Host-specific differences in the membrane fusion activity of influenza A viruses

The transmission of influenza A viruses from avian to other species involves numerous adaptive processes to overcome the species barrier. One major determinant of host-range restriction is the viral hemagglutinin (HA). HA plays a crucial role in virus entry into the host cell by mediating receptor-binding and membrane fusion. Virus adaptation to mammals results in alteration of receptor-binding specificity. There is growing evidence that the HA-mediated membrane fusion activity contributes to host range restriction as well. This study aimed to identify host specific differences in membrane fusion properties and to characterise potential alterations during interspecies transmission. In the first part of the thesis Eurasian avian-like swine viruses that emerged by transmission of an avian H1N1 virus in pigs in the late 1970s in Europe were shown to have a higher pH optimum of HA-mediated fusion (pH 5.1-5.4) and a decreased HA stability when compared to avian precursors (pH 4.9-5.2). These results indicate that this avian-to-swine transmission was accompanied by changes in HA stability. Sequence comparison revealed eight amino acid substitutions that separate the HA of early avian-like swine viruses from their putative avian precursor. Furthermore, mutations in one of these positions contribute to the low stability phenotype. In agreement with natural avian-to-swine transmission, experimental adaptation of a potential avian precursor of the avian-like swine lineage to pigs resulted in a decreased HA stability. This states the first formal proof that viral membrane fusion and stability properties change during interspecies transmission. The second part of the thesis investigated differences in membrane fusion activity among different avian virus species. Comparison of H7 viruses from wild birds and domestic poultry suggests that Eurasian H7 poultry viruses have a higher pH optimum of membrane fusion (pH 6.2) and thus possess a lower stability than H7 viruses from wild birds (pH 5.2). Moreover, all tested Eurasian H7 viruses express a lower HA stability than HAs from other subtypes (H2, H3, H4, H5, H13, H14 und H16). Previous studies indicate that H5 viruses with low HA stability replicate but do not transmit via respiratory droplets in the ferret model (Imai et al., 2012; Herfst et al., 2012). Thus, it is feasible, that H7 viruses originated from poultry are restricted in ferrets and humans to similar extend. In the last part, fusion properties of human pandemic and zoonotic viruses were studied. HAs of pandemic viruses from the last century initiated fusion in a narrow pH range between pH 5.0 and 5.2. In contrast, the swine-origin 2009 pandemic virus HA starts to fuse at a pH 0.2 units higher, which might be due to the swine origin of this HA. This further suggests that fusion characteristics continue to adapt in the course of subsequent circulation. The pH optimum of fusion of a zoonotic human H7N9 (2013) virus represents an intermediate in that it is lower when compared to putative ancestors circulating in wild birds, but still higher than that of typical human-adapted viruses. This may account for limited human-to-human transmission observed for this virus. In order to further investigate which changes in HA are needed for the emergence of avian viruses in humans, HA substitutions separating the 1968 Hong Kong pandemic virus HA from the putative avian precursor were examined. In addition to the well-known switch in receptor specificity, binding avidity changed prior to or during the emergence in humans. In this study, no difference in viral stability was observed between the pandemic virus and the putative avian precursor. This indicates that the avian ancestor was already sufficiently stable to facilitate replication and transmission in humans. In sum, this study shows that membrane fusion properties vary between host species and alter during influenza A virus emergence in new hosts. This suggests HA-mediated fusion and HA stability to act as host range restriction factors. Alterations in membrane fusion activity and viral stability may not be essential for initial infection of new host individuals. However, an optimal stability seems to be necessary to facilitate transmission within populations of new host species

Reconstructing Human Motion

This thesis presents methods for reconstructing human motion in a variety of applications and begins with an introduction to the general motion capture hardware and processing pipeline. Then, a data-driven method for the completion of corrupted marker-based motion capture data is presented. The approach is especially suitable for challenging cases, e.g., if complete marker sets of multiple body parts are missing over a long period of time. Using a large motion capture database and without the need for extensive preprocessing the method is able to fix missing markers across different actors and motion styles. The approach can be used for incrementally increasing prior-databases, as the underlying search technique for similar motions scales well to huge databases. The resulting clean motion database could then be used in the next application: a generic data-driven method for recognizing human full body actions from live motion capture data originating from various sources. The method queries an annotated motion capture database for similar motion segments, able to handle temporal deviations from the original motion. The approach is online-capable, works in realtime, requires virtually no preprocessing and is shown to work with a variety of feature sets extracted from input data including positional data, sparse accelerometer signals, skeletons extracted from depth sensors and even video data. Evaluation is done by comparing against a frame-based Support Vector Machine approach on a freely available motion database as well as a database containing Judo referee signal motions. In the last part, a method to indirectly reconstruct the effects of the human heart's pumping motion from video data of the face is applied in the context of epileptic seizures. These episodes usually feature interesting heart rate patterns like a significant increase at seizure start as well as seizure-type dependent drop-offs near the end. The pulse detection method is evaluated for applicability regarding seizure detection in a multitude of scenarios, ranging from videos recorded in a controlled clinical environment to patient supplied videos of seizures filmed with smartphones

ICD-11 Adjustment Disorder among Organ Transplant Patients and Their Relatives

Adjustment disorder (AD) is one of the most frequent mental health conditions after stressful life experiences in the medical setting. The diagnosis has been conceptually redefined in International Classification of Diseases (ICD-11) and now includes specific symptoms of preoccupations and failure to adapt. The current study assesses the prevalence of self-reported ICD-11 AD among organ transplantation patients and their relatives, explores the association of patients' demographic-, transplant-, and health-related characteristics and ICD-11 AD symptoms, and evaluates the role of social support in the post- transplant context. A total of N = 140 patient-relative dyads were examined cross-sectionally. Hierarchical linear regression analyses were conducted to explore potential predictive factors of AD. The results revealed an AD prevalence of 10.7% among patients and 16.4% among relatives at an average of 13.5 years after the transplantation. The time that had passed since the transplantation was unrelated to AD symptom severity. Women tended to be at a higher risk in both groups. Somatic issues were predictive for AD only among patients and social support was predictive mainly among relatives. The results suggest that ICD-11 AD is a relevant diagnosis after organ transplantations for patients and relatives and its specific symptom clusters may provide important information for developing intervention strategies

Constrained-Differential-Kinematics-Decomposition-Based NMPC for Online Manipulator Control with Low Computational Costs

Flexibility combined with the ability to consider external constraints comprises the main advantages of nonlinear model predictive control (NMPC). Applied as a motion controller, NMPC enables applications in varying and disturbed environments, but requires time-consuming computations. Hence, given the full nonlinear multi-DOF robot model, a delay-free execution providing short control horizons at appropriate prediction horizons for accurate motions is not applicable in common use. This contribution introduces an approach that analyzes and decomposes the differential kinematics similar to the inverse kinematics method to assign Cartesian boundary conditions to specific systems of equations during the model building, reducing the online computational costs. The resulting fully constrained NMPC realizes the translational obstacle avoidance during trajectory tracking using a reduced model considering both joint and Cartesian constraints coupled with a Jacobian transposed controller performing the end-effector’s orientation correction. Apart from a safe distance from the obstacles, the presented approach does not lead to any limitations of the reachable workspace, and all degrees of freedom (DOFs) of the robot are used. The simulative evaluation in Gazebo using the Stäubli TX2-90 commanded of ROS on a standard computer emphasizes the significantly lower online computational costs, accuracy analysis, and extended adaptability in obstacle avoidance, providing additional flexibility. An interpretation of the new concept is discussed for further use and extensions

Growth of sulfate-reducing bacteria in the high concentrations of iron ions

Sulphate-reducing bacteria (SRB) are anaerobic microorganisms that use sulphate as a terminal electron acceptor in, for example, the degradation of organic compounds. They are ubiquitous in anoxic habitats, where they have an important role in both the sulphur and carbon cycles. SRB can cause a serious problem for industries, such as the offshore oil industry, because of the production of sulphide, which is highly reactive, corrosive and toxic. However, these organisms can also be beneficial by removing sulphate and heavy metals from waste streams. Although SRB have been studied for more than a century, it is only with the recent emergence of new molecular biological and genomic techniques that we have begun to obtain detailed information on their way of life

If motion sounds: Movement sonification based on inertial sensor data

Within last years, movement sonification turned out to be an appropriate support for motor perception and motor control that can display physical motion in a very rich and direct way. But how should movement sonification be configured to support motor learning? The appropriate selection of movement parameters and their transformation into characteristic motion features is essential for an auditory display to become effective. In this paper, we introduce a real-time sonification framework for all common MIDI environments based on acceleration and orientation data from inertial sensors. Fundamental processing steps to transform motion information into meaningful sound will be discussed. The proposed framework of inertial motion capturing, kinematic parameter selection and possible kinematic acoustic mapping provides a basis for mobile real-time movement sonification which is a prospective powerful training tool for rehabilitation and sports and offers a broad variety of application possibilities.EU/EFRE/W2-8011866

Exploring the Environmental Benefits of In-Process Isolation for Software Resilience

Memory-related errors remain an important cause of software vulnerabilities. While mitigation techniques such as using memory-safe languages are promising solutions, these do not address software resilience and availability. In this paper, we propose a solution to build resilience against memory attacks into software, which contributes to environmental sustainability and security

Analysis of ceiling effects occurring with speech recognition tests in adult cochlear-implanted patients

This article presents a simple method of analysing speech test scores which are biased through ceiling effects. Eighty postlingually deafened adults implanted with a MED-EL COMBI 40/40+ cochlear implant (CI) were administered a numbers test and a sentence test at initial device activation and at 1, 3, 6, 12 and 24 months thereafter. As a measure for speech recognition performance, the number of patients who scored at the `ceiling level' (i.e. at least 95% correct answers) was counted at each test interval. Results showed a quick increase in this number soon after device activation as well as a continuous improvement over time ( numbers test: 1 month: 51%; 6 months: 73%; 24 months: 88%; sentence test: 1 month: 33%; 6 months: 49%; 24 months: 64%). The new method allows for the detection of speech recognition progress in CI patient samples even at late test intervals, where improvement curves based on averaged scores are usually assuming a flat shape. Copyright (C) 2004 S. Karger AG, Basel