated and explored with haptic technology. Development of cost effective haptic-based simulators and their introduction in the minimally invasive surgery learning cycle is still in its infancy. Receiving pretraining in a core set of surgical skills can reduce skill acquisition time and risks. We present the development of a visuo-haptic simulator module designed to train internal organs disease diagnostics through palpation. The module is part of a set of tools designed to train and improve basic surgical skills for minimally invasive surgery.

Multimodal simulations augment the presentation of abstract concepts facilitating theoretical models understanding and learning. Most simulations only engage two of our five senses: sight and hearing. If we employ additional sensory communication channels in simulations, we may gain a deeper understanding of illustrated concepts by increasing the communication bandwidth and providing alternative perspectives. We implemented the sense of touch in 3D simulations to teach important concepts in introductory physics. Specifically, we developed a visual/haptic simulation for friction. We prove that interactive 3D haptic simulations, if carefully developed and deployed, are useful in engaging students and allowing them to understand concepts faster. We hypothesize that large scale deployment of such haptic-based simulators in science laboratories is now possible due to the advancements in haptic software and hardware technology.

Preoperative gestures include tactile sampling of the mechanical properties of biological tissue for both histological and pathological considerations. Tactile properties used in conjunction with visual cues can provide useful feedback to the surgeon. Development of novel cost effective haptic-based simulators and their introduction in the minimally invasive surgery learning cycle can absorb the learning curve for your residents. Receiving pre-training in a core set of surgical skills can reduce skill acquisition time and risks. We present the integration of a real-time surface stiffness adjustment algorithm and a novel paradigm -- force maps -- in a visuo-haptic simulator module designed to train internal organs disease diagnostics through palpation., Comment: arXiv admin note: text overlap with arXiv:1812.03325

Surgeons must accomplish complex technical and intellectual tasks that can generate unexpected and serious challenges with little or no room for error. In the last decade, computer simulations have played an increasing role in surgical training, pre-operative planning, and biomedical research. Specifically, visuo-haptic simulations have been the focus of research to develop advanced e-Learning systems facilitating surgical training. The cost of haptic hardware was reduced through mass scale production and as haptics gained popularity in the gaming industry. Visuo-haptic simulations combine the tactile sense with visual information and provide training scenarios with a high degree of reality. For surgical training, such scenarios can be used as ways to gain, improve, and assess resident and expert surgeons' skills and knowledge.

Knowledge creation occurs in the process of social interaction. As our service-based society is evolving into a knowledge-based society there is an acute need for more effective collaboration and knowledge-sharing systems to be used by geographically scattered people. We present the use of Web3D components and standards, such as X3D, in combination with the haptic (tactile) paradigm, for the development of new communication channels for e-Learning and simulation., Comment: ISBN:978-3-642-01343-0

Distributed systems technologies supporting 3D visualization and social collaboration will be increasing in frequency and type over time. An emerging type of head-mounted display referred to as the head-mounted projection display (HMPD) was recently developed that only requires ultralight optics (i.e., less than 8 g per eye) that enables immersive multiuser, mobile augmented reality 3D visualization, as well as remote 3D collaborations. In this paper a review of the development of lightweight HMPD technology is provided, together with insight into what makes this technology timely and so unique. Two novel emerging HMPD-based technologies are then described: a teleportal HMPD(T-HMPD) enabling face-to-face communication and visualization of shared 3D virtual objects, and a mobile HMPD (M-HMPD) designed for outdoor wearable visualization and communication. Finally, the use of HMPD in medical visualization and training, as well as in infospaces, two applications developed in the ODA and MIND labs respectively, are discussed.

With the expansion of e-learning course curricula and the affordability of haptic devices, at-home virtual laboratories are emerging as an increasingly viable option for e-learners. We outline three novel haptic simulations for the introductory physics concepts of friction, the Coriolis Effect, and Precession. These simulations provide force feedback through one or more Novint Falcon devices, allowing students to "feel" the forces at work in a controlled learning environment. This multi-modal approach to education (beyond the audiovisual) may lead to increased interest and immersion for e-learners and appeal to the kinesthetic learners who may struggle in a traditional e-learning course setting.

Urban planning often raises complex issues that are difficult to visualize and challenging to communicate. The increasing availability of 3D modeling standards has provided the opportunity for many developers, engineers, designers, planners, investors, and government officials to effectively collaborate to bring projects to fruition. Because of its real-time interactivity and widespread web-based content players, X3D proves to be a good choice for developing and visualizing 3D city content on the Web for planning purposes. Passenger rail is a viable and cost-effective transportation solution in many areas, especially in view of rising energy costs. The Savannah in 3D (or S3D) project is a multimedia tool for a feasibility study designed to bring passenger rail to Savannah; thereby opening up the historic, tourist-friendly city to a wider audience. The paper outlines the development process of an interactive 3D train model as it journeys from Atlanta to Savannah, Georgia - focusing on user interactivity and scene immersion to supplement the city and transportation planning agenda., Comment: ACM-SE 2013