Recycling of epidermal growth factor-receptor complexes in A431 cells: identification of dual pathways

The intracellular sorting of EGF-receptor complexes (EGF-RC) has been studied in human epidermoid carcinoma A431 cells. Recycling of EGF was found to occur rapidly after internalization at 37 degrees C. The initial rate of EGF recycling was reduced at 18 degrees C. A significant pool of internalized EGF was incapable of recycling at 18 degrees C but began to recycle when cells were warmed to 37 degrees C. The relative rate of EGF outflow at 37 degrees C from cells exposed to an 18 degrees C temperature block was slower (t1/2 approximately 20 min) than the rate from cells not exposed to a temperature block (t1/2 approximately 5-7 min). These data suggest that there might be both short- and long-time cycles of EGF recycling in A431 cells. Examination of the intracellular EGF-RC dissociation and dynamics of short- and long-time recycling indicated that EGF recycled as EGF-RC. Moreover, EGF receptors that were covalently labeled with a photoactivatable derivative of 125I-EGF recycled via the long-time pathway at a rate similar to that of 125I-EGF. Since EGF-RC degradation was also blocked at 18 degrees C, we propose that sorting to the lysosomal and long-time recycling pathway may occur after a highly temperature-sensitive step, presumably in the late endosomes

Estimation of the geographical coordinates of objects on the image with multi-task convolutional neural networks

Determining GPS coordinates of the objects on the image is exceptionally complex problem. Images often contain enough information such as landmarks, cloud texture, grass type, road signs or architectural features that allow suggesting the location where the photo was taken. Previously, such issue was solved with image search methods. In contrast, the problem is stated as a classification task, subdividing the Earth's surface into geographical cells using a special type of space- filling curve. Thousands of differently scaled geographical cells, used to train the model. In this paper, several deep learning methods that follow the latter approach and take advantage of multitask learning are presented. Taking into account the content of the scene of the image, i.e. inside, outside, wild or urban setting, etc. is proposed. As a result, additional information with different spatial resolutions as well as more specific features for different environments are included in the learning process of the convolutional neural network. Reported metrics demonstrate the effectiveness of our out-of-the-box approach, while using a helper network to combine two datasets combined to spread scene labels on GPS dataset and receive more robust model. This model does not rely on search methods, which require an enormous amount of computational power, and implements a probabilistic approach

EPIDEMIOLOGICAL FEATURES OF MELANOMA SKIN CANCER AND SURVIVAL OF ONCOLOGY PATIENTS IN KRASNODAR REGION

Aim. To assess the effectiveness of preventive, diagnostic and therapeutic work of the oncological service of Krasnodar Region, analyze the epidemiological features of morbidity, mortality, indicators reflecting the diagnosis (the proportion of early detection, neglect) in patients with melanoma skin cancer for the period 2007–2017, and the survival of cancer patients in Krasnodar Region for the period 2007–2016.Materials and methods. Subjects of the study were patients with newly diagnosed melanoma skin cancer in Krasnodar Region for the period 2007–2017. Using an automated information and analytical system the Population Cancer Registry, survival of 3 961 patients with melanoma skin cancer for the period 2007–2016 was analyzed. Standardized rates of morbidity and mortality were calculated according to the accepted world standard with the same age groupings. Statistical processing of data according to the studied indicators was carried out using statistical software packages Statistica. The reliability of the difference in the relative indicators was determined by the t test of the Student, the significance level was adopted as p <0.05.Results. For the period from 2007 to 2017, there has been a significant trend towards an increase in the incidence of melanoma skin cancer of the population of Krasnodar Region. The incidence of melanoma skin cancer in Krasnodar Region is higher than the average for the Russian Federation, which may be due to the presence of an increased level of insolation. During the analyzed period there has been a decrease in the indicator of neglect. With the increase in the stage of melanoma skin cancer, the survival rates both in general among all the diseased and among patients of working age are decreasing. The highest rates of observed and adjusted survival in patients with melanoma skin cancer reduce in the first three years from the date of diagnosis. The indicators of the observed and corrected survival of men of working age with melanoma skin cancer are lower than in women of working age. The indicators of the observed and corrected survival of women of working age with melanoma skin cancer are higher than among the population of all age groups.Сonclusion. The study showed a high level of early diagnosis and quality of treatment for patients with melanoma skin cancer in the Krasnodar Region, as positive trends in the rates of observed and adjusted survival of patients were noted

Patient routing and process approach implementation for regional oncology service

Background. Cancer care involves a multidisciplinary approach to diagnosis and treatment of patients. A complex interaction of actors in the deployment of oncology services dictates usage of modern management technologies for improving the quality and efficiency of patient care through processes optimisation.Objectives. Provision of recommendations for patient routing based on research into the oncology service inter-level information exchange, integration of the process approach and electronic services. The lack of a unified information space with a regional oncology service has been explained. Measures are proposed for the patient routing optimisation as part of establishing a unified digital oncology service circuit.Methods. The oncology service was effectively remodelled through functional and information engineering of electronic services and the process management integration to establish a horizontal decision flow between facilities and employees on a process level bypassing the supervisor coordination. Statistical approaches were used to analyse the oncological patient population.Results. The following electronic services have been implemented: specialised patient referral routing, telemedicine and teleradiology. A comprehensive information framework has been created comprising medical, laboratory and radiological information subsystems integrated through regional electronic services of the unified state healthcare information platform. The goals, objectives, general principles, architecture and expected social economic impact on healthcare of Krasnodar Krai have been defined.Conclusion. Use of electronic services ensures an improved quality of specialised care and effective routing of patients. We perceive prospects of the integrated information platform in the extension and improvement of its subsystems’ functionality and content, sourcing more data providers and the circuit expansion to the federal and regional levels

Ce-doped Li6Ln(BO3)3 (Ln = Y, Gd) Single crystals fibers grown by micro-pulling down method and luminescence properties

Ce3+-doped borate crystal fibers of Li6Gd(BO 3)3 (LGBO) and Li6Y(BO3)3 (LYBO) compositions are grown by the micro-pulling down (μ-PD) method for potential application in developing new neutron detectors. The ternary equilibrium diagram of Li2O-Gd2O3-B 2O3 is drawn and the preparations of homogeneous mixed LGBO and LYBO powders and growth conditions for single crystal fibers are discussed. Absorption, excitation and X-ray luminescence spectra are investigated. Absolute light yield derived from energy spectra and kinetic decay curves measured under α- and γ-scintillations of Ce 3+-doped LGBO and LYBO single crystal fibers is provided. © 2012 Elsevier B.V. All rights reserved

Antithrombotic therapy in patients with atrial flutter before planned cardioversion

Резюме. Вступ: фібриляція/тріпотіння передсердь (ФП, ТП) - порушення ритму серця, на фоні яких зростає ризик життєнебезпечних ускладнень – кардіоемболічного інсульту, тромбоемболії легеневої артерії. Рекомендації щодо ведення хворих з ФП-ТП, з тривалістю пароксизму понад 48 годин, вимагають антикоагулянтної терапії. З метою периманіпуляційної підготовки пацієнтів з ТП до відновлення синусового ритму (СР) методом черезстравохідної електрокардіостимуляції (ЧСЕКС) використовують пероральні антикоагулянти - антагоністи вітаміну К (варфарин), нові оральні антикоагулянти (ривароксабан). Ціль дослідження: порівняти ефективність та безпечність варфарину та ривароксабану у хворих з ТП перед проведенням планової кардіоверсії методом ЧСЕКС. Матеріали та методи: 42 хворим на ішемічну хворобу серця з супутньою артеріальною гіпертензією та пароксизмом ТП неклапанної етіології тривалістю >48 год, розділеним на 2 групи, призначали варфарин (КГ), в еквівалентних для досягнення цільового МНВ дозах, або ривароксабан (ДГ) 20 мг. Проводили загальноклінічне, ехокардіоскопічне (ЕхоКС) обстеження. Тромботичний ризик оцінювали за шкалою CHA2DS2-VASc, геморагічний ризик - за шкалою HAS-BLED, клінічну симптоматику - за шкалою EHRA. Ритм відновлювали ЧСЕКС. Результати: у пацієнтів ДГ , на відміну від пацієнтів КГ (термін з підбором цільового МНВ складав 30,76±0,62 днів), спостерігалось скорочення терміну підготовки (згідно рекомендацій 21 день), у динаміці спостерігалося зменшення вираженості симптомів за EHRA. За результатами ЧСЕКС у хворих ДГ відновлено СР у 15 хворих, у 6 хворих переведено в ФП. У хворих КГ, СР - відновлено у 6 хворих, у 10 хворих - ФП. Висновок: застосування ривароксабану з метою периманіпуляційної підготовки до планової кардіоверсії шляхом ЧСЕКС призводить до скорочення термінів підготовки, зменшує ризик розвитку проявів серцевої недостатності, сприяє відновленню СР у пацієнтів з ТП. Abstract. Introduction: atrium flutter and fibrillation are the heart rhythm disorders that increase the risk of life-dangerous complications, e.g. cardioembolic stroke, pulmonary embolism. Recommendations for managing patients with atrial fibrillation – atrial flutter, with paroxysm duration over 48 hours, demand anticoagulant therapy. Oral anticoagulants, which are the antagonists of K vitamin (Varpharin) and the new oral anticoagulants (Rivaroxaban), are used during the per-manipulative procedure of patients with atrial flutter before restoring the sinus rhythm with transesophageal cardiac pacing. Aim: the present investigation aims to compare efficiency and safety of Varpharin and Rivaaroxaban in treatment patients with atrial flutter before planned cardioversion with transesophageal heart pacing. Materials and methods: Varpharin (control group) – in doses equivalent for reaching the target МНВ – or Rivaroxaban (research group), 20 mg., were prescribed to 42 patients with coronary heart disease, concomitant arterial hypertension, and non-valvular paroxysm of atrial flutter with more than 48-hour duration, divided into two groups. There was held the general clinical, echocardioscopy examination. Thrombotic Risk Factor Assessment was made according to the CHA2DS2-VASc scale, Hemorrhagic Risk Factor Assessment was performed according to the HAS-BLED scale, and clinical symptoms assessment was made according to the EHRA scale. The heart rhythm was restored with the transesophageal heart pacing. Results: the per-manipulative procedure of the patients of research group (21 days were suggested according to the guidelines) shortened, unlike the patients of control group (the period of target МНВ selection had made 30,76±0,62days), the reduction of the symptoms severity by EHRA was considered in dynamics. According to the results of transesophageal heart pacing, the heart rhythm of 15 research group patients restored, and 6 research group patients had atrial fibrillation. Among the patients of the control group, 6 had their heart rhythm restored, as 10 patients had the atrial fibrillation. Conclusions: the use of Rivaroxaban during the per-manipulative procedure before planned cardioversion with transesophageal heart pacing causes shortening of the per-manipulative period, reduces the risk of development of symptoms of heart failure, helps to restore the heart rhythm of the patients with atrium flutter

MrBayes 3.2: Efficient Bayesian Phylogenetic Inference and Model Choice Across a Large Model Space

Since its introduction in 2001, MrBayes has grown in popularity as a software package for Bayesian phylogenetic inference using Markov chain Monte Carlo (MCMC) methods. With this note, we announce the release of version 3.2, a major upgrade to the latest official release presented in 2003. The new version provides convergence diagnostics and allows multiple analyses to be run in parallel with convergence progress monitored on the fly. The introduction of new proposals and automatic optimization of tuning parameters has improved convergence for many problems. The new version also sports significantly faster likelihood calculations through streaming single-instruction-multiple-data extensions (SSE) and support of the BEAGLE library, allowing likelihood calculations to be delegated to graphics processing units (GPUs) on compatible hardware. Speedup factors range from around 2 with SSE code to more than 50 with BEAGLE for codon problems. Checkpointing across all models allows long runs to be completed even when an analysis is prematurely terminated. New models include relaxed clocks, dating, model averaging across time-reversible substitution models, and support for hard, negative, and partial (backbone) tree constraints. Inference of species trees from gene trees is supported by full incorporation of the Bayesian estimation of species trees (BEST) algorithms. Marginal model likelihoods for Bayes factor tests can be estimated accurately across the entire model space using the stepping stone method. The new version provides more output options than previously, including samples of ancestral states, site rates, site dN/dS rations, branch rates, and node dates. A wide range of statistics on tree parameters can also be output for visualization in FigTree and compatible software