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Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally. To resolve these two constraints, we injected EVs directly at the lesion site acutely after spinal cord injury. We report here that intralesional application of EVs resulted in a more robust improvement of motor recovery, assessed with the BBB score and sub-score, as compared to the intravenous delivery. Moreover, the intralesional application was more potent in reducing inflammation and scarring after spinal cord injury than intravenous administration. Hence, the development of EV-based therapy for spinal cord injury should aim at an early application of vesicles close to the lesion.
Bone grafts can be engineered by differentiating human mesenchymal stromal cells (MSCs) via the endochondral and intramembranous ossification pathways. We evaluated the effects of each pathway on the properties of engineered bone grafts and their capacity to drive bone regeneration. Bone-marrow-derived MSCs were differentiated on silk scaffolds into either hypertrophic chondrocytes (hyper) or osteoblasts (osteo) over 5 weeks of in vitro cultivation, and were implanted subcutaneously for 12 weeks. The pathways' constructs were evaluated over time with respect to gene expression, composition, histomorphology, microstructure, vascularization and biomechanics. Hypertrophic chondrocytes expressed higher levels of osteogenic genes and deposited significantly more bone mineral and proteins than the osteoblasts. Before implantation, the mineral in the hyper group was less mature than that in the osteo group. Following 12 weeks of implantation, the hyper group had increased mineral density but a similar overall mineral composition compared with the osteo group. The hyper group also displayed significantly more blood vessel infiltration than the osteo group. Both groups contained M2 macrophages, indicating bone regeneration. These data suggest that, similar to the body's repair processes, endochondral pathway might be more advantageous when regenerating large defects, whereas intramembranous ossification could be utilized to guide the tissue formation pattern with a scaffold architecture.
Regeneration of bone defects is often limited due to compromised bone tissue physiology. Previous studies suggest that engineered extracellular matrices enhance the regenerative capacity of mesenchymal stromal cells. In this study, we used human-induced pluripotent stem cells, a scalable source of young mesenchymal progenitors (hiPSC-MPs), to generate extracellular matrix (iECM) and test its effects on the osteogenic capacity of human bone-marrow mesenchymal stromal cells (BMSCs). iECM was deposited as a layer on cell culture dishes and into three-dimensional (3D) silk-based spongy scaffolds. After decellularization, iECM maintained inherent structural proteins including collagens, fibronectin and laminin, and contained minimal residual DNA. Young adult and aged BMSCs cultured on the iECM layer in osteogenic medium exhibited a significant increase in proliferation, osteogenic marker expression, and mineralization as compared to tissue culture plastic. With BMSCs from aged donors, matrix mineralization was only detected when cultured on iECM, but not on tissue culture plastic. When cultured in 3D iECM/silk scaffolds, BMSCs exhibited significantly increased osteogenic gene expression levels and bone matrix deposition. iECM layer showed a similar enhancement of aged BMSC proliferation, osteogenic gene expression, and mineralization compared with extracellular matrix layers derived from young adult or aged BMSCs. However, iECM increased osteogenic differentiation and decreased adipocyte formation compared with single protein substrates including collagen and fibronectin. Together, our data suggest that the microenvironment comprised of iECM can enhance the osteogenic activity of BMSCs, providing a bioactive and scalable biomaterial strategy for enhancing bone regeneration in patients with delayed or failed bone healing.
A major challenge for breath research is the lack of standardization in sampling and analysis. To address this, a test that utilizes a standardized intervention and a defined study protocol has been proposed to explore disparities in breath research across different analytical platforms and to provide benchmark values for comparison. Specifically, the Peppermint Experiment involves the targeted analysis in exhaled breath of volatile constituents of peppermint oil after ingestion of the encapsulated oil. Data from the Peppermint Experiment performed by proton transfer reaction mass spectrometry (PTR-MS) and selected ion flow tube mass spectrometry (SIFT-MS) are presented and discussed herein, including the product ions associated with the key peppermint volatiles, namely limonene, α- and β-pinene, 1,8-cineole, menthol, menthone and menthofuran. The breath washout profiles of these compounds from 65 individuals were collected, comprising datasets from five PTR-MS and two SIFT-MS instruments. The washout profiles of these volatiles were evaluated by comparing the log-fold change over time of the product ion intensities associated with each volatile. Benchmark values were calculated from the lower 95% confidence interval of the linear time-to-washout regression analysis for all datasets combined. Benchmark washout values from PTR-MS analysis were 353 min for the sum of monoterpenes and 1,8-cineole (identical product ions), 173 min for menthol, 330 min for menthofuran, and 218 min for menthone; from SIFT-MS analysis values were 228 min for the sum of monoterpenes, 281 min for the sum of monoterpenes and 1,8-cineole, and 370 min for menthone plus 1,8-cineole. Large inter- and intra-dataset variations were observed, whereby the latter suggests that biological variability plays a key role in how the compounds are absorbed, metabolized and excreted from the body via breath. This variability seems large compared to the influence of sampling and analytical procedures, but further investigations are recommended to clarify the effects of these factors.
MS SPIDOC is a novel sample delivery system designed for single (isolated) particle imaging at X-ray Free-Electron Lasers
that is adaptable towards most large-scale facility beamlines. Biological samples can range from small proteins to MDa
particles. Following nano-electrospray ionization, ionic samples can be m/z-filtered and structurally separated before being
oriented at the interaction zone. Here, we present the simulation package developed alongside this prototype. The first part
describes how the front-to-end ion trajectory simulations have been conducted. Highlighted is a quadrant lens; a simple but
efficient device that steers the ion beam within the vicinity of the strong DC orientation field in the interaction zone to ensure
spatial overlap with the X-rays. The second part focuses on protein orientation and discusses its potential with respect to
diffractive imaging methods. Last, coherent diffractive imaging of prototypical T = 1 and T = 3 norovirus capsids is shown.
We use realistic experimental parameters from the SPB/SFX instrument at the European XFEL to demonstrate that low-
resolution diffractive imaging data (q < 0.3 nm −1 ) can be collected with only a few X-ray pulses. Such low-resolution data
are sufficient to distinguish between both symmetries of the capsids, allowing to probe low abundant species in a beam if
MS SPIDOC is used as sample delivery.
Background
Online symptom checkers are digital health solutions that provide a differential diagnosis based on a user’s symptoms. During the coronavirus disease 2019 (COVID-19) pandemic, symptom checkers have become increasingly important due to physical distance constraints and reduced access to in-person medical consultations. Furthermore, various symptom checkers specialised in the assessment of COVID-19 infection have been produced.
Objectives
Assess the correlation between COVID-19 risk assessments from an online symptom checker and current trends in COVID-19 infections. Analyse whether those correlations are reflective of various country-wise quality of life measures. Lastly, determine whether the trends found in symptom checker assessments predict or lag relative to those of the COVID-19 infections.
Materials and methods
In this study, we compile the outcomes of COVID-19 risk assessments provided by the symptom checker Symptoma (www.symptoma.com) in 18 countries with suitably large user bases. We analyse this dataset’s spatial and temporal features compared to the number of newly confirmed COVID-19 cases published by the respective countries.
Results
We find an average correlation of 0.342 between the number of Symptoma users assessed to have a high risk of a COVID-19 infection and the official COVID-19 infection numbers. Further, we show a significant relationship between that correlation and the self-reported health of a country. Lastly, we find that the symptom checker is, on average, ahead (median +3 days) of the official infection numbers for most countries.
Conclusion
We show that online symptom checkers can capture the national-level trends in coronavirus infections. As such, they provide a valuable and unique information source in policymaking against pandemics, unrestricted by conventional resources.
Technologiemanagement
(2023)
Stellhebel beim Aufbau von Corporate Start-ups. Dargestellt am Start-Up-Projekt „Hallo Sonne“
(2023)
Bucket increasing trees are multilabelled generalizations of increasing trees, where each non-leaf node carries b labels, with a fixed integer. We provide a fundamental result, giving a complete characterization of all families of bucket increasing trees that can be generated by a tree evolution process. We also provide several equivalent properties, complementing and extending earlier results for ordinary increasing trees to bucket trees. Additionally, we state second order results for the number of descendants of label j, again extending earlier results in the literature.
Dieser Beitrag soll interessierten Laien eine Hilfestellung an die Hand geben, ihre Infomaterialien barriereärmer zu gestalten. Einführend erfolgt eine kurze Darstellung der rechtlichen und gesellschaftlichen Situation rund um das Thema Behinderung. Verschiedene Ebenen von Barrieren und Lösungsansätze werden vorgestellt: Organisationale Barrieren von Bildungseinrichtungen werden ebenso wie Barrieren rund um das Bildungsberatungsgespräch adressiert. Der Schwerpunkt liegt bei auf der Gestaltung von Informationsmaterial. Neben einem theoretischen Hintergrund über Lösungsansätze werden praktische Umsetzungen für verschiedene Medien vorgestellt. Der Beitrag wird durch Beispiele guter Praxis in der Umsetzung, eine Checkliste zur Anwendung und weiterführende Ressourcen abgerundet.
Design of State-Space Controllers with the Help of Signal Flow Graphs Shown for a Buck Converter
(2022)
Connecting material degradation and power loss of PV modules using advanced statistical methodology
(2023)
Using nylon bag techniques, Cornell net carbohydrates and protein systems (CNCPS), and scanning electron microscopy, the authors examined the digestibility and structure of Vicia ervilia (ervil, bitter vetch) after steam flaking, roasting, and microwave processing. During the in situ technique, the samples were incubated at 0, 2, 4, 6, 8, 12, 16, 24, 36, and 48 h. For the description of the ruminal DM (dry matter) and CP (crude protein) degradation kinetics of treated and untreated Vicia ervilia, different models were selected as the best fit for the dry matter (DM) and crude protein (CP) degradation parameters of steam flaked samples. The results showed that both the steam flaking and microwave treatment samples contained high levels of non-protein nitrogen and buffer soluble protein, respectively. In comparison with steam flaking and microwave treatment, roasting decreased and increased the buffer soluble protein and neutral detergent insoluble protein, respectively. The control treatments showed the highest levels of neutral detergent soluble protein and the lowest levels of acid detergent soluble protein. Moreover, steam flaking and roasting decreased and increased the amount of acid detergent insoluble protein, respectively. When using dry heat (microwave and roasting), the acid detergent soluble and insoluble protein fractions were increased. As a result of this experiment, the nitrogen fractions were altered using heat processing. Hence, protein fermented feed and ruminal fermentation conditions can be expressed using these results.
Greenhouse Gas Emission Reduction Potential of Lavender Meal and Essential Oil for Dairy Cows
(2023)
This research aims to evaluate the potential of lavender meal (LM) and lavender essential oil (LEO) to mitigate methane emissions by dairy cows. Locally grown lavender was collected fresh for this purpose, and its oil was extracted using the cold-press method. The resultant LEO and LM and whole lavender (WL) were added to dairy cow concentrate feed at 0%, 0.05%, and 0.10%, and their effects on vitro gas production values and gas concentrations were subsequently assessed. Out of the 30 bioactive compounds isolated from LEO, linalool and linalyl acetate were the most common—accounting for 70.4% of the total. The lavender dose had a significant influence on gas production for up to 12 h. No significant variations were found across the lavender forms when gas kinetics, in vitro degradability, and predicted energy values were compared. The addition of WL to the concentrate feed of dairy cows produced the greatest quantities of methane, carbon dioxide, and hydrogen sulfide, whereas LEO resulted in the lowest values. In contrast, no significant difference in ammonia content was found across the various lavender forms added into dairy cow concentrate feed. The results of this research suggest that adding 0.05–0.10% LM and LEO to concentrate feed may decrease greenhouse gas emissions from dairy cows.
We explore the different notions of completeness applied in the EPR discussion following and amending the thorough analysis of Arthur Fine. To this aim, we propose a classification scheme for scientific theories that provides a methodology for analyzing the different levels at which interpretive approaches come into play. This allows us to contrast several concepts of completeness that operate on specific levels of the theory. We introduce the notion of theory completeness and compare it with the established notions of Born completeness, Schrödinger completeness and bijective completeness. We relate these notions to the recent concept of ????-completeness and predictable completeness. The paper shows that the EPR argument contains conflicting versions of completeness. The confusion of these notions led to misunderstandings in the EPR debate and hindered its progress. Their clarification will thus contribute to recent debates on interpretational issues of quantum mechanics. Finally, we discuss the connection between the EPR paper and the Einstein–Rosen paper with regard to the question of completeness.
DC/DC-Konverter wandeln eine Eingangsspannung in eine Ausgangsspannung. In diesem Beitrag werden drei solche Konverter behandelt, die aus den drei Grundschaltungen hergeleitet sind. Im Gegensatz zu den Originalstrukturen sind diese nur für einen geringeren Spannungsübersetzungsbereich geeignet, haben aber den Vorteil, dass die elektronischen Schalter immer bei Strom null schalten und die Dioden nicht zwangsweise, sondern immer von selbst ausschalten. Die Gewinnung der Konverterschaltungen wird erläutert, und die Funktionsweisen werden durch mathematische Beschreibung, durch Skizzen und mithilfe des uZ-i-Diagramms erklärt. Weiters werden einige mögliche Erweiterungen der Schaltungen gezeigt.
The use of fault detection and tolerance measures in wireless sensor networks is inevitable to ensure the reliability of the data sources. In this context, immune-inspired concepts offer suitable characteristics for developing lightweight fault detection systems, and previous works have shown promising results. In this article, we provide a literature review of immune-inspired fault detection approaches in sensor networks proposed in the last two decades. We discuss the unique properties of the human immune system and how the found approaches exploit them. With the information from the literature review extended with the findings of our previous works, we discuss the limitations of current approaches and consequent future research directions. We have found that immune-inspired techniques are well suited for lightweight fault detection, but there are still open questions concerning the effective and efficient use of those in sensor networks.
The aim of this study was to investigate the effect of different forms of Lentilactobacillus buchneri on the in vitro methane production, fermentation characteristics, nutritional quality, and aerobic stability of corn silage treated with or without urea. The following treatments were applied prior to ensiling: (1) no urea treatment and LB; (2) no urea treatment+freeze dried LB; (3) no urea treatment+preactivated LB; (4) with urea treatment+no LB; (5) with urea treatment+freeze dried LB; (6) with urea treatment+preactivated. LB was applied at a rate of 3 × 108 cfu/kg on a fresh basis, while urea was applied at a rate of 1% on the basis of dry matter. Data measured at different time points were analyzed according to a completely randomized design, with a 2 × 3 × 5 factorial arrangement of treatments, while the others were analyzed with a 2 × 3 factorial arrangement. Preactivated LB was more effective than freeze-dried LB in reducing silage pH, ammonia nitrogen, cell-wall components, yeast count, and carbon dioxide production, as well as increasing lactic acid and residual water-soluble carbohydrate and aerobic stability (p < 0.0001). A significant reduction in the methane ratio was observed after 24 h and 48 h incubation with preactivated forms of LB (p < 0.001). The results indicated that preactivated LB combined with urea improved fermentation characteristics, nutritional quality, and aerobic stability and reduced the methane ratio of corn silages.
This study aimed to investigate the effects of slaughter age (young vs. old), muscle type (Longissimus dorsi (LD), Gluteus medius (GM)) and fat deposits (kidney knob and channel fat, subcutaneous fat, intramuscular fat) on chemical, organoleptic, textural characteristics and fatty acid composition of Holstein Friesian bull meat. For this purpose, the carcasses of 26 Holstein Friesian bulls that had been fattened on the same private farm were assigned to two experimental groups based on their age at slaughter: a young group (YG) (average age: 17.0 ± 1.0 months old) and an old group (OG) (average age: 22.0 ± 1.0 months old). The percentage of crude protein, panel tenderness score, polyunsaturated fatty acid (PUFA) and saturated fatty acid (SFA) content, the PUFA/SFA ratio and the hypocholesterolemic fatty acid (DFA)/hypercholesterolemic fatty acid (OFA) ratio of the bull carcasses decreased significantly with increasing slaughter age. By contrast, the OFA content of the carcasses significantly increased (p < 0.05) with increasing slaughter age. Advanced slaughter age resulted in lower panel tenderness scores. Additionally, the meat of the bulls in the OG was considered to be less healthy because of the less desirable fatty acid composition and nutritional indices, such as the PUFA/SFA and hypocholesterolemic/hypercholesterolemic ratios, compared to the meat from the bulls in the YG. Furthermore, the intramuscular fat and internal fat contained high percentages of PUFA and SFA and high PUFA/SFA and hypocholesterolemic/hypercholesterolemic ratios. Interestingly, the percentage of OFA content in the internal and intramuscular fat tissues decreased with increasing slaughter age. In conclusion, this study provided evidence that slaughter age and muscle and fat type are essential sources of variations in the textural characteristics, sensory panel attributes and fatty acid profile of meat from Holstein Friesian bulls.
The ERA-Net SES project Regional Renewable Energy Cells (R2EC) [1] aims at developing a scalable system for decentralized, interacting ‘energy cells’ with a high concentration of locally generated renewable energy. ‘Energy cells’ are essentially Renewable Energy Communities (ECs) in the European context. The system aims at maximizing the utilization of locally generated renewable energy through Electrical Storage (ES) as well as high-electric applications like e‑heating, Heat Pumps (HPs), and E‑Vehicles (EVs). The system is also designed to interact with other energy cells locally, thus, improving the utilization of locally generated energy.
A variety of different adjacent energy cells in three countries, Austria (AT), Belgium (BE), and Norway (NO), are analyzed, and the results are used for the development of regional and renewable energy cell systems. This approach aims at developing tailor-made solutions that meet the different local and regional requirements and the electrical energy demand of the observed energy cells. A unique opportunity is created, as the three countries are at varying levels of regional development in the field of energy communities, and the regional requirements and conditions differ significantly. A comprehensive investigation of the technical and economic viability of the ECs in the three regions is conducted on a simulation level. The technical simulation results show an increased self-consumption of individual users and the overall cell in all of the observed testbeds, while the economic analysis shows economic benefits at varying levels in each of the observed testbeds. The implemented R2EC system ascertains both technical and economic viability in the observed testbeds.
We compare results of simulations of solar facular-like conditions performed using the numerical codes MURaM and STAGGER. Both simulation sets have a similar setup, including the initial condition of ≈200 G vertical magnetic flux. After interpolating the output physical quantities to constant optical depth, we compare them and test them against inversion results from solar observations. From the snapshots, we compute the monochromatic continuum in the visible and infrared, and the full Stokes vector of the Fe i spectral line pair around 6301–6302 Å. We compare the predicted spectral lines (at the simulation resolution and after smearing to the HINODE SP/SOT resolution) in terms of their main parameters for the Stokes I line profiles, and of their area and amplitude asymmetry for the Stokes V profiles. The codes produce magnetoconvection with similar appearance and distribution in temperature and velocity. The results also closely match the values from recent relevant solar observations. Although the overall distribution of the magnetic field is similar in both radiation-magnetohydrodynamic (RMHD) simulation sets, a detailed analysis reveals substantial disagreement in the field orientation, which we attribute to the differing boundary conditions. The resulting differences in the synthetic spectra disappear after spatial smearing to the resolution of the observations. We conclude that the two sets of simulations provide robust models of solar faculae. Nevertheless, we also find differences that call for caution when using results from RMHD simulations to interpret solar observational data.
A system is invariant with respect to an input transformation if we can transform any dynamic input by this function and obtain the same output dynamics after adjusting the initial conditions appropriately. Often, the set of all such input transformations forms a Lie group, the most prominent examples being scale-invariant (, ) and translational-invariant () systems, the latter comprising linear systems with transfer function zeros at the origin. Here, we derive a necessary and sufficient normal form for invariant systems and, by analyzing this normal form, provide a complete characterization of the mechanism by which invariance can be achieved. In this normal form, all invariant systems (i) estimate the applied input transformation by means of an integral feedback, and (ii) then apply the inverse of this estimate to the input before processing it in any other way. We demonstrate our results based on three examples: a scale-invariant “feed-forward loop”, a bistable switch, and a system resembling the core of the mammalian circadian network.
Bidirectional electric vehicle supply equipment and charging stations (EVSE) offer new business models and can provide services to the electrical grid. The smart grid lab in Vienna gives unique testing possibilities of future smart grids, as different type of electrical equipment can be operated at a reconstructed, well-known distribution grid. In this work the harmonic and supraharmonic emissions of a bidirectional EVSE are measured according to IEC61000-4-7 and IEC61000-4-30 Ed3 standard as well as the high-frequency grid impedance. In addition, the efficiency and the power factor are determined at various operating points. Although THDi at nominal power (10 kW) is very low and the efficiency and power factor is very high, at low power levels the opposite situation arise. Supraharmonic emissions remain stable independent of the charging/discharging power, and both wideband and narrowband emissions occur. The additional capacitance when connecting the EVSE impacts the high-frequency grid impedance substantially and generates resonance points.
Methane emission from enteric fermentation in ruminants is the single most relevant greenhouse gas source in agriculture, and it is amongst the largest anthropogenic ones. As ruminants are needed globally for meat, milk and other goods production on a huge scale, feed additives could offer an interesting solution to reduce CH4 emissions. Methane emission strategies are investigated to maintaining productivity and the overall health of the animal. Some strategies have shown to reduce the propagation and/or eliminate ruminal flora affecting the health and productivity of the animal. Therefore, identifying beneficial strategies leads to improving productivity and the health of the animal and environment.
Quail is used in cookery, but mainly for its egg production around the globe, and sustainable poultry farming practices have been searched. The use of colostrum (beestings or first milk from cows) in quails’ diet can play an important role in providing probiotics and reducing the need for antibiotics, which, in addition to better quail performance, is effective in reducing environmental impacts. The results of the current research show that the continuous use of bovine colostrum (BC) in laying quails’ diets has beneficial effects on their performance, egg traits, blood indexes and antioxidant status.
The traditional methods of fighting metal fires are not always safe for firefighters. The sand and salts that are thrown onto the fire to suffocate the flames can lead to splashes of molten metal, putting the firefighters and the surroundings at risk. A novel process is described where magnesium fires are brought under control using a simple two-step process. First, coated cellulose flakes, which contain approx. 30% inorganic salts, are blown onto the fire from a distance of several meters. Due to its low bulk density, the material settles smoothly on the fire and immediately covers the flames for several seconds. Before the hot metal can break through this cover, a fine water spray is applied to the fire. The water spray wets the top layer of the cellulose flakes, which will begin to char from the bottom. The water evaporates from within the cellulose flake layer and withdraws heat. It was observed that no hydrogen is formed and that this technique can safely control fires. It is judged that 90 kg of flakes could safely bring a pile of 75 kg of burning Mg flakes under control. By using a pneumatic conveying unit for the flakes, firefighters can effectively and efficiently cover the flames from a safe distance. This novel method could be recommended to firefighters in industrial magnesium processing plants, as well as local firefighters in the vicinity of such plants.
In general, composite materials are difficult to recycle. Tires belong to this class of materials. On top, one of their main constitutents, vulcanized rubber, is as elastomer, which cannot be remolten and hence is particularly challenging to put to a new use. Today, the main end-of-life routes of tires and other rubber products are landfilling, incineration in e.g., cement plants, and grinding to a fine powder, generating huge quantities and indicating a lack of sustainable recycling of this valuable material. True feedstock recycling is not feasible for complex mixtures such as tires, but devulcanization can be done to reactivate the cross-linked polymer for material recycling in novel rubber products. Devulcanization, i.e., the breaking up of sulfur bonds by chemical, thermophysical, or biological means, is a promising route that has been investigated for more than 50 years. This review article presents an update on the state-of-the art in rubber devulcanization. The article addresses established devulcanization technologies and novel processes described in the scientific and patent literatures. On the one hand, tires have become high-tech products, where the simultaneous improvement of wet traction, rolling resistance, and abrasion resistance (the so-called “magic triangle”) is hard to achieve. On the other hand, recycling and sustainable end-of-life uses are becoming more and more important. It is expected that the public discussion of environmental impacts of thermoplastics will soon spill over to thermosets and elastomers. Therefore, the industry needs to develop and market solutions proactively. Every year, approximately 40 million tons of tires are discarded. Through the devulcanization of end-of-life tires (ELT), it is possible to produce new raw materials with good mechanical properties and a superior environmental footprint over virgin products. The devulcanization process has become an interesting technology that is able to support the circular economy concept.
Methane is the main greenhouse gas (GHG) emitted by ruminants. Mitigation strategies are required to alleviate this negative environmental impact while maintaining productivity and ruminants’ health. To date, numerous methane mitigation strategies have been investigated, reported and suggested by scientists to the livestock industry. In this review, the authors will focus on the commonly practiced and available techniques expanding the knowledge of the reader on the advances of methane mitigation strategies with a focus on the recent literature. Furthermore, the authors will attempt to discuss the drawbacks of the strategies in terms of animal health and performance reduction as well as the concept of feed and energy loss, adding an economic perspective to methane emission mitigation which is in the farmers’ direct interest. As a whole, many factors are effective in reducing undesired methane production, but this is definitely a complex challenge. Conclusively, further research is required to offer effective and efficient methane production mitigation solutions in ruminants worldwide, thus positively contributing to climate change.
This study aimed to assess the impact of essential oils (EOs) on in vitro gas formation and the degradability of dairy and beef cattle diets. This study also aimed to investigate the effects of different types of EOs on nutrient utilization and rumen microbial activity. The current study was conducted using a fully randomized design consisting of eight experimental treatments, including two control treatments without any additives, and treatments with cinnamon essential oil (CEO), flaxseed essential oil (FEO), and lemon seed essential oil (LEO) at a concentration of 60 mg/kg fresh mass. Two control treatments were used, one with alfalfa silage and dairy concentrate (DC, CON-DC) and the other with alfalfa silage and fattening concentrate (FC, CON-FC). Gas formation, dry matter (DM) digestibility, crude protein (CP) digestibility, effective degradability (ED), and soluble fractions of DM and organic matter (OM) were evaluated. CEO had a substantial effect on gas formation (p < 0.05). When EOs were added to the diets, they increased dry matter digestibility after 24 h of incubation as compared to control treatments. After 24 h of incubation, FCCEO and FCFEO had the highest CP digestibility among the diets. FCLEO considerably enhanced ED, as well as the soluble fraction of DM (a) at a passage rate of 2% per hour. Treatment with FCCEO resulted in a significant increase in soluble fractions compared to the control diets. At a passage rate of 2% h, DCCEO had the maximum ED value. When EOs were introduced to the diet, they dramatically decreased the insoluble portion of CP (b). Compared to the control treatments, gas production was significantly lower in the presence of LEO (FCLEO; p < 0.05). The addition of EOs to cattle diets may increase nutrient utilization and enhance rumen microbial activity. EOs extracted from lemon seeds (at a dose of 60 mg/kg of diet) lowered gas production in both dairy cattle and fattening diets.
Short-term Incentives of Research Evaluations: Evidence from the UK Research Excellence Framework
(2023)
Cyclic Tensile Stress Induces Skeletal Muscle Hypertrophy and Myonuclear Accretion in a 3D Model
(2023)
Skeletal muscle is highly adaptive to mechanical stress due to its resident stem cells and the pronounced level of myotube plasticity. Herein, we study the adaptation to mechanical stress and its underlying molecular mechanisms in a tissue-engineered skeletal muscle model. We subjected differentiated 3D skeletal muscle-like constructs to cyclic tensile stress using a custom-made bioreactor system, which resulted in immediate activation of stress-related signal transducers (Erk1/2, p38). Cell cycle re-entry, increased proliferation, and onset of myogenesis indicated subsequent myoblast activation. Furthermore, elevated focal adhesion kinase and β-catenin activity in mechanically stressed constructs suggested increased cell adhesion and migration. After 3 days of mechanical stress, gene expression of the fusogenic markers MyoMaker and MyoMixer, myotube diameter, myonuclear accretion, as well as S6 activation, were significantly increased. Our results highlight that we established a promising tool to study sustained adaptation to mechanical stress in healthy, hypertrophic, or regenerating skeletal muscle.
The rat median nerve model is a well-established and frequently used model for peripheral nerve injury and repair. The grasping test is the gold-standard to evaluate functional recovery in this model. However, no comprehensive review exists to summarize the course of functional recovery in regard to the lesion type. According to PRISMA-guidelines, research was performed, including the databases PubMed and Web of Science. Groups were: (1) crush injury, (2) transection with end-to-end or with (3) end-to-side coaptation and (4) isogenic or acellular allogenic grafting. Total and respective number, as well as rat strain, type of nerve defect, length of isogenic or acellular allogenic allografts, time at first signs of motor recovery (FSR) and maximal recovery grasping strength (MRGS), were evaluated. In total, 47 articles met the inclusion criteria. Group I showed earliest signs of motor recovery. Slow recovery was observable in group III and in graft length above 25 mm. Isografts recovered faster compared to other grafts. The onset and course of recovery is heavily dependent from the type of nerve injury. The grasping test should be used complementary in addition to other volitional and non-volitional tests. Repetitive examinations should be planned carefully to optimize assessment of valid and reliable data.
Extracorporeal shockwave therapy (ESWT) can stimulate processes to promote regeneration, including cell proliferation and modulation of inflammation. Specific miRNA expression panels have been established to define correlations with regulatory targets within these pathways. This study aims to investigate the influence of low-energy ESWT-applied within the subacute and chronic phase of SCI (spinal cord injury) on recovery in a rat spinal cord contusion model. Outcomes were evaluated by gait analysis, µCT and histological analysis of spinal cords. A panel of serum-derived miRNAs after SCI and after ESWT was investigated to identify injury-, regeneration- and treatment-associated expression patterns. Rats receiving ESWT showed significant improvement in motor function in both a subacute and a chronic experimental setting. This effect was not reflected in changes in morphology, µCT-parameters or histological markers after ESWT. Expression analysis of various miRNAs, however, revealed changes after SCI and ESWT, with increased miR-375, indicating a neuroprotective effect, and decreased miR-382-5p potentially improving neuroplasticity via its regulatory involvement with BDNF. We were able to demonstrate a functional improvement of ESWT-treated animals after SCI in a subacute and chronic setting. Furthermore, the identification of miR-375 and miR-382-5p could potentially provide new targets for therapeutic intervention in future studies.
Investigations reporting positive effects of extracorporeal shockwave therapy (ESWT) on nerve regeneration are limited to the rat sciatic nerve model. The effects of ESWT on muscle-in-vein conduits (MVCs) have also not been investigated yet. This study aimed to evaluate the effects of ESWT after repair of the rat median nerve with either autografts (ANGs) or MVCs. In male Lewis rats, a 7 mm segment of the right median nerve was reconstructed either with an ANG or an MVC. For each reconstructive technique, one group of animals received one application of ESWT while the other rats served as controls. The animals were observed for 12 weeks, and nerve regeneration was assessed using computerized gait analysis, the grasping test, electrophysiological evaluations and histological quantification of axons, blood vessels and lymphatic vasculature. Here, we provide for the first time a comprehensive analysis of ESWT effects on nerve regeneration in a rat model of median nerve injury. Furthermore, this study is among the first reporting the quantification of lymphatic vessels following peripheral nerve injury and reconstruction in vivo. While we found no significant direct positive effects of ESWT on peripheral nerve regeneration, results following nerve repair with MVCs were significantly inferior to those after ANG repair.
Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on the tissue level, as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here, we showed for the first time that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease.
Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane as the joint capsule's inner layer is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, RA's synovial-chondral axis has not yet been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue coculture model that simulates the reciprocal cross talk between individual synovial and chondral organoids. When co-cultivated with synovial organoids, we could demonstrate that chondral organoids induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross talk in the modelling of arthritic diseases.
Coculture systems employing adipose tissue-derived mesenchymal stromal/stem cells (ASC) and endothelial cells (EC) represent a widely used technique to model vascularization. Within this system, cell-cell communication is crucial for the achievement of functional vascular network formation. Extracellular vesicles (EVs) have recently emerged as key players in cell communication by transferring bioactive molecules between cells. In this study we aimed to address the role of EVs in ASC/EC cocultures by discriminating between cells, which have received functional EV cargo from cells that have not. Therefore, we employed the Cre-loxP system, which is based on donor cells expressing the Cre recombinase, whose mRNA was previously shown to be packaged into EVs and reporter cells containing a construct of floxed dsRed upstream of the eGFP coding sequence. The evaluation of Cre induced color switch in the reporter system via EVs indicated that there is no EV-mediated RNA transmission either between EC themselves or EC and ASC. However, since Cre mRNA was not found present in EVs, it remains unclear if Cre mRNA is generally not packaged into EVs or if EVs are not taken up by the utilized cell types. Our data indicate that this technique may not be applicable to evaluate EV-mediated cell-to-cell communication in an in vitro setting using EC and ASC. Further investigations will require a functional system showing efficient and specific loading of Cre mRNA or protein into EVs.
Extracellular vesicles (EVs), such as exosomes, microvesicles, and apoptotic bodies, are cell-derived, lipid bilayer-enclosed particles mediating intercellular communication and are therefore vital for transmitting a plethora of biological signals. The vascular endothelium substantially contributes to the circulating particulate secretome, targeting important signaling pathways that affect blood cells and regulate adaptation and plasticity of endothelial cells in a paracrine manner. Different molecular signatures and functional properties of endothelial cells reflect their heterogeneity among different vascular beds and drive current research to understand varying physiological and pathological effects of blood and lymphatic endothelial EVs. Endothelial EVs have been linked to the development and progression of various vascular diseases, thus having the potential to serve as biomarkers and clinical treatment targets. This review aims to provide a brief overview of the human vasculature, the biology of extracellular vesicles, and the current knowledge of endothelium-derived EVs, including their potential role as biomarkers in disease development.
Multi-photon lithography (MPL) has proven to be a suitable tool to precisely control the microenvironment of cells in terms of the biochemical and biophysical properties of the hydrogel matrix. In this work, we present a novel method, based on multi-photon photografting of 4,4′-diazido-2,2′-stilbenedisulfonic acid (DSSA), and its capabilities to induce cell alignment, directional cell migration and endothelial sprouting in a gelatin-based hydrogel matrix. DSSA-photografting allows for the fabrication of complex patterns at a high-resolution and is a biocompatible, universally applicable and straightforward process that is comparably fast. We have demonstrated the preferential orientation of human adipose-derived stem cells (hASCs) in response to a photografted pattern. Co-culture spheroids of hASCs and human umbilical vein endothelial cells (HUVECs) have been utilized to study the directional migration of hASCs into the modified regions. Subsequently, we have highlighted the dependence of endothelial sprouting on the presence of hASCs and demonstrated the potential of photografting to control the direction of the sprouts. MPL-induced DSSA-photografting has been established as a promising method to selectively alter the microenvironment of cells.
Recent progress in machine learning and deep learning has enabled the implementation of plant and crop detection using systematic inspection of the leaf shapes and other morphological characters for identification systems for precision farming. However, the models used for this approach tend to become black-box models, in the sense that it is difficult to trace characters that are the base for the classification. The interpretability is therefore limited and the explanatory factors may not be based on reasonable visible characters. We investigate the explanatory factors of recent machine learning and deep learning models for plant classification tasks. Based on a Daucus carota and a Beta vulgaris image data set, we implement plant classification models and compare those models by their predictive performance as well as explainability. For comparison we implemented a feed forward convolutional neuronal network as a default model. To evaluate the performance, we trained an unsupervised Bayesian Gaussian process latent variable model as well as a convolutional autoencoder for feature extraction and rely on a support vector machine for classification. The explanatory factors of all models were extracted and analyzed. The experiments show, that feed forward convolutional neuronal networks (98.24%
and 96.10% mean accuracy) outperforms the Bayesian Gaussian process latent variable pipeline (92.08% and 94.31% mean accuracy) as well as the convolutional autoenceoder pipeline (92.38% and 93.28%
mean accuracy) based approaches in terms of classification accuracy, even though not significant for Beta vulgaris images. Additionally, we found that the neuronal network used biological uninterpretable image regions for the plant classification task. In contrast to that, the unsupervised learning models rely on explainable visual characters. We conclude that supervised convolutional neuronal networks must be used carefully to ensure biological interpretability. We recommend unsupervised machine learning, careful feature investigation, and statistical feature analysis for biological applications. View Full-Text
Keywords: deep learning; machine learning; plant leaf morphometrics; explainable AI
Abstract: The biological investigation of a population’s shape diversity using digital images is typi-
cally reliant on geometrical morphometrics, which is an approach based on user-defined landmarks.
In contrast to this traditional approach, the progress in deep learning has led to numerous applications
ranging from specimen identification to object detection. Typically, these models tend to become black
boxes, which limits the usage of recent deep learning models for biological applications. However, the
progress in explainable artificial intelligence tries to overcome this limitation. This study compares
the explanatory power of unsupervised machine learning models to traditional landmark-based
approaches for population structure investigation. We apply convolutional autoencoders as well
as Gaussian process latent variable models to two Nile tilapia datasets to investigate the latent
structure using consensus clustering. The explanatory factors of the machine learning models were
extracted and compared to generalized Procrustes analysis. Hypotheses based on the Bayes factor are
formulated to test the unambiguity of population diversity unveiled by the machine learning models.
The findings show that it is possible to obtain biologically meaningful results relying on unsupervised
machine learning. Furthermore we show that the machine learning models unveil latent structures
close to the true population clusters. We found that 80% of the true population clusters relying on
the convolutional autoencoder are significantly different to the remaining clusters. Similarly, 60% of
the true population clusters relying on the Gaussian process latent variable model are significantly
different. We conclude that the machine learning models outperform generalized Procrustes analysis,
where 16% of the population cluster was found to be significantly different. However, the applied
machine learning models still have limited biological explainability. We recommend further in-depth
investigations to unveil the explanatory factors in the used model.
Keywords: generalized procrustes analysis; machine learning; convolutional autoencoder; Gaussian
process latent variable models
Background: Most clinical studies report the symptoms experienced by those infected with coronavirus disease 2019 (COVID-19) via patients already hospitalized. Here we analyzed the symptoms experienced outside of a hospital setting.
Methods: The Vienna Social Fund (FSW; Vienna, Austria), the Public Health Services of the City of Vienna (MA15) and the private company Symptoma collaborated to implement Vienna's official online COVID-19 symptom checker. Users answered 12 yes/no questions about symptoms to assess their risk for COVID-19. They could also specify their age and sex, and whether they had contact with someone who tested positive for COVID-19. Depending on the assessed risk of COVID-19 positivity, a SARS-CoV‑2 nucleic acid amplification test (NAAT) was performed. In this publication, we analyzed which factors (symptoms, sex or age) are associated with COVID-19 positivity. We also trained a classifier to correctly predict COVID-19 positivity from the collected data.
Results: Between 2 November 2020 and 18 November 2021, 9133 people experiencing COVID-19-like symptoms were assessed as high risk by the chatbot and were subsequently tested by a NAAT. Symptoms significantly associated with a positive COVID-19 test were malaise, fatigue, headache, cough, fever, dysgeusia and hyposmia. Our classifier could successfully predict COVID-19 positivity with an area under the curve (AUC) of 0.74.
Conclusion: This study provides reliable COVID-19 symptom statistics based on the general population verified by NAATs.
Keywords: Chatbot; Machine learning; Self-reported; Symptom assessment; Symptom checker.
Interference of more and more massive objects provides a spectacular confirmation of quantum theory. It is usually regarded as support for “wave–particle duality” and in an extension of this duality even as support for “complementarity”. We first give an outline of the historical development of these notions. Already here it becomes evident that they are hard to define rigorously, i.e. have mainly a heuristic function. Then we discuss recent interference experiments of large and complex molecules which seem to support this heuristic function of “duality”. However, we show that in these experiments the diffraction of a delocalized center-of-mass wave function depends on the interaction of the localized structure of the molecule with the diffraction element. Thus, the molecules display “dual features” at the same time, which contradicts the usual understanding of wave–particle duality. We conclude that the notion of “wave–particle duality” deserves no place in modern quantum physics.
In this work we analyse bucket increasing tree families. We introduce two simple stochastic growth processes, generating random bucket increasing trees of size n, complementing the earlier result of Mahmoud and Smythe (1995, Theoret. Comput. Sci.144 221–249.) for bucket recursive trees. On the combinatorial side, we define multilabelled generalisations of the tree families d-ary increasing trees and generalised plane-oriented recursive trees. Additionally, we introduce a clustering process for ordinary increasing trees and relate it to bucket increasing trees. We discuss in detail the bucket size two and present a bijection between such bucket increasing tree families and certain families of graphs called increasing diamonds, providing an explanation for phenomena observed by Bodini et al. (2016, Lect. Notes Comput. Sci.9644 207–219.). Concerning structural properties of bucket increasing trees, we analyse the tree parameter Kn . It counts the initial bucket size of the node containing label n in a tree of size n and is closely related to the distribution of node types. Additionally, we analyse the parameters descendants of label j and degree of the bucket containing label j, providing distributional decompositions, complementing and extending earlier results (Kuba and Panholzer (2010), Theoret. Comput. Sci.411(34–36) 3255–3273.).
In this work we discuss a parameter σ on weighted k-element multisets of [n]={1,…,n}. The sums of weighted k-multisets are related to k-subsets, k-multisets, as well as special instances of truncated interpolated multiple zeta values. We study properties of this parameter using symbolic combinatorics. We rederive and extend certain identities for ζtn({m}k). Moreover, we introduce random variables on the k-element multisets and derive their distributions, as well as limit laws for k or n tending to infinity.
Fibrin hydrogels have proven highly suitable scaffold materials for skeletal muscle tissue engineering in the past. Certain parameters of those types of scaffolds, however, greatly affect cellular mechanobiology and therefore the myogenic outcome. The aim of this study was to identify the influence of apparent elastic properties of fibrin scaffolds in 2D and 3D on myoblasts and evaluate if those effects differ between murine and human cells. Therefore, myoblasts were cultured on fibrin-coated multiwell plates (“2D”) or embedded in fibrin hydrogels (“3D”) with different elastic moduli. Firstly, we established an almost linear correlation between hydrogels’ fibrinogen concentrations and apparent elastic moduli in the range of 7.5 mg/ml to 30 mg/ml fibrinogen (corresponds to a range of 7.7–30.9 kPa). The effects of fibrin hydrogel elastic modulus on myoblast proliferation changed depending on culture type (2D vs 3D) with an inhibitory effect at higher fibrinogen concentrations in 3D gels and vice versa in 2D. The opposite effect was evident in differentiating myoblasts as shown by gene expression analysis of myogenesis marker genes and altered myotube morphology. Furthermore, culture in a 3D environment slowed down proliferation compared to 2D, with a significantly more pronounced effect on human myoblasts. Differentiation potential was also substantially impaired upon incorporation into 3D gels in human, but not in murine, myoblasts. With this study, we gained further insight in the influence of apparent elastic modulus and culture type on cellular behavior and myogenic outcome of skeletal muscle tissue engineering approaches. Furthermore, the results highlight the need to adapt parameters of 3D culture setups established for murine cells when applied to human cells.
Peripheral nerve injuries pose a major clinical concern world-wide, and functional recovery after segmental peripheral nerve injury is often unsatisfactory, even in cases of autografting. Although it is well established that angiogenesis plays a pivotal role during nerve regeneration, the influence of lymphangiogenesis is strongly under-investigated. In this study, we analyzed the presence of lymphatic vasculature in healthy and regenerated murine peripheral nerves, revealing that nerve autografts contained increased numbers of lymphatic vessels after segmental damage. This led us to elucidate the interaction between lymphatic endothelial cells (LECs) and Schwann cells (SCs) in vitro. We show that SC and LEC secretomes did not influence the respective other cell types' migration and proliferation in 2D scratch assay experiments. Furthermore, we successfully created lymphatic microvascular structures in SC-embedded 3D fibrin hydrogels, in the presence of supporting cells; whereas SCs seemed to exert anti-lymphangiogenic effects when cultured with LECs alone. Here, we describe, for the first time, increased lymphangiogenesis after peripheral nerve injury and repair. Furthermore, our findings indicate a potential lymph-repellent property of SCs, thereby providing a possible explanation for the lack of lymphatic vessels in the healthy endoneurium. Our results highlight the importance of elucidating the molecular mechanisms of SC-LEC interaction.
Temporary scaffolds that mimic the extracellular matrix's structure and provide a stable substratum for the natural growth of cells are an innovative trend in the field of tissue engineering. The aim of this study is to obtain and design porous 2D fibroin-based cell matrices by femtosecond laser-induced microstructuring for future applications in muscle tissue engineering. Ultra-fast laser treatment is a non-contact method, which generates controlled porosity-the creation of micro/nanostructures on the surface of the biopolymer that can strongly affect cell behavior, while the control over its surface characteristics has the potential of directing the growth of future muscle tissue in the desired direction. The laser structured 2D thin film matrices from silk were characterized by means of SEM, EDX, AFM, FTIR, Micro-Raman, XRD, and 3D-roughness analyses. A WCA evaluation and initial experiments with murine C2C12 myoblasts cells were also performed. The results show that by varying the laser parameters, a different structuring degree can be achieved through the initial lifting and ejection of the material around the area of laser interaction to generate porous channels with varying widths and depths. The proper optimization of the applied laser parameters can significantly improve the bioactive properties of the investigated 2D model of a muscle cell matrix.
Keywords: biopolymers; femtosecond laser processing; muscle cell matrix 2D model; muscle tissue engineering; silk fibroin.
In order to enhance the strength of 3D-printed parts made of polymer materials and reduce the anisotropy caused by the fused filament fabrication process, this paper proposes an inter-layer interleaved composite path planning method based on the directional partition of the principal stress field. This method not only ensures intra-layer reinforcement under specific working conditions but also increases the strength of the printed part by enhancing the adhesion of adjacent layers through staggered filling between layers. The mechanical performance is improved by 10 to 30% compared to other conventional filling patterns such as the zigzag filling algorithm. Inter-layer interleaved composite enhancement path planning method is suitable for path planning of structures with complex shapes and is easily integrated into existing general computer-aided engineering processes.
Dry powder inhalers are used by a large number of patients worldwide to treat respiratory diseases. The objective of this work is to experimentally investigate changes in aerosol particle diameter and particle number concentration of pharmaceutical aerosols generated by four dry powder inhalers under realistic inhalation and exhalation conditions. To simulate patients undergoing inhalation therapy, the active respiratory system model (xPULM™) was used. A mechanical upper airway model was developed, manufactured, and introduced as a part of the xPULM™ to represent the human upper respiratory tract with high fidelity. Integration of optical aerosol spectrometry technique into the setup allowed for evaluation of pharmaceutical aerosols. The results show that there is a significant difference (p < 0.05) in mean particle diameter between inhaled and exhaled particles with the majority of the particles depositing in the lung, while particles with the size of (>0.5 μm) are least influenced by deposition mechanisms. The fraction of exhaled particles ranges from 2.13% (HandiHaler®) over 2.94% (BreezHaler®), and 6.22% (Turbohaler®) to 10.24% (Ellipta®). These values are comparable to previously published studies. Furthermore, the mechanical upper airway model increases the resistance of the overall system and acts as a filter for larger particles (>3 μm). In conclusion, the xPULM™ active respiratory system model is a viable option for studying interactions of pharmaceutical aerosols and the respiratory tract regarding applicable deposition mechanisms. The model strives to support the reduction of animal experimentation in aerosol research and provides an alternative to experiments with human subjects.
In the present work, using the recently introduced framework of local geometric deformations, special types of vector fields – so-called hidden Killing vector fields – are constructed, which solve the Killing equation not globally, but only locally, i.e. in local subregions of spacetime. Taking advantage of the fact that the vector fields coincide locally with Killing fields and therefore allow the consideration of integral laws that convert into exact physical conservation laws on local scales, balance laws in dynamical systems without global Killing symmetries are derived that mimic as closely as possible the conservation laws for energy and angular momentum of highly symmetric models. The utility of said balance laws is demonstrated by a concrete geometric example, namely a toy model for the binary merger of two extremal Reissner–Nordström black holes.
In this paper, using the quasilocal formalism of Brown and York, the flow of energy through a closed surface containing a gravitating physical system is calculated in a way that augments earlier results on the subject by Booth and Creighton. To this end, by performing a variation of the total gravitational Hamiltonian (bulk plus boundary part), it is shown that associated tidal heating and deformation effects generally are larger than expected. This is because the aforementioned variation leads to previously unrecognized correction terms, including a bulk-to-boundary inflow term that does not appear in the original calculation of the time derivative of the Brown-York energy and leads to corrective extensions of Einstein’s quadrupole formula in the large sphere limit.
Wissensarbeiter:innen verbringen den überwiegenden Teil ihrer Arbeitszeit sitzend vor dem Computer. Die negativen Folgen von langem Sitzen für die Gesundheit sind bekannt: Zu langes Sitzen bedingt einen niedrigen Kalorienverbrauch, der Stoffwechsel und das Herz-Kreislaufsystem laufen auf Sparflamme. Entsprechend steigt das Risiko für Übergewicht, Diabetes, Bandscheibenvorfall und Herz-Kreislauf- Erkrankungen. Unter den Folgen von langem Sitzen leiden aber nicht nur die betroffenen Mitarbeiter:innen selbst, sondern auch deren Arbeitgeber:innen, weil Mitarbeiter:innen mit einem auf Bewegungsmangel zurückzuführenden reduzierten physischen und psychischen Wohlbefinden weniger produktiv und kreativ arbeiten bzw. aufgrund von Erkrankungen erst gar nicht arbeiten können. Der vorliegende Beitrag zeigt auf, wie Unternehmen durch das Setzen sanfter Bewegungszwänge, den Einsatz dynamischer Arbeitsstationen sowie die Integration niederschwelliger Fitnessmodule in die Bürolandschaft für mehr körperliche Aktivität im Arbeitsalltag sorgen können.
Hybrid courses with a focus on practice-orientated education and self-guided learning phases are on the rise on the higher education sector. Disciplines in Life Sciences implicate a high degree of practical laboratory expertise. The University of Applied Sciences (UAS) in Vienna, Austria, has thus been endeavoured offering students a high qualitative education integrating hybrid courses based on PBL principles, which consist of on-site (including the transmission of necessary background and practical laboratory training) and off-site (including self-study phases) sessions. As practical laboratory units are central in those courses, the restrictive measures, including the transition to a complete online teaching format due to the first Covid-19-pandemic lock-down, had severe effects on the implementation and the quality of the curriculum. According to surveys made specifically to address this problematic situation, it can be concluded that on-site practical units are fundamental for certain disciplines such as Life Sciences.
The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.
The natural extracellular matrix (ECM) provides the optimal environment for cells. Many enzymatic or non-enzymatic based strategies to extract ECM proteins from tissues were published over the past years. However, every single isolation strategy reported so far is associated with specific bottlenecks. In this study, frequently used strategies to isolate ECM from human placenta or adipose tissue using Tris-, serum-, or pepsin-based buffers were compared. The resulting ECM proteins were biochemically characterized by analysis of cellular remnants using Hoechst DNA staining, glycosaminoglycan (GAG) content by dimethylmethylene blue, visualization of protein bands using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis combined with amino acid quantification, and assessment of the proangiogenic profile using an angiogenesis array. Tris-NaCl-extracted ECM proteins showed a high heterogenic degree of extracted proteins, bioactive growth factors, and GAGs, but no collagen-I. Active serum-extracted ECM showed significant lower DNA remnants when compared with the Tris-NaCl isolation strategy. Pepsin-extracted ECM was rich in collagen-I and low amounts of remaining bioactive growth factors. This strategy was most effective to reduce DNA amounts when compared with the other isolation strategies. Pepsin-extracted ECM from both tissues easily gelled at 37°C, whereas the other extracted ECM strategies did not gel at 37°C (Tris-NaCl: liquid; serum: sponge). All relevant characteristics (DNA residues, ECM diversity and bioactivity, shape) of the extracted ECM proteins highly depend on its isolation strategy and could still be optimized. Impact statement The natural human extracellular matrix (ECM) is the ideal cell niche. Various strategies were reported to isolate human ECM components from various sources. In this article, we compared frequently used methods and compared their characteristics (DNA remnants, glycosaminoglycan content, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, amino acid quantification, angiogenesis array, and gel formation). We conclude that more research is still necessary to optimize current isolation approaches for in vitro or in vivo applications of human ECM.
The additive manufacturing of low elastic modulus alloys that have a certain level of porosity for biomedical needs is a growing area of research. Here, we show the results of manufacturing of porous and dense samples by a laser powder bed fusion (LPBF) of Ti-Nb alloy, using two distinctive fusion strategies. The nanostructured Ti-Nb alloy powders were produced by mechanical alloying and have a nanostructured state with nanosized grains up to 90 nm. The manufactured porous samples have pronounced open porosity and advanced roughness, contrary to dense samples with a relatively smooth surface profile. The structure of both types of samples after LPBF is formed by uniaxial grains having micro- and nanosized features. The inner structure of the porous samples is comprised of an open interconnected system of pores. The volume fraction of isolated porosity is 2 vol. % and the total porosity is 20 vol. %. Cell viability was assessed in vitro for 3 and 7 days using the MG63 cell line. With longer culture periods, cells showed an increased cell density over the entire surface of a porous Ti-Nb sample. Both types of samples are not cytotoxic and could be used for further in vivo studies.
Due to their strong biomimetic potential, silk fibroin (SF) hydrogels are impressive candidates for tissue engineering, due to their tunable mechanical properties, biocompatibility, low immunotoxicity, controllable biodegradability, and a remarkable capacity for biomaterial modification and the realization of a specific molecular structure. The fundamental chemical and physical structure of SF allows its structure to be altered using various crosslinking strategies. The established crosslinking methods enable the formation of three-dimensional (3D) networks under physiological conditions. There are different chemical and physical crosslinking mechanisms available for the generation of SF hydrogels (SFHs). These methods, either chemical or physical, change the structure of SF and improve its mechanical stability, although each method has its advantages and disadvantages. While chemical crosslinking agents guarantee the mechanical strength of SFH through the generation of covalent bonds, they could cause some toxicity, and their usage is not compatible with a cell-friendly technology. On the other hand, physical crosslinking approaches have been implemented in the absence of chemical solvents by the induction of β-sheet conformation in the SF structure. Unfortunately, it is not easy to control the shape and properties of SFHs when using this method. The current review discusses the different crosslinking mechanisms of SFH in detail, in order to support the development of engineered SFHs for biomedical applications.
Injury of articular cartilage leads to an imbalance in tissue homeostasis, and due to the poor self-healing capacity of cartilage the affected tissue often exhibits osteoarthritic changes. In recent years, injectable and highly tunable composite hydrogels for cartilage tissue engineering and drug delivery have been introduced as a desirable alternative to invasive treatments. In this study, we aimed to formulate injectable hydrogels for drug delivery and cartilage tissue engineering by combining different concentrations of hyaluronic acid-tyramine (HA-Tyr) with regenerated silk-fibroin (SF) solutions. Upon enzymatic crosslinking, the gelation and mechanical properties were characterized over time. To evaluate the effect of the hydrogel compositions and properties on extracellular matrix (ECM) deposition, bovine chondrocytes were embedded in enzymatically crosslinked HA-Tyr/SF composites (in further work abbreviated as HA/SF) or HA-Tyr hydrogels. We demonstrated that all hydrogel formulations were cytocompatible and could promote the expression of cartilage matrix proteins allowing chondrocytes to produce ECM, while the most prominent chondrogenic effects were observed in hydrogels with HA20/SF80 polymeric ratios. Unconfined mechanical testing showed that the compressive modulus for HA20/SF80 chondrocyte-laden constructs was increased almost 10-fold over 28 days of culture in chondrogenic medium which confirmed the superior production of ECM in this hydrogel compared to other hydrogels in this study. Furthermore, in hydrogels loaded with anabolic and anti-inflammatory drugs, HA20/SF80 hydrogel showed the longest and the most sustained release profile over time which is desirable for the long treatment duration typically necessary for osteoarthritic joints. In conclusion, HA20/SF80 hydrogel was successfully established as a suitable injectable biomaterial for cartilage tissue engineering and drug delivery applications.
Background: In spite of advances in the treatment of cartilage defects using cell and scaffold-based therapeutic strategies, the long-term outcome is still not satisfying since clinical scores decline years after treatment. Scaffold materials currently used in clinical settings have shown limitations in providing suitable biomechanical properties and an authentic and protective environment for regenerative cells. To tackle this problem, we developed a scaffold material based on decellularised human articular cartilage.
Methods: Human articular cartilage matrix was engraved using a CO2 laser and treated for decellularisation and glycosaminoglycan removal. Characterisation of the resulting scaffold was performed via mechanical testing, DNA and GAG quantification and in vitro cultivation with adipose-derived stromal cells (ASC). Cell vitality, adhesion and chondrogenic differentiation were assessed. An ectopic, unloaded mouse model was used for the assessment of the in vivo performance of the scaffold in combination with ASC and human as well as bovine chondrocytes. The novel scaffold was compared to a commercial collagen type I/III scaffold.
Findings: Crossed line engravings of the matrix allowed for a most regular and ubiquitous distribution of cells and chemical as well as enzymatic matrix treatment was performed to increase cell adhesion. The biomechanical characteristics of this novel scaffold that we term CartiScaff were found to be superior to those of commercially available materials. Neo-tissue was integrated excellently into the scaffold matrix and new collagen fibres were guided by the laser incisions towards a vertical alignment, a typical feature of native cartilage important for nutrition and biomechanics. In an ectopic, unloaded in vivo model, chondrocytes and mesenchymal stromal cells differentiated within the incisions despite the lack of growth factors and load, indicating a strong chondrogenic microenvironment within the scaffold incisions. Cells, most noticeably bone marrow-derived cells, were able to repopulate the empty chondrocyte lacunae inside the scaffold matrix.
Interpretation: Due to the better load-bearing, its chondrogenic effect and the ability to guide matrix-deposition, CartiScaff is a promising biomaterial to accelerate rehabilitation and to improve long term clinical success of cartilage defect treatment.
Funding: Austrian Research Promotion Agency FFG ("CartiScaff" #842455), Lorenz Böhler Fonds (16/13), City of Vienna Competence Team Project Signaltissue (MA23, #18-08).
Keywords: Cartilage regeneration; Decellularisation; Ectopic animal model; Laser engraving; Mechanical testing; Repopulation.
Vascular grafts with a diameter of less than 6 mm are made from a variety of materials and techniques to provide alternatives to autologous vascular grafts. Decellularized materials have been proposed as a possible approach to create extracellular matrix (ECM) vascular prostheses as they are naturally derived and inherently support various cell functions. However, these desirable graft characteristics may be limited by alterations of the ECM during the decellularization process leading to decreased biomechanical properties and hemocompatibility. In this study, arteries from the human placenta chorion were decellularized using two distinct detergents (Triton X-100 or SDS), which differently affect ECM ultrastructure. To overcome biomechanical strength loss and collagen fiber exposure after decellularization, riboflavin-mediated UV (RUV) crosslinking was used to uniformly crosslink the collagenous ECM of the grafts. Graft characteristics and biocompatibility with and without RUV crosslinking were studied in vitro and in vivo. RUV-crosslinked ECM grafts showed significantly improved mechanical strength and smoothening of the luminal graft surfaces. Cell seeding using human endothelial cells revealed no cytotoxic effects of the RUV treatment. Short-term aortic implants in rats showed cell migration and differentiation of host cells. Functional graft remodeling was evident in all grafts. Thus, RUV crosslinking is a preferable tool to improve graft characteristics of decellularized matrix conduits.
Erosion of the epigenetic DNA methylation landscape is a widely recognized hallmark of aging. Emerging advances in high throughput sequencing techniques, in particular DNA methylation data analysis, have resulted in the establishment of precise human and murine age prediction tools. In vertebrates, methylation of cytosine at the C5 position of CpG dinucleotides is executed by DNA methyltransferases (DNMTs) whereas the process of enzymatic demethylation is highly dependent on the activity of the ten-eleven translocation methylcytosine dioxygenase (TET) family of enzymes. Here, we report the identification of the key players constituting the DNA methylation machinery in the short-lived teleost aging model Nothobranchius furzeri. We present a comprehensive spatio-temporal expression profile of the methylation-associated enzymes from embryogenesis into late adulthood, thereby covering the complete killifish life cycle. Data mining of the N. furzeri genome produced five dnmt gene family orthologues corresponding to the mammalian DNMTs (DNMT1, 2, 3A, and 3B). Comparable to other teleost species, N. furzeri harbors multiple genomic copies of the de novo DNA methylation subfamily. A related search for the DNMT1 recruitment factor UHRF1 and TET family members resulted in the identification of N. furzeri uhrf1, tet1, tet2, and tet3. Phylogenetic analysis revealed high cross-species similarity on the amino acid level of all individual dnmts, tets, and uhrf1, emphasizing a high degree of functional conservation. During early killifish development all analyzed dnmts and tets showed a similar expression profile characterized by a strong increase in transcript levels after fertilization, peaking either at embryonic day 6 or at the black eye stage of embryonic development. In adult N. furzeri, DNA methylation regulating enzymes showed a ubiquitous tissue distribution. Specifically, we observed an age-dependent downregulation of dnmts, and to some extent uhrf1, which correlated with a significant decrease in global DNA methylation levels in the aging killifish liver and muscle. The age-dependent DNA methylation profile and spatio-temporal expression characteristics of its enzymatic machinery reported here may serve as an essential platform for the identification of an epigenetic aging clock in the new vertebrate model system N. furzeri.
There is critical unmet need for new vascularized tissues to support or replace injured tissues and organs. Various synthetic and natural materials were already established for use of two-dimensional (2D) and three-dimensional (3D) in vitro neovascularization assays, however, they still cannot mimic the complex functions of the sum of the extracellular matrix (ECM) in native intact tissue. Currently, this issue is only addressed by artificial products such as Matrigel™, which comprises a complex mixture of ECM proteins, extracted from animal tumor tissue. Despite its outstanding bioactivity, the isolation from tumor tissue hinders its translation into clinical applications. Since nonhuman ECM proteins may cause immune reactions, as are frequently observed in clinical trials, human ECM proteins represent the best option when aiming for clinical applications. Here, we describe an effective method of isolating a human placenta substrate (hpS) that induces the spontaneous formation of an interconnected network of green fluorescence-labeled human umbilical vein endothelial cells (gfpHUVECs) in vitro. The substrate was biochemically characterized by using a combination of bicinchoninic acid (BCA) assay, DNA, and glycosaminoglycan (GAG) content assays, sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis and Western blot, angiogenesis arrays, chromatographic thrombin detection, high performance liquid chromatography (HPLC)-based amino acid quantification analysis, and assessment of antimicrobial properties. 2D in vitro cell culture experiments have been performed to determine the vasculogenic potential of hpS, which demonstrated that cell networks developed on hpS show a significantly higher degree of complexity (number of tubules/junctions; total/mean tube length) when compared with Matrigel. As 3D cell culture techniques represent a more accurate representation of the in vivo condition, the substrate was 3D solidified using various natural polymers. 3D in vitro vasculogenesis assays have been performed by seeding gfpHUVECs in an hpS-fibrinogen clot. In conclusion, hpS provides a potent human/material-based alternative to xenogenic-material-based biomaterials for vascularization strategies in tissue engineering.
It has recently been shown that matter-wave interferometry can be used to imprint a periodic nanostructure onto a molecular beam, which provides a highly sensitive tool for beam displacement measurements. Herein, we used this feature to measure electronic properties of provitamin A, vitamin E, and vitamin K1 in the gas phase for the first time. The shift of the matter-wave fringes in a static electric field encodes the molecular susceptibility and the time-averaged dynamic electric dipole moment. The dependence of the fringe pattern on the intensity of the central light-wave diffraction grating was used to determine the molecular optical polarizability. Comparison of our experimental findings with molecular dynamics simulations and density functional theory provides a rich picture of the electronic structures and dynamics of these biomolecules in the gas phase with β-carotene as a particularly interesting example.