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Noise transfer for unsupervised domain adaptation of retinal OCT images.
Optical coherence tomography (OCT) imaging from different camera devices causes challenging domain shifts and can cause a severe drop in accuracy for machine learning models. In this work, we introduce a minimal noise adaptation method based on a singular value decomposition (SVDNA) to overcome the domain gap between target domains from three different device manufacturers in retinal OCT imaging. Our method utilizes the difference in noise structure to successfully bridge the domain gap between different OCT devices and transfer the style from unlabeled target domain images to source images for which manual annotations are available. We demonstrate how this method, despite its simplicity, compares or even outperforms state-of-the-art unsupervised domain adaptation methods for semantic segmentation on a public OCT dataset. SVDNA can be integrated with just a few lines of code into the augmentation pipeline of any network which is in contrast to many state-of-the-art domain adaptation methods which often need to change the underlying model architecture or train a separate style transfer model. The full code implementation for SVDNA will be made available at https://github.com/ValentinKoch/SVDNA
<em>ULYSSES</em>: An efficient and easy to use semiempirical library for C+.
We introduce ULYSSES, a user-friendly and robust C++ library for semiempirical quantum chemical calculations. In its current version, ULYSSES is equipped with a large set of different semiempirical models, most of which are based on the Neglect of Diatomic Differential Overlap (NDDO) approximation. Empirical corrections for dispersion and hydrogen bonding are available for most methods, so that higher quality is achieved in the calculation of energies of nonbonded complexes. The library is furthermore equipped with geometry optimization, as well as modules for calculating molecular properties of general interest. Ideal gas thermodynamics is available and allows single structure as well as conformer (multistructure) averaged properties to be calculated. We offer the possibility to use several vibrational partition functions according to the nature of interactions being studied: for covalent systems, the traditional harmonic oscillator approximation is available; for nonbonded complexes, we systematically extended the partition function proposed by Grimme for all thermodynamic functions. The library is also capable of running Born-Oppenheimer molecular dynamics
Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model.
Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells (ADSPCs) in peripheral nerve recovery. Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs. This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned (2% oxygen for 72 hours) autologous ADSPCs (n = 9). This treatment mode was compared with three others: fibrin conduit seeded with ADSPCs cultivated under normoxic conditions (n = 9); non-cell-carrying conduit (n = 9); and nerve autograft only (n = 9). A 16-week follow-up included functional testing (sciatic functional index and static sciatic index) as well as postmortem muscle mass analyses and morphometric nerve evaluations (histology, g-ratio, axon density, and diameter). At 8 weeks, the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups, indicating faster functional regeneration. Furthermore, histologic evaluation showed significantly increased axon outgrowth/branching, axon density, remyelination, and a reduced relative connective tissue area. Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts. Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice
Response of C-cycling enzymes in soil aggregate-size fractions to slurry application over a one year period in two contrasting soil types.
The distribution of enzymatic activity in soil aggregates is a key determinant in the turnover of organic matter. This study aimed to address how the application of a carbon-rich slurry influences extracellular enzymatic activity within aggregate-size fractions over a one-year period. Twenty-four pots of either a loam or sand soil, sown with Lolium perenne, were kept slurry-free (control), or were treated with a high dry matter slurry. Pots were sampled after 31, 137 and 361 days (n = 4). Soils were physically fractionated to obtain four aggregate-size fractions: ≥2 mm, ≥250 μm, ≤250 μm and ≤53 μm with enzyme assays of seven C-cycling enzymes conducted on each, and the potential extracellular enzymatic activity (pEEA) calculated. The strongest response in individual pEEA was seen after 137 days, where the pEEA of at least one C-cycling enzyme was significantly higher in the slurry treatment in each of the four aggregate-size fractions in both soil types (all at least P ≤ 0.05). Additionally, nearly all seven C-cycling enzymes were significantly higher in the slurry treatment compared to the control in the ≤53 μm fraction (all at least P ≤ 0.05) in both. No significant increase in pEEA was seen in the slurry treatment in any aggregate-size fraction after 361 days in the loam soil (all P > 0.05), and this was also largely the case for the sand soil. The results of this study clearly indicate that pEEA within aggregate-size fractions was strongly influenced by slurry application in the initial months, though this was not sustained
Dietary digestible carbohydrates are associated with higher prevalence of asthma in humans and with aggravated lung allergic inflammation in mice.
BACKGROUND: Dietary carbohydrates and fats are intrinsically correlated within the habitual diet. We aimed to disentangle the associations of starch and sucrose from those of fat, in relation to allergic sensitization, asthma and rhinoconjuctivitis prevalence in humans, and to investigate underlying mechanisms using murine models. METHODS: Epidemiological data from participants of two German birth cohorts (age 15) were used in logistic regression analyses testing cross-sectional associations of starch and sucrose (and their main dietary sources) with aeroallergen sensitization, asthma and rhinoconjunctivitis, adjusting for correlated fats (saturated, monounsaturated, omega-6 and omega-3 polyunsaturated) and other covariates. For mechanistic insights, murine models of aeroallergen-induced allergic airway inflammation (AAI) fed with a low-fat-high-sucrose or -high-starch versus a high-fat diet were used to characterize and quantify disease development. Metabolic and physiologic parameters were used to track outcomes of dietary interventions and cellular and molecular responses to monitor the development of AAI. Oxidative stress biomarkers were measured in murine sera or lung homogenates. RESULTS: We demonstrate a direct association of dietary sucrose with asthma prevalence in males, while starch was associated with higher asthma prevalence in females. In mice, high-carbohydrate feeding, despite scant metabolic effects, aggravated AAI compared to high-fat in both sexes, as displayed by humoral response, mucus hypersecretion, lung inflammatory cell infiltration and TH 2-TH 17 profiles. Compared to high-fat, high-carbohydrate intake was associated with increased pulmonary oxidative stress, signals of metabolic switch to glycolysis and decreased systemic anti-oxidative capacity. CONCLUSION: High consumption of digestible carbohydrates is associated with increased prevalence of asthma in humans and aggravated lung allergic inflammation in mice, involving oxidative stress-related mechanisms
Biallelic TLR4 deficiency in humans.
BACKGROUND: Toll-like receptors (TLRs) mediate functions for host defense and inflammatory responses. TLR4 recognizes LPS, a component of gram-negative bacteria as well as host-derived endogenous ligands such as S100A8 and S100A9 proteins. OBJECTIVE: We sought to report phenotype and cellular function of individuals with complete TLR4 deficiency. METHODS: We performed genome sequencing and investigated exome and genome sequencing databases. Cellular responses were studied on primary monocytes, macrophages, and neutrophils, as well as cell lines using flow cytometry, reporter, and cytokine assays. RESULTS: We identified 2 individuals in a family of Qatari origin carrying a homozygous stop codon variant p.Q188X in TLR4 presenting with a variable phenotype (asymptomatic and inflammatory bowel disease consistent with severe perianal Crohn disease). A third individual with homozygous p.Y794X was identified in a population database. In contrast to hypomorphic polymorphisms p.D299G and p.T399I, the variants p.Q188X and p.Y794X completely abrogated LPS-induced cytokine responses whereas TLR2 response was normal. TLR4 deficiency causes a neutrophil CD62L shedding defect, whereas antimicrobial activity toward intracellular Salmonella was intact. CONCLUSIONS: Biallelic TLR4 deficiency in humans causes an inborn error of immunity in responding to LPS. This complements the spectrum of known primary immunodeficiencies, in particular myeloid differentiation primary response 88 (MYD88) or the IL-1 receptor-associated kinase 4 (IRAK4) deficiency that are downstream of TLR4 and TLR2 signaling
Reactive oxygen species (ROS) in mycorrhizal fungi and symbiotic interactions with plants.
The interaction of plant roots with mycorrhizal fungi leads to the formation of a novel structure, the ectomycorrhiza. Ectomycorrhizal symbioses benefit both organisms by mutual nutrient exchange and improve the host´s stress resilience. Here, we review the roles of reactive oxygen species and antioxidative systems in the fungal partner and the host plant for the establishment of the symbiosis and for the induction of local and systemic mycorrhizal resistance. Ectomycorrhizal symbioses can be formed with different fungal species each equipped with a distinct set of extracellular oxidative enzymes. While one function of the extracellular enzymes is the access to recalcitrant nutrient sources, some examples suggest neofunctionalization to enable intraradical colonization. The colonization also involves small secreted proteins, NADPH oxidases, H2O2 production, and affects the plant catalase, superoxide dismutase and peroxidase-based defenses. The fungal antioxidative defense is mainly based on glutathione and thioredoxin-based systems but its role in host colonization is largely unexplored. Among signals likely involved in systemic responses are jasmonates and salicylic acid in the plant, and volatile organic compounds released by the fungus. An emerging player with a role in plant-fungal interactions is nitric oxide. Higher stress tolerance of the mycorrhizal fungal species generally confers higher stress tolerance to the host and can vary among different isolates of the same fungal species. This review emphasizes that many puzzle parts are present, but that a complete picture has not yet emerged. We discuss further studies required to increase our understanding of the inter-kingdom dialog of both organisms
A macrophage-hepatocyte glucocorticoid receptor axis coordinates fasting ketogenesis.
Fasting metabolism and immunity are tightly linked; however, it is largely unknown how immune cells contribute to metabolic homeostasis during fasting in healthy subjects. Here, we combined cell-type-resolved genomics and computational approaches to map crosstalk between hepatocytes and liver macrophages during fasting. We identified the glucocorticoid receptor (GR) as a key driver of fasting-induced reprogramming of the macrophage secretome including fasting-suppressed cytokines and showed that lack of macrophage GR impaired induction of ketogenesis during fasting as well as endotoxemia. Mechanistically, macrophage GR suppressed the expression of tumor necrosis factor (TNF) and promoted nuclear translocation of hepatocyte GR to activate a fat oxidation/ketogenesis-related gene program, cooperatively induced by GR and peroxisome proliferator-activated receptor alpha (PPARα) in hepatocytes. Together, our results demonstrate how resident liver macrophages directly influence ketogenesis in hepatocytes, thereby also outlining a strategy by which the immune system can set the metabolic tone during inflammatory disease and infection
Luminescence dosimetry for evaluation of the external exposure in Metlino, upper Techa River valley, Southern Urals, Russia: Analysis of new results.
Luminescence dosimetry was applied in the former settlement of Metlino, Southern Urals, Russia as part of a full-scale study to validate the Techa River Dosimetry System (TRDS) 2016 for the upper Techa River region. The village, which was evacuated in 1956, was located 7 km downstream of the release point of liquid radioactive waste by the Mayak plutonium facility. Several brick samples were taken from north-eastern and south-eastern walls of the granary, facing the former Techa river shoreline and floodplain. Samples were all taken at the same height and measured at different depths into the brick. For the majority of brick samples, good Optically Stimulated Luminescence properties of the quartz grains were observed. In some cases, however, strong levels of sensitization and/or signal recuperation were encountered which necessitated adjustment in the measurement protocols. Anthropogenic doses in bricks varied from 1.5 to 6.6 Gy and the horizontal profiles along both walls showed significant variation, which is explained on a qualitative basis. A dose depth profile is observed for selected samples, which is different from the dose depth profile measured and simulated for samples from the north-western wall of the granary in previous studies. This is qualitatively explained by the differences in source configuration
Post-reclamation microbial diversity and functions in hexachlorocyclohexane (HCH) contaminated soil in relation to spontaneous HCH tolerant vegetation.
The toxicity, volatility and persistence of the obsolete organochlorine pesticide hexachlorocyclohexane (HCH), makes reclamation of contaminated areas a priority for the health and welfare of neighboring human communities. Microbial diversity and functions and their relation to spontaneous vegetation in post-excavation situations, are essential indicators to consider in bioaugmentation or microbe-assisted phytoremediation strategies at field scale. Our study aimed to evaluate the effects of long-term HCH contamination on soil and plant-associated microbial communities, and whether contaminated soil has the potential to act as a bacterial inoculum in post-excavation bioremediation strategies. To scrutinize the role of vegetation, the potential nitrogen fixation of free-living and symbiotic diazotrophs of the legume Lotus tenuis was assessed as a measure of nutrient cycling functions in soil under HCH contamination. Potential nitrogen fixation was generally not affected by HCH, with the exception of lower nifH gene counts in excavated contaminated rhizospheres, most probably a short-term HCH effect on early bacterial succession in this compartment. HCH shaped microbial communities in long-term contaminated bulk soil, where we identified possible HCH tolerants such as Sphingomonas and Altererythrobacter. In L. tenuis rhizosphere, microbial community composition was additionally influenced by plant growth stage. Sphingobium and Massilia were the bacterial genera characteristic for HCH contaminated rhizospheres. Long-term HCH contamination negatively affected L. tenuis growth and development. However, root-associated bacterial community composition was driven solely by plant age, with negligible HCH effect. Results showed that L. tenuis acquired possible HCH tolerant bacteria such as the Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium clade, Sphingomonas, Massilia or Pantoea which could simultaneously offer plant growth promoting (PGP) benefits for the host. Finally, we identified an inoculum with possibly HCH tolerant, PGP bacteria transferred from the contaminated bulk soil to L. tenuis roots through the rhizosphere compartment, consisting of Mesorhizobium loti, Neorhizobium galegae, Novosphingobium lindaniclasticum, Pantoea agglomerans and Lysobacter bugurensis