RESUMEN
The general sourceless efficiency calibration has two major methods, Monte Carlo simulation and numerical calculation. Monte Carlo simulation as an important method to address the efficiency calibration in complex measurement systems, despite it being highly accurate, but inefficient and time-consuming. And although the numerical calculation is computationally efficient, its accuracy is highly influenced by the multiple Compton scattering of rays in sensitive body, and it is difficult to deal with complex measurement systems. To solve the above problems, this paper proposes a discrete numerical calculation combined with the graphical Boolean operations method for sourceless efficiency calibration. The method starts with a Monte Carlo simulation to obtain the rays deposition process in an infinite sensitive body and record deposition locations as a matrix; then, for different measurement systems, discrete numerical calculations are used to rapidly obtain the transmission process of rays to the sensitive body of the detector; finally, the two are combined to obtain the detection efficiency of the rays by using graphical Boolean operations. For the given two test models, the error between the measured and calculated results of 241Am, 137Cs, 60Co at 60 positions is within -3.61â¼9.71%, and the error between the measured and calculated results of the soil source is within -1.27 to 4.26%, indicating that the method has high reliability in sourceless efficiency calibration. And in comparison with Monte Carlo simulations, it is found that the method has a good agreement with Monte Carlo simulation in efficiency calibration and the computational speed has been greatly improved.
RESUMEN
The adult mammalian heart is thought to be a terminally differentiated organ given the postmitotic nature of cardiomyocytes. Consequently, the potential for cardiac repair through cardiomyocyte proliferation is extremely limited. Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor that is required for embryonic heart development. In this study we investigated the role of LRP6 in heart repair through regulation of cardiomyocyte proliferation. Lrp6 deficiency increased cardiomyocyte cell cycle activity in neonatal, juvenile and adult mice. Cardiomyocyte-specific deletion of Lrp6 in the mouse heart induced a robust regenerative response after myocardial infarction (MI), led to reduced MI area and improvement in left ventricular systolic function. In vivo genetic lineage tracing revealed that the newly formed cardiomyocytes in Lrp6-deficient mouse hearts after MI were mainly derived from resident cardiomyocytes. Furthermore, we found that the pro-proliferative effect of Lrp6 deficiency was mediated by the ING5/P21 signaling pathway. Gene therapy using the adeno-associated virus (AAV)9 miRNAi-Lrp6 construct promoted the repair of heart injury in mice. Lrp6 deficiency also induced the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our study identifies LRP6 as a critical regulator of cardiomyocyte proliferation, which may lead to the development of a novel molecular strategy to promote myocardial regeneration and repair.
Asunto(s)
Corazón/fisiología , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/metabolismo , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Regulación hacia Abajo , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/antagonistas & inhibidores , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio/patología , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , RegeneraciónRESUMEN
Infection with human papillomavirus, particularly type 16 (HPV16), is highly associated with the development of cervical intraepithelial neoplasia and cervical cancer. The two early viral oncogenes, E6 and E7, are selectively retained and constitutively expressed in tumor cells and are therefore attractive immunotherapeutic targets. Thus a vaccine strategy based on recombinant HPV16 E6/E7 fusion protein represents an efficient approach against HPV16-associated tumors. Although the expression level of HPV16 E6/E7 fusion protein was presumed to be low, direct experimental proof in vivo was lacking. To enhance the expression level and investigate its antitumor efficacy in vivo, we constructed a modified HPV16 E6/E7 fusion gene with three point-mutations and expressed it in Escherichia coli. The encoded protein, denoted mE6(1-120)/mE7(1-60), comprises 120 N-terminus amino acids of E6 and 60 N-terminus amino acids of E7 plus a histine tag, was purified on an affinity column, and subsequently characterized by Western blotting. Immunization of mice with mE6(1-120)/mE7(1-60) completely protected them against subsequent challenge and rechallenge with TC-1 tumor cells expressing HPV16 E6 and E7 proteins. In the therapeutic experiments, most mice eliminated the preexisting tumors and had a long-term protection. Consistent with the results of in vivo experiments, the splenocytes from immunized mice elicited cytotoxic T lymphocytes and specifically lysed TC-1 cells in vitro. More importantly, the expression level of mE6(1-120)/mE7(1-60) was significantly improved, meeting the necessary quantity required for a vaccine clinical trial. In conclusion, these data provide a scientific basis for the use of modified mE6(1-120)/mE7(1-60) in future human trials.
Asunto(s)
Vacunas contra el Cáncer/inmunología , Proteínas Oncogénicas Virales/inmunología , Proteínas Recombinantes de Fusión/inmunología , Proteínas Represoras/inmunología , Infecciones Tumorales por Virus/prevención & control , Animales , Western Blotting , Vacunas contra el Cáncer/genética , Línea Celular Tumoral , Citotoxicidad Inmunológica , Modelos Animales de Enfermedad , Femenino , Inmunización , Ratones , Ratones Endogámicos C57BL , Proteínas Oncogénicas Virales/genética , Papillomaviridae/inmunología , Proteínas E7 de Papillomavirus , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Proteínas Represoras/genética , Bazo/inmunología , Factores de Tiempo , Infecciones Tumorales por Virus/inmunologíaRESUMEN
OBJECTIVE: To study the effect of tongbiling, a complex preparation of Chinese traditional medicine, on the expression of MCP-1 mRNA of synovial cells in rats with adjuvant arthritis. METHOD: The expression level of MCP-1 mRNA in synoviocytes from rats with adjuvant arthritis was assayed by the method of RT-PCR. RESULT: The amounts of MCP-1 mRNA expression in synoviocytes from rats with adjuvant arthritis were distinctly decreased by tongbiling. It suggested that tongbiling had inhibition effect on rheumatoid arthritis by a down regulation for the expression of MCP-1 mRNA in the inflamed synoviocytes.