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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.
Tapped inductor DC-to-DC converters are interesting circuits, the winding ratio of the two windings mounted on the same core change the voltage transformation ratio compared to the untapped inductor. The tapped inductor converters are especially useful, when high or low voltage transformation ratios have to be realized. The disadvantage of this concept is that the coupling between the two windings is not total and can be described by the stray or leakage inductance. This stray inductance leads to a high overvoltage at the active switch, and therefore also across other elements of the converter. After a short summery of the ideal tapped Boost converter, the design of an RCD snubber which limits the overvoltage is explained. To improve the efficiency of the converter two active snubber networks are treated, which feed the energy stored in the snubber capacitor into the input source or into the output circuit. Simulations are used to prove these considerations.
Electrolytic capacitors have the disadvantage of
pronounced aging. Non-electrolytic capacitors are therefore used
in applications where long-life is important. In this paper we
present a driving stage for LEDs without any capacitive
elements. The basic topology is a Buck converter with one coil,
one active, and one passive switch. Instead of the output
capacitor, series connections of one or more LEDs and an active
switch are connected. An additional diode is connected between
the output and the input to achieve a current path, when all LED-
paths are off. A nonlinear hysteresis controller is used to achieve
a robust control. A system with three switchable LED-strings is
analyzed. Design hints are given and the function is proved with
the help of LTSpice simulations. The system can be used for
lighting purposes with the possibility to change the chrominance.
The potentiality to transmit data is also treated.
Two-Stage Step-up Converter with Different Voltage Transformation Ratios depending on the Duty Cycle
(2022)
A two-stage converter with high output voltage
ratio and reduced current stress of the inductors and partly
reduced voltage stress is discussed. The function is explained
with the help of voltage and current diagrams. The voltage
transformation ratio changes between a quadratic step-up for
duty cycles lower 0.5 and a double Boost converter for duty
cycles higher than 0.5. Dimensioning hints, the control law for
feed-forward controls, the transient when the supply is turned on
is discussed and some simulations are given. A comparison to
other two-stage converters is also treated.
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.
Design of State-Space Controllers with the Help of Signal Flow Graphs Shown for a Buck Converter
(2022)
A Model-Based Approach for Remote Development of Embedded Software for Object Avoidance Applications
(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.
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.