Schistosoma mansoni tetraspanning orphan receptor - SmTOR

Schistosomiasis is a neglected tropical disease affecting more than 207 million people worldwide with an estimated number of 700 million people at risk in 74 endemic countries. There are five species of schistosoma that are known to infect humans by contact with its larval stage, the cercariae: Schistosoma mekongi, S. intercalatum, S. mansoni, S. japonicum and S. haematobium, the latter three being the main schistosome species that affect humans. Although the infection can be treated by using chemotherapeutics, it is hardly possible to influence strongly the risk of re-infection and a vaccine against schistosomiasis is a desirable goal. Schistosome parasites need to adapt to survive at various points of their complex life cycle. In the vertebrate definitive host, this involves the avoidance of the host immune system in general and the battle against the host complement system participating in the first line of immune defenses against the invading parasite in particular. There are several complement regulators found on schistosomes. We are interested in complement regulation at the level of the formation of the C3 convertase by a complement C2 binding receptor. This C2 binding receptor was first characterised in one of the human schistosoma species S. haematobium and denominated ShTOR for trispanning orphan receptor. After the S. mansoni genome had been sequenced, we had a closer look at the ShTOR receptor homologue in this species. The aims of the project were to characterise the S. haematobium TOR receptor homologue SmTOR in S. mansoni (PART I), to test if the first extracellular domain 1 of SmTOR binds C2 and to define its antigenicity (PART II) and to define the immunogenicity of SmTORed1 in mice and test it as a vaccine candidate against schistosomiasis in a murine vaccination and challenge model (PART III). In line with the structure of the project outline presented above, the work presented in this thesis can be summarised as follows: At first, we found that SmTOR is a tetraspanning receptor expressed in the tegumental membranes of schistsosomes. As compared to the truncated receptor versions described before, it possesses a longer extracellular domain 1 still comprising the C2 binding motif. Its expression was highest in the infectious stage of the parasite, in the S. mansoni cercariae. SmTOR might play an important role in skin penetration of S. mansoni larvae and it is an interesting target for vaccination since it is an early antigen on schistosoma cercariae and has a complement inhibitory activity. We then overexpressed SmTOR extracellular domain 1 (rSmTORed1) in E. coli, which was purified by immobilised metal affinity chromatography. We were able to show that full length recombinant SmTORed1 binds C2. We moreover detected specific antibodies against rSmTORed1 in sera of patients infected with S. mansoni and also in some normal human sera. Specificity of antibody to rSmTORed1 was ensured by pre-incubation of sera with the Halo-tagged version of SmTORed1 immobilised on a solid support. SmTORed1 N-terminally fused to HaloTag and the corresponding control constructs were produced in E. coli as well. Thirdly, we tested the immunogenicity of rSmTORed1 in two different mouse strains, BALB/c and C57BL/6 using muramyl dipeptide (MDP) and Complete/Incomplete FreundÕs adjuvant (CFA/IFA) as adjuvants. BALB/c mice immunised with rSmTORed1 in CFA/IFA generated the highest titer of specific antibodies to rSmTORed1 and were subsequently tested in an immunisation challenge experimental setup. For this, immunised mice were infected with S. mansoni cercariae and status of infection assessed by adult worm count. Immunised mice showed a 60 % reduction of worm burden when compared to the two control groups. Taken together, we managed to newly characterise the S. mansoni TOR receptor and to show that it is an interesting anti-schistosome vaccine target to be followed up in additional experiments

Influence of material choice on the force delivery of bimaxillary tooth positioners on canine malpositions

Objective: Since their introduction in 1945, tooth positioners have been used to treat a range of malpositions. Although the original appliance was made of natural rubber, today's tooth positioners are fabricated from various elastic, transparent materials. It was the aim of this study to evaluate the forces and moments produced by current positioners on various upper canine malpositions. Material and methods: Seven positioners of different materials were tested on 11 upper canine malpositions: 0.25, 0.5, 1mm supraposition; 0.25, 0.5, 1mm infraposition; 5°, 10°, 20° mesiorotation; 5° mesioinclination, 5° buccal root torque. We measured forces and moments in vitro after bite closure by 0.5mm, and opening by 1mm using a three-dimensional robotic device. All measurements were taken in a temperature-controlled environment at 36°C. Results: The forces and moments measured at the canine varied greatly among the different positioners, with the thermoformed EVA positioner showing much greater forces and moments in almost all malpositions. At initial closure, we observed intrusive forces of 6-32N for suprapositions, 0-11N intrusive forces for infrapositions, 0-20Nmm for mesiorotations, 6-12Nmm for mesioinclinations, and − 23Nmm to 5Nmm for buccal root torque. All positioners were most effective on suprapositioned teeth. Very low or negligible correctional forces and moments in conjunction with all infrapositions and 5° with rotation were noted. Labial root torque led to unpredictable moments. Conclusion: Positioner material plays a major role in delivering forces to the teeth. However, tooth positioners did not induce corrective forces in all the malpositions tested. Clinically relevant correctional forces or moments in conjunction with all suprapositions, rotations of 10° and 20° as well as mesial tipping of the canine were observe

Probabilistic Path Discovery with Snakes in Ad Hoc Networks

Many routing protocols for wireless ad hoc networks proposed in the literature use flooding to discover paths between the source and the destination node. Despite various broadcast optimization techniques, flooding remains expensive in terms of bandwidth and energy consumption. In general, O(N) nodes are involved to discover a path. In this thesis, we prove through a theoretical model that probabilistic path discovery is possible by involving O(sqrt(N)) nodes only. The constant factor depends on the desired path discovery probability. Using a novel network primitive that we call snakes, we introduce practical and cheap probabilistic path discovery algorithms. These algorithms rely on the same network model and assumptions as its flooding counterparts, i. e., that the network is unstructured and that nodes only know their immediate (one-hop) neighbors. Numerical simulations in a static network show that these algorithms achieve path discovery probabilities close to the theoretical optimum. We further present a snake-based algorithm for mobile ad hoc networks and several techniques to enhance the performance in some specific networks

Schistosoma mansoni TOR is a tetraspanning orphan receptor on the parasite surface

A trispanning orphan receptor (TOR) has been described in Schistosoma haematobium and S. mansoni. Here we report the complete molecular organization of the S. mansoni TOR gene, also known as SmCRIT (complement C2 receptor inhibitor trispanning). The SmTOR gene consists of 4 exons and 3 introns as shown by cloning the single exons from S. mansoni genomic DNA and the corresponding cDNA from the larval stage (cercaria) and the adult worm. The SmTOR ORF consists of 1260 bp and is longer than previously reported, with a fourth trans-membrane domain (proposed new name: Tetraspanning Orphan Receptor) and with, however, an unchanged C2-binding domain on the extracellular domain 1 (ed1). This domain differs in S. japonicum. A protein at the approximate expected molecular weight (55 kDa) was detected in adult worm extracts with polyclonal and monoclonal antibodies, and was found to be expressed on the tegumental surface of cercaria

Base Stations in Mobile Ad-Hoc Networks

Multi-hop ad-hoc networks consist of nodes which cooperate by forwarding packets for each other to allow communication beyond the power range of each node. In pure ad-hoc networks, no additional infrastructure is required to allow the nodes to communicate. Multi-hop hybrid networks are a combination of ad-hoc and cellular networks. As in ad-hoc networks, the nodes forward packets on behalf of other nodes. However, a few base stations are introduced. This enables long-range communication, increases connectivity and allows centralized services. In our work, we investigate the problem of placing base stations in multi-hop hybrid networks. Since nodes extend the service area by themselves, conventional cellular approaches are not suitable for such networks. We propose the Cluster Covering Algorithm, an algorithm which takes into account the percolation phenomenon, and compare it with several greedy algorithms. We measure the connectivity through different simulations on real population distribution data of Zurich (CH), the Surselva Valley (CH) and Finland. The simulation results show that the Cluster Covering Algorithm outperforms the greedy algorithms

Tracking an Odor Plume in a Laminar Wind Field with the Crosswind-Surge Algorithm

We introduce a novel bio-inspired odor source localization algorithm (surge-cast) for environments with a main wind flow and compare it to two well- known algorithms. With all three algorithms, systematic experiments with real robots are carried out in a wind tunnel under laminar flow conditions. The algo- rithms are compared in terms of distance overhead when tracking the plume up to the source, but a variety of other experimentally measured results are provided as well. We conclude that the surge-cast algorithm yields significantly better performance than the casting algorithm, and slightly better performance than the surge-spiral algorithm

Simulation Experiments with Bio-Inspired Algorithms for Odor Source Localization in Laminar Wind Flow

We compare three bio-inspired odor source localization algorithm (casting, surge-spiral and surge-cast) for environments with a main wind flow in simulation. The wind flow is laminar and the simulation setup similar to the setup in the wind tunnel in which we have carried out similar experiments with real robots. The algorithms are compared in terms of success rate and distance overhead when tracking the plume up to the source. We conclude that the algorithms based on upwind surge yield significantly better performance than pure casting

Educational Concerns, Health Concerns and Mental Health During Early COVID-19 School Closures: The Role of Perceived Support by Teachers, Family, and Friends

This study investigated whether school closures and health-related uncertainties in the early phases of the COVID-19 pandemic posed risk factors for adolescents’ mental health and whether perceived social support by parents, teachers, and friends functioned as protective factors. In particular, we argued that perceived social support would buffer negative associations between educational and health concerns and mental health. Based on a person-centered approach, we first examined resilience profiles. These profiles reflect configurations regarding the levels of these risk and protective factors and levels of mental health. Second, we analyzed whether these risk and protective factors predicted adolescents’ mental health differently by using a variable-centered approach. The sample consisted of 1’562 adolescents (Mage = 16.18, SD = 1.48, range = 14-20 years; 72% females) in lower and higher secondary education from three regions: German-speaking part of Switzerland, N = 486; Italian-speaking part of Switzerland, N = 760; and Northern Italy N = 316. Results from the person-centered approach revealed three latent profiles characterized by low (19%), average (47%), or high resilience (34%). Lower resilience was associated with higher educational concerns, lower perceived social support, and lower mental health, while high resilience was characterized by lower concerns, higher support, and higher mental health. Importantly, educational concerns varied more between profiles than health concerns, and perceived teacher and family support varied more than perceived friend support. Corroborating these findings, the variable-centered approach (i.e., a path analysis) revealed that educational concerns were a stronger predictor than health concerns and pointed to a higher relative importance of perceived family support for adolescents’ mental health relative to perceived teacher and friend support. Taken together, the findings suggest that adolescents’ educational concerns and perceived family support, respectively, were stronger risk and protective factors for their mental health during school closures related to the COVID-19 pandemic. Finally, adolescents from regions being more exposed to the COVID-19 pandemic, namely, Italian-speaking part of Switzerland and Northern Italy, were more likely classified in the low or the average rather than in the high resilience profile compared to students from the region with lower exposure, that is, the German-speaking part of Switzerland