•A comprehensive grand-challenge is organized for abdominal organ segmentation.•The results obtained from top models among 1500 participants are analyzed in detail.•The submissions are evaluated as 5 ...tasks including cross-modality and multi-modal segmentation.•Deep models reach almost inter-expert accuracy for CT segmentations but not for MR.•Cross-modality performance and multiple submissions causing peeking remain main pitfalls.
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Segmentation of abdominal organs has been a comprehensive, yet unresolved, research field for many years. In the last decade, intensive developments in deep learning (DL) introduced new state-of-the-art segmentation systems. Despite outperforming the overall accuracy of existing systems, the effects of DL model properties and parameters on the performance are hard to interpret. This makes comparative analysis a necessary tool towards interpretable studies and systems. Moreover, the performance of DL for emerging learning approaches such as cross-modality and multi-modal semantic segmentation tasks has been rarely discussed. In order to expand the knowledge on these topics, the CHAOS – Combined (CT-MR) Healthy Abdominal Organ Segmentation challenge was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI), 2019, in Venice, Italy. Abdominal organ segmentation from routine acquisitions plays an important role in several clinical applications, such as pre-surgical planning or morphological and volumetric follow-ups for various diseases. These applications require a certain level of performance on a diverse set of metrics such as maximum symmetric surface distance (MSSD) to determine surgical error-margin or overlap errors for tracking size and shape differences. Previous abdomen related challenges are mainly focused on tumor/lesion detection and/or classification with a single modality. Conversely, CHAOS provides both abdominal CT and MR data from healthy subjects for single and multiple abdominal organ segmentation. Five different but complementary tasks were designed to analyze the capabilities of participating approaches from multiple perspectives. The results were investigated thoroughly, compared with manual annotations and interactive methods. The analysis shows that the performance of DL models for single modality (CT / MR) can show reliable volumetric analysis performance (DICE: 0.98 ± 0.00 / 0.95 ± 0.01), but the best MSSD performance remains limited (21.89 ± 13.94 / 20.85 ± 10.63 mm). The performances of participating models decrease dramatically for cross-modality tasks both for the liver (DICE: 0.88 ± 0.15 MSSD: 36.33 ± 21.97 mm). Despite contrary examples on different applications, multi-tasking DL models designed to segment all organs are observed to perform worse compared to organ-specific ones (performance drop around 5%). Nevertheless, some of the successful models show better performance with their multi-organ versions. We conclude that the exploration of those pros and cons in both single vs multi-organ and cross-modality segmentations is poised to have an impact on further research for developing effective algorithms that would support real-world clinical applications. Finally, having more than 1500 participants and receiving more than 550 submissions, another important contribution of this study is the analysis on shortcomings of challenge organizations such as the effects of multiple submissions and peeking phenomenon.
The fundamental concept of superfluidity gives rise to fascinating effects and collective behaviour such as vortex creation and second sound. Using quantum gases in optical lattices, superfluids can ...be realized over a wide range of tunable parameters, with a continuous connection to the regime of strong correlation. However, for full experimental access and a comprehensive comparison with condensed-matter systems, there is a need for new detection techniques to probe their essential physics. Here we report on a comprehensive study of superfluids in optical lattices by Bragg spectroscopy. We present fully momentum-resolved measurements of the band structure and associated interaction effects at several lattice depths. In addition, we directly study the composition of excitations and observe strong indications for Bogoliubov backscattering. Our measurements demonstrate the applicability and limits of the Bogoliubov theory to describe excitation properties of superfluids in periodic potentials and should pave the way for detailed studies of strongly correlated phases. PUBLICATION ABSTRACT
Senescence is a cellular state that is involved in aging-associated diseases but may also prohibit the development of pre-cancerous lesions and tumor growth. Senescent cells are actively secreting ...chemo- and cytokines, and this senescence-associated secretory phenotype (SASP) can contribute to both early anti-tumorigenic and long-term pro-tumorigenic effects. Recently, complex mechanisms of cellular senescence and their influence on cellular processes have been defined in more detail and, therefore, facilitate translational development of targeted therapies. In this review, we aim to discuss major molecular pathways involved in cellular senescence and potential therapeutic strategies, with a specific focus on myeloid malignancies.
, a member of the Ustilaginaceae family, is a promising host for the production of several metabolites including itaconic acid. This dicarboxylate has great potential as a bio-based building block in ...the polymer industry, and is of special interest for pharmaceutical applications. Several itaconate overproducing
strains have been generated by metabolic and morphology engineering. This yielded stabilized unicellular morphology through
deletion, reduction of by-product formation through deletion of genes responsible for itaconate oxidation and (glyco)lipid production, and the overexpression of the regulator of the itaconate cluster
and the mitochondrial tricarboxylate transporter encoded by
from
. In this study, itaconate production was further optimized by consolidating these different optimizations into one strain. The combined modifications resulted in itaconic acid production at theoretical maximal yield, which was achieved under biotechnologically relevant fed-batch fermentations with continuous feed.
Currently, Aspergillus terreus is used for the industrial production of itaconic acid. Although, alternative feedstock use in fermentations is crucial for cost-efficient and sustainable itaconic acid ...production, their utilisation with A. terreus most often requires expensive pretreatment. Ustilaginacea are robust alternatives for itaconic acid production, evading the challenges, including the pretreatment of crude feedstocks regarding reduction of manganese concentration, that A. terreus poses. In this study, five different Ustilago strains were screened for their growth and production of itaconic acid on defined media. The most promising strains were then used to find a suitable alternative feedstock, based on the local food industry. U. cynodontis ITA Max pH, a highly engineered production strain, was selected to determine the biologically available nitrogen concentration in thick juice and molasses. Based on these findings, thick juice was chosen as feedstock to ensure the necessary nitrogen limitation for itaconic acid production. U. cynodontis ITA Max pH was further characterised regarding osmotolerance and product inhibition and a successful scale-up to a 2 L stirred tank reactor was accomplished. A titer of 106.4 g.sub.itaconic acid/L with a theoretical yield of 0.50 g.sub.itaconic acid/g.sub.sucrose and a space-time yield of 0.72 g.sub.itaconic acid/L/h was reached. This study demonstrates the utilisation of alternative feedstocks to produce ITA with Ustilaginaceae, without drawbacks in either titer or yield, compared to glucose fermentations.
Industrial by-products accrue in most agricultural or food-related production processes, but additional value chains have already been established for many of them. Crude glycerol has a 60% lower ...market value than commercial glucose, as large quantities are produced in the biodiesel industry, but its valorisation is still underutilized. Due to its high carbon content and the natural ability of many microorganisms to metabolise it, microbial upcycling is a suitable option for this waste product.
In this work, the use of crude glycerol for the production of the value-added compound itaconate is demonstrated using the smut fungus Ustilago maydis. Starting with a highly engineered strain, itaconate production from an industrial glycerol waste stream was quickly established on a small scale, and the resulting yields were already competitive with processes using commercial sugars. Adaptive laboratory evolution resulted in an evolved strain with a 72% increased growth rate on glycerol. In the subsequent development and optimisation of a fed-batch process on a 1.5-2 L scale, the use of molasses, a side stream of sugar beet processing, eliminated the need for other expensive media components such as nitrogen or vitamins for biomass growth. The optimised process was scaled up to 150 L, achieving an overall titre of 72 g L
, a yield of 0.34 g g
, and a productivity of 0.54 g L
h
.
Pilot-scale itaconate production from the complementary waste streams molasses and glycerol has been successfully established. In addition to achieving competitive performance indicators, the proposed dual feedstock strategy offers lower process costs and carbon footprint for the production of bio-based itaconate.
Background and Purpose
Transient receptor potential melastatin 3 (TRPM3) is a non‐selective cation channel that plays a pivotal role in the peripheral nervous system as a transducer of painful heat ...signals. Alternative splicing gives rise to several TRPM3 variants. The functional consequences of these splice isoforms are poorly understood. Here, the pharmacological properties of TRPM3 variants arising from alternative splicing in the pore‐forming region were compared.
Experimental Approach
Calcium microfluorimetry and patch clamp recordings were used to compare the properties of heterologously expressed TRPM3α1 (long pore variant) and TRPM3α2–α6 (short pore variants). Furthermore, site‐directed mutagenesis was done to investigate the influence of the length of the pore loop on the channel function.
Key Results
All short pore loop TRPM3α variants (TRPM3α2–α6) were activated by the neurosteroid pregnenolone sulphate (PS) and by nifedipine, whereas the long pore loop variant TRPM3α1 was insensitive to either compound. In contrast, TRPM3α1 was robustly activated by clotrimazole, a compound that does not directly activate the short pore variants but potentiates their responses to PS. Clotrimazole‐activated TRPM3α1 currents were largely insensitive to established TRPM3α2 antagonists and were only partially inhibited upon activation of the μ opioid receptor. Finally, by creating a set of mutant channels with pore loops of intermediate length, we showed that the length of the pore loop dictates differential channel activation by PS and clotrimazole.
Conclusion and Implications
Alternative splicing in the pore‐forming region of TRPM3 defines the channel's pharmacological properties, which depend critically on the length of the pore‐forming loop.
LINKED ARTICLES
This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc
Bio-based bulk chemicals such as carboxylic acids continue to struggle to compete with their fossil counterparts on an economic basis. One possibility to improve the economic feasibility is the use ...of crude substrates in biorefineries. However, impurities in these substrates pose challenges in fermentation and purification, requiring interdisciplinary research. This work demonstrates a holistic approach to biorefinery process development, using itaconic acid production on thick juice based on sugar beets with
sp. as an example. A conceptual process design with data from artificially prepared solutions and literature data from fermentation on glucose guides the simultaneous development of the upstream and downstream processes up to a 100 L scale. Techno-economic analysis reveals substrate consumption as the main constituent of production costs and therefore, the product yield is the driver of process economics. Aligning pH-adjusting agents in the fermentation and the downstream process is a central lever for product recovery. Experiments show that fermentation can be transferred from glucose to thick juice by changing the feeding profile. In downstream processing, an additional decolorization step is necessary to remove impurities accompanying the crude substrate. Moreover, we observe an increased use of pH-adjusting agents compared to process simulations.
Highly charged ions are a well-known tool for the nanostructuring of surfaces. We report on the thickness dependence of nanostructures produced by single 260 keV Xe38+ ions on ultrathin poly(methyl ...methacrylate) (PMMA) films (1 nm to 60 nm) deposited onto Si substrates. The nanostructures induced by slow highly charged ions are rimless craters with a diameter of around 15 nm, which are roughly independent of the thickness of the films down to layers of about 2 nm. The crater depth and thus the overall crater volume are, however, thickness-dependent, decreasing in size in films thinner than ~25 nm. Our findings indicate that although the potential energy of the highly charged ions is the predominant source of deposited energy, the depth of the excited material contributing to crater formation is much larger than the neutralization depth of the ions, which occurs in the first nanometer of the solid at the projectile velocity employed here. This suggests synergism between kinetic and potential-driven processes in nanostructure formation in PMMA.
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