Search

Abstract Batteries with high energy densities become essential with the increased uptake of electric vehicles. Battery housing, a protective casing encapsulating the battery, must fulfil competing engineering requirements of high stiffness and effective thermal management whilst being lightweight. In this study, a graded lattice design framework is developed based on topology optimisation to effectively tackle the multidisciplinary objectives associated with battery housing. It leverages the triply periodic minimal surfaces lattices, aiming for high mechanical stiffness and efficient heat dissipation considering heat conduction and convection. The effectiveness of the proposed framework was demonstrated through the battery housing design, showcasing its ability to address multidisciplinary objectives as evidenced by the analysis of the Pareto front. This study identifies the potential of lattices in lightweight applications incorporating multiphysics and offers an efficient lattice design framework readily extended to other engineering challenges.

Abstract Nuclear spin hyperpolarization increases the sensitivity of magnetic resonance dramatically, enabling many new applications, including real-time metabolic imaging. Parahydrogen-based signal amplification by reversible exchange (SABRE) was employed to hyperpolarize [1-13C]pyruvate and demonstrate 13C imaging in situ at 120 µT, about twice Earth’s magnetic field, with two different signal amplification by reversible exchange variants: SABRE in shield enables alignment transfer to heteronuclei (SABRE-SHEATH), where hyperpolarization is transferred from parahydrogen to [1-13C]pyruvate at a magnetic field below 1 µT, and low-irradiation generates high tesla (LIGHT-SABRE), where hyperpolarization was prepared at 120 µT, avoiding magnetic field cycling. The 3-dimensional images of a phantom were obtained using a superconducting quantum interference device (SQUID) based magnetic field detector with submillimeter resolution. These 13C images demonstrate the feasibility of low-field 13C metabolic magnetic resonance imaging (MRI) of 50 mM [1-13C]pyruvate hyperpolarized by parahydrogen in reversible exchange imaged at about twice Earth’s magnetic field. Using thermal 13C polarization available at 120 µT, the same experiment would have taken about 300 billion years.

Abstract In biological tissues, 19F magnetic resonance (MR) enables the non-invasive, background-free detection of 19F-containing biomarkers. However, the signal-to-noise ratio (SNR) is usually low because biomarkers are typically present at low concentrations. Measurements at low magnetic fields further reduce the SNR. In a proof-of-principal study we applied LED-based photo-chemically induced dynamic nuclear polarization (photo-CIDNP) to amplify the 19F signal at 0.6 T. For the first time, 19F MR imaging (MRI) and spectroscopy (MRS) of a fully biocompatible model system containing the antiviral drug favipiravir has been successfully performed. This fluorinated drug has been used to treat Ebola and COVID-19. Since the partially cyclic reaction scheme for photo-CIDNP allows for multiple data acquisitions, averaging further improved the SNR. The mean signal gain factor for 19F has been estimated to be in the order of 103. An in-plane resolution of 0.39 × 0.39 mm2 enabled the analysis of spatially varying degrees of hyperpolarization. The minimal detectable amount of favipiravir per voxel was estimated to about 500 pmol. The results show that 19F photo-CIDNP is a promising method for the non-invasive detection of suitable 19F-containing drugs and other compounds with very low levels of the substance.

Battery Electric Vehicles (BEVs) have an increasingly large share of the vehicle market. To ensure a safe and long operation of the mostly large underfloor-mounted traction batteries, they must be developed and tested in advance under realistic conditions. Current standards often do not provide sufficiently realistic requirements for environmental and lifetime testing, as these are mostly based on data measured on cars with an Internal Combustion Engine (ICE). Prior to this work, vibration measurements were performed on two battery-powered electric vehicles and a battery-powered commercial mini truck over various road surfaces and other influences. The measurement data are statistically evaluated so that a statement can be made about the influence of various parameters on the vibrations measured at the battery pack housing and the scatter of the influencing parameters. By creating a load profile based on the existing measurement data, current standards can be questioned and new insights gained in the development of a vibration profile for the realistic testing of battery packs for BEVs.

Background: Amblyopia is associated with unbalanced suppression between the two eyes. Existing clinical measures of suppression, such as the Worth 4 Dot test, provide qualitative information about suppression but cannot precisely quantify it. The Synoptophore, a well-established instrument in binocular vision clinics, has historically been used to gauge suppression qualitatively as well but has the capability to quantify suppression. We extended the capability of the Synoptophore through the development of a systematic protocol of illumination manipulation to quantify suppression in amblyopia. Methods: Twenty-six previously treated adult amblyopes underwent our protocol on the Synoptophore to measure the illumination balance needed to obtain fusion responses. Separately, these same amblyopes were tested with Worth 4 Dot as it is classically performed in the United States, utilizing different test distances and room illuminations to qualify the suppression response. Results: Smaller, more central targets revealed larger magnitudes of suppression for both the Synoptophore and Worth 4 Dot tests (Synoptophore: χ25,26 = 25.538, p < 0.001; Worth 4 Dot: χ23,26 = 39.020, p < 0.001). There was a significant correlation between the two tests for depth of suppression measurements (rΤ > 0.345, p < 0.036), with more sensitivity measured by the Synoptophore, as suppression could be graded on a quantitative scale. Strabismic amblyopes demonstrated more suppression than non-strabismic amblyopes (z > 2.410, p < 0.016). Additionally, depth of suppression was correlated with interocular difference in both visual acuity (rΤ = 0.604, p < 0.001) and stereoacuity (rΤ = 0.488, p = 0.001). Conclusions: We extended the utility of the Synoptophore by measuring its illuminance outputs and developing a suppression testing protocol that compared favorably with Worth 4 Dot (clinic standard) while improving upon the latter through more sensitive quantification of suppression.

Resection margin adequacy plays a critical role in the local control of sarcomas. Fluorescence-guided surgery has increased complete resection rates and local recurrence-free survival in several oncological disciplines. The purpose of this study was to determine whether sarcomas exhibit sufficient tumor fluorescence (photodynamic diagnosis (PDD)) after administration of 5-aminolevulinic acid (5-ALA) and whether photodynamic therapy (PDT) has an impact on tumor vitality in vivo. Sixteen primary cell cultures were derived from patient samples of 12 different sarcoma subtypes and transplanted onto the chorio-allantoic membrane (CAM) of chick embryos to generate 3-dimensional cell-derived xenografts (CDXs). After treatment with 5-ALA, the CDXs were incubated for another 4 h. Subsequently accumulated protoporphyrin IX (PPIX) was excited by blue light and the intensity of tumor fluorescence was analyzed. A subset of CDXs was exposed to red light and morphological changes of both CAMs and tumors were documented. Twenty-four hours after PDT, the tumors were excised and examined histologically. High rates of cell-derived engraftments on the CAM were achieved in all sarcoma subtypes and an intense PPIX fluorescence was observed. PDT of CDXs resulted in a disruption of tumor-feeding vessels and 52.4% of CDXs presented as regressive after PDT treatment, whereas control CDXs remained vital in all cases. Therefore, 5-ALA mediated PDD and PDT appear to be promising tools in defining sarcoma resection margins (PDD) and adjuvant treatment of the tumor bed (PDT).

BackgroundPhysical inactivity is a major contributor to the development and persistence of chronic diseases. Mobile health apps that foster physical activity have the potential to assist in behavior change. However, the quality of the mobile health apps available in app stores is hard to assess for making informed decisions by end users and health care providers. ObjectiveThis study aimed at systematically reviewing and analyzing the content and quality of physical activity apps available in the 2 major app stores (Google Play and App Store) by using the German version of the Mobile App Rating Scale (MARS-G). Moreover, the privacy and security measures were assessed. MethodsA web crawler was used to systematically search for apps promoting physical activity in the Google Play store and App Store. Two independent raters used the MARS-G to assess app quality. Further, app characteristics, content and functions, and privacy and security measures were assessed. The correlation between user star ratings and MARS was calculated. Exploratory regression analysis was conducted to determine relevant predictors for the overall quality of physical activity apps. ResultsOf the 2231 identified apps, 312 met the inclusion criteria. The results indicated that the overall quality was moderate (mean 3.60 [SD 0.59], range 1-4.75). The scores of the subscales, that is, information (mean 3.24 [SD 0.56], range 1.17-4.4), engagement (mean 3.19 [SD 0.82], range 1.2-5), aesthetics (mean 3.65 [SD 0.79], range 1-5), and functionality (mean 4.35 [SD 0.58], range 1.88-5) were obtained. An efficacy study could not be identified for any of the included apps. The features of data security and privacy were mainly not applied. Average user ratings showed significant small correlations with the MARS ratings (r=0.22, 95% CI 0.08-0.35; P

Nuclear spin hyperpolarization increases the sensitivity of magnetic resonance dramatically, enabling many new applications, including real-time metabolic imaging. Parahydrogen-based signal amplification by reversible exchange (SABRE) was employed to hyperpolarize [1-13C]pyruvate and demonstrate 13C imaging in situ at 120 µT, about twice Earth's magnetic field, with two different signal amplification by reversible exchange variants: SABRE in shield enables alignment transfer to heteronuclei (SABRE-SHEATH), where hyperpolarization is transferred from parahydrogen to [1-13C]pyruvate at a magnetic field below 1 µT, and low-irradiation generates high tesla (LIGHT-SABRE), where hyperpolarization was prepared at 120 µT, avoiding magnetic field cycling. The 3-dimensional images of a phantom were obtained using a superconducting quantum interference device (SQUID) based magnetic field detector with submillimeter resolution. These 13C images demonstrate the feasibility of low-field 13C metabolic magnetic resonance imaging (MRI) of 50 mM [1-13C]pyruvate hyperpolarized by parahydrogen in reversible exchange imaged at about twice Earth's magnetic field. Using thermal 13C polarization available at 120 µT, the same experiment would have taken about 300 billion years. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic hit the German education system unexpectedly and forced its universities to shift to Emergency Remote Teaching (ERT). The Data Integration Center (DIC) of the University Hospital Magdeburg and the Institute of Biometry and Medical Informatics (IBMI) has developed a concept based on existing structures that can be quickly implemented and used by the Medical Faculty at Otto von Guericke University. This manuscript focuses on the IT support for lecturers, which allows them to concentrate on teaching their lessons, although the authors are aware that this is only a small part of the entire subject. Additionally, there is a great awareness that ERT can never replace well-structured in-person classes.Concept: The key feature of the concept uses the well-working management system for all physical rooms of the university by designing a virtual video conference room for every physical room. This allows high interactivity for lectures and seminars while applying proven teaching methods. Additionally, a collaboration software system to document all lessons learned and a technical support team have been available for the teaching staff. Courses with a hands-on approach require more personal interaction than lectures. Therefore, the issues of practical trainings have not been solved with this concept, but been tackled by using questionnaires and minimizing contacts during attestations.Applied IT tools: The concept’s requirements were met by and .Discussion and Conclusion: The concept helped the lecturers to provide high-quality teaching for students at universities. Additionally, it allows for a dynamic response to new needs and problems. The concept will be reviewed as part of a higher concept and may support lecturers in the following semesters in hybrid meetings with real and virtual attendees.

Background: We aimed to investigate the potential effects of a 4-week motor–cognitive dual-task training on cognitive and motor function as well as exercise motivation in young, healthy, and active adults. Methods: A total of 26 participants (age 25 ± 2 years; 10 women) were randomly allocated to either the intervention group or a control group. The intervention group performed a motor–cognitive training (3×/week), while the participants of the control group received no intervention. Before and after the intervention period of 4 weeks, all participants underwent cognitive (d2-test, Trail Making Test) and motor (lower-body choice reaction test and time to stabilization test) assessments. Following each of the 12 workouts, self-reported assessments (rating of perceived exertion, enjoyment and pleasant anticipation of the next training session) were done. Analyses of covariances and 95% confidence intervals plotting for between group and time effects were performed. Results: Data from 24 participants were analysed. No pre- to post-intervention improvement nor a between-group difference regarding motor outcomes (choice-reaction: F = 0.5; time to stabilization test: F = 0.7; p > 0.05) occurred. No significant training-induced changes were found in the cognitive tests (D2: F = 0.02; Trail Making Test A: F = 0.24; Trail Making Test B: F = 0.002; p > 0.05). Both enjoyment and anticipation of the next workout were rated as high. Discussion: The neuro-motor training appears to have no significant effects on motor and cognitive function in healthy, young and physically active adults. This might be explained in part by the participants’ very high motor and cognitive abilities, the comparably low training intensity or the programme duration. The high degree of exercise enjoyment, however, may qualify the training as a facilitator to initiate and maintain regular physical activity. The moderate to vigorous intensity levels further point towards potential health-enhancing cardiorespiratory effects.

ASAP1 is a multi-domain adaptor protein that regulates cytoskeletal dynamics, receptor recycling and intracellular vesicle trafficking. Its expression is associated with poor prognosis for a variety of cancers, and promotes cell migration, invasion and metastasis. Little is known about its physiological role. In this study, we used mice with a gene-trap inactivated ASAP1 locus to study the functional role of ASAP1 in vivo, and found defects in tissues derived from mesenchymal progenitor cells. Loss of ASAP1 led to growth retardation and delayed ossification typified by enlarged hypertrophic zones in growth plates and disorganized chondro-osseous junctions. Furthermore, loss of ASAP1 led to delayed adipocyte development and reduced fat depot formation. Consistently, deletion of ASAP1 resulted in accelerated chondrogenic differentiation of mesenchymal cells in vitro, but suppressed osteo- and adipogenic differentiation. Mechanistically, we found that FAK/Src and PI3K/AKT signaling is compromised in Asap1GT/GT MEFs, leading to impaired adipogenic differentiation. Dysregulated FAK/Src and PI3K/AKT signaling is also associated with attenuated osteogenic differentiation. Together these observations suggest that ASAP1 plays a decisive role during the differentiation of mesenchymal progenitor cells.

Purpose: While recent studies described the role of IKZF1/3 proteins in multiple myeloma (MM) cells, few have highlighted the significance of IKZF1/3 expression in T-cells. In this study we examine the prognostic and predictive value of IKZF1/3 expression in T-cells in patients with MM stage III. Experimental design: We analysed the IKZF1/3 expression levels in T-cells from 45 MM stage I (MMI) and 50 newly diagnosed MM stage III (MMIII) patients, according to Durie-Salmon staging system, by flow cytometry to examine their prognostic and predictive value. We also combined in vivo observations with in vitro assays to determine the effect of IKZF1/3 expression on the T-cell immunophenotype and anti-tumour T-cell response in 162 MMIII patients. Results: We found that high IKZF3, but not IKZF1, expression in T-cells correlates with superior overall survival in MMIII patients treated with immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide). Moreover, we show that higher IKZF3 expression in T-cells inhibits myeloma-specific T-cell response in vitro and that the immunophenotype of patients with high IKZF3 expression shows features that are contrary to the changes induced by immunomodulatory drugs. Although we observed higher IKZF3 expression levels in T-cells from patients with MMIII compared to MMI, IKZF3 expression was unaffected by the tumour microenvironment. Conclusion: In conclusion, IKZF3 expression in T-cells is a predictive value for clinical outcome in MMIII patients treated with immunomodulatory drugs due to its profound modulation of T-cell functionality.

Purpose: Refractions based on the optimisation of single‐value wavefront‐derived metrics may help determine appropriate corrections for individuals with Down syndrome where clinical techniques fall short. This study compared dioptric differences between refractions obtained using standard clinical techniques and two metric‐optimised methods: visual Strehl ratio (VSX) and pupil fraction tessellated (PFSt), and investigated characteristics that may contribute to the differences between refraction types. Methods: Thirty adults with Down syndrome (age = 29 ± 10 years) participated. Three refractive corrections (VSX, PFSt and clinical) were determined and converted to vector notation (M, J0, J45) to calculate the dioptric difference between pairings of each type using a mixed model repeated measures approach. Linear correlations and multivariable regression were performed to examine the relationship between dioptric differences and the following participant characteristics: higher order root mean square (RMS) for a 4 mm pupil diameter, spherical equivalent refractive error and Vineland Adaptive Behavior Scales (a measure of developmental ability). Results: The least squares mean estimates (standard error) of the dioptric differences for each pairing were as follows: VSX versus PFSt = 0.51 D (0.11); VSX versus clinical = 1.19 D (0.11) and PFSt versus clinical = 1.04 D (0.11). There was a statistically significant difference in the dioptric differences between the clinical refraction and each of the metric‐optimised refractions (p < 0.001). Increased dioptric differences in refraction were correlated with increased higher order RMS (R = 0.64, p < 0.001 [VSX vs. clinical] and R = 0.47, p < 0.001 [PFSt vs. clinical]) as well as increased myopic spherical equivalent refractive error (R = 0.37, p = 0.004 [VSX vs. clinical] and R = 0.51, p < 0.001 [PFSt vs. clinical]). Conclusions: The observed differences in refraction demonstrate that a significant portion of the refractive uncertainty is related to increased higher order aberrations and myopic refractive error. Methodology surrounding clinical techniques and metric‐optimisation based on wavefront aberrometry may explain the difference in refractive endpoints. [ABSTRACT FROM AUTHOR]

Background: Amblyopia is associated with unbalanced suppression between the two eyes. Existing clinical measures of suppression, such as the Worth 4 Dot test, provide qualitative information about suppression but cannot precisely quantify it. The Synoptophore, a well-established instrument in binocular vision clinics, has historically been used to gauge suppression qualitatively as well but has the capability to quantify suppression. We extended the capability of the Synoptophore through the development of a systematic protocol of illumination manipulation to quantify suppression in amblyopia. Methods: Twenty-six previously treated adult amblyopes underwent our protocol on the Synoptophore to measure the illumination balance needed to obtain fusion responses. Separately, these same amblyopes were tested with Worth 4 Dot as it is classically performed in the United States, utilizing different test distances and room illuminations to qualify the suppression response. Results: Smaller, more central targets revealed larger magnitudes of suppression for both the Synoptophore and Worth 4 Dot tests (Synoptophore: χ25,26 = 25.538, p < 0.001; Worth 4 Dot: χ23,26 = 39.020, p < 0.001). There was a significant correlation between the two tests for depth of suppression measurements (rΤ > 0.345, p < 0.036), with more sensitivity measured by the Synoptophore, as suppression could be graded on a quantitative scale. Strabismic amblyopes demonstrated more suppression than non-strabismic amblyopes (z > 2.410, p < 0.016). Additionally, depth of suppression was correlated with interocular difference in both visual acuity (rΤ = 0.604, p < 0.001) and stereoacuity (rΤ = 0.488, p = 0.001). Conclusions: We extended the utility of the Synoptophore by measuring its illuminance outputs and developing a suppression testing protocol that compared favorably with Worth 4 Dot (clinic standard) while improving upon the latter through more sensitive quantification of suppression. [ABSTRACT FROM AUTHOR]

19F-based magnetic resonance is a powerful tool to overcome several difficulties of standard 1H MR. We present the syntheses and characterization (including cell viability and stability tests) of two Tm3+ complexes. Both complexes allow the detection of temperature (ΔCT = −0.2319 ppm K−1 and −0.2122 ppm K−1) without a reference compound. [ABSTRACT FROM AUTHOR]

Many fungal pathogens carry accessory regions in their genome, which are not required for vegetative fitness. Often, although not always, these regions occur as relatively small chromosomes in different species. Such mini chromosomes appear to be a typical feature of many filamentous plant pathogens. Since these regions often carry genes coding for effectors or toxin-producing enzymes, they may be directly related to virulence of the respective pathogen. In this review, we outline the situation of small accessory chromosomes in the genus Colletotrichum, which accounts for ecologically important plant diseases. We summarize which species carry accessory chromosomes, their gene content, and chromosomal makeup. We discuss the large variation in size and number even between different isolates of the same species, their potential roles in host range, and possible mechanisms for intra- and interspecies exchange of these interesting genetic elements.

The hemibiotrophic plant pathogen Colletotrichum higginsianum infects Brassicaceae and in combination with Arabidopsis thaliana, represents an important model system to investigate various ecologically important fungal pathogens and their infection strategies. After penetration of plant cells by appressoria, C. higginsianum establishes large biotrophic primary hyphae in the first infected cell. Shortly thereafter, a switch to necrotrophic growth occurs leading to the invasion of neighboring cells by secondary hyphae. In a forward genetic screen for virulence mutants by insertional mutagenesis, we identified mutants that penetrate the plant but show a defect in the passage from biotrophy to necrotrophy. Genome sequencing and pulsed-field gel electrophoresis revealed that two mutants were lacking chromosome 11, encoding potential pathogenicity genes. We established a chromosome loss assay to verify that strains lacking this small chromosome abort infection during biotrophy, while their ability to grow on artificial media was not affected. C. higginsianum harbors a second small chromosome, which can be lost without effects on virulence or growth on agar plates. Furthermore, we found that chromosome 11 is required to suppress Arabidopsis thaliana plant defense mechanisms dependent on tryptophan derived secondary metabolites.

Magnetic resonance imaging (MRI) at ultra-high fields (UHF), such as 7 T, provides an enhanced signal-to-noise ratio and has led to unprecedented high-resolution anatomic images and brain activation maps. Although a variety of radio frequency (RF) coil architectures have been developed for imaging at UHF conditions, they usually are specialized for small volumes of interests (VoI). So far, whole-body coil resonators are not available for commercial UHF human whole-body MRI systems. The goal of the present study was the development and validation of a transmit and receive system for large VoIs that operates at a 7 T human whole-body MRI system. A Metamaterial Ring Antenna System (MRAS) consisting of several ring antennas was developed, since it allows for the imaging of extended VoIs. Furthermore, the MRAS not only requires lower intensities of the irradiated RF energy, but also provides a more confined and focused injection of excitation energy on selected body parts. The MRAS consisted of several antennas with 50 cm inner diameter, 10 cm width and 0.5 cm depth. The position of the rings was freely adjustable. Conformal resonant right-/left-handed metamaterial was used for each ring antenna with two quadrature feeding ports for RF power. The system was successfully implemented and demonstrated with both a silicone oil and a water-NaCl-isopropanol phantom as well as in vivo by acquiring whole-body images of a crab-eating macaque. The potential for future neuroimaging applications was demonstrated by the acquired high-resolution anatomic images of the macaque's head. Phantom and in vivo measurements of crab-eating macaques provided high-resolution images with large VoIs up to 40 cm in xy-direction and 45 cm in z-direction. The results of this work demonstrate the feasibility of the MRAS system for UHF MRI as proof of principle. The MRAS shows a substantial potential for MR imaging of larger volumes at 7 T UHF. This new technique may provide new diagnostic potential in spatially extended pathologies such as searching for spread-out tumor metastases or monitoring systemic inflammatory processes.