Genetic algorithms (GA) based on the principle of mimicing Darwinian evolution and survival of the fittest in a natural environment was used to optimize the medium for astaxanthin production by the mutant strain W6-8 ...Genetic algorithms (GA) based on the principle of mimicing Darwinian evolution and survival of the fittest in a natural environment was used to optimize the medium for astaxanthin production by the mutant strain W6-8 of Xantho-phyllomyces dendrorhous. The 50 concentration levels of 6 medium components were optimized within 50 experiments (full experimental plan: 50^6 experiments). The results showed that GA could be applied in the medium optimization and better results were obtained. By employing optimized medium components (glucose 39.8 g l^-1, yeast extract 4.08 g l^-1,(NH4)2SO4 7.36 g l^-1, MgSO4 2 g l^-1, K2HPO4 2.04 g l^-1 and KH2PO4 3.48 g l^-1), the highest astaxanthin production was 9.855 mg l^-1, approximately 31% higher than that under the initial conditions, and was approximately 15.46% higher than that by orthogonal array but only slightly higher than that by response surface methodology. In the sequent scale-up experiments, the astaxanthin yield was obtained approximately 14.753 mg l^-1, employing the optimal medium. The results indicated that GA, as an euiicient method for medium optimization, was superior to other optimal means such as orthogonal array.展开更多
Fermentation of Phaffia rhodozyma is a major method for producing astaxanthin, an important pigment with industrial and pharmaceutical application. To improve astaxanthin productivity, single factor and mixture design...Fermentation of Phaffia rhodozyma is a major method for producing astaxanthin, an important pigment with industrial and pharmaceutical application. To improve astaxanthin productivity, single factor and mixture design experiments were used to investigate the effects of nitrogen source on Phaffia rhodozyma cultivation and astaxanthin production. Results of single factor experiments showed nitrogen source could significantly affect P. rhodozyma cultivation with respect to carbon source utilization, yeast growth and astaxanthin accumulation. Further studies of mixture design experiments using (NH4)2SO4, KNO3 and beef extract as nitrogen sources indicated that the proportion of three nitrogen sources was very important to astaxanthin production. Validation experiments showed that the optimal nitrogen source was composed of 0.28 g/L (NH4)2SO4, 0.49 g/L KNO3 and 1.19 g/L beef extract. The kinetic characteristics of batch cultivation were investigated in a 5-L pH-stat fermentor. The maximum amount of biomass and highest astaxanthin yield in terms of volume and in terms of biomass were 7.71 mg/L and 1.00 mg/g, respectively.展开更多
method of extracting astaxanthin from Phaffia rhodozyma with various solvents after acid washing was investigated. The extraction efficiency was distinctly increased after acid washing of P. rhodozyma cells. When the ...method of extracting astaxanthin from Phaffia rhodozyma with various solvents after acid washing was investigated. The extraction efficiency was distinctly increased after acid washing of P. rhodozyma cells. When the concentration of HCl was 0.4 mol.L^-1, the highest extraction efficiency of astaxanthin was achieved which was about three times higher than the control. Acetone or benzene as single polar or non-polar solvent was the most ef- fective solvent in our research. With a combination of isopropanol and n-hexane (volume ratio of 2 : 1), the maxi- mal extraction efficiency was achieved, approximately 60% higher than that obtained with a single solvent. The liquid-solid ratio and the extracting time were also optimized. Under the optimum extraction conditions, the extraction yield of astaxanthin exceeded 98%.展开更多
This study investigated the embryonic development of Maldives clownfish Amphiprion nigripes under natural conditions (28 - 30℃) at a lagoon of Agatti Island, Lakshadweep, India. The newly deposited fish egg was capsu...This study investigated the embryonic development of Maldives clownfish Amphiprion nigripes under natural conditions (28 - 30℃) at a lagoon of Agatti Island, Lakshadweep, India. The newly deposited fish egg was capsule-shaped and orange-red, with a (0.73 ± 0.04) mm3 yolk containing 5 - 10 fat globules. The embryonic development of fertilized eggs was divided into 26 stages and the time elapsing for each stage was recorded. Results showed that the cleavage was rapid, with the first division observed 1 h 20 min after fertilization. Blastulation occurred 4 h later, followed by gastrulation 12 h after fertilization, with a yolk volume of (0.61 ± 0.06) mm3. The organogenesis process started 22 h after fertilization when the blastopores closed and notochord formation began. The embryonic stage was recorded 24 h later, with the appearance of forebrain, midbrain, hindbrain, melanophores on yolk-sac and 22 somites, and a decreased yolk volume of (0.54 ± 0.08) mm3. Other organs developed well 31 h after fertilization, whereas the heart started beating and blood circulation began 78 h later. Red pigmentation (erytrophores) appeared 96 h after fertilization, with a small yolk volume of (0.22 ± 0.02) mm3. Mouth developed well and eyes were noticeable 120 h later, with head, pectoral fin and tail frequently moving 144 h after fertilization. The embryo reached the pre-hatching stage 168 h later and started to hatch after 170 - 180 h incubation. This study first detailed the embryonic development and yolk absorption of A. nigripes under natural conditions.展开更多
The dynamics of regional convergence include spatial and temporal dimensions. Spatial Markov chain can be used to explore how regions evolve by considering both individual regions and their geographic neighbors. Based...The dynamics of regional convergence include spatial and temporal dimensions. Spatial Markov chain can be used to explore how regions evolve by considering both individual regions and their geographic neighbors. Based on per capita GDP data set of 77 counties from 1978 to 2000, this paper attempts to investigate the spatial-temporal dynamics of regional convergence in Jiangsu. First, traditional Markov matrix for five per capita GDP classes is constructed for later comparison. Moreover, each region’s spatial lag is derived by averaging all its neighbors’ per capita GDP data. Conditioning on per capita GDP class of its spatial lag at the beginning of each year, spatial Markov transition probabilities of each region are calculated accordingly. Quantitatively, for a poor region, the probability of moving upward is 3.3% if it is surrounded by its poor neighbors, and even increases to 18.4% if it is surrounded by its rich neighbors, but it goes down to 6.2% on average if ignoring regional context. For a rich region, the probability of moving down ward is 1.2% if it is surrounded by its rich neighbors, but increases to 3.0% if it is surrounded by its poor neighbors, and averages 1.5% irrespective of regional context. Spatial analysis of regional GDP class transitions indicates those 10 upward moves of both regions and their neighbors are unexceptionally located in the southern Jiangsu, while downward moves of regions or their neighbors are almost in the northern Jiangsu. These empirical results provide a spatial explanation to the "convergence clubs" detected by traditional Markov chain.展开更多
The pathogenesis of autoimmune hepatitis (AIH) is complex. However,it is believed that a susceptible individual,owing to his genetic background,sex and age,can develop the disease following exposure to an environmenta...The pathogenesis of autoimmune hepatitis (AIH) is complex. However,it is believed that a susceptible individual,owing to his genetic background,sex and age,can develop the disease following exposure to an environmental trigger. Autoimmune hepatitis does not follow a Mendelian pattern of inheritance; hence no single causative genetic locus has been identified. However,several genes,inside and outside the HLA locus,have been linked to an increased susceptibility to AIH. Epidemiological evidence also suggests that the sex and age of the patient plays a role in AIH pathogenesis as the disease onset occurs mainly in the two first decades of life and a higher disease incidence is observed in females. No environmental trigger has been identified,but several have been proposed,mainly viruses and xenobiotics. This article aims at reviewing the current knowledge on susceptibility factors leading to AIH and putative triggers,emphasizing fundamental mechanisms responsible for the break of liver immunological tolerance.展开更多
Embryogenic calli were induced from the seeds of creeping bentgrass ( Agrostis palustris Huds.) cv. Regent and colonial bentgrass ( Agrostis Tenuis Sibth. Fl. Oxen.) cv. Tiger. The embryogenic calli were precult...Embryogenic calli were induced from the seeds of creeping bentgrass ( Agrostis palustris Huds.) cv. Regent and colonial bentgrass ( Agrostis Tenuis Sibth. Fl. Oxen.) cv. Tiger. The embryogenic calli were precultured on fresh medium for 4-7 days and then co cultivated with Agrobacterium tumefaciens , LBA4404, which contains plasmid vector pSBGM harboring bar coding region, synthetic green fluorescent protein (sGFP) coding region and matrix attachment region (MAR). After 3 days of co cultivation, the calli were washed thoroughly and transferred to MS medium containing 2 mg/L of 2, 4 D, 12-15 mg/L phosphinothricin (PPT) and 250 mg/L of cefotaxime. After 2-3 months of selection, the actively growing calli of 'Regent' and 'Tiger' were transferred to MS medium with 12-15 mg/L PPT and 250 mg/L cefotaxime for regeneration. The putative transformants were maintained on MS medium with 3 mg/L PPT for long period but control died within 1 month. After establishing in greenhouse, the transformants also showed strong resistance to 0.4% of herbicide Basta but control plants died within 2 weeks. Under confocal microscope, both young leaves and roots showed significant GFP expression. PCR analysis revealed the presence of a DNA fragment of GFP gene at the expected size (380 bp) in the transformants and its absence in a randomly selected control plant.展开更多
The fundamental problem of an elastic-plastic body subjected to incremental loading is reviewed using a compact internal variable approach based on work carried out at the University of Cape Town in which a quadratic ...The fundamental problem of an elastic-plastic body subjected to incremental loading is reviewed using a compact internal variable approach based on work carried out at the University of Cape Town in which a quadratic functional was developed for the free energy using Taylor series. Now the departure from that approach is the focus on developing the Liapunov function for the nonlinear differential equations of motion. Static and dynamic equations of motion are derived and shown to meet the requirements of the Liapunov function. As a consequence, time integration parameters that are used in the discrete formulations are easily obtained based on the same requirements. The resulting generalized Newton-Raphson scheme is stable in the sense of Liapunov's direct method.展开更多
Stars are born in dense cores of molecular clouds. The core mass function (CMF), which is the mass distribution of dense cores, is important for understanding the stellar initial mass function (IMF). We obtained ...Stars are born in dense cores of molecular clouds. The core mass function (CMF), which is the mass distribution of dense cores, is important for understanding the stellar initial mass function (IMF). We obtained 350μm dust continuum data using the SHARC-II camera at the Caltech Submillimeter Observatory (CSO) telescope. A 350μm map covering 0.25 deg2 of the Ophiuchus molecular cloud was created by mosaicing 56 separate scans. The CSO telescope had an angular resolution of 9", corresponding to 1.2 ×103 AU at the distance of the Ophiuchus molecular cloud (131 pc). The data was reduced using the Comprehensive Reduction Utility for SHARC-II (CRUSH). The flux density map was analyzed using the GaussClumps algorithm, within which 75 cores has been identified. We used the Spitzer c2d catalogs to separate the cores into 63 starless cores and 12 protostellar cores. By locating Jeans instabilities, 55 prestellar cores (a subcategory of starless cores) were also identified. The excitation temperatures, which were derived from FCRAO 12CO data, help to improve the accuracy of the masses of the cores. We adopted a Monte Carlo approach to analyze the CMF with two types of functional forms; power law and log-normal. The whole and prestellar CMF are both well fitted by a log-normal distribution, with p = -1. 18 ±0.10, σ = 0.58 ± 0.05 and μ= 1.40 + 0.10, σ= 0.50 + 0.05 respectively. This finding suggests that turbulence influences the evolution of the Ophiuchus molecular cloud.展开更多
Background:Infliximab(IFX)is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn’s disease(CD);however,9%–40%of patients do not respond to primary IFX treatment.This s...Background:Infliximab(IFX)is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn’s disease(CD);however,9%–40%of patients do not respond to primary IFX treatment.This study aimed to construct and validate nomograms to predict IFX response in CD patients.Methods:A total of 343 patients diagnosed with CD who had received IFX induction from four tertiary centers between September 2008 and September 2019 were enrolled in this study and randomly classified into a training cohort(n=240)and a validation cohort(n=103).The primary outcome was primary non-response(PNR)and the secondary outcome was mucosal healing(MH).Nomograms were constructed from the training cohort using multivariate logistic regression.Performance of nomograms was evaluated by area under the receiver-operating characteristic curve(AUC)and calibration curve.The clinical usefulness of nomograms was evaluated by decision-curve analysis.Results:The nomogram for PNR was developed based on four independent predictors:age,C-reactive protein(CRP)at week 2,body mass index,and non-stricturing,non-penetrating behavior(B1).AUC was 0.77 in the training cohort and 0.76 in the validation cohort.The nomogram for MH included four independent factors:baseline Crohn’s Disease Endoscopic Index of Severity,CRP at week 2,B1,and disease duration.AUC was 0.79 and 0.72 in the training and validation cohorts,respectively.The two nomograms showed good calibration in both cohorts and were superior to single factors and an existing matrix model.The decision curve indicated the clinical usefulness of the PNR nomogram.Conclusions:We established and validated nomograms for the prediction of PNR to IFX and MH in CD patients.This graphical tool is easy to use and will assist physicians in therapeutic decision-making.展开更多
We study spontaneous excitation of both a static detector (modelled by a two-level atom) immersed in a thermal bath and a uniformly accelerated one in the Minkowski vacuum interacting with a real massive scalar fiel...We study spontaneous excitation of both a static detector (modelled by a two-level atom) immersed in a thermal bath and a uniformly accelerated one in the Minkowski vacuum interacting with a real massive scalar field. Our results show that the mass of the scalar field manifests itself in the spontaneous excitation rate of the static detector in a thermal bath (and in vacuum) in the form of a selection rule for transitions among states of the detector. However, this selection rule disappears for the accelerated ones, demonstrating that an accelerated detector does not necessarily behave the same as an inertial one in a thermal bath. We lind the imprint left by the mass is the appearance of a grey-body factor in the spontaneous excitation and de-excitation rates, which maintains the detailed balance condition between them and thus ensures a thermal equilibrium at the Unruh temperature the same as that of the massless case. We also analyze quantitatively the effect of the mass on the rate of change of the detector's energy and find that when the mass is very small, it only induces a small negative correction. However, when it is very large, it then exponentially damps the rate, thus essentially forbidding any transitions among states of the detector.展开更多
文摘Genetic algorithms (GA) based on the principle of mimicing Darwinian evolution and survival of the fittest in a natural environment was used to optimize the medium for astaxanthin production by the mutant strain W6-8 of Xantho-phyllomyces dendrorhous. The 50 concentration levels of 6 medium components were optimized within 50 experiments (full experimental plan: 50^6 experiments). The results showed that GA could be applied in the medium optimization and better results were obtained. By employing optimized medium components (glucose 39.8 g l^-1, yeast extract 4.08 g l^-1,(NH4)2SO4 7.36 g l^-1, MgSO4 2 g l^-1, K2HPO4 2.04 g l^-1 and KH2PO4 3.48 g l^-1), the highest astaxanthin production was 9.855 mg l^-1, approximately 31% higher than that under the initial conditions, and was approximately 15.46% higher than that by orthogonal array but only slightly higher than that by response surface methodology. In the sequent scale-up experiments, the astaxanthin yield was obtained approximately 14.753 mg l^-1, employing the optimal medium. The results indicated that GA, as an euiicient method for medium optimization, was superior to other optimal means such as orthogonal array.
基金Project supported by the National Natural Science Foundation of China (No.30571450)the Foundation for Young Professors of Jimei University of Xiamen,China
文摘Fermentation of Phaffia rhodozyma is a major method for producing astaxanthin, an important pigment with industrial and pharmaceutical application. To improve astaxanthin productivity, single factor and mixture design experiments were used to investigate the effects of nitrogen source on Phaffia rhodozyma cultivation and astaxanthin production. Results of single factor experiments showed nitrogen source could significantly affect P. rhodozyma cultivation with respect to carbon source utilization, yeast growth and astaxanthin accumulation. Further studies of mixture design experiments using (NH4)2SO4, KNO3 and beef extract as nitrogen sources indicated that the proportion of three nitrogen sources was very important to astaxanthin production. Validation experiments showed that the optimal nitrogen source was composed of 0.28 g/L (NH4)2SO4, 0.49 g/L KNO3 and 1.19 g/L beef extract. The kinetic characteristics of batch cultivation were investigated in a 5-L pH-stat fermentor. The maximum amount of biomass and highest astaxanthin yield in terms of volume and in terms of biomass were 7.71 mg/L and 1.00 mg/g, respectively.
基金Supported by the Fundamental Research Funds for the Central Universities (FRF-AS-10-001B) and the National Natural Science Foundation of China (11071013).
文摘method of extracting astaxanthin from Phaffia rhodozyma with various solvents after acid washing was investigated. The extraction efficiency was distinctly increased after acid washing of P. rhodozyma cells. When the concentration of HCl was 0.4 mol.L^-1, the highest extraction efficiency of astaxanthin was achieved which was about three times higher than the control. Acetone or benzene as single polar or non-polar solvent was the most ef- fective solvent in our research. With a combination of isopropanol and n-hexane (volume ratio of 2 : 1), the maxi- mal extraction efficiency was achieved, approximately 60% higher than that obtained with a single solvent. The liquid-solid ratio and the extracting time were also optimized. Under the optimum extraction conditions, the extraction yield of astaxanthin exceeded 98%.
基金the funding from the Ministry of Environment and Forests (India)
文摘This study investigated the embryonic development of Maldives clownfish Amphiprion nigripes under natural conditions (28 - 30℃) at a lagoon of Agatti Island, Lakshadweep, India. The newly deposited fish egg was capsule-shaped and orange-red, with a (0.73 ± 0.04) mm3 yolk containing 5 - 10 fat globules. The embryonic development of fertilized eggs was divided into 26 stages and the time elapsing for each stage was recorded. Results showed that the cleavage was rapid, with the first division observed 1 h 20 min after fertilization. Blastulation occurred 4 h later, followed by gastrulation 12 h after fertilization, with a yolk volume of (0.61 ± 0.06) mm3. The organogenesis process started 22 h after fertilization when the blastopores closed and notochord formation began. The embryonic stage was recorded 24 h later, with the appearance of forebrain, midbrain, hindbrain, melanophores on yolk-sac and 22 somites, and a decreased yolk volume of (0.54 ± 0.08) mm3. Other organs developed well 31 h after fertilization, whereas the heart started beating and blood circulation began 78 h later. Red pigmentation (erytrophores) appeared 96 h after fertilization, with a small yolk volume of (0.22 ± 0.02) mm3. Mouth developed well and eyes were noticeable 120 h later, with head, pectoral fin and tail frequently moving 144 h after fertilization. The embryo reached the pre-hatching stage 168 h later and started to hatch after 170 - 180 h incubation. This study first detailed the embryonic development and yolk absorption of A. nigripes under natural conditions.
基金Under the auspices ofthe National Natural Science Foundation of China (No .40301038)
文摘The dynamics of regional convergence include spatial and temporal dimensions. Spatial Markov chain can be used to explore how regions evolve by considering both individual regions and their geographic neighbors. Based on per capita GDP data set of 77 counties from 1978 to 2000, this paper attempts to investigate the spatial-temporal dynamics of regional convergence in Jiangsu. First, traditional Markov matrix for five per capita GDP classes is constructed for later comparison. Moreover, each region’s spatial lag is derived by averaging all its neighbors’ per capita GDP data. Conditioning on per capita GDP class of its spatial lag at the beginning of each year, spatial Markov transition probabilities of each region are calculated accordingly. Quantitatively, for a poor region, the probability of moving upward is 3.3% if it is surrounded by its poor neighbors, and even increases to 18.4% if it is surrounded by its rich neighbors, but it goes down to 6.2% on average if ignoring regional context. For a rich region, the probability of moving down ward is 1.2% if it is surrounded by its rich neighbors, but increases to 3.0% if it is surrounded by its poor neighbors, and averages 1.5% irrespective of regional context. Spatial analysis of regional GDP class transitions indicates those 10 upward moves of both regions and their neighbors are unexceptionally located in the southern Jiangsu, while downward moves of regions or their neighbors are almost in the northern Jiangsu. These empirical results provide a spatial explanation to the "convergence clubs" detected by traditional Markov chain.
文摘The pathogenesis of autoimmune hepatitis (AIH) is complex. However,it is believed that a susceptible individual,owing to his genetic background,sex and age,can develop the disease following exposure to an environmental trigger. Autoimmune hepatitis does not follow a Mendelian pattern of inheritance; hence no single causative genetic locus has been identified. However,several genes,inside and outside the HLA locus,have been linked to an increased susceptibility to AIH. Epidemiological evidence also suggests that the sex and age of the patient plays a role in AIH pathogenesis as the disease onset occurs mainly in the two first decades of life and a higher disease incidence is observed in females. No environmental trigger has been identified,but several have been proposed,mainly viruses and xenobiotics. This article aims at reviewing the current knowledge on susceptibility factors leading to AIH and putative triggers,emphasizing fundamental mechanisms responsible for the break of liver immunological tolerance.
文摘Embryogenic calli were induced from the seeds of creeping bentgrass ( Agrostis palustris Huds.) cv. Regent and colonial bentgrass ( Agrostis Tenuis Sibth. Fl. Oxen.) cv. Tiger. The embryogenic calli were precultured on fresh medium for 4-7 days and then co cultivated with Agrobacterium tumefaciens , LBA4404, which contains plasmid vector pSBGM harboring bar coding region, synthetic green fluorescent protein (sGFP) coding region and matrix attachment region (MAR). After 3 days of co cultivation, the calli were washed thoroughly and transferred to MS medium containing 2 mg/L of 2, 4 D, 12-15 mg/L phosphinothricin (PPT) and 250 mg/L of cefotaxime. After 2-3 months of selection, the actively growing calli of 'Regent' and 'Tiger' were transferred to MS medium with 12-15 mg/L PPT and 250 mg/L cefotaxime for regeneration. The putative transformants were maintained on MS medium with 3 mg/L PPT for long period but control died within 1 month. After establishing in greenhouse, the transformants also showed strong resistance to 0.4% of herbicide Basta but control plants died within 2 weeks. Under confocal microscope, both young leaves and roots showed significant GFP expression. PCR analysis revealed the presence of a DNA fragment of GFP gene at the expected size (380 bp) in the transformants and its absence in a randomly selected control plant.
文摘The fundamental problem of an elastic-plastic body subjected to incremental loading is reviewed using a compact internal variable approach based on work carried out at the University of Cape Town in which a quadratic functional was developed for the free energy using Taylor series. Now the departure from that approach is the focus on developing the Liapunov function for the nonlinear differential equations of motion. Static and dynamic equations of motion are derived and shown to meet the requirements of the Liapunov function. As a consequence, time integration parameters that are used in the discrete formulations are easily obtained based on the same requirements. The resulting generalized Newton-Raphson scheme is stable in the sense of Liapunov's direct method.
基金by the California Institute of Technology under cooperative agreement with the National Science Foundation (Grant No. AST0838261)supported by National Basic Research Program of China (Grant No. 2012CB821800)+2 种基金National Aeronautics and Space Administration Undergraduate Student Research Program of USANational Natural Science Foundation of China (Grant Nos. 11373038 and 11163002)Graduate Innovative Fund of Gui Zhou University (Grant Nos. 2013024)
文摘Stars are born in dense cores of molecular clouds. The core mass function (CMF), which is the mass distribution of dense cores, is important for understanding the stellar initial mass function (IMF). We obtained 350μm dust continuum data using the SHARC-II camera at the Caltech Submillimeter Observatory (CSO) telescope. A 350μm map covering 0.25 deg2 of the Ophiuchus molecular cloud was created by mosaicing 56 separate scans. The CSO telescope had an angular resolution of 9", corresponding to 1.2 ×103 AU at the distance of the Ophiuchus molecular cloud (131 pc). The data was reduced using the Comprehensive Reduction Utility for SHARC-II (CRUSH). The flux density map was analyzed using the GaussClumps algorithm, within which 75 cores has been identified. We used the Spitzer c2d catalogs to separate the cores into 63 starless cores and 12 protostellar cores. By locating Jeans instabilities, 55 prestellar cores (a subcategory of starless cores) were also identified. The excitation temperatures, which were derived from FCRAO 12CO data, help to improve the accuracy of the masses of the cores. We adopted a Monte Carlo approach to analyze the CMF with two types of functional forms; power law and log-normal. The whole and prestellar CMF are both well fitted by a log-normal distribution, with p = -1. 18 ±0.10, σ = 0.58 ± 0.05 and μ= 1.40 + 0.10, σ= 0.50 + 0.05 respectively. This finding suggests that turbulence influences the evolution of the Ophiuchus molecular cloud.
基金supported by grants from the National Natural Science Foundation of China(#81870374,#81670498)Guangdong Science and Technology(#2017A030306021)+1 种基金Science and Technology Innovation Young Talents of Guangdong Special Support Plan(#2016TQ03R296)the Fundamental Research Funds for the Central Universities(#19ykzd11).
文摘Background:Infliximab(IFX)is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn’s disease(CD);however,9%–40%of patients do not respond to primary IFX treatment.This study aimed to construct and validate nomograms to predict IFX response in CD patients.Methods:A total of 343 patients diagnosed with CD who had received IFX induction from four tertiary centers between September 2008 and September 2019 were enrolled in this study and randomly classified into a training cohort(n=240)and a validation cohort(n=103).The primary outcome was primary non-response(PNR)and the secondary outcome was mucosal healing(MH).Nomograms were constructed from the training cohort using multivariate logistic regression.Performance of nomograms was evaluated by area under the receiver-operating characteristic curve(AUC)and calibration curve.The clinical usefulness of nomograms was evaluated by decision-curve analysis.Results:The nomogram for PNR was developed based on four independent predictors:age,C-reactive protein(CRP)at week 2,body mass index,and non-stricturing,non-penetrating behavior(B1).AUC was 0.77 in the training cohort and 0.76 in the validation cohort.The nomogram for MH included four independent factors:baseline Crohn’s Disease Endoscopic Index of Severity,CRP at week 2,B1,and disease duration.AUC was 0.79 and 0.72 in the training and validation cohorts,respectively.The two nomograms showed good calibration in both cohorts and were superior to single factors and an existing matrix model.The decision curve indicated the clinical usefulness of the PNR nomogram.Conclusions:We established and validated nomograms for the prediction of PNR to IFX and MH in CD patients.This graphical tool is easy to use and will assist physicians in therapeutic decision-making.
基金Supported in part by the National Natural Science Foundation of China under Grant Nos. 11075083,10935013 and 11005013the Zhejiang Provincial Natural Science Foundation of China under Grant No. Z6100077+3 种基金the National Basic Research Program of China under Grant No. 2010CB832803the PCSIRT under Grant No. IRT0964the Research Foundation of Education Bureau of Hunan Province under Grant No. 10C0377Provincial Natural Science Foundation of China under Grant No. 11JJ700
文摘We study spontaneous excitation of both a static detector (modelled by a two-level atom) immersed in a thermal bath and a uniformly accelerated one in the Minkowski vacuum interacting with a real massive scalar field. Our results show that the mass of the scalar field manifests itself in the spontaneous excitation rate of the static detector in a thermal bath (and in vacuum) in the form of a selection rule for transitions among states of the detector. However, this selection rule disappears for the accelerated ones, demonstrating that an accelerated detector does not necessarily behave the same as an inertial one in a thermal bath. We lind the imprint left by the mass is the appearance of a grey-body factor in the spontaneous excitation and de-excitation rates, which maintains the detailed balance condition between them and thus ensures a thermal equilibrium at the Unruh temperature the same as that of the massless case. We also analyze quantitatively the effect of the mass on the rate of change of the detector's energy and find that when the mass is very small, it only induces a small negative correction. However, when it is very large, it then exponentially damps the rate, thus essentially forbidding any transitions among states of the detector.