A novel RNA aptamer identifies plasma membrane ATP synthase beta subunit as an early marker and therapeutic target in aggressive cancer

PURPOSE: Primary breast and prostate cancers can be cured, but metastatic disease cannot. Identifying cell factors that predict metastatic potential could guide both prognosis and treatment. METHODS: We used Cell-SELEX to screen an RNA aptamer library for differential binding to prostate cancer cell lines with high vs. low metastatic potential. Mass spectroscopy, immunoblot, and immunohistochemistry were used to identify and validate aptamer targets. Aptamer properties were tested in vitro, in xenograft models, and in clinical biopsies. Gene expression datasets were queried for target associations in cancer. RESULTS: We identified a novel aptamer (Apt63) that binds to the beta subunit of F1Fo ATP synthase (ATP5B), present on the plasma membrane of certain normal and cancer cells. Apt63 bound to plasma membranes of multiple aggressive breast and prostate cell lines, but not to normal breast and prostate epithelial cells, and weakly or not at all to non-metastasizing cancer cells; binding led to rapid cell death. A single intravenous injection of Apt63 induced rapid, tumor cell-selective binding and cytotoxicity in MDA-MB-231 xenograft tumors, associated with endonuclease G nuclear translocation and DNA fragmentation. Apt63 was not toxic to non-transformed epithelial cells in vitro or adjacent normal tissue in vivo. In breast cancer tissue arrays, plasma membrane staining with Apt63 correlated with tumor stage (p < 0.0001, n = 416) and was independent of other cancer markers. Across multiple datasets, ATP5B expression was significantly increased relative to normal tissue, and negatively correlated with metastasis-free (p = 0.0063, 0.00039, respectively) and overall (p = 0.050, 0.0198) survival. CONCLUSION: Ecto-ATP5B binding by Apt63 may disrupt an essential survival mechanism in a subset of tumors with high metastatic potential, and defines a novel category of cancers with potential vulnerability to ATP5B-targeted therapy. Apt63 is a unique tool for elucidating the function of surface ATP synthase, and potentially for predicting and treating metastatic breast and prostate cancer

Submental Myodermal Flap in Buccal Reconstruction after Extended Combined Resection

Background. Oral mucosal cancer is the most prevalent squamous cell cancer of head and neck, with 6,723 cases registered in Russia, including 94 per Volgograd Region, in 2018. A high tumour advancement and complex topography of the surgical area result in extensive soft-tissue defects and impaired swallowing, chewing and speech.Aim. Efficacy assessment of submental myodermal flap application in buccal reconstruction after extended combined oncological resections.Materials and methods. Submental myodermal flap was used as a buccal reconstruction technique in 112 patients aged 42 to 75 years during 2015–2020. Surgery for primary tumour was performed in 88 cases, and in 24 — for recurrence after radiotherapy or surgical excision.Results and discussion. A six-year experience of the submental myodermal flap usage in reconstructive surgery allowed evidently wider indications for extensive oral resection combined with extended, also bilateral, lymphadenectomy. Clinical records on the technique application in primary and recurrent cancer are presented.Conclusion. The submental myodermal flap technique in combination with extended or extended combined surgery for oral mucosal cancer notably increases the tumour resectability at this location and improves function restore in patients. The method widens indications for higher-volume operative aid, considerably reduces postoperative complications and holds a promise to enable more radical surgery. This plastic surgery technique is aesthetic and effectively repairs speech and digestive functions, bringing improvement to the patients’ quality of life and social adaptation

Relative luminosity measurement of the LHC with the ATLAS forward calorimeter

In this paper it is shown that a measurement of the relative luminosity changes at the LHC may be obtained by analysing the currents drawn from the high voltage power supplies of the electromagnetic section of the forward calorimeter of the ATLAS detector. The method was verified with a reproduction of a small section of the ATLAS forward calorimeter using proton beams of known beam energies and variable intensities at the U-70 accelerator at IHEP in Protvino, Russia. The experimental setup and the data taking during a test beam run in April 2008 are described in detail. A comparison of the measured high voltage currents with reference measurements from beam intensity monitors shows a linear dependence on the beam intensity. The non-linearities are measured to be less than 0.5 % combining statistical and systematic uncertainties.Comment: 16 page

COMPARATIVE STUDIES OF VR SIMULATOR EFFECTIVENESS AND ALTERNATIVE PRESENTATION SKILLS TRAINING METHODS

The paper analyzes the results of the experiment (conducted at the School of Advanced Studies (SAS), the University of Tyumen in collaboration with the Saint Petersburg State University “Digital Technologies in Education” Science and education center from 23.05.2022 to 28.05.2022) comparing teaching English language public presentation skills using a VR simulator in comparison with self-study and exercises with the instructor. The researched teaching methods are compared for effectiveness in teaching various skills of the set (emotional control, speech structuration and contact with the audience).Анализируются результаты эксперимента обучения навыкам публичных выступлений на английском языке с использованием VR-тренажера в сравнении с самообучением и взаимодействием с тренером, проведенного в Школе перспективных исследований Тюменского государственного университета совместно с сотрудниками Научнообразовательного центра «Цифровые технологии в образовании» Санкт-Петербургского государственного университета в период с 23.05.2022 по 28.05.2022. Рассматривается сравнительная эффективность сравниваемых методов обучения для улучшения различных навыков (эмоционального контроля, структурирования речи, контакта с аудиторией)

Моделирование процесса смешения теплоносителя в опускном участке и напорной камере смешения ВВЭР-1200 (В-491)

The most representative accident scenario is determined and a physical and mathematical model is developed for studying the mixing of non-isothermal coolant flows in the structural elements of the V-491 reactor facility (VVER-1200), in which the motion of the medium is described in a three-dimensional non-stationary formulation. Based on the analytical estimates of the list of initiating events, a scenario was chosen with the connection of an idle loop of the main circulation pipeline to three operating ones without a preliminary power reduction. A computational algorithm and a numerical method have been developed for the computational analysis of the selected accident scenario and the justification of the safety of operation of the V-491 reactor facility (VVER-1200). During the numerical simulation, the RANS method was used, which consists in solving the Reynolds-averaged Navier–Stokes equations, the continuity equation and the energy equation. The SST k–ω model of turbulence by Florian Menter is used to close the equations. The verification of the developed physical and mathematical model and calculation procedure was carried out by modeling thermohydraulic processes in models with both a relatively simple geometric design (tee connection) and in a scale model of the reactor vessel (ROCOM experiment), including a lowering section and a pressure mixing chamber. The qualitative agreement of the numerical simulation results with the available data of physical experiments is shown. The results of numerical simulation of the mixing process of non-isothermal coolant flows in the section from the branch pipe of the “cold” thread of the main circulation pipeline to the lower boundary of the fuel of the VVER-1200 core (V-491) are presented. It is shown that the heterogeneity in the temperature distribution at the entrance to the core manifests itself up to 15.5 s of the calculated accident scenario. For calculations the following code coupling were used: Ansys Fluent/Rainbow-TPP.Определен наиболее представительный аварийный сценарий и разработана физико-математическая модель для исследования смешения неизотермических потоков теплоносителя в конструктивных элементах реакторной установки В-491 (ВВЭР-1200), в которой движение среды описывается в трехмерной нестационарной постановке. Исходя из аналитических оценок перечня исходных событий, выбран сценарий с подключением неработающей петли главного циркуляционного трубопровода к трем работающим без предварительного снижения мощности. Разработаны расчетная методика и численный метод для анализа выбранного аварийного сценария и обоснования безопасности эксплуатации реакторной установки В-491 (ВВЭР-1200). При проведении численного моделирования использован метод RANS, заключающийся в решении осредненных по Рейнольдсу уравнений Навье–Стокса, уравнения неразрывности и уравнения энергии. Для замыкания уравнений использована SST k–ω модель турбулентности Флориана Ментера. Проведена верификация разработанной физико-математической модели и процедуры расчета посредством моделирования теплогидравлических процессов в моделях как с относительно простой геометрической конструкцией (тройниковое соединение), так и в масштабной модели корпуса реактора (эксперимент ROCOM), включающего опускной участок и напорную камеру смешения. Показано качественное согласование численных результатов моделирования с доступными данными физических экспериментов. Представлены результаты численного моделирования процесса смешения неизотермических потоков теплоносителя на участке от патрубка «холодной» нитки главного циркуляционного трубопровода до нижней границы топлива активной зоны ВВЭР-1200 (В-491). Показано, что неоднородность в распределении температуры на входе в активную зону проявляется до 15,5 с расчетного аварийного сценария. При выполнении вычислений использовалась связка специализированных расчетных средств Ansys Fluent/Rainbow-TPP

Construction, assembly and testing of the ATLAS hadronic end-cap calorimeter

The construction and assembly of the four wheels of the ATLAS hadronic end-cap calorimeter and their insertion into the two end-cap cryostats are described. The results of the qualification tests prior to installation of the two cryostats in the ATLAS experimental cavern are reviewed