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1.
Clin Chem ; 70(1): 273-284, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175592

RESUMO

BACKGROUND: Somatic hypermutation (SHM) status of the immunoglobulin heavy variable (IGHV) gene plays a crucial role in determining the prognosis and treatment of patients with chronic lymphocytic leukemia (CLL). A common approach for determining SHM status is multiplex polymerase chain reaction and Sanger sequencing of the immunoglobin heavy locus; however, this technique is low throughput, is vulnerable to failure, and does not allow multiplexing with other diagnostic assays. METHODS: Here we designed and validated a DNA targeted capture approach to detect immunoglobulin heavy variable somatic hypermutation (IGHV SHM) status as a submodule of a larger next-generation sequencing (NGS) panel that also includes probes for ATM, BIRC3, CHD2, KLHL6, MYD88, NOTCH1, NOTCH2, POT1, SF3B1, TP53, and XPO1. The assay takes as input FASTQ files and outputs a report containing IGHV SHM status and V allele usage following European Research Initiative on CLL guidelines. RESULTS: We validated the approach on 35 CLL patient samples, 34 of which were characterized using Sanger sequencing. The NGS panel identified the IGHV SHM status of 34 of 35 CLL patients. We showed 100% sensitivity and specificity among the 33 CLL samples with both NGS and Sanger sequencing calls. Furthermore, we demonstrated that this panel can be combined with additional targeted capture panels to detect prognostically important CLL single nucleotide variants, insertions/deletions, and copy number variants (TP53 copy number loss). CONCLUSIONS: A targeted capture approach to IGHV SHM detection can be integrated into broader sequencing panels, allowing broad CLL prognostication in a single molecular assay.


Assuntos
Leucemia Linfocítica Crônica de Células B , Hipermutação Somática de Imunoglobulina , Humanos , Alelos , Sequenciamento de Nucleotídeos em Larga Escala , Imunoglobulinas , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Fatores de Transcrição
2.
J Appl Toxicol ; 44(1): 28-40, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37340727

RESUMO

The study aimed to investigate the underlying molecular mechanisms of prostate injury induced by 4,4'-sulfonyldiphenol (BPS) exposure and propose a novel research strategy to systematically explore the molecular mechanisms of toxicant-induced adverse health effects. By utilizing the ChEMBL, STITCH, and GeneCards databases, a total of 208 potential targets associated with BPS exposure and prostate injury were identified. Through screening the potential target network in the STRING database and Cytoscape software, we determined 21 core targets including AKT1, EGFR, and MAPK3. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses conducted through the DAVID database illustrated that the potential targets of BPS in prostatic toxicity were primarily enriched in cancer signaling pathways and calcium signaling pathways. These findings suggest that BPS may actively participate in the occurrence and development of prostate inflammation, prostatic hyperplasia, prostate cancer, and other aspects of prostate injury by regulating prostate cancer cell apoptosis and proliferation, activating inflammatory signaling pathways, and modulating prostate adipocytes and fibroblasts. This research provides a theoretical basis for understanding the molecular mechanism of underlying BPS-induced prostatic toxicity and establishes a foundation for the prevention and treatment of prostatic diseases associated with exposure to plastic products containing BPS and certain BPS-overwhelmed environments.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos de Ervas Chinesas , Doenças Prostáticas , Neoplasias da Próstata , Masculino , Humanos , Próstata , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/genética , Adipócitos , Apoptose , Simulação de Acoplamento Molecular
3.
Pharmacogenomics J ; 23(4): 61-72, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36424525

RESUMO

Our previous studies demonstrated that the FOXM1 pathway is upregulated and the PPARA pathway downregulated in breast cancer (BC), and especially in the triple negative breast cancer (TNBC) subtype. Targeting the two pathways may offer potential therapeutic strategies to treat BC, especially TNBC which has the fewest effective therapies available among all BC subtypes. In this study we identified small molecule compounds that could modulate the PPARA and FOXM1 pathways in BC using two methods. In the first method, data were initially curated from the Connectivity Map (CMAP) database, which provides the gene expression profiles of MCF7 cells treated with different compounds as well as paired controls. We then calculated the changes in the FOXM1 and PPARA pathway activities from the compound-induced gene expression profiles under each treatment to identify compounds that produced a decreased activity in the FOXM1 pathway or an increased activity in the PPARA pathway. In the second method, the CMAP database tool was used to identify compounds that could reverse the expression pattern of the two pathways in MCF7 cells. Compounds identified as repressing the FOXM1 pathway or activating the PPARA pathway by the two methods were compared. We identified 19 common compounds that could decrease the FOXM1 pathway activity scores and reverse the FOXM1 pathway expression pattern, and 13 common compounds that could increase the PPARA pathway activity scores and reverse the PPARA pathway expression pattern. It may be of interest to validate these compounds experimentally to further investigate their effects on TNBCs.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Células MCF-7 , Biologia Computacional , PPAR alfa/genética , Regulação Neoplásica da Expressão Gênica
4.
Molecules ; 27(15)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35897886

RESUMO

Facile construction of functional nanomaterials with laccase-like activity is important in sustainable chemistry since laccase is featured as an efficient and promising catalyst especially for phenolic degradation but still has the challenges of high cost, low activity, poor stability and unsatisfied recyclability. In this paper, we report a simple method to synthesize nanozymes with enhanced laccase-like activity by the self-assembly of copper ions with various imidazole derivatives. In the case of 1-methylimidazole as the ligand, the as-synthesized nanozyme (denoted as Cu-MIM) has the highest yield and best activity among the nanozymes prepared. Compared to laccase, the Km of Cu-MIM nanozyme to phenol is much lower, and the vmax is 6.8 times higher. In addition, Cu-MIM maintains excellent stability in a variety of harsh environments, such as high pH, high temperature, high salt concentration, organic solvents and long-term storage. Based on the Cu-MIM nanozyme, we established a method for quantitatively detecting phenol concentration through a smartphone, which is believed to have important applications in environmental protection, pollutant detection and other fields.


Assuntos
Imidazóis , Lacase , Catálise , Cobre/química , Lacase/química , Fenol , Fenóis
5.
Bioinformatics ; 36(16): 4483-4489, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32369563

RESUMO

MOTIVATION: Combination therapies have been widely used to treat cancers. However, it is cost and time consuming to experimentally screen synergistic drug pairs due to the enormous number of possible drug combinations. Thus, computational methods have become an important way to predict and prioritize synergistic drug pairs. RESULTS: We proposed a Deep Tensor Factorization (DTF) model, which integrated a tensor factorization method and a deep neural network (DNN), to predict drug synergy. The former extracts latent features from drug synergy information while the latter constructs a binary classifier to predict the drug synergy status. Compared to the tensor-based method, the DTF model performed better in predicting drug synergy. The area under precision-recall curve (PR AUC) was 0.58 for DTF and 0.24 for the tensor method. We also compared the DTF model with DeepSynergy and logistic regression models, and found that the DTF outperformed the logistic regression model and achieved similar performance as DeepSynergy using several performance metrics for classification task. Applying the DTF model to predict missing entries in our drug-cell-line tensor, we identified novel synergistic drug combinations for 10 cell lines from the 5 cancer types. A literature survey showed that some of these predicted drug synergies have been identified in vivo or in vitro. Thus, the DTF model could be a valuable in silico tool for prioritizing novel synergistic drug combinations. AVAILABILITY AND IMPLEMENTATION: Source code and data are available at https://github.com/ZexuanSun/DTF-Drug-Synergy. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biologia Computacional , Combinação de Medicamentos , Humanos , Neoplasias/tratamento farmacológico , Redes Neurais de Computação , Software
6.
BMC Cancer ; 21(1): 648, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059012

RESUMO

BACKGROUND: Predicting patient drug response based on a patient's molecular profile is one of the key goals of precision medicine in breast cancer (BC). Multiple drug response prediction models have been developed to address this problem. However, most of them were developed to make sensitivity predictions for multiple single drugs within cell lines from various cancer types instead of a single cancer type, do not take into account drug properties, and have not been validated in cancer patient-derived data. Among the multi-omics data, gene expression profiles have been shown to be the most informative data for drug response prediction. However, these models were often developed with individual genes. Therefore, this study aimed to develop a drug response prediction model for BC using multiple data types from both cell lines and drugs. METHODS: We first collected the baseline gene expression profiles of 49 BC cell lines along with IC50 values for 220 drugs tested in these cell lines from Genomics of Drug Sensitivity in Cancer (GDSC). Using these data, we developed a multiple-layer cell line-drug response network (ML-CDN2) by integrating a one-layer cell line similarity network based on the pathway activity profiles and a three-layer drug similarity network based on the drug structures, targets, and pan-cancer IC50 profiles. We further used ML-CDN2 to predict the drug response for new BC cell lines or patient-derived samples. RESULTS: ML-CDN2 demonstrated a good predictive performance, with the Pearson correlation coefficient between the observed and predicted IC50 values for all GDSC cell line-drug pairs of 0.873. Also, ML-CDN2 showed a good performance when used to predict drug response in new BC cell lines from the Cancer Cell Line Encyclopedia (CCLE), with a Pearson correlation coefficient of 0.718. Moreover, we found that the cell line-derived ML-CDN2 model could be applied to predict drug response in the BC patient-derived samples from The Cancer Genome Atlas (TCGA). CONCLUSIONS: The ML-CDN2 model was built to predict BC drug response using comprehensive information from both cell lines and drugs. Compared with existing methods, it has the potential to predict the drug response for BC patient-derived samples.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Modelos Biológicos , Antineoplásicos/uso terapêutico , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Conjuntos de Dados como Assunto , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Concentração Inibidora 50 , Medicina de Precisão/métodos , RNA-Seq
7.
Genome ; 64(4): 400-415, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33197212

RESUMO

In the absence of a vaccine, the treatment of SARS-CoV2 has focused on eliminating the virus with antivirals or mitigating the cytokine storm syndrome (CSS) that leads to the most common cause of death: respiratory failure. Herein we discuss the mechanisms of antiviral treatments for SARS-CoV2 and treatment strategies for the CSS. Antivirals that have shown in vitro activity against SARS-CoV2, or the closely related SARS-CoV1 and MERS-CoV, are compared on the enzymatic level and by potency in cells. For treatment of the CSS, we discuss medications that reduce the effects or expression of cytokines involved in the CSS with an emphasis on those that reduce IL-6 because of its central role in the development of the CSS. We show that some of the medications covered influence the activity or expression of enzymes involved in epigenetic processes and specifically those that add or remove modifications to histones or DNA. Where available, the latest clinical data showing the efficacy of the medications is presented. With respect to their mechanisms, we explain why some medications are successful, why others have failed, and why some untested medications may yet prove useful.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Citocinas , Epigênese Genética , Expressão Gênica , Humanos , Interleucina-6 , SARS-CoV-2/efeitos dos fármacos
8.
BMC Cardiovasc Disord ; 20(1): 310, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600304

RESUMO

BACKGROUND: Correct detection of human cardiomyocyte death is essential for definitive diagnosis and appropriate management of cardiovascular diseases. Although current strategies have proven utility in clinical cardiology, they have some limitations. Our aim was to develop a new approach to monitor myocardial death using methylation patterns of circulating cell-free DNA (cf-DNA). METHODS: We first examined the methylation status of FAM101A in heart tissue and blood of individual donors using quantitative methylation-sensitive PCR (qMS-PCR). The concentrations and kinetics of cardiac cf-DNA in plasma from five congenital heart disease (CHD) children before and after they underwent cardiac surgery at serial time points were then investigated. RESULTS: We identified demethylated FAM101A specifically present in heart tissue. Importantly, our time course experiments demonstrated that the plasma cardiac cf-DNA level increased quickly during the early post-cardiac surgery phase, peaking at 4-6 h, decreased progressively (24 h) and returned to baseline (72 h). Moreover, cardiac cf-DNA concentrations pre- and post-operation were closely correlated with plasma troponin levels. CONCLUSIONS: We proposed a novel strategy for the correct detection of cardiomyocyte death, based on analysis of plasma cf-DNA carrying the cardiac-specific methylation signature. Our pilot study may lead to new tests for human cardiac pathologies.


Assuntos
Ácidos Nucleicos Livres/genética , Metilação de DNA , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Miócitos Cardíacos/patologia , Procedimentos Cirúrgicos Cardíacos , Morte Celular , Pré-Escolar , Epigenoma , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas dos Microfilamentos/genética , Projetos Piloto , Fatores de Tempo , Resultado do Tratamento
9.
Anal Chem ; 90(21): 12840-12845, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30274512

RESUMO

An online gas-free KOH electrodialytic eluent generator (EDG) with two-membrane configuration is described for ion chromatography (IC). A central eluent channel is separated from two outer regenerant channels bearing KOH solution (or one is water) by stacked cation-exchange membranes (sCEMs) and a bipolar membrane (BPM) plus stacked CEMs (BPM-sCEMs), in which the anion-exchange membrane (AEM) of BPM is facing the central channel (the anode direction). Independent fluid input or output ports address all channels. One platinum screen electrode is put in each outer channel, and the sCEM side is anode with respect to the cathode of the BPM-sCEM side. Under the electric field, enhanced water splitting at the intermediate layer of BPM will occur, offering hydroxide and hydronium; hydroxide electromigrates through AEM into the central channel, while the potassium of KOH feed solution at the anode migrates into the central channel to combine with hydroxide to form a solution of KOH. Because the central eluent channel is spatially isolated from both electrodes, the generated KOH solution is gas-free and no gas-removal device is required. More important, the AEM side of BPM is contactless with the alkaline solution, nearly avoiding possible AEM degradation when immersed into concentrated alkaline solution. This ensures long-term running stability of the EDG and high purity of the produced KOH solution (as indicated by the typical suppressed background conductance of 0.28 µS/cm). The EDG has a pressure tolerance (at least 21 MPa), and the produced KOH concentration is up to 101 µeq/min with near-unity faradaic efficiency. When operated in both isocratic and gradient modes, the EDG demonstrates excellent reproducibility, as indicated by the retention time of RSD ≤ 0.08% and the peak area of RSD ≤ 0.6%. To the best of our knowledge, this is the first description of gas-free EDG matched conventional IC system.

10.
BMC Cancer ; 18(1): 473, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29699511

RESUMO

BACKGROUND: Breast cancer is a heterogeneous disease and personalized medicine is the hope for the improvement of the clinical outcome. Multi-gene signatures for breast cancer stratification have been extensively studied in the past decades and more than 30 different signatures have been reported. A major concern is the minimal overlap of genes among the reported signatures. We investigated the breast cancer signature genes to address our hypothesis that the genes of different signature may share common functions, as well as to use these previously reported signature genes to build better prognostic models. METHODS: A total of 33 signatures and the corresponding gene lists were investigated. We first examined the gene frequency and the gene overlap in these signatures. Then the gene functions of each signature gene list were analysed and compared by the KEGG pathways and gene ontology (GO) terms. A classifier built using the common genes was tested using the METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) data. The common genes were also tested for building the Yin Yang gene mean expression ratio (YMR) signature using public datasets (GSE1456 and GSE2034). RESULTS: Among a total of 2239 genes collected from the 33 breast cancer signatures, only 238 genes overlapped in at least two signatures; while from a total of 1979 function terms enriched in the 33 signature gene lists, 429 terms were common in at least two signatures. Most of the common function terms were involved in cell cycle processes. While there is almost no common overlapping genes between signatures developed for ER-positive (e.g. 21-gene signature) and those developed for ER-negative (e.g. basal signatures) tumours, they have common function terms such as cell death, regulation of cell proliferation. We used the 62 genes that were common in at least three signatures as a classifier and subtyped 1141 METABRIC cases including 144 normal samples into nine subgroups. These subgroups showed different clinical outcome. Among the 238 common genes, we selected those genes that are more highly expressed in normal breast tissue than in tumours as Yang genes and those more highly expressed in tumours than in normal as Yin genes and built a YMR model signature. This YMR showed significance in risk stratification in two datasets (GSE1456 and GSE2034). CONCLUSIONS: The lack of significant numbers of overlapping genes among most breast cancer signatures can be partially explained by our discovery that these signature genes represent groups with similar functions. The genes collected from these previously reported signatures are valuable resources for new model development. The subtype classifier and YMR signature built from the common genes showed promising results.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Anotação de Sequência Molecular , Prognóstico , Reprodutibilidade dos Testes
11.
BMC Cancer ; 18(1): 22, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29301506

RESUMO

BACKGROUND: Triple Negative Breast Cancers (TNBCs) lack the appropriate targets for currently used breast cancer therapies, conferring an aggressive phenotype, more frequent relapse and poorer survival rates. The biological heterogeneity of TNBC complicates the clinical treatment further. We have explored and compared the biological pathways in TNBC and other subtypes of breast cancers, using an in silico approach and the hypothesis that two opposing effects (Yin and Yang) pathways in cancer cells determine the fate of cancer cells. Identifying breast subgroup specific components of these opposing pathways may aid in selecting potential therapeutic targets as well as further classifying the heterogeneous TNBC subtype. METHODS: Gene expression and patient clinical data from The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used for this study. Gene Set Enrichment Analysis (GSEA) was used to identify the more active pathways in cancer (Yin) than in normal and the more active pathways in normal (Yang) than in cancer. The clustering analysis was performed to compare pathways of TNBC with other types of breast cancers. The association of pathway classified TNBC sub-groups to clinical outcomes was tested using Cox regression model. RESULTS: Among 4729 curated canonical pathways in GSEA database, 133 Yin pathways (FDR < 0.05) and 71 Yang pathways (p-value <0.05) were discovered in TNBC. The FOXM1 is the top Yin pathway while PPARα is the top Yang pathway in TNBC. The TNBC and other types of breast cancers showed different pathways enrichment significance profiles. Using top Yin and Yang pathways as classifier, the TNBC can be further subtyped into six sub-groups each having different clinical outcomes. CONCLUSION: We first reported that the FOMX1 pathway is the most upregulated and the PPARα pathway is the most downregulated pathway in TNBC. These two pathways could be simultaneously targeted in further studies. Also the pathway classifier we performed in this study provided insight into the TNBC heterogeneity.


Assuntos
Proteína Forkhead Box M1/genética , Recidiva Local de Neoplasia/genética , PPAR alfa/genética , Neoplasias de Mama Triplo Negativas/genética , Simulação por Computador , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Heterogeneidade Genética , Humanos , Recidiva Local de Neoplasia/patologia , Transdução de Sinais/genética , Neoplasias de Mama Triplo Negativas/patologia
12.
Dig Dis Sci ; 63(10): 2593-2603, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29959727

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. AIM: The present study aimed to validate the underlying mechanism of UPF1 in UC. METHODS: UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. RESULTS: UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. CONCLUSION: UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC.


Assuntos
Colite Ulcerativa , Inflamação/metabolismo , Mucosa Intestinal , Transativadores , Animais , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , NF-kappa B/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais , Transativadores/genética , Transativadores/metabolismo , Dedos de Zinco
13.
Sensors (Basel) ; 18(1)2018 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-29316627

RESUMO

The recently developed direct phase measuring deflectometry (DPMD) method can directly measure the three-dimensional (3D) shape of specular objects with discontinuous surfaces, but requires a calibrated distance between a reference plane and liquid crystal display screen. Because the plane and screen are different distances from the imaging device, they cannot be clearly captured given the limited depth of field (DOF) of the lens. Therefore, existing machine vision-based methods cannot be used to effectively calibrate a DPMD system. In this paper, a new distance calibration method that uses a mirror with a hollow ring matrix pattern and a mobile stage is presented. The direction of the mobile stage in the camera coordinate system is determined by the mirror's pattern at several positions in the camera's DOF so that the reference position outside of the DOF can be calculated. The screen's position can also be calibrated by displaying patterns at a known scale. Therefore, the required distance is accurately obtained in the camera coordinate system. Evaluation results show that the maximum value of the absolute error is less than 0.031 mm. The experimental results on an artificial stepped mirror and a reflected diamond distribution surface demonstrate the accuracy and practicality of the proposed method.

14.
Int J Cancer ; 140(6): 1413-1424, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-27925180

RESUMO

Breast cancer is one of the leading causes of cancer death in women. It is a complex and heterogeneous disease with different clinical outcomes. Stratifying patients into subgroups with different outcomes could help guide clinical decision making. In this study, we used two opposing groups of genes, Yin and Yang, to develop a prognostic expression ratio signature. Using the METABRIC cohort we identified a16-gene signature capable of stratifying breast cancer patients into four risk levels with intention that low-risk patients would not undergo adjuvant systemic therapy, intermediate-low-risk patients will be treated with hormonal therapy only, and intermediate-high- and high-risk groups will be treated by chemotherapy in addition to the hormonal therapy. The 16-gene signature for four risk level stratifications of breast cancer patients has been validated using 14 independent datasets. Notably, the low-risk group (n = 51) of 205 estrogen receptor-positive and node negative (ER+/node-) patients from three different datasets who had not had any systemic adjuvant therapy had 100% 15-year disease-specific survival rate. The Concordance Index of YMR for ER+/node negative patients is close to the commercially available signatures. However, YMR showed more significance (HR = 3.7, p = 8.7e-12) in stratifying ER+/node- subgroup than OncotypeDx (HR = 2.7, p = 1.3e-7), MammaPrint (HR = 2.5, p = 5.8e-7), rorS (HR = 2.4, p = 1.4e-6), and NPI (HR = 2.6, p = 1.2e-6). YMR signature may be developed as a clinical tool to select a subgroup of low-risk ER+/node- patients who do not require any adjuvant hormonal therapy (AHT).


Assuntos
Neoplasias da Mama/genética , Estrogênios , Genes Neoplásicos , Proteínas de Neoplasias/genética , Neoplasias Hormônio-Dependentes/genética , Receptores de Estrogênio/análise , Transcriptoma , Adulto , Biomarcadores Tumorais/análise , Mama/química , Neoplasias da Mama/química , Neoplasias da Mama/terapia , Conjuntos de Dados como Assunto/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Neoplasias Hormônio-Dependentes/química , Neoplasias Hormônio-Dependentes/terapia , Prognóstico , Modelos de Riscos Proporcionais , Resultado do Tratamento , Yin-Yang
15.
Liver Int ; 37(8): 1202-1208, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28106941

RESUMO

BACKGROUND & AIMS: Cross-sectional studies have shown that apolipoprotein B (apoB) is positively associated with the prevalence of non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the prospective relationship between the serum apoB levels and the development of NAFLD in a Chinese population. METHODS: A cohort of 7077 initially NAFLD-free participants was enrolled in this prospectively study. The incidence of NAFLD was calculated among participants with different baseline serum apoB quintiles. Cox proportional hazards regression analyses were conducted to calculate the risks for incident NAFLD. RESULTS: During 41 555 person-year follow-ups, 1139 incident NAFLD cases were identified. The baseline apoB levels were linear and positively correlated with NAFLD incidence. The incidence was 16.99, 22.63, 24.73, 37.51 and 42.77 per 1000 person-year follow-up for participants with baseline apoB levels in quintiles 1-5, respectively. Compared with participants with baseline apoB levels in quintile 1, the hazard ratios (95% confidence interval) for incident NAFLD were 1.353 (1.100-1.663), 1.482 (1.207-1.820), 2.232 (1.832-2.720) and 2.543 (2.082-3.106) for participants with baseline apoB levels in quintile 2-5, respectively. The hazard ratios were attenuated but remained statistically significant after adjusting for age, gender, body mass index and variables associated with metabolic syndrome. CONCLUSION: Elevated serum apoB levels independently predict an increased risk for incident NAFLD.


Assuntos
Apolipoproteína B-100/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , China , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
16.
Sensors (Basel) ; 17(5)2017 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-28481263

RESUMO

The refractive index of a lens varies for different wavelengths of light, and thus the same incident light with different wavelengths has different outgoing light. This characteristic of lenses causes images captured by a color camera to display chromatic aberration (CA), which seriously reduces image quality. Based on an analysis of the distribution of CA, a full-field calibration method based on absolute phase maps is proposed in this paper. Red, green, and blue closed sinusoidal fringe patterns are generated, consecutively displayed on an LCD (liquid crystal display), and captured by a color camera from the front viewpoint. The phase information of each color fringe is obtained using a four-step phase-shifting algorithm and optimum fringe number selection method. CA causes the unwrapped phase of the three channels to differ. These pixel deviations can be computed by comparing the unwrapped phase data of the red, blue, and green channels in polar coordinates. CA calibration is accomplished in Cartesian coordinates. The systematic errors introduced by the LCD are analyzed and corrected. Simulated results show the validity of the proposed method and experimental results demonstrate that the proposed full-field calibration method based on absolute phase maps will be useful for practical software-based CA calibration.

17.
Sensors (Basel) ; 17(12)2017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29215600

RESUMO

The fast development in the fields of integrated circuits, photovoltaics, the automobile industry, advanced manufacturing, and astronomy have led to the importance and necessity of quickly and accurately obtaining three-dimensional (3D) shape data of specular surfaces for quality control and function evaluation. Owing to the advantages of a large dynamic range, non-contact operation, full-field and fast acquisition, high accuracy, and automatic data processing, phase-measuring deflectometry (PMD, also called fringe reflection profilometry) has been widely studied and applied in many fields. Phase information coded in the reflected fringe patterns relates to the local slope and height of the measured specular objects. The 3D shape is obtained by integrating the local gradient data or directly calculating the depth data from the phase information. We present a review of the relevant techniques regarding classical PMD. The improved PMD technique is then used to measure specular objects having discontinuous and/or isolated surfaces. Some influential factors on the measured results are presented. The challenges and future research directions are discussed to further advance PMD techniques. Finally, the application fields of PMD are briefly introduced.

18.
Opt Express ; 24(11): 12026-42, 2016 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-27410124

RESUMO

Augmented reality system can be applied to provide precise guidance for various kinds of manual works. The adaptability and guiding accuracy of such systems are decided by the computational model and the corresponding calibration method. In this paper, a novel type of augmented reality guiding system and the corresponding designing scheme are proposed. Guided by external positioning equipment, the proposed system can achieve high relative indication accuracy in a large working space. Meanwhile, the proposed system is realized with a digital projector and the general back projection model is derived with geometry relationship between digitized 3D model and the projector in free space. The corresponding calibration method is also designed for the proposed system to obtain the parameters of projector. To validate the proposed back projection model, the coordinate data collected by a 3D positioning equipment is used to calculate and optimize the extrinsic parameters. The final projecting indication accuracy of the system is verified with subpixel pattern projecting technique.

19.
Opt Express ; 23(19): 25171-81, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-26406715

RESUMO

This paper makes use of Hilbert transform to analyze and compensate the phase error caused by the nonlinear effect in phase shifting profilometry (PSP). The characteristics of the phase error distribution in Hilbert transform domain was analyzed and compared with spatial domain. A simple and flexible phase error compensation method was proposed to directly process the phase-shifting fringe images without any auxiliary conditions or complicated computation. Experimental results demonstrated that the phase error can be reduced by about 80% in three-step PSP, and more than 95% in four or more step PSP, which verified the effectiveness, flexibility, robustness and automation of the proposed phase error compensation method.

20.
Appl Opt ; 54(4): 789-95, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25967789

RESUMO

Digital light processing (DLP) projectors have been widely utilized to project digital structured-light patterns in 3D imaging systems. In order to obtain accurate 3D shape data, it is important to calibrate DLP projectors to obtain the internal parameters. The existing projector calibration methods have complicated procedures or low accuracy of the obtained parameters. This paper presents a novel method to accurately calibrate a DLP projector by using an optical coaxial camera. The optical coaxial geometry is realized by a plate beam splitter, so the DLP projector can be treated as a true inverse camera. A plate having discrete markers on the surface is used to calibrate the projector. The corresponding projector pixel coordinate of each marker on the plate is determined by projecting vertical and horizontal sinusoidal fringe patterns on the plate surface and calculating the absolute phase. The internal parameters of the DLP projector are obtained by the corresponding point pair between the projector pixel coordinate and the world coordinate of discrete markers. Experimental results show that the proposed method can accurately calibrate the internal parameters of a DLP projector.

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