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1.
Front Neurosci ; 18: 1349204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38410158

RESUMO

State-of-the-art image object detection computational models require an intensive parameter fine-tuning stage (using deep convolution network, etc). with tens or hundreds of training examples. In contrast, human intelligence can robustly learn a new concept from just a few instances (i.e., few-shot detection). The distinctive perception mechanisms between these two families of systems enlighten us to revisit classical handcraft local descriptors (e.g., SIFT, HOG, etc.) as well as non-parametric visual models, which innately require no learning/training phase. Herein, we claim that the inferior performance of these local descriptors mainly results from a lack of global structure sense. To address this issue, we refine local descriptors with spatial contextual attention of neighbor affinities and then embed the local descriptors into discriminative subspace guided by Kernel-InfoNCE loss. Differing from conventional quantization of local descriptors in high-dimensional feature space or isometric dimension reduction, we actually seek a brain-inspired few-shot feature representation for the object manifold, which combines data-independent primitive representation and semantic context learning and thus helps with generalization. The obtained embeddings as pattern vectors/tensors permit us an accelerated but non-parametric visual similarity computation as the decision rule for final detection. Our approach to few-shot object detection is nearly learning-free, and experiments on remote sensing imageries (approximate 2-D affine space) confirm the efficacy of our model.

2.
Opt Express ; 31(3): 3865-3880, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36785369

RESUMO

The use of supervised neural networks is a new approach to solving digital image correlation (DIC) problems, but the existing methods solely adopt the black-box neural network, i.e., the mapping from speckle image pair (reference image and deformed image) to multiple deformation fields (displacement fields and strain fields) is directly established without considering the physical constraints between the fields, causing a low level of accuracy that is even inferior to that of Subset-DIC. In this work, we proposed a deep learning model by introducing strain-displacement relations into a neural network, in which the effect of errors both in displacement and strain are considered in the network training. The back-propagation process of the proposed model is derived, and the solution scheme is implemented by Python. The performance of the proposed model is evaluated by simulation and real DIC experiments, and the results show that adding physical constraints to the neural network can significantly improve prediction accuracy.

3.
Cell Death Differ ; 30(1): 195-207, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36171331

RESUMO

Despite remarkable efficacy, targeted treatments often yield a subpopulation of residual tumor cells in part due to non-genetic adaptions. Previous mechanistic understanding on the emergence of these drug-tolerant persisters (DTPs) has been limited to epigenetic and transcriptional reprogramming. Here, by comprehensively interrogating therapy-induced early dynamic protein changes in diverse oncogene-addicted non-small cell lung cancer models, we identified adaptive MCL1 increase as a new and universal mechanism to confer apoptotic evasion and DTP formation. In detail, acute MAPK signaling disruption in the presence of genotype-based tyrosine kinase inhibitors (TKIs) prompted mitochondrial accumulation of pro-apoptotic BH3-only protein BIM, which sequestered MCL1 away from MULE-mediated degradation. A small-molecule combination screen uncovered that PI3K-mTOR pathway blockade prohibited MCL1 upregulation. Biochemical and immunocytochemical evidence indicated that mTOR complex 2 (mTORC2) bound and phosphorylated MCL1, facilitating its interaction with BIM. As a result, short-term polytherapy combining antineoplastic TKIs with PI3K, mTOR or MCL1 inhibitors sufficed to prevent DTP development and promote cancer eradication. Collectively, these findings support that upfront and transient targeting of BIM-dependent, mTORC2-regulated adaptive MCL1 preservation holds enormous promise to improve the therapeutic index of molecular targeted agents.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Apoptose , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Serina-Treonina Quinases TOR , Fosfatidilinositol 3-Quinases
4.
Brain Sci ; 12(9)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36138897

RESUMO

Emotion analysis has emerged as one of the most prominent study areas in the field of Brain Computer Interface (BCI) due to the critical role that the human brain plays in the creation of human emotions. In this study, a Multi-objective Immunogenetic Community Division Algorithm Based on Memetic Framework (MFMICD) was suggested to study different emotions from the perspective of brain networks. To improve convergence and accuracy, MFMICD incorporates the unique immunity operator based on the traditional genetic algorithm and combines it with the taboo search algorithm. Based on this approach, we examined how the structure of people's brain networks alters in response to different emotions using the electroencephalographic emotion database. The findings revealed that, in positive emotional states, more brain regions are engaged in emotion dominance, the information exchange between local modules is more frequent, and various emotions cause more varied patterns of brain area interactions than in negative brain states. A brief analysis of the connections between different emotions and brain regions shows that MFMICD is reliable in dividing emotional brain functional networks into communities.

5.
Cancer Res ; 82(19): 3588-3602, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-35857807

RESUMO

Therapeutic perturbation of cyclin-dependent kinase 12 (CDK12) is proposed to have pleiotropic effects in ovarian cancer, including direct cytotoxicity against tumor cells and indirect induction of immunogenicity that confer synthetic sensitivity to immune-based treatment. However, formal testing of this hypothesis has been hindered by an insufficient mechanistic understanding of CDK12 and its close homolog CDK13, as well as generally unfavorable pharmacokinetics of available CDK12/CDK13 covalent inhibitors. In this study, we used an innovative arsenous warhead modality to develop an orally bioavailable CDK12/CDK13 covalent compound. The dual CDK12/CDK13 inhibitors ZSQ836 exerted potent anticancer activity in cell culture and mouse models and induced transcriptional reprogramming, including downregulation of DNA damage response genes. CDK12 and CDK13 were both ubiquitously expressed in primary and metastatic ovarian cancer, and the two kinases performed independent and synergistic functions to promote tumorigenicity. Unexpectedly, although ZSQ836 triggered genomic instability in malignant cells, it counterintuitively impaired lymphocytic infiltration in neoplastic lesions by interfering with T-cell proliferation and activation. These findings highlight the Janus-faced effects of dual CDK12/CDK13 inhibitors by simultaneously suppressing tumor and immune cells, offering valuable insights into the future direction of drug discovery to pharmacologically target CDK12. SIGNIFICANCE: This study dissects the specific roles of CDK12 and CDK13 in ovarian cancer and develops a CDK12/CDK13 inhibitor that impairs both tumor and immune cells, which could guide future CDK12 inhibitor development.


Assuntos
Proteína Quinase CDC2 , Neoplasias Ovarianas , Animais , Carcinoma Epitelial do Ovário/genética , Quinases Ciclina-Dependentes/genética , Feminino , Genes cdc , Humanos , Camundongos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética
6.
Technol Cancer Res Treat ; 20: 1533033821990037, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33641530

RESUMO

BACKGROUND: To investigate the relationship of circulating tumor cells (CTCs) and the clinical characteristic parameters and prognosis in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The retrospective clinical study included 95 patients with HNSCC who after surgery in Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine between December 2015 and December 2016. All patients were followed up for survival until the end of June 2019. The CTCs detection was performed by negative enrichment (NE) immunofluorescence-in situ hybridization (im-FISH) of chromosome 8. RESULTS: Patients with higher CTCs counts are associated with a worse prognosis with an area under the receiver operator characteristic (ROC) curve of 0.756 [95% confidence interval (CI) 0.640-0.872, p = 0.001]. The CTCs-positive rate of HNSCC patients was 58.9% (56/95) by using the cut-point of 3. Both the chi-square test and binary logistic regression analysis showed that the N stage and clinical stage were significantly associated with CTCs-positive in patients with HNSCC (p < 0.05). Further Non-parametric test analysis indicated that more CTCs counts were detected in late N and clinical stages patients (p < 0.001). The Kaplan-Meier survival analysis indicated that CTCs-positive were correlated with shorter progression-free survival (PFS) (p < 0.001) and overall survival (OS) (p = 0.001). Further, the CTCs-positive was an independent prognostic factor for PFS and OS according to the Cox multivariate regression analysis (p < 0.05). CONCLUSION: More CTCs were associated with N stage, clinical stage, poor prognosis in patients with HNSCC, which might be used as a prognostic biomarker.


Assuntos
Biomarcadores Tumorais , Células Neoplásicas Circulantes/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto , Idoso , Biópsia , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/metabolismo , Prognóstico , Curva ROC , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia
7.
Sensors (Basel) ; 20(9)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32365948

RESUMO

Digital cameras represented by industrial cameras are widely used as image acquisition sensors in the field of image-based mechanics measurement, and their thermal effect inevitably induces thermal-induced errors of the mechanics measurement. To deeply understand the errors, the research for digital camera's thermal effect is necessary. This study systematically investigated the heat transfer processes and temperature characteristics of a working digital camera. Concretely, based on the temperature distribution of a typical working digital camera, the heat transfer of the working digital camera was investigated, and a model describing the temperature variation and distribution was presented and verified experimentally. With this model, the thermal equilibrium time and thermal equilibrium temperature of the camera system were calculated. Then, the influences of thermal parameters of digital camera and environmental temperature on the temperature characteristics of working digital camera were simulated and experimentally investigated. The theory analysis and experimental results demonstrate that the presented model can accurately describe the temperature characteristics and further calculate the thermal equilibrium state of working digital camera, all of which contribute to guiding mechanics measurement and thermal design based on such camera sensors.

8.
BMC Endocr Disord ; 20(1): 42, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32209072

RESUMO

BACKGROUND: 47,XYY is a chromosomal abnormality syndrome that is typically observed in patients with a male phenotype. Few patients with XYY syndrome will have infertility. We here report a case of 46,XY/47,XYY syndrome diagnosed in a patient with a female phenotype. CASE PRESENTATION: A 15-year-old patient with a female phenotype visited our hospital owing to a chief complaint of short stature as of the age of 6 years. She was diagnosed with dwarf syndrome at the age of 10, but no change was noted after 2 months of growth hormone treatment. The patient's height was 136 cm and the weight was 29 kg, both of which were below the third percentile for her age/gender. In addition to short stature, the 4th and 5th metacarpals were short and there was no significant sex development. Karyotype analysis showed 47,XYY, and chromosomal microarray examination showed a chimera of 46,XY/47,XYY. CONCLUSION: This is an extremely rare case of 47,XYY abnormality in a patient with a female phenotype, with only one such known case reported previously. Since the cause is unknown, and symptoms of this syndrome are highly atypical and variable in childhood, clinicians should be aware of this possibility to avoid misdiagnosis and offer counseling and hormone therapy as needed to patients and their parents to improve their quality of life.


Assuntos
Transtornos do Crescimento/patologia , Qualidade de Vida , Transtornos dos Cromossomos Sexuais/patologia , Cariótipo XYY/patologia , Adolescente , Feminino , Transtornos do Crescimento/genética , Humanos , Fenótipo , Prognóstico , Transtornos dos Cromossomos Sexuais/genética , Cariótipo XYY/genética
9.
Future Oncol ; 16(10): 559-571, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32166977

RESUMO

Aim: To explore the prognostic value of the systemic inflammatory marker (SIM) based on neutrophil, lymphocyte and monocyte counts in head and neck squamous cell carcinoma (HNSCC) patients. Patients & methods: We retrospectively collected the data of 367 patients with HNSCC who underwent surgery. The Kaplan-Meier survival analysis and Cox regression analysis were conducted on disease-free survival and overall survival. Results: A high SIM (>1.34) was associated with larger tumor size, advanced clinical stage and shorter survival time. The survival analysis showed that only clinical stage and SIM were independent prognostic indicators of disease-free survival and overall survival. Conclusion: The SIM positively correlated with tumor progression and might be a powerful prognostic indicator of poor outcome in patients with HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Idoso , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Inflamação , Contagem de Leucócitos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Neutrófilos/patologia , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Taxa de Sobrevida
10.
Int J Colorectal Dis ; 34(4): 589-597, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30627849

RESUMO

PURPOSE: This study aimed to evaluate the prognostic value of circulating tumor cells (CTCs) in advanced colorectal cancer (CRC) patients during chemotherapy course. METHODS: From January 2016 to September 2017, the clinicopathological variables, such as gender, age, tumor location, tumor de-differentiation, depth of invasion, lymphatic invasion, distant metastasis, TNM stage, CTCs enumeration during 2-6 cycles of chemotherapy, and serum carcinoembryonic antigen (CEA) level during the same period, of 121 newly acquired and histopathologically confirmed CRC patients were collected from the Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. All patients were followed up for survival until the end of November 2018. Statistical analysis focused on the associations between CTCs counts and clinicopathological variables. Overall survival (OS) and progression-free survival (PFS) among different prognostic factors were calculated using the Kaplan-Meier method, and the differences between the survival curves were compared by using the log-rank test. Factors of prognostic significance were investigated with the multivariate Cox regression analysis. RESULTS: Here, 71 of 121 patients were CTC-positive, in which CTC-positive rate was positively correlated with the depth of invasion, lymphatic invasion, distant metastasis, TNM stage, and serum CEA level (P < 0.05 for all). However, no significant difference was found between CTC-positive and other clinicopathological variables (P > 0.05 for all), such as gender, age, tumor location, and tumor de-differentiation. CTCs counts gradually increased with the advancement of depth of invasion (P = 0.002), lymphatic invasion (P = 0.004), distant metastasis (P = 0.007), TNM stage (P = 0.001), serum CEA level (P = 0.001), and decreased tumor de-differentiation (P = 0.011). Furthermore, the Kaplan-Meier survival curves showed that patients with CTC-positive had a significantly unfavorable PFS (14 vs. 23 months, P = 0.001) and OS (18 vs. 25 months, P = 0.003). The multivariate Cox regression analyses revealed that the presence of CTCs during chemotherapy was an independent factor for unfavorable PFS (hazard ratio (HR) 2.682, P = 0.017, 95% confidence interval (CI) 1.193-6.029) and OS (HR 2.790, P = 0.048, 95% CI 1.010-7.705) in advanced CRC patients. CONCLUSIONS: This study provided an evidence that the presence of CTCs may be valuable for predicting survival outcome, and CTCs was associated with unfavorable survival in advanced CRC patients during chemotherapy.


Assuntos
Neoplasias Colorretais/patologia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
11.
Chem Asian J ; 12(15): 1861-1864, 2017 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-28557361

RESUMO

Porphyrin-based molecules have been widely used in dye-sensitized solar cells and bulk heterojunction solar cells, but their application in field-effect transistors (FETs) is limited. In this work, two conjugated polymers based on diketopyrrolopyrrole and porphyrin units were developed for FETs. The polymers exhibit extra-low band gap with energy levels close to -4.0 eV and -5.0 eV due to the strong electron-donating and withdrawing ability of porphyrin and diketopyrrolopyrrole. With additionally high crystalline properties, ambipolar charge carrier transports with a hole mobility of 0.1 cm2 V-1 s-1 in FETs were realized in these polymers, representing the highest performance in solution-processed FETs based on porphyrin unit.

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