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1.
Nature ; 620(7972): 47-60, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532811

RESUMO

Artificial intelligence (AI) is being increasingly integrated into scientific discovery to augment and accelerate research, helping scientists to generate hypotheses, design experiments, collect and interpret large datasets, and gain insights that might not have been possible using traditional scientific methods alone. Here we examine breakthroughs over the past decade that include self-supervised learning, which allows models to be trained on vast amounts of unlabelled data, and geometric deep learning, which leverages knowledge about the structure of scientific data to enhance model accuracy and efficiency. Generative AI methods can create designs, such as small-molecule drugs and proteins, by analysing diverse data modalities, including images and sequences. We discuss how these methods can help scientists throughout the scientific process and the central issues that remain despite such advances. Both developers and users of AI toolsneed a better understanding of when such approaches need improvement, and challenges posed by poor data quality and stewardship remain. These issues cut across scientific disciplines and require developing foundational algorithmic approaches that can contribute to scientific understanding or acquire it autonomously, making them critical areas of focus for AI innovation.


Assuntos
Inteligência Artificial , Projetos de Pesquisa , Inteligência Artificial/normas , Inteligência Artificial/tendências , Conjuntos de Dados como Assunto , Aprendizado Profundo , Projetos de Pesquisa/normas , Projetos de Pesquisa/tendências , Aprendizado de Máquina não Supervisionado
2.
Immunology ; 172(1): 109-126, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38316548

RESUMO

Dendritic cells (DCs) are the most significant antigen presenting cells of the immune system, critical for the activation of naïve T cells. The pathways controlling DC development, maturation, and effector function therefore require precise regulation to allow for an effective induction of adaptive immune response. MYSM1 is a chromatin binding deubiquitinase (DUB) and an activator of gene expression via its catalytic activity for monoubiquitinated histone H2A (H2A-K119ub), which is a highly abundant repressive epigenetic mark. MYSM1 is an important regulator of haematopoiesis in mouse and human, and a systemic constitutive loss of Mysm1 in mice results in a depletion of many haematopoietic progenitors, including DC precursors, with the downstream loss of most DC lineage cells. However, the roles of MYSM1 at the later checkpoints in DC development, maturation, activation, and effector function at present remain unknown. In the current work, using a range of novel mouse models (Mysm1flCreERT2, Mysm1flCD11c-cre, Mysm1DN), we further the understanding of MYSM1 functions in the DC lineage: assessing the requirement for MYSM1 in DC development independently of other complex developmental phenotypes, exploring its role at the later checkpoints in DC maintenance and activation in response to microbial stimulation, and testing the requirement for the DUB catalytic activity of MYSM1 in these processes. Surprisingly, we demonstrate that MYSM1 expression and catalytic activity in DCs are dispensable for the maintenance of DC numbers in vivo or for DC activation in response to microbial stimulation. In contrast, MYSM1 acts via its DUB catalytic activity specifically in haematopoietic progenitors to allow normal DC lineage development, and its loss results not only in a severe DC depletion but also in the production of functionally altered DCs, with a dysregulation of many housekeeping transcriptional programs and significantly altered responses to microbial stimulation.


Assuntos
Transativadores , Proteases Específicas de Ubiquitina , Animais , Humanos , Camundongos , Diferenciação Celular , Cromatina/genética , Células Dendríticas/metabolismo , Endopeptidases/genética , Endopeptidases/metabolismo , Histonas/metabolismo , Camundongos Knockout , Transativadores/genética , Transativadores/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
4.
BMC Biol ; 21(1): 134, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280593

RESUMO

BACKGROUND: Sapria himalayana (Rafflesiaceae) is an endoparasitic plant characterized by a greatly reduced vegetative body and giant flowers; however, the mechanisms underlying its special lifestyle and greatly altered plant form remain unknown. To illustrate the evolution and adaptation of S. himalayasna, we report its de novo assembled genome and key insights into the molecular basis of its floral development, flowering time, fatty acid biosynthesis, and defense responses. RESULTS: The genome of S. himalayana is ~ 1.92 Gb with 13,670 protein-coding genes, indicating remarkable gene loss (~ 54%), especially genes involved in photosynthesis, plant body, nutrients, and defense response. Genes specifying floral organ identity and controlling organ size were identified in S. himalayana and Rafflesia cantleyi, and showed analogous spatiotemporal expression patterns in both plant species. Although the plastid genome had been lost, plastids likely biosynthesize essential fatty acids and amino acids (aromatic amino acids and lysine). A set of credible and functional horizontal gene transfer (HGT) events (involving genes and mRNAs) were identified in the nuclear and mitochondrial genomes of S. himalayana, most of which were under purifying selection. Convergent HGTs in Cuscuta, Orobanchaceae, and S. himalayana were mainly expressed at the parasite-host interface. Together, these results suggest that HGTs act as a bridge between the parasite and host, assisting the parasite in acquiring nutrients from the host. CONCLUSIONS: Our results provide new insights into the flower development process and endoparasitic lifestyle of Rafflesiaceae plants. The amount of gene loss in S. himalayana is consistent with the degree of reduction in its body plan. HGT events are common among endoparasites and play an important role in their lifestyle adaptation.


Assuntos
Genoma Mitocondrial , Transferência Genética Horizontal , Plantas/genética , Flores/genética , Filogenia
5.
Phys Rev Lett ; 131(15): 156703, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37897743

RESUMO

The Hanle magnetoresistance is a telltale signature of spin precession in nonmagnetic conductors, in which strong spin-orbit coupling generates edge spin accumulation via the spin Hall effect. Here, we report the existence of a large Hanle magnetoresistance in single layers of Mn with weak spin-orbit coupling, which we attribute to the orbital Hall effect. The simultaneous observation of a sizable Hanle magnetoresistance and vanishing small spin Hall magnetoresistance in BiYIG/Mn bilayers corroborates the orbital origin of both effects. We estimate an orbital Hall angle of 0.016, an orbital relaxation time of 2 ps and diffusion length of the order of 2 nm in disordered Mn. Our findings indicate that current-induced orbital moments are responsible for magnetoresistance effects comparable to or even larger than those determined by spin moments, and provide a tool to investigate nonequilibrium orbital transport phenomena.

6.
Phys Rev Lett ; 131(23): 239901, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38134810

RESUMO

This corrects the article DOI: 10.1103/PhysRevLett.131.156703.

8.
Phys Rev Lett ; 130(9): 096701, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36930935

RESUMO

We report on coherent propagation of antiferromagnetic (AFM) spin waves over a long distance (∼10 µm) at room temperature in a canted AFM α-Fe_{2}O_{3} owing to the Dzyaloshinskii-Moriya interaction (DMI). Unprecedented high group velocities (up to 22.5 km/s) are characterized by microwave transmission using all-electrical spin wave spectroscopy. We derive analytically AFM spin-wave dispersion in the presence of the DMI which accounts for our experimental results. The AFM spin waves excited by nanometric coplanar waveguides have large wave vectors in the exchange regime and follow a quasilinear dispersion relation. Fitting of experimental data with our theoretical model yields an AFM exchange stiffness length of 1.7 Å. Our results provide key insights on AFM spin dynamics and demonstrate high-speed functionality for AFM magnonics.

9.
Phys Rev Lett ; 130(4): 046701, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36763421

RESUMO

A leading nonlinear effect in magnonics is the interaction that splits a high-frequency magnon into two low-frequency magnons with conserved linear momentum. Here, we report experimental observation of nonlocal three-magnon scattering between spatially separated magnetic systems, viz. a CoFeB nanowire and a yttrium iron garnet (YIG) thin film. Above a certain threshold power of an applied microwave field, a CoFeB Kittel magnon splits into a pair of counterpropagating YIG magnons that induce voltage signals in Pt electrodes on each side, in excellent agreement with model calculations based on the interlayer dipolar interaction. The excited YIG magnon pairs reside mainly in the first excited (n=1) perpendicular standing spin-wave mode. With increasing power, the n=1 magnons successively scatter into nodeless (n=0) magnons through a four-magnon process. Our results demonstrate nonlocal detection of two separately propagating magnons emerging from one common source that may enable quantum entanglement between distant magnons for quantum information applications.

11.
Nano Lett ; 21(14): 6237-6244, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34270271

RESUMO

Spin waves can transfer information free of electron transport and are promising for wave-based computing technologies with low-power consumption as a solution to severe energy losses in modern electronics. Logic circuits based on the spin-wave interference have been proposed for more than a decade, while it has yet been realized at the nanoscale. Here, we demonstrate the interference of spin waves with wavelengths down to 50 nm in a low-damping magnetic insulator. The constructive and destructive interference of spin waves is detected in the frequency domain using propagating spin-wave spectroscopy, which is further confirmed by the Brillouin light scattering. The interference pattern is found to be highly sensitive to the distance between two magnetic nanowires acting as spin-wave emitters. By controlling the magnetic configurations, one can switch the spin-wave interferometer on and off. Our demonstrations are thus key to the realization of spin-wave computing system based on nonvolatile nanomagnets.

12.
J Cell Mol Med ; 25(14): 7089-7094, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34114734

RESUMO

MYSM1 is a chromatin-binding protein, widely investigated for its functions in haematopoiesis in human and mouse; however, its role in haematologic malignancies remains unexplored. Here, we investigate the cross-talk between MYSM1 and oncogenic cMYC in the transcriptional regulation of genes encoding ribosomal proteins, and the implications of these mechanisms for cMYC-driven carcinogenesis. We demonstrate that in cMYC-driven B cell lymphoma in mouse models, MYSM1-loss represses ribosomal protein gene expression and protein synthesis. Importantly, the loss of MYSM1 also strongly inhibits cMYC oncogenic activity and protects against B cell lymphoma onset and progression in the mouse models. This advances the understanding of the molecular and transcriptional mechanisms of lymphomagenesis, and suggests MYSM1 as a possible drug target for cMYC-driven malignancies.


Assuntos
Linfoma de Células B/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transativadores/deficiência , Proteases Específicas de Ubiquitina/deficiência , Animais , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Linfoma de Células B/genética , Camundongos , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Transativadores/genética , Transativadores/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
13.
Phys Rev Lett ; 127(11): 117204, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34558947

RESUMO

Dzyaloshinskii-Moriya interaction in magnets, which is usually derived from inversion symmetry breaking at interfaces or in noncentrosymmetric crystals, plays a vital role in chiral spintronics. Here we report that an emergent Dzyaloshinskii-Moriya interaction can be achieved in a centrosymmetric material, La_{0.67}Sr_{0.33}MnO_{3}, by a graded strain. This strain-driven Dzyaloshinskii-Moriya interaction not only exhibits distinctive two coexisting nonreciprocities of spin-wave propagation in one system, but also brings about a robust room-temperature magnetic skyrmion lattice as well as a spiral lattice at zero magnetic field. Our results demonstrate the feasibility of investigating chiral spintronics in a large category of centrosymmetric magnetic materials.

14.
Opt Lett ; 45(16): 4476-4479, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32796987

RESUMO

We report results of a study of the laser induced damage threshold (LIDT) behavior of ion beam sputtered HfO2/SiO2 multilayer coatings on Yb:YAG using 1-on-1 and N-on-1 test protocols. The tests were conducted at ambient, vacuum, and cryogenic conditions using 280 ps pulses at λ=1030nm. The 1-on-1 LIDT of antireflection (AR) stacks is found to be only slightly reduced under vacuum and cryogenic conditions, while that of high reflectivity (HR) stacks is insensitive to environmental conditions within the uncertainty of the measurements. Cryogenic N-on-1 tests show the LIDT of the HR coating is almost the same as in the 1-on-1 tests. Conversely, the cryogenic N-on-1 test of the AR coating shows damage at ∼13J/cm2, a fluence lower than the 20.4J/cm2 of 1-on-1 tests. The AR damage behavior is found to be affected by imperfections at the Yb:YAG surface. These findings show that high surface quality is required to increase energy extraction from active mirror laser amplifiers.

15.
Phys Rev Lett ; 124(2): 027203, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-32004033

RESUMO

Spin waves can probe the Dzyaloshinskii-Moriya interaction (DMI), which gives rise to topological spin textures, such as skyrmions. However, the DMI has not yet been reported in yttrium iron garnet (YIG) with arguably the lowest damping for spin waves. In this work, we experimentally evidence the interfacial DMI in a 7-nm-thick YIG film by measuring the nonreciprocal spin-wave propagation in terms of frequency, amplitude, and most importantly group velocities using all electrical spin-wave spectroscopy. The velocities of propagating spin waves show chirality among three vectors, i.e., the film normal direction, applied field, and spin-wave wave vector. By measuring the asymmetric group velocities, we extract a DMI constant of 16 µJ/m^{2}, which we independently confirm by Brillouin light scattering. Thickness-dependent measurements reveal that the DMI originates from the oxide interface between the YIG and garnet substrate. The interfacial DMI discovered in the ultrathin YIG films is of key importance for functional chiral magnonics as ultralow spin-wave damping can be achieved.

16.
Int J Mol Sci ; 21(8)2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32344625

RESUMO

MYSM1 has emerged as an important regulator of hematopoietic stem cell function, blood cell production, immune response, and other aspects of mammalian physiology. It is a metalloprotease family protein with deubiquitinase catalytic activity, as well as SANT and SWIRM domains. MYSM1 normally localizes to the nucleus, where it can interact with chromatin and regulate gene expression, through deubiquitination of histone H2A and non-catalytic contacts with other transcriptional regulators. A cytosolic form of MYSM1 protein was also recently described and demonstrated to regulate signal transduction pathways of innate immunity, by promoting the deubiquitination of TRAF3, TRAF6, and RIP2. In this work we review the current knowledge on the molecular mechanisms of action of MYSM1 protein in transcriptional regulation, signal transduction, and potentially other cellular processes. The functions of MYSM1 in different cell types and aspects of mammalian physiology are also reviewed, highlighting the key checkpoints in hematopoiesis, immunity, and beyond regulated by MYSM1. Importantly, mutations in MYSM1 in human were recently linked to a rare hereditary disorder characterized by leukopenia, anemia, and other hematopoietic and developmental abnormalities. Our growing knowledge of MYSM1 functions and mechanisms of actions sheds important insights into its role in mammalian physiology and the etiology of the MYSM1-deficiency disorder in human.


Assuntos
Enzimas Desubiquitinantes/genética , Hematopoese , Transativadores/genética , Proteases Específicas de Ubiquitina/genética , Animais , Diferenciação Celular/genética , Linhagem da Célula/genética , Enzimas Desubiquitinantes/metabolismo , Regulação da Expressão Gênica , Hematopoese/genética , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Imunidade Inata , Transdução de Sinais , Relação Estrutura-Atividade , Transativadores/química , Transativadores/metabolismo , Proteases Específicas de Ubiquitina/química , Proteases Específicas de Ubiquitina/metabolismo
17.
J Sci Food Agric ; 100(15): 5395-5402, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32535914

RESUMO

BACKGROUND: Ultrahigh-pressure (UHP) treatment, a non-thermal processing technology, exerts a bactericidal effect and affects food texture. How UHP treatments influence starch-polyphenol complexes has not yet been reported. Here, we studied the effects of UHP treatment on the structure of common rice starch (CRS)-apple polyphenol (AP) and common corn starch (CCS)-AP mixtures. RESULTS: Overall, UHP treatment decreased the particle size of the CRS-AP and CCS-AP composites. Furthermore, the ΔH values of the CRS-AP and CCS-AP mixtures decreased, and the heating stability was improved after UHP treatment. X-ray diffraction indicated that the relative crystallinity of the mixtures was unaffected by UHP treatment. Fourier-transform infrared spectroscopy proved that no new absorption peaks were observed in the infrared spectra, and the order of starch-AP was decreased after UHP treatment. These results indicated that UHP treatment inhibited the retrogradation of the starch-AP mixture. Our analyses of the microstructures of CRS-AP and CCS-AP mixtures showed increased folding and more pronounced network structures under high-pressure. CONCLUSIONS: These results provide a theoretical basis for further exploring the properties of starch-AP mixtures following UHP treatment and provide insights regarding the use of UHP treatments for food production. © 2020 Society of Chemical Industry.


Assuntos
Malus/química , Oryza/química , Extratos Vegetais/química , Polifenóis/química , Amido/química , Zea mays/química , Manipulação de Alimentos , Tamanho da Partícula , Pressão , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
18.
Opt Express ; 27(24): 35325-35335, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31878703

RESUMO

We report the demonstration of a pulse synthesizer based on spatial beam splitting and pulse stacking for the generation of picosecond laser pulses of Joule-level energy with arbitrary shape. An array of liquid crystals is used to control the amplitude of ten individual sub-pulses, and sliding retroreflectors are used to adjust their temporal separations. The synthesizer was used in combination with a λ=1.03 µm diode-pumped cryogenically-cooled Yb: YAG chirped pulse amplification laser to synthesize 1.3 J pulses or pulse trains of arbitrary shapes up to 9 ns duration with a temporal resolution as short as 8 ps. This pulse synthesizer offers the opportunity to incorporate a self-learning system to search for the optimal laser pulse shapes for various applications including optimized plasma conditions in laser-plasma based soft x-ray lasers and plasma sources for extreme ultraviolet lithography.

19.
Opt Express ; 26(5): 5240-5252, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29529729

RESUMO

Heat generation is a key obstacle to scaling high energy solid-state lasers to the multi-kilowatt average powers required for several key applications. We demonstrate an accurate, in situ, noninvasive optical technique to that makes three-dimensional (3-D) temperature maps within cryogenic amplifiers operating at high average power. The temperature is determined by analyzing the fluorescence spectra with a neural network function. The accuracy of the technique relies on a calibration that does not depend on simulations. Results are presented for a cryogenic Yb:YAG active mirror laser amplifier operating at different pump conditions. The technique is applicable to other solid-state lasers materials.

20.
Biochem Biophys Res Commun ; 485(2): 360-365, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28216162

RESUMO

GLABRA3 (GL3), a bHLH transcription factor, has previously proved to be involved in anthocyanin biosynthesis and trichome formation in Arabidopsis, however, its downstream targeted genes are still largely unknown. Here, we found that GL3 was widely present in Arabidopsis vegetative and reproductive organs. New downstream targeted genes of GL3 for anthocyanin biosynthesis and trichome formation were identified in young shoots and expanding true leaves by RNA sequencing. GL3-mediated gene expression was tissue specific in the two biological processes. This study provides new clues to further understand the GL3-mediated regulatory network of anthocyanin biosynthesis and trichome formation in Arabidopsis.


Assuntos
Antocianinas/biossíntese , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Regulação da Expressão Gênica de Plantas , Tricomas/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/genética , Genoma de Planta/genética , Mutação , Folhas de Planta/genética , Folhas de Planta/metabolismo , Brotos de Planta/genética , Brotos de Planta/metabolismo , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNA/métodos , Transdução de Sinais/genética , Tricomas/metabolismo
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