Search results for: Răzvan Florian

Authors: Felicia Segeth, Florian G. Klein, Lea Berger, Andreas Kolk, Per S. Holm

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The entry of oncolytic viruses (OVs) into clinical application opens groundbreaking changes in current and future treatment regimens. However, despite their potent anti-cancer activity in vitro, clinical studies revealed limitations of OVs as monotherapy. The same applies to CDK 4/6 inhibitors (CDK4/6i) targeting cell cycle as well as bromodomain and extra-terminal domain inhibitors (BETi) targeting gene expression. In this study, the anti-tumoral effect of XVir-N-31, an YB-1 dependent oncolytic adenovirus, was evaluated in combination with Ribociclib, a CDK4/6i, and JQ1, a BETi. The head and neck squamous cell carcinoma (HNSCC) cell lines Fadu, SAS, and Cal-33 were used. DNA replication and gene expression of XVir-N-31 was measured by RT-qPCR, protein expression by western blotting, and cell lysis by SRB assays. Treatment with CDK4/6i and BETi increased viral gene expression, viral DNA replication, and viral particle formation. The data show that the combination of oncolytic adenovirus XVir-N-31 with CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore, additional molecular analyses on this subject demonstrate that the positive transcription elongation factor P-TEFb plays a decisive role in this regard, indicating an influence of the combinational therapy on gene transcription control. The combination of CDK4/6i & BETi and XVir-N-31 is an attractive strategy to achieve substantial cancer cell killing and is highly suitable for clinical testing.

Keywords: adenovirus, BET, CDK4/6, HNSCC, P-TEFb, YB-1

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Authors: Bernardo Cortez, Florian Peter, Thomas Lausenhammer, Paulo Oliveira

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Designing missiles’ autopilot controllers have been a complex task, given the extensive flight envelope and the nonlinear flight dynamics. A solution that can excel both in nominal performance and in robustness to uncertainties is still to be found. While Control Theory often debouches into parameters’ scheduling procedures, Reinforcement Learning has presented interesting results in ever more complex tasks, going from videogames to robotic tasks with continuous action domains. However, it still lacks clearer insights on how to find adequate reward functions and exploration strategies. To the best of our knowledge, this work is a pioneer in proposing Reinforcement Learning as a framework for flight control. In fact, it aims at training a model-free agent that can control the longitudinal non-linear flight dynamics of a missile, achieving the target performance and robustness to uncertainties. To that end, under TRPO’s methodology, the collected experience is augmented according to HER, stored in a replay buffer and sampled according to its significance. Not only does this work enhance the concept of prioritized experience replay into BPER, but it also reformulates HER, activating them both only when the training progress converges to suboptimal policies, in what is proposed as the SER methodology. The results show that it is possible both to achieve the target performance and to improve the agent’s robustness to uncertainties (with low damage on nominal performance) by further training it in non-nominal environments, therefore validating the proposed approach and encouraging future research in this field.

Keywords: Reinforcement Learning, flight control, HER, missile autopilot, TRPO

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Authors: Florian Wagner, Christoph Schmidt, Vincent Bagnoud

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Understanding the interaction of ultra-intense laser pulses with overcritical targets is of major interest for many applications such as laser-driven ion acceleration, fast ignition in the frame of inertial confinement fusion or high harmonic generation and the creation of attosecond pulses. One particular aspect of this interaction is the shift of the critical surface, where the laser pulse is stopped and the absorption is at maximum, due to the radiation pressure induced by the laser pulse, also referred to as laser hole boring. We investigate laser-hole boring experimentally by measuring the backscattered spectrum which is doppler-broadened because of the movement of the reflecting surface. Using the high-power, high-energy laser system PHELIX in Darmstadt, we gathered an extensive set of data for different laser intensities ranging from 10^18 W/cm2 to 10^21 W/cm2, two different levels of the nanosecond temporal contrast (10^6 vs. 10^11), elliptical and linear polarization and varying target configurations. In this contribution we discuss how the maximum velocity of the critical surface depends on these parameters. In particular we show that by increasing the temporal contrast the maximum hole boring velocity is decreased by more than a factor of three. Our experimental findings are backed by a basic analytical model based on momentum and mass conservation as well as particle in cell simulations. These results are of particular importance for fast ignition since they contribute to a better understanding of the transport of the ignitor pulse into the overdense region.

Keywords: laser-hole boring, interaction of ultra-intense lasers with overcritical targets, fast ignition, relativistic laser motter interaction

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Authors: Joel Ballesteros, Harriet Jane Caleja, Florian Del Mundo, Cherrie Pascual

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Diffraction-based sensing was utilized in the quantification of human ferritin in blood serum to provide an alternative to label-based immunoassays currently used in clinical diagnostics and researches. The diffraction intensity was measured by the diffractive optics technology or dotLab™ system. Two methods were evaluated in this study: direct immunoassay and direct sandwich immunoassay. In the direct immunoassay, human ferritin was captured by human ferritin antibodies immobilized on an avidin-coated sensor while the direct sandwich immunoassay had an additional step for the binding of a detector human ferritin antibody on the analyte complex. Both methods were repeatable with coefficient of variation values below 15%. The direct sandwich immunoassay had a linear response from 10 to 500 ng/mL which is wider than the 100-500 ng/mL of the direct immunoassay. The direct sandwich immunoassay also has a higher calibration sensitivity with value 0.002 Diffractive Intensity (ng mL-1)-1) compared to the 0.004 Diffractive Intensity (ng mL-1)-1 of the direct immunoassay. The limit of detection and limit of quantification values of the direct immunoassay were found to be 29 ng/mL and 98 ng/mL, respectively, while the direct sandwich immunoassay has a limit of detection (LOD) of 2.5 ng/mL and a limit of quantification (LOQ) of 8.2 ng/mL. In terms of accuracy, the direct immunoassay had a percent recovery of 88.8-93.0% in PBS while the direct sandwich immunoassay had 94.1 to 97.2%. Based on the results, the direct sandwich immunoassay is a better diffraction-based immunoassay in terms of accuracy, LOD, LOQ, linear range, and sensitivity. The direct sandwich immunoassay was utilized in the determination of human ferritin in blood serum and the results are validated by Chemiluminescent Magnetic Immunoassay (CMIA). The calculated Pearson correlation coefficient was 0.995 and the p-values of the paired-sample t-test were less than 0.5 which show that the results of the direct sandwich immunoassay was comparable to that of CMIA and could be utilized as an alternative analytical method.

Keywords: biosensor, diffraction, ferritin, immunoassay

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Authors: Sara Ramos Contioso

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The premiere of Anton Bruckner's Requiem in Dm, in September 1849, represents a turning point in the composer's creative evolution. This Mass of the Dead, which was dedicated to the memory of his esteemed friend and mentor Franz Sailer, establishes the beginning of a new creative aesthetic in the composer´s production and links its liturgical development, which is contextualized in the monastery of St. Florian, to the use of a range of musicals possibilities that are projected by Bruckner on an orchestral texture with choir and organ. Set on a strict tridentine ritual model, this requiem exemplifies the religious aesthetics of a composer that is committed to the Catholic faith and that also links to its structure the reinterpretation of a religious model that, despite being romantic, shows a strong influence derived from the baroque or the Viennese Classicism language. Consequently, the study responds to the need to show the survival of the Requiem Mass within the romantic context of Vienna. Therefore, it draws on a detailed analysis of the score and the creative context of the composer with the intention of linking the work to the tradition of the genre and also specifying the stylistic particularities of its musical model within a variability of possibilities such as the contrasting precedents of Mozart, Haydn, Cherubini or Berlioz´s requiems. Tradition or modernity, liturgy or concert hall are aesthetic references that will condition the development of the Requiem Mass in the middle of the nineteenth century. In this context, this paper tries to recover Bruckner's Requiem in Dm as a musical model of the romantic ritual of deceased and as a stylistic reference of a creative composition that will condition the development of later liturgical works such as Liszt or DeLange (1868) ones.

Keywords: liturgy, religious symbolism, requiem, romanticism

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Authors: Luna Sequier, Florian Forelli, Maude Traulle, Amaury Vandebrouck, Pascal Duffiet, Louis Ratte, Jean Mazeas

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The study's objective is to compare the muscular activity of the flexor knee muscle in patients who underwent an anterior cruciate ligament reconstruction with hamstring autograft and the individuals who have not undergone surgery. Methods: The participants were divided into two groups: a healthy group and an experimental group who had undergone an anterior cruciate ligament reconstruction with a hamstring graft. All participants had to perform a knee flexion strength test on an isokinetic dynamometer. The medial Gastrocnemius, lateral Gastrocnemius, Biceps femoris, and medial Hamstring muscle activity were measured during this test. Each group’s mean muscle activity was tested with statistical analysis, and a muscle activity ratio of gastrocnemius and hamstring muscles was calculated Results: The results showed a significant difference in activity of the medial gastrocnemius (p = 0,004901), the biceps femoris (p = 5,394.10-6), and the semitendinosus muscles (p = 1,822.10-6), with a higher Biceps femoris and Semitendinosus activity for the experimental group. It is however noticeable that inter-subject differences were important. Conclusion: This study has shown a difference in the gastrocnemius and hamstring muscle activity between patients who underwent an anterior cruciate ligament reconstruction surgery and healthy participants. With further results, this could show a modification of muscle activity patterns after surgery which could lead to compensatory behaviors at a return to sport and eventually explain a higher injury risk for our patients.

Keywords: anterior cruciate ligament, electromyography, muscle activity, physiotherapy

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Authors: Chenlu Zhang, Wanni Zhang, Florian Schaule

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Indoor environment in office buildings directly affects comfort, productivity, health, and well-being of building occupants. Wireless environmental sensor networks have been deployed in many modern offices to monitor and control the indoor environments. However, indoor environmental variables are not strong enough predictors of comfort and productivity levels of every occupant due to personal differences, both physiologically and psychologically. This study proposes human-centric sensor networks that integrate wireless environmental sensors, body area network sensors and participatory sensing technologies to collect data from both environment and human and support building operations. The sensor networks have been tested in one small-size and one medium-size office rooms with 22 participants for five months. Indoor environmental data (e.g., air temperature and relative humidity), physiological data (e.g., skin temperature and Galvani skin response), and physiological responses (e.g., comfort and self-reported productivity levels) were obtained from each participant and his/her workplace. The data results show that: (1) participants have different physiological and physiological responses in the same environmental conditions; (2) physiological variables are more effective predictors of comfort and productivity levels than environmental variables. These results indicate that the human-centric sensor networks can support human-centric building control and improve comfort and productivity in offices.

Keywords: body area network, comfort and productivity, human-centric sensors, internet of things, participatory sensing

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Authors: Sabine Pau, Sophia Volz, Emanuel Bauer, Amelie De Gregorio, Frank Reister, Wolfgang Janni, Florian Ebner

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Purpose: The umbilical cord pH is a well evaluated contributor for prediction of neonatal outcome. This study correlates nenonatal umbilical cord pH with the weekday of delivery, the time of birth as well as the staff hand over times (midwifes and doctors). Material and Methods: This retrospective study included all deliveries of a 20 year period (1994-2014) at our primary obstetric center. All deliveries with a newborn cord pH under 7,20 were included in this analysis (6929 of 48974 deliveries (14,4%)). Further subgroups were formed according to the pH (< 7,05; 7,05 – 7,09; 7,10 – 7,14; 7,15 – 7,19). The data were then separated in day- and night time (8am-8pm/8pm-8am) for a first analysis. Finally, handover times were defined at 6 am – 6.30 am, 2 pm -2.30 pm, 10 pm- 10.30 pm (midwives) and for the doctors 8-8.30 am, 4 – 4.30 pm (Monday- Thursday); 2 pm -2.30 pm (Friday) and 9 am – 9.30 am (weekend). Routinely a shift consists of at least three doctors as well as three midwives. Results: During the last 20 years, 6929 neonates were born with an umbilical cord ph < 7,20 ( < 7,05 : 7,1%; 7,05 – 7,09 : 10,9%; 7,10 – 7,14 : 30,2%; 7,15 – 7,19:51,8%). There was no significant difference between either night/day delivery (p = 0.408), delivery on different weekdays (p = 0.253), delivery between Monday to Thursday, Friday and the weekend (p = 0.496 ) or delivery during the handover times of the doctors as well as the midwives (p = 0.221). Even the standard deviation showed no differences between the groups. Conclusion: Despite an increased workload over the last 20 years, the standard of care remains high even during the handover times and night shifts. This applies for midwives and doctors. As the neonatal outcome depends on various factors, further studies are necessary to take more factors influencing the fetal outcome into consideration. In order to maintain this high standard of care, an adaption of work-load and changing conditions is necessary.

Keywords: delivery, fetal umbilical cord pH, day time, hand over times

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Authors: Florian Lienert, Peter Costa, Caroline Aurensan, Elaine Melander

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Introduction: Rabies pre-exposure prophylaxis (PrEP) can be given before travel and simplifies post-exposure prophylaxis (PEP). We studied the knowledge about rabies, the uptake of PrEP, and reasons for deciding for or against PrEP in at-risk travelers. We also examined how healthcare professionals (HCPs) counsel on rabies prevention. Methods: On behalf of Bavarian Nordic, Ipsos MORI conducted two online surveys in the USA. Fieldwork from February 24th to April 23rd, 2021, 689 participants aged 18-85 years, visited one of 91 endemic rabies countries in the past 3 years for at least one week, involved in at least 1 of 7 at-risk activities, heard of rabies, positive towards vaccination and chose to take part (surveyed travelers). Secondly, 76 HCPs, with responsibility for advising/ making decisions about vaccination requirements for their patients, personally recommend or prescribe vaccines for rabies, positive towards vaccination and chose to take part (surveyed HCPs). Results: A minority (36%) of surveyed travelers classified rabies as a life-threatening disease. A third of surveyed HCPs (37%) did not discuss rabies vaccination with at-risk travelers, 18% discussed only PEP, 23% only PrEP and 22% both. A minority (21%) of surveyed travelers reported having received rabies vaccination since they were 18. Among those participants (n=145), the most common reasons for deciding to get PrEP were for their own peace of mind (35%) and following an HCP recommendation (32%). Of those who decided not to receive the rabies vaccine (n=319), the most common reasons were that they did not think their risk of rabies was sufficient (23%) and that the HCP did not suggest it (23%). Conclusions: The survey demonstrated knowledge gaps around rabies and low PrEP coverage among surveyed travelers. It also highlighted the role of HCP recommendations and showed that most HCPs did not discuss PrEP with at-risk travelers.

Keywords: rabies, pre-exposure prophylaxis, travel, travel health, post-travel care, rabies treatment, vaccine, post-exposure, prophylaxis, at-risk, education, PrEP, PEP

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Authors: Florian Billing, Soren Segan, Meike Jakobi, Elsa Arefaine, Aliki Jerch, Xin Xiong, Matthias Becker, Thomas Joos, Burkhard Schlosshauer, Ulrich Rothbauer, Nicole Schneiderhan-Marra, Hanna Hartmann, Christopher Shipp

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The immune response plays a major role in implant biocompatibility, but an understanding of how to design biomaterials for specific immune responses is yet to be achieved. We aimed to better understand how changing certain material properties can drive immune responses. To this end, we tested immune response to experimental implant coatings that vary in specific characteristics. A layer-by-layer approach was employed to vary surface charge and wettability. Human-based in vitro models (THP-1 macrophages and primary peripheral blood mononuclear cells (PBMCS)) were used to assess immune responses using multiplex cytokine analysis, flow cytometry (CD molecule expression) and microscopy (cell morphology). We observed dramatic differences in immune response due to specific alterations in coating properties. For example altering the surface charge of coating A from anionic to cationic resulted in the substantial elevation of the pro-inflammatory molecules IL-1beta, IL-6, TNF-alpha and MIP-1beta, while the pro-wound healing factor VEGF was significantly down-regulated. We also observed changes in cell surface marker expression in relation to altered coating properties, such as CD16 on NK Cells and HLA-DR on monocytes. We furthermore observed changes in the morphology of THP-1 macrophages following cultivation on different coatings. A correlation between these morphological changes and the cytokine expression profile is ongoing. Targeted changes in biomaterial properties can produce vast differences in immune response. The properties of the coatings examined here may, therefore, be a method to direct specific biological responses in order to improve implant biocompatibility.

Keywords: biomaterials, coatings, immune system, implants

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Authors: Graham Hancox, Saydia Razak, Sue Hignett, Jo Barnes, Jyri Silmari, Florian Kading

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In the event of a Chemical, Biological, Radiological and Nuclear (CBRN) incident rapidly gaining, situational awareness is of paramount importance and advanced technologies have an important role to play in improving detection, identification, monitoring (DIM) and patient tracking. Understanding how these advanced technologies can fit into current response systems is essential to ensure they are optimally designed, usable and meet end-users’ needs. For this reason, Human Factors (Ergonomics) methods have been used within an EU Horizon 2020 project (TOXI-Triage) to firstly describe (map) the hierarchical structure in a CBRN response with adapted Accident Map (AcciMap) methodology. Secondly, Hierarchical Task Analysis (HTA) has been used to describe and review the sequence of steps (sub-tasks) in a CBRN scenario response as a task system. HTA methodology was then used to map one advanced technology, ‘Tag and Trace’, which tags an element (people, sample and equipment) with a Near Field Communication (NFC) chip in the Hot Zone to allow tracing of (monitoring), for example casualty progress through the response. This HTA mapping of the Tag and Trace system showed how the provider envisaged the technology being used, allowing for review and fit with the current CBRN response systems. These methodologies have been found to be very effective in promoting and supporting a dialogue between end-users and technology providers. The Human Factors methods have given clear diagrammatic (visual) representations of how providers see their technology being used and how end users would actually use it in the field; allowing for a more user centered approach to the design process. For CBRN events usability is critical as sub-optimum design of technology could add to a responders’ workload in what is already a chaotic, ambiguous and safety critical environment.

Keywords: AcciMap, CBRN, ergonomics, hierarchical task analysis, human factors

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Authors: Sandrine Cardinal, Jean-Marc Pelletier, Guang Xie, Florian Mercier, Florent Delmas

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Bulk metallic glasses exhibit several superior properties, compared to their corresponding crystalline counterpart, such as high strength, high elastic limit or good corrosion resistance. Therefore they can be considered as good candidates for structural applications in many sectors. However, they are generally brittle and do not exhibit plastic deformation at room temperature. These materials are mainly obtained by rapid cooling from a liquid state to prevent crystallization, which limits their size. To overcome these two drawbacks: fragility and limited dimensions, composite metallic glass matrix reinforced by a second phase whose role is to slow crack growth are developed. Concerning the limited size of the pieces, the proposed solution is to get the material from amorphous powders by densifying under load. In this study, Cu50Zr45Al5 bulk metallic glassy matrix composites (MGMCs) containing different volume fraction (Vf) of Zr crystalline particles were manufactured by spark plasma sintering (SPS). Microstructure, thermal stability and mechanical properties of the MGMCs were investigated. Matrix of the composites remains a fully amorphous phase after consolidation at 420°C under 600 MPa. A good dispersion of the particles in the glassy matrix is obtained. Results show that the compressive strength decreases with Vf : 1670 MPa (Vf=0%) to 1300MPa (Vf=30%), the elastic modulus decreases but only slighty respectively 97.3GPa and 94.5 GPa and plasticity is improved from 0 to 4%. Fractographic investigation indicates a good bonding between amorphous and crystalline particles. In conclusion, present study has demonstrated that SPS method is useful for the synthesis of the bulk glassy composites. Large controlled microstructure specimens with interesting ductility can be obtained compared with others methods.

Keywords: composite, mechanical properties, metallic glasses, spark plasma sintering

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Authors: Florian Vincent Haase, Adrian Dierl, Anna Henke, Ralf Woll, Ennes Sarradj

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Structured sheet metals and structured sandwich sheet metals are three-dimensional, lightweight structures with increased stiffness which are used in the automotive industry. The impedance, a figure of resistance of a structure to vibrations, will be determined regarding plain sheets, structured sheets, and structured sandwich sheets. The aim of this paper is generating an experimental design in order to minimize costs and duration of experiments. The design of experiments will be used to reduce the large number of single tests required for the determination of correlation between the impedance and its influencing factors. Full and fractional factorials are applied in order to systematize and plan the experiments. Their major advantages are high quality results given the relatively small number of trials and their ability to determine the most important influencing factors including their specific interactions. The developed full factorial experimental design for the study of plain sheets includes three factor levels. In contrast to the study of plain sheets, the respective impedance analysis used on structured sheets and structured sandwich sheets should be split into three phases. The first phase consists of preliminary tests which identify relevant factor levels. These factor levels are subsequently employed in main tests, which have the objective of identifying complex relationships between the parameters and the reference variable. Possible post-tests can follow up in case additional study of factor levels or other factors are necessary. By using full and fractional factorial experimental designs, the required number of tests is reduced by half. In the context of this paper, the benefits from the application of design for experiments are presented. Furthermore, a multistage approach is shown to take into account unrealizable factor combinations and minimize experiments.

Keywords: structured sheet metals, structured sandwich sheet metals, impedance measurement, design of experiment

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Authors: Javier Muro, Anja Linstadter, Florian Manner, Lisa Schwarz, Stephan Wollauer, Paul Magdon, Gohar Ghazaryan, Olena Dubovyk

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Monitoring the trade-off between biomass production and biodiversity in grasslands is critical to evaluate the effects of management practices across environmental gradients. New generations of remote sensing sensors and machine learning approaches can model grasslands’ characteristics with varying accuracies. However, studies often fail to cover a sufficiently broad range of environmental conditions, and evidence suggests that prediction models might be case specific. In this study, biomass production and biodiversity indices (species richness and Fishers’ α) are modeled in 150 grassland plots for three sites across Germany. These sites represent a North-South gradient and are characterized by distinct soil types, topographic properties, climatic conditions, and management intensities. Predictors used are derived from Sentinel-1 & 2 and a set of topoedaphic variables. The transferability of the models is tested by training and validating at different sites. The performance of feed-forward deep neural networks (DNN) is compared to a random forest algorithm. While biomass predictions across gradients and sites were acceptable (r2 0.5), predictions of biodiversity indices were poor (r2 0.14). DNN showed higher generalization capacity than random forest when predicting biomass across gradients and sites (relative root mean squared error of 0.5 for DNN vs. 0.85 for random forest). DNN also achieved high performance when using the Sentinel-2 surface reflectance data rather than different combinations of spectral indices, Sentinel-1 data, or topoedaphic variables, simplifying dimensionality. This study demonstrates the necessity of training biomass and biodiversity models using a broad range of environmental conditions and ensuring spatial independence to have realistic and transferable models where plot level information can be upscaled to landscape scale.

Keywords: ecosystem services, grassland management, machine learning, remote sensing

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Authors: Douglas MacCutcheon, Florian Pausch, Robert Ljung, Lorna Halliday, Stuart Rosen

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Contemporary classrooms are increasingly inclusive of children with mild to moderate disabilities and children from different language backgrounds (bilinguals, multilinguals), but classroom environments and standards have not yet been adapted adequately to meet these challenges brought about by this inclusivity. Additionally, classrooms are becoming noisier as a learner-centered as opposed to teacher-centered teaching paradigm is adopted, which prioritizes group work and peer-to-peer learning. Challenging listening conditions with distracting sound sources and background noise are known to have potentially negative effects on children, particularly those that are prone to struggle with speech perception in noise. Therefore, this research investigates two groups vulnerable to these environmental effects, namely children with a mild to moderate hearing loss (MMHLs) and sequential bilinguals learning in their second language. In the MMHL study, this group was assessed on speech-in-noise perception, and a number of receptive language and cognitive measures (auditory working memory, auditory attention) and correlations were evaluated. Speech reception thresholds were found to be predictive of language and cognitive ability, and the nature of correlations is discussed. In the bilinguals study, sequential bilingual children’s listening comprehension, speech-in-noise perception, listening effort and release from masking was evaluated under a number of different ecologically valid acoustic scenarios in order to pinpoint the extent of the ‘native language benefit’ for Swedish children learning in English, their second language. Scene manipulations included target-to-distractor ratios and introducing spatially separated noise. This research will contribute to the body of findings from which educational institutions can draw when designing or adapting educational environments in inclusive schools.

Keywords: sequential bilinguals, classroom acoustics, mild to moderate hearing loss, speech-in-noise, release from masking

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Authors: Florian Tille, Heide Weishaar, Bernhard Gibis, Susanne Schnitzer

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Introduction: The quality of patient-doctor communication and of written health information is central to organizational health literacy (HL). Whether patients understand their doctors’ explanations and textual material on health, however, is understudied. This study identifies the overall levels of patient understanding of health information and its associations with patients’ social characteristics in outpatient health care in Germany. Materials & Methods: This analysis draws on data collected via a 2017 national health survey with a sample of 6,105 adults. Quality of communication was measured for consultations with general practitioners (GPs) and specialists (SPs) via the Ask Me 3 program questions, and through a question on written health material. Correlations with social characteristics were explored employing bivariate and multivariate logistic regression analyses. Results: Over 90% of all respondents reported that they had understood their doctors’ explanations during the last consultation. Failed understanding was strongly correlated with patients’ very poor health (Odds Ratio [OR]: 5.19; 95% confidence interval [CI]: 2.23–12.10; ref. excellent/very good health), current health problem (OR: 6.54, CI: 1.70–25.12; ref. preventive examination) and age 65 years and above (OR: 2.97, CI: 1.10–8.00; ref. 18 to 34 years). Fewer patients answered they understood written material well (86.7% for las visit at GP, 89.7% at SP). Understanding written material poorly was highly associated with basic education (OR: 4.20, CI: 2.76–6.39; ref. higher education) and 65 years old and above (OR: 2.66, CI: 1.43–4.96). Discussion: Overall ratings of oral patient-doctor communication and written communication of health information are high. Yet, a considerable share of patients reports not-understanding their doctors and poor understanding of the written health-related material. Interventions that can contribute to improving organizational HL in outpatient care in Germany include HL training for doctors, reducing system barriers to easily-accessible health information for patients and combining oral and written health communication means. Conclusion: This work adds to the study of organizational HL in Germany. To increase patient understanding of health-relevant information and thereby possibly reduce health disparities, meeting the communication needs especially of persons in different age groups, with basic education and in very poor health is suggested.

Keywords: health survey, organizational health literacy, patient-doctor communication, social characteristics, outpatient care, Ask Me 3

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Authors: Alma Mendoza-Ponce, Rogelio Corona-Núñez, Florian Kraxner

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Mexico is a megadiverse country and it has nearly halved its natural vegetation in the last century due to agricultural and livestock expansion. Impacts of land use cover change and climate change are unevenly distributed and spatial prioritization to minimize the affectations on biodiversity is crucial. Global and national efforts for prioritizing biodiversity conservation show that ~33% to 45% of Mexico should be protected. The width of these targets makes difficult to lead resources. We use a framework based on vulnerability and irreplaceability to prioritize conservation efforts in Mexico. Vulnerability considered exposure, sensitivity and adaptive capacity under two scenarios (business as usual, BAU based, on the SSP2 and RCP 4.5 and a Green scenario, based on the SSP1 and the RCP 2.6). Exposure to land use is the magnitude of change from natural vegetation to anthropogenic covers while exposure to climate change is the difference between current and future values for both scenarios. Sensitivity was considered as the number of endemic species of terrestrial vertebrates which are critically endangered and endangered. Adaptive capacity is used as the ration between the percentage of converted area (natural to anthropogenic) and the percentage of protected area at municipality level. The results suggest that by 2050, between 11.6 and 13.9% of Mexico show vulnerability ≥ 50%, and by 2070, between 12.0 and 14.8%, in the Green and BAU scenario, respectively. From an ecosystem perspective cloud forests, followed by tropical dry forests, natural grasslands and temperate forests will be the most vulnerable (≥ 50%). Amphibians are the most threatened vertebrates; 62% of the endemic amphibians are critically endangered or endangered while 39%, 12% and 9% of the mammals, birds, and reptiles, respectively. However, the distribution of these amphibians counts for only 3.3% of the country, while mammals, birds, and reptiles in these categories represent 10%, 16% and 29% of Mexico. There are 5 municipalities out of the 2,457 that Mexico has that represent 31% of the most vulnerable areas (70%).These municipalities account for 0.05% of Mexico. This multiscale approach can be used to address resources to conservation targets as ecosystems, municipalities or species considering land use cover change, climate change and biodiversity uniqueness.

Keywords: biodiversity, climate change, land use change, Mexico, vulnerability

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Authors: Christian Louis Kühner, Florian Pfeffel, Valentin Nickolai

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Taking care of children, dependents, or pets can be a difficult and time-consuming task. Especially for part- and full-time employees, it can feel exhausting and overwhelming to meet these obligations besides working a job. Thus, working mostly at home and not having to drive to the company can save valuable time and stress. This study aims to show the influence that the working model has on the job satisfaction of employees with care responsibilities in comparison to employees who do not have such obligations. Using structural equation modeling (SEM), the three work models, “work from home”, “working remotely”, and a hybrid model, have been analyzed based on 13 influencing constructs on job satisfaction. These 13 factors have been further summarized into three groups “classic influencing factors”, “influencing factors changed by remote working”, and “new remote working influencing factors”. Based on the influencing factors on job satisfaction, an online survey was conducted with n = 684 employees from the service sector. Here, Cronbach’s alpha of the individual constructs was shown to be suitable. Furthermore, the construct validity of the constructs was confirmed by face validity, content validity, convergent validity (AVE > 0.5: CR > 0.7), and discriminant validity. In addition, confirmatory factor analysis (CFA) confirmed the model fit for the investigated sample (CMIN/DF: 2.567; CFI: 0.927; RMSEA: 0.048). The SEM-analysis has shown that the most significant influencing factor on job satisfaction is “identification with the work” with β = 0.540, followed by “Appreciation” (β = 0.151), “Compensation” (β = 0.124), “Work-Life-Balance” (β = 0.116), and “Communication and Exchange of Information” (β = 0.105). While the significance of each factor can vary depending on the work model, the SEM-analysis shows that the identification with the work is the most significant factor in all three work models and, in the case of the traditional office work model, it is the only significant influencing factor. The study shows that among the employees with care responsibilities, the higher the proportion of working from home in comparison to working from the office, the more satisfied the employees are with their job. Since the work models that meet the requirements of comprehensive care led to higher job satisfaction amongst employees with such obligations, adapting as a company to such private obligations by employees can be crucial to sustained success. Conversely, the satisfaction level of the working model where employees work at the office is higher for workers without caregiving responsibilities.

Keywords: care responsibilities, home office, job satisfaction, structural equation modeling

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Authors: Florian Misoc, Cyril Okhio, Joshua Tolbert, Nick Carlin, Thomas Ramey

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This project is focused on designing a Stirling engine system for a solar-thermal-electrical system that can supply electric power to a single residential unit. Since Stirling engines are heat engines operating any available heat source, is notable for its ability to generate clean and reliable energy without emissions. Due to the need of finding alternative energy sources, the Stirling engines are making a comeback with the recent technologies, which include thermal energy conservation during the heat transfer process. Recent reviews show mounting evidence and positive test results that Stirling engines are able to produce constant energy supply that ranges from 5kW to 20kW. Solar Power source is one of the many uses for Stirling engines. Using solar energy to operate Stirling engines is an idea considered by many researchers, due to the ease of adaptability of the Stirling engine. In this project, the Stirling engine developed was designed and tested to operate from biomass source of energy, i.e., wood pellets stove, during low solar radiation, with good results. A 20% efficiency of the engine was estimated, and 18% efficiency was measured, making it suitable and appropriate for residential applications. The effort reported was aimed at exploring parameters necessary to design, build and test a ‘Solar Powered Stirling Engine (SPSE)’ using Water (H₂O) as the Heat Transfer medium, with Nitrogen as the working gas that can reach or exceed an efficiency of 20%. The main objectives of this work consisted in: converting a V-twin cylinder air compressor into an alpha-type Stirling engine, construct a Solar Water Heater, by using an automotive radiator as the high-temperature reservoir for the Stirling engine, and an array of fixed mirrors that concentrate the solar radiation on the automotive radiator/high-temperature reservoir. The low-temperature reservoir is the surrounding air at ambient temperature. This work has determined that a low-cost system is sufficiently efficient and reliable. Off-the-shelf components have been used and estimates of the ability of the Engine final design to meet the electricity needs of small residence have been determined.

Keywords: stirling engine, solar-thermal, power inverter, alternator

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Authors: Florian Keipert, Hagen Schmitd

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The size selective separation of different species in a microfluidic system is an actual task in biological or medical research. Former works dealt with the utilisation of the acoustic radiation force (ARF) caused by a plane travelling Surface Acoustic Wave (tSAW). In literature the ARF is described by a dimensionless parameter κ, depending on the wavelength and the particle diameter. To our knowledge research was done for values 0.2 < κ < 5.8 showing that the ARF is dominating the acoustic streaming force (ASF) for κ > 1.2. As a consequence the particle separation is limited by κ. In addition the dependence on the electrical power level was examined but only for κ > 1 pointing out an increased particle deflection for higher electrical power levels. Nevertheless a detailed study on the ASF and ARF especially for κ < 1 is still missing. In our setup we used a tSAW with a wavelength λ = 90 µm and 3 µm PS particles corresponding to κ = 0.3. Herewith the influence of the applied electrical power level on the particle deflection in a polydimethylsiloxan micro channel was investigated. Our results show an increased particle deflection for an increased electrical power level, which coincides with the reported results for κ > 1. Therefore particle separation is in contrast to literature also possible for lower κ values. Thereby the experimental setup can be generally simplified by a coordinated electrical power level for the specific particle size. Furthermore this raises the question of whether this particle deflection is caused only by the ARF as adopted so far or by the ASF or the sum of both forces. To investigate this fact a 0% - 24% saline solution was used and thus the mismatch between the compressibility of the PS particle and the working fluid could be changed. Therefore it is possible to change the relative strength between ARF and ASF and consequently the particle deflection. We observed a decreasing in the particle deflection for an increased NaCl content up to a 12% saline solution and subsequently an increasing of the particle deflection. Our observation could be explained by the acoustic contrast factor Φ, which depends on the compressibility mismatch. The compressibility of water is increased by the NaCl and the range of a 0% - 24% saline solution covers the PS particle compressibility. Hence the particle deflection reaches a minimum value for the accordance between compressibility of PS particle and saline solution. This minimum value can be estimated as the particle deflection only caused by the ASF. Knowing the particle deflection due to the ASF the particle deflection caused by the ARF can be calculated and thus finally the relation between both forces. Concluding, the particle deflection and therefore the size selective particle separation generated by a tSAW can be achieved for values κ < 1, simplifying actual setups by adjusting the electrical power level. Beyond we studied for the first time the relative strength between ARF and ASF to characterise the particle deflection in a microchannel.

Keywords: ARF, ASF, particle separation, saline solution, tSAW

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Authors: Florian Pfeffel, Valentin Nickolai, Christian Louis Kühner

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Digitalization has disrupted the traditional workplace environment by allowing many employees to work from anywhere at any time. This trend of working from home was further accelerated due to the COVID-19 crisis, which forced companies to rethink their workplace models. While in many companies, this shift happened out of pure necessity; many employees were left more satisfied with their job due to the opportunity to work from home. This study focuses on employees’ job satisfaction in the service sector in dependence on the different work models, which are defined as a “work from home” model, the traditional “work in office” model, and a hybrid model. Using structural equation modeling (SEM), these three work models have been analyzed based on 13 influencing factors on job satisfaction that have been further summarized in the three groups “classic influencing factors”, “influencing factors changed by remote working”, and “new remote working influencing factors”. Based on the influencing factors on job satisfaction, a survey has been conducted with n = 684 employees in the service sector. Cronbach’s alpha of the individual constructs was shown to be suitable. Furthermore, the construct validity of the constructs was confirmed by face validity, content validity, convergent validity (AVE > 0.5: CR > 0.7), and discriminant validity. Additionally, confirmatory factor analysis (CFA) confirmed the model fit for the investigated sample (CMIN/DF: 2.567; CFI: 0.927; RMSEA: 0.048). The SEM-analysis has shown that the most significant influencing factor on job satisfaction is “identification with the work” with β = 0.540, followed by “Appreciation” (β = 0.151), “Compensation” (β = 0.124), “Work-Life-Balance” (β = 0.116), and “Communication and Exchange of Information” (β = 0.105). While the significance of each factor can vary depending on the work model, the SEM-analysis shows that the identification with the work is the most significant factor in all three work models and, in the case of the traditional office work model, it is the only significant influencing factor. The study shows that employees who work entirely remotely or have a hybrid work model are significantly more satisfied with their job, with a job satisfaction score of 5.0 respectively on a scale from 1 (very dissatisfied) to 7 (very satisfied), than employees do not have the option to work from home with a score of 4.6. This comes as a result of the lower identification with the work in the model without any remote working. Furthermore, the responses indicate that it is important to consider the individual preferences of each employee when it comes to the work model to achieve overall higher job satisfaction. Thus, it can be argued that companies can profit off of more motivation and higher productivity by considering the individual work model preferences, therefore, increasing the identification with the respective work.

Keywords: home-office, identification with work, job satisfaction, new work, remote work, structural equation modeling

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Authors: Marwa Abida, Florian Gehring, Jamel Mars, Alexandre Vivet, Fakhreddine Dammak, Mohamed Haddar

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The demand for bio-based materials in semi-structural and structural applications is constantly growing to conform to new environmental policies. Among them, Plant Fiber Reinforced Composites (PFRC) are attractive for the scientific community as well as the industrial world. Due to their relatively low densities and low environmental impact, vegetal fibers appear to be suitable as reinforcing materials for polymers. However, the major issue of plant fibers and PFRC in general is their hydrophilic behavior (high affinity to water molecules). Indeed, when absorbed, water causes fiber swelling and a loss of mechanical properties. Thus, the environmental loadings (moisture, temperature, UV) can strongly affect their mechanical properties and therefore play a critical role in the service life of PFRC. In order to analyze the influence of conditioning at relative humidity on the behavior of flax fiber reinforced composites, a preliminary study on flax fabrics has been conducted. The conditioning of the fabrics in different humid atmospheres made it possible to study the influence of the water content on the hygro-mechanical behavior of flax reinforcement through mechanical tensile tests. This work shows that increasing the relative humidity of the atmosphere induces an increase of the water content in the samples. It also brings up the significant influence of water content on the stiffness and elongation at break of the fabric, while no significant change of the breaking load is detected. Non-linear decrease of flax fabric rigidity and increase of its elongation at maximal force with the increase of water content are observed. It is concluded that water molecules act as a softening agent on flax fabrics. Two kinds of typical tensile curves are identified. Most of the tensile curves of samples show one unique linear region where the behavior appears to be linear prior to the first yarn failure. For some samples in which water content is between 2.7 % and 3.7 % (regardless the conditioning atmosphere), the emergence of a two-linear region behavior is pointed out. This phenomenon could be explained by local heterogeneities of water content which could induce premature local plasticity in some regions of the flax fabric sample behavior.

Keywords: hygro-mechanical behavior, hygroscopy, flax fabric, relative humidity, mechanical properties

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Authors: Florian Kiebert, Hagen Schmidt

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Standing surface acoustic waves (sSAWs) have already been used to manipulate particles in a microfluidic channel made of polydimethylsiloxan (PDMS). Usually two identical facing interdigital transducers (IDTs) are exploited to form an sSAW. Further, it has been reported that an sSAW can be generated by a single IDT using a superstrate resonating cavity or a PDMS post. Nevertheless, both setups utilising a traveling surface acoustic wave (tSAW) to create an sSAW for particle manipulation are costly. We present a simplified setup with a tSAW and a PDMS channel to form an sSAW. The incident tSAW is reflected at the rear PDMS channel wall and superimposed with the reflected tSAW. This superpositioned waves generates an sSAW but only at regions where the distance to the rear channel wall is smaller as the attenuation length of the tSAW minus the channel width. Therefore in a channel of 500µm width a tSAW with a wavelength λ = 120 µm causes a sSAW over the whole channel, whereas a tSAW with λ = 60 µm only forms an sSAW next to the rear wall of the channel, taken into account the attenuation length of a tSAW in water. Hence, it is possible to concentrate and trap particles in a defined region of the channel by adjusting the relation between the channel width and tSAW wavelength. Moreover, it is possible to generate a particle gradient over the channel width by picking the right ratio between channel wall and wavelength. The particles are moved towards the rear wall by the acoustic streaming force (ASF) and the acoustic radiation force (ARF) caused by the tSAW generated bulk acoustic wave (BAW). At regions in the channel were the sSAW is dominating the ARF focuses the particles in the pressure nodes formed by the sSAW caused BAW. On the one side the ARF generated by the sSAW traps the particle at the center of the tSAW beam, i. e. of the IDT aperture. On the other side, the ASF leads to two vortices, one on the left and on the right side of the focus region, deflecting the particles out of it. Through variation of the applied power it is possible to vary the number of particles trapped in the focus points, because near to the rear wall the amplitude of the reflected tSAW is higher and, therefore, the ARF of the sSAW is stronger. So in the vicinity of the rear wall the concentration of particles is higher but decreases with increasing distance to the wall, forming a gradient of particles. The particle gradient depends on the applied power as well as on the flow rate. Thus by variation of these two parameters it is possible to change the particle gradient. Furthermore, we show that the particle gradient can be modified by changing the relation between the channel width and tSAW wavelength. Concluding a single IDT generates an sSAW in a PDMS microchannel enables particle gradient generation in a well-defined microfluidic flow system utilising the ARF and ASF of a tSAW and an sSAW.

Keywords: ARF, ASF, particle manipulation, sSAW, tSAW

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Authors: Valentin Nickolai, Florian Pfeffel, Christian Louis Kühner

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In many industrialized nations, the demand for skilled workers rises, causing the current market for employees to be more candidate-driven than employer-driven. Therefore, losing highly skilled and experienced employees due to early or partial retirement negatively impacts firms. Therefore, finding new ways to incentivize older employees (Silver Workers) to stay longer with the company and in their job can be crucial for the success of a firm. This study analyzes how working remotely can be a valid incentive for experienced Silver Workers to stay in their job and instead work from home with more flexible working hours. An online survey with n = 684 respondents, who are employed in the service sector, has been conducted based on 13 constructs that influence job satisfaction. These have been further categorized into three groups “classic influencing factors,” “influencing factors changed by remote working,” and new remote working influencing factors,” and were analyzed using structural equation modeling (SEM). Here, Cronbach’s alpha of the individual constructs was shown to be suitable. Furthermore, the construct validity of the constructs was confirmed by face validity, content validity, convergent validity (AVE > 0.5: CR > 0.7), and discriminant validity. Additionally, confirmatory factor analysis (CFA) confirmed the model fit for the investigated sample (CMIN/DF: 2.567; CFI: 0.927; RMSEA: 0.048). It was shown in the SEM-analysis that the influencing factor on job satisfaction, “identification with the work,” is the most significant with β = 0.540, followed by “Appreciation” (β = 0.151), “Compensation” (β = 0.124), “Work-Life-Balance” (β = 0.116), and “Communication and Exchange of Information” (β = 0.105). While the significance of each factor can vary depending on the work model, the SEM-analysis also shows that the identification with the work is the most significant factor in all three work models mentioned above and, in the case of the traditional office work model, it is the only significant influencing factor. The study shows that employees between the ages of 56 and 65 years have the highest job satisfaction when working entirely from home or remotely. Furthermore, their job satisfaction score of 5.4 on a scale from 1 (very dissatisfied) to 7 (very satisfied) is the highest amongst all age groups in any of the three work models. Due to the significantly higher job satisfaction, it can be argued that giving Silver Workers the offer to work from home or remotely can incentivize them not to opt for early retirement or partial retirement but to stay in their job full-time Furthermore, these findings can indicate that employees in the Silver Worker age are much more inclined to leave their job for early retirement if they have to entirely work in the office.

Keywords: home office, remote work instead of early or partial retirement, silver worker, structural equation modeling

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Authors: Yamina Boughari, Ruxandra Mihaela Botez, Florian Theel, Georges Ghazi

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Clearance of flight control laws of a civil aircraft is a long and expensive process in the Aerospace industry. Thousands of flight combinations in terms of speeds, altitudes, gross weights, centers of gravity and angles of attack have to be investigated, and proved to be safe. Nonetheless, in this method, a worst flight condition can be easily missed, and its missing would lead to a critical situation. Definitively, it would be impossible to analyze a model because of the infinite number of cases contained within its flight envelope, that might require more time, and therefore more design cost. Therefore, in industry, the technique of the flight envelope mesh is commonly used. For each point of the flight envelope, the simulation of the associated model ensures the satisfaction or not of specifications. In order to perform fast, comprehensive and effective analysis, other varying parameters models were developed by incorporating variations, or uncertainties in the nominal models, known as Linear Fractional Representation LFR models; these LFR models were able to describe the aircraft dynamics by taking into account uncertainties over the flight envelope. In this paper, the LFRs models are developed using the speeds and altitudes as varying parameters; The LFR models were built using several flying conditions expressed in terms of speeds and altitudes. The use of such a method has gained a great interest by the aeronautical companies that have seen a promising future in the modeling, and particularly in the design and certification of control laws. In this research paper, we will focus on the Cessna Citation X open loop stability analysis. The data are provided by a Research Aircraft Flight Simulator of Level D, that corresponds to the highest level flight dynamics certification; this simulator was developed by CAE Inc. and its development was based on the requirements of research at the LARCASE laboratory. The acquisition of these data was used to develop a linear model of the airplane in its longitudinal and lateral motions, and was further used to create the LFR’s models for 12 XCG /weights conditions, and thus the whole flight envelope using a friendly Graphical User Interface developed during this study. Then, the LFR’s models are analyzed using Interval Analysis method based upon Lyapunov function, and also the ‘stability and robustness analysis’ toolbox. The results were presented under the form of graphs, thus they have offered good readability, and were easily exploitable. The weakness of this method stays in a relatively long calculation, equal to about four hours for the entire flight envelope.

Keywords: flight control clearance, LFR, stability analysis, robustness analysis

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Authors: Katharina Eberhardt, Florian Klaus Kaiser, Frank Schultmann

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Last-mile distribution is one of the most critical parts of a disaster relief operation. Various uncertainties, such as infrastructure conditions, resource availability, and fluctuating beneficiary demand, render last-mile distribution challenging in disaster relief operations. The need to balance critical performance criteria like response time, meeting demand and cost-effectiveness further complicates the task. The occurrence of disasters cannot be controlled, and the magnitude is often challenging to assess. In summary, these uncertainties create a need for additional flexibility, agility, and preparedness in logistics operations. As a result, strategic planning and efficient network design are critical for an effective and efficient response. Furthermore, the increasing frequency of disasters and the rising cost of logistical operations amplify the need to provide robust and resilient solutions in this area. Therefore, we formulate a scenario-based bi-objective optimization model that integrates pre-positioning, allocation, and distribution of relief supplies extending the general form of a covering location problem. The proposed model aims to minimize underlying logistics costs while maximizing demand coverage. Using a set of disruption scenarios, the model allows decision-makers to identify optimal network solutions to address the risk of disruptions. We provide an empirical case study of the public authorities’ emergency food storage strategy in Germany to illustrate the potential applicability of the model and provide implications for decision-makers in a real-world setting. Also, we conduct a sensitivity analysis focusing on the impact of varying stockpile capacities, single-site outages, and limited transportation capacities on the objective value. The results show that the stockpiling strategy needs to be consistent with the optimal number of depots and inventory based on minimizing costs and maximizing demand satisfaction. The strategy has the potential for optimization, as network coverage is insufficient and relies on very high transportation and personnel capacity levels. As such, the model provides decision support for public authorities to determine an efficient stockpiling strategy and distribution network and provides recommendations for increased resilience. However, certain factors have yet to be considered in this study and should be addressed in future works, such as additional network constraints and heuristic algorithms.

Keywords: humanitarian logistics, bi-objective optimization, pre-positioning, last mile distribution, decision support, disaster relief networks

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Ben Otange, Wolfgang Parak, Florian Schulz, Michael Alexander Rubhausen

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The feasibility of extending the usage of molecular imprinting technique in complex biomolecules is demonstrated in this research. This technique is promising in diverse applications in areas such as drug delivery, diagnosis of diseases, catalysts, and impurities detection as well as treatment of various complications. While molecularly imprinted polymers MIP remain robust in the synthesis of molecules with remarkable binding sites that have high affinities to specific molecules of interest, extending the usage to complex biomolecules remains futile. This work reports on the successful synthesis of MIP from complex proteins: BSA, Transferrin, and MUC1. We show in this research that despite the heterogeneous binding sites and higher conformational flexibility of the chosen proteins, relying on their respective epitopes and motifs rather than the whole template produces highly sensitive and selective MIPs for specific molecular binding. Introduction: Proteins are vital in most biological processes, ranging from cell structure and structural integrity to complex functions such as transport and immunity in biological systems. Unlike other imprinting templates, proteins have heterogeneous binding sites in their complex long-chain structure, which makes their imprinting to be marred by challenges. In addressing this challenge, our attention is inclined toward the targeted delivery, which will use molecular imprinting on the particle surface so that these particles may recognize overexpressed proteins on the target cells. Our goal is thus to make surfaces of nanoparticles that specifically bind to the target cells. Results and Discussions: Using epitopes of BSA and MUC1 proteins and motifs with conserved receptors of transferrin as the respective templates for MIPs, significant improvement in the MIP sensitivity to the binding of complex protein templates was noted. Through the Fluorescence Correlation Spectroscopy FCS measurements on the size of protein corona after incubation of the synthesized nanoparticles with proteins, we noted a high affinity of MIPs to the binding of their respective complex proteins. In addition, quantitative analysis of hard corona using SDS-PAGE showed that only a specific protein was strongly bound on the respective MIPs when incubated with similar concentrations of the protein mixture. Conclusion: Our findings have shown that the merits of MIPs can be extended to complex molecules of higher biomolecular mass. As such, the unique merits of the technique, including high sensitivity and selectivity, relative ease of synthesis, production of materials with higher physical robustness, and higher stability, can be extended to more templates that were previously not suitable candidates despite their abundance and usage within the body.

Keywords: molecularly imprinted polymers, specific binding, drug delivery, high biomolecular mass-templates

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Authors: Vincent Schlageter, Maroua Mestiri, Florian Denzinger, Hugo Raetzo, Michel Demierre

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Precise landslide monitoring with differential global navigation satellite system (GNSS) is well known, but technical or economic reasons limit its application by geotechnical companies. This study demonstrates the reliability and the usefulness of Geomon (Infrasurvey Sàrl, Switzerland), a stand-alone and cost-effective rover network. The system permits deploying up to 15 rovers, plus one reference station for differential GNSS. A dedicated radio communication links all the modules to a base station, where an embedded computer automatically provides all the relative positions (L1 phase, open-source RTKLib software) and populates an Internet server. Each measure also contains information from an internal inclinometer, battery level, and position quality indices. Contrary to standard GNSS survey systems, which suffer from a limited number of beacons that must be placed in areas with good GSM signal, Geomon offers greater flexibility and permits a real overview of the whole landslide with good spatial resolution. Each module is powered with solar panels, ensuring autonomous long-term recordings. In this study, we have tested the system on several sites in the Swiss mountains, setting up to 7 rovers per site, for an 18 month-long survey. The aim was to assess the robustness and the accuracy of the system in different environmental conditions. In one case, we ran forced blind tests (vertical movements of a given amplitude) and compared various session parameters (duration from 10 to 90 minutes). Then the other cases were a survey of real landslides sites using fixed optimized parameters. Sub centimetric-accuracy with few outliers was obtained using the best parameters (session duration of 60 minutes, baseline 1 km or less), with the noise level on the horizontal component half that of the vertical one. The performance (percent of aborting solutions, outliers) was reduced with sessions shorter than 30 minutes. The environment also had a strong influence on the percent of aborting solutions (ambiguity search problem), due to multiple reflections or satellites obstructed by trees and mountains. The length of the baseline (distance reference-rover, single baseline processing) reduced the accuracy above 1 km but had no significant effect below this limit. In critical weather conditions, the system’s robustness was limited: snow, avalanche, and frost-covered some rovers, including the antenna and vertically oriented solar panels, leading to data interruption; and strong wind damaged a reference station. The possibility of changing the sessions’ parameters remotely was very useful. In conclusion, the rover network tested provided the foreseen sub-centimetric-accuracy while providing a dense spatial resolution landslide survey. The ease of implementation and the fully automatic long-term survey were timesaving. Performance strongly depends on surrounding conditions, but short pre-measures should allow moving a rover to a better final placement. The system offers a promising hazard mitigation technique. Improvements could include data post-processing for alerts and automatic modification of the duration and numbers of sessions based on battery level and rover displacement velocity.

Keywords: GNSS, GSM, landslide, long-term, network, solar, spatial resolution, sub-centimeter.

Procedia PDF Downloads 111