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Currently indexing 57,441 bioRxiv papers from 264,501 authors.

Most downloaded bioRxiv papers, since beginning of last month

Results 1 through 20 out of 56052


1: An integrated brain-machine interface platform with thousands of channels

Elon Musk, Neuralink

65,513 downloads (posted 17 Jul 2019) neuroscience

Brain-machine interfaces (BMIs) hold promise for the restoration of sensory and motor function and the treatment of neurological disorders, but clinical BMIs have not yet been widely adopted, in part because modest channel counts have limited their potential. In this white paper, we describe Neuralink’s first steps toward a scalable high-bandwidth BMI system. We have built arrays of small and flexible electrode “threads”, with as many as 3,072 electrodes per array distributed across 96 threads. We have also built a neurosurgical robot capable of inserting six threads (192 electrodes) per minute. Each thread can be individually inserted into the brain with micron precision for avoidance of surface vasculature and targeting specific brain regions. The electrode array is packaged into a small implantable device that contains custom chips for low-power on-board amplification and digitization: the package for 3,072 channels occupies less than (23 × 18.5 × 2) mm3. A single USB-C cable provides full-bandwidth data streaming from the device, recording from all channels simultaneously. This system has achieved a spiking yield of up to 70% in chronically implanted electrodes. Neuralink’s approach to BMI has unprecedented packaging density and scalability in a clinically relevant package.


2: Population genomics of the Viking world

Ashot Margaryan, Daniel John Lawson et al.

7,089 downloads (posted 17 Jul 2019) genetics

The Viking maritime expansion from Scandinavia (Denmark, Norway, and Sweden) marks one of the swiftest and most far-flung cultural transformations in global history. During this time (c. 750 to 1050 CE), the Vikings reached most of western Eurasia, Greenland, and North America, and left a cultural legacy that persists till today. To understand the genetic structure and influence of the Viking expansion, we sequenced the genomes of 442 ancient humans from across Europe and Greenland ranging from the Bronze Age (c. 2400 B...


3: Background free tracking of single RNA in living cells using catalytically inactive CasE

Chunyu Han, Feng Gao et al.

6,515 downloads (posted 13 May 2019) molecular biology

RNAs have important and diverse functions. Visualizing an isolated RNA in living cells provide us essential information of its roles. By now, there are two kinds of live RNA imaging systems invented, one is the MS2 system and the other is the Cas13a system. In this study, we show that when fused with split-Fp, CasE can be engineered into a live RNA tracking tool.


4: Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming

Yuancheng Lu, Anitha Krishnan et al.

4,967 downloads (posted 31 Jul 2019) molecular biology

Ageing is a degenerative process leading to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise, which disrupts youthful gene expression patterns that are required for cells to function optimally and recover from damage. Changes to DNA methylation patterns over time form the basis of an 'ageing clock', but whether old individuals retain information to reset the clock and, if so, whether this would improve tissue function is not known. Of all the tissues in the body, the centr...


5: The "sewing machine" for minimally invasive neural recording

Timothy L Hanson, Camilo A Diaz-Botia et al.

4,224 downloads (posted 14 Mar 2019) neuroscience

We present a system for scalable and customizable recording and stimulation of neural activity. In large animals and humans, the current benchmark for high spatial and temporal resolution neural interfaces are fixed arrays of wire or silicon electrodes inserted into the parenchyma of the brain. However, probes that are large and stiff enough to penetrate the brain have been shown to cause acute and chronic damage and inflammation, which limits their longevity, stability, and yield. One approach to this problem is to sep...


6: Automated Reconstruction of a Serial-Section EM Drosophila Brain with Flood-Filling Networks and Local Realignment

Peter H Li, Larry F. Lindsey et al.

3,933 downloads (posted 11 Apr 2019) neuroscience

Reconstruction of neural circuitry at single-synapse resolution is an attractive target for improving understanding of the nervous system in health and disease. Serial section transmission electron microscopy (ssTEM) is among the most prolific imaging methods employed in pursuit of such reconstructions. We demonstrate how Flood-Filling Networks (FFNs) can be used to computationally segment a forty-teravoxel whole-brain Drosophila ssTEM volume. To compensate for data irregularities and imperfect global alignment, FFNs we...


7: 7 Tesla MRI of the ex vivo human brain at 100 micron resolution

Brian L Edlow, Azma Mareyam et al.

3,451 downloads (posted 31 May 2019) neuroscience

We present an ultra-high resolution magnetic resonance imaging (MRI) dataset of an ex vivo human brain specimen. The brain specimen was donated by a 58-year-old woman who had no history of neurological disease and died of non-neurological causes. After fixation in 10% formalin, the specimen was imaged on a 7 Tesla MRI scanner at 100 micron isotropic resolution using a custom-built 31-channel receive array coil. Single-echo multi-flip Fast Low-Angle SHot (FLASH) data were acquired over 100 hours of scan time (25 hours pe...


8: A Critique of Pure Learning: What Artificial Neural Networks can Learn from Animal Brains

Anthony M Zador

2,958 downloads (posted 20 Mar 2019) neuroscience

Over the last decade, artificial neural networks (ANNs), have undergone a revolution, catalyzed in large part by better tools for supervised learning. However, training such networks requires enormous data sets of labeled examples, whereas young animals (including humans) typically learn with few or no labeled examples. This stark contrast with biological learning has led many in the ANN community posit that instead of supervised paradigms, animals must rely instead primarily on unsupervised learning, leading the search...


9: Toxicity of JUUL Fluids and Aerosols Correlates Strongly with Nicotine and Some Flavor Chemical Concentrations

Esther Omaiye, Kevin J McWhirter et al.

2,907 downloads (posted 09 Dec 2018) pharmacology and toxicology

While JUUL electronic cigarettes (ECs) have captured the majority of the EC market with a large fraction of their sales going to adolescents, little is known about their cytotoxicity and potential effects on health. The purpose of this study was to determine flavor chemical and nicotine concentrations in the eight currently marketed pre-filled JUUL EC cartridges (pods) and to evaluate the cytotoxicity of the different variants (e.g., Cool Mint and Creme Brulee) using in vitro assays. Nicotine and flavor chemicals were a...


10: Supercentenarians and the oldest-old are concentrated into regions with no birth certificates and short lifespans

Saul Justin Newman

2,867 downloads (posted 16 Jul 2019) developmental biology

The observation of individuals attaining remarkable ages, and their concentration into geographic sub-regions or 'blue zones', has generated considerable scientific interest. Proposed drivers of remarkable longevity include high vegetable intake, strong social connections, and genetic markers. Here, we reveal new predictors of remarkable longevity and 'supercentenarian' status. In the United States, supercentenarian status is predicted by the absence of vital registration. The state-specific introduction of birth certif...


11: Homologous recombination-based genome editing by clade F AAVs is inefficient in the absence of a targeted DNA break

Geoffrey L. Rogers, Hsu-Yu Chen et al.

2,852 downloads (posted 21 Jul 2019) synthetic biology

Adeno-associated virus (AAV) vectors are frequently used as donor templates for genome editing by homologous recombination. Although modification rates are typically under 1%, they are greatly enhanced by targeted double-stranded DNA breaks (DSBs). A recent report described clade F AAVs mediating high-efficiency homologous recombination-based editing in the absence of DSBs. The clade F vectors included AAV9 and a series isolated from human hematopoietic stem/progenitor cells (HSPCs). We evaluated these vectors by packag...


12: Report of Partial findings from the National Toxicology Program Carcinogenesis Studies of Cell Phone Radiofrequency Radiation in Hsd: Sprague Dawley® SD rats (Whole Body Exposure)

Michael Wyde, Mark Cesta et al.

2,840 downloads (posted 26 May 2016) cancer biology

The U.S. National Toxicology Program (NTP) has carried out extensive rodent toxicology and carcinogenesis studies of radiofrequency radiation (RFR) at frequencies and modulations used in the U.S. telecommunications industry. This report presents partial findings from these studies. The occurrences of two tumor types in male Harlan Sprague Dawley rats exposed to RFR, malignant gliomas in the brain and schwannomas of the heart, were considered of particular interest and are the subject of this report. The findings in this...


13: Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase associated stress responses

Ciara H O'Flanagan, Kieran R Campbell et al.

2,722 downloads (posted 27 Jun 2019) genomics

Background: Single-cell RNA sequencing (scRNAseq) is a powerful tool for studying complex biological systems, such as tumour heterogeneity and tissue microenvironments. However, the sources of technical and biological variation in primary solid tumour tissues and patient-derived mouse xenografts for scRNAseq, are not well understood. Here, we used low temperature (6C) protease and collagenase (37C) to identify the transcriptional signatures associated with tissue dissociation across a diverse scRNAseq dataset comprising...


14: The Genetic History of France

Aude SAINT PIERRE, Joanna Giemza et al.

2,516 downloads (posted 23 Jul 2019) genetics

The study of the genetic structure of different countries within Europe has provided significant insights into their demographic history and their actual stratification. Although France occupies a particular location at the end of the European peninsula and at the crossroads of migration routes, few population genetic studies have been conducted so far with genome-wide data. In this study, we analyzed SNP-chip genetic data from 2 184 individuals born in France who were enrolled in two independent population cohorts. Usi...


15: A guide to performing Polygenic Risk Score analyses

Shing Wan Choi, Timothy Mak et al.

2,511 downloads (posted 14 Sep 2018) genomics

The application of polygenic risk scores (PRS) has become routine in genetic epidemiological studies. Among a range of applications, PRS are commonly used to assess shared aetiology among different phenotypes and to evaluate the predictive power of genetic data, while they are also now being exploited as part of study design, in which experiments are performed on individuals, or their biological samples (eg. tissues, cells), at the tails of the PRS distribution and contrasted. As GWAS sample sizes increase and PRS becom...


16: Comprehensive integration of single cell data

Tim Stuart, Andrew Butler et al.

2,336 downloads (posted 02 Nov 2018) genomics

Single cell transcriptomics (scRNA-seq) has transformed our ability to discover and annotate cell types and states, but deep biological understanding requires more than a taxonomic listing of clusters. As new methods arise to measure distinct cellular modalities, including high-dimensional immunophenotypes, chromatin accessibility, and spatial positioning, a key analytical challenge is to integrate these datasets into a harmonized atlas that can be used to better understand cellular identity and function. Here, we devel...


17: Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression

Christoph Hafemeister, Rahul Satija

2,222 downloads (posted 14 Mar 2019) genomics

Single-cell RNA-seq (scRNA-seq) data exhibits significant cell-to-cell variation due to technical factors, including the number of molecules detected in each cell, which can confound biological heterogeneity with technical effects. To address this, we present a modeling framework for the normalization and variance stabilization of molecular count data from scRNA-seq experiments. We propose that the Pearson residuals from 'regularized negative binomial regression', where cellular sequencing depth is utilized as a covaria...


18: A 6-nm ultra-photostable DNA Fluorocube for fluorescence imaging

Stefan Niekamp, Nico Stuurman et al.

2,182 downloads (posted 27 Jul 2019) biophysics

Photobleaching limits extended imaging of fluorescent biological samples. Here, we developed DNA origami-based Fluorocubes that are similar in size to the green fluorescent protein (GFP), have single-point attachment to proteins, have a 50-fold higher photobleaching lifetime and emit 40-fold more photons than single organic dyes. We demonstrate that DNA Fluorocubes provide outstanding tools for single-molecule imaging, allowing the tracking of single motor proteins for >800 steps with nanometer precision.


19: Mapping Vector Field of Single Cells

Xiaojie Qiu, Yan Zhang et al.

2,147 downloads (posted 09 Jul 2019) systems biology

Understanding how gene expression in single cells progress over time is vital for revealing the mechanisms governing cell fate transitions. RNA velocity, which infers immediate changes in gene expression by comparing levels of new (unspliced) versus mature (spliced) transcripts (La Manno et al. 2018), represents an important advance to these efforts. A key question remaining is whether it is possible to predict the most probable cell state backward or forward over arbitrary time-scales. To this end, we introduce an incl...


20: The Genomic Formation of South and Central Asia

Vagheesh M Narasimhan, Nick J Patterson et al.

2,116 downloads (posted 31 Mar 2018) genomics

The genetic formation of Central and South Asian populations has been unclear because of an absence of ancient DNA. To address this gap, we generated genome-wide data from 362 ancient individuals, including the first from eastern Iran, Turan (Uzbekistan, Turkmenistan, and Tajikistan), Bronze Age Kazakhstan, and South Asia. Our data reveal a complex set of genetic sources that ultimately combined to form the ancestry of South Asians today. We document a southward spread of genetic ancestry from the Eurasian Steppe, corre...