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1.
Nature ; 616(7955): 50-55, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36949196

RESUMO

The ambition of harnessing the quantum for computation is at odds with the fundamental phenomenon of decoherence. The purpose of quantum error correction (QEC) is to counteract the natural tendency of a complex system to decohere. This cooperative process, which requires participation of multiple quantum and classical components, creates a special type of dissipation that removes the entropy caused by the errors faster than the rate at which these errors corrupt the stored quantum information. Previous experimental attempts to engineer such a process1-7 faced the generation of an excessive number of errors that overwhelmed the error-correcting capability of the process itself. Whether it is practically possible to utilize QEC for extending quantum coherence thus remains an open question. Here we answer it by demonstrating a fully stabilized and error-corrected logical qubit whose quantum coherence is substantially longer than that of all the imperfect quantum components involved in the QEC process, beating the best of them with a coherence gain of G = 2.27 ± 0.07. We achieve this performance by combining innovations in several domains including the fabrication of superconducting quantum circuits and model-free reinforcement learning.

2.
Plant Physiol ; 192(4): 2923-2942, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37204801

RESUMO

Nitrogen (N) is a critical factor for crop growth and yield. Improving N use efficiency (NUE) in agricultural systems is crucial for sustainable food production. However, the underlying regulation of N uptake and utilization in crops is not well known. Here, we identified OsSNAC1 (stress-responsive NAC 1) as an upstream regulator of OsNRT2.1 (nitrate transporter 2.1) in rice (Oryza sativa) by yeast 1-hybridization screening. OsSNAC1 was mainly expressed in roots and shoots and induced by N deficiency. We observed similar expression patterns of OsSNAC1, OsNRT2.1/2.2, and OsNRT1.1A/B in response to NO3- supply. Overexpression of OsSNAC1 resulted in increased concentrations of free NO3- in roots and shoots, as well as higher N uptake, higher NUE, and N use index (NUI) in rice plants, which conferred increased plant biomass and grain yield. On the contrary, mutations in OsSNAC1 resulted in decreased N uptake and lower NUI, which inhibited plant growth and yield. OsSNAC1 overexpression significantly upregulated OsNRT2.1/2.2 and OsNRT1.1A/B expression, while the mutation in OsSNAC1 significantly downregulated OsNRT2.1/2.2 and OsNRT1.1A/B expression. Y1H, transient co-expression, and ChIP assays showed OsSNAC1 directly binds to the upstream promoter regions of OsNRT2.1/2.2 and OsNRT1.1A/1.1B. In conclusion, we identified a NAC transcription factor in rice, OsSNAC1, with a positive role in regulating NO3- uptake through direct binding to the upstream promoter regions of OsNRT2.1/2.2 and OsNRT1.1A/1.1B and activating their expression. Our results provide a potential genetic approach for improving crop NUE in agriculture.


Assuntos
Transportadores de Nitrato , Oryza , Oryza/metabolismo , Proteínas de Transporte de Ânions/genética , Proteínas de Transporte de Ânions/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Nitrogênio/metabolismo , Expressão Gênica , Nitratos/metabolismo
3.
BMC Cardiovasc Disord ; 22(1): 165, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413813

RESUMO

BACKGROUND: The potential prognostic role of total bilirubin (TBIL) in patients with new-onset non-ST elevation myocardial infarction (NSTEMI) is not fully understood. This study aims to evaluate the potential predictive value of TBIL for long-term prognosis in patients with new-onset NSTEMI. METHODS: Patients with new-onset NSTEMI that underwent emergency coronary angiography in our department from June 2015 to March 2020 were included. Baseline TBIL was measured at admission. SYNTAX scores were used to indicate the severity of coronary lesions. The association between TBIL and SYNTAX scores was analyzed using multivariate logistic regression. The patients were followed for the incidence of major adverse cardiac and cerebrovascular events (MACCEs). The association between TBIL and MACCEs was analyzed using Kaplan-Meier survival methods. RESULTS: In total 327 patients were included in this study. Patients were divided according to tertiles of TBIL (first tertile < 10.23 µmol/L, n = 109; second tertile 10.23-14.30 µmol/L, n = 109; and third tertile ≥ 14.30 µmol/L, n = 109). TBIL was independently associated with the severity of coronary lesions in patients with NSTEMI, with an adjusted odds ratio (OR) and 95% confidence interval (CI) for the third tertile and the second tertile compared with the first tertile of TBIL of 2.259 (1.197-4.263) and 2.167 (1.157-4.059), respectively (both p < 0.05). After a mean follow-up of 30.33 months, MACCE had occurred in 57 patients. TBIL was independently associated with the increased risk of MACCEs, with an adjusted hazard ratio (HR) and 95% CI for the third tertile and the second tertile compared with the first tertile of TBIL of 2.737 (1.161-6.450) and 3.272 (1.408-7.607), respectively (both p < 0.05). CONCLUSIONS: Higher myocardial infarction admission TBIL might independently predict poor prognosis in patients with NSTEMI.


Assuntos
Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Bilirrubina , Estudos de Coortes , Humanos , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Prognóstico , Fatores de Risco
4.
J Biopharm Stat ; 30(1): 18-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31135263

RESUMO

We propose an adaptive enrichment approach to test an active factor, which is a factor whose effect is non-zero in at least one subpopulation. We implement a two-stage play-the-winner design where all subjects in the second stage are enrolled from the subpopulation that has the highest observed effect in the first stage. We recommend a weighted Fisher's combination of the most powerful test for each stage, respectively: the first stage Hotelling's test and the second stage noncentral chi-square test. The test is further extended to cover binary outcomes and time-to-event outcomes.


Assuntos
Ensaios Clínicos Adaptados como Assunto/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Catastrofização/genética , Catastrofização/psicologia , Catecol O-Metiltransferase/genética , Interpretação Estatística de Dados , Humanos , Modelos Estatísticos , Polimorfismo de Nucleotídeo Único , Dor de Ombro/genética , Dor de Ombro/psicologia
5.
Zhonghua Yi Xue Za Zhi ; 100(10): 779-784, 2020 Mar 17.
Artigo em Chinês | MEDLINE | ID: mdl-32192293

RESUMO

Objective: To investigate the mechanism of epoxyeicosatrienoic acids (EET) on renal ischemia/reperfusion (I/R). Methods: Thirty 10-week male C57BL6 mice were randomly divided into five groups: sham goup, I/R group, I/R with EET group, I/R with toll-like receptor 4 (TLR4) inhibitor (TAK242) group, I/R with EET and TAK242 group. Blood urea nitrogen (BUN) and serum creatinine (Scr) as well as renal pathological changes were observed 24 h after reperfusion. The protein expression of NOD-like receptor pyrin domain containing 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (caspase-1), interleukin-1ß (IL-1ß), TLR4 and myeloid differentiation factor 88 (MyD88) were evaluated using Western blot. Results: Severe renal tubular epithelial cell injury and decreased renal function [BUN:(10.37±0.53) vs (6.70±0.82)mmol/L, t=9.17, P<0.001; Scr: (83.67±3.88) vs (32.50±3.51)µmol/L, t=23.96, P<0.001] occurred in I/R group. Compared to the sham group, the relative expression of NLRP3 (1.54±0.10 vs 0.71±0.05, t=13.14, P<0.001), caspase-1 (2.35±0.05 vs 0.62±0.02, t=73.77, P<0.001), IL-1ß (3.11±0.11 vs 1.26±0.05, t=35.97, P<0.001), TLR4 (1.58±0.03 vs 0.39±0.01, t=86.00, P<0.001), MyD88 (0.94±0.02 vs 0.26±0.01, t=72.61, P<0.001) were significantly increased. Mice pretreated with EET analog featured lower kidney damage and diminished levels of above proteins than I/R group (all P<0.001). Besides, the co-administration of TAK242 and EET analog could even markedly reduced the expression levels of each proteins than those in I/R group and I/R with EET group (all P<0.001). Conclusion: EET exerts a protective effect on attenuating renal I/R injury possibly through inhibiting TLR4 pathway to regulate the activation of NLRP3-induced pyroptosis.


Assuntos
Piroptose , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide , Proteína 3 que Contém Domínio de Pirina da Família NLR , Traumatismo por Reperfusão
6.
Appl Microbiol Biotechnol ; 102(2): 995-1003, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29181569

RESUMO

Anaerobic ammonium oxidation (anammox) process is regarded as a promising nitrogen removal technology to treat ammonium wastewaters in a wide concentration range. Oligotrophic anaerobic ammonia oxidation bacteria (O-AnAOB) culture has been successfully achieved from a new anammox system to treat superlow ammonium concentration wastewaters. In this work, the O-AnAOB culture was compared with the eutrophic AnAOB (E-AnAOB) culture to reveal its physiological, morphological, and ecological features. Results showed that the specific anammox activity (SAA) of O-AnAOB culture was 0.07 kgN/(kgVSS·d) with the nitrogen removal rate (NRR) of 0.20 kgN/ (m3 d) in the reactor, while the SAA of E-AnAOB culture was 2.11 kgN/(kgVSS·d) with the NRR of 11.10 kgN/(m3 d). The hzs gene transcription levels (hzs-mRNA) of O-AnAOB and E-AnAOB cultures were 1.32 × 109 copies/gVSS and 1.51 × 1010 copies/gVSS, respectively. Morphologically, the O-AnAOB culture took on the unique brown color rather than the typical red color of E-AnAOB. The O-AnAOB cells lived in a disperse pattern in the culture. The cells were seriously deformed with deep craters on the cell wall. The size of anammoxsome and paryphoplasm compartments inside the O-AnAOB cells was smaller than that inside the E-AnAOB cells. Ecologically, the O-AnAOB culture had special microbial community with a higher bacterial diversity than the E-AnAOB. The most dominant genera in O-AnAOB were Anaerolineaceae (33.7%, fermentative bacteria), Candidatus Kuenenia (17.4%, anammox bacteria), and Nitrospira (7.3%, nitrite oxidizing bacteria). This study provided an insight into the new anammox process for deep nitrogen removal from wastewaters.


Assuntos
Amônia/metabolismo , Bactérias Anaeróbias/metabolismo , Consórcios Microbianos , Águas Residuárias/microbiologia , Anaerobiose , Reatores Biológicos/microbiologia , Eutrofização , Nitrogênio/metabolismo , Oxirredução , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química
7.
Faraday Discuss ; 200: 271-288, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28573268

RESUMO

In terms of the global aerosol particle number load, atmospheric new particle formation (NPF) dominates over primary emissions. The key for quantifying the importance of atmospheric NPF is to understand how gas-to-particle conversion (GTP) takes place at sizes below a few nanometers in particle diameter in different environments, and how this nano-GTP affects the survival of small clusters into larger sizes. The survival probability of growing clusters is tied closely to the competition between their growth and scavenging by pre-existing aerosol particles, and the key parameter in this respect is the ratio between the condensation sink (CS) and the cluster growth rate (GR). Here we define their ratio as a dimensionless survival parameter, P, as P = (CS/10-4 s-1)/(GR/nm h-1). Theoretical arguments and observations in clean and moderately-polluted conditions indicate that P needs to be smaller than about 50 for a notable NPF to take place. However, the existing literature shows that in China, NPF occurs frequently in megacities such as in Beijing, Nanjing and Shanghai, and our analysis shows that the calculated values of P are even larger than 200 in these cases. By combining direct observations and conceptual modelling, we explore the variability of the survival parameter P in different environments and probe the reasons for NPF occurrence under highly-polluted conditions.

8.
Genet Mol Res ; 15(2)2016 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-27323069

RESUMO

The TCP family is a transcription factor family, members of which are extensively involved in plant growth and development as well as in signal transduction in the response against many physiological and biochemical stimuli. In the present study, 61 TCP genes were identified in tobacco (Nicotiana tabacum) genome. Bioinformatic methods were employed for predicting and analyzing the gene structure, gene expression, phylogenetic analysis, and conserved domains of TCP proteins in tobacco. The 61 NtTCP genes were divided into three diverse groups, based on the division of TCP genes in tomato and Arabidopsis, and the results of the conserved domain and sequence analyses further confirmed the classification of the NtTCP genes. The expression pattern of NtTCP also demonstrated that majority of these genes play important roles in all the tissues, while some special genes exercise their functions only in specific tissues. In brief, the comprehensive and thorough study of the TCP family in other plants provides sufficient resources for studying the structure and functions of TCPs in tobacco.


Assuntos
Evolução Molecular , Nicotiana/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos/genética , Arabidopsis/genética , Cromossomos de Plantas/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Solanum lycopersicum/genética , Família Multigênica/genética , Filogenia , Proteínas de Plantas/biossíntese , Alinhamento de Sequência , Nicotiana/crescimento & desenvolvimento , Fatores de Transcrição/biossíntese
10.
Genet Mol Res ; 14(4): 15188-200, 2015 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-26634482

RESUMO

Members of the GRAS gene family are important transcriptional regulators. In this study, 21 GRAS genes were identified from tobacco, and were classified into eight subgroups according to the classification of Arabidopsis thaliana. Here, we provide a preliminary overview of this gene family in tobacco, describing the gene structure, gene expression, protein motif organization, phylogenetic analysis, and comparative analysis in tobacco, Arabidopsis, and rice. Using the sequences of 21 GRAS genes in Arabidopsis to search against the American tobacco genome database, 21 homologous GRAS genes in tobacco were identified. Sequence analysis indicates that these GRAS proteins have five conserved domains, which is consistent with their counterparts in other plants. Phylogenetic analyses divided the GRAS gene family into eight subgroups, each of which has distinct conserved domains and biological functions. Furthermore, the expression pattern of these 21 GRAS genes reveals that most are expressed in all six tissues studied; however, some have tissue specificity. Taken together, this comprehensive analysis will provide a rich resource to assist in the study of GRAS protein functions in tobacco.


Assuntos
Genes de Plantas/genética , Família Multigênica/genética , Nicotiana/genética , Motivos de Aminoácidos/genética , Sequência de Aminoácidos , Arabidopsis/genética , Evolução Molecular , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Genoma de Planta/genética , Especificidade de Órgãos/genética , Filogenia , Proteínas de Plantas/genética , Estrutura Terciária de Proteína/genética , Alinhamento de Sequência
11.
Genet Mol Res ; 13(1): 2310-22, 2014 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-24737479

RESUMO

As a model plant, mechanisms of the cytoplasmic male sterility/restoration of fertility (CMS/Rf) system in tobacco are seldom studied. Using Rf gene sequences from other Solanaceae plants and the draft genome of Nicotiana benthamiana, degenerate primers were designed to amplify the cDNA pool of N. tomentosiformis. In total, six possible Rf sequences were identified, two of which contained base-deletion mutations. The other four were intact open reading frames, of which NtomPPR5 harbored a 3-pentatricopeptide repeat (PPR) motif deletion. Structure analysis revealed that they all encoded a PPR-containing protein with putative mitochondrial targeting signals at their N-terminus, and they all belong to the P subfamily. Phylogenetic analysis showed that all of the Rf-coding PPRs clustered together, and recent duplication events might have occurred in tobacco after the divergence of the species. Quantitative reverse transcription polymerase chain reaction analysis demonstrated that the NtomRfs were expressed in all tissues of N. tomentosiformis and (CMS) K326, although the expression levels varied with gene, organ, and developmental stage. Furthermore, the expression levels of Rf sequences in K326 were lower than those in CMS K326. The molecular basis of the CMS/Rf system in tobacco requires further investigation.


Assuntos
Clonagem Molecular , Expressão Gênica , Nicotiana/genética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Domínios e Motivos de Interação entre Proteínas/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Sequência de Bases , Sequência Consenso , Dados de Sequência Molecular , Família Multigênica , Filogenia , Matrizes de Pontuação de Posição Específica , Nicotiana/classificação
12.
Stat Sin ; 24(4): 1613-1631, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26401093

RESUMO

We propose a new method to use a constrained local polynomial regression to estimate the unknown parameters in ordinary differential equation models with a goal of improving the smoothing-based two-stage pseudo-least squares estimate. The equation constraints are derived from the differential equation model and are incorporated into the local polynomial regression in order to estimate the unknown parameters in the differential equation model. We also derive the asymptotic bias and variance of the proposed estimator. Our simulation studies show that our new estimator is clearly better than the pseudo-least squares estimator in estimation accuracy with a small price of computational cost. An application example on immune cell kinetics and trafficking for influenza infection further illustrates the benefits of the proposed new method.

13.
Water Sci Technol ; 67(8): 1873-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23579845

RESUMO

A Pd/C gas-diffusion cathode which generated H2O2 through a two-electron reduction process of fed oxygen molecule was used to degrade 4-chlorophenol in an undivided electrolysis device. The kinetics of 4-chlorophenol degradation has been investigated by the electrochemical oxidation processes. By inspecting the relationship between the rate constants (k) and influencing factors, using first-order kinetics to describe the electrochemical oxidation process of 4-chlorophenol, a kinetic model of 4-chlorophenol degradation process was proposed to calculate the 4-chlorophenol effluent concentration: C = C0 exp( -3:76 × 10(-6) C(-0.5)0 J(2) M(-0.7) Q(0.17) Dt). It was found that the electrocatalytic degradation rate of 4-chlorophenol was affected by current density, electrode distance, air-feeding rate, electrolyte concentration and initial 4-chlorophenol concentration. The kinetics obtained from the experiments under corresponding electrochemical conditions could provide an accurate estimation of 4-chlorophenol effluent concentration and lead to better design of the electrochemical reactor.


Assuntos
Carbono/química , Clorofenóis/química , Eletrólise , Paládio/química , Poluentes Químicos da Água/química , Ar , Eletrodos , Eletrólitos/química , Cinética , Modelos Químicos
14.
J Lipid Res ; 53(5): 829-838, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22393161

RESUMO

Atherosclerotic disease is a leading cause of morbidity and mortality in developed countries, and oxidized LDL (OxLDL) plays a key role in the formation, rupture, and subsequent thrombus formation in atherosclerotic plaques. In the current study, anti-mouse OxLDL polyclonal antibody and nonspecific IgG antibody were conjugated to polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, and a carotid perivascular collar model in apolipoprotein E-deficient mice was imaged at 7.0 Tesla MRI before contrast administration and at 8 h and 24 h after injection of 30 mg Fe/kg. The results showed MRI signal loss in the carotid atherosclerotic lesions after administration of targeted anti-OxLDL-USPIO at 8 h and 24 h, which is consistent with the presence of the nanoparticles in the lesions. Immunohistochemistry confirmed the colocalization of the OxLDL/macrophages and iron oxide nanoparticles. The nonspecific IgG-USPIO, unconjugated USPIO nanoparticles, and competitive inhibition groups had limited signal changes (p < 0.05). This report shows that anti-OxLDL-USPIO nanoparticles can be used to directly detect OxLDL and image atherosclerotic lesions within 24 h of nanoparticle administration and suggests a strategy for the therapeutic evaluation of atherosclerotic plaques in vivo.


Assuntos
Apolipoproteínas E/deficiência , Artérias Carótidas , Compostos Férricos , Lipoproteínas LDL/metabolismo , Imageamento por Ressonância Magnética/métodos , Nanopartículas , Placa Aterosclerótica/diagnóstico , Animais , Constrição , Meios de Contraste/química , Meios de Contraste/metabolismo , Compostos Férricos/química , Compostos Férricos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/metabolismo , Polietilenoglicóis/química
15.
Fish Physiol Biochem ; 38(5): 1409-17, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22395532

RESUMO

Aquatic animals are faced with the challenge of extracting oxygen from water, a medium that is metabolically expensive to ventilate and that contains just a fraction of the oxygen concentration relative to air, yet the physiologies of fishes have evolved to support a wide range of activity levels in nature. Oxygen delivery components, including gill surface area (oxygen uptake), blood chemistry (oxygen transport), and the heart (system pump), have been positively correlated to activity level in teleost fishes, yet relatively little is known about how these components are related to activity in elasmobranches. The current study addresses this question by examining heart mass, hemoglobin concentration, hematocrit level, and gill surface area in wild-caught representatives of the benthic Atlantic stingray (Dasyatis sabina) and active cownose ray (Rhinoptera bonasus). Allometric scaling exponents are similar for all four measures between the study species. Heart mass, gill surfaces areas, and hemoglobin concentrations were 2.1 times, approximately 7.1 times, and 2.0 times higher, respectively, in active cownose rays, when compared to benthic Atlantic stingrays, after correcting for differences in body mass. When considered in the context of functional plasticity within the oxygen delivery systems of benthic and active species, data from the current study indicate that higher activity levels in cownose rays are supported by modifications that, at least in part, are likely to enhance oxygen uptake.


Assuntos
Brânquias/metabolismo , Coração/anatomia & histologia , Hemoglobinas/metabolismo , Atividade Motora/fisiologia , Rajidae/sangue , Rajidae/fisiologia , Animais , Feminino , Masculino , Rajidae/genética , Especificidade da Espécie
16.
Lifetime Data Anal ; 18(4): 397-407, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22388514

RESUMO

We provide a copula identifiability condition for dependent truncated data model. The identifiability is characterized by the strong lower-left tail identifiability of the copula family. We show that the commonly used Archimedean copula families with analytic generator functions satisfy this condition.


Assuntos
Interpretação Estatística de Dados , Modelos Estatísticos , Análise de Sobrevida , Ensaios Clínicos como Assunto , Humanos
17.
Oncogene ; 41(3): 414-426, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34773072

RESUMO

Oncogene induced senescence is a tumor suppressing defense mechanism, in which the cell cycle-dependent protein kinase (CDK) inhibitor p16INK4A (encoded by the CDKN2A gene) plays a key role. We previously reported that a transcriptional co-activator chromodomain helicase DNA binding protein 7 (CHD7) mediates oncogenic ras-induced senescence by inducing transcription of the p16INK4A gene. In the current study, we identified myeloid zinc finger 1 (MZF1) as the transcriptional factor that recruits CHD7 to the p16INK4A promoter, where it mediates oncogenic ras-induced p16INK4A transcription and senescence through CHD7, in primary human cells from multiple origins. Moreover, the expression of MZF1 is induced by oncogenic ras in senescent cells through the c-Jun and Ets1 transcriptional factors upon their activation by the Ras-Raf-1-MEK-ERK signaling pathway. In non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma (PAAD) where activating ras mutations occur frequently, reduced MZF1 expression is observed in tumors, as compared to corresponding normal tissues, and correlates with poor patient survival. Analysis of single cell RNA-sequencing data from PAAD patients revealed that among the tumor cells with normal RB expression levels, those with reduced levels of MZF1 are more likely to express lower p16INK4A levels. These findings have identified novel signaling components in the pathway that mediates induction of the p16INK4A tumor suppressor and the senescence response, and suggested that MZF1 is a potential tumor suppressor in at least some cancer types, the loss of which contributes to the inactivation of the p16INK4A/RB pathway and disruption of senescence in tumor cells with intact RB.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Animais , Células Cultivadas , Humanos , Camundongos , Camundongos Knockout , Oncogenes , Fatores de Transcrição
18.
Biometrics ; 67(3): 719-29, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21039394

RESUMO

Recurrent events data are commonly seen in longitudinal follow-up studies. Dependent censoring often occurs due to death or exclusion from the study related to the disease process. In this article, we assume flexible marginal regression models on the recurrence process and the dependent censoring time without specifying their dependence structure. The proposed model generalizes the approach by Ghosh and Lin (2003, Biometrics 59, 877-885). The technique of artificial censoring provides a way to maintain the homogeneity of the hypothetical error variables under dependent censoring. Here we propose to apply this technique to two Gehan-type statistics. One considers only order information for pairs whereas the other utilizes additional information of observed censoring times available for recurrence data. A model-checking procedure is also proposed to assess the adequacy of the fitted model. The proposed estimators have good asymptotic properties. Their finite-sample performances are examined via simulations. Finally, the proposed methods are applied to analyze the AIDS linked to the intravenous experiences cohort data.


Assuntos
Modelos Estatísticos , Recidiva , Análise de Regressão , Síndrome da Imunodeficiência Adquirida/patologia , Biometria/métodos , Seguimentos , Humanos , Estudos Longitudinais
19.
J Exp Med ; 167(3): 1154-70, 1988 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-3127523

RESUMO

Murine Kupffer cells (KCs), which constitute one of the largest populations of tissue macrophages, differ from most other cells of the myelomonocytic lineage in lacking the capacity for a respiratory burst. A collagenase perfusion technique followed by adherence to plastic at low temperature yielded pure cultures of KCs uniformly expressing receptors for Fc and C3bi, and containing virtually no morphologically detectable intracytoplasmic debris. Such KCs took up and oxidized glucose via the hexose monophosphate shunt about the same as peritoneal macrophages (PCs). Respiratory burst stimuli failed to enhance the hexose monophosphate shunt in KCs, probably because no H2O2 was produced. Detergent-permeabilized KCs generated no O2- in the presence of 1 mM NADPH, in striking contrast to all PC populations studied. Yet, KCs contained at least one component of the O2(-)-producing oxidase, cytochrome b559, in the same quantities as PCs and neutrophils. Cytochrome b559 was demonstrated by a novel double-reduction spectral technique that eliminated interference from hemoglobin and mitochondrial cytochromes. Consistent with the presence of the oxidase, KCs acquired normal respiratory burst capacity after prolonged incubation in vitro. The defect in triggering the respiratory burst in KCs was selective for the reduction of O2 by NADPH, in that reduction of O2 by endogenous arachidonate was readily demonstrate in response to zymosan. The percent of arachidonate released, the percent oxygenated, and the suppression of prostacyclin and leukotriene C production, as well as the pattern of LFA-1 expression, all resembled the pattern reported with PCs several days after exposure to bacteria. Indeed, exposure of PCs to low numbers of zymosan particles led gradually to complete suppression of respiratory burst capacity and refractoriness to its enhancement by rIFN-gamma, as evident in KCs both before and after their explanation. Thus, the modulation of oxidative metabolism that characterizes KCs probably arises from frequent endocytic encounters. This phenomenon may permit macrophages to act as scavengers without oxidative damage to bystander cells.


Assuntos
Células de Kupffer/metabolismo , Ativação de Macrófagos , Consumo de Oxigênio , Complexo de Proteína do Fotossistema II , Animais , Ácido Araquidônico , Ácidos Araquidônicos/metabolismo , Grupo dos Citocromos b/metabolismo , Feminino , Glucose/metabolismo , Interferon gama/farmacologia , Células de Kupffer/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , NADH NADPH Oxirredutases/metabolismo , NADPH Oxidases , Via de Pentose Fosfato , Cavidade Peritoneal/citologia , Proteínas Recombinantes/farmacologia
20.
J Exp Med ; 165(3): 733-49, 1987 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-3102677

RESUMO

Several features of activation of mouse peritoneal macrophages were elicited by 1-2-d exposure to submicrogram concentrations of anti-Mac-1 (M1/70), a rat monoclonal antibody that reacts with the alpha chain of complement receptor type 3 (Mac-1). The changes induced included enhanced capacity to secrete H2O2 when triggered with PMA, decreased secretion of proteins, increased expression of Ia antigen and decreased phagocytosis of particles. These changes closely resembled those induced by rIFN-gamma in type, extent, and time course. The concentration of M1/70 IgG resulting in 50% of the maximal activation of macrophage H2O2-releasing capacity averaged 0.18 +/- 0.03 micrograms/ml. This activation was not blocked by anti-FcR mAb, and could be reproduced with M18/2, a mAb against beta chain of Mac-1, suggesting that a direct ligation of Mac-1 with mAb was responsible for the activation. Neither depletion of T cells nor addition of neutralizing Abs to IFN-gamma or TNF-alpha prevented M1/70-mediated macrophage activation. Moreover, F(ab')2 of M1/70, or plating of macrophages on C3bi-coated surfaces, inhibited the activation of macrophages by rIFN-gamma. These findings suggest that Mac-1 (CR3) may play an important role in macrophage activation.


Assuntos
Anticorpos Monoclonais/fisiologia , Antígenos de Superfície/imunologia , Ativação de Macrófagos , Animais , Feminino , Glicoproteínas/farmacologia , Antígenos de Histocompatibilidade Classe II/biossíntese , Peróxido de Hidrogênio/metabolismo , Fragmentos Fab das Imunoglobulinas/fisiologia , Interferon gama/farmacologia , Cinética , Antígeno de Macrófago 1 , Camundongos , Camundongos Endogâmicos ICR , Fagocitose , Biossíntese de Proteínas , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa
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