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To date, the establishment of high-titer stable viral packaging cells (VPCs) at large scale for gene therapeutic applications is very time- and cost-intensive. Here we report the establishment of three human suspension 293-F-derived ecotropic MLV-based VPCs. The classic stable transfection of an EGFP-expressing transfer vector resulted in a polyclonal VPC pool that facilitated cultivation in shake flasks of 100 mL volumes and yielded high functional titers of more than 1 × 106 transducing units/mL (TU/mL). When the transfer vector was flanked by transposon terminal inverted repeats (TIRs) and upon co-transfection of a plasmid encoding for the transposase, productivities could be slightly elevated to more than 3 × 106 TU/mL. In contrast and using mRNA encoding for the transposase, as a proof of concept, productivities were drastically improved by more than ten-fold exceeding 5 × 107 TU/mL. In addition, these VPC pools were generated within only 3 weeks. The production volume was successfully scaled up to 500 mL employing a stirred-tank bioreactor (STR). We anticipate that the stable transposition of transfer vectors employing transposase transcripts will be of utility for the future establishment of high-yield VPCs producing pseudotype vector particles with a broader host tropism on a large scale.
In recent years there have been numerous technical innovations such as CGM systems or insulin pumps that have made life easier for people with type 1 diabetes. However, this also means that more and more information is available. The aim of the present study is to find out more about the daily handling of information. The following research question was asked: What information do people with type 1 diabetes use? To answer this research question, a quantitative online survey of people with type 1 diabetes was conducted by Prof. Dr. Matthias Fank at the Technical University of Cologne. The online survey mainly consisted of 25 closed questions, which were asked on a scale from 0 to 10. The responses of 1,025 people who are at least 18 years old were included in the evaluation. The most important information for type 1 diabetics is the "current value". 67.5% have this on Place 1 placed. Current glucose levels are provided by CGM systems used by 94.2% of people with type 1 diabetes. Quarterly visits to the diabetologist are important and provide important information. 30.8% “completely” agree with this statement on a scale from 0 to 10. Only 2.2% of people with type 1 diabetes are satisfied with their current diabetes management apps. There is a desire for a manufacturer-independent app. The strongest agreement with a value of 10 was chosen by almost a quarter (24.6%) of the people with type 1 diabetes. The study provides an insight into diabetes therapy and shows the need for action.
Austria is committed to the net-zero climate goal along with the European Union. This requires all sectors to be decarbonized. Hereby, hydrogen plays a vital role as stated in the national hydrogen strategy. A report commissioned by the Austrian government predicts a minimum hydrogen demand of 16 TWh per year in Austria in 2040. Besides hydrogen imports, domestic production can ensure supply. Hence, this study analyses the levelized cost of hydrogen for an off-grid production plant including a proton exchange membrane electrolyzer, wind power and solar photovoltaics in Austria. In the first step, the capacity factors of the renewable electricity sources are determined by conducting a geographic information system analysis. Secondly, the levelized cost of electricity for wind power and solarphotovoltaics plants in Austria is calculated. Thirdly, the most cost-efficient portfolio of wind power and solar photovoltaics plants is determined using electricity generation profiles with a 10-min granularity. The modelled system variants differ among location, capacity factors of the renewable electricity sources and the full load hours of the electrolyzer. Finally, selected variables are tested for their sensitivities. With the applied model, the hydrogen production cost for decentralized production plants can be calculated for any specific location. The levelized cost of hydrogen estimates range from 3.08 EUR/kg to 13.12 EUR/kg of hydrogen, whereas it was found that the costs are most sensitive to the capacity factors of the renewable electricity sources and the full load hours of the electrolyzer. The novelty of the paper stems from the model applied that calculates the levelized cost of renewable hydrogen in an off-grid hydrogen production system. The model finds a cost-efficient portfolio of directly coupled wind power and solar photovoltaics systems for 80 different variants in an Austria-specific context.
In this work, we propose a novel data-driven approach to recover missing or corrupted motion capture data, either in the form of 3D skeleton joints or 3D marker trajectories. We construct a knowledge-base that contains prior existing knowledge, which helps us to make it possible to infer missing or corrupted information of the motion capture data. We then build a kd-tree in parallel fashion on the GPU for fast search and retrieval of this already available knowledge in the form of nearest neighbors from the knowledge-base efficiently. We exploit the concept of histograms to organize the data and use an off-the-shelf radix sort algorithm to sort the keys within a single processor of GPU. We query the motion missing joints or markers, and as a result, we fetch a fixed number of nearest neighbors for the given input query motion. We employ an objective function with multiple error terms that substantially recover 3D joints or marker trajectories in parallel on the GPU. We perform comprehensive experiments to evaluate our approach quantitatively and qualitatively on publicly available motion capture datasets, namely CMU and HDM05. From the results, it is observed that the recovery of boxing, jumptwist, run, martial arts, salsa, and acrobatic motion sequences works best, while the recovery of motion sequences of kicking and jumping results in slightly larger errors. However, on average, our approach executes outstanding results. Generally, our approach outperforms all the competing state-of-the-art methods in the most test cases with different action sequences and executes reliable results with minimal errors and without any user interaction.
As the population ages, the demand for care for older adults is increasing. To maintain their independence and autonomy, even with declining health, assistive technologies such as connected medical devices or social robots can be useful. In previous work, we introduced a novel health monitoring system that combines commercially available products with apps designed specifically for older adults. The system is intended for the long-term collection of subjective and objective health data. In this work, we present an exploratory user experience (UX) and usability study we conducted with older adults as the target group of the system and with younger expert users who tested our msystem. All participants interacted with a social robot conducting a health assessment and tested sensing devices and an app for data visualization. The UX and usability of the individual components of the system were rated highly in questionnaires in all sessions. All participants also said they would use such a system in their everyday lives, demonstrating the potential of these systems for self-managing users’ health. Finally, we found factors such as previous experience with social robots and technological expertise to have an influence on the reported UX of the users.
One-step preparation of bilayered films from kraft lignin and cellulose acetate to mimic tree bark
(2020)
This contribution presents the development of a dry-cast method for the one-step preparation of bio-based films from wood polymers that mimic the bilayered structure of tree bark, the natural protective layer of the tree. In a simplified view, natural bark can be considered as the superposition of an external homogeneous and non-porous layer (outer bark) and a porous substructure layer (inner bark). This work is a first step for the future development of bio-based biomimetic wood coatings. The film had a bark-like appearance and its total density, bulk density and porosity were similar to values measured in natural bark. Furthermore, the structural characteristics of the studied film, namely specific surface area (BET) and pore size distribution, as well as the performance of the water adsorption ability were investigated and discussed.
High-quality rendering of spatial sound fields in real-time is becoming increasingly important with the steadily growing interest in virtual and augmented reality technologies. Typically, a spherical microphone array (SMA) is used to capture a spatial sound field. The captured sound field can be reproduced over headphones in real-time using binaural rendering, virtually placing a single listener in the sound field. Common methods for binaural rendering first spatially encode the sound field by transforming it to the spherical harmonics domain and then decode the sound field binaurally by combining it with head-related transfer functions (HRTFs). However, these rendering methods are computationally demanding, especially for high-order SMAs, and require implementing quite sophisticated real-time signal processing. This paper presents a computationally more efficient method for real-time binaural rendering of SMA signals by linear filtering. The proposed method allows representing any common rendering chain as a set of precomputed finite impulse response filters, which are then applied to the SMA signals in real-time using fast convolution to produce the binaural signals. Results of the technical evaluation show that the presented approach is equivalent to conventional rendering methods while being computationally less demanding and easier to implement using any real-time convolution system. However, the lower computational complexity goes along with lower flexibility. On the one hand, encoding and decoding are no longer decoupled, and on the other hand, sound field transformations in the SH domain can no longer be performed. Consequently, in the proposed method, a filter set must be precomputed and stored for each possible head orientation of the listener, leading to higher memory requirements than the conventional methods. As such, the approach is particularly well suited for efficient real-time binaural rendering of SMA signals in a fixed setup where usually a limited range of head orientations is sufficient, such as live concert streaming or VR teleconferencing.
3d printing is capable of providing dose individualization for pediatric medicines and translating the precision medicine approach into practical application. In pediatrics, dose individualization and preparation of small dosage forms is a requirement for successful therapy, which is frequently not possible due to the lack of suitable dosage forms. For precision medicine, individual characteristics of patients are considered for the selection of the best possible API in the most suitable dose with the most effective release profile to improve therapeutic outcome. 3d printing is inherently suitable for manufacturing of individualized medicines with varying dosages, sizes, release profiles and drug combinations in small batch sizes, which cannot be manufactured with traditional technologies. However, understanding of critical quality attributes and process parameters still needs to be significantly improved for this new technology. To ensure health and safety of patients, cleaning and process validation needs to be established. Additionally, adequate analytical methods for the in-process control of intermediates, regarding their printability as well as control of the final 3d printed tablets considering any risk of this new technology will be required. The PolyPrint consortium is actively working on developing novel polymers for fused deposition modeling (FDM) 3d printing, filament formulation and manufacturing development as well as optimization of the printing process, and the design of a GMP-capable FDM 3d printer. In this manuscript, the consortium shares its views on quality aspects and measures for 3d printing from drug-loaded filaments, including formulation development, the printing process, and the printed dosage forms. Additionally, engineering approaches for quality assurance during the printing process and for the final dosage form will be presented together with considerations for a GMP-capable printer design.
We study p-adic L-functions Lp(s, 휒) for Dirichlet characters 휒. We show that Lp(s, 휒) has a Dirichlet series expansion for each regularization parameter c that is prime to p and the conductor of 휒. The expansion is proved by transforming a known formula for p-adic L-functions and by controlling the limiting behavior. A fnite number of Euler factors can be factored of in a natural manner from the p-adic Dirichlet series. We also provide an alternative proof of the expansion using p-adic measures and give an explicit formula for the values of the regularized Bernoulli distribution. The result is particularly simple for c = 2, where we obtain a Dirichlet series expansion that is similar to the complex case.