Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 145
Filtrar
1.
ACS Nano ; 18(19): 12333-12340, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38688009

RESUMO

In this study, we investigated the optical properties of a transition metal dichalcogenide (TMD) substrate via Mie-scattering-induced surface analysis (MISA). Employing near-field optical microscopy and finite-difference time-domain (FDTD) simulations, we systemically prove and directly visualize the Mie scattering of superspherical gold nanoparticles (s-AuNPs) at the nanoscale. Molybdenum disulfide substrates exhibited optical isotropy, while rhenium disulfide (ReS2) substrates showed anisotropic behavior attributed to the interaction with incident light's electric field. Our study revealed substantial anisotropic trends in Mie scattering, particularly in the near-infrared energy range, with ReS2 exhibiting more pronounced spectral and angular responses in satellite peaks. Our results emphasize the application of Mie scattering, exploring the optical properties of substrates and contributing to a deeper understanding of nanoscale light-matter interactions.

2.
Res Vet Sci ; 171: 105201, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38442531

RESUMO

Infectious bronchitis virus (IBV) is a contagious coronavirus causing respiratory and urogenital disease in chickens and is responsible for significant economic losses for both the broiler and table egg layer industries. Despite IBV being regularly monitored using standard epidemiologic surveillance practices, knowledge and evidence of risk factors associated with IBV transmission remain limited. The study objective was to compare risk factor modeling outcomes between a traditional stepwise variable selection approach and a machine learning-based random forest Boruta algorithm using routinely collected IBV antibody titer data from broiler flocks. IBV antibody sampling events (n = 1111) from 166 broiler sites between 2016 and 2021 were accessed. Ninety-two geospatial-related and poultry-density variables were obtained using a geographic information system and data sets from publicly available sources. Seventeen and 27 candidate variables were screened to potentially have an association with elevated IBV antibody titers according to the manual selection and machine learning algorithm, respectively. Selected variables from both methods were further investigated by construction of multivariable generalized mixed logistic regression models. Six variables were shortlisted by both screening methods, which included year, distance to urban areas, main roads, landcover, density of layer sites and year, however, final models for both approaches only shared year as an important predictor. Despite limited significance of clinical outcomes, this work showcases the potential of a novel explorative modeling approach in combination with often unutilized resources such as publicly available geospatial data, surveillance health data and machine learning as potential supplementary tools to investigate risk factors related to infectious diseases.


Assuntos
Infecções por Coronavirus , Vírus da Bronquite Infecciosa , Doenças das Aves Domésticas , Animais , Galinhas , Doenças das Aves Domésticas/prevenção & controle , Aves Domésticas , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/prevenção & controle , Algoritmos
3.
ACS Photonics ; 11(3): 1006-1011, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38523747

RESUMO

Photonic integrated circuits are paving the way for novel on-chip functionalities with diverse applications in communication, computing, and beyond. The integration of on-chip light sources, especially single-mode lasers, is crucial for advancing those photonic chips to their full potential. Recently, novel concepts involving topological designs introduced a variety of options for tuning device properties, such as the desired single-mode emission. Here, we introduce a novel cavity design that allows amplification of the topological interface mode by deterministic placement of gain material within a topological lattice. The proposed design is experimentally implemented by a selective epitaxy process to achieve closely spaced Si and InGaAs nanorods embedded within the same layer. This results in the first demonstration of a single-mode laser in the telecom band using the concept of amplified topological modes without introducing artificial losses.

4.
Nanomaterials (Basel) ; 13(24)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38133049

RESUMO

Topological nature in different areas of physics and electronics has often been characterized and controlled through topological invariants depending on the global properties of the material. The validity of bulk-edge correspondence and symmetry-related topological invariants has been extended to non-Hermitian systems. Correspondingly, the value of geometric phases, such as the Pancharatnam-Berry or Zak phases, under the adiabatic quantum deformation process in the presence of non-Hermitian conditions, are now of significant interest. Here, we explicitly calculate the Zak phases of one-dimensional topological nanobeams that sustain guided-mode resonances, which lead to energy leakage to a continuum state. The retrieved Zak phases show as zero for trivial and as π for nontrivial photonic crystals, respectively, which ensures bulk-edge correspondence is still valid for certain non-Hermitian conditions.

5.
Vaccine ; 41(49): 7369-7376, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37932132

RESUMO

Highly pathogenic avian influenza virus (HPAIV) has caused widespread outbreaks in poultry in the Americas. Because of the duration and extent of these outbreaks, vaccine use may be an additional tool to limit virus spread. Three vaccines were evaluated for efficacy in chickens against a current North American clade 2.3.4.4b H5 HPAIV isolate, A/turkey/Indiana/3703-003/2022 H5N1. The vaccines included: 1) a commercial inactivated reverse genetics (rg) generated H5N1 product with a clade 2.3.4.4c H5 hemagglutinin (HA) (rgH5N1); 2) a commercial alphavirus RNA particle (RP) vaccine with the TK/IN/22 HA; and 3) an in-house inactivated rg produced vaccine with the TK/IN/22 HA and a North American lineage N9 neuraminidase (NA) (SEP-22-N9). Both inactivated vaccines were produced with HA genes that were modified to be low pathogenic and with the remaining genes from the PR8 influenza strain. All vaccines provided 100% protection against mortality and morbidity and all vaccines reduced virus shed by the oropharyngeal and cloacal routes significantly compared to sham vaccinates. However, differences were observed among the vaccines in quantities of virus shed at two- and four-days post challenge (DPC). To determine if infected birds could be identified after vaccination to aid surveillance programs, serum was collected from the RP and SEP-22-N9 vaccine groups at 7, 10, and 14 DPC to detect antibody to the NA and nucleoprotein (NP) of the challenge virus by enzyme linked lectin assay (ELLA) and ELISA. As early as 7DPC ELLA detected antibody in sera from 100% of the chickens in the RP vaccinated group and 70% of the chickens in the SEP-22-N9 vaccinated group. Antibody to the NP was detected by commercial ELISA in more than 50% of the birds in the RP vaccinated group at each time point.


Assuntos
Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Vacinas contra Influenza , Influenza Aviária , Animais , Galinhas , Vacinas de Produtos Inativados , América do Norte , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética
6.
Pathogens ; 12(10)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37887747

RESUMO

To enhance the efficacy of the current Newcastle disease vaccine, we have selected potential adjuvants that target well-characterized pattern recognition receptors: the toll-like receptors (TLRs). Imiquimod is a small-molecule activator of TLR7, which is a sensor of dsDNA. ODN-1826 is a mimetic of CpG DNA and ligates TLR21 (a chicken homologue of TLR9 in mammals). The activation of TLRs leads to antiviral responses, including the induction of type I interferons (IFNs). In this study, birds were vaccinated intranasally with a live LaSota strain with or without imiquimod or ODN-1826 (50 µg/bird). Two weeks after vaccination, the birds were challenged with a virulent Newcastle disease virus (chicken/CA/212676/2002). Both adjuvants (imiquimod or ODN-1826) induced higher and more uniform antibody titers among vaccinated birds compared with the live vaccine-alone group. In addition, adjuvanted vaccines demonstrated greater protective efficacy in terms of the reduction in virus-shedding titer and the number of birds shedding the challenge virus at 2 and 4 days post-challenge. A differential expression of antiviral and immune-related genes was observed among groups from tissues (Harderian gland, trachea, cecal tonsil, and spleen) collected 1 and 3 days after treatment. These results demonstrate the potential of TLR-targeted adjuvants as mucosal vaccine enhancers and warrant a further characterization of immune correlates and optimization for efficacy.

7.
Viruses ; 15(10)2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37896883

RESUMO

Influenza A virus (IAV) populations harbor large subpopulations of defective-interfering particles characterized by internally deleted viral genomes. These internally deleted genomes have demonstrated the ability to suppress infectivity and boost innate immunity, rendering them promising for therapeutic and immunogenic applications. In this study, we aimed to investigate the diversity and complexity of the internally deleted IAV genomes within a panel of plaque-purified avian influenza viruses selected for their enhanced interferon-inducing phenotypes. Our findings unveiled that the abundance and diversity of internally deleted viral genomes were contingent upon the viral subculture and plaque purification processes. We observed a heightened occurrence of internally deleted genomes with distinct junctions in viral clones exhibiting enhanced interferon-inducing phenotypes, accompanied by additional truncation in the nonstructural 1 protein linker region (NS1Δ76-86). Computational analyses suggest the internally deleted IAV genomes can encode a broad range of carboxy-terminally truncated and intrinsically disordered proteins with variable lengths and amino acid composition. Further research is imperative to unravel the underlying mechanisms driving the increased diversity of internal deletions within the genomes of viral clones exhibiting enhanced interferon-inducing capacities and to explore their potential for modulating cellular processes and immunity.


Assuntos
Vírus da Influenza A , Influenza Humana , Animais , Humanos , Interferons/genética , Imunidade Inata , RNA Viral/genética , Genoma Viral , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/genética
8.
ACS Appl Mater Interfaces ; 15(23): 28763-28771, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37269552

RESUMO

Plasma enhanced atomic layer deposition (PEALD) of silicon nitride (SiNx) using very high frequency (VHF, 162 MHz) plasma source was investigated at the process temperatures of 100, 200, and 300 °C. Two aminosilane precursors having different numbers of amino ligands, bis(tert-butylamino)silane (BTBAS) and di(sec-butylamino)silane (DSBAS), were used as Si precursors. A comparative study was also conducted to verify the effect of the number of amino ligands on the properties of SiNx film. At all process temperatures, DSBAS, having one amino ligand, performed better than BTBAS in various aspects. SiNx films deposited using DSBAS had lower surface roughness, higher film density, lower wet etch rate, improved electrical characteristics, and higher growth rate than those deposited using BTBAS. With the combination of a VHF plasma source and DSBAS with one amino ligand, the SiNx films grown at 300 °C exhibited low wet etch rates (≤2 nm/min) in a dilute HF solution (100:1 of deionized water:HF) as well as low C content below the XPS detection limit. Also, excellent step coverage close to 100% on high aspect ratio (30:1) trench structures was obtained by using VHF plasma, which could provide sufficient flux of plasma species inside the trenches in conjunction with DSBAS having fewer amino ligands than BTBAS.

9.
bioRxiv ; 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37293019

RESUMO

Bioactive metabolites produced by symbiotic microbiota causally impact host health and disease, nonetheless, incomplete functional annotation of genes as well as complexities and dynamic nature of microbiota make understanding species-level contribution in production and actions difficult. Alpha-galactosylceramides produced by Bacteroides fragilis (BfaGC) are one of the first modulators of colonic immune development, but biosynthetic pathways and the significance of the single species in the symbiont community still remained elusive. To address these questions at the microbiota level, we have investigated the lipidomic profiles of prominent gut symbionts and the metagenome-level landscape of responsible gene signatures in the human gut. We first elucidated the chemical diversity of sphingolipid biosynthesis pathways of major bacterial species. In addition to commonly shared ceramide backbone synthases showing two distinct intermediates, alpha-galactosyltransferase (agcT), the necessary and sufficient component for BfaGC production and host colonic type I natural killer T (NKT) cell regulation by B. fragilis, was characterized by forward-genetics based targeted metabolomic screenings. Phylogenetic analysis of agcT in human gut symbionts revealed that only a few ceramide producers have agcT and hence can produce aGCs, on the other hand, structurally conserved homologues of agcT are widely distributed among species lacking ceramides. Among them, alpha-glucosyl-diacylglycerol(aGlcDAG)-producing glycosyltransferases with conserved GT4-GT1 domains are one of the most prominent homologs in gut microbiota, represented by Enterococcus bgsB . Of interest, aGlcDAGs produced by bgsB can antagonize BfaGC-mediated activation of NKT cells, showing the opposite, lipid structure-specific actions to regulate host immune responses. Further metagenomic analysis of multiple human cohorts uncovered that the agcT gene signature is almost exclusively contributed by B. fragilis , regardless of age, geographical and health status, where the bgsB signature is contributed by >100 species, of which abundance of individual microbes is highly variable. Our results collectively showcase the diversities of gut microbiota producing biologically relevant metabolites in multiple layers-biosynthetic pathways, host immunomodulatory functions and microbiome-level landscapes in the host.

10.
Avian Dis ; 67(1): 33-41, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37140109

RESUMO

A complete genome sequence of a VG/GA -like strain of avian orthoavulavirus 1 (AOAV-1) was identified by nontargeted next-generation sequencing of an oropharyngeal swab sample collected from a carcass of a 12-mo-old backyard chicken. The isolate has a fusion (F) protein cleavage site motif consistent with a low virulent AOAV-1, but it has a unique motif with phenylalanine at position 117 (112G-R-Q-G-R↓F117), which is typical for virulent AOAV-1 strains. The one nucleotide difference at the cleavage site compared to other low-virulence viruses made the isolate detectable by F-gene-specific real-time reverse transcription-PCR (rRT-PCR) developed as a diagnostic test to specifically detect virulent strains. The mean death time determined in eggs and intracerebral pathogenicity index determined in chickens classified the isolate as lentogenic. This is the first report of a lentogenic VG/GA-like virus with a phenylalanine residue at position 117 of the F protein cleavage site in the United States. In addition to concern for potential pathogenic shift of the virus through additional changes at the cleavage site, our finding warrants increased awareness of diagnosticians of potential false positive F-gene rRT-PCR tests.


Secuenciación y caracterización del genoma de un aislado similar a VG/GA del ortoavulavirus aviar 1 con un motivo único en el sitio de disociación del gene de fusión. Se identificó una secuencia genómica completa de una cepa similar a la cepa Villegas-Glisson/Universidad de Georgia (VG/GA) del ortoavulavirus aviar 1 (AOAV-1) mediante secuenciación no dirigida de nueva generación de una muestra de hisopo orofaríngeo recolectada de una gallina muerta de traspatio de 12 meses. El aislado tiene un motivo en el sitio de disociación de la proteína de fusión (F) consistente con un ortoavulavirus aviar de baja virulencia, pero tiene un motivo único con fenilalanina en la posición 117 (112G-R-Q-G-R↓F117), que es típico para cepas virulentas del AOAV-1. La diferencia de un nucleótido en el sitio de escisión en comparación con otros virus de baja virulencia hizo que el aislado fuera detectable mediante transcripción reversa y PCR en tiempo real en tiempo real específica del gene F (rtRT-PCR) desarrollada como una prueba de diagnóstico para detectar específicamente a las cepas virulentas. El tiempo medio de muerte determinado en huevos y el índice de patogenicidad intracerebral determinado en pollos clasificaron al aislado como lentogénico. Este es el primer informe en los Estados Unidos de un virus lentogénico similar a VG/GA con un residuo de fenilalanina en la posición 117 del sitio de disociación de la proteína F. Además de la preocupación por el posible cambio patogénico del virus a través de cambios adicionales en el sitio de disociación, nuestro contribuye con un mayor conocimiento por parte del personal de diagnóstico acerca de posibles falsos positivos en las pruebas rtRT-PCR del gene F.


Assuntos
Doença de Newcastle , Doenças das Aves Domésticas , Animais , Galinhas , Doenças das Aves Domésticas/patologia , Vírus da Doença de Newcastle/genética , Sequência de Bases , Virulência/genética , Filogenia
11.
Avian Dis ; 67(1): 94-101, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37140117

RESUMO

Despite the essential role of innate immunity in defining the outcome of viral infections, the roles played by different components of the avian innate immune system are poorly delineated. Here, we investigated the potential implication of avian toll-like receptor (TLR) 3 (TLR3) and melanoma differentiation-associated (MDA) gene 5 (MDA5) receptors of double-stranded RNA (dsRNA) in induction of the interferon pathway and avian orthoavulavirus 1 (AOAV-1) replication in chicken-origin DF-1 fibroblast cells. TLR3 and MDA5 knockout (KO) DF-1 cells were generated using our avian-specific CRISPR/Cas9 system and stimulated with a synthetic dsRNA ligand polyinosinic:polycytidylic acid [poly(I:C)] or infected with AOAV-1 (previously known as Newcastle disease virus). Poly(I:C) treatment in cell culture media resulted in significant upregulation of interferon (IFN)α, IFNß, and Mx1 gene expression in wild type (WT) DF-1 cells but not in TLR3-MDA5 double KO cells. Interestingly, poly(I:C) treatment induced rapid cell degeneration in WT and MDA5 KO cells, but not in TLR3 knockout or TRL3-MDA5 double knockout (DKO) cells, directly linking poly(I:C)-induced cell degeneration to TLR3-mediated host response. The double knockout cells supported significantly higher replication of AOAV-1 virus than did the WT cells. However, no correlation between the level of virus replication and type I IFN response was observed. Our study suggests that innate immune response is host- and pathogen specific, and further investigation is needed to understand the relevance of dsRNA receptor-mediated immune responses in viral replication and pathogenesis in avian species.


Nota de investigación- En bloqueo de los genes TLR3 y MDA5 en las células DF-1 mejoran la replicación de Ortoavulavirus aviar 1. A pesar del papel esencial de la inmunidad innata en la definición del resultado de las infecciones virales, las funciones que desempeñan los diferentes componentes del sistema inmunitario innato aviar no están completamente definidas. En este estudio se investigó el posible papel del receptor aviar tipo toll (TLR) número 3 (TLR3) y los receptores de ARN de doble cadena (dsRNA del gene asociado a la diferenciación de melanoma (MDA) número 5 (MDA5) en la inducción de la vía del interferón y en la replicación del Ortoavulavirus 1 (AOAV-1) en células de fibroblastos DF-1 de origen en pollo. Las células DF-1 con los genes TLR3 y MDA5 bloqueado (KO) se generaron utilizando nuestro sistema CRISPR/Cas9 específico para aves y se estimularon con un ligando de dsRNA sintético poliinosínico: ácido policitidílico [poli(I:C)] o se infectaron con AOAV-1 (anteriormente conocido como el virus de la enfermedad de Newcastle). El tratamiento con poli(I:C) en medios de cultivo celular resultó en una regulación positiva significativa de la expresión génica de interferón (IFN)α, IFNß y Mx1 en células DF-1 de tipo silvestre (WT) pero no en células con doble bloqueo TLR3-MDA5 (DKO). Curiosamente, el tratamiento con poli(I:C) indujo una rápida degeneración celular en las células silvestres (WT) y las células con el gene MDA5 bloqueado, pero no en las células con bloqueo del gene TLR3 o con las células con doble bloqueo de TRL3-MDA5, lo que vincula directamente la degeneración celular inducida por poli(I:C) con la respuesta de la huésped mediada por TLR3. Las células con doble bloqueo soportaron una replicación significativamente mayor del Ortoavulavirus 1 que las células silvestres. Sin embargo, no se observó correlación entre el nivel de replicación del virus y la respuesta de IFN tipo I. Este estudio sugiere que la respuesta inmune innata es específica del huésped y del patógeno, y se necesita más investigación para comprender la relevancia de las respuestas inmunes mediadas por el receptor dsRNA en la replicación viral y en la patogénesis en las especies aviares.


Assuntos
Doenças das Aves Domésticas , Receptor 3 Toll-Like , Animais , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Vírus da Doença de Newcastle/genética , Imunidade Inata , RNA de Cadeia Dupla , Interferons/genética
12.
Nat Commun ; 14(1): 931, 2023 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-36805660

RESUMO

Connexin family proteins assemble into hexameric hemichannels in the cell membrane. The hemichannels dock together between two adjacent membranes to form gap junction intercellular channels (GJIChs). We report the cryo-electron microscopy structures of Cx43 GJICh, revealing the dynamic equilibrium state of various channel conformations in detergents and lipid nanodiscs. We identify three different N-terminal helix conformations of Cx43-gate-covering (GCN), pore-lining (PLN), and flexible intermediate (FIN)-that are randomly distributed in purified GJICh particles. The conformational equilibrium shifts to GCN by cholesteryl hemisuccinates and to PLN by C-terminal truncations and at varying pH. While GJIChs that mainly comprise GCN protomers are occluded by lipids, those containing conformationally heterogeneous protomers show markedly different pore sizes. We observe an α-to-π-helix transition in the first transmembrane helix, which creates a side opening to the membrane in the FIN and PLN conformations. This study provides basic structural information to understand the mechanisms of action and regulation of Cx43 GJICh.


Assuntos
Conexina 43 , Canais Iônicos , Humanos , Microscopia Crioeletrônica , Subunidades Proteicas , Junções Comunicantes
13.
Vaccine ; 41(11): 1848-1858, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36669965

RESUMO

Emerging avian influenza viruses pose a high risk to poultry production, necessitating the need for more broadly protective vaccines. Live attenuated influenza vaccines offer excellent protective efficacies but their use in poultry farms is discouraged due to safety concerns related to emergence of reassortant viruses. Vaccination of chicken embryos inside eggs (in ovo) induces early immunity in young chicks while reduces the safety concerns related to the use of live vaccines on farms. However, in ovo vaccination using influenza viruses severely affects the egg hatchability. We previously engineered a high interferon-inducing live attenuated influenza vaccine candidate with an enhanced protective efficacy in chickens. Here, we asked whether we could further modify this high interferon-inducing vaccine candidate to develop an in ovo-compatible live attenuated influenza vaccine. We first showed that the enhanced interferon responses induced by the vaccine is not enough to attenuate the virus in ovo. To reduce the pathogenicity of the virus for chicken embryos, we replaced the hemagglutinin cleavage site of the H7 vaccine virus (PENPKTR/GL) with that of the H6-subtype viruses (PQIETR/GL) and disrupted the ribosomal frameshifting site responsible for viral polymerase acidic X protein expression. In ovo vaccination of chickens with up to 105 median egg infectious dose of the modified vaccine had minimal effects on hatchability while protecting the chickens against a heterologous challenge virus at two weeks of age. This study demonstrates that targeted genetic mutations can be applied to further attenuate and enhance the safety of live attenuated influenza vaccines to develop future in ovo vaccines for poultry.


Assuntos
Vacinas contra Influenza , Influenza Aviária , Embrião de Galinha , Animais , Galinhas , Hemaglutininas , Proteínas Virais/genética , Vacinas Atenuadas , Interferons , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Anticorpos Antivirais
14.
JAMA Intern Med ; 183(3): 275-276, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36716020

RESUMO

This cross-sectional study assesses Medicaid spending associated with citrate-free vs original adalimumab.


Assuntos
Ácido Cítrico , Medicaid , Humanos , Estados Unidos , Adalimumab , Citratos , Gastos em Saúde
15.
Opt Express ; 30(15): 26570-26580, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36236845

RESUMO

We present a new controllable superflash, a maximum transient peak at the falling edge of a square pulse, using a three-level electromagnetically induced transparency (EIT). The superflash in a two-level system occurs at a certain value of the detuning of the probe laser (Δpeak) when the optical depth (OD) of the medium is sufficiently large and constant. Here, we show the external tunability of the Δpeak for obtaining the maximum transient peak by introducing a three-level EIT. Owing to the EIT dispersion properties, we effectively tune the phase of the forward-scattered light (Es) by externally controlling the EIT coupling light intensities associated with the Rabi frequency (Ωc). When the incident light is turned off, the total transmitted field (Et) experiences an out-of-phase shift, producing a peak intensity that is three times higher than the input. We observe that this new class of superflash (Type II) occurs near the EIT window and exhibits inverse-linearity of the OD, which is in contrast with the characteristics of the previously reported two-level superflash (Type I). Furthermore, we find the quadratic nature of tunability in Δpeak(Ωc).The new tunability of the superflash by the Rabi frequency may facilitate more rapid and effective control of the superflash compared to a passive optical medium.

16.
JCO Oncol Pract ; 18(9): e1522-e1532, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35731996

RESUMO

PURPOSE: Regulatory agencies have sought to speed up the review of new cancer medicines and reduce delays in approval between countries. We examined trends in regulatory review times and association with clinical benefit for new cancer medicines in six jurisdictions: United States (Food and Drug Administration [FDA]), European Union (European Medicines Agency [EMA]), Switzerland (Swissmedic), Japan (Pharmaceuticals and Medical Devices Agency [PMDA]), Canada (Health Canada), and Australia (Therapeutic Goods Administration). METHODS: We studied all new cancer drugs approved in the six aforementioned jurisdictions from 2007 to 2020. We extracted all applicable expedited programs, total regulatory review times, and, for drugs first approved by the FDA, times to subsequent regulatory approval. Clinical benefit was assessed using the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale value framework and ASCO-Cancer Research Committee's targets. Nonparametric Kruskal-Wallis test was used to compare total review times for high versus low clinical benefit drugs. RESULTS: One hundred and twenty eight drugs received initial approval in at least one of the six included jurisdictions. Most drugs approved by the FDA (91%) and Health Canada (59%) qualified for at least one expedited program within those jurisdictions, compared with 46% of EMA approvals and 18% of PMDA approvals. The FDA was the first regulator to approve 102 (80%) drugs. Delays in submission accounted for a median of 20.2% (EMA) to 83.8% (PMDA) of the time to subsequent approval. There was no association between high clinical benefit and shorter total review times. CONCLUSION: Most new cancer therapies were approved first by the FDA, and delays in submission of regulatory applications accounted for substantial delays in approving cancer drugs in other countries. Regulators should prioritize faster review for drugs with high clinical benefit.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Aprovação de Drogas , União Europeia , Humanos , Japão , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Preparações Farmacêuticas , Suíça , Estados Unidos
17.
ACS Appl Bio Mater ; 5(6): 2812-2818, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35543024

RESUMO

Recently, 3D printing has provided opportunities for designing complex structures with ease. These printed structures can serve as molds for complex materials such as DNA and cetyltrimethylammonium chloride (CTMA)-modified DNA that have easily tunable functionalities via the embedding of various nanomaterials such as ions, nanoparticles, fluorophores, and proteins. Herein, we develop a simple and efficient method for constructing DNA flat and curved films containing water-soluble/thermochromatic dyes and di/trivalent ions and CTMA-modified DNA films embedded with organic light-emitting molecules (OLEM) with the aid of 2D/3D frames made by a 3D printer. We study the Raman spectra, current, and resistance of Cu2+-doped and Tb3+-doped DNA films and the photoluminescence of OLEM-embedded CTMA-modified DNA films to better understand the optoelectric characteristics of the samples. Compared to pristine DNA, ion-doped DNA films show noticeable variation of Raman peak intensities, which might be due to the interaction between the ion and phosphate backbone of DNA and the intercalation of ions in DNA base pairs. As expected, ion-doped DNA films show an increase of current with an increase in bias voltage. Because of the presence of metallic ions, DNA films with embedded ions showed relatively larger current than pristine DNA. The photoluminescent emission peaks of CTMA-modified DNA films with OLEMRed, OLEMGreen, and OLEMBlue were obtained at the wavelengths of 610, 515, and 469 nm, respectively. Finally, CIE color coordinates produced from CTMA-modified DNA films with different OLEM color types were plotted in color space. It may be feasible to produce multilayered DNA films as well. If so, multilayered DNA films embedded with different color dyes, ions, fluorescent materials, nanoparticles, proteins, and drug molecules could be used to realize multifunctional physical devices such as energy harvesting and chemo-bio sensors in the near future.


Assuntos
DNA , Nanoestruturas , Cetrimônio , Corantes , DNA/química , Íons , Nanoestruturas/química
18.
Sensors (Basel) ; 22(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35458856

RESUMO

This study proposes a 3D global localization method that implements mobile LiDAR mapping and point cloud registration to recognize the locations of objects in an underground mine. An initial global point cloud map was built for an entire underground mine area using mobile LiDAR; a local LiDAR scan (local point cloud) was generated at the point where underground positioning was required. We calculated fast point feature histogram (FPFH) descriptors for the global and local point clouds to extract point features. The match areas between the global and the local point clouds were searched and aligned using random sample consensus (RANSAC) and iterative closest point (ICP) registration. The object's location on the global coordinate system was measured using the LiDAR sensor trajectory. Field experiments were performed at the Gwan-in underground mine using three mobile LiDAR systems. The local point cloud dataset formed for the six areas of the underground mine precisely matched the global point cloud, with a low average error of approximately 0.13 m, regardless of the type of mobile LiDAR system used. In addition, the LiDAR senor trajectory was aligned on the global coordinate system to confirm the change in the dynamic object's position over time.

20.
Nature ; 600(7888): 302-307, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34759313

RESUMO

Small molecules derived from symbiotic microbiota critically contribute to intestinal immune maturation and regulation1. However, little is known about the molecular mechanisms that control immune development in the host-microbiota environment. Here, using a targeted lipidomic analysis and synthetic approach, we carried out a multifaceted investigation of immunomodulatory α-galactosylceramides from the human symbiont Bacteroides fragilis (BfaGCs). The characteristic terminal branching of BfaGCs is the result of incorporation of branched-chain amino acids taken up in the host gut by B. fragilis. A B. fragilis knockout strain that cannot metabolize branched-chain amino acids showed reduced branching in BfaGCs, and mice monocolonized with this mutant strain had impaired colonic natural killer T (NKT) cell regulation, implying structure-specific immunomodulatory activity. The sphinganine chain branching of BfaGCs is a critical determinant of NKT cell activation, which induces specific immunomodulatory gene expression signatures and effector functions. Co-crystal structure and affinity analyses of CD1d-BfaGC-NKT cell receptor complexes confirmed the interaction of BfaGCs as CD1d-restricted ligands. We present a structural and molecular-level paradigm of immunomodulatory control by interactions of endobiotic metabolites with diet, microbiota and the immune system.


Assuntos
Aminoácidos de Cadeia Ramificada/imunologia , Aminoácidos de Cadeia Ramificada/metabolismo , Bacteroides fragilis/metabolismo , Galactosilceramidas/imunologia , Galactosilceramidas/metabolismo , Microbioma Gastrointestinal/imunologia , Simbiose/imunologia , Aminoácidos de Cadeia Ramificada/química , Animais , Antígenos CD1d/imunologia , Bacteroides fragilis/genética , Humanos , Camundongos , Modelos Animais , Modelos Moleculares , Células T Matadoras Naturais/citologia , Células T Matadoras Naturais/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...