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Currently indexing 70,482 bioRxiv papers from 307,800 authors.

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Results 341 through 360 out of 430


341: Interpretable multimodal deep learning for real-time pan-tissue pan-disease pathology search on social media

Andrew J. Schaumberg, Wendy Juarez et al.

1 tweets (posted 21 Aug 2018) pathology

Background Pathologists are responsible for rapidly providing a diagnosis on critical health issues, from infection to malignancy. Challenging cases benefit from additional opinions of pathologist colleagues. In addition to on-site colleagues, there is an active worldwide community of pathologists on social media for complementary opinions. Such access to pathologists worldwide has the capacity to (i) improve diagnostic accuracy and (ii) generate broader consensus on next steps in patient care. Methods and findings From Twitter we curate 13,626 images from 6,351 tweets from 25 pathologists from 13 countries. We supplement the Twitter data with 113,161 images from 1,074,484 PubMed articles. We develop machine learning and deep learning models to (i) accurately identify histopathology stains, (ii) discriminate between tissues, and (iii) differentiate disease states. For deep learning, we derive novel regularization and activation functions for set representations related to set cardinality and the Heaviside step function. Area Under Receiver Operating Characteristic is 0.805-0.996 for these tasks. We repurpose the disease classifier to search for similar disease states given an image and clinical covariates. We report precision@k=1 = 0.701±0.003 (chance 0.397±0.004, mean±stdev). The classifiers find texture and tissue are important clinico-visual features of disease. For search, deep features and cell nuclei features are less important. We implement a social media bot (@pathobot on Twitter) to use the trained classifiers to aid pathologists in obtaining real-time feedback on challenging cases. The bot activates when mentioned in a social media post containing pathology text and images. The bot generates quantitative predictions of disease state (normal/artifact/ infection/injury/nontumor, pre-neoplastic/benign/low-grade-malignant-potential, or malignant) and provides a ranked list of similar cases across social media and PubMed. Conclusions Our project has become a globally distributed expert system that facilitates pathological diagnosis and brings expertise to underserved regions or hospitals with less expertise in a particular disease. This is the first pan-tissue pan-disease (i.e. from infections to malignancy) method for prediction and search on social media, and the first pathology study prospectively tested in public on social media. We expect our project to cultivate a more connected world of physicians and improve patient care worldwide. Why was this study done? What did the researchers do and find? What do these findings mean?


342: Most cancers carry a substantial deleterious load due to Hill-Robertson interference

Susanne Tilk, Christina Curtis et al.

1 tweets (posted 14 Sep 2019) evolutionary biology

Introduction Cancer genomes exhibit surprisingly weak signatures of negative selection[1][1],[2][2]. This may be because tumors evolve either under very weak selective pressures (‘weak selection’) or under conditions that prevent the elimination of many deleterious passenger mutations (‘poor efficacy of selection’)xs. Rationale The weak selection model argues that the majority of genes are only important for multicellular function. The poor efficacy of selection model argues, in contrast, that genome-wide linkage in ca...


343: The photoreceptor UVR8 mediates the perception of both UV-B and UV-A wavelengths up to 350 nm of sunlight with responsivity moderated by cryptochromes

Neha Rai, Andrew O'Hara et al.

1 tweets (posted 22 Jan 2020) plant biology

The photoreceptors UV RESISTANCE LOCUS 8 (UVR8) and CRYPTOCHROMES 1 and 2 (CRYs) play major roles in the perception of UVB (280-315 nm) and UVA/blue radiation (315-500 nm), respectively. However, it is poorly understood how they function in sunlight. The roles of UVR8 and CRYs were assessed in a factorial experiment with Arabidopsis thaliana wild-type and photoreceptor mutants exposed to sunlight for 6 h or 12 h under five types of filters with cut-offs in UV and blue-light regions. Transcriptome-wide responses triggere...


344: Live-cell imaging of early events following pollen perception in self-incompatible Arabidopsis thaliana

Frédérique Rozier, Lucie Riglet et al.

1 tweets (posted 08 Sep 2019) plant biology

Early events occurring at the surface of the female organ are critical for plant reproduction, especially in species with a dry stigma. Following landing on the stigmatic papilla cells, the pollen hydrates and germinates a tube, which penetrates the cell wall and grows towards the ovules to convey the male gametes to the embryo sac. In self-incompatible (SI) species within the Brassicaceae, these processes are blocked when the stigma encounters an incompatible pollen. Here, based on the generation of SI-Arabidopsis line...


345: Characterising open chromatin identifies novel cis-regulatory elements important for paraxial mesoderm formation and axis extension

Gi Fay Mok, Leighton Folkes et al.

1 tweets (posted 20 Jan 2020) developmental biology

The development of multicellular organisms is exquisitely regulated through differential gene activity, which governs cell differentiation programs. However, many details of spatiotemporal control of gene regulation are still poorly understood. We used the accessibility of chick embryos to examine genome-wide signatures characterizing the progressive differentiation of paraxial mesoderm along the head-to-tail axis. Paraxial mesoderm becomes organized into repetitive units, termed somites, the hallmark of the segmented v...


346: Rapid detection of identity-by-descent tracts for mega-scale datasets

Ruhollah Shemirani, Gillian M. Belbin et al.

1 tweets (posted 08 Sep 2019) genomics

The ability to identify segments of genomes identical-by-descent (IBD) is a part of standard workflows in both statistical and population genetics. However, traditional methods for finding local IBD across all pairs of individuals scale poorly leading to a lack of adoption in very large-scale datasets. Here, we present iLASH, IBD by LocAlity-Sensitive Hashing, an algorithm based on similarity detection techniques that shows equal or improved accuracy in simulations compared to the current leading method and speeds up an...


347: Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments

Verena Henrichs, Lenka Grycova et al.

1 tweets (posted 22 Jan 2020) cell biology

Intracellular trafficking of organelles, driven by kinesin-1 stepping along microtubules, underpins essential processes including neuronal activity. In absence of other proteins on the microtubule surface, kinesin-1 performs micron-long runs. Under protein crowding conditions, however, kinesin-1 motility is drastically impeded. It is thus unclear how kinesin-1 acts as an efficient transporter in crowded intracellular environments. Here, we demonstrate that TRAK1 (Milton), an adaptor protein essential for mitochondrial t...


348: Genome-wide discovery of lupus genetic risk variant allelic regulatory activity

Xiaoming Lu, Xiaoting Chen et al.

1 tweets (posted 20 Jan 2020) genomics

Genome-wide association studies of Systemic Lupus Erythematosus (SLE) nominate 3,073 genetic variants at 91 risk loci. To systematically screen these variants for allelic transcriptional enhancer activity, we constructed a massively parallel reporter assay (MPRA) library comprising 12,396 DNA oligonucleotides containing the genomic context around every allele of each SLE variant. Transfection into EBV-infected B cells revealed 482 variants with enhancer activity, with 51 variants showing genotype-dependent (allelic) enh...


349: Land use impacts poison frog chemical defenses through changes in leaf litter ant communities

Nora A Moskowitz, Barbara Dorritie et al.

1 tweets (posted 30 Aug 2019) ecology

Much of the worlds biodiversity is held within tropical rainforests, which are increasingly fragmented by agricultural practices. In these threatened landscapes, there are many organisms that acquire chemical defenses from their diet and are therefore intimately connected with their local food webs. Poison frogs (Family Dendrobatidae) are one such example, as they acquire alkaloid-based chemical defenses from their diet of leaf litter ants and mites. It is currently unknown how habitat fragmentation impacts chemical def...


350: Large scale active-learning-guided exploration to maximize cell-free production

Olivier Borkowski, Mathilde Koch et al.

1 tweets (posted 30 Aug 2019) synthetic biology

Lysate-based cell-free systems have become a major platform to study gene expression but batch-to-batch variation makes protein production difficult to predict. Here we describe an active learning approach to explore a combinatorial space of ~4,000,000 cell-free compositions, maximizing protein production and identifying critical parameters involved in cell-free productivity. We also provide a one-step-method to achieve high quality predictions for protein production using minimal experimental effort regardless of the l...



Michael Skocik, John Collins et al.

1 tweets (posted 03 Oct 2016) neuroscience

Machine learning is a powerful set of techniques that has enhanced the abilities of neuroscientists to interpret information collected through EEG, fMRI, MEG, and PET data. With these new techniques come new dangers of overfitting that are not well understood by the neuroscience community. In this article, we use Support Vector Machine (SVM) classifiers, and genetic algorithms to demonstrate the ease by which overfitting can occur, despite the use of cross validation. We demonstrate that comparable and non-generalizable...


352: Ion-networks: a sparse data format capturing full data integrity of data independent acquisition mass spectrometry

Sander Willems, S. Daled et al.

1 tweets (posted 21 Aug 2019) bioinformatics

Data-independent acquisition (DIA) mass spectrometry (MS) has introduced deter-ministic, periodic and simultaneous acquisition of all fragment ions. Despite the chimeric side-effects associated with this unprecedented data integrity, DIA data analysis approaches still use conventional spectra and extracted ion chromatograms (XICs) that represent individual precursors and fragments. Here, we introduce ion-networks, an alternative data format wherein nodes correspond to reproducible fragment ions from multiple runs and ed...


353: Ultrasound imaging links soleus muscle neuromechanics and energetics during human walking with elastic ankle exoskeletons

Richard W Nuckols, Taylor J.M. Dick et al.

1 tweets (posted 20 Jan 2020) bioengineering

Unpowered exoskeletons with springs in parallel to human plantar flexor muscle-tendons can reduce the metabolic cost of walking. We used ultrasound imaging to look 'under the skin' and measure how exoskeleton stiffness alters soleus muscle contractile dynamics and shapes the user's metabolic rate during walking. Eleven participants (4F, 7M; age: 27.7 ± 3.3 years) walked on a treadmill at 1.25 m s-1 and 0% grade with elastic ankle exoskeletons (rotational stiffness: 0-250 Nm rad-1) in one training and two testing days. M...


354: BiofilmQ, a software tool for quantitative image analysis of microbial biofilm communities

Raimo Hartmann, Hannah Jeckel et al.

1 tweets (posted 15 Aug 2019) microbiology

Biofilms are now considered to be the most abundant form of microbial life on Earth, playing critical roles in biogeochemical cycles, agriculture, and health care. Phenotypic and genotypic variations in biofilms generally occur in three-dimensional space and time, and biofilms are therefore often investigated using microscopy. However, the quantitative analysis of microscopy images presents a key obstacle in phenotyping biofilm communities and single-cell heterogeneity inside biofilms. Here, we present BiofilmQ, a compr...


355: KAT2-mediated acetylation switches the mode of PALB2 chromatin association to safeguard genome integrity

Marjorie Fournier, Jean-Yves Bleuyard et al.

1 tweets (posted 15 Aug 2019) cell biology

The tumour suppressor PALB2 stimulates error-free repair of DNA breaks, whilst its steady-state chromatin association protects active genes from genotoxic stress. Here, we report that the lysine acetyltransferases 2A and 2B (KAT2A/B), commonly known to promote transcriptional activation, acetylate the PALB2 chromatin association motif (ChAM), providing a dynamic regulatory mechanism for PALB2. ChAM acetylation within a cluster of seven lysine residues (7K), detected in the chromatin-enriched fraction in undamaged cells,...


356: Six-state amino acid recoding is not an effective strategy to offset the effects of compositional heterogeneity and saturation in phylogenetic analyses

Alexandra M. Hernandez, Joseph F Ryan

1 tweets (posted 08 Aug 2019) evolutionary biology

Six-state amino acid recoding strategies are commonly applied to combat the effects of compositional heterogeneity and substitution saturation in phylogenetic analyses. While these methods have been endorsed from a theoretical perspective, their performance has never been extensively tested. Here, we test the effectiveness of 6-state recoding approaches by comparing the performance of analyses on recoded and non-recoded datasets that have been simulated under gradients of compositional heterogeneity or saturation. In al...


357: Nucleic acid amplification by a transparent graphene Visual-PCR chip and a disposable thermocycler

Guozhi Zhu, Miao Qiao

1 tweets (posted 07 Aug 2019) molecular biology

Polymerase chain reaction (PCR) is a method widely used to amplify trace amount of nucleic acids. It needs a process of thermocycling (repeated alternation of temperature). Traditional thermocycler relies on bulk size of metal block to achieve thermocycling, which results in high cost and the lack of portability. Here, a PCR chip made of graphene Transparent Conductive Films (TCFs) was employed. The thermocycling of the chip was fulfilled by a temperature programed microcontroller and a cooling fan under a low driving v...


358: EnhancerP-2L: A Gene regulatory site identification tool for DNA enhancer region using CREs motifs

Ahmad Hassan Butt, Salem Alkhalaf et al.

1 tweets (posted 20 Jan 2020) bioinformatics

Enhancers are DNA fragments that do not encode RNA molecules and proteins, but they act critically in the production of RNAs and proteins by controlling gene expression. Prediction of enhancers and their strength plays significant role in regulating gene expression. Prediction of enhancer regions, in sequences of DNA, is considered a difficult task due to the fact that they are not close to the target gene, have less common motifs and are mostly tissue/cell specific. In recent past, several bioinformatics tools were dev...


359: A defect in thymic tolerance causes T cell-mediated autoimmunity in a murine model of COPA syndrome

Zimu Deng, Christopher S Law et al.

1 tweets (posted 22 Jan 2020) immunology

COPA syndrome is a recently described Mendelian autoimmune disorder caused by missense mutations in the Coatomer protein complex subunit alpha (COPA) gene. Patients with COPA syndrome develop arthritis and lung disease that presents as pulmonary hemorrhage or interstitial lung disease (ILD). Immunosuppressive medications can stabilize the disease, but many patients develop progressive pulmonary fibrosis that requires life-saving measures such as lung transplantation. Because very little is understood about the pathogene...


360: Fronto-striatal oscillations predict vocal output in bats

Kristin Weineck, Francisco García-Rosales et al.

1 tweets (posted 05 Aug 2019) neuroscience

The ability to vocalize is ubiquitous in vertebrates, but neural networks leading to vocalization production remain poorly understood. Here we performed simultaneous, large scale, neuronal recordings in the frontal cortex and dorsal striatum (caudate nucleus) during the production of echolocation and non-echolocation calls in bats. This approach allows to assess the general aspects underlying vocalization production in mammals and the unique evolutionary adaptations of bat echolocation. Our findings show that distinct i...