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1.
Nature ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961303

RESUMEN

Mass is commonly considered an intrinsic property of matter, but modern physics reveals particle masses to have complex origins1, such as the Higgs mechanism in high-energy physics2,3. In crystal lattices such as graphene, relativistic Dirac particles can exist as low-energy quasiparticles4 with masses imparted by lattice symmetry-breaking perturbations5-8. These mass-generating mechanisms all assume Hermiticity, or the conservation of energy in detail. Using a photonic synthetic lattice, we show experimentally that Dirac masses can be generated by means of non-Hermitian perturbations based on optical gain and loss. We then explore how the spacetime engineering of the gain and loss-induced Dirac mass affects the quasiparticles. As we show, the quasiparticles undergo Klein tunnelling at spatial boundaries, but a local breaking of a non-Hermitian symmetry can produce a new flux non-conservation effect at the domain walls. At a temporal boundary that abruptly flips the sign of the Dirac mass, we observe a variant of the time-reflection phenomenon: in the non-relativistic limit, the Dirac quasiparticle reverses its velocity, whereas in the relativistic limit, the original velocity is retained.

2.
PLoS Genet ; 20(4): e1011246, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38648211

RESUMEN

Genome-wide association studies (GWAS) have identified many genetic loci associated with complex traits and diseases in the past 20 years. Multiple heritable covariates may be added into GWAS regression models to estimate direct effects of genetic variants on a focal trait, or to improve the power by accounting for environmental effects and other sources of trait variations. When one or more covariates are causally affected by both genetic variants and hidden confounders, adjusting for them in GWAS will produce biased estimation of SNP effects, known as collider bias. Several approaches have been developed to correct collider bias through estimating the bias by Mendelian randomization (MR). However, these methods work for only one covariate, some of which utilize MR methods with relatively strong assumptions, both of which may not hold in practice. In this paper, we extend the bias-correction approaches in two aspects: first we derive an analytical expression for the collider bias in the presence of multiple covariates, then we propose estimating the bias using a robust multivariable MR (MVMR) method based on constrained maximum likelihood (called MVMR-cML), allowing the presence of invalid instrumental variables (IVs) and correlated pleiotropy. We also established the estimation consistency and asymptotic normality of the new bias-corrected estimator. We conducted simulations to show that all methods mitigated collider bias under various scenarios. In real data analyses, we applied the methods to two GWAS examples, the first a GWAS of waist-hip ratio with adjustment for only one covariate, body-mass index (BMI), and the second a GWAS of BMI adjusting metabolomic principle components as multiple covariates, illustrating the effectiveness of bias correction.


Asunto(s)
Sesgo , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Estudio de Asociación del Genoma Completo/métodos , Análisis de la Aleatorización Mendeliana/métodos , Humanos , Modelos Genéticos , Índice de Masa Corporal
3.
Am J Hum Genet ; 110(4): 592-605, 2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-36948188

RESUMEN

Mendelian randomization (MR) is a powerful tool for causal inference with observational genome-wide association study (GWAS) summary data. Compared to the more commonly used univariable MR (UVMR), multivariable MR (MVMR) not only is more robust to the notorious problem of genetic (horizontal) pleiotropy but also estimates the direct effect of each exposure on the outcome after accounting for possible mediating effects of other exposures. Despite promising applications, there is a lack of studies on MVMR's theoretical properties and robustness in applications. In this work, we propose an efficient and robust MVMR method based on constrained maximum likelihood (cML), called MVMR-cML, with strong theoretical support. Extensive simulations demonstrate that MVMR-cML performs better than other existing MVMR methods while possessing the above two advantages over its univariable counterpart. An application to several large-scale GWAS summary datasets to infer causal relationships between eight cardiometabolic risk factors and coronary artery disease (CAD) highlights the usefulness and some advantages of the proposed method. For example, after accounting for possible pleiotropic and mediating effects, triglyceride (TG), low-density lipoprotein cholesterol (LDL), and systolic blood pressure (SBP) had direct effects on CAD; in contrast, the effects of high-density lipoprotein cholesterol (HDL), diastolic blood pressure (DBP), and body height diminished after accounting for other risk factors.


Asunto(s)
Enfermedad de la Arteria Coronaria , Análisis de la Aleatorización Mendeliana , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Causalidad , Enfermedad de la Arteria Coronaria/genética , HDL-Colesterol/genética
4.
PLoS Genet ; 19(5): e1010762, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37200398

RESUMEN

Mendelian randomization (MR) has been increasingly applied for causal inference with observational data by using genetic variants as instrumental variables (IVs). However, the current practice of MR has been largely restricted to investigating the total causal effect between two traits, while it would be useful to infer the direct causal effect between any two of many traits (by accounting for indirect or mediating effects through other traits). For this purpose we propose a two-step approach: we first apply an extended MR method to infer (i.e. both estimate and test) a causal network of total effects among multiple traits, then we modify a graph deconvolution algorithm to infer the corresponding network of direct effects. Simulation studies showed much better performance of our proposed method than existing ones. We applied the method to 17 large-scale GWAS summary datasets (with median N = 256879 and median #IVs = 48) to infer the causal networks of both total and direct effects among 11 common cardiometabolic risk factors, 4 cardiometabolic diseases (coronary artery disease, stroke, type 2 diabetes, atrial fibrillation), Alzheimer's disease and asthma, identifying some interesting causal pathways. We also provide an R Shiny app (https://zhaotongl.shinyapps.io/cMLgraph/) for users to explore any subset of the 17 traits of interest.


Asunto(s)
Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/genética , Análisis de la Aleatorización Mendeliana/métodos , Estudio de Asociación del Genoma Completo , Causalidad , Polimorfismo de Nucleótido Simple
5.
Nature ; 565(7741): 622-626, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30626966

RESUMEN

Confining photons in a finite volume is highly desirable in modern photonic devices, such as waveguides, lasers and cavities. Decades ago, this motivated the study and application of photonic crystals, which have a photonic bandgap that forbids light propagation in all directions1-3. Recently, inspired by the discoveries of topological insulators4,5, the confinement of photons with topological protection has been demonstrated in two-dimensional (2D) photonic structures known as photonic topological insulators6-8, with promising applications in topological lasers9,10 and robust optical delay lines11. However, a fully three-dimensional (3D) topological photonic bandgap has not been achieved. Here we experimentally demonstrate a 3D photonic topological insulator with an extremely wide (more than 25 per cent bandwidth) 3D topological bandgap. The composite material (metallic patterns on printed circuit boards) consists of split-ring resonators (classical electromagnetic artificial atoms) with strong magneto-electric coupling and behaves like a 'weak' topological insulator (that is, with an even number of surface Dirac cones), or a stack of 2D quantum spin Hall insulators. Using direct field measurements, we map out both the gapped bulk band structure and the Dirac-like dispersion of the photonic surface states, and demonstrate robust photonic propagation along a non-planar surface. Our work extends the family of 3D topological insulators from fermions to bosons and paves the way for applications in topological photonic cavities, circuits and lasers in 3D geometries.

6.
PLoS Genet ; 18(5): e1010205, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35576237

RESUMEN

To infer a causal relationship between two traits, several correlation-based causal direction (CD) methods have been proposed with the use of SNPs as instrumental variables (IVs) based on GWAS summary data for the two traits; however, none of the existing CD methods can deal with SNPs with correlated pleiotropy. Alternatively, reciprocal Mendelian randomization (MR) can be applied, which however may perform poorly in the presence of (unknown) invalid IVs, especially for bi-directional causal relationships. In this paper, first, we propose a CD method that performs better than existing CD methods regardless of the presence of correlated pleiotropy. Second, along with a simple but yet effective IV screening rule, we propose applying a closely related and state-of-the-art MR method in reciprocal MR, showing its almost identical performance to that of the new CD method when their model assumptions hold; however, if the modeling assumptions are violated, the new CD method is expected to better control type I errors. Notably bi-directional causal relationships impose some unique challenges beyond those for uni-directional ones, and thus requiring special treatments. For example, we point out for the first time several scenarios where a bi-directional relationship, but not a uni-directional one, can unexpectedly cause the violation of some weak modeling assumptions commonly required by many robust MR methods. We also offer some numerical support and a modeling justification for the application of our new methods (and more generally MR) to binary traits. Finally we applied the proposed methods to 12 risk factors and 4 common diseases, confirming mostly well-known uni-directional causal relationships, while identifying some novel and plausible bi-directional ones such as between body mass index and type 2 diabetes (T2D), and between diastolic blood pressure and stroke.


Asunto(s)
Diabetes Mellitus Tipo 2 , Análisis de la Aleatorización Mendeliana , Causalidad , Diabetes Mellitus Tipo 2/genética , Pleiotropía Genética , Estudio de Asociación del Genoma Completo , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Polimorfismo de Nucleótido Simple
7.
Hum Mol Genet ; 31(14): 2462-2470, 2022 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-35043938

RESUMEN

Transcriptome-wide association studies (TWAS) integrate genome-wide association study (GWAS) data with gene expression (GE) data to identify (putative) causal genes for complex traits. There are two stages in TWAS: in Stage 1, a model is built to impute gene expression from genotypes, and in Stage 2, gene-trait association is tested using imputed gene expression. Despite many successes with TWAS, in the current practice, one only assumes a linear relationship between GE and the trait, which however may not hold, leading to loss of power. In this study, we extend the standard TWAS by considering a quadratic effect of GE, in addition to the usual linear effect. We train imputation models for both linear and quadratic gene expression levels in Stage 1, then include both the imputed linear and quadratic expression levels in Stage 2. We applied both the standard TWAS and our approach first to the ADNI gene expression data and the IGAP Alzheimer's disease GWAS summary data, then to the GTEx (V8) gene expression data and the UK Biobank individual-level GWAS data for lipids, followed by validation with different GWAS data, suitable model checking and more robust TWAS methods. In all these applications, the new TWAS approach was able to identify additional genes associated with Alzheimer's disease, LDL and HDL cholesterol levels, suggesting its likely power gains and thus the need to account for potentially nonlinear effects of gene expression on complex traits.


Asunto(s)
Enfermedad de Alzheimer , Transcriptoma , Enfermedad de Alzheimer/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/métodos , Humanos , Herencia Multifactorial , Polimorfismo de Nucleótido Simple/genética , Sitios de Carácter Cuantitativo/genética , Transcriptoma/genética
8.
Hum Mol Genet ; 31(19): 3207-3215, 2022 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-34791233

RESUMEN

Transcriptome-wide association studies increase the yield of loci associated with disease phenotypes by focusing on expression quantitative trait loci (eQTL). The major source of eQTL data for is the Gene and Tissue Expression (GTEx) project, which is comprised entirely of adults, mainly those >50 years of age at death. Since gene expression levels differ by developmental stage, it is not clear whether eQTLs derived from adult data sources are best suited for use in young-onset diseases such as pediatric cancers. To fill in this knowledge gap, we performed a large-scale eQTL mapping analysis in the GenCord study with newborn samples and compared it with GTEx. Under matched conditions, we found around 80% of the eQTLs in one study can be replicated in the other. However, among all eQTLs identified in GenCord (GTEx), 584 (1045) showed statistically significant differences in effect sizes in GTEx (GenCord). We further investigated how using fetal eQTL data can facilitate the genetic association study of acute lymphoblastic leukemia. GenCord and GTEx identified the same genetic loci with statistical significance; however, the overall association pattern was only weakly correlated. Our paper demonstrates age-differential eQTLs and shows their potential influence on childhood leukemia research.


Asunto(s)
Leucemia , Sitios de Carácter Cuantitativo , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Leucemia/genética , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo/genética , Transcriptoma/genética
9.
Am J Hum Genet ; 108(7): 1251-1269, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34214446

RESUMEN

With the increasing availability of large-scale GWAS summary data on various complex traits and diseases, there have been tremendous interests in applications of Mendelian randomization (MR) to investigate causal relationships between pairs of traits using SNPs as instrumental variables (IVs) based on observational data. In spite of the potential significance of such applications, the validity of their causal conclusions critically depends on some strong modeling assumptions required by MR, which may be violated due to the widespread (horizontal) pleiotropy. Although many MR methods have been proposed recently to relax the assumptions by mainly dealing with uncorrelated pleiotropy, only a few can handle correlated pleiotropy, in which some SNPs/IVs may be associated with hidden confounders, such as some heritable factors shared by both traits. Here we propose a simple and effective approach based on constrained maximum likelihood and model averaging, called cML-MA, applicable to GWAS summary data. To deal with more challenging situations with many invalid IVs with only weak pleiotropic effects, we modify and improve it with data perturbation. Extensive simulations demonstrated that the proposed methods could control the type I error rate better while achieving higher power than other competitors. Applications to 48 risk factor-disease pairs based on large-scale GWAS summary data of 3 cardio-metabolic diseases (coronary artery disease, stroke, and type 2 diabetes), asthma, and 12 risk factors confirmed its superior performance.


Asunto(s)
Algoritmos , Pleiotropía Genética , Funciones de Verosimilitud , Análisis de la Aleatorización Mendeliana/métodos , Asma/etiología , Enfermedades Cardiovasculares/etiología , Causalidad , Simulación por Computador , Diabetes Mellitus Tipo 2/etiología , Humanos , Modelos Estadísticos , Factores de Riesgo
10.
Cancer Causes Control ; 35(6): 897-906, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38332239

RESUMEN

PURPOSE: We aimed to characterize genetic correlations and causal associations between circulating C-reactive protein (CRP) levels and the risk of lung cancer (LC). METHODS: Leveraging summary statistics from genome-wide association studies of circulating CRP levels among 575,531 individuals of European ancestry, and LC risk among 29,266 cases and 56,450 controls, we investigated genetic associations of circulating CRP levels with the risk of overall lung cancer and its histological subtypes, by using linkage disequilibrium score (LDSC) regression and Mendelian randomization (MR) analyses. RESULTS: Significant positive genetic correlations between circulating CRP levels and the risk of LC and its histological subtypes were identified from LDSC regression, with correlation coefficients ranging from 0.12 to 0.26, and all false discovery adjusted p < 0.05. Univariable MR demonstrated a nominal association between CRP levels and an increased risk of lung squamous cell carcinoma (SCC) (inverse variance-weighted OR = 1.15, 95% CI 1.01-1.30). However, this association disappeared when multivariable MR included cigarettes per day and/or body mass index. By using our recently developed constrained maximum likelihood-based MR method, we identified significant associations of CRP levels with the risk of overall LC (OR 1.06, 95% CI 1.03-1.09), SCC (OR 1.06, 95% CI 1.02-1.09), and small cell lung cancer (SCLC, OR 1.09, 95% CI 1.03-1.15). Moreover, most univariable and multivariable MR analyses also revealed consistent CRP-SCLC associations. CONCLUSION: There may be a genetic and causal association between circulating CRP levels and the risk of SCLC, which is in line with previous population-based observational studies.


Asunto(s)
Proteína C-Reactiva , Estudio de Asociación del Genoma Completo , Neoplasias Pulmonares , Análisis de la Aleatorización Mendeliana , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/epidemiología , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/genética , Factores de Riesgo , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Desequilibrio de Ligamiento , Masculino , Femenino
11.
Phys Rev Lett ; 132(23): 236401, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38905662

RESUMEN

Braiding is a geometric concept that manifests itself in a variety of scientific contexts from biology to physics, and has been employed to classify bulk band topology in topological materials. Topological edge states can also form braiding structures, as demonstrated recently in a type of topological insulators known as Möbius insulators, whose topological edge states form two braided bands exhibiting a Möbius twist. While the formation of Möbius twist is inspiring, it belongs to the simple Abelian braid group B_{2}. The most fascinating features about topological braids rely on the non-Abelianness in the higher-order braid group B_{N} (N≥3), which necessitates multiple edge bands, but so far it has not been discussed. Here, based on the gauge enriched symmetry, we develop a scheme to realize non-Abelian braiding of multiple topological edge bands. We propose tight-binding models of topological insulators that are able to generate topological edge states forming non-Abelian braiding structures. Experimental demonstrations are conducted in two acoustic crystals, which carry three and four braided acoustic edge bands, respectively. The observed braiding structure can correspond to the topological winding in the complex eigenvalue space of projective translation operator, akin to the previously established point-gap winding topology in the bulk of the Hatano-Nelson model. Our Letter also constitutes the realization of non-Abelian braiding topology on an actual crystal platform, but not based on the "virtual" synthetic dimensions.

12.
Phys Rev Lett ; 132(15): 156602, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38682981

RESUMEN

Photonic Chern insulators are known for their topological chiral edge states (CESs), whose absolute existence is determined by the bulk band topology, but concrete dispersion can be engineered to exhibit various properties. For example, the previous theory suggested that the edge dispersion can wind many times around the Brillouin zone to slow down light, which can potentially overcome fundamental limitations in conventional slow-light devices: narrow bandwidth and keen sensitivity to fabrication imperfection. Here, we report the first experimental demonstration of this idea, achieved by coupling CESs with resonance-induced nearly flat bands. We show that the backscattering-immune hybridized CESs are significantly slowed down over a relatively broad bandwidth. Our work thus paves an avenue to broadband topological slow-light devices.

13.
Genet Epidemiol ; 46(8): 572-588, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35766062

RESUMEN

Transcriptome-Wide Association Studies (TWASs) have become increasingly popular in identifying genes (or other endophenotypes or exposures) associated with complex traits. In TWAS, one first builds a predictive model for gene expressions using an expression quantitative trait loci (eQTL) data set in stage 1, then tests the association between the predicted gene expression and a trait based on a large, independent genome-wide association study (GWAS) data set in stage 2. However, since the sample size of the eQTL data set is usually small and the coefficient of multiple determination (i.e., R 2 ${R}^{2}$ ) of the model for many genes is also small, a question of interest is to what extent these factors affect the statistical power of TWAS. In addition, in contrast to a standard (univariate) TWAS (UV-TWAS) considering only a single gene at a time, multivariate TWAS (MV-TWAS) methods have recently emerged to account for the effects of multiple genes, or a gene's nonlinear effects, simultaneously. With the absence of the power analysis for these MV-TWAS methods, it would be of interest to investigate whether one can gain or lose power by using the newly proposed MV-TWAS instead of UV-TWAS. In this paper, we first outline a general method for sample size/power calculations for two-sample TWAS, then use real data-the Alzheimer's Disease Neuroimaging Initiative (ADNI) expression quantitative trait loci (eQTL) data and the Genotype-Tissue Expression (GTEx) eQTL data for stage 1, the International Genomics of Alzheimer's Project Alzheimer's disease (AD) GWAS summary data and UK Biobank (UKB) individual-level data for stage 2-to empirically address these questions. Our most important conclusions are the following. First, a sample size of a few thousands (~8000) would suffice in stage 1, where the power of TWAS would be more determined by cis-heritability of gene expression. Second, as in the general case of simple regression versus multiple regression, the power of MV-TWAS may be higher or lower than that of UV-TWAS, depending on the specific relationships among the GWAS trait and multiple genes (or linear and nonlinear terms of the same gene's expression levels), such as their correlations and effect sizes. Interestingly, several top genes with large power gains in MV-TWAS (over that in UV-TWAS) were known to be (and in our data more significantly) associated with AD. We also reached similar conclusions in an application to the GTEx whole blood gene expression data and UKB GWAS data of high-density lipoprotein cholesterol. The proposed method and the conclusions are expected to be useful in planning and designing future TWAS and other related studies (e.g., Proteome- or Metabolome-Wide Association Studies) when determining the sample sizes for the two stages.


Asunto(s)
Enfermedad de Alzheimer , Transcriptoma , Humanos , Estudio de Asociación del Genoma Completo/métodos , Enfermedad de Alzheimer/genética , Modelos Genéticos , Sitios de Carácter Cuantitativo/genética , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad
14.
New Phytol ; 240(5): 2058-2071, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37717220

RESUMEN

Distyly has evolved independently in numerous animal-pollinated angiosperm lineages. Understanding of its molecular basis has been restricted to a few species, primarily Primula. Here, we investigate the genetic architecture of the single diallelic locus (S-locus) supergene, a linkage group of functionally associated genes, and explore how it may have evolved in distylous Nymphoides indica, a lineage of flowering plants not previously investigated. We assembled haplotype-resolved genomes, used read-coverage-based genome-wide association study (rb-GWAS) to locate the S-locus supergene, co-expression network analysis to explore gene networks underpinning the development of distyly, and comparative genomic analyses to investigate the origins of the S-locus supergene. We identified three linked candidate S-locus genes - NinBAS1, NinKHZ2, and NinS1 - that were only evident in the short-styled morph and were hemizygous. Co-expression network analysis suggested that brassinosteroids contribute to dimorphic sex organs in the short-styled morph. Comparative genomic analyses indicated that the S-locus supergene likely evolved via stepwise duplications and has been affected by transposable element activities. Our study provides novel insight into the structure, regulation, and evolution of the supergene governing distyly in N. indica. It also provides high-quality genomic resources for future research on the molecular mechanisms underlying the striking evolutionary convergence in form and function across heterostylous taxa.


Asunto(s)
Estudio de Asociación del Genoma Completo , Primula , Haplotipos/genética , Primula/genética , Genómica , Flores/genética
15.
Phys Rev Lett ; 130(10): 103602, 2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36962029

RESUMEN

In a Hermitian system, bound states must have quantized energies, whereas free states can form a continuum. We demonstrate how this principle fails for non-Hermitian systems, by analyzing non-Hermitian continuous Hamiltonians with an imaginary momentum and Landau-type vector potential. The eigenstates, which we call "continuum Landau modes" (CLMs), have Gaussian spatial envelopes and form a continuum filling the complex energy plane. We present experimentally realizable 1D and 2D lattice models that host CLMs; the lattice eigenstates are localized and have other features matching the continuous model. One of these lattices can serve as a rainbow trap, whereby the response to an excitation is concentrated at a position proportional to the frequency. Another lattice can act a wave funnel, concentrating an input excitation onto a boundary over a wide frequency bandwidth. Unlike recent funneling schemes based on the non-Hermitian skin effect, this requires a simple lattice design with reciprocal couplings.

16.
Phys Rev Lett ; 131(24): 249901, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38181164

RESUMEN

This corrects the article DOI: 10.1103/PhysRevLett.129.254301.

17.
Phys Rev Lett ; 130(21): 213603, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37295078

RESUMEN

Photonic topological states, providing light-manipulation approaches in robust manners, have attracted intense attention. Connecting photonic topological states with far-field degrees of freedom (d.o.f.) has given rise to fruitful phenomena. Recently emerged higher-order topological insulators (HOTIs), hosting boundary states two or more dimensions lower than those of bulk, offer new paradigms to localize or transport light topologically in extended dimensionalities. However, photonic HOTIs have not been related to d.o.f. of radiation fields yet. Here, we report the observation of polarization-orthogonal second-order topological corner states at different frequencies on a designer-plasmonic kagome metasurface in the far field. Such phenomenon stands on two mechanisms, i.e., projecting the far-field polarizations to the intrinsic parity d.o.f. of lattice modes and the parity splitting of the plasmonic corner states in spectra. We theoretically and numerically show that the parity splitting originates from the underlying interorbital coupling. Both near-field and far-field experiments verify the polarization-orthogonal nondegenerate second-order topological corner states. These results promise applications in robust optical single photon emitters and multiplexed photonic devices.


Asunto(s)
Frutas , Fotones , Femenino , Embarazo , Humanos
18.
J Thromb Thrombolysis ; 55(1): 175-180, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36352057

RESUMEN

The SAMe-TT2R2 score predicts optimal long-term oral Vitamin K Antagonist (VKA) anticoagulation for homogenous Caucasian and homogenous Asian populations for non-valvular atrial fibrillation but at different score thresholds. The score that predicts optimal VKA anticoagulation in significantly diverse populations for multiple indications for systemic anticoagulation has not been reported. We determined whether optimal VKA anticoagulation is predicted by SAMe-TT2R2 score in a diverse inner-city population for non-valvular atrial fibrillation (NVAF), unprovoked venous and pulmonary thromboembolic disease (VTE), mechanical prosthetic heart valves and all other indications. All patients on long term VKA's that attended an inner-city anticoagulation clinic between February 2016 and October 2017 were included in this study. Eligible patients were grouped according to oral anticoagulation indication: (1) NVAF, (2) VTE, (3) prosthetic valves and (4) other indications. Each patient's SAMe-TT2R2 score and percent time of INR in the therapeutic range (TTR) was calculated with optimal international normalized ratio (INR) control defined as TTR ≥ 65%. The correlation between SAMe-TT2R2 score and TTR was determined by logistic regression for each oral anticoagulant indication. Receiver operating characteristic curves were then used to identify the best cutoff for prediction of ≥ 65% TTR. Of 316 patients meeting study criteria, 54% were non-Caucasian and there was a significant negative correlation between the SAMe-TT2R2 score and TTR (coefficient - 0.35, P < 0.0001) for all patients. A SAMe-TT2R2 score < 4 was identified as the best threshold for predicting optimal TTR (Youden's J-statistics = 0.238) with accuracy and positive likelihood ratio of 63.4% and 1.73, respectively. The SAMe-TT2R2 score predicts optimal VKA anticoagulation for systemic anticoagulation for multiple indications in a diverse urban population at a higher score than the original report for non-valvular atrial fibrillation of a cohort where < 10% non-Caucasians.


Asunto(s)
Fibrilación Atrial , Tromboembolia Venosa , Humanos , Fibrilación Atrial/epidemiología , Tromboembolia Venosa/tratamiento farmacológico , Coagulación Sanguínea , Anticoagulantes/uso terapéutico , Anticoagulantes/farmacología , Relación Normalizada Internacional , Vitamina K
19.
PLoS Genet ; 16(11): e1009105, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33137120

RESUMEN

Orienting the causal relationship between pairs of traits is a fundamental task in scientific research with significant implications in practice, such as in prioritizing molecular targets and modifiable risk factors for developing therapeutic and interventional strategies for complex diseases. A recent method, called Steiger's method, using a single SNP as an instrument variable (IV) in the framework of Mendelian randomization (MR), has since been widely applied. We report the following new contributions. First, we propose a single SNP-based alternative, overcoming a severe limitation of Steiger's method in simply assuming, instead of inferring, the existence of a causal relationship. We also clarify a condition necessary for the validity of the methods in the presence of hidden confounding. Second, to improve statistical power, we propose combining the results from multiple, and possibly correlated, SNPs as multiple instruments. Third, we develop three goodness-of-fit tests to check modeling assumptions, including those required for valid IVs. Fourth, by relaxing one of the three IV assumptions in MR, we propose several methods, including an Egger regression-like approach and its multivariable version (analogous to multivariable MR), to account for horizontal pleiotropy of the SNPs/IVs, which is often unavoidable in practice. All our methods can simultaneously infer both the existence and (if so) the direction of a causal relationship, largely expanding their applicability over that of Steiger's method. Although we focus on uni-directional causal relationships, we also briefly discuss an extension to bi-directional relationships. Through extensive simulations and an application to infer the causal directions between low density lipoprotein (LDL) cholesterol, or high density lipoprotein (HDL) cholesterol, and coronary artery disease (CAD), we demonstrate the superior performance and advantage of our proposed methods over Steiger's method and bi-directional MR. In particular, after accounting for horizontal pleiotropy, our method confirmed the well known causal direction from LDL to CAD, while other methods, including bi-directional MR, might fail.


Asunto(s)
Biología Computacional/métodos , Pleiotropía Genética , Estudio de Asociación del Genoma Completo , Modelos Genéticos , HDL-Colesterol/genética , Enfermedad de la Arteria Coronaria/genética , Conjuntos de Datos como Asunto , Estudios de Factibilidad , Humanos , Polimorfismo de Nucleótido Simple , Programas Informáticos
20.
J Anim Physiol Anim Nutr (Berl) ; 107(5): 1198-1205, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37203256

RESUMEN

Blidingia sp. is a prominent fouling green macroalga and we previously found that extracts from Blidingia sp. alleviated intestinal inflammation in mice challenged with lipopolysaccharides. However, whether these extracts are effective in weanling piglets remains unknown. In the present study, Blidingia sp. extracts were supplemented in the diet and their effects on growth performance, incidence of diarrhoea and intestinal function in weanling piglets were explored. The results showed that diets supplemented with 0.1% or 0.5% Blidingia sp. extract significantly increased average daily body weight gain and feed intake in weanling piglets. Meanwhile, piglets supplemented with 0.5% Blidingia sp. extract showed decreased incidence of diarrhoea as well as reduced fecal water and Na+ content. Furthermore, the diet supplemented with 0.5% Blidingia sp. extracts improved intestinal morphology, as indicated by the results of hematoxylin and eosin staining. Diet supplemented with 0.5% Blidingia sp. extracts also improved tight junction function, as indicated by increased expression of Occludin, Claudin-1 and Zonula occludens-1, and alleviated the inflammatory response, as indicated by decreased tumor necrosis factor-α and interleukin-6 (IL6) contents and increased IL10 levels. Taken together, our results showed that Blidingia sp. extracts had beneficial effects in weanling piglets and we suggest that Blidingia sp. extracts could be potentially used as an additive for piglets.


Asunto(s)
Diarrea , Intestinos , Porcinos , Animales , Ratones , Intestinos/fisiología , Diarrea/prevención & control , Diarrea/veterinaria , Suplementos Dietéticos , Dieta/veterinaria , Ocludina , Aumento de Peso , Alimentación Animal/análisis
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