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Automatic classification of a full-thickness macular hole in optical coherence tomography images
(2023)
A Turbulent Context
(2023)
Interface with WP123200
(2023)
Requirements from WP123200
(2022)
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)