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1.
Am J Hum Genet ; 111(2): 280-294, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38183988

RESUMO

Eosinophilic esophagitis (EoE) is a rare atopic disorder associated with esophageal dysfunction, including difficulty swallowing, food impaction, and inflammation, that develops in a small subset of people with food allergies. Genome-wide association studies (GWASs) have identified 9 independent EoE risk loci reaching genome-wide significance (p < 5 × 10-8) and 27 additional loci of suggestive significance (5 × 10-8 < p < 1 × 10-5). In the current study, we perform linkage disequilibrium (LD) expansion of these loci to nominate a set of 531 variants that are potentially causal. To systematically interrogate the gene regulatory activity of these variants, we designed a massively parallel reporter assay (MPRA) containing the alleles of each variant within their genomic sequence context cloned into a GFP reporter library. Analysis of reporter gene expression in TE-7, HaCaT, and Jurkat cells revealed cell-type-specific gene regulation. We identify 32 allelic enhancer variants, representing 6 genome-wide significant EoE loci and 7 suggestive EoE loci, that regulate reporter gene expression in a genotype-dependent manner in at least one cellular context. By annotating these variants with expression quantitative trait loci (eQTL) and chromatin looping data in related tissues and cell types, we identify putative target genes affected by genetic variation in individuals with EoE. Transcription factor enrichment analyses reveal possible roles for cell-type-specific regulators, including GATA3. Our approach reduces the large set of EoE-associated variants to a set of 32 with allelic regulatory activity, providing functional insights into the effects of genetic variation in this disease.


Assuntos
Enterite , Eosinofilia , Esofagite Eosinofílica , Gastrite , Humanos , Esofagite Eosinofílica/genética , Esofagite Eosinofílica/complicações , Estudo de Associação Genômica Ampla , Genótipo , Locos de Características Quantitativas/genética
2.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35193980

RESUMO

Shrub recruitment, a key component of vegetation dynamics beyond forests, is a highly sensitive indicator of climate and environmental change. Warming-induced tipping points in Arctic and alpine treeless ecosystems are, however, little understood. Here, we compare two long-term recruitment datasets of 2,770 shrubs from coastal East Greenland and from the Tibetan Plateau against atmospheric circulation patterns between 1871 and 2010 Common Era. Increasing rates of shrub recruitment since 1871 reached critical tipping points in the 1930s and 1960s on the Tibetan Plateau and in East Greenland, respectively. A recent decline in shrub recruitment in both datasets was likely related to warmer and drier climates, with a stronger May to July El Niño Southern Oscillation over the Tibetan Plateau and a stronger June to July Atlantic Multidecadal Oscillation over Greenland. Exceeding the thermal optimum of shrub recruitment, the recent warming trend may cause soil moisture deficit. Our findings suggest that changes in atmospheric circulation explain regional climate dynamics and associated response patterns in Arctic and alpine shrub communities, knowledge that should be considered to protect vulnerable high-elevation and high-latitude ecosystems from the cascading effects of anthropogenic warming.


Assuntos
Desenvolvimento Vegetal , Temperatura , Regiões Árticas , Mudança Climática , Ecossistema , Groenlândia , Tibet
3.
PLoS Genet ; 18(5): e1009973, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35576187

RESUMO

Atopic dermatitis (AD) is one of the most common skin disorders among children. Disease etiology involves genetic and environmental factors, with 29 independent AD risk loci enriched for risk allele-dependent gene expression in the skin and CD4+ T cell compartments. We investigated the potential epigenetic mechanisms responsible for the genetic susceptibility of CD4+ T cells. To understand the differences in gene regulatory activity in peripheral blood T cells in AD, we measured chromatin accessibility (an assay based on transposase-accessible chromatin sequencing, ATAC-seq), nuclear factor kappa B subunit 1 (NFKB1) binding (chromatin immunoprecipitation with sequencing, ChIP-seq), and gene expression levels (RNA-seq) in stimulated CD4+ T cells from subjects with active moderate-to-severe AD, as well as in age-matched non-allergic controls. Open chromatin regions in stimulated CD4+ T cells were highly enriched for AD genetic risk variants, with almost half of the AD risk loci overlapping AD-dependent ATAC-seq peaks. AD-specific open chromatin regions were strongly enriched for NF-κB DNA-binding motifs. ChIP-seq identified hundreds of NFKB1-occupied genomic loci that were AD- or control-specific. As expected, the AD-specific ChIP-seq peaks were strongly enriched for NF-κB DNA-binding motifs. Surprisingly, control-specific NFKB1 ChIP-seq peaks were not enriched for NFKB1 motifs, but instead contained motifs for other classes of human transcription factors, suggesting a mechanism involving altered indirect NFKB1 binding. Using DNA sequencing data, we identified 63 instances of altered genotype-dependent chromatin accessibility at 36 AD risk variant loci (30% of AD risk loci) that might lead to genotype-dependent gene expression. Based on these findings, we propose that CD4+ T cells respond to stimulation in an AD-specific manner, resulting in disease- and genotype-dependent chromatin accessibility alterations involving NFKB1 binding.


Assuntos
Linfócitos T CD4-Positivos , Dermatite Atópica , Linfócitos T CD4-Positivos/metabolismo , Criança , Cromatina/genética , DNA , Dermatite Atópica/genética , Epigênese Genética , Humanos , NF-kappa B/metabolismo
4.
Ecol Lett ; 27(4): e14403, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577961

RESUMO

Species interactions such as facilitation and competition play a crucial role in driving species range shifts. However, density dependence as a key feature of these processes has received little attention in both empirical and modelling studies. Herein, we used a novel, individual-based treeline model informed by rich in situ observations to quantify the contribution of density-dependent species interactions to alpine treeline dynamics, an iconic biome boundary recognized as an indicator of global warming. We found that competition and facilitation dominate in dense versus sparse vegetation scenarios respectively. The optimal balance between these two effects was identified at an intermediate vegetation thickness where the treeline elevation was the highest. Furthermore, treeline shift rates decreased sharply with vegetation thickness and the associated transition from positive to negative species interactions. We thus postulate that vegetation density must be considered when modelling species range dynamics to avoid inadequate predictions of its responses to climate warming.


Assuntos
Ecossistema , Árvores , Árvores/fisiologia , Aquecimento Global , Mudança Climática , Clima
5.
New Phytol ; 241(1): 142-153, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37932883

RESUMO

Plant litter is known to affect soil, community, and ecosystem properties. However, we know little about the capacity of litter to modulate grassland responses to climate change. Using a 7-yr litter removal experiment in a semiarid grassland, here we examined how litter removal interacts with a 2-yr drought to affect soil environments, plant community composition, and ecosystem function. Litter loss exacerbates the negative impacts of drought on grasslands. Litter removal increased soil temperature but reduced soil moisture and nitrogen mineralization, which substantially increased the negative impacts of drought on primary productivity and the abundance of perennial rhizomatous graminoids. Moreover, complete litter removal shifted plant community composition from grass-dominated to forb-dominated and reduced species and functional group asynchrony, resulting in lower ecosystem temporal stability. Our results suggest that ecological processes that lead to reduction in litter, such as burning, grazing, and haying, may render ecosystems more vulnerable and impair the capacity of grasslands to withstand drought events.


Assuntos
Ecossistema , Pradaria , Secas , Plantas , Solo
6.
Bioconjug Chem ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38889324

RESUMO

Full-spectrum flow cytometry has increased antibody-based multiplexing, yet further increases remain potentially impactful. We recently proposed how fluorescence multiplexing using spectral imaging and combinatorics (MuSIC) could do so using tandem dyes and an oligo-based antibody labeling method. In this work, we found that such labeled antibodies had significantly lower signal intensities than conventionally labeled antibodies in human cell experiments. To improve signal intensity, we tested moving the fluorophores from the original external (ext.) 5' or 3' end-labeled orientation to internal (int.) fluorophore modifications. Cell-free spectrophotometer measurements showed a ∼6-fold signal intensity increase of the new int. configuration compared to the previous ext. configuration. Time-resolved fluorescence and fluorescence correlation spectroscopy showed that the ∼3-fold brightness difference is due to static quenching most likely by the oligo or solution in the ext. configuration. Spectral flow cytometry experiments using peripheral blood mononuclear cells show int. MuSIC probe-labeled antibodies (i) retained increased signal intensity while having no significant difference in the estimated % of CD8+ lymphocytes and (ii) labeled with Atto488, Atto647, and Atto488/647 combinations can be demultiplexed in triple-stained samples. The antibody labeling approach is general and can be broadly applied to many biological and diagnostic applications where spectral detection is available.

7.
Opt Express ; 31(12): 19336-19346, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381350

RESUMO

The image of an optical point source is blurred due to light diffraction so that estimating small displacements of the point source with direct imaging demands elaborate processing on the observation data of a camera. Using quantum parameter estimation, we show that for the imaging systems with a real point spread function, any measurement basis constituted by a complete set of real-valued spatial-mode functions is optimal for estimating the displacement. For small displacements, we can concentrate the information about the value of displacement to the measurement of a few spatial modes, which can be selected in terms of the Fisher information distribution. We use digital holography with a phase-only spatial light modulator to implement two simple estimation strategies that are mainly based on the projection measurement of two spatial modes and the readout of a single pixel of a camera.

8.
Anticancer Drugs ; 34(3): 439-450, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36441004

RESUMO

BACKGROUND: Dysregulation of cancer-associated fibroblasts (CAFs) still greatly challenges the treatments for bladder cancer (BC), where exosomal miRNAs derived from CAFs are one of the essential effectors for tumor progression. miR-93-5p is reported to be upregulated in BC, however, it is barely investigated in BC-derived CAFs. METHOD: The CAF markers were immunofluorescent-labeled and examined by western blotting assay in CAFs and normal fibroblasts (NFs). CAFs- and NFs-derived exosomes (CAFs-exo/NFs-exo) were authenticated by transmission electron microscope and nanoparticle tracking analysis. Cell viability was determined by cell counting kit-8 assay, and cell mobility was evaluated by wound healing and transwell assays. Real-time quantitative PCR was used to quantify the RNA expressions, and a western blotting assay was used for protein expression. Interaction between miR-93-5p and Platelet-Activating Factor Acetylhydrolase IB Subunit Beta (PAFAH1B1) was verified by luciferase reporter assay. HE staining assay was applied to assess the histological changes of xenografts. RESULTS: CAFs-exo notably enhanced cell mobility and the expression levels of miR-93-5p of BC cells compared to NFs-exo. However, inhibition of miR-93-5p in CAFs-exo exhibited attenuated pro-metastatic ability on BC cells. PAFAH1B1 was one of the predicted targets of miR-93-5p, whose mRNA level was most significantly downregulated after miR-93-5p transfection. The interaction between PAFAH1B1 and miR-93-5p was verified, and miR-93-5p negatively regulated the protein level of PAFAH1B1. Overexpression of PAFAH1B1 could efficiently reverse the effects of miR-93-5p mimic on BC cell mobility. Finally, inhibition of miR-93-5p was proved to impair the carcinogenic function of CAFs-exo in vivo . CONCLUSION: Exosomal miR-93-5p derived from CAFs confers oncogenicity on BC cells via sponging PAFAH1B1, suggesting a novel therapeutic strategy for BC.


Assuntos
Fibroblastos Associados a Câncer , MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , MicroRNAs/genética , Neoplasias da Bexiga Urinária/patologia , Fibroblastos , Linhagem Celular Tumoral , Fenótipo , Proliferação de Células , Proteínas Associadas aos Microtúbulos/genética , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , 1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo
9.
Ann Bot ; 131(7): 1081-1095, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-36661120

RESUMO

BACKGROUND AND AIMS: Growing evidence has suggested that plant responses to model soil microorganisms are context dependent; however, few studies have investigated the effects of whole soil microbial communities on plant performance in different abiotic and biotic conditions. To address this, we examined how soil phosphorus (P) availability and different planting patterns regulate soil microbial effects on the growth of two native plant species in a semiarid steppe. METHODS: We carried out a glasshouse experiment to explore the effects of the whole indigenous soil microbiota on the growth and performance of Leymus chinensis and Cleistogenes squarrosa using soil sterilization with different soil P availabilities and planting patterns (monoculture and mixture). Transcriptome sequencing (RNA-seq) was used to explain the potential molecular mechanisms of the soil microbial effects on C. squarrosa. KEY RESULTS: The soil sterilization treatment significantly increased the biomass of L. chinensis and C. squarrosa in both monoculture and mixture conditions, which indicated that the soil microbiota had negative growth effects on both plants. The addition of P neutralized the negative microbial effects for both L. chinensis and C. squarrosa, whereas the mixture treatment amplified the negative microbial effects on L. chinensis but alleviated them on C. squarrosa. Transcriptomic analysis from C. squarrosa roots underscored that the negative soil microbial effects were induced by the upregulation of defence genes. The P addition treatment resulted in significant decreases in the number of differentially expressed genes attributable to the soil microbiota, and some defence genes were downregulated. CONCLUSIONS: Our results underline that indigenous soil microbiota have negative effects on the growth of two dominant plant species from a semiarid steppe, but their effects are highly dependent on the soil P availability and planting patterns. They also indicate that defence genes might play a key role in controlling plant growth responses to the soil microbiota.


Assuntos
Fósforo , Solo , Microbiologia do Solo , Plantas , Poaceae/fisiologia
10.
Stat Med ; 42(12): 1909-1930, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37194500

RESUMO

In this article, we propose a two-level copula joint model to analyze clinical data with multiple disparate continuous longitudinal outcomes and multiple event-times in the presence of competing risks. At the first level, we use a copula to model the dependence between competing latent event-times, in the process constructing the submodel for the observed event-time, and employ the Gaussian copula to construct the submodel for the longitudinal outcomes that accounts for their conditional dependence; these submodels are glued together at the second level via the Gaussian copula to construct a joint model that incorporates conditional dependence between the observed event-time and the longitudinal outcomes. To have the flexibility to accommodate skewed data and examine possibly different covariate effects on quantiles of a non-Gaussian outcome, we propose linear quantile mixed models for the continuous longitudinal data. We adopt a Bayesian framework for model estimation and inference via Markov Chain Monte Carlo sampling. We examine the performance of the copula joint model through a simulation study and show that our proposed method outperforms the conventional approach assuming conditional independence with smaller biases and better coverage probabilities of the Bayesian credible intervals. Finally, we carry out an analysis of clinical data on renal transplantation for illustration.


Assuntos
Modelos Estatísticos , Humanos , Teorema de Bayes , Simulação por Computador , Modelos Lineares , Probabilidade
11.
Cell Mol Biol (Noisy-le-grand) ; 69(7): 196-204, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37715385

RESUMO

Major depressive disorder (MDD) affects approximately 16% of the global population. Our previous study has demonstrated that icariin (ICA) exhibits anti-depressant activity by increasing the expression of Brain-Derived Neurotrophic Factor (BDNF) in a rat model of chronic unpredictable mild stress (CUMS). In this study, we investigated whether and how ICA can prevent CUMS-induced depression-like behaviors in rats by modulating hippocampus neuronal apoptosis. Forty male rats were randomly divided into control, CUMS, CUMS-fluoxetine (Flx) (10 mg/kg), and CUMS-ICA (20 mg/kg) groups. Behavior tests including sucrose preference test (SPT), open field test (OFT), elevated plus-maze (EPM), and forced swimming tests (FST) were performed. The Nissl staining and TUNNEL assay were used to determine neuronal apoptosis. Subsequently, expression of the glucocorticoid receptor (GR), Bcl-2, cytochrome C, caspase-3 and Bax in the hippocampus was tested by western blot. Our results show that a chronic administration of ICA (20 mg/kg) can prevent CUMS-induced depressant-like behaviors in male model rats. Additionally, ICA significantly inhibited mitochondrial translocation of GR, reduced mitochondrial outer membrane permeabilization (MOMP) to suppress the release of cytochrome C, and then inhibit the activation of caspase-3. In conclusion, our research provides new evidence to understand the anti-depressant activity of ICA, which relates to its inhibition of neuronal apoptosis in the hippocampus through the mitochondrial apoptotic pathway.


Assuntos
Citocromos c , Transtorno Depressivo Maior , Animais , Masculino , Ratos , Apoptose , Proteína X Associada a bcl-2 , Caspase 3 , Citoplasma , Transtorno Depressivo Maior/tratamento farmacológico
12.
BMC Urol ; 23(1): 44, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36973802

RESUMO

BACKGROUND: Perineal ultrasound as a non-invasive method for the diagnosis of female stress urinary incontinence has attracted more and more attention. However, the criteria for stress urinary incontinence in women using perineal ultrasound have not been fully established. Our study aimed to evaluate characteristics of the urethral spatial movement with perineal ultrasonography. METHODS: A total of 136 female patients with stress urinary incontinence and 44 controls were enrolled. Stress urinary incontinence was diagnosed using the International Consultation on Incontinence Questionnaire Short Form, medical history and physical examination, and severity was assessed using a 1 h pad test. We described the mobility of four equidistant points (A-D) located along the urethra length. The retrovesical and urethral rotation angles were measured using perineal ultrasonography at rest and during the maximal Valsalva maneuver. RESULTS: Patients with stress urinary incontinence showed a more significant vertical movement at Points A, B and C than controls. The mean variations in the retrovesical angle were significantly larger in patients with stress urinary incontinence at rest and during the Valsalva maneuver than in controls (21.0 ± 16.5° vs. 14.7 ± 20.1°, respectively). The cut-off value for the retrovesical angle variation was 10.7° with 72% sensitivity and 54% specificity. There was a receiver-operating characteristic curve area of 0.73 and 0.72 for Points A and B, respectively. A cut-off of 10.8 mm, and 9.4 mm provided 71% sensitivity and 68% specificity and 67% sensitivity and 75% specificity, respectively. CONCLUSIONS: The spatial movement of the bladder neck and proximal urethra, and variations in the retrovesical angle may be correlated with clinical symptoms and facilitate to the assessment of SUI.


Assuntos
Períneo , Uretra , Bexiga Urinária , Incontinência Urinária por Estresse , Feminino , Humanos , Ultrassonografia/métodos , Uretra/diagnóstico por imagem , Uretra/fisiopatologia , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/fisiopatologia , Incontinência Urinária por Estresse/diagnóstico por imagem , Incontinência Urinária por Estresse/fisiopatologia , Períneo/diagnóstico por imagem
13.
Int J Mol Sci ; 24(20)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37895090

RESUMO

Hypocotyl length is a botanical trait that affects the cold tolerance of Brassica napus L. (B. napus). In this study, we constructed an F2 segregating population using the cold-resistant short hypocotyl variety '16VHNTS158' and the cold-sensitive long hypocotyl variety 'Tianyou 2288' as the parents, and BSA-seq was employed to identify candidate genes for hypocotyl length in B. napus. The results of parental differences showed that the average hypocotyl lengths of '16VHNTS158' and 'Tianyou 2288' were 0.41 cm and 0.77 cm at the 5~6 leaf stage, respectively, after different low-temperature treatments, and '16VHNTS158' exhibited lower relative ion leakage rates compared to 'Tianyou 2288'. The contents of indole acetic acid (IAA), gibberellin (GA), and brassinosteroid (BR) in hypocotyls of '16VHNTS158' and 'Tianyou 2288' increased with decreasing temperatures, but the IAA and GA contents were significantly higher than those of 'Tianyou 2288', and the BR content was lower than that of 'Tianyou 2288'. The genetic analysis results indicate that the genetic model for hypocotyl length follows the 2MG-A model. By using SSR molecular markers, a QTL locus associated with hypocotyl length was identified on chromosome C04. The additive effect value of this locus was 0.025, and it accounted for 2.5% of the phenotypic variation. BSA-Seq further localized the major effect QTL locus on chromosome C04, associating it with 41 genomic regions. The total length of this region was 1.06 Mb. Within this region, a total of 20 non-synonymous mutation genes were identified between the parents, and 26 non-synonymous mutation genes were found within the pooled samples. In the reference genome of B. napus, this region was annotated with 24 candidate genes. These annotated genes are predominantly enriched in four pathways: DNA replication, nucleotide excision repair, plant hormone signal transduction, and mismatch repair. The findings of this study provide a theoretical basis for cloning genes related to hypocotyl length in winter rapeseed and their utilization in breeding.


Assuntos
Brassica napus , Brassica napus/genética , Locos de Características Quantitativas/genética , Hipocótilo/genética , Melhoramento Vegetal , Mapeamento Cromossômico
14.
J UOEH ; 45(4): 217-220, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38057110

RESUMO

In this technical note, we primarily demonstrate the computation of confidence limits for a novel measure of average lifespan shortened (ALSS). We identified women who had died from cervical and ovarian cancer between 2000 and 2020 from the Alberta cancer registry. Years of life lost (YLL) was calculated using the national life tables of Canada. We estimated the ALSS as a ratio of YLL in relation to the expected lifespan. We computed the confidence limits of the measure using various approaches, including the normal distribution, gamma distribution, and bootstrap method. The new ALSS measure shows a modest gain in lifespan of women, particularly women with ovarian cancer, over the study period.


Assuntos
Longevidade , Neoplasias Ovarianas , Humanos , Feminino , Expectativa de Vida , Alberta , Tábuas de Vida
15.
Opt Lett ; 47(19): 5164-5167, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36181212

RESUMO

In this Letter, we experimentally investigate a new kind of nanosecond pre-pulse, which originates from the bidirectional scattering of crystals in traditional Ti:sapphire multi-pass amplifiers. The experimental results demonstrate that the intensity of scattering-induced pre-pulses is very sensitive to the scattering angle, and the delay time between the pre-pulse and the main pulse is an integer multiple of the light path in each pass of the amplifier. An optimized multi-pass amplifier configuration is proposed, for what is believed to be the first time, to suppress the scattering-induced pre-pulses. The contrast ratio between pre-pulses and the main pulse is enhanced by more than two orders of magnitude, reaching a level of 10-10. This novel multi-pass amplifier configuration is very simple and economical, and provides an effective solution for the temporal contrast enhancement in the nanosecond range.

16.
Crit Rev Food Sci Nutr ; 62(30): 8467-8496, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34058922

RESUMO

This review highlights main bioactive compounds and important biological functions especially anticancer effects of the garlic. In addition, we review current literature on the stability and bioavailability of garlic components. Finally, this review aims to provide a potential strategy for using nanotechnology to increase the stability and solubility of garlic components, providing guidelines for the qualities of garlic products to improve their absorption and prevent their early degradation, and extend their circulation time in the body. The application of nanotechnology to improve the bioavailability and targeting of garlic compounds are expected to provide a theoretical basis for the functional components of garlic to treat human health. We review the improvement of bioavailability and bioactivity of garlic bioactive compounds via nanotechnology, which could promisingly overcome the limitations of conventional garlic products, and would be used to prevent and treat cancer and other diseases in the near future.


Assuntos
Alho , Humanos , Disponibilidade Biológica , Antioxidantes , Nanotecnologia , Solubilidade
17.
Appl Opt ; 61(15): 4627-4632, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-36256306

RESUMO

It is of crucial significance to investigate and suppress pre-pulses on nanosecond time scale because the intense pre-plasma generated by them may have enough time to expand and, thus, cause fatal impact on laser-matter interactions. In this research, we analyze the potential origins of pre-pulses on nanosecond time scale in a typical Ti:sapphire chirped pulse amplification laser system. Based on the analysis, the initial status of these generated pre-pulses in the SULF-1PW laser is measured and investigated. Then different measures, including fine control on the time synchronization and the replacement for the Ti:sapphire, are adopted in the SULF-1PW laser to suppress these pre-pulses with respective origins, which can promote the energy ratio between the main pulse and these pre-pulses by 2-3 orders of magnitude. This research not only improves the temporal contrast of the SULF-1PW laser on nanosecond time scale but also provides beneficial guidance for the design and construction of similar laser facilities.

18.
J Allergy Clin Immunol ; 147(1): 255-266, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33446330

RESUMO

BACKGROUND: Eosinophilic esophagitis (EoE) is an emerging, chronic, rare allergic disease associated with marked eosinophil accumulation in the esophagus. Previous genome-wide association studies have provided strong evidence for 3 genome-wide susceptibility loci. OBJECTIVE: We sought to replicate known and suggestive EoE genetic risk loci and conduct a meta-analysis of previously reported data sets. METHODS: An EoE-Custom single-nucleotide polymophism (SNP) Chip containing 956 candidate EoE risk single-nucleotide polymorphisms was used to genotype 627 cases and 365 controls. Statistical power was enhanced by adding 1959 external controls and performing meta-analyses with 2 independent EoE genome-wide association studies. RESULTS: Meta-analysis identified replicated association and genome-wide significance at 6 loci: 2p23 (2 independent genetic effects) and 5q22, 10p14, 11q13, and 16p13. Seven additional loci were identified at suggestive significance (P < 10-6): 1q31, 5q23, 6q15, 6q21, 8p21, 17q12, and 22q13. From these risk loci, 13 protein-coding EoE candidate risk genes were expressed in a genotype-dependent manner. EoE risk genes were expressed in disease-relevant cell types, including esophageal epithelia, fibroblasts, and immune cells, with some expressed as a function of disease activity. The genetic risk burden of EoE-associated genetic variants was markedly larger in cases relative to controls (P < 10-38); individuals with the highest decile of genetic burden had greater than 12-fold risk of EoE compared with those within the lowest decile. CONCLUSIONS: This study extends the genetic underpinnings of EoE, highlighting 13 genes whose genotype-dependent expression expands our etiologic understanding of EoE and provides a framework for a polygenic risk score to be validated in future studies.


Assuntos
Esofagite Eosinofílica/genética , Loci Gênicos , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Esofagite Eosinofílica/imunologia , Estudo de Associação Genômica Ampla , Humanos , Fatores de Risco
19.
Opt Express ; 29(6): 8861-8871, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33820327

RESUMO

Controllable single-photon routing takes the central roles in optical quantum networks for quantum information processing. Given that most of the schemes previously proposed are specifically designed for the photons with selected frequencies, here we investigate how to implement the routings of single photons with different frequencies. We show that the routing capabilities of the photons with different frequencies are manipulatable by properly designing the configuration of the scatters such as the cavity with embedded atoms and the channel boundaries. This is particularly important to implement the bandwidth routings of photons in future.

20.
Opt Express ; 29(23): 37443-37452, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808815

RESUMO

In this paper, we report that the conversion efficiency and spectrum of femtosecond optical parametric amplification (fs-OPA) can be significantly enhanced by employing a compact cascaded femtosecond OPA (CF-OPA) scheme with the self-compensation of the temporal walk-off between two nonlinear gain media. Correspondingly, the gain related temporal contrast can also be improved. The feasibility of the CF-OPA method using three cascaded BBO crystals is numerically and experimentally analyzed. Moreover, by replacing the conventional fs-OPA with the CF-OPA and optimizing the design, the performance of a nonlinear temporal filter combining cross-polarized wave generation and fs-OPA is comprehensively improved. The experimental results demonstrate the superiority of the CF-OPA scheme, which can generate high-performance cleaned pulses at 1 kHz repetition rate with energy of 340µJ, energy fluctuation below 0.9% (RMS), spectral width of 97 nm (FWHM), Fourier-transform-limited pulse width of 12 fs and temporal contrast better than 10-12. To the best of our knowledge, this is the first reported temporal walk-off self-compensated quasi-collinear CF-OPA geometry adopting three cascaded BBO crystals, which can be easily generalized to other wavelengths or nonlinear crystals. The above nonlinear temporal filter with a CF-OPA scheme has the rarest comprehensive parameters, which can provide excellent seed pulses for PW and 10 PW class femtosecond laser systems.

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