AIM To assess the accuracy of serum procalcitionin(PCT)as a diagnostic marker in verifying upper and lower gastrointestinal perforation(GIP).METHODS This retrospective study included 46 patients from the surgical inte...AIM To assess the accuracy of serum procalcitionin(PCT)as a diagnostic marker in verifying upper and lower gastrointestinal perforation(GIP).METHODS This retrospective study included 46 patients from the surgical intensive care unit(ICU)of the Second Affiliated Hospital of Harbin Medical University who were confirmed to have GIP between June 2013 and December 2016.Demographic and clinical patient data were recorded on admission to ICU.Patients were divided into upper(n=19)and lower(n=27)GIP groups according to the perforation site(above or below Treitz ligament).PCT and WBC count was obtained before laparotomy and then compared between groups.Meanwhile,the diagnostic accuracy of PCT was analyzed.RESULTS Patients with lower GIP exhibited significantly higher APACHE II score,SOFA score and serum PCT level than patients with upper GIP(P=0.017,0.004,and0.001,respectively).There was a significant positive correlation between serum PCT level and APACHE II score or SOFA score(r=0.715 and r=0.611,respectively),while there was a significant negative correlation between serum PCT level and prognosis(r=-0.414).WBC count was not significantly different between the two groups,and WBC count showed no significant correlation with serum PCT level,APACHE II score,SOFA score or prognosis.The area under the receiver operating characteristic curve of PCT level to distinguish upper or lower GIP was 0.778.Patients with a serum PCT level above 17.94 ng/d L had a high likelihood of lower GIP,with a sensitivity of 100%and a specificity of 42.1%.CONCLUSION Serum PCT level is a reliable and accurate diagnostic marker in identifying upper or lower GIP before laparotomy.展开更多
In order to research the characteristic and mechanism of fracture of rock-like materials,the morphology of rock fracture surface under the breakages of uniaxial compression and triaxial compression was observed and me...In order to research the characteristic and mechanism of fracture of rock-like materials,the morphology of rock fracture surface under the breakages of uniaxial compression and triaxial compression was observed and measured by means of a new-type 3D laser scanning system.Based on geographic information system(GIS)technique,the fracture surfaces were 3D visualized and reestablished.According to GIS 3D statistics,the geometrical characteristics of fracture surfaces under different breakage conditions were analyzed,and then based on fractal theory,the change laws of fractal dimension of fracture surfaces were discussed under the conditions of different cell pressures and initial water contents of rock.Furthermore,the relationships between characteristics of fracture surface and mechanical properties of rock were discussed.The results indicate that cell pressure,initial water content,and mechanical parameters of rock are the important factors to influence on the geometrical characteristics of fracture surface.The research provides a new experimental method for quantitative study on the fracture characteristics of various materials under different breakage conditions.展开更多
Objective Small cell carcinoma(SCC) is mostly found in the lungs. It is extremely rare in the gastric remnant. Here, we report a case and review the literature in order to improve the diagnosis and treatment of SCC of...Objective Small cell carcinoma(SCC) is mostly found in the lungs. It is extremely rare in the gastric remnant. Here, we report a case and review the literature in order to improve the diagnosis and treatment of SCC of the gastric remnant.Methods We report a case of SCC of the gastric remnant in a 71-year-old male Chinese patient who presented with epigastric pain, acid regurgitation, and belching and who underwent Billroth II gastrectomy more than 38 years ago.Results Physical examination showed no obvious abnormalities. Laboratory data were within normal limits, except for anemia. Pathology of the mass showed a protruded tumor measuring 5.0 × 5.0 × 2.5 cm at the anastomotic edge of the gastric remnant that infiltrated through the full wall of the stomach; this was confirmed by immunohistochemical staining for cytokeratin [CK(-)], leukocyte common antigen(LCA)(+), synaptophysin(+), CD56(+), and Ki-67(+ > 50%).Conclusion SCC of the gastric remnant is extremely rare, although the pathology, symptoms, diagnosis, treatment, and prognosis of SCC are similar to those of gastric SCC. Although the standard treatment of SCC of the gastric remnant remains unclear, effective surgical resection and subsequent multiagent chemotherapy should be performed for long-term survival. Our case shows the efficacy of tegafurgimeracil-oteracil-potassium capsule chemotherapy. Examination of a large series is required to determine the optimal treatment strategy for SCC of the gastric remnant.展开更多
Numerical analysis of the optimal supporting time and long-term stability index of the surrounding rocks in the underground plant of Xiangjiaba hydro-power station was carried out based on the rheological theory. Firs...Numerical analysis of the optimal supporting time and long-term stability index of the surrounding rocks in the underground plant of Xiangjiaba hydro-power station was carried out based on the rheological theory. Firstly,the mechanical parameters of each rock group were identified from the experimental data; secondly,the rheological calculation and analysis for the cavern in stepped excavation without supporting were made; finally,the optimal time for supporting at the characteristic point in a typical section was obtained while the creep rate and displacement after each excavation step has satisfied the criterion of the optimal supporting time. Excavation was repeated when the optimal time for supporting was identified,and the long-term stability creep time and the maximum creep deformation of the characteristic point were determined in accordance with the criterion of long-term stability index. It is shown that the optimal supporting time of the characteristic point in the underground plant of Xiangjiaba hydro-power station is 5-8 d,the long-term stability time of the typical section is 126 d,and the corresponding largest creep deformation is 24.30 mm. While the cavern is supported,the cavern deformation is significantly reduced and the stress states of the surrounding rock masses are remarkably improved.展开更多
Vertical nanowire arrays are increasingly investigated for their applications in steering cell behavior. The geometry of the array is an important parameter, which influences the morphology and adhesion of cells. Here...Vertical nanowire arrays are increasingly investigated for their applications in steering cell behavior. The geometry of the array is an important parameter, which influences the morphology and adhesion of cells. Here, we investigate the effects of array geometry on the morphology of MCF7 cancer cells and MCF10A normal-like epithelial cells. Different gallium phosphide nanowire array-geometries were produced by varying the nanowire density and diameter. Our results show that the cell size is smaller on nanowires compared to flat gallium phosphide. The cell area decreases with increasing the nanowire density on the substrate. We observed an effect of the nanowire diameter on MCF10A cells, with a decreased cell area on 40 nm diameter nanowires, compared to 60 and 80 nm diameter nanowires in high-density arrays. The focal adhesion morphology depends on the extent to which cells are contacting the substrate. For low nanowire densities and diameters, ceils are lying on the substrate and we observed large focal adhesions at the cell edges. In contrast, for high nanowire densities and diameters, cells are lying on top of the nanowires and we observed point-like focal adhesions distributed over the whole cell. Our results constitute a step towards the ability to fine-tune cell behavior on nanowire arrays.展开更多
The fire extinguishment time is a major factor to evaluate the efficiency of fire extinguishment with water mist. In this paper the fire extinguishment time with water mist in an enclosed room is calculated. Before ad...The fire extinguishment time is a major factor to evaluate the efficiency of fire extinguishment with water mist. In this paper the fire extinguishment time with water mist in an enclosed room is calculated. Before adding water mist, the chemical kinetics plays the role in combustion, where a dimensionless math model is established by us-ing the Semenov theory. After adding water mist, the diffusion plays the role instead. Then another math model containing water mist and dominated by oxygen concentration is established. The fire temperature is integrated from Tm to extinguishment temperature TB and the extinguishment time can be obtained. The calculated values are compared with the experimental data under different conditions. The results show that this model can predict the fire extinguishment time accurately. Besides, this model also can be used to determine the critical water mist flux and evaluate which fire extinguishment mechanisms dominate the extinguishment.展开更多
Proteins are essential players of life activities, lntraceUular protein levels directly affect cellular functions and cell fate. Upon cell division, the proteins in the mother cell are inherited by the daughters. Howe...Proteins are essential players of life activities, lntraceUular protein levels directly affect cellular functions and cell fate. Upon cell division, the proteins in the mother cell are inherited by the daughters. However, what factors and by how much they affect this epigenetic inheritance of protein abundance remains unclear. Using both computational and experimental approaches, we systematically investigated this problem. We derived an analytical expression for the dependence of protein inheritance on various factors and showed that it agreed with numerical simulations of protein production and experimental results. Our work provides a framework for quantitative studies of protein inheritance and for the potential application of protein memory manipulation.展开更多
The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here,...The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 (PHF20) functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Casg-based targeted knockout (KO) for high-throughput screening of gene function in NB cell differentiation. The expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients. Deletion of PHF20 inhibited NB cell proliferation, invasive migration, and stem ceU-Uke traits. Mechanistically, PHF20 interacts with poly(ADP-ribose) polymerase 1 (PARP1) and directly binds to promoter regions of octamer-binding transcription factor 4 (OCT4) and sex determining region Y-box 2 (SOX2) to modulate a histone mark associated with active transcription, trimethylation of lysine 4 on histone H3 protein subunit (H3K4me3). Overexpression of OCT4 and SOX2 restored growth and progression of PHF20 KO tumor cells. Consistently, OCT4 and SOX2 protein levels in clinical NB specimens were positively correlated with PHF20 expression. Our results establish PHF20 as a key driver of NB stem cell-like properties and aggressive behaviors, with implications for prognosis and therapy.展开更多
Medullary thymic epithelial cells(mTECs) act as one of the major stromal components in the thymus for selection and maturation of both conventional T cells and non-conventional T cells. Extensive efforts have been spe...Medullary thymic epithelial cells(mTECs) act as one of the major stromal components in the thymus for selection and maturation of both conventional T cells and non-conventional T cells. Extensive efforts have been spent to understand how mTEC development and function are regulated. Although RelB has been well accepted to be a critical transcriptional factor for mTEC development, the underlying mechanisms still remain largely unclear. In this study, by generating thymic epithelial cell specific RelB deficient mice, we found that epithelial intrinsic RelB is required for mTEC homeostatic proliferation. Mechanistically, RelB regulates the expression of genes involved in cell cycle. Functionally, lack of intrinsic RelB in thymic epithelial cells results in dramatically reduced population of mTECs and impaired development of thymic invariant natural killer T(iNKT) cells and intraepithelial lymphocyte precursors(IELPs). This study thus reveals an epithelial intrinsic role of RelB on mTEC development and function.展开更多
The HIV infection model of CD4+ T-cells corresponds to a class of nonlinear ordinary differential equation systems. In this study, we provide the approximate solution of this model by using orthonormal Bernstein poly...The HIV infection model of CD4+ T-cells corresponds to a class of nonlinear ordinary differential equation systems. In this study, we provide the approximate solution of this model by using orthonormal Bernstein polynomials (OBPs). By applying the proposed method, the nonlinear system of ordinary differential equations reduces to a nonlinear system of algebraic equations which can be solved by using a suitable numerical method such as Newton's method. We prove some useful theorems concerning the convergence and error estimate associated to the present method. Finally, we apply the proposed method to get the numerical solution of this model with the arbitrary initial conditions and values. Furthermore, the numerical results obtained by the suggested method are compared with the results achieved by other previous methods. These results indicate that this method agrees with other previous methods.展开更多
This paper carries out an experiment study of decoupling performance for a novel lateral axis micromachined gyroscope with varying environmental parameters. The non-ideal mathematical model for the coupling mechanism ...This paper carries out an experiment study of decoupling performance for a novel lateral axis micromachined gyroscope with varying environmental parameters. The non-ideal mathematical model for the coupling mechanism of the gyroscope is estab-lished through the gyro dynamic response matrix. The coupling components varying with ambient pressure and temperature induced by stiffness coupling, damping coupling and electrostatic force coupling are semi-analytically discussed. The overall coupling ratio is evaluated via experiments in the custom-built installation. The testing results show that the decoupling per-formance of the gyroscope is sensitive to the environmental parameters and all the non-ideal errors are determined as a function of ambient pressure and temperature. The coupling error varies from 0.05% to 0.25% within the pressure range of 100 Pa-100 kPa. The characteristics of coupling with temperature are measured from 20℃ to 100℃ with a variation from 0.35% to 0.41%. The results also indicate that within the range of measured ambient pressure and temperature, the minimum coupling ratio occurs at 100 Pa and room temperature. The overall performance of the gyroscope is tested under the pressure of about 2000 Pa and room temperature to achieve a relatively low coupling ratio. The scale factor is measured to be 7.8 mV (°)-1 s-1 with nonlinearity about 0.45% in the full-scale range of 600 (°) s-1. The short-term bias stability is approximately 0.06 (°)s-1 (1σ) for 20 min with noise equivalent angular rate evaluated to be 0.077 (°) s-1 Hz-1/2.展开更多
Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral m RNA from t...Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral m RNA from the nucleus to the cytoplasm and transcription of viral m RNA by RNA polymerase II. We previously showed that Nullbasic inhibits transduction of human cells including T cells by HIV-1-based lentiviral vectors. Here we investigated whether the Nullbasic antagonists huTat2(a Tat targeting intrabody), HIV-1 Tat or Rev proteins or cellular DDX1 protein could improve transduction by a HIV-1 lentiviral vector conveying Nullbasic-Zs Green1 to human T cells. We show that overexpression of huTat2, Tat-FLAG and DDX1-HA in virus-like particle(VLP) producer cells significantly improved transduction efficiency of VLPs that convey Nullbasic in Jurkat cells. Specifically, co-expression of Tat-FLAG and DDX1-HA in the VLP producer cell improved transduction efficiency better than if used individually. Transduction efficiencies could be further improved by including a spinoculation step. However, the same optimised protocol and using the same VLPs failed to transduce primary human CD4^+T cells. The results imply that the effects of Nullbasic on VLPs on early HIV-1 replication are robust in human CD4^+T cells. Given this significant block to lentiviral vector transduction by Nullbasic in primary CD4^+T cells, our data indicate that gammaretroviral, but not lentiviral, vectors are suitable for delivering Nullbasic to primary human T cells.展开更多
The correlation between oxygen concentration and fire temperature when fire was extinguished with water mist was theoretically studied. The Semenov theory was applied to analyze the critical condition when fire was ex...The correlation between oxygen concentration and fire temperature when fire was extinguished with water mist was theoretically studied. The Semenov theory was applied to analyze the critical condition when fire was extin- guished with water mist, from which the correlation could be obtained. The water mist experiments were carded out by varying the fire size, atomizer number, ceiling height, system pressure, and pre-burn time in an enclosed room. The oxygen concentration near the edge of the liquid pool and the fire temperature above the center of the liquid pool were measured. A comparison of the experimental data with the correlation was made under different conditions. The results showed that fire extinguishment was a stochastic process which could be affected by many factors. This theoretical model could predict the correlation between ftre temperature and oxygen concentration when fire was extinguished with water mist in an enclosed room and it can also be treated as a critical condition for fire extinguishment.展开更多
Human immunodeficiency virus (HIV) emerged as one of the most serious health issues of the modern era. Till date, it challenges the scientists working in the fields related to its prevention, least spread and eradic...Human immunodeficiency virus (HIV) emerged as one of the most serious health issues of the modern era. Till date, it challenges the scientists working in the fields related to its prevention, least spread and eradication. It affects not only the person suffering from it but also the communities and their economies. Mathematical modeling is one of the ways to explore the possibilities of prediction (and control) strategies for contagious deceases. In this paper, we have tried to extend the scope of a currently available prediction model for a continuous time span. For this purpose, an analytical investigation of the system of nonlinear differential equations, governing the HIV infection of CD4 + T-cells, is carried out. A new emerging analytical technique Optimal Variational Iteration Method (OVIM) has been used to obtain an analytical and convergent solution. Analytical solutions are continuous solutions that can be used to predict the phenomena without the involvement of interpolation or extrapolation errors. On the other hand, their use in the derived equations, depending upon solution itself, is far easier than the numerical solutions. We have presented the error analysis and the prediction curves graphically. Moreover, a comparison with traditional Variational Iteration is also provided. It is concluded that the traditional method fails to converge for the updated models which involve the delayed differential equations.展开更多
基金Supported by National Natural Science Foundation of China,No.81571871
文摘AIM To assess the accuracy of serum procalcitionin(PCT)as a diagnostic marker in verifying upper and lower gastrointestinal perforation(GIP).METHODS This retrospective study included 46 patients from the surgical intensive care unit(ICU)of the Second Affiliated Hospital of Harbin Medical University who were confirmed to have GIP between June 2013 and December 2016.Demographic and clinical patient data were recorded on admission to ICU.Patients were divided into upper(n=19)and lower(n=27)GIP groups according to the perforation site(above or below Treitz ligament).PCT and WBC count was obtained before laparotomy and then compared between groups.Meanwhile,the diagnostic accuracy of PCT was analyzed.RESULTS Patients with lower GIP exhibited significantly higher APACHE II score,SOFA score and serum PCT level than patients with upper GIP(P=0.017,0.004,and0.001,respectively).There was a significant positive correlation between serum PCT level and APACHE II score or SOFA score(r=0.715 and r=0.611,respectively),while there was a significant negative correlation between serum PCT level and prognosis(r=-0.414).WBC count was not significantly different between the two groups,and WBC count showed no significant correlation with serum PCT level,APACHE II score,SOFA score or prognosis.The area under the receiver operating characteristic curve of PCT level to distinguish upper or lower GIP was 0.778.Patients with a serum PCT level above 17.94 ng/d L had a high likelihood of lower GIP,with a sensitivity of 100%and a specificity of 42.1%.CONCLUSION Serum PCT level is a reliable and accurate diagnostic marker in identifying upper or lower GIP before laparotomy.
文摘In order to research the characteristic and mechanism of fracture of rock-like materials,the morphology of rock fracture surface under the breakages of uniaxial compression and triaxial compression was observed and measured by means of a new-type 3D laser scanning system.Based on geographic information system(GIS)technique,the fracture surfaces were 3D visualized and reestablished.According to GIS 3D statistics,the geometrical characteristics of fracture surfaces under different breakage conditions were analyzed,and then based on fractal theory,the change laws of fractal dimension of fracture surfaces were discussed under the conditions of different cell pressures and initial water contents of rock.Furthermore,the relationships between characteristics of fracture surface and mechanical properties of rock were discussed.The results indicate that cell pressure,initial water content,and mechanical parameters of rock are the important factors to influence on the geometrical characteristics of fracture surface.The research provides a new experimental method for quantitative study on the fracture characteristics of various materials under different breakage conditions.
文摘Objective Small cell carcinoma(SCC) is mostly found in the lungs. It is extremely rare in the gastric remnant. Here, we report a case and review the literature in order to improve the diagnosis and treatment of SCC of the gastric remnant.Methods We report a case of SCC of the gastric remnant in a 71-year-old male Chinese patient who presented with epigastric pain, acid regurgitation, and belching and who underwent Billroth II gastrectomy more than 38 years ago.Results Physical examination showed no obvious abnormalities. Laboratory data were within normal limits, except for anemia. Pathology of the mass showed a protruded tumor measuring 5.0 × 5.0 × 2.5 cm at the anastomotic edge of the gastric remnant that infiltrated through the full wall of the stomach; this was confirmed by immunohistochemical staining for cytokeratin [CK(-)], leukocyte common antigen(LCA)(+), synaptophysin(+), CD56(+), and Ki-67(+ > 50%).Conclusion SCC of the gastric remnant is extremely rare, although the pathology, symptoms, diagnosis, treatment, and prognosis of SCC are similar to those of gastric SCC. Although the standard treatment of SCC of the gastric remnant remains unclear, effective surgical resection and subsequent multiagent chemotherapy should be performed for long-term survival. Our case shows the efficacy of tegafurgimeracil-oteracil-potassium capsule chemotherapy. Examination of a large series is required to determine the optimal treatment strategy for SCC of the gastric remnant.
基金Projects(50911130366, 50979030) supported by the National Natural Science Foundation of ChinaProject(2008BAB29B01) supported by the National Key Technology R&D Program of China
文摘Numerical analysis of the optimal supporting time and long-term stability index of the surrounding rocks in the underground plant of Xiangjiaba hydro-power station was carried out based on the rheological theory. Firstly,the mechanical parameters of each rock group were identified from the experimental data; secondly,the rheological calculation and analysis for the cavern in stepped excavation without supporting were made; finally,the optimal time for supporting at the characteristic point in a typical section was obtained while the creep rate and displacement after each excavation step has satisfied the criterion of the optimal supporting time. Excavation was repeated when the optimal time for supporting was identified,and the long-term stability creep time and the maximum creep deformation of the characteristic point were determined in accordance with the criterion of long-term stability index. It is shown that the optimal supporting time of the characteristic point in the underground plant of Xiangjiaba hydro-power station is 5-8 d,the long-term stability time of the typical section is 126 d,and the corresponding largest creep deformation is 24.30 mm. While the cavern is supported,the cavern deformation is significantly reduced and the stress states of the surrounding rock masses are remarkably improved.
基金supported by the Swedish Research Council (VR)Nano Lund, the Crafoord Foundation+1 种基金the China Scholarship Council (CSC)by a Donation from Carolina Le Prince with the “Kalenderflickorna” and Associated Sponsors
文摘Vertical nanowire arrays are increasingly investigated for their applications in steering cell behavior. The geometry of the array is an important parameter, which influences the morphology and adhesion of cells. Here, we investigate the effects of array geometry on the morphology of MCF7 cancer cells and MCF10A normal-like epithelial cells. Different gallium phosphide nanowire array-geometries were produced by varying the nanowire density and diameter. Our results show that the cell size is smaller on nanowires compared to flat gallium phosphide. The cell area decreases with increasing the nanowire density on the substrate. We observed an effect of the nanowire diameter on MCF10A cells, with a decreased cell area on 40 nm diameter nanowires, compared to 60 and 80 nm diameter nanowires in high-density arrays. The focal adhesion morphology depends on the extent to which cells are contacting the substrate. For low nanowire densities and diameters, ceils are lying on the substrate and we observed large focal adhesions at the cell edges. In contrast, for high nanowire densities and diameters, cells are lying on top of the nanowires and we observed point-like focal adhesions distributed over the whole cell. Our results constitute a step towards the ability to fine-tune cell behavior on nanowire arrays.
文摘The fire extinguishment time is a major factor to evaluate the efficiency of fire extinguishment with water mist. In this paper the fire extinguishment time with water mist in an enclosed room is calculated. Before adding water mist, the chemical kinetics plays the role in combustion, where a dimensionless math model is established by us-ing the Semenov theory. After adding water mist, the diffusion plays the role instead. Then another math model containing water mist and dominated by oxygen concentration is established. The fire temperature is integrated from Tm to extinguishment temperature TB and the extinguishment time can be obtained. The calculated values are compared with the experimental data under different conditions. The results show that this model can predict the fire extinguishment time accurately. Besides, this model also can be used to determine the critical water mist flux and evaluate which fire extinguishment mechanisms dominate the extinguishment.
基金supported by the Chinese Ministry of Science and Technology (2015CB910300)the National Natural Science Foundation of China (NSFC31700733)
文摘Proteins are essential players of life activities, lntraceUular protein levels directly affect cellular functions and cell fate. Upon cell division, the proteins in the mother cell are inherited by the daughters. However, what factors and by how much they affect this epigenetic inheritance of protein abundance remains unclear. Using both computational and experimental approaches, we systematically investigated this problem. We derived an analytical expression for the dependence of protein inheritance on various factors and showed that it agreed with numerical simulations of protein production and experimental results. Our work provides a framework for quantitative studies of protein inheritance and for the potential application of protein memory manipulation.
基金This work was supported by grants from the National Natural Science Foundation of China (81572766 and 31771630), the National Key Research and Development Program of China (2017YFA0103800), Guangdong Innovative and Entrepreneurial Research Team Program (2016ZT06S029), Guangdong Natural Science Foundation (2016A030313215 and 2016A030313238), SYSU Young Teachers Training Program (16YKZD14) and grants (CA101795 and IU54CA210181) from U.S. National Cancer Institute, National Institutes of Health (NIH), DOD (W81XWH-16- 1-0417), and CPRIT (DP150099, RP170537, and RP150611).
文摘The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 (PHF20) functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Casg-based targeted knockout (KO) for high-throughput screening of gene function in NB cell differentiation. The expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients. Deletion of PHF20 inhibited NB cell proliferation, invasive migration, and stem ceU-Uke traits. Mechanistically, PHF20 interacts with poly(ADP-ribose) polymerase 1 (PARP1) and directly binds to promoter regions of octamer-binding transcription factor 4 (OCT4) and sex determining region Y-box 2 (SOX2) to modulate a histone mark associated with active transcription, trimethylation of lysine 4 on histone H3 protein subunit (H3K4me3). Overexpression of OCT4 and SOX2 restored growth and progression of PHF20 KO tumor cells. Consistently, OCT4 and SOX2 protein levels in clinical NB specimens were positively correlated with PHF20 expression. Our results establish PHF20 as a key driver of NB stem cell-like properties and aggressive behaviors, with implications for prognosis and therapy.
基金supported by the Ministry of Science and Technology (2011CB946103 to Mingzhao Zhu)the National Natural Science Foundation of China (81373110 and 31570888 to Mingzhao Zhu)
文摘Medullary thymic epithelial cells(mTECs) act as one of the major stromal components in the thymus for selection and maturation of both conventional T cells and non-conventional T cells. Extensive efforts have been spent to understand how mTEC development and function are regulated. Although RelB has been well accepted to be a critical transcriptional factor for mTEC development, the underlying mechanisms still remain largely unclear. In this study, by generating thymic epithelial cell specific RelB deficient mice, we found that epithelial intrinsic RelB is required for mTEC homeostatic proliferation. Mechanistically, RelB regulates the expression of genes involved in cell cycle. Functionally, lack of intrinsic RelB in thymic epithelial cells results in dramatically reduced population of mTECs and impaired development of thymic invariant natural killer T(iNKT) cells and intraepithelial lymphocyte precursors(IELPs). This study thus reveals an epithelial intrinsic role of RelB on mTEC development and function.
文摘The HIV infection model of CD4+ T-cells corresponds to a class of nonlinear ordinary differential equation systems. In this study, we provide the approximate solution of this model by using orthonormal Bernstein polynomials (OBPs). By applying the proposed method, the nonlinear system of ordinary differential equations reduces to a nonlinear system of algebraic equations which can be solved by using a suitable numerical method such as Newton's method. We prove some useful theorems concerning the convergence and error estimate associated to the present method. Finally, we apply the proposed method to get the numerical solution of this model with the arbitrary initial conditions and values. Furthermore, the numerical results obtained by the suggested method are compared with the results achieved by other previous methods. These results indicate that this method agrees with other previous methods.
文摘This paper carries out an experiment study of decoupling performance for a novel lateral axis micromachined gyroscope with varying environmental parameters. The non-ideal mathematical model for the coupling mechanism of the gyroscope is estab-lished through the gyro dynamic response matrix. The coupling components varying with ambient pressure and temperature induced by stiffness coupling, damping coupling and electrostatic force coupling are semi-analytically discussed. The overall coupling ratio is evaluated via experiments in the custom-built installation. The testing results show that the decoupling per-formance of the gyroscope is sensitive to the environmental parameters and all the non-ideal errors are determined as a function of ambient pressure and temperature. The coupling error varies from 0.05% to 0.25% within the pressure range of 100 Pa-100 kPa. The characteristics of coupling with temperature are measured from 20℃ to 100℃ with a variation from 0.35% to 0.41%. The results also indicate that within the range of measured ambient pressure and temperature, the minimum coupling ratio occurs at 100 Pa and room temperature. The overall performance of the gyroscope is tested under the pressure of about 2000 Pa and room temperature to achieve a relatively low coupling ratio. The scale factor is measured to be 7.8 mV (°)-1 s-1 with nonlinearity about 0.45% in the full-scale range of 600 (°) s-1. The short-term bias stability is approximately 0.06 (°)s-1 (1σ) for 20 min with noise equivalent angular rate evaluated to be 0.077 (°) s-1 Hz-1/2.
基金supported by the National Health and Medical Research Council Project Grant (1085359)supported by Prime Minister’s Australia Asia Endeavour Postgraduate (Ph.D.) Award funded by the Australian Government,epartment of Education and Training,UQ international scholarship (UQI) and UQ Centenial scholarship (UQCent)
文摘Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral m RNA from the nucleus to the cytoplasm and transcription of viral m RNA by RNA polymerase II. We previously showed that Nullbasic inhibits transduction of human cells including T cells by HIV-1-based lentiviral vectors. Here we investigated whether the Nullbasic antagonists huTat2(a Tat targeting intrabody), HIV-1 Tat or Rev proteins or cellular DDX1 protein could improve transduction by a HIV-1 lentiviral vector conveying Nullbasic-Zs Green1 to human T cells. We show that overexpression of huTat2, Tat-FLAG and DDX1-HA in virus-like particle(VLP) producer cells significantly improved transduction efficiency of VLPs that convey Nullbasic in Jurkat cells. Specifically, co-expression of Tat-FLAG and DDX1-HA in the VLP producer cell improved transduction efficiency better than if used individually. Transduction efficiencies could be further improved by including a spinoculation step. However, the same optimised protocol and using the same VLPs failed to transduce primary human CD4^+T cells. The results imply that the effects of Nullbasic on VLPs on early HIV-1 replication are robust in human CD4^+T cells. Given this significant block to lentiviral vector transduction by Nullbasic in primary CD4^+T cells, our data indicate that gammaretroviral, but not lentiviral, vectors are suitable for delivering Nullbasic to primary human T cells.
文摘The correlation between oxygen concentration and fire temperature when fire was extinguished with water mist was theoretically studied. The Semenov theory was applied to analyze the critical condition when fire was extin- guished with water mist, from which the correlation could be obtained. The water mist experiments were carded out by varying the fire size, atomizer number, ceiling height, system pressure, and pre-burn time in an enclosed room. The oxygen concentration near the edge of the liquid pool and the fire temperature above the center of the liquid pool were measured. A comparison of the experimental data with the correlation was made under different conditions. The results showed that fire extinguishment was a stochastic process which could be affected by many factors. This theoretical model could predict the correlation between ftre temperature and oxygen concentration when fire was extinguished with water mist in an enclosed room and it can also be treated as a critical condition for fire extinguishment.
文摘Human immunodeficiency virus (HIV) emerged as one of the most serious health issues of the modern era. Till date, it challenges the scientists working in the fields related to its prevention, least spread and eradication. It affects not only the person suffering from it but also the communities and their economies. Mathematical modeling is one of the ways to explore the possibilities of prediction (and control) strategies for contagious deceases. In this paper, we have tried to extend the scope of a currently available prediction model for a continuous time span. For this purpose, an analytical investigation of the system of nonlinear differential equations, governing the HIV infection of CD4 + T-cells, is carried out. A new emerging analytical technique Optimal Variational Iteration Method (OVIM) has been used to obtain an analytical and convergent solution. Analytical solutions are continuous solutions that can be used to predict the phenomena without the involvement of interpolation or extrapolation errors. On the other hand, their use in the derived equations, depending upon solution itself, is far easier than the numerical solutions. We have presented the error analysis and the prediction curves graphically. Moreover, a comparison with traditional Variational Iteration is also provided. It is concluded that the traditional method fails to converge for the updated models which involve the delayed differential equations.