Biomedical imaging is a driver of scientific discovery and a core component of medical care and is being stimulated by the field of deep learning. While semantic segmentation algorithms enable image ...analysis and quantification in many applications, the design of respective specialized solutions is non-trivial and highly dependent on dataset properties and hardware conditions. We developed nnU-Net, a deep learning-based segmentation method that automatically configures itself, including preprocessing, network architecture, training and post-processing for any new task. The key design choices in this process are modeled as a set of fixed parameters, interdependent rules and empirical decisions. Without manual intervention, nnU-Net surpasses most existing approaches, including highly specialized solutions on 23 public datasets used in international biomedical segmentation competitions. We make nnU-Net publicly available as an out-of-the-box tool, rendering state-of-the-art segmentation accessible to a broad audience by requiring neither expert knowledge nor computing resources beyond standard network training.
The Central Asian Orogenic Belt (CAOB) evolved through complex closure of the Paleo-Asian Ocean from the Neoproterozoic to the late Phanerozoic. This caused the Chinese cratons to collide with ...Eurasia and led to the formation of the world's largest Phanerozoic orogenic belt. Ocean closure commenced in the west and was completed in the east near Changchun. Closure of the Paleo-Asian Ocean in NE China was along the Solonker–Xar Moron–Changchun–Yanji suture and this was likely completed in the Late Permian, although associated activity continued into the Triassic. There was an overlap in the latest Permian–Early Triassic between terminal activity associated with Paleo-Asian Ocean closure and the onset of tectonism associated with subduction of the Paleo-Pacific plate. This switch in geodynamic setting occurred at ~260–250Ma, and is reflected by a relaxing of north–south directed compression and the onset of east–west directed processes related to Paleo-Pacific subduction. By the Early Jurassic, events associated with the westward advance of the Paleo-Pacific plate dominated, leading to extensive development of I-type granites as far inland as the Great Xing'an Range. From ~140Ma, the Paleo-Pacific plate retreated eastward, resulting in an extensional setting in the Early Cretaceous, the effects of which were enhanced by regional thinning of the lithosphere, commonly attributed to delamination. Throughout this period, the eastern Asian margin was tectonically complex. The north–south oriented Jiamusi–Khanka(–Bureya) block was rifted away from the eastern margin of the CAOB in the Late Triassic, but was then re-united in the Jurassic by westward-advancing subduction that affected both the western and eastern margins of the block. Accretionary complexes continued to evolve in the Cretaceous along the whole eastern margin of Asia, with final accretion of the Nadanhada Terrane (part of the Sikhote–Alin accretionary terrane) with the CAOB at ~130Ma, followed by the emplacement of S-type granites.
•Paleo-Asian Ocean closed diachronously along Solonker suture.•Closure completed in late Permian•Paleo-Pacific subduction affected eastern CAOB.•Precambrian rocks rare in CAOB of NE China•Chinese terranes originated in Siberia
Real-time monitoring of changes in cells or cell products released from malignant lesions into the blood has opened new diagnostic avenues (“liquid biopsy”). In this issue of Cancer Cell, Best and ...colleagues describe that tumor-associated blood platelets provide specific information on the location and molecular composition of the primary tumor.
Real-time monitoring of changes in cells or cell products released from malignant lesions into the blood has opened new diagnostic avenues (“liquid biopsy”). In this issue of Cancer Cell, Best and colleagues describe that tumor-associated blood platelets provide specific information on the location and molecular composition of the primary tumor.
A combination of a convolutional neural network, which belongs to the deep learning research field, and support vector machines is presented as an efficient automatic target recognition system. ...Additional training methods that incorporate prior knowledge to the classifier and further improve its robustness against imaging errors and target variations are also presented. These methods generate artificial training data by elastic distortion and affine transformations that represent typical examples of image errors, like a changing range scale dependent on the depression angle or an incorrectly estimated aspect angle. With these examples presented to the classifier during the training, the system should become invariant against these variations and thus more robust. For the classification, the spotlight synthetic aperture radar images of the moving and stationary target acquisition and recognition database are used. Results are shown for the ten class database with a forced decision classification as well as with rejection class.
Abstract
We explore the possibility of testing the quantum nature of the gravitational field with an ensemble of ultra-cold atoms. The use of many microscopic particles may circumvent some of the ...experimental obstacles encountered in recent proposals involving a pair of particles with mesoscopic mass. We employ multi-parameter estimation techniques, including the quantum and classical Fisher information to provide a criteria for the observability of the quantum effects, and compare to other recently proposed schemes. Crucially, we find that by preparing the appropriate initial state, interactions mediated via a quantum-valued gravitational field provide a signature that is distinct from classical gravitational interactions. We find that a definitive demonstration of the quantum gravitational interaction is not possible with current experimental capabilities, due to uncertainty in the residual electromagnetic interactions between the atoms. However, it may be possible with significant improvements to current experimental techniques.
Global hydrographic and air–sea freshwater flux datasets are used to investigate ocean salinity changes over 1950–2010 in relation to surface freshwater flux. On multi-decadal timescales, surface ...salinity increases (decreases) in evaporation (precipitation) dominated regions, the Atlantic–Pacific salinity contrast increases, and the upper thermocline salinity maximum increases while the salinity minimum of intermediate waters decreases. Potential trends in E–P are examined for 1950–2010 (using two reanalyses) and 1979–2010 (using four reanalyses and two blended products). Large differences in the 1950–2010 E–P trend patterns are evident in several regions, particularly the North Atlantic. For 1979–2010 some coherency in the spatial change patterns is evident but there is still a large spread in trend magnitude and sign between the six E–P products. However, a robust pattern of increased E–P in the southern hemisphere subtropical gyres is seen in all products. There is also some evidence in the tropical Pacific for a link between the spatial change patterns of salinity and E–P associated with ENSO. The water cycle amplification rate over specific regions is subsequently inferred from the observed 3-D salinity change field using a salt conservation equation in variable isopycnal volumes, implicitly accounting for the migration of isopycnal surfaces. Inferred global changes of E–P over 1950–2010 amount to an increase of 1 ± 0.6 % in net evaporation across the subtropics and an increase of 4.2 ± 2 % in net precipitation across subpolar latitudes. Amplification rates are approximately doubled over 1979–2010, consistent with accelerated broad-scale warming but also coincident with much improved salinity sampling over the latter period.
The Catalogue of Somatic Mutations in Cancer (COSMIC) Cancer Gene Census (CGC) is an expert-curated description of the genes driving human cancer that is used as a standard in cancer genetics across ...basic research, medical reporting and pharmaceutical development. After a major expansion and complete re-evaluation, the 2018 CGC describes in detail the effect of 719 cancer-driving genes. The recent expansion includes functional and mechanistic descriptions of how each gene contributes to disease generation in terms of the key cancer hallmarks and the impact of mutations on gene and protein function. These functional characteristics depict the extraordinary complexity of cancer biology and suggest multiple cancer-related functions for many genes, which are often highly tissue-dependent or tumour stage-dependent. The 2018 CGC encompasses a second tier, describing an expanding list of genes (currently 145) from more recent cancer studies that show supportive but less detailed indications of a role in cancer.
Recent developments in third-gen long read sequencing and diploid-aware assemblers have resulted in the rapid release of numerous reference-quality assemblies for diploid genomes. However, assembly ...of highly heterozygous genomes is still problematic when regional heterogeneity is so high that haplotype homology is not recognised during assembly. This results in regional duplication rather than consolidation into allelic variants and can cause issues with downstream analysis, for example variant discovery, or haplotype reconstruction using the diploid assembly with unpaired allelic contigs.
A new pipeline-Purge Haplotigs-was developed specifically for third-gen sequencing-based assemblies to automate the reassignment of allelic contigs, and to assist in the manual curation of genome assemblies. The pipeline uses a draft haplotype-fused assembly or a diploid assembly, read alignments, and repeat annotations to identify allelic variants in the primary assembly. The pipeline was tested on a simulated dataset and on four recent diploid (phased) de novo assemblies from third-generation long-read sequencing, and compared with a similar tool. After processing with Purge Haplotigs, haploid assemblies were less duplicated with minimal impact on genome completeness, and diploid assemblies had more pairings of allelic contigs.
Purge Haplotigs improves the haploid and diploid representations of third-gen sequencing based genome assemblies by identifying and reassigning allelic contigs. The implementation is fast and scales well with large genomes, and it is less likely to over-purge repetitive or paralogous elements compared to alignment-only based methods. The software is available at https://bitbucket.org/mroachawri/purge_haplotigs under a permissive MIT licence.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metronidazole, a nitroimidazole, remains a front-line choice for treatment of infections related to inflammatory disorders of the gastrointestinal tract including colitis linked to Clostridium ...difficile. Despite >60 years of research, the metabolism of metronidazole and associated cytotoxicity is not definitively characterized. Nitroimidazoles are prodrugs that are reductively activated (the nitro group is reduced) under low oxygen tension, leading to imidazole fragmentation and cytotoxicity. It remains unclear if nitroimidazole reduction (activation) contributes to the cytotoxicity profile, or whether subsequent fragmentation of the imidazole ring and formed metabolites alone mediate cytotoxicity. A molecular mechanism underpinning high level (>256 mg/L) bacterial resistance to metronidazole also remains elusive. Considering the widespread use of metronidazole and other nitroimidazoles, this review was undertaken to emphasize the structure-cytotoxicity profile of the numerous metabolites of metronidazole in human and murine models and to examine conflicting reports regarding metabolite-DNA interactions. An alternative hypothesis, that DNA synthesis and repair of existing DNA is indirectly inhibited by metronidazole is proposed. Prokaryotic metabolism of metronidazole is detailed to discuss new resistance mechanisms. Additionally, the review contextualizes the history and current use of metronidazole, rates of metronidazole resistance including metronidazole MDR as well as the biosynthesis of azomycin, the natural precursor of metronidazole. Changes in the gastrointestinal microbiome and the host after metronidazole administration are also reviewed. Finally, novel nitroimidazoles and new antibiotic strategies are discussed.
This article reviews the development of the immune response through neonatal, infant and adult life, including pregnancy, ending with the decline in old age. A picture emerges of a child born with an ...immature, innate and adaptive immune system, which matures and acquires memory as he or she grows. It then goes into decline in old age. These changes are considered alongside the risks of different types of infection, autoimmune disease and malignancy.