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Breastfeeding is widely recognized as the gold standard for infant nutrition, benefitting infants' gastrointestinal tracts. Stool analysis helps in understanding pediatric gastrointestinal health, but the effectiveness of automated fecal consistency evaluation by parents of breastfeeding infants has not been investigated. Photographs of one-month-old infants' feces on diapers were taken via a smartphone app and independently categorized by Artificial Intelligence (AI), parents, and researchers. The accuracy of the evaluations of the AI and the parents was assessed and compared. The factors contributing to assessment bias and app user characteristics were also explored. A total of 98 mother-infant pairs contributed 905 fecal images, 94.0% of which were identified as loose feces. AI and standard scores agreed in 95.8% of cases, demonstrating good agreement (intraclass correlation coefficient (ICC) = 0.782, Kendall's coefficient of concordance W (Kendall's W) = 0.840, Kendall's tau = 0.690), whereas only 66.9% of parental scores agreed with standard scores, demonstrating low agreement (ICC = 0.070, Kendall's W = 0.523, Kendall's tau = 0.058). The more often a mother had one or more of the following characteristics, unemployment, education level of junior college or below, cesarean section, and risk for postpartum depression (PPD), the more her appraisal tended to be inaccurate (p < 0.05). Each point increase in the Edinburgh Postnatal Depression Scale (EPDS) score increased the deviation by 0.023 points (p < 0.05), which was significant only in employed or cesarean section mothers (p < 0.05). An AI-based stool evaluation service has the potential to assist mothers in assessing infant stool consistency by providing an accurate, automated, and objective assessment, thereby helping to monitor and ensure the well-being of infants.
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Lactancia Materna , Madres , Humanos , Lactante , Niño , Femenino , Embarazo , Estudios de Cohortes , Inteligencia Artificial , Cesárea , ChinaRESUMEN
Docosahexaenoic acid (DHA) is highly enriched in the brain, and is essential for normal brain development and function. However, evidence suggests that currently used supplements, such as fish oil, do not significantly increase brain DHA levels. Therefore, this study aimed to investigate whether combined fish oil and choline supplementation could affect the type and enrich the content of DHA in the brain. The results revealed that the combined intake of fish oil and choline upregulated the expression of key transporters and receptors, including MFSD2A, FATP1, and FABP5, which increased the uptake of DHA in the brain. Additionally, this supplementation improved the synthesis and release of acetylcholine in the brain, which, in turn, enhanced the learning and memory abilities of mice. These findings suggest that the combined intake of fish oil and choline improves the bioavailability of DHA in the brain.
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Background: Epidermal growth factor receptor (EGFR) is a well-known target for cancer treatment. However, the authorized anti-EGFR monoclonal antibodies generally cause several toxic effects, especially severe cutaneous toxicities as well as infusion reactions, and the clinical indications are limited. Here we developed Ametumumab, a fully human recombinant anti-EGFR monoclonal antibody. Objectives: To assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity of Ametumumab. Design: A first-in-human phase Ia dose escalation study of Ametumumab in patients with advanced solid malignancies. Methods: An open-label, first-in-human dose escalation study was done in 22 patients with advanced malignancies who received six ascending dosages ranging from 75 to 750 mg/m2. Following a single dosage and a 28-day dose-limiting toxicity (DLT) monitoring period, patients were given repeated doses weekly. Blood samples were taken to determine the PK parameters of Ametumumab and anti-drug antibody concentrations. Every 8 weeks, radiographic tumor evaluations were conducted. Results: In this trial, no DLT was observed, and the maximum tolerated dose was not reached at doses up to 750 mg/m2. There were no severe adverse events but mild and moderate adverse effects, such as headache, proteinuria, and rash. Single-dose PK results demonstrated a straightforward linear relationship with dosage escalation. The medication concentrations accumulated and attained steady-state after four rounds of injections. It was calculated that 10 patients with disease control would be observed in the 22 evaluable patients. The disease control rate was 45.5%. Conclusion: The Ametumumab was well tolerated and safe in patients with advanced solid malignancies, exhibiting minimal immunogenicity, a long half-life, high levels of drug exposure in the blood, and preliminary effectiveness. Registration: The trial was registered with CTR20170343 on 10 April 2017, The China Center for Drug Evaluation.
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With the rapid progress of deepfake techniques in recent years, facial video forgery can generate highly deceptive video content and bring severe security threats. And detection of such forgery videos is much more urgent and challenging. Most existing detection methods treat the problem as a vanilla binary classification problem. In this article, the problem is treated as a special fine-grained classification problem since the differences between fake and real faces are very subtle. It is observed that most existing face forgery methods left some common artifacts in the spatial domain and time domain, including generative defects in the spatial domain and interframe inconsistencies in the time domain. And a spatial-temporal model is proposed which has two components for capturing spatial and temporal forgery traces from a global perspective, respectively. The two components are designed using a novel long-distance attention mechanism. One component of the spatial domain is used to capture artifacts in a single frame, and the other component of the time domain is used to capture artifacts in consecutive frames. They generate attention maps in the form of patches. The attention method has a broader vision which contributes to better assembling global information and extracting local statistic information. Finally, the attention maps are used to guide the network to focus on pivotal parts of the face, just like other fine-grained classification methods. The experimental results on different public datasets demonstrate that the proposed method achieves state-of-the-art performance, and the proposed long-distance attention method can effectively capture pivotal parts for face forgery.
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Background: Growing evidence has shown the association between vitamin E intake and the risk of cognitive decline, but the conclusions were inconsistent. This study aimed to verify the hypothesis that vitamin E intake is associated with incident dementia and deterioration of global cognition. Materials and methods: We followed 1,550 non-demented community residents aged ≥60 years for an average of 5.2 years in the Shanghai Aging Study. Baseline vitamin E intake were measured by the Food Frequency Questionnaire. Cognitive function was evaluated by a battery of neuropsychological tests. Consensus diagnosis of incident dementia was made based on the DSM-IV criteria. Results: During the follow-up, 135 cases (8.7%) of incident dementia were identified. The incidence rates of dementia in low, low-medium, medium-high, and high vitamin E intake groups were 2.8, 1.5, 1.6, and 0.7 per 100 person-years, respectively (P < 0.001). Participants with low vitamin E intake had a significantly higher risk of incident dementia than those with higher intake [compared with the highest intake group: hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.20-4.57] after adjusting for confounders. Vitamin E intake was negatively correlated to the rate of annual decline of Mini-Mental State Examination score with the adjustment of confounders (ß = 0.019, p = 0.001). Conclusion: Vitamin E intake is negatively correlated with the risk of dementia in older adults. An appropriate high amount of vitamin E intake from the diet might be helpful to prevent future cognitive decline.
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The elderly population in China is expected to exceed 300 million and enter the stage of moderate aging during the 14th Five-Year plan period from 2021 to 2025. From the sustainable development perspective of elderly care enterprises, the supply of elderly care services would be unsustainable if enterprises suffer long-term losses. In the latter pursuit of high profits, the burden on consumers will increase. Equity financing of these enterprises is the key to achieving high-quality transformation and development by considering economic and social benefits. This study considers 20 well-known China-based elderly care enterprises as the research object. It uses a fuzzy set to explore system logic, operation mode, management performance, and attitude of elderly care enterprises toward investment through the qualitative comparative analysis method. The causal relationship between them is clarified-because, before the endowment enterprise equity financing intention of China, it is important to explore the effective path of equity financing of endowment enterprises. In the past, this helped Chinese elderly care enterprises actively cope with the trend of population aging, meet the needs of diversified and multi-level elderly care services, establish a sustainable development mode, and achieve high-quality transformation and development. The results show that (1) the operating performance of elderly care enterprises under the mode of public construction and private operation is poor; (2) elderly care enterprises driven by public welfare logic are more likely to achieve higher business performance, and (3) elderly care enterprises driven by business logic are more willing to introduce investment when they have made profits.
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Financiación del Capital , Intención , Humanos , Anciano , China , Envejecimiento , LógicaRESUMEN
Toxoplasmosis caused by the protozoan Toxoplasma gondii is one of the most common parasitic diseases in humans and almost all warm-blooded animals. Lys, Glu, and Gln-specific tRNAs contain a super-modified 2-thiourea (s2U) derivatives at the position 34, which is essential for all living organisms by maintaining the structural stability and aminoacylation of tRNA, and the precision and efficiency of codon recognition during protein translation. However, the enzyme(s) involved in this modification in T. gondii remains elusive. In this report, three putative tRNA-specific 2-thiolation enzymes were identified, of which two were involved in the s2U34 modification of tRNALys, tRNAGlu, and tRNAGln. One was named TgMnmA, an apicoplast-located tRNA-specific 2-thiolation enzyme in T. gondii. Knockout of TgMnmA showed that this enzyme is important for the lytic cycle of tachyzoites. Loss of TgMnmA also led to abnormities in apicoplast biogenesis and severely disturbed apicoplast genomic transcription. Notably, mice survived from the infection with 10 TgMnmA-KO RH tachyzoites. These findings provide new insights into s2U34 tRNA modification in Apicomplexa, and suggest TgMnmA, the first apicoplast tRNA thiouridylase identified in all apicomplexans, as a potential drug target.
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Apicoplastos , Toxoplasma , Toxoplasmosis , Animales , Apicoplastos/genética , Apicoplastos/metabolismo , Humanos , Ratones , Ratones Noqueados , Proteínas Protozoarias/genética , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Toxoplasmosis/parasitologíaRESUMEN
Toxoplasma gondii, a worldwide distributed apicomplexan protozoan, can infect almost all warm-blooded animals and may cause toxoplasmosis. In order to provide a point-of-care detection method for T. gondii infection, an immunochromatographic test (ICT) was established. The proposed test uses recombinant T. gondii rhoptry protein 14 (ROP14) conjugated with 20 nm gold particles, recombinant protein A as the detection line and monoclonal antibody TgROP14-5D5 as the control line. The specificity, sensitivity, positive predictive value, negative predictive value and stability of this new ICT were evaluated. rTgROP14 was specifically recognized by positive serum of T. gondii but not negative serum. mAb TgROP14-5D5 showed higher specific recognition of T. gondii antigens and was therefore selected for subsequent colloidal gold strip construction. The new ICT based on TgROP14 exhibited good diagnostic performance with high specificity (86.9%) and sensitivity (90.9%) using IHA as a "reference standard". Among 436 field porcine sera, ICT and IHA detected 134 (30.7%) and 99 (22.7%) positive samples, respectively. The relative agreement was 87.8%. These data indicate that this new ICT based on TgROP14 is a suitable candidate for routine testing of T. gondii in the field.
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Resistance (R) proteins are important components of plant innate immunity. Most known R proteins are nucleotide-binding site leucine-rich repeat (NLR) proteins. Although a number of signaling components downstream of NLRs have been identified, we lack a general understanding of the signaling pathways. Here, we used the interaction between rice (Oryza sativa) and Magnaporthe oryzae to study signaling of rice NLRs in response to blast infection. We found that in blast resistance mediated by the NLR PIRICULARIA ORYZAE RESISTANCE IN DIGU 3 (PID3), the guanine nucleotide exchange factor OsSPK1 works downstream of PID3. OsSPK1 activates the small GTPase OsRac1, which in turn transduces the signal to the transcription factor RAC IMMUNITY1 (RAI1). Further investigation revealed that the three signaling components also play important roles in disease resistance mediated by the distantly related NLR protein Pi9, suggesting that the OsSPK1-OsRac1-RAI1 signaling pathway could be conserved across rice NLR-induced blast resistance. In addition, we observed changes in RAI1 levels during blast infection, which led to identification of OsRPT2a, a subunit of the 19S regulatory particle of the 26S proteasome. OsRPT2a seemed to be responsible for RAI1 turnover in a 26S proteasome-dependent manner. Collectively, our results suggest a defense signaling route that might be common to NLR proteins in response to blast infection.
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Magnaporthe/fisiología , Proteínas NLR/genética , Oryza/genética , Enfermedades de las Plantas/genética , Inmunidad de la Planta/genética , Transducción de Señal , Resistencia a la Enfermedad/genética , Proteínas NLR/metabolismo , Oryza/microbiología , Enfermedades de las Plantas/microbiologíaRESUMEN
Seashore habitats are located between terrestrial and marine ecosystems, which are a hotspot for anthropogenic impacts. Shenzhen is one of the most developed cities in south China, but the microbial functions of its coastal ecosystems remain poorly understood. The study applied 16S rRNA gene sequencing methods to identify the bacterial community from twenty sites of Shenzhen inshore waters. The microbial structure of the samples between eastern Shenzhen and western Shenzhen seashores is notably different, suggesting the spatial variability. Proteobacteria, Cyanobacteria, Actinobacteria, and Bacteroidetes were dominant phyla in the community, and the relative abundance of Bacteroidetes was significantly higher in eastern seashores. Specifically, samples from western Shenzhen contained much more Prochlorococcus, while Synechococcus was more abundant in eastern samples. Moreover, the metabolism of terpenoids and polyketides, and transport and catabolism were significantly more abundant in eastern samples, while antibiotic-resistant pathways were enriched in western samples. The results have important significance to understand bacterial ecosystem of coastal water and promote water quality management and protection activity in Shenzhen. This study can also help developing an optimal strategy for the green economy development and the policy planning of Guangdong-Hong Kong-Macao Greater Bay Area.
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Cianobacterias , Microbiota , Secuenciación de Nucleótidos de Alto Rendimiento , ARN Ribosómico 16S/genética , Calidad del AguaRESUMEN
Eukaryotic microorganisms are ubiquitous in the marine environment, and have a wide variety of ecosystem functions. Shenzhen is one of the most developed cities in South China, but the eukaryotic communities in the water along its coastlines remain poorly understood. The study applied 18S rRNA gene ITS (internal transcribed spacer) sequencing to identify the eukaryotic community from twenty sites of Shenzhen coast water. The alpha-diversity of the samples between these sites were significantly different, and the seawater of eastern coast had higher alpha-diversity compared to that of the western coast. The abundance of Chlorophyta was notably higher in the seawater of western coast, but Picozoa was relatively depleted. Specifically, Cryptocaryon, Pseudovorticella, and Cyclotella were significantly higher in the water of western coast, while Guinardia, Minutocellus, and Amoebophrya were increased in eastern samples. The spatially variations of eukaryotic microorganism community in the seawater of Shenzhen coast were associated with the water quality. The results have important significance for the understanding of coastal eukaryotic community, their interaction network, and build a foundation for future management and protection of coastal water quality.
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Ecosistema , Eucariontes , China , Eucariontes/genética , Agua de Mar , Calidad del AguaRESUMEN
BACKGROUND: Toxoplasma gondii is an obligate parasite of all warm-blooded animals around the globe. Once infecting a cell, it manipulates the host's DNA damage response that is yet to be elucidated. The objectives of the present study were three-fold: (i) to assess DNA damages in T. gondii-infected cells in vitro; (ii) to ascertain causes of DNA damage in T. gondii-infected cells; and (iii) to investigate activation of DNA damage responses during T. gondii infection. METHODS: HeLa, Vero and HEK293 cells were infected with T. gondii at a multiplicity of infection (MOI) of 10:1. Infected cells were analyzed for a biomarker of DNA double-strand breaks (DSBs) γH2AX at 10 h, 20 h or 30 h post-infection using both western blot and immunofluorescence assay. Reactive oxygen species (ROS) levels were measured using 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA), and ROS-induced DNA damage was inhibited by a ROS inhibitor N-acetylcysteine (NAC). Lastly, DNA damage responses were evaluated by detecting the active form of ataxia telangiectasia mutated/checkpoint kinase 2 (ATM/CHK2) by western blot. RESULTS: γH2AX levels in the infected HeLa cells were significantly increased over time during T. gondii infection compared to uninfected cells. NAC treatment greatly reduced ROS and concomitantly diminished γH2AX in host cells. The phosphorylated ATM/CHK2 were elevated in T. gondii-infected cells. CONCLUSIONS: Toxoplasma gondii infection triggered DNA DSBs with ROS as a major player in host cells in vitro. It also activated DNA damage response pathway ATM/CHK2. Toxoplasma gondii manages to keep a balance between survival and apoptosis of its host cells for the benefit of its own survival.
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Roturas del ADN de Doble Cadena , Especies Reactivas de Oxígeno/metabolismo , Toxoplasma/fisiología , Toxoplasmosis/genética , Apoptosis , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Quinasa de Punto de Control 2/genética , Quinasa de Punto de Control 2/metabolismo , Células HEK293 , Células HeLa , Humanos , Fosforilación , Toxoplasma/genética , Toxoplasmosis/metabolismo , Toxoplasmosis/parasitología , Toxoplasmosis/fisiopatologíaRESUMEN
In the past two decades, corporate hypocrisy has become a phenomenon that cannot be ignored in Corporate Social Responsibility (CSR) practice (Wagner et al., 2009) and has thus become a concern for management scholars (Cho and Lee, 2019). Using smartPLS, based on attribution theory, this paper takes 28 Chinese listed enterprises as examples to explore the influence of CSR motivation on its communication and implementation, as well as the impact of CSR implementation and promotion on consumers' perception of corporate hypocrisy. The research finds a negative correlation between value-driven motivation and corporate hypocrisy and a positive correlation of performance-driven motivation and stakeholder-driven motivation with corporate hypocrisy. The theoretical contribution of this paper is mainly reflected in the following four aspects. (1) It describes the scale of CSR implementation research and enriches the measurement tools of CSR implementation. (2) It enriches and expands research results in the field of CSR motivation perception. From the perspective of CSR and attribution theory, this study explores the influence of consumers' perception of CSR motivation on CSR communication and CSR implementation. (3) It supplements research results in the field of corporate hypocrisy. The influence of CSR communication and CSR implementation on corporate hypocrisy is clarified. (4) It clarifies the impact of CSR communication on CSR implementation so as to help enterprises better match CSR communication strategy and CSR implementation in practice and reduce consumers' perception of corporate hypocrisy. It is suggested that enterprises find their own positioning on CSR motivation, which provides a reference with which enterprises can make better decisions on CSR communication strategy after implementing CSR behavior and provides empirical evidence for the research on CSR motivation perception and corporate hypocrisy in China.
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Genotyping and phenotyping large natural populations provide opportunities for population genomic analysis and genome-wide association studies (GWAS). Several rice populations have been re-sequenced in the past decade; however, many major Chinese rice cultivars were not included in these studies. Here, we report large-scale genomic and phenotypic datasets for a collection mainly comprised of 1,275 rice accessions of widely planted cultivars and parental hybrid rice lines from China. The population was divided into three indica/Xian and three japonica/Geng phylogenetic subgroups that correlate strongly with their geographic or breeding origins. We acquired a total of 146 phenotypic datasets for 29 agronomic traits under multi-environments for different subpopulations. With GWAS, we identified a total of 143 significant association loci, including three newly identified candidate genes or alleles that control heading date or amylose content. Our genotypic analysis of agronomically important genes in the population revealed that many favorable alleles are underused in elite accessions, suggesting they may be used to provide improvements in future breeding efforts. Our study provides useful resources for rice genetics research and breeding.
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Genoma de Planta , Oryza/genética , Sitios de Carácter Cuantitativo/genética , Alelos , China , Frecuencia de los Genes , Genes de Plantas , Estudio de Asociación del Genoma Completo , Genómica , Fenotipo , Filogenia , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Haemonchus contortus, a blood-feeding parasite, is constantly surrounded by large quantities of heme released from the catabolism of host red blood cells. To cope with the toxicity of free heme, H. contortus needs to uptake and detoxify the heme, a process believed to be paramount for parasite survival. METHODS: A heme-responsive gene Hc-hrg-2 was identified which is the homologue of Ce-hrg-2. The transcriptional levels in all developmental stages and heme-responsive ability of Hc-hrg-2 were analyzed by qRT-PCR. Immunofluorescence analysis and cell transfections were performed to analyze the expression pattern of Hc-HGR-2. Statistical analyses were performed with GraghPad Prism 6.0 using Student's t-test. RESULTS: To investigate the heme homeostasis of H. contortus, we first identified a heme-responsive gene Hc-hrg-2, a homolog of Ce-hrg-2 that is involved in heme transport in the hypodermis of Caenorhabditis elegans. Using qRT-PCR, we showed that Hc-hrg-2 mRNA was expressed throughout all life-cycle stages of H. contortus with the highest level in the third-stage larvae (L3s). Notably, transcription of Hc-hrg-2 in the exsheathed L3s was significantly upregulated in the presence of high concentration of heme. We found that Hc-HRG-2 protein was mainly located in the hypodermal tissues of adult H. contortus in vivo and the endoplasmic reticulum in the transfected mammalian cells. Our in vitro assay demonstrated that Hc-HRG-2 is a heme-binding protein with glutathione S-transferase activity and heme had a significant effect on its enzymatic activity when a model substrate 1-chloro-2, 4-dinitrobenzene (CDNB) was used. CONCLUSIONS: Hc-hrg-2 is a heme-responsive gene and engaged in heme homeostasis regulation in hypodermal tissues during the free-living stages of H. contortus.
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Glutatión Transferasa/genética , Haemonchus/genética , Hemo/metabolismo , Hemoproteínas/genética , Secuencia de Aminoácidos , Animales , Caenorhabditis elegans/enzimología , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Retículo Endoplásmico/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente , Glutatión Transferasa/química , Glutatión Transferasa/metabolismo , Haemonchus/enzimología , Haemonchus/metabolismo , Hemoproteínas/química , Hemoproteínas/metabolismo , Homeostasis/genética , Masculino , Ratones , Ratones Endogámicos ICR , Reacción en Cadena en Tiempo Real de la Polimerasa , Alineación de Secuencia , Activación Transcripcional , Regulación hacia ArribaRESUMEN
Using the Grounded theory, we took 15 Chinese entrepreneurs as the research objects and constructed the entrepreneurial process model of dynamic evolution of entrepreneurial motivation. The model includes seven themes, such as egoist motivation, bottleneck, altruistic motivation, TP/MTP, empathy, responsible leadership, CSR implementation and entrepreneurial performance. Through the analysis of the internal relations between these elements, we abstracts the law of the dynamic evolution process of entrepreneurial motivation of Chinese entrepreneurs, and reveals the mechanism of the dynamic evolution process of entrepreneurial motivation. The theoretical contribution of this paper is mainly reflected in the following two aspects: (1) it enriches and expands the research results in the field of entrepreneurship motivation of Chinese entrepreneurs. From the perspective of entrepreneurial motivation, this study analyzes the dynamic evolution process of Internet entrepreneurs' entrepreneurial motivation, extracts the rules of entrepreneurial process of dynamic evolution of Internet entrepreneurs, and provides a new path for enriching and expanding the research on Internet entrepreneurs' entrepreneurial motivation. (2) The study of turning point (TP) that enriches and complements the dynamic evolution of entrepreneurs' entrepreneurial motivation. Using grounded theory, this paper deeply analyzes the reasons for the dynamic evolution of entrepreneurial motivation, and provides empirical evidence for the research on the evolution of localized entrepreneurial motivation in China.
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In this paper, the leader-following consensus problem of a class of nonlinearly multi-dimensional multi-agent systems with actuator faults is addressed by developing a novel neural network learning strategy. In order to achieve the desirable consensus results, a neural network learning algorithm composed of adaptive technique is proposed to on-line approximate the unknown nonlinear functions and estimate the unknown bounds of actuator faults. Then, on the basis of the approximations and estimations, a robust adaptive distributed fault-tolerant consensus control scheme is investigated so that the bounded results of all signals of the resulting closed-loop leader-following system can be achieved by using Lyapunov stability theorem. Finally, efficiency of the proposed adaptive neural network learning strategy-based consensus control strategies is demonstrated by a coupled nonlinear forced pendulums system.
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Aprendizaje Automático , Redes Neurales de la Computación , Consenso , Dinámicas no LinealesRESUMEN
Emergence of clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph-) cells in chronic myeloid leukemia (CML) patients during the treatment with tyrosine kinase inhibitors (TKIs) is an interesting phenomenon. Although previous studies revealed some potential impact of CCA/Ph- on CML patients' outcome, clinical significance of CCA/Ph- in CML patients remains to be further elucidated. We retrospectively reviewed the patients with CML evaluated at Genoptix Medical Laboratory in Carlsbad, California from 2005 to 2015. Twenty-four CML patients with CCA/Ph- cells were identified. These include 18 patients with single chromosomal abnormality, 4 patients with double chromosomal abnormalities, and two patients with complex cytogenetic abnormalities. In addition to trisomy 8 and monosomy 7, we identified that 20q- was also a common abnormality in CCA/Ph- cells. Most of the patients with CCA/Ph- cells demonstrated no significant dysplasia or increased blasts with two exceptions: one patient with persistent 7q- exhibiting mild dysmegakaryopoiesis, suggestive of an early evolving myelodysplastic syndrome, and another patient with complex cytogenetic abnormalities who developed acute myeloid leukemia after gained MLL amplification. One patient with complex cytogenetic abnormalities showed optimal response to TKI treatment, no overt dysplasia, and no disease progression during almost 4-years of follow-up. More interestingly, FISH tests could identify more cases with double chromosomal abnormalities and these cases showed suboptimal responses to TKI treatments. Our observation indicates that 20q- was also a common abnormality in CCA/Ph- cells, further FISH tests revealed additional CCA/Ph-, and the majority of CML patients with two or more chromosomal abnormalities in Ph- cells showed inferior response to TKI treatments. The results of our study suggest that CML cases with CCA/Ph- may represent a group of patients with heterogeneous genetic alterations.
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Aberraciones Cromosómicas , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/tratamiento farmacológico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Persona de Mediana EdadRESUMEN
Plants depend on Resistance (R) genes, most of which encode nucleotide-binding site leucine-rich repeat (NLR) proteins, for pathogen race-specific disease resistance. However, only a few immediate downstream targets of R proteins have been characterized, and the signalling pathways for R-protein-induced immunity are largely unknown. In rice (Oryza sativa), NLR proteins serve as important immune receptors in the response to rice blast disease caused by the fungus Magnaporthe oryzae. We used site-directed mutagenesis to create an autoactive form of the NLR protein PID3 that confers blast resistance and used transgenic rice to test the resulting immunity and gene expression changes. We identified OsRac1, a known GTPase, as a signalling molecule in PID3-mediated blast resistance, implicating OsRac1 as a possible common factor downstream of rice NLR proteins. We also identified RAI1, a transcriptional activator, as a PID3 interactor required for PID3-mediated blast resistance and showed that RAI1 expression is induced by PID3 via a process mediated by OsRac1. This study describes a new signalling pathway for NLR protein-mediated blast resistance and shows that OsRac1 and RAI1 act together to play a critical role in this process.
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Resistencia a la Enfermedad , Nucleótidos/metabolismo , Oryza/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/metabolismo , Proteínas/metabolismo , Transducción de Señal , Sitios de Unión , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas , Proteínas Repetidas Ricas en Leucina , Oryza/genética , Oryza/inmunología , Oryza/metabolismo , Enfermedades de las Plantas/genética , Inmunidad de la Planta , Proteínas de Plantas/genética , Unión Proteica , Proteínas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
OBJECTIVES: While others have reported that milk from coastal Chinese women contains high levels of lutein and zeaxanthin, no research has determined the corresponding infant plasma response. Whether infant plasma levels increase commensurately provides important guidance for supplementation of these increasingly intriguing carotenoids in breast-feeding mothers and formula-fed infants. METHODS: Fifty-six mother-infant pairs with a maternal diet rich in eggs, green leafy vegetables, and fruit were enrolled between 6 and 16 weeks of lactation. Milk samples and blood samples from both the mother and infant were collected at entry. Maternal 3-day dietary records and a second milk sample were collected 1 to 3 weeks later. RESULTS: Mean milk lutein concentrations in samples 1 and 2 were 6.5 and 7.7 µg/dL (range 1-22.5 µg/dL), and for zeaxanthin, 1.6 and 1.7 µg/dL (range 1-5.9 µg/dL). Lutein concentrations in infant plasma (18.2 µg/dL) were similar to those in maternal plasma (21.6 µg/dL); zeaxanthin was lower than lutein in both maternal (3.1 µg/dL) and infant (2.9 µg/dL) plasma. Infant and maternal mean plasma lutein and zeaxanthin concentrations were higher than those in both milk samples 1 and 2 (lutein, 6.9 and 8.2 µg/dL; zeaxanthin, 1.9 and 2.0 µg/dL). Infant plasma lutein and zeaxanthin concentrations positively correlated with those in milk sample 1 (lutein, r2 = 0.15, p = 0.004; zeaxanthin, r2 = 0.21, p < 0.001). CONCLUSIONS: Together, these results reveal that high milk concentrations of lutein and zeaxanthin driven by healthy maternal intakes of xanthophyll rich foods are associated with high infant plasma concentrations. These findings will be useful for determining appropriate lutein fortification strategies. Clinical Study.gov registration number: NCT01669655.