Modelos de ajuste de carga para evaluar estructuralmente capas de suelos de un pavimento flexible

Esta investigación es de enfoque cuantitativo, que surge ante el problema causado por el deterioro de un pavimento, como huecos, ahuellamientos, hundimientos y falta de capacidad de soporte estructural, trazándose como objetivo determinar modelos de ajuste de carga a fin de evaluar, estructuralmente, las capas de suelos de un pavimento flexible, a través de una representación gráfica obtenida con las datas de campo. Para solucionarlo, previo a la ejecución de capas estructurales de suelos en un pavimento flexible, se recurrió, al estudio del diseño estructural del pavimento y programa computacional Pitrapave, obteniendo, un modelo de análisis mecánico del suelo, que determina la deflexión admisible de las capas de suelos de 04 tipos de pavimentos flexibles. Al término de la conformación de estas capas de suelos mencionados, se realizó ensayos con un equipo liviano portátil denominado Light Falling Weight Deflectometer, el cual, con la data proporcionada, se determinó un modelo matemático de deformación del suelo que, determina la deflexión a una proyección de carga de 41 KN, estos resultados se compararon con los resultados patrones, obtenidos mediante ensayos realizados con el equipo Viga Benkelman. De igual manera, con los datos de ensayo proporcionados por el equipo Light Falling Weight Deflectometer, se determinó otro modelo matemático de resistencia del suelo, obteniendo como resultado promedio, el módulo resiliente de cada capa estructural, este resultado se comparó con los resultados de módulos resilientes adoptados en el diseño y el material conformado. Concluyendo que, los modelos de ajuste de carga, y los modelos matemáticos obtienen resultados con aproximaciones al +/- 7.50%

TAMU: A New Space Mission Operations Paradigm

The Transferable, Adaptable, Modular and Upgradeable (TAMU) Flight Production Process (FPP) is a model-centric System of System (SoS) framework which cuts across multiple organizations and their associated facilities, that are, in the most general case, in geographically diverse locations, to develop the architecture and associated workflow processes for a broad range of mission operations. Further, TAMU FPP envisions the simulation, automatic execution and re-planning of orchestrated workflow processes as they become operational. This paper provides the vision for the TAMU FPP paradigm. This includes a complete, coherent technique, process and tool set that result in an infrastructure that can be used for full lifecycle design and decision making during any flight production process. A flight production process is the process of developing all products that are necessary for flight

Assessment of ifosfamide pharmacokinetics, toxicity, and relation to CYP3A4 activity as measured by the erythromycin breath test in patients with sarcoma

BACKGROUND. Ifosfamide is a chemotherapeutic agent that requires cytochrome P450 3A (CYP3A) for bioactivation and metabolism. To the authors' knowledge, the correlation between dose, pharmacokinetics, CYP3A, and toxicity has not been fully evaluated. A randomized Phase II trial was performed on 22 soft tissue sarcoma patients treated with doxorubicin (60 mg/m 2 /cycle) and either high-dose ifosfamide (12 g/m 2 /cycle) or standard-dose ifosfamide (6 g/m 2 /cycle). The pharmacokinetics of ifosfamide and CYP3A measurements observed are reported. METHODS. Pharmacokinetic parameters for ifosfamide, 2-dichloroethylifosfamide (2-DCE), and 3-dichloroethylifosfamide (3-DCE) were collected after the first ifosfamide infusion in 13 patients. Bayesian designed limited pharmacokinetic data were collected from an additional 41 patients. The erythromycin breath test (ERMBT) was performed on 81 patients as an in vivo phenotypic assessment of CYP3A activity. RESULTS. Fourteen-hour (peak) plasma levels of ifosfamide, 2-DCE, and 3-DCE were found to correlate strongly with the respective area under the curve (AUC) 0–24 values ( r = 0.97, 0.94, and 0.95; P < .0001). Patients who experienced a grade 3–4 absolute neutrophil count (ANC), platelet, or creatinine toxicity (using the National Cancer Institute Common Toxicity Criteria [version 2]) were found to have statistically significantly higher median 14-hour plasma levels of ifosfamide, 2-DCE, and 3-DCE compared with patients with grade 0–2 toxicity. ERMBT was not found to correlate with pharmacokinetic parameters of ifosfamide and metabolites or toxicity. CONCLUSIONS. The 14-hour plasma level of ifosfamide, 2-DCE, and 3-DCE is a simple and appropriate substitute for describing the AUC of ifosfamide after 1 day of a 1-hour to 2-hour infusion of drug. Fourteen-hour plasma levels of ifosfamide and metabolites are useful predictors of neutropenia, thrombocytopenia, and creatinine toxicity. ERMBT was not found to accurately correlate with ifosfamide pharmacokinetics or clinical toxicity. Cancer 2007. © 2007 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56045/1/22669_ftp.pd

Modulation of erlotinib pharmacokinetics in mice by a novel cytochrome P450 3A4 inhibitor, BAS 100

Administration of BAS 100, a novel mechanism-based CYP3A4 inhibitor isolated from grapefruit juice, resulted in a 2.1-fold increase in erlotinib exposure following oral administration to wild-type and humanised CYP3A4 transgenic mice. This study illustrates the potential of BAS 100 to increase the low and variable oral bioavailability of erlotinib in cancer patients

Determination of Drug Toxicity Using 3D Spheroids Constructed From an Immortal Human Hepatocyte Cell Line

Numerous publications have documented that the immortal cells grown in three-dimensional (3D) cultures possess physiological behavior, which is more reminiscent of their parental organ than when the same cells are cultivated using classical two-dimensional (2D) culture techniques. The goal of this study was to investigate whether this observation could be extended to the determination of LD50 values and whether 3D data could be correlated to in vivo observations. We developed a noninvasive means to estimate the amount of protein present in a 3D spheroid from it is planar area (± 21%) so that a precise dose can be provided in a manner similar to in vivo studies. This avoided correction of the actual dose given based on a protein determination after treatment (when some cells may have lysed). Conversion of published in vitro LC50 data (mM) for six common drugs (acetaminophen, amiodarone, diclofenac, metformin, phenformin, and valproic acid) to LD50 data (mg compound/mg cellular protein) showed that the variation in LD50 values was generally less than that suggested by the original LC50 data. Toxicological analysis of these six compounds in 3D spheroid culture (either published or presented here) demonstrated similar LD50 values. Although in vitro 2D HepG2 data showed a poor correlation, the primary hepatocyte and 3D spheroid data resulted in a much higher degree of correlation with in vivo lethal blood plasma levels. These results corroborate that 3D hepatocyte cultures are significantly different from 2D cultures and are more representative of the liver in vivo

A Semi-Physiologically Based Pharmacokinetic Model Describing the Altered Metabolism of Midazolam Due to Inflammation in Mice

This is the author's accepted manuscript.Purpose To investigate influence of inflammation on metabolism and pharmacokinetics (PK) of midazolam (MDZ) and construct a semi-physiologically based pharmacokinetic (PBPK) model to predict PK in mice with inflammatory disease. Methods Glucose-6-phosphate isomerase (GPI)-mediated inflammation was used as a preclinical model of arthritis in DBA/1 mice. CYP3A substrate MDZ was selected to study changes in metabolism and PK during the inflammation. The semi-PBPK model was constructed using mouse physiological parameters, liver microsome metabolism, and healthy animal PK data. In addition, serum cytokine, and liver-CYP (cytochrome P450 enzymes) mRNA levels were examined. Results The in vitro metabolite formation rate was suppressed in liver microsomes prepared from the GPI-treated mice as compared to the healthy mice. Further, clearance of MDZ was reduced during inflammation as compared to the healthy group. Finally, the semi-PBPK model was used to predict PK of MDZ after GPI-mediated inflammation. IL-6 and TNF-α levels were elevated and liver-cyp3a11 mRNA was reduced after GPI treatment. Conclusion The semi-PBPK model successfully predicted PK parameters of MDZ in the disease state. The model may be applied to predict PK of other drugs under disease conditions using healthy animal PK and liver microsomal data as inputs

Bathymetric records of marine shelled mollusca from the northeastern shelf of Yucatan, Mexico

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Bibliography: leaves 166-173.Not availabl

Modelos de ajuste de carga para evaluar estructuralmente capas de suelos de un pavimento flexible

Esta investigación es de enfoque cuantitativo, que surge ante el problema causado por el deterioro de un pavimento, como huecos, ahuellamientos, hundimientos y falta de capacidad de soporte estructural, trazándose como objetivo determinar modelos de ajuste de carga a fin de evaluar, estructuralmente, las capas de suelos de un pavimento flexible, a través de una representación gráfica obtenida con las datas de campo. Para solucionarlo, previo a la ejecución de capas estructurales de suelos en un pavimento flexible, se recurrió, al estudio del diseño estructural del pavimento y programa computacional Pitrapave, obteniendo, un modelo de análisis mecánico del suelo, que determina la deflexión admisible de las capas de suelos de 04 tipos de pavimentos flexibles. Al término de la conformación de estas capas de suelos mencionados, se realizó ensayos con un equipo liviano portátil denominado Light Falling Weight Deflectometer, el cual, con la data proporcionada, se determinó un modelo matemático de deformación del suelo que, determina la deflexión a una proyección de carga de 41 KN, estos resultados se compararon con los resultados patrones, obtenidos mediante ensayos realizados con el equipo Viga Benkelman. De igual manera, con los datos de ensayo proporcionados por el equipo Light Falling Weight Deflectometer, se determinó otro modelo matemático de resistencia del suelo, obteniendo como resultado promedio, el módulo resiliente de cada capa estructural, este resultado se comparó con los resultados de módulos resilientes adoptados en el diseño y el material conformado. Concluyendo que, los modelos de ajuste de carga, y los modelos matemáticos obtienen resultados con aproximaciones al +/- 7.50%.Tesi