Somatic deletion of the NF1 gene in a neurofibromatosis type 1-associated malignant melanoma demonstrated by digital PCR

BACKGROUND: Neurofibromatosis type 1 (NF1) is the most common hereditary neurocutaneous disorder and it is associated with an elevated risk for malignant tumors of tissues derived from neural crest cells. The NF1 gene is considered a tumor suppressor gene and inactivation of both copies can be found in NF1-associated benign and malignant tumors. Melanocytes also derive from neural crest cells but melanoma incidence is not markedly elevated in NF1. In this study we could analyze a typical superficial spreading melanoma of a 15-year-old boy with NF1 for loss of heterozygosity (LOH) within the NF1 gene. Neurofibromatosis in this patient was transmitted by the boy's farther who carried the mutation NF1 c. 5546 G/A. RESULTS: Melanoma cells were isolated from formalin-fixed tissue by liquid coverslip laser microdissection. In order to obtain statistically significant LOH data, digital PCR was performed at the intragenic microsatellite IVS27AC28 with DNA of approx. 3500 melanoma cells. Digital PCR detected 23 paternal alleles and one maternal allele. Statistical analysis by SPRT confirmed significance of the maternal allele loss. CONCLUSION: To our knowledge, this is the first molecular evidence of inactivation of both copies of the NF1 gene in a typical superficial spreading melanoma of a patient with NF1. The classical double-hit inactivation of the NF1 gene suggests that the NF1 genetic background promoted melanoma genesis in this patient

A distinct four-value blood signature of pyrexia under combination therapy of malignant melanoma with dabrafenib and trametinib evidenced by an algorithm-defined pyrexia score

Pyrexia is a frequent adverse event of BRAF/MEK-inhibitor combination therapy in patients with metastasized malignant melanoma (MM). The study’s objective was to identify laboratory changes which might correlate with the appearance of pyrexia. Initially, data of 38 MM patients treated with dabrafenib plus trametinib, of which 14 patients developed pyrexia, were analysed retrospectively. Graphical visualization of time series of laboratory values suggested that a rise in C-reactive-protein, in parallel with a fall of leukocytes and thrombocytes, were indicative of pyrexia. Additionally, statistical analysis showed a significant correlation between lactate dehydrogenase (LDH) and pyrexia. An algorithm based on these observations was designed using a deductive and heuristic approach in order to calculate a pyrexia score (PS) for each laboratory assessment in treated patients. A second independent data set of 28 MM patients, 8 with pyrexia, was used for the validation of the algorithm. PS based on the four parameters CRP, LDH, leukocyte and thrombocyte numbers, were statistically significantly higher in pyrexia patients, differentiated between groups (F = 20.8; p = <0.0001) and showed a significant predictive value for the diagnosis of pyrexia (F = 6.24; p = 0.013). We provide first evidence that pyrexia in patients treated with BRAF/MEK-blockade can be identified by an algorithm that calculates a score

Моделирование процесса синтеза в воздушной плазме оксидных композиций для дисперсионного плутоний-ториевого ядерного топлива

Целью работы являлось исследование процесса плазмохимического синтеза наноразмерных оксидных композиций для дисперсионного плутоний-ториевого ядерного топлива из водно-органических нитратных растворов (ВОНР). В результате было показано, что плазменная переработка диспергированных растворов ВОНР в воздушно-плазменном потоке позволяет осуществлять плазмохимический синтез наноразмерных порошков оксидных композиций с высокими физико-химическими и технологическими свойствами.The aim of this paper was to study the process of plasma-chemical synthesis of nanosized oxide compositions for dispersive plutonium-thorium nuclear fuel from water-organic nitrate solutions (WONS). As a result, it was shown that the plasma processing of dispersed WONS solutions in an air-plasma flow allows plasma-chemical synthesis of nanosized powders of oxide compositions with high physical, chemical and technological properties

Influence of atmospheric circulation on turbulent air-sea heat fluxes over the Mediterranean Sea during winter

The influence of the winter atmospheric circulation on the turbulent variables of the air-sea boundary layer in the Mediterranean Sea is investigated. We examine the effects of several climatic indices and the corresponding large scale atmospheric patterns on the above variables by using a correlation analysis. The spatial characteristics and the behavior of the turbulent variables are also examined based on standard deviation and EOF analysis. Two main types of response to the index-specified atmospheric patterns have been identified: (1) A relatively uniform response of the entire basin associated with the influence of the East Atlantic pattern and (2) opposite responses in the western and eastern sub-basins linked mainly to the intrabasin SLP. The latter is a combined effect of the first four modes of atmospheric variability in the North Atlantic/Eurasia region, the North Atlantic Oscillation (NAO), the East Atlantic Pattern (EA), the Scandinavian Pattern (SCAND), and the East Atlantic-West Russia Pattern (EAWR). The two identified responses of the Mediterranean Sea to the atmospheric forcing are also in accordance with the primary modes of variability of the turbulent variables that result in the EOF analysis. All of the statistically independent indices (NAO, EA, SCAND, EAWR) have to be considered in order to fully account for the modulation of the turbulent variables in the Mediterranean Sea. As an example we refer to the mechanism through which, independent modes of atmospheric variability contributed to the Eastern Mediterranean Transient event between 1987 and 1995. © 2012 by the American Geophysical Union.Peer Reviewe

Исследование влияния изменения конструкций топочной камеры ТЭС БКЗ -420 на распределения продуктов горения

Объектом исследования является топочная камера котла БКЗ-420 АТЭЦ-2. Цель работы – 3D моделирование процессов тепломасса переноса, исследование влияния изменения конструкций топочной камеры на распределения продуктов горения. В процессе исследования проводились вычислительные эксперименты по исследованию аэродинамических, тепловых и концентрационных характеристик топочной камеры, поля скоростей, температуры, турбулентных характеристик, концентраций всех вредных пылегазовых выбросов и энергии. В результате исследования разработана оптимальная технология сжигания энергетического высокозольного топлива и наилучшие конструкционные параметры топочной камеры.The object of research is the combustion chamber of the boiler BKZ-420 TPP-2. Objective - 3D modeling transfer processes, the study of influence of structural changes of the combustion chamber to the distribution of the products of combustion. The study carried out computational experiments on the aerodynamic, thermal and concentration characteristics of the combustion chamber, the velocity field, temperature, turbulent characteristics, concentrations of harmful dust and gas emissions and energy. The study developed the optimum combustion technology of high-energy fuel and best structural parameters of the combustion chamber