Isolation and propagation of Trypanosoma brucei gambiense from sleeping sickness patients in south Sudan

This study aimed at isolating Trypanosoma brucei gambiense from human African trypanosomiasis (HAT) patients from south Sudan. Fifty HAT patients identified during active screening surveys were recruited, most of whom (49/50) were in second-stage disease. Blood and cerebrospinal fluid samples collected from the patients were cryopreserved using Triladyl® as the cryomedium. The samples were stored at −150 °C in liquid nitrogen vapour in a dry shipper. Eighteen patient stabilates could be propagated in immunosuppressed Mastomys natalensis and/or SCID mice. Parasitaemia was highest in SCID mice. Further subpassages in M. natalensis increased the virulence of the trypanosomes and all 18 isolates recovered from M. natalensis or SCID mice became infective to other immunosuppressed mouse breeds. A comparison of immunosuppressed M. natalensis and Swiss White, C57/BL and BALB/c mice demonstrated that all rodent breeds were susceptible after the second subpassage and developed a parasitaemia >106/ml by Day 5 post infection. The highest parasitaemias were achieved in C57/BL and BALB/c mice. These results indicate that propagation of T. b. gambiense isolates after initial isolation in immunosuppressed M. natalensis or SCID mice can be done in a range of immunosuppressed rodent

Crosstalk between Trypanosoma brucei and the tsetse fly

Trypanosoma brucei cause the fatal disease sleeping sickness in humans and the morbid disease nagana in animals. About 36 sub-Saharan African countries are affected by these diseases. The parasites are transmitted by tsetse flies (Glossina spp.) exclusively where they colonise the alimentary tract and the salivary glands. The trypanosomes establish first in the midgut as procyclic forms from where they colonise then the proventriculus (that connects the mid- with the foregut) and migrate later as epimastigote forms into the salivary glands via the foregut and proboscis. In the salivary glands epimastigote forms attach to the epithelium and give rise to the mammalian infective forms, the metacyclics. During transmission through the fly, trypanosomes are frequently severely reduced when they invade a new compartment. Trypanosomes either recover and develop an infection or fail to establish an infection and are eliminated by the tsetse fly’s defence. This complex interaction between vector and parasite shows that both counterparts specifically regulate genes. In this thesis we wanted to shed light into this complex crosstalk in three projects: We established a model to analyse how the severe reductions during the life cycle influence the diversity of trypanosomes. Short variable DNA sequences were integrated into the trypanosome’s genome to establish an artificial diversity. These transfected trypanosomes were cyclically transmitted through flies and mice. Tag DNA was isolated from infected flies and/ or mice and identified by sequencing. This allowed us to monitor diversity of the trypanosomes throughout their life cycle. We found that diversity was moderately reduced in the tsetse fly’s midgut but that migration into the salivary glands decreases the diversity. This decrease is mainly due to a shift in relative frequency which leads to a very uneven distribution of the tags. The diversity constantly decreased during mouse infection due to the constant gain of trypanosomes bearing the dominant tag. Surprisingly, the number of different tags was not reduced during the whole life cycle of the trypanosomes. The two anti-microbial peptides (AMPs), attacin and defensin, of tsetse flies were reported to play an important role in eliminating trypanosomes in the midgut. The mRNA of these AMPs was shown to be up-regulated upon trypanosome infection and it was hypothesised that procyclins might specifically induce its activation. We wanted to test this with different trypanosome strains as well with trypanosomes with incomplete or deleted procyclin coats. Tsetse flies were infected and mRNA isolated after various times of trypanosome exposition. None of the flies showed an up-regulated level of attacin and defensin mRNA. This result is in strong contradiction to some publications dealing with AMP regulation in infected tsetse flies. The tsetse flies, from the colony in Bratislava (Slovakia), show a high level of attacin and defensin mRNA in teneral flies (what not all G. m. morsitans do), show a midgut infection rate of about 50% (which is high compared to the infection rate in other laboratories), and are infected sometimes with the salivary gland hypertrophy virus (SGHV). It is very possible that attacin and defensin are not always up-regulated and that its activation is dependent on tsetse colony and origin. During the establishment in the midgut trypanosomes express procyclins, a stage specific surface protein coat that was suggested to protect against proteolytic enzymes or to be important to direct the parasite in the host. To test this hypothesis all procyclin genes were deleted and tsetse fly infection experiments were carried out. Interestingly, the null-mutant (Δprocyclin) was able to infect the midgut comparable to wild type trypanosomes, disclosing that procyclins are not needed for the establishment in the midgut and that probably free glycosylphosphatidylinositol (GPI) anchors, which are loaded with procyclins in wild type trypanosomes, overtook their function. Surprisingly, Δprocyclin was able to infect the salivary glands even though at very low rates, which reflects difficulties of trypanosomes to re-load the free GPIs with epimastigote specific surface proteins (e.g. BARP) for efficient migration. In competition, Δprocyclin was completely overgrown by wild type trypanosomes in the tsetse midgut, reflecting the selective advantage of a procyclin coat

Local Differential Privacy In Smart Manufacturing: Application Scenario, Mechanisms and Tools

To utilize the potential of machine learning and deep learning, enormous amounts of data are required. To find the optimal solution, it is beneficial to share and publish data sets. Due to privacy leaks in publically released datasets and the exposure of sensitive information of individuals by attackers, the research field of differential privacy addresses solutions to avoid this in the future. Compared to other domains, the application of differential privacy in the manufacturing context is very challenging. Manufacturing data contains sensitive information about the companies and their process knowledge, products, and orders. Furthermore, data of individuals operating machines could be exposed and thus their performance evaluated. This paper describes scenarios of how differential privacy can be used in the manufacturing context. In particular, the potential threats that arise when sharing manufacturing data are addressed. This is described by identifying different manufacturing parameters and their variable types. Simplified examples show how the differentially private mechanisms can be applied to binary, numeric, categorical variables, and time series. Finally, libraries are presented which enable the productive use of differential privacy

Cardiovascular fitness associated with cognitive performance in heart failure patients enrolled in cardiac rehabilitation

Abstract Background Reduced cognitive function is common in persons with heart failure (HF). Cardiovascular fitness is a known contributor to cognitive function in many patient populations, but has only been linked to cognition based on estimates of fitness in HF. The current study examined the relationship between fitness as measured by metabolic equivalents (METs) from a standardized stress test and cognition in persons with HF, as well as the validity of office-based predictors of fitness in this population. Methods Forty-one HF patients enrolled in cardiac rehabilitation completed a standardized exercise stress test protocol, a brief neuropsychological battery, the 2-minute step test (2MST), and a series of medical history and self-report questionnaires. Results Maximum METs from stress testing demonstrated incremental predictive validity for attention (β = .41,p = .03), executive function (β = .37,p = .04), and memory domains (β = .46,p = .04). Partial correlations accounting for key medical and demographic characteristics revealed greater METs was associated with the 2MST (r(32) = .41,p = .02) but not with the Duke Activity Status Index (DASI) (r(32) = .24,p = .17). Conclusion The current findings indicate that better fitness levels measured by METs is independently associated with better cognitive function in older adults with HF. Results also showed that METs was closely associated with one office-based measure of fitness (2MST), but not another (DASI). Prospective studies are needed to clarify the mechanisms linking fitness and cognitive function in HF

Comparing Research Trends and Industrial Adoption of Manufacturing Operations Management Solutions

For decades, the operations on the shop floor of manufacturing organizations have been supported by Manufacturing Execution Systems. In this paper, we investigate the trends of Manufacturing Operations Management in the research community and analyze of the adoption in the industry. Our literature review identifies the following trends for Manufacturing Operations Management: distributed system architectures, cloud technology, and use of standards. We conducted a survey targeting Manufacturing Operations Management solution providers and adopters to explore the adoption of these trends. The survey results show that the use of standards is already addressed to some extent by the industry. Practitioners anticipate distributed system architectures for Manufacturing Operations Management solutions in the future. However, practitioners are still reluctant towards cloud-only technology and will continue to be so in the foreseeable future

Pathways to Carbon-Free Transport in Germany until 2050

The transport sector has to be widely decarbonized by 2050 to reach the targets of the Paris Agreement. This can be performed with different drive trains and energy carriers. This paper explored four pathways to a carbon-free transport sector in Germany in 2050 with foci on electricity, hydrogen, synthetic methane, or liquid synthetic fuels. We used a transport demand model for future vehicle use and a simulation model for the determination of alternative fuel vehicle market shares. We found a large share of electric vehicles in all scenarios, even in the scenarios with a focus on other fuels. In all scenarios, the final energy consumption decreased significantly, most strongly when the focus was on electricity and almost one-third lower in primary energy demand compared with the other scenarios. A further decrease of energy demand is possible with an even faster adoption of electric vehicles, yet fuel cost then has to be even higher or electricity prices lower

Towards A Design Of A Software-Defined Manufacturing System Based On A Systematic Literature Review For Enabling A Decentralised High-Rate Electrolyser Production

Hydrogen is critical for the transition to an environmentally sound and reliable energy supply. This transition requires large capacities of performant and cost-effective electrolysers. Although performant electrolysers already exist, they cannot yet be manufactured at a high rate in series production. The project H2Giga-FRHY is researching a reference factory for large-scale production of electrolysers, developing new production and testing modules. As an essential building block of the reference factory, a research group at Fraunhofer IPA is designing and implementing a comprehensive software-defined manufacturing system (SDMS), which supports the decentralized high-rate production of electrolysers and allows for far-reaching insights regarding high-rate capability, quality, and cost of products, processes, and technologies involved. For the SDMS implementation, different enterprise architecture (EA) approaches are considered and evaluated in the scope of a structured literature review with respect to criteria arising from the project context and related research questions. In this paper, an approach to designing a software-defined manufacturing system is described, and its necessity is based on the use case-specific criteria discussed

Giant Slalom: Analysis of Course Setting, Steepness and Performance of Different Age Groups - A Pilot Study

Introduction: Giant slalom is the core discipline of alpine skiing, and each race has its own specific course and terrain characteristics. These variations may explain differences in the speed and time per turn profiles, which are essential for performance development and injury prevention. This study aims to address the differences in course setting and steepness of the different course sections (flat-medium-steep) and compare them to the performance parameters among young (U12, U14, U16) and older (U18, U21, elite) male athletes. Methods: The study examined a total sample size of 57 male athletes; 7 from elite level, 11 from U21, 13 from U18, 6 from U16, 13 from U14, and 7 from U12. The athletes wore a portable global navigation satellite system (GNSS) sensor to extract performance parameters. The course profiles and gate positions of nine runs were measured with differential GNSS. The runs were divided into flat, medium and steep sections. From the performance parameters (speed, time per turn, etc.) and the course setting variables, the mean value per section was calculated and used for the further analysis. Results: In total, 192 run sections from 88 runs were recorded and analyzed. Comparisons between course settings in young and older classes showed no significant differences. However, the turning angles and horizontal gate distances were smaller in flat sections. Average speed (49.77 vs. 65.33 km/h) and time per turn (1.74 vs. 1.41 s) differed significantly between young and U21/elite categories. In medium terrain sections U21 and elite athletes spent more time in the gliding phase compared to all other athletes. Discussion: It seems to be a reasonable that, given similar course setting and steepness, speed increases concurrently with the technical and tactical skills of the athlete. Moreover, the finding that the elite athletes spent more time in the gliding phase could be crucial for understanding technique and performance development in young athletes