Low thrust orbit determination program

Logical flow and guidelines are provided for the construction of a low thrust orbit determination computer program. The program, tentatively called FRACAS (filter response analysis for continuously accelerating spacecraft), is capable of generating a reference low thrust trajectory, performing a linear covariance analysis of guidance and navigation processes, and analyzing trajectory nonlinearities in Monte Carlo fashion. The choice of trajectory, guidance and navigation models has been made after extensive literature surveys and investigation of previous software. A key part of program design relied upon experience gained in developing and using Martin Marietta Aerospace programs: TOPSEP (Targeting/Optimization for Solar Electric Propulsion), GODSEP (Guidance and Orbit Determination for SEP) and SIMSEP (Simulation of SEP)

Mission Analysis Program for Solar Electric Propulsion (MAPSEP). Volume 2: User's manual

A user's manual which describes input/output routines and recommended operating procedures relating to MAPSEP is presented. Samples runs are included

Mission Analysis Program for Solar Electric Propulsion (MAPSEP). Volume 1: Analytical manual

The mission analysis program for solar electric propulsion (MAPSEP) is comprised of the basic modes: TOPSEP (trajectory generation), GODSEP (linear error analysis), and SIMSEP (simulation). The program is designed to analyze any low thrust mission with respect to trajectory performance, guidance and navigation, and to provide system related requirements for the purpose of vehicle design. The MAPSEP organization is described along with all models and algorithms. Topics discussed include: trajectory and error covariance propagation methods, orbit determination processes, thrust modeling, and trajectory correction (guidance) schemes

Mission Analysis Program for Solar Electric Propulsion (MAPSEP). Volume 3: Program manual

The internal structure of MAPSEP is described. Topics discussed include: macrologic, variable definition, subroutines, and logical flow. Information is given to facilitate modifications to the models and algorithms of MAPSEP

Vasa vasorum lumen narrowing in brain vascular hyalinosis in systemic hypertension patients who died of ischemic stroke

Ischemic stroke is a major cause of death among patients with systemic hypertension. The narrowing of the lumen of the brain vasculature contributes to the increased incidence of stroke. While hyalinosis represents the major pathological lesions contributing to vascular lumen narrowing and stroke, the pathogenic mechanism of brain vascular hyalinosis has not been well characterized. Thus, the present study examined the postmortem brain vasculature of human patients who died of ischemic stroke due to systemic hypertension. Hematoxylin and eosin staining and immunohistochemistry showed the occurrence of brain vascular hyalinosis with infiltrated plasma proteins along with the narrowing of the vasa vasorum and oxidative stress. Transmission electron microscopy revealed endothelial cell bulge protrusion into the vasa vasorum lumen and the occurrence of endocytosis in the vasa vasorum endothelium. The treatment of cultured microvascular endothelial cells with adrenaline also promoted the formation of the bulge as well as endocytic vesicles. The siRNA knockdown of sortin nexin-9 (a mediator of clathrin-mediated endocytosis) inhibited adrenaline-induced endothelial cell bulge formation. Adrenaline promoted protein-protein interactions between sortin nexin-9 and neural Wiskott–Aldrich syndrome protein (a regulator of actin polymerization). Spontaneously hypertensive stroke-prone rats also exhibited lesions indicative of brain vascular hyalinosis, the endothelial cell protrusion into the lumen of the vasa vasorum, and endocytosis in vasa vasorum endothelial cells. We propose that endocytosis-dependent endothelial cell bulge protrusion narrows the vasa vasorum, resulting in ischemic oxidative damage to cerebral vessels, the formation of hyalinosis, the occurrence of ischemic stroke, and death in systemic hypertension patients

Covalent enzyme coupling on cellulose acetate membranes for glucose sensor development

International audienceMethods for immobilizing glucose oxidase (GOx) on cellulose acetate (CA) membranes are compared. The optimal method involves covalent coupling of bovine serum albumin (BSA) to CA membrane and a subsequent reaction of the membrane with GOx, which has previously been activated with an excess of p-benzoquinone. This coupling procedure is fairly reproducible and allows the preparation of thin membranes (5-20 µm) showing high surface activities (1-3 U/cm2) which are stable over a period of 1-3 months. Electrochemical and radiolabeling experiments show that enzyme inactivation as a result of immobilization is negligible. A good correlation between surface activity of membranes and their GOx load is observed

A phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in patients with colorectal cancer

Inhibition of epidermal growth factor receptor (EGFR) signalling contributes to the therapy of colorectal cancer. Gefitinib, an oral EGFR tyrosine kinase inhibitor, shows supra-additive growth inhibition with irinotecan and fluoropyrimidines in xenograft models. We designed a study to determine the tolerability and efficacy of gefitinib in combination with irinotecan, infusional 5-fluorouracil (5-FU) and leucovorin (LV), on a 2-week schedule. Among 13 patients with advanced colorectal cancer, 10 required dose reductions of irinotecan and 5-FU because of dehydration, diarrhoea, and neutropenia, seven of whom required hospitalisation, three with neutropenic fever. One patient achieved partial response and seven had disease stabilisation. The combination of this standard chemotherapy regimen with gefitinib is associated with excessive toxicity, suggesting an interaction at a pharmacokinetic or pharmacodynamic level

Treatment of CoQ10 Deficient Fibroblasts with Ubiquinone, CoQ Analogs, and Vitamin C: Time- and Compound-Dependent Effects

Background: Coenzyme Q(10) (CoQ(10)) and its analogs are used therapeutically by virtue of their functions as electron carriers, antioxidant compounds, or both. However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress.Methodology/Principal Findings: To test these concepts, we have evaluated the effects of CoQ(10), coenzyme Q(2) (CoQ(2)), idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ(10) deficiency. A final concentration of 5 mu M of each compound was chosen to approximate the plasma concentration of CoQ(10) of patients treated with oral ubiquinone. CoQ(10) supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ(10) deficient fibroblasts therein normalizing the bioenergetics status of the cells. Other compounds did not affect cellular bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production and oxidative stress-induced cell death were normalized by all supplements.Conclusions/Significance: These results indicate that: 1) pharmacokinetics of CoQ(10) in reaching the mitochondrial respiratory chain is delayed; 2) short-tail ubiquinone analogs cannot replace CoQ(10) in the mitochondrial respiratory chain under conditions of CoQ(10) deficiency; and 3) oxidative stress and cell death can be counteracted by administration of lipophilic or hydrophilic antioxidants. The results of our in vitro experiments suggest that primary CoQ(10) deficiencies should be treated with CoQ(10) supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ(2). Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present

Сравнительная оценка параметров безопасности на доклиническом и клиническом этапах исследования лекарственного препарата Реамберин® (ООО «НТФФ «ПОЛИСАН»)

Relevance. Interpretation of the preclinical trials data is fundamental importance. The correctness of extrapolation of data obtained from animals to humans is due to the qualitative and quantitative diversity of the systems tested the recorded parameters and approaches to their interpretation, as well as statistical methods in determining the possible risk to humans. Aim. Comparative assessment of the safety and tolerability parameters obtained during the preclinical and clinical trials of the Reamberin® (LLC «POLYSAN») and the development of approaches to improving clinical trial planning processes for assessing safety and tolerability, taking into accounts the results of preclinical studies. Materials and methods. A comparative analysis of the safety parameters that arose during a clinical study involving healthy volunteers and deviations from the control levels of clinical and laboratory parameters established at the stage of a preclinical study on outbred rats and rabbits of the chinchilla breed of a drug with an international non-proprietary name (INN): meglumine sodium succinate (trade name (TN) Reamberin® (LLC «POLYSAN»)). Results. Unidirectional deviations from normal (control) values were established. Isolated cases of adverse events among healthy volunteers (increased activity of hepatic transaminases, changes in blood pressure) were identified. This facts didn't correlate with the preclinical study. The number of comparable indicators in laboratory animals, for which statistically significant differences were established between the experimental and control groups, significantly exceeded the number of signs in the form of adverse events among healthy volunteers.Актуальность. Интерпретация данных доклинических испытаний лекарственных средств имеет принципиальное значение. Кор­ректность экстраполяции данных, полученных на животных, на человека обусловлены, в том числе, качественным и количественным разнообразием тестируемых систем, регистрируемых параметров и подходов к их интерпретации, а также статистических методов при определении возможного риска для человека.Цель. Сравнительная оценка параметров безопасности и переносимости, полученных в ходе доклинического и клинического ис­следования лекарственного препарата Реамберин® (ООО «НТФФ «ПОЛИСАН»), и выработка подходов к совершенствованию процессов планирования клинических исследований по оценке безопасности и переносимости с учётом результатов доклинических исследований.Материалы и методы. Был проведён сравнительный анализ параметров безопасности, возникших в ходе клинического исследования с участием здоровых добровольцев, и отклонений от контрольных уровней клинико-лабораторных показателей, установленных на этапе доклинического исследования на беспородных крысах и кроликах породы шиншилла лекарственного препарата с международным непатентованным наименованием (МНН) - меглюмина натрия сук­цинат (торговое наименование (ТН) Реамберин® (ООО «НТФФ «ПОЛИСАН»)).Результаты. Установлены однонаправленные отклонения от нормальных (контрольных) значений, выявленные единичные случаи нежелательные явления у добровольцев (повышение активности печёночных трансаминаз, изменения артериального давления), которые не соотносились с данными доклинического исследования. Количество сопоставляемых показателей у лабораторных животных, для которых были установлены статистически значимые различия между опытными и контрольными группами, значительно превышало численность признаков в виде НЯ у добровольцев