Autonomous Materials Discovery Driven by Gaussian Process Regression with Inhomogeneous Measurement Noise and Anisotropic Kernels

A majority of experimental disciplines face the challenge of exploring large and high-dimensional parameter spaces in search of new scientific discoveries. Materials science is no exception; the wide variety of synthesis, processing, and environmental conditions that influence material properties gives rise to particularly vast parameter spaces. Recent advances have led to an increase in efficiency of materials discovery by increasingly automating the exploration processes. Methods for autonomous experimentation have become more sophisticated recently, allowing for multi-dimensional parameter spaces to be explored efficiently and with minimal human intervention, thereby liberating the scientists to focus on interpretations and big-picture decisions. Gaussian process regression (GPR) techniques have emerged as the method of choice for steering many classes of experiments. We have recently demonstrated the positive impact of GPR-driven decision-making algorithms on autonomously steering experiments at a synchrotron beamline. However, due to the complexity of the experiments, GPR often cannot be used in its most basic form, but rather has to be tuned to account for the special requirements of the experiments. Two requirements seem to be of particular importance, namely inhomogeneous measurement noise (input dependent or non-i.i.d.) and anisotropic kernel functions, which are the two concepts that we tackle in this paper. Our synthetic and experimental tests demonstrate the importance of both concepts for experiments in materials science and the benefits that result from including them in the autonomous decision-making process

DNA-directed nanofabrication of high-performance carbon nanotube field-effect transistors

生物自组装结构具有精细的三维形貌，其关键结构参数小于光刻等传统纳米加工手段的分辨率极限。利用自组装的生物分子为加工模板，已经实现了金属、碳基、氧化物等材料的形貌可控合成。然而，基于生物模板的电学器件，其性能往往远落后于通过蚀刻或薄膜方法制备的同类器件，并且缺乏长程取向规整性，制约了生物模板在高性能器件中的应用。针对上述挑战，我校化学化工学院朱志教授课题组与北京大学孙伟研究员课题组、清华大学唐建石研究员课题组、美国国家标准与技术研究院郑明博士合作，探索了生物-碳纳米管复合界面及大面积取向排列的调控新方法。北京大学孙伟研究员团队长期从事核酸引导的精准纳米组装研究，厦门大学朱志教授团队长期从事微纳加工及微流控研究，双方紧密合作，优势互补，联合清华大学和美国国家标准与技术研究院等多团队联合攻关完成该工作。共同第一作者厦门大学化学化工学院2011协同创新中心博士研究生陈雅鸿负责了碳纳米管组装及大面积阵列化工作，孙伟研究员和朱志教授为论文的共同通讯作者。Biofabricated semiconductor arrays exhibit smaller channel pitches than existing lithographic feasibility. However, the metal ions within biolattices and the submicrometer dimensions of typical biotemplates result in both poor transport performance and small array uniformity. Using DNA-templated parallel carbon nanotube (CNT) arrays as model systems, we developed a rinsing-after-fixing approach to improve the key transport performance metrics by more than a factor of 10 folds over previous biotemplated field-effect transistors. We also used spatially confined placement of assembled CNT arrays within polymethyl methacrylate cavities to demonstrate centimeter-scale alignment. At the interface of high-performance electronics and biomolecular self-assembly, current approaches may enable scalable biotemplated electronics sensitive to local biological environments.W.S.,M.Z., Y.C., K.W., and Z.Z. acknowledge the National Science Foundation of China (Grant No. 21875003, 21991134, and 61621061) and PKU for financial support. Y.C., C.Y., and Z.Z. acknowledge the National Science Foundation of China (Grant No. 21775128, 21435004, and 21974113) for financial support. J.K.S., J.A.F., and M.Z. acknowledge NIST internal fund. 该研究工作得到国家自然科学基金等资助

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion

Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. Here, we test the function of DAN, a BMP antagonist we detected by analysis of chick cranial mesoderm. Our analysis shows that, prior to neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells, in vivo and in vitro respectively. In vivo loss-of-function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Taken together, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with inhibition of BMP signaling

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 x 10(-13)) and African ancestries (rs2066702; P = 2.2 x 10(-9)). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.Peer reviewe

A Low Energy Route to DNA-Wrapped Carbon Nanotubes via Replacement of Bile Salt Surfactants

DNA-wrapped carbon nanotubes are a class of bionano hybrid molecules that have enabled carbon nanotube sorting, controlled assembly, and biosensing and bioimaging applications. The current method of synthesizing these hybrids via direct sonication of DNA/nanotube mixtures is time-consuming and not suitable for high-throughput synthesis and combinatorial sequence screening. Additionally, the direct sonication method does not make use of nanotubes presorted by extensively developed surfactant-based methods, is not effective for large diameter (>1 nm) tubes, and cannot maintain secondary and tertiary structural and functional domains present in certain DNA sequences. Here, we report a simple, quick, and robust process to produce DNA-wrapped carbon nanotube hybrids with nanotubes of broad diameter range and DNA of arbitrary sequence. This is accomplished by exchanging strong binding bile salt surfactant coating with DNA in methanol/water mixed solvent and subsequent precipitation with isopropyl alcohol. The exchange process can be completed within 10 min and converts over 90% nanotubes into the DNA wrapped form. Applying the exchange process to nanotubes presorted by surfactant-based methods, we show that the resulting DNA-wrapped carbon nanotubes can be further sorted to produce nanotubes with defined handedness, helicity, and endohedral filling. The exchange method greatly expands the structural and functional variety of DNA-wrapped carbon nanotubes and opens possibilities for DNA-directed assembly of structurally sorted nanotubes and high-throughput screening of properties that are controlled by the wrapping DNA sequences

Chromatic Aberration Short-Wave Infrared Spectroscopy: Nanoparticle Spectra without a Spectrometer

A new method is described for measuring the short-wave infrared (SWIR) emission wavelengths of numerous individual nanoparticles without using a dedicated spectrometer. Microscope objectives designed for use at visible wavelengths often show severe axial chromatic aberration in the SWIR. This makes coplanar objects emitting at different SWIR wavelengths appear to focus at different depths. After this aberration has been calibrated for a particular objective lens, the depth at which an emissive nanoparticle appears brightest and best focused can be used to deduce its peak emission wavelength. The method is demonstrated using a dilute, structurally polydisperse sample of single-walled carbon nanotubes deposited onto a microscope slide. Discrete emission centers in this sample have different peak wavelengths corresponding to specific nanotube structural species. A set of images was recorded at stepped focus settings and analyzed to find the sharpest focus depth of each nanotube. The chromatic aberration calibration curve converted these depths into peak emission wavelengths with a spectral resolution better than 3 nm, allowing identification of each nanotube’s structure. Chromatic aberration spectroscopy is a practical tool for using existing microscopic equipment to extract significant spectral information on coplanar nanoparticle samples that emit or scatter light

Differentiating Left- and Right-Handed Carbon Nanotubes by DNA

New structural characteristics emerge when solid-state crystals are constructed in lower dimensions. This is exemplified by single-wall carbon nanotubes, which exhibit a degree of freedom in handedness and a multitude of helicities that give rise to three distinct types of electronic structures: metals, quasi-metals, and semiconductors. Here we report the use of intrinsically chiral single-stranded DNA to achieve simultaneous handedness and helicity control for all three types of nanotubes. We apply polymer aqueous two-phase systems to select special DNA-wrapped carbon nanotubes, each of which we argue must have an ordered DNA structure that binds to a nanotube of defined handedness and helicity and resembles a well-folded biomacromolecule with innate stereoselectivity. We have screened over 300 short single-stranded DNA sequences with palindrome symmetry, leading to the selection of more than 20 distinct carbon nanotube structures that have defined helicity and handedness and cover the entire chiral angle range and all three electronic types. The mechanism of handedness selection is illustrated by a DNA sequence that adopts two distinct folds on a pair of (6,5) nanotube enantiomers, rendering them large differences in fluorescence intensity and chemical reactivity. This result establishes a first example of functionally distinguishable left- and right-handed carbon nanotubes. Taken together, our work demonstrates highly efficient enantiomer differentiation by DNA and offers a first comprehensive solution to achieve simultaneous handedness and helicity control for all three electronic types of carbon nanotubes

Variance Spectroscopy

Spectroscopic analysis and study of nanoparticle samples is often hampered by structural diversity that presents a complex superposition of spectral signatures. By probing the spectra of small volumes within dilute samples, we can expose statistical variations in composition to obtain information unavailable from bulk spectroscopy. This new approach is demonstrated using fluorescence spectra of unsorted single-walled carbon nanotube samples to deduce structure-specific abundances and emissive efficiencies. Furthermore, correlations between intensity variations at different wavelengths provide two-dimensional covariance maps that isolate the spectra of homogeneous subpopulations. Covariance analysis is also a sensitive probe of particle aggregation. It shows that well-dispersed nanotube samples can spontaneously form loose aggregates of a type not previously recognized. Variance spectroscopy is a simple and practical technique that should find application in many nanoparticle studies