МОДЕЛИРОВАНИЕ УДАРНОГО КОНТАКТА ИНДЕНТОРА С НЕЖЕСТКИМИ СТАЛЬНЫМИ КОНСТРУКЦИЯМИ ПРИ ИЗМЕРЕНИИ ТВЕРДОСТИ

The problems of measuring hardness of constructions with insufficient rigidity by the dynamic indentation are discussed. The disadvantages of the existing dynamic hardness testers are described, the operation of which consists in impact indentation and determination of the hardness, depending on the restitution coefficient. Finite-element models of the contact of the indenter and the pipes samples with various wall thicknesses and diameters and cantilevered plates of various thicknesses are developed. Indentation diagrams for the investigated samples of pipes and plates in the coordinate plane of force-displacement are obtained. The results of the simulation have good convergence with the experimental data. With the help of the finite element models the separation of local penetration and deflection of construction is made. It is shown the influence of steel construction deflection on the process of indenter impression into the material tested and the change of indentation parameters as restitution coefficient, contact force, penetration depth and time of the active part of the impact. The limits of possible application of dynamic hardness testers have been determined. The ways of the increasing of the hardness measurement accuracy on the base of the data obtained during impact interaction are shown. It is established that the use of dependences between hardness and the time of the active stage of impact, as well as the ratio of the contact force to the depth of penetration at the loading stage, makes it possible to evaluate the hardness for pipes with the wall thickness exceeding 5 mm and cantilevered plates at the distance from the fixed support up to 100 mm. Рассматриваются вопросы измерения твердости конструкций недостаточной жесткости методом ударного вдавливания индентора. Описываются недостатки существующих динамических твердомеров, принцип действия которых заключается в нанесении удара по испытуемому образцу и регистрации коэффициента восстановления скорости, зависящего от твердости. Построены конечно-элементные модели ударного взаимодействия индентора с образцами труб с различной толщиной стенки и диаметром, а также консольно закрепленных пластин разной толщины. Получены диаграммы вдавливания индентора в исследуемые образцы труб и пластин в координатах контактное усилие – перемещение. Показана достаточно хорошая сходимость между результатами моделирования и экспериментальными данными, полученными на твердомере, позволяющем регистрировать кривую нагружения в процессе ударного взаимодействия. С помощью построенных конечно-элементных моделей выделен вклад локальной деформации и прогиба в общий отклик конструкции при индентировании. Установлено влияние прогиба конструкций на процесс внедрения индентора в материал, а также на такие параметры индентирования, как коэффициент восстановления скорости, контактное усилие, перемещение и время активного этапа удара. Определены границы допустимого использования твердомеров ударного действия. Показаны пути повышения точности измерения твердости на основе данных, получаемых на этапе внедрения индентора. Установлено, что использование градуировочных зависимостей между твердостью и временем активного этапа удара, а также отношением контактного усилия к глубине внедрения на этапе нагружения позволяет провести оценку твердости для труб с толщиной стенки свыше 5 мм и консольно закрепленных пластин на расстоянии от места закрепления вплоть до 100 мм.

Clinical case of de novo anaplastic ganglioglioma and current status of the problem

The authors report a rare case of de novo malignant ganglioglioma (WHO grade III) in a 26-year old female. The patient has complained of periodic feeling fear, anxiety, episodes of impaired consciousness with extremity muscle cramps sometimes followed by urination, as well as flashes before eyes. Computed tomography perfusion and magnetic resonance spectroscopy were carried out for differential diagnosis between different types of tumors. Stereotactic biopsy was performed for histological examination. High surgical risk became a contraindication to gross total resection of the tumor. The patient has received radiation therapy (Trilogy linear accelerator) in a total dose of 60 Gy. The tumor shrank significantly. In 7 months, monitoring MRT did not detect further growth of the tumor. The authors have analyzed the case and reviewed the existing literature data regarding gangliogliomas. Taking into account low prevalence of these tumors (0.4-1% of all brain tumors), especially of their malignant forms (3-10% of gangliogliomas), lack of sufficient data regarding prognostic factors, life expectancy, time of recurrence, lack of accurate indications for different methods of treatment (surgery, radiation, chemotherapy), these tumors still need further research that should also involve supplementary neuroimaging techniques and stereotactic biopsy

ОСОБЕННОСТИ ПОРАЖЕНИЯ СИГНАЛЬНЫХ ЛИМФАТИЧЕСКИХ УЗЛОВ ПРИ ПЕРВИЧНОЙ МЕЛАНОМЕ КОЖИ

Introduction. Each tenth tumor of skin is melanoma. Presence of tumor cells in sentinel lymph node influenced the medical tactics.The objective of the research was to study the metastasis of skin melanoma into the clinically negative regional lymph nodes.Material and methods. Histological, immunohistochemical, cytological and immunocytochemical methods were used to study biopsies of regional lymph nodes in 60 patients with skin melanoma.Results. 5 % of patients were diagnosed with melanoma in situ, 15 % – Т1, 28.3 % – Т2, 23.3 % – Т3, 28.3 % – Т4. At outflow of the lymph through 1 collector, the metastases in sentinel lymph node (SLN) was defined in 51 %, through 2 collectors – in 81.8 % of cases. Tumor cells damaged single lymph node in 35.3 % of cases, two and more lymph nodes in 64.7 % of cases. Metastases in SLN with formation of secondary tumor at the T1 melanoma were observed at 11.1 %, T2 – 5.9 %, T3 – 21.4 %, T4 – 47.1 % of studies. Clusters of cells or isolated cells of melanoma in SLN at Т1 were noted in 22.2 %, at Т2 – in 41.2 %, at Т3 – in 42.9 %, at Т4 – in 35.3 % of cases. At outflow of lymph through 1 collector, metastasises of melanoma in non-sentinel lymph nodes (NSLN) were revealed in 24 %, through 2 collectors – in 44.4 % of cases. Secondary changes of NSLN were noted in 16.7 % of cases of defeat of single SLN, in 31.8 % of cases of defeat of two and more SLN. Metastases of melanoma were revealed in 69.2 % of cases of formation of secondary tumor and in 4.8 % of cases of presence of clusters in SLN in removed NSLN.Conclusion. At increase of Тmelanoma of the skin, the quantity of sentinel lymph nodes with reactive changes decreased, and their number with metastases increased. Metastatic defeat of sentinel lymph nodes at outflow of lymph through 2 lymph collectors in two and more SLN and NSLN exceeded the defeat of SLN at outflow of lymph through 1 lymph collector in single lymph nodes. The use of immunocytochemical method of research allowed to expand pathomorphological verification of metastatic defeat of sentinel lymph nodes by 66.7%.Введение. Каждая 10-я опухоль кожи – меланома, на план лечения которой влияет наличие опухолевых клеток в сигнальном лимфоузле.Цель исследования – изучение метастазирования меланомы кожи в клинически негативные региональные лимфатические узлы.Материал и методы. Гистологическим, иммуногистохимическим, цитологическим и иммуноцитохимическим методами исследованы биоптаты региональных лимфатических узлов 60 пациентов с меланомой кожи.Результаты. У 5 % пациентов диагностирована меланома в стадии in situ, у 15 % – Т1, у 28,3 % – Т2, у 23,3 % – Т3, у 28,3 % – Т4. При оттоке лимфы через 1 лимфоколлектор метастазы в сигнальном лимфоузле (СЛУ) определили в 51 %, через 2 лимфоколлектора – в 81,8 % случаев. В 35,3 % случаев опухолевые клетки поражали единичный лимфоузел, в 64,7 % – 2 и более лимфоузла. Метастазы в СЛУ с формированием вторичной опухоли при меланоме Т1 наблюдали в 11,1 %, Т2 – в 5,9 %, Т3 – в 21,4 %, Т4 – в 47,1 % исследований. Скопления клеток по типу кластера или разрозненные клетки меланомы в СЛУ при Т1 отмечены в 22,2 %, при Т2 – в 41,2 %, при Т3 – в 42,9 %, при Т4 – в 35,3 % случаев. При оттоке лимфы через 1 коллектор метастазы меланомы в несигнальных лимфоузлах (НСЛУ) выявлены в 24 %, через 2 коллектора – в 44,4 % случаев. Вторичные изменения НСЛУ отметили в 16,7 % случаев поражения единичного СЛУ, в 31,8 % наблюдений – поражения 2 и более СЛУ. В 69,2 % случаев формирования вторичной опухоли и в 4,8 % наличия кластеров в СЛУ в удаленных НСЛУ обнаружены метастазы меланомы.Выводы. При нарастании Т меланомы кожи уменьшалось число сигнальных лимфатических узлов с реактивными изменениями, и возрастала их численность с метастазами. Метастатическое поражение сигнальных лимфатических узлов при оттоке лимфы через 2 лимфоколлектора в 2 и более СЛУ и НСЛУ превышало поражение СЛУ при оттоке лимфы через 1 лимфоколлектор в единичные лимфоузлы. Использование иммуноцитохимического метода исследования позволило на 66,7 % расширить патоморфологическую верификацию метастатического поражения сигнальных лимфатических узлов

Motor step size and ATP coupling efficiency of the dsDNA translocase EcoR124I

The Type I restriction-modification enzyme EcoR124I is an archetypical helicase-based dsDNA translocase that moves unidirectionally along the 3′–5′ strand of intact duplex DNA. Using a combination of ensemble and single-molecule measurements, we provide estimates of two physicochemical constants that are fundamental to a full description of motor protein activity—the ATP coupling efficiency (the number of ATP consumed per base pair) and the step size (the number of base pairs transported per motor step). Our data indicate that EcoR124I makes small steps along the DNA of 1 bp in length with 1 ATP consumed per step, but with some uncoupling of the ATPase and translocase cycles occurring so that the average number of ATP consumed per base pair slightly exceeds unity. Our observations form a framework for understanding energy coupling in a great many other motors that translocate along dsDNA rather than ssDNA

MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens

The PITX3 bicoid-type homeodomain transcription factor plays an important role in lens development in vertebrates. PITX3 deficiency results in a spectrum of phenotypes from isolated cataracts to microphthalmia in humans, and lens degeneration in mice and zebrafish. While identification of downstream targets of PITX3 is vital for understanding the mechanisms of normal ocular development and human disease, these targets remain largely unknown. To isolate genes that are directly regulated by PITX3, we performed a search for genomic sequences that contain evolutionarily conserved bicoid/PITX3 binding sites and are located in the proximity of known genes. Two bicoid sites that are conserved from zebrafish to human were identified within the human promoter of the major intrinsic protein of lens fiber, MIP/AQP0. MIP/AQP0 deficiency was previously shown to be associated with lens defects in humans and mice. We demonstrate by both chromatin immunoprecipitation and electrophoretic mobility shift assay that PITX3 binds to MIP/AQP0 promoter region in vivo and is able to interact with both bicoid sites in vitro. In addition, we show that wild-type PITX3 is able to activate the MIP/AQP0 promoter via interaction with the proximal bicoid site in cotransfection experiments and that the introduction of mutations disrupting binding to this site abolishes this activation. Furthermore, mutant forms of PITX3 fail to produce the same levels of transactivation as wild-type when cotransfected with the MIP/AQP0 reporter. Finally, knockdown of pitx3 in zebrafish affects formation of a DNA-protein complex associated with mip1 promoter sequences; and examination of expression in pitx3 morphant and control zebrafish revealed a delay in and reduction of mip1 expression in pitx3-deficient embryos. Therefore, our data suggest that PITX3 is involved in direct regulation of MIP/AQP0 expression and that the alteration of MIP/AQP0 expression is likely to contribute to the lens phenotype in cataract patients with PITX3 mutations