Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 61
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33591708

RESUMO

Tactile sensors are indispensable to wearable electronics, but still lack self-powering, high resolution, and flexibility. Herein, we present direct-written piezoelectric poly(vinylidene difluoride) fibers that are orthogonally assembled into nanofibrous grids (NFGs) as self-powered tactile sensors. Five nanofibrous strips (NFSs) are written on a polyurethane film via a uniform-field electrospinning (UFES) process, and two polyurethane films are orthogonally assembled into 5 × 5 NFGs with 25 pixels. Benefited from the mechanical flexibility and helical architecture of UFES fibers, stable piezoelectric outputs have been detected according to different locations or different pressures on an NFS, and a sensitivity of 7.1 mV/kPa is detected from the slope of voltage-pressure curves. In the orthogonally assembled NFGs, the pressure on a pixel of an NFS causes corresponding deformations of neighboring NFSs. The piezoelectric outputs vary with the distance from the pressing point, enabling us to position the pressing points and track the pressing trajectory in real time. Through judging piezoelectric outputs of all NFSs, precise locations of any pressed pixel with a resolution of 1 mm are presented vividly via luminous light-emitting diodes (LED), and the mapping profiles are displayed by pressing metal letters (S, W, J, T, and U) on multiple pixels. Furthermore, the coordinates of pressure either on an NFS or between NFSs with a resolution of 0.5 mm are reported digitally on a liquid crystal display (LCD). Thus, we developed novel self-powered tactile sensors with orthogonal NFGs to achieve real-time motion tracking, accurate spatial sensing, and location identification with high resolutions, which provide potential applications in electronic skin, robotics, and interface of artificial intelligence.

2.
J Proteome Res ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200940

RESUMO

Rapid early triage and dose estimation is vital for limited medical resource allocation and treatment of a large number of the wounded after radiological accidents. Lipidomics has been utilized to delineate biofluid lipid signatures after irradiation. Here, high-coverage targeted lipidomics was employed to screen radiosensitive lipids after 0, 1, 2, 3, 5, and 8 Gy total body irradiation at 4, 24, and 72 h postirradiation in rat plasma. Ultra-performance liquid chromatography-tandem mass spectrometry with a multiple reaction monitoring method was utilized. In total, 416 individual lipids from 18 major classes were quantified and those biomarkers altered in a dose-dependent manner constituted panel A-panel D. Receiver operator characteristic curve analysis using combined lipids showed good to excellent sensitivity and specificity in triaging different radiation exposure levels (area under curve = 0.814-1.000). The equations for dose estimation were established by stepwise regression analysis for three time points. A novel strategy for radiation early triage and dose estimation was first established and validated using panels of lipids. Our study suggests that it is feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage, which can provide further insights in developing lipidomics strategies for radiation biodosimetry in humans.

3.
J Bioinform Comput Biol ; : 2050042, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33215966

RESUMO

A front-end method based on random forest proximity distance (PD) is used to screen the test set to improve protein-protein interaction site (PPIS) prediction. The assessment of a distance metric is done under the assumption that a distance definition of higher quality leads to higher classification. On an independent test set, the numerical analysis based on statistical inference shows that the PD has the advantage over Mahalanobis and Cosine distance. Based on the fact that the proximity distance depends on the tree composition of the random forest model, an iterative method is designed to optimize the proximity distance, which adjusts the tree composition of the random forest model by adjusting the size of the training set. Two PD metrics, 75PD and 50PD, are obtained by the iterative method. On two independent test sets, compared with the PD produced by the original training set, the values of 75PD in Matthews correlation coefficient and F1 score were higher, and the differences between them were statistically significant. All numerical experiments show that the closer the distance between the test data and the training data, the better the prediction results of the predictor. These indicate that the iterative method can optimize proximity distance definition and the distance information provided by PD can be used to indicate the reliability of prediction results.

4.
Biomed Microdevices ; 22(3): 56, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32821970

RESUMO

The mechanical and electrical properties of biomaterials are essential in cell function regulation during cell-biomaterial interaction. However, previous studies focused on probing cell regulation mechanisms under one type of stimulus, and a platform that enables the study of electromechanical coupling effects of a biomaterial on cells is still lacking. Here, we present an in-situ electromechanical testing and loading system to image live cells when co-cultured with electroactive biomaterials. The system can provide accurate and repeatable stretch on biomaterials and cells to mimic in vivo tension microenvironment. Besides, the integrated displacement transducer, force sensor, and electrical signal detector enable the real time detection of electromechanical signals on electroactive biomaterials under various stretch loading. Combined with a microscope, live cell imaging can be realized to probe cell behavior. The feasibility of the system is validated by culturing mesenchymal stem cells on piezoelectric nanofiber and conductive hydrogel. Experiment results show the device as a reliable and accurate tool to investigate electromechanical properties of biomaterials and probe essential features of live cells. Our system provides a way to correlate cell behavior with electromechanical cues directly and is useful for exploration of cell function during cell-biomaterial interaction.

5.
ACS Med Chem Lett ; 11(6): 1221-1227, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32551004

RESUMO

Novel tricyclic analogues were designed, synthesized, and evaluated as RORγt inverse agonists. Several of these compounds were potent in an IL-17 human whole blood assay and exhibited excellent oral bioavailability in mouse pharmacokinetic studies. This led to the identification of compound 5, which displayed dose-dependent inhibition of IL-17F production in a mouse IL-2/IL-23 stimulated pharmacodynamic model. In addition, compound 5 was studied in mouse acanthosis and imiquimod-induced models of skin inflammation, where it demonstrated robust efficacy comparable to a positive control. As a result of this excellent overall profile, compound 5 (BMS-986251) was selected as a clinically viable developmental candidate.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32591332

RESUMO

OBJECTIVES: The aim of this study was to examine whether oromaxillofacial computed tomography (CT) examination causes biologic damage in lymphocytes and whether the biologic damage is related to radiation dose, patient age, or gender. STUDY DESIGN: Peripheral blood was taken from 51 individuals and divided into control, in vivo, and in vitro irradiation groups. Biologic damage was assessed by comparing rates of chromosomal aberrations (CAs), including dicentric chromosomes (dics), centric rings, and acentric fragments; and nuclear aberrations, including micronuclei (MN), nuclear buds (NBUDs), and nucleoplasmic bridges (NPBs) in the peripheral blood before and after CT examination. Absorbed and effective doses were calculated with the software VirtualDose, and the blood dose was estimated accordingly. RESULTS: The rates of acentric fragments, MN, NBUDs, and NPBs in the in vivo (P ≤ .008) and in vitro (P ≤ .003) irradiation groups were significantly higher than those in the control groups. The acentric fragment rate (P = .013) and MN rate (P = .002) were higher in the in vitro group than in the in vivo group. There was no correlation between change rates of CAs and nuclear aberrations with radiation dose. Positive correlations of MN rates with age were found in all groups (ρ ≥ 0.590). CONCLUSIONS: Certain doses of radiation in oromaxillofacial CT examination may induce CAs and nuclear aberrations in lymphocytes.


Assuntos
Dano ao DNA , Linfócitos , Humanos , Testes para Micronúcleos , Tomografia , Tomografia Computadorizada por Raios X
7.
Sensors (Basel) ; 20(9)2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32384766

RESUMO

Salient object detection (SOD) is a fundamental task in computer vision, which attempts to mimic human visual systems that rapidly respond to visual stimuli and locate visually salient objects in various scenes. Perceptual studies have revealed that visual contrast is the most important factor in bottom-up visual attention process. Many of the proposed models predict saliency maps based on the computation of visual contrast between salient regions and backgrounds. In this paper, we design an end-to-end multi-scale global contrast convolutional neural network (CNN) that explicitly learns hierarchical contrast information among global and local features of an image to infer its salient object regions. In contrast to many previous CNN based saliency methods that apply super-pixel segmentation to obtain homogeneous regions and then extract their CNN features before producing saliency maps region-wise, our network is pre-processing free without any additional stages, yet it predicts accurate pixel-wise saliency maps. Extensive experiments demonstrate that the proposed network generates high quality saliency maps that are comparable or even superior to those of state-of-the-art salient object detection architectures.

8.
Phys Rev Lett ; 124(15): 153903, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32357032

RESUMO

Exceptional points (EPs) are branch point singularities of self-intersecting Riemann sheets, and they can be observed in a non-Hermitian system with complex eigenvalues. It has been revealed recently that dynamically encircling EPs by adiabatically changing the parameters of a system composed of lossy optical waveguides could lead to asymmetric (input-output) mode transfer. However, the length of the waveguides had to be considerable to ensure adiabatic evolution. Here we demonstrate that the parameters can change adiabatically along a smaller encircling loop by utilizing moving EPs, leading to significant shortening of the structures compared to fixed EPs. Meanwhile, the mode transmittance is remarkably improved and the transfer efficiency persists at ∼90%. Moving EPs are very promising for applications such as highly integrated broadband optical switches and convertors operating at telecommunication wavelengths.

9.
Int J Radiat Biol ; 96(6): 748-758, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32149567

RESUMO

Purpose: Simple, rapid and high-throughput dose assessment is critical for clinical diagnosis, treatment and emergency intervention in a large-scale radiological accident. The goal of this study is to screen and identify new ionizing radiation-responsive protein biomarkers in rat plasma.Materials and methods: Sprague-Dawley rats were exposed to single doses of 0, 1, 3, 5 Gy of Cobalt-60 γ-rays total body irradiation at a dose rate of 1 Gy/min. The tandem mass tag labeling (TMT) combined with liquid chromatography mass spectrometry (LC-MS/MS) approach was used to screen the differentially expressed proteins in rat plasma collected at 1, 3, 5 and 7 days post-irradiation. Bioinformatics analysis was conducted to explore the biological functions of these proteins. The expression levels of candidate radiation-sensitive protein biomarkers were confirmed using enzyme-linked immune-sorbent assay (ELISA).Results: A total of 503 differentially expressed proteins were identified. Most of these proteins were implicated in immune response, phagocytosis and signal transduction following ionizing radiation. Five up-regulated proteins including alpha-2-macroglobulin (A2m), chromogranin-A (CHGA), glutathione pertidase 3 (GPX3), clusterin (Clu) and ceruloplasmin (Cp) were selected for ELISA analysis. It was found that the expression levels of A2m, CHGA and GPX3 protein were increased in a dose-dependent manner at 1, 3 and 5 days after irradiation.Conclusion: Proteomics analysis revealed radiation-induced differentially expressed proteins in rat plasma. Our results suggested that A2m, CHGA, GPX3 protein expressions alterations in rat plasma may have potential as biomarkers to evaluate radiation exposure.


Assuntos
Proteínas Sanguíneas/metabolismo , Raios gama/efeitos adversos , Regulação da Expressão Gênica/efeitos da radiação , Animais , Biomarcadores/sangue , Proteínas Sanguíneas/genética , Ontologia Genética , Mapas de Interação de Proteínas/efeitos da radiação , Ratos , Ratos Sprague-Dawley
10.
J Hazard Mater ; 385: 121556, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31711724

RESUMO

The widespread contamination and high poisonousness have created significant concerns and thus demands for facile, rapid and selective monitoring of trace Hg2+. Inspired from the unique aggregation-induced emission (AIE) feature, in the current study, novel tetraphenylethylene (TPE) derivatives are prepared containing sulfonic groups for water solubility modulation and carboxyl dithioacetals for Hg2+ sensing. The TPE derivatives are grafted on electrospun fiber as test papers to initiate the AIE activities, while the Hg2+-specific cleavage of dithioacetal groups leads to the release of TPE derivatives and fluorescence turn-off. The decrease in the fluorescence intensities of fibrous mats could be fitted with Hg2+ levels for quantitative analysis, and the fibrous mats turn from green to bluish-green and then to blue in the presence of different Hg2+ levels. The limit of detection (LOD) reaches as low as 20 nM Hg2+, satisfying the threshold detection in drinking water, and the Hg2+ sensing indicates negligible interference from other metal ions and pH variations. The detected Hg2+ levels in lake water are consistent with the added amount with a recovery rate of over 98 %. It demonstrates a feasible strategy to integrate Hg2+-cleavable AIE probes on fibrous strips for real-time, highly specific and naked-eye detection of trace Hg2+.

11.
Sensors (Basel) ; 21(1)2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33396776

RESUMO

This paper addresses the Multi-Athlete Tracking (MAT) problem, which plays a crucial role in sports video analysis. There exist specific challenges in MAT, e.g., athletes share a high similarity in appearance and frequently occlude with each other, making existing approaches not applicable for this task. To address this problem, we propose a novel online multiple athlete tracking approach which make use of long-term temporal pose dynamics for better distinguishing different athletes. Firstly, we design a Pose-based Triple Stream Network (PTSN) based on Long Short-Term Memory (LSTM) networks, capable of modeling long-term temporal pose dynamics of athletes, including pose-based appearance, motion and athletes' interaction clues. Secondly, we propose a multi-state online matching algorithm based on bipartite graph matching and similarity scores produced by PTSN. It is robust to noisy detections and occlusions due to the reliable transitions of multiple detection states. We evaluate our method on the APIDIS, NCAA Basketball and VolleyTrack databases, and the experiment results demonstrate its effectiveness.

12.
J Med Chem ; 62(21): 9931-9946, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31638797

RESUMO

RORγt is an important nuclear receptor that regulates the production of several pro-inflammatory cytokines such as IL-17 and IL-22. As a result, RORγt has been identified as a potential target for the treatment of various immunological disorders such as psoriasis, psoriatic arthritis, and inflammatory bowel diseases. Structure and computer-assisted drug design led to the identification of a novel series of tricyclic RORγt inverse agonists with significantly improved in vitro activity in the reporter (Gal4) and human whole blood assays compared to our previous chemotype. Through careful structure activity relationship, several potent and selective RORγt inverse agonists have been identified. Pharmacokinetic studies allowed the identification of the lead molecule 32 with a low peak-to-trough ratio. This molecule showed excellent activity in an IL-2/IL-23-induced mouse pharmacodynamic study and demonstrated biologic-like efficacy in an IL-23-induced preclinical model of psoriasis.


Assuntos
Desenho de Fármacos , Agonismo Inverso de Drogas , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/agonistas , Pirrolidinas/farmacologia , Animais , Humanos , Células Jurkat , Camundongos , Modelos Moleculares , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/química , Conformação Proteica , Pirrolidinas/química , Pirrolidinas/farmacocinética , Relação Estrutura-Atividade , Distribuição Tecidual
13.
Nanoscale ; 11(38): 17831-17840, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31552986

RESUMO

The rapid and sensitive identification of bacteria has long been a major challenge in quality control, environmental monitoring and food safety. In the current study, the "motion-capture-lighting" strategy is proposed via integration of motion-enhanced capture of bacteria and capture-induced fluorescence turn-on of micromotors. Compared with the commonly used microtubes and microparticles, micromotors of flexible fiber rods could offer multiple interactions with the bacterial surface with less steric hindrance. Janus fiber rods (JFRs) are prepared by cryocutting of aligned fibers prepared by side-by-side electrospinning. Catalase is grafted on one side of JFRs to produce oxygen bubbles for propulsion of Janus micromotors (JMs), and mannose is conjugated on the other side for specific recognition of FimH proteins from fimbriae on the bacterial surface. The biphasic Janus structure of JFRs and the separate grafting of catalase and mannose on the opposite sides of JMs are confirmed after fluorescent labelling. JMs with aspect ratios of 0.5, 1, 2 and 4 are fabricated, and the aspect ratios of JMs show significant effects on the tracking trajectories and motion speed. JMs with the aspect ratio of 2 exhibit significantly higher magnitudes of mean square displacement (MSD) with a directional motion trajectory, leading to higher bacterial capture and larger fluorescence intensity changes. The bacteria capture leads to lighting up of JMs due to the aggregation-induced emission (AIE) effect of tetraphenylethene (TPE) derivatives. Under an ultraviolet lamp, the fluorescence color of JM suspensions turns from blue to bluish-green and to green after incubation with E. coli of 102 and 105 CFU mL-1, respectively. The fluorescence intensities of JM suspensions could be fitted to an equation versus bacterial concentrations, and the limit of detection (LOD) was around 45 CFU mL-1 within 1 min. Thus, this study demonstrates a motion-capture-lighting strategy for visual, rapid and real-time detection of bacteria without complicated sample pretreatment, expensive apparatus, and trained operators.


Assuntos
Escherichia coli/metabolismo , Fluorescência , Manose/metabolismo , Escherichia coli/citologia
14.
Radiat Res ; 192(4): 399-409, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31373872

RESUMO

In a large-scale radiological incident, rapid and high-throughput biodosimetry would be needed. Gene expression-based biodosimetry is a promising approach to determine the dose received after radiation exposure. We previously identified 35 candidate genes as biodosimetry markers based on a systematic review. The goal of the current study was to establish and validate a specific gene expression-based radiological biodosimetry using a panel of highly radioresponsive genes in human peripheral blood for improving the accuracy of dose estimation. Human peripheral blood samples from 30 adult donors were irradiated to 0, 0.5, 1, 2, 3, 4, 6 and 8 Gy with 60Co γ rays at a dose rate of 1 Gy/min. We examined the expression patterns of candidate genes using real-time polymerase chain reaction (qRT-PCR) at 6, 12, 24 and 48 h postirradiation. Stepwise regression analysis was employed to develop the gene expression-based dosimetry models at each time point. Samples from another 10 healthy donors (blind samples) and four total-body irradiated (TBI) patients were used to validate the radiation dosimetry models. We observed significant linear dose-response relationships of CDKN1A, BAX, MDM2, XPC, PCNA, FDXR, GDF-15, DDB2, TNFRSF10B, PHPT1, ASTN2, RPS27L, BBC3, TNFSF4, POLH, CCNG1, PPM1D and GADD45A in human peripheral blood at the various time points. However, the expression levels of these genes were affected by inter-individual variations and gender. We found that the gender-dependent regression models could explain 0.85 of variance at 24 h postirradiation and could also accurately estimate the absorbed radiation doses with dose range of 0-5 Gy, in human peripheral blood samples irradiated ex vivo and from TBI patients, respectively. This study demonstrates that developing gender-specific biodosimetry based on a panel of highly radioresponsive genes may help advance the application of gene expression signature for dose estimation in the event of a radiological accident or in clinical treatment.


Assuntos
Sangue/metabolismo , Sangue/efeitos da radiação , Radiometria/métodos , Caracteres Sexuais , Transcriptoma/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Modelos Biológicos , Fatores de Tempo
15.
Nanotechnology ; 30(37): 375301, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31195376

RESUMO

Electrospinning is becoming an efficient method to produce fibers in the submicron range, but the bending instability of conventional electrospinning system (CES) brings limitations in the distinctive deposition of electrospun fibers. Herein, we proposed a strategy to update the electrospinning system through establishment of a uniform electric field, realizing 3D printing of electrospun fibers with well-controlled, low-cost, and template-free manners. The uniform field electrospinning (UFES) apparatus is configured by inserting the electrospinning nozzle into the center of an aided metal plate. The electric field simulation of UFES indicates a uniform distribution between the aided metal plate and the collector, while a diverging and weaker electric field is produced by CES. The collector of UFES is mounted on a translation stage, which moves along x and y axes under computer control. The distinctive deposition of electrospun fibers produces fibrous mats with rectangular patterns of different grid sizes, and butterfly and TaiJi figures with high resolutions are directly written by UFES. The layer-by-layer deposition of electrospun fibers under UFES produces microscale Mongolian yurts with distinct hollow structure. Fibrous blocks with an average width of 120 µm and height of 630 µm were printed by UFES from conductive polymer composites and constructed into strain sensors. The electric current strength of fibrous microblocks changes sharply in response to the finger bending and release, indicating the capability to monitor human motions. Thus, this study demonstrates that the UFES becomes an easy-handling strategy for 3D printing of electrospun fibers to create complex geometries.

16.
Opt Express ; 27(10): 13858-13870, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31163844

RESUMO

We investigate the topological bound modes in a binary optical waveguide array with anti-parity-time (PT) symmetry. The anti-PT-symmetric arrays are realized by incorporating additional waveguides to the bare arrays, such that the effective coupling coefficients are imaginary. The systems experience two kinds of phase transition, including global topological order transition and quantum phase transition. As a result, the system supports two kinds of robust bound modes, which are protected by the global topological order and the quantum phase, respectively. The study provides a promising approach to realizing robust light transport by utilizing mediating components.

17.
BMC Cardiovasc Disord ; 19(1): 144, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200660

RESUMO

BACKGROUND: Using the current meta-analysis as well as systematic review, to determine the curative effect of Nicorandil in comparison of no Nicorandil after elective percutaneous coronary intervention(PCI) on patients. METHODS: Published literatures were identified via a computerized literature search of CENTRAL, PubMed, Cochrane, Embase Databases of Systematic Reviews. A set of randomized trials evaluating Nicorandil in comparison of no Nicorandil administered following PCI in patients harboring coronary artery disease were included. Outcomes were revealed based on the following parameters: peak creatine kinase-MB (CK-MB) value, left ventricular ejection fraction (LVEF), peak troponin I (cTnI), and major adverse cardiovascular events (MACEs) per randomized patients. RESULTS: We included a total of 14 RCTs involving 1864 subjects in the present review. According to this meta-analysis, LVEF was significantly improved in Nicorandil group; the peak CK-MB level and the incidence of adverse cardiovascular events were remarkably lower in Nicorandil group. Nicorandil and no Nicorandil administered group appeared to be equivalent with regards to cTnI. CONCLUSIONS: Nicorandil is effective for patients undergoing elective PCI with coronary artery disease in terms of reducing the incidence of adverse cardiovascular events as well as improving heart function. Nicorandil may exert potential role as a valid and adjunctive therapy accompanied with PCI.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doença da Artéria Coronariana/terapia , Nicorandil/uso terapêutico , Intervenção Coronária Percutânea , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Biomarcadores/sangue , Fármacos Cardiovasculares/efeitos adversos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Creatina Quinase Forma MB/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicorandil/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Resultado do Tratamento , Troponina I/sangue
18.
J Med Chem ; 62(7): 3228-3250, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30893553

RESUMO

Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fcε receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacological inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clinical studies.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Descoberta de Drogas , Indóis/farmacologia , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Animais , Artrite Reumatoide/tratamento farmacológico , Relação Dose-Resposta a Droga , Humanos , Indóis/farmacocinética , Indóis/uso terapêutico , Concentração Inibidora 50 , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Macaca fascicularis , Camundongos , Piperidinas/farmacocinética , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico
19.
Sensors (Basel) ; 19(2)2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30650645

RESUMO

Building damage accounts for a high percentage of post-natural disaster assessment. Extracting buildings from optical remote sensing images is of great significance for natural disaster reduction and assessment. Traditional methods mainly are semi-automatic methods which require human-computer interaction or rely on purely human interpretation. In this paper, inspired by the recently developed deep learning techniques, we propose an improved Mask Region Convolutional Neural Network (Mask R-CNN) method that can detect the rotated bounding boxes of buildings and segment them from very complex backgrounds, simultaneously. The proposed method has two major improvements, making it very suitable to perform building extraction task. Firstly, instead of predicting horizontal rectangle bounding boxes of objects like many other detectors do, we intend to obtain the minimum enclosing rectangles of buildings by adding a new term: the principal directions of the rectangles θ. Secondly, a new layer by integrating advantages of both atrous convolution and inception block is designed and inserted into the segmentation branch of the Mask R-CNN to make the branch to learn more representative features. We test the proposed method on a newly collected large Google Earth remote sensing dataset with diverse buildings and very complex backgrounds. Experiments demonstrate that it can obtain promising results.

20.
Opt Express ; 26(16): 20929-20943, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30119400

RESUMO

We investigate the topological phase transition between Type-I and Type-II Weyl points (WPs) in a composite three-dimensional lattice composed of a two-dimensional brick-wall waveguide array and a synthetic frequency dimension created by dynamic modulation. By imposing different modulation amplitudes and phases in the two sublattices, we can break either parity or time-reversal symmetry and realize the phase transition between Type-I and Type-II WPs. As the array is truncated to have two edges, two Fermi-arc surface states will emerge, which propagate in opposite directions for Type-I WPs while in same directions for Type-II WPs, accompanied by bidirectional and unidirectional frequency shifts for the optical modes. Particularly at the phase transition point, we find that one of two bands becomes flat with a vanished group velocity along frequency axis in the vicinity of WPs. The study paves a way towards realizing different topological phases in the same photonic structure, which offers new opportunities to control wave transportation both in spatial and frequency domains.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...